AKT1 MODULATORS CROSS-REFERENCE TO RELATED APPLICATION [0001] This application claims the benefit of U.S. Patent Application No.63/377,183, filed on September 26, 2022; U.S. Patent Application No.63/498,770, filed on April 27, 2023; U.S. Patent Application No.63/508,418, filed on June 15, 2023; U.S. Patent Application No. 63/580,327, filed on September 1, 2023; and U.S. Patent Application No.63/582,697, filed on September 14, 2023, all of which are hereby incorporated by reference in their entirety. BACKGROUND [0002] AKT is a protein kinase and mediates cell survival and proliferation by inhibiting pathways which promotes apoptosis. AKT signaling cascade dysfunction is observed in several cancer types and may be associated with tumor aggressiveness. Additionally, malfunction of AKT typically lead to enhanced proliferation, growth, survival, and resistance to apoptosis. Pharmaceutical agents with the ability to modulate AKT1 activity would be useful in the treatment of disease, such as cancer. BRIEF SUMMARY OF THE INVENTION [0003] Provided herein are inhibitors of AKT1, pharmaceutical compositions comprising said inhibitory compounds, and methods for using said inhibitory compounds for the treatment of disease. [0004] One embodiment provides a compound having the structure of Formula (I), or a pharmaceutically acceptable salt or solvate thereof: wherein: Z ¹ is N, C-H, or C-R ³ ; Z ² is N, C-H, or C-R ⁴ ; Z ³ is N, C-OH, or C-R ⁹ ; Ar is selected from:

X ¹ is N or C-R ⁷ ; X ² is N or C-R ⁷ ; X ³ is N or C-R ⁷ ; X ⁴ is N or C-R ⁷ ; Y is O, S, or N-R ⁹ ; R ¹ is selected from hydrogen, optionally substituted C1-C6 alkyl, optionally substituted aryl, or optionally substituted heteroaryl; R ² is selected from hydrogen, halogen, -OH, -CN, -N(R ⁹ ) ₂ , -OR ⁹ , -SR ⁹ , -SO ₂ R ⁹ , -CO ₂ R ⁹ , -CON(R ⁹ ) ₂ , -SR ⁹ , -S(O)R ⁹ , - S(O) ₂ R ⁹ , optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkoxy, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C3-C7 carbocyclyl, optionally substituted 4-membered to 6-membered heterocyclyl, optionally substituted aryl, aryl substituted with an optionally substituted 4- membered to 6-membered heterocyclyl, optionally substituted heteroaryl or heteroaryl substituted with an optionally substituted 3-membered to 6-membered carbocyclyl; R ³ is selected from optionally substituted C1-C6 alkyl, or optionally substituted aryl; R ⁴ is selected from halogen, -CN, optionally substituted C1-C6 alkyl, or optionally substituted aryl; R ⁵ and R ⁶ are each independently hydrogen, deuterium, halogen, -OH, or optionally substituted C1-C6 alkyl; or R ⁵ and R ⁶ together form an oxo; or R ⁵ and R ⁶ join together to form a carbocycle or heterocycle; each R ⁷ is independently selected from hydrogen, deuterium, halogen, -OH, -SH, optionally substituted C1-C6 alkoxy, -S-(optionally substituted C1-C6 alkyl), -CN, optionally substituted C1-C6 alkyl, and optionally substituted aryl; L is selected from -N(R ⁸ )-, or a divalent radical selected from: wherein the asterisk (*) indicates the bond to the -CO-Ar group; R ⁸ is hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C7 cycloalkyl, or optionally substituted heterocyclyl; each R ⁹ is hydrogen, or optionally substituted C1-C6 alkyl; R ¹⁰ is optionally substituted C1-C6 alkyl; m is 0, 1, or 2; n is 1, 2, or 3; and q is 0 or 1. [0005] One embodiment provides a pharmaceutical composition comprising a compound of Formula (I), or pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient. [0006] One embodiment provides a method of treating a disease or disorder in a patient in need thereof comprising administering to the patient a compound of Formula (I), or pharmaceutically acceptable salt or solvate thereof. Another embodiment provides the method wherein the disease or disorder is cancer. INCORPORATION BY REFERENCE [0007] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference for the specific purposes identified herein. DETAILED DESCRIPTION OF THE INVENTION [0008] As used herein and in the appended claims, the singular forms "a," "and," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "an agent" includes a plurality of such agents, and reference to "the cell" includes reference to one or more cells (or to a plurality of cells) and equivalents thereof known to those skilled in the art, and so forth. When ranges are used herein for physical properties, such as molecular weight, or chemical properties, such as chemical formulae, all combinations and subcombinations of ranges and specific embodiments therein are intended to be included. The term "about" when referring to a number or a numerical range means that the number or numerical range referred to is an approximation within experimental variability (or within statistical experimental error), and thus the number or numerical range, in some instances, will vary between 1% and 15% of the stated number or numerical range. The term "comprising" (and related terms such as "comprise" or "comprises" or "having" or "including") is not intended to exclude that in other certain embodiments, for example, an embodiment of any composition of matter, composition, method, or process, or the like, described herein, "consist of" or "consist essentially of" the described features. Definitions [0009] As used in the specification and appended claims, unless specified to the contrary, the following terms have the meaning indicated below. [0010] "Amino" refers to the –NH ₂ radical. [0011] "Cyano" refers to the -CN radical. [0012] "Nitro" refers to the -NO ₂ radical. [0013] "Oxa" refers to the -O- radical. [0014] "Oxo" refers to the =O radical. [0015] "Thioxo" refers to the =S radical. [0016] "Imino" refers to the =N-H radical. [0017] "Oximo" refers to the =N-OH radical. [0018] "Hydrazino" refers to the =N-NH ₂ radical. [0019] "Alkyl" refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, having from one to fifteen carbon atoms (e.g., C ₁ -C ₁₅ alkyl). In certain embodiments, an alkyl comprises one to thirteen carbon atoms (e.g., C ₁ -C ₁₃ alkyl). In certain embodiments, an alkyl comprises one to eight carbon atoms (e.g., C ₁ -C ₈ alkyl). In other embodiments, an alkyl comprises one to five carbon atoms (e.g., C ₁ -C ₅ alkyl). In other embodiments, an alkyl comprises one to four carbon atoms (e.g., C ₁ - C4 alkyl). In other embodiments, an alkyl comprises one to three carbon atoms (e.g., C ₁ -C ₃ alkyl). In other embodiments, an alkyl comprises one to two carbon atoms (e.g., C ₁ -C ₂ alkyl). In other embodiments, an alkyl comprises one carbon atom (e.g., C ₁ alkyl). In other embodiments, an alkyl comprises five to fifteen carbon atoms (e.g., C ₅ -C ₁₅ alkyl). In other embodiments, an alkyl comprises five to eight carbon atoms (e.g., C ₅ -C ₈ alkyl). In other embodiments, an alkyl comprises two to five carbon atoms (e.g., C ₂ -C ₅ alkyl). In other embodiments, an alkyl comprises three to five carbon atoms (e.g., C3-C5 alkyl). In other embodiments, the alkyl group is selected from methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl (iso-propyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (iso-butyl), 1,1-dimethylethyl (tert-butyl), 1-pentyl (n-pentyl). The alkyl is attached to the rest of the molecule by a single bond. Unless stated otherwise specifically in the specification, an alkyl group is optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR ^a , -SR ^a , -OC(O)-R ^a , -N(R ^a ) ₂ , -C(O)R ^a , -C(O)OR ^a , -C(O)N(R ^a ) ₂ , - N(R ^a )C(O)OR ^a , -OC(O)-N(R ^a ) ₂ , -N(R ^a )C(O)R ^a , -N(R ^a )S(O) _t R ^a (where t is 1 or 2), -S(O) _t ORa (where t is 1 or 2), -S(O) _t R ^a (where t is 1 or 2) and -S(O) _t N(R ^a ) ₂ (where t is 1 or 2) where each R ^a is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl). In certain embodiments, an optionally substituted alkyl is a haloalkyl. In other embodiments, an optionally substituted alkyl is a fluoroalkyl. In other embodiments, an optionally substituted alkyl is a -CF3 group. [0020] "Alkoxy" refers to a radical bonded through an oxygen atom of the formula –O-alkyl, where alkyl is an alkyl chain as defined above. [0021] "Alkenyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon double bond, and having from two to twelve carbon atoms. In certain embodiments, an alkenyl comprises two to eight carbon atoms. In other embodiments, an alkenyl comprises two to four carbon atoms. The alkenyl is attached to the rest of the molecule by a single bond, for example, ethenyl (i.e., vinyl), prop-1-enyl (i.e., allyl), but-1-enyl, pent-1-enyl, penta-1,4-dienyl, and the like. Unless stated otherwise specifically in the specification, an alkenyl group is optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR ^a , -SR ^a , -OC(O)-R ^a , -N(R ^a ) ₂ , -C(O)R ^a , -C(O)OR ^a , -C(O)N(R ^a ) ₂ , - N(R ^a )C(O)OR ^a , -OC(O)-N(R ^a ) ₂ , -N(R ^a )C(O)R ^a , -N(R ^a )S(O) _t R ^a (where t is 1 or 2), -S(O) _t OR ^a (where t is 1 or 2), -S(O) _t R ^a (where t is 1 or 2) and -S(O) _t N(R ^a ) ₂ (where t is 1 or 2) where each R ^a is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl). [0022] "Alkynyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond, having from two to twelve carbon atoms. In certain embodiments, an alkynyl comprises two to eight carbon atoms. In other embodiments, an alkynyl comprises two to six carbon atoms. In other embodiments, an alkynyl comprises two to four carbon atoms. The alkynyl is attached to the rest of the molecule by a single bond, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like. Unless stated otherwise specifically in the specification, an alkynyl group is optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR ^a , -SR ^a , -OC(O)-R ^a , -N(R ^a ) ₂ , -C(O)R ^a , -C(O)OR ^a , - C(O)N(R ^a ) ₂ , -N(R ^a )C(O)OR ^a , -OC(O)-N(R ^a ) ₂ , -N(R ^a )C(O)R ^a , -N(R ^a )S(O) _t R ^a (where t is 1 or 2), -S(O) _t OR ^a (where t is 1 or 2), -S(O) _t R ^a (where t is 1 or 2) and -S(O) _t N(R ^a ) ₂ (where t is 1 or 2) where each R ^a is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl). [0023] "Alkylene" or "alkylene chain" refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing no unsaturation, and having from one to twelve carbon atoms, for example, methylene, ethylene, propylene, n-butylene, and the like. The alkylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkylene chain to the rest of the molecule and to the radical group are through one carbon in the alkylene chain or through any two carbons within the chain. In certain embodiments, an alkylene comprises one to eight carbon atoms (e.g., C ₁ -C ₈ alkylene). In other embodiments, an alkylene comprises one to five carbon atoms (e.g., C ₁ -C ₅ alkylene). In other embodiments, an alkylene comprises one to four carbon atoms (e.g., C ₁ -C ₄ alkylene). In other embodiments, an alkylene comprises one to three carbon atoms (e.g., C ₁ -C ₃ alkylene). In other embodiments, an alkylene comprises one to two carbon atoms (e.g., C ₁ -C ₂ alkylene). In other embodiments, an alkylene comprises one carbon atom (e.g., C ₁ alkylene). In other embodiments, an alkylene comprises five to eight carbon atoms (e.g., C ₅ -C ₈ alkylene). In other embodiments, an alkylene comprises two to five carbon atoms (e.g., C ₂ -C ₅ alkylene). In other embodiments, an alkylene comprises three to five carbon atoms (e.g., C ₃ -C ₅ alkylene). Unless stated otherwise specifically in the specification, an alkylene chain is optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR ^a , -SR ^a , -OC(O)-R ^a , -N(R ^a ) ₂ , -C(O)R ^a , -C(O)OR ^a , - C(O)N(R ^a ) ₂ , -N(R ^a )C(O)OR ^a , -OC(O)-N(R ^a ) ₂ , -N(R ^a )C(O)R ^a , -N(R ^a )S(O) _t R ^a (where t is 1 or 2), -S(O) _t OR ^a (where t is 1 or 2), -S(O) _t R ^a (where t is 1 or 2) and -S(O) _t N(R ^a ) ₂ (where t is 1 or 2) where each R ^a is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl). [0024] "Alkenylene" or "alkenylene chain" refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one carbon-carbon double bond, and having from two to twelve carbon atoms. The alkenylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. In certain embodiments, an alkenylene comprises two to eight carbon atoms (e.g., C ₂ -C ₈ alkenylene). In other embodiments, an alkenylene comprises two to five carbon atoms (e.g., C ₂ -C ₅ alkenylene). In other embodiments, an alkenylene comprises two to four carbon atoms (e.g., C ₂ -C ₄ alkenylene). In other embodiments, an alkenylene comprises two to three carbon atoms (e.g., C ₂ -C ₃ alkenylene). In other embodiments, an alkenylene comprises two carbon atoms (e.g., C ₂ alkenylene). In other embodiments, an alkenylene comprises five to eight carbon atoms (e.g., C ₅ -C ₈ alkenylene). In other embodiments, an alkenylene comprises three to five carbon atoms (e.g., C ₃ -C ₅ alkenylene). Unless stated otherwise specifically in the specification, an alkenylene chain is optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR ^a , -SR ^a , -OC(O)-R ^a , -N(R ^a ) ₂ , -C(O)R ^a , -C(O)OR ^a , -C(O)N(R ^a ) ₂ , - N(R ^a )C(O)OR ^a , -OC(O)-N(R ^a ) ₂ , -N(R ^a )C(O)R ^a , -N(R ^a )S(O) _t R ^a (where t is 1 or 2), -S(O) _t ORa (where t is 1 or 2), -S(O) _t R ^a (where t is 1 or 2) and -S(O) _t N(R ^a ) ₂ (where t is 1 or 2) where each R ^a is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl). [0025] "Alkynylene" or "alkynylene chain" refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one carbon-carbon triple bond, and having from two to twelve carbon atoms. The alkynylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. In certain embodiments, an alkynylene comprises two to eight carbon atoms (e.g., C ₂ -C ₈ alkynylene). In other embodiments, an alkynylene comprises two to five carbon atoms (e.g., C ₂ -C ₅ alkynylene). In other embodiments, an alkynylene comprises two to four carbon atoms (e.g., C ₂ -C ₄ alkynylene). In other embodiments, an alkynylene comprises two to three carbon atoms (e.g., C ₂ -C ₃ alkynylene). In other embodiments, an alkynylene comprises two carbon atoms (e.g., C ₂ alkynylene). In other embodiments, an alkynylene comprises five to eight carbon atoms (e.g., C ₅ -C ₈ alkynylene). In other embodiments, an alkynylene comprises three to five carbon atoms (e.g., C ₃ -C ₅ alkynylene). Unless stated otherwise specifically in the specification, an alkynylene chain is optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR ^a , -SR ^a , -OC(O)-R ^a , -N(R ^a ) ₂ , -C(O)R ^a , -C(O)OR ^a , - C(O)N(R ^a ) ₂ , -N(R ^a )C(O)OR ^a , -OC(O)-N(R ^a ) ₂ , -N(R ^a )C(O)R ^a , -N(R ^a )S(O) _t R ^a (where t is 1 or 2), -S(O) _t OR ^a (where t is 1 or 2), -S(O) _t R ^a (where t is 1 or 2) and -S(O) _t N(R ^a ) ₂ (where t is 1 or 2) where each R ^a is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl). [0026] "Aryl" refers to a radical derived from an aromatic monocyclic or multicyclic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. The aromatic monocyclic or multicyclic hydrocarbon ring system contains only hydrogen and carbon from five to eighteen carbon atoms, where at least one of the rings in the ring system is fully unsaturated, i.e., it contains a cyclic, delocalized (4n+2) –electron system in accordance with the Hückel theory. The ring system from which aryl groups are derived include, but are not limited to, groups such as benzene, fluorene, indane, indene, tetralin and naphthalene. Unless stated otherwise specifically in the specification, the term "aryl" or the prefix "ar-" (such as in "aralkyl") is meant to include aryl radicals optionally substituted by one or more substituents independently selected from optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, halo, cyano, nitro, -R ^b -OR ^a , -R ^b -OC(O)-R ^a , -R ^b -OC(O)-OR ^a , -R ^b - OC(O)-N(R ^a ) ₂ , -R ^b -N(R ^a ) ₂ , -R ^b -C(O)R ^a , -R ^b -C(O)OR ^a , -R ^b -C(O)N(R ^a ) ₂ , -R ^b -O-R ^c -C(O)N(R ^a ) ₂ , - R ^b -N(R ^a )C(O)OR ^a , -R ^b -N(R ^a )C(O)R ^a , -R ^b -N(R ^a )S(O) _t R ^a (where t is 1 or 2), -R ^b -S(O) _t R ^a (where t is 1 or 2), -R ^b -S(O) _t OR ^a (where t is 1 or 2) and -R ^b -S(O) _t N(R ^a ) ₂ (where t is 1 or 2), where each R ^a is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), cycloalkylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), each R ^b is independently a direct bond or a straight or branched alkylene or alkenylene chain, and R ^c is a straight or branched alkylene or alkenylene chain, and where each of the R ^a , R ^b , or R ^c substituents is unsubstituted unless otherwise indicated. [0027] "Aralkyl" refers to a radical of the formula -R ^c -aryl where R ^c is an alkylene chain as defined above, for example, methylene, ethylene, and the like. The alkylene chain part of the aralkyl radical is optionally substituted as described above for an alkylene chain. The aryl part of the aralkyl radical is optionally substituted as described above for an aryl group. [0028] "Aralkenyl" refers to a radical of the formula –R ^d -aryl where R ^d is an alkenylene chain as defined above. The aryl part of the aralkenyl radical is optionally substituted as described above for an aryl group. The alkenylene chain part of the aralkenyl radical is optionally substituted as defined above for an alkenylene group. [0029] "Aralkynyl" refers to a radical of the formula -R ^e -aryl, where R ^e is an alkynylene chain as defined above. The aryl part of the aralkynyl radical is optionally substituted as described above for an aryl group. The alkynylene chain part of the aralkynyl radical is optionally substituted as defined above for an alkynylene chain. [0030] "Aralkoxy" refers to a radical bonded through an oxygen atom of the formula -O-R ^c -aryl where R ^c is an alkylene chain as defined above, for example, methylene, ethylene, and the like. The alkylene chain part of the aralkyl radical is optionally substituted as described above for an alkylene chain. The aryl part of the aralkyl radical is optionally substituted as described above for an aryl group. [0031] "Carbocyclyl" refers to a stable non-aromatic monocyclic or polycyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms, which includes fused or bridged ring systems, having from three to fifteen carbon atoms. In certain embodiments, a carbocyclyl comprises three to ten carbon atoms. In other embodiments, a carbocyclyl comprises five to seven carbon atoms. The carbocyclyl is attached to the rest of the molecule by a single bond. Carbocyclyl is saturated (i.e., containing single C-C bonds only) or unsaturated (i.e., containing one or more double bonds or triple bonds). A fully saturated carbocyclyl radical is also referred to as "cycloalkyl." Examples of monocyclic cycloalkyls include, e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. An unsaturated carbocyclyl is also referred to as "cycloalkenyl." Examples of monocyclic cycloalkenyls include, e.g., cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Polycyclic carbocyclyl radicals include, for example, adamantyl, norbornyl (i.e., bicyclo[2.2.1]heptanyl), norbornenyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl, and the like. Unless otherwise stated specifically in the specification, the term "carbocyclyl" is meant to include carbocyclyl radicals that are optionally substituted by one or more substituents independently selected from optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, halo, oxo, thioxo, cyano, nitro, -R ^b -OR ^a , -R ^b -OC(O)-R ^a , -R ^b -OC(O)-OR ^a , -R ^b -OC(O)-N(R ^a ) ₂ , -R ^b - N(R ^a ) ₂ , -R ^b -C(O)R ^a , -R ^b -C(O)OR ^a , -R ^b -C(O)N(R ^a ) ₂ , -R ^b -O-R ^c -C(O)N(R ^a ) ₂ , -R ^b -N(R ^a )C(O)OR ^a , -R ^b -N(R ^a )C(O)R ^a , -R ^b -N(R ^a )S(O) _t R ^a (where t is 1 or 2), -R ^b -S(O) _t R ^a (where t is 1 or 2), -R ^b - S(O) _t OR ^a (where t is 1 or 2) and -R ^b -S(O) _t N(R ^a ) ₂ (where t is 1 or 2), where each R ^a is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), cycloalkylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), each R ^b is independently a direct bond or a straight or branched alkylene or alkenylene chain, and R ^c is a straight or branched alkylene or alkenylene chain, and where each of the R ^a , R ^b , or R ^c substituents is unsubstituted unless otherwise indicated. [0032] "Carbocyclylalkyl" refers to a radical of the formula –R ^c -carbocyclyl where R ^c is an alkylene chain as defined above. The alkylene chain and the carbocyclyl radical is optionally substituted as defined above. [0033] "Carbocyclylalkynyl" refers to a radical of the formula –R ^c -carbocyclyl where R ^c is an alkynylene chain as defined above. The alkynylene chain and the carbocyclyl radical is optionally substituted as defined above. [0034] "Carbocyclylalkoxy" refers to a radical bonded through an oxygen atom of the formula – O-R ^c -carbocyclyl where R ^c is an alkylene chain as defined above. The alkylene chain and the carbocyclyl radical is optionally substituted as defined above. [0035] "Halo" or "halogen" refers to bromo, chloro, fluoro or iodo substituents. [0036] "Fluoroalkyl" refers to an alkyl radical, as defined above, that is substituted by one or more fluoro radicals, as defined above, for example, trifluoromethyl, difluoromethyl, fluoromethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, and the like. In some embodiments, the alkyl part of the fluoroalkyl radical is optionally substituted as defined above for an alkyl group. [0037] "Heterocyclyl" refers to a stable 3- to 18-membered non-aromatic ring radical that comprises two to twelve carbon atoms and from one to six heteroatoms selected from nitrogen, oxygen and sulfur. Unless stated otherwise specifically in the specification, the heterocyclyl radical is a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which optionally includes fused or bridged ring systems. The heteroatoms in the heterocyclyl radical are optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. The heterocyclyl radical is partially or fully saturated. The heterocyclyl is attached to the rest of the molecule through any atom of the ring(s). Examples of such heterocyclyl radicals include, but are not limited to, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl. Unless stated otherwise specifically in the specification, the term "heterocyclyl" is meant to include heterocyclyl radicals as defined above that are optionally substituted by one or more substituents selected from optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, halo, fluoroalkyl, oxo, thioxo, cyano, nitro, - R ^b -OR ^a , -R ^b -OC(O)-R ^a , -R ^b -OC(O)-OR ^a , -R ^b -OC(O)-N(R ^a ) ₂ , -R ^b -N(R ^a ) ₂ , -R ^b -C(O)R ^a , -R ^b - C(O)OR ^a , -R ^b -C(O)N(R ^a ) ₂ , -R ^b -O-R ^c -C(O)N(R ^a ) ₂ , -R ^b -N(R ^a )C(O)OR ^a , -R ^b -N(R ^a )C(O)R ^a , -R ^b - N(R ^a )S(O) _t R ^a (where t is 1 or 2), -R ^b -S(O) _t R ^a (where t is 1 or 2), -R ^b -S(O) _t OR ^a (where t is 1 or 2) and -R ^b -S(O) _t N(R ^a ) ₂ (where t is 1 or 2), where each R ^a is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), cycloalkylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), each R ^b is independently a direct bond or a straight or branched alkylene or alkenylene chain, and R ^c is a straight or branched alkylene or alkenylene chain, and where each of the R ^a , R ^b , or R ^c substituents is unsubstituted unless otherwise indicated. [0038] "N-heterocyclyl" or “N-attached heterocyclyl” refers to a heterocyclyl radical as defined above containing at least one nitrogen and where the point of attachment of the heterocyclyl radical to the rest of the molecule is through a nitrogen atom in the heterocyclyl radical. An N-heterocyclyl radical is optionally substituted as described above for heterocyclyl radicals. Examples of such N-heterocyclyl radicals include, but are not limited to, 1-morpholinyl, 1- piperidinyl, 1-piperazinyl, 1-pyrrolidinyl, pyrazolidinyl, and imidazolidinyl. [0039] "C-heterocyclyl" or “C-attached heterocyclyl” refers to a heterocyclyl radical as defined above containing at least one heteroatom and where the point of attachment of the heterocyclyl radical to the rest of the molecule is through a carbon atom in the heterocyclyl radical. A C-heterocyclyl radical is optionally substituted as described above for heterocyclyl radicals. Examples of such C-heterocyclyl radicals include, but are not limited to, 2-morpholinyl, 2- or 3- or 4-piperidinyl, 2-piperazinyl, 2- or 3-pyrrolidinyl, and the like. [0040] "Heterocyclylalkyl" refers to a radical of the formula –R ^c -heterocyclyl where R ^c is an alkylene chain as defined above. If the heterocyclyl is a nitrogen-containing heterocyclyl, the heterocyclyl is optionally attached to the alkyl radical at the nitrogen atom. The alkylene chain of the heterocyclylalkyl radical is optionally substituted as defined above for an alkylene chain. The heterocyclyl part of the heterocyclylalkyl radical is optionally substituted as defined above for a heterocyclyl group. [0041] "Heterocyclylalkoxy" refers to a radical bonded through an oxygen atom of the formula –O-R ^c -heterocyclyl where R ^c is an alkylene chain as defined above. If the heterocyclyl is a nitrogen-containing heterocyclyl, the heterocyclyl is optionally attached to the alkyl radical at the nitrogen atom. The alkylene chain of the heterocyclylalkoxy radical is optionally substituted as defined above for an alkylene chain. The heterocyclyl part of the heterocyclylalkoxy radical is optionally substituted as defined above for a heterocyclyl group. [0042] "Heteroaryl" refers to a radical derived from a 3- to 18-membered aromatic ring radical that comprises two to seventeen carbon atoms and from one to six heteroatoms selected from nitrogen, oxygen, and sulfur. As used herein, the heteroaryl radical is a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, wherein at least one of the rings in the ring system is fully unsaturated, i.e., it contains a cyclic, delocalized (4n+2) –electron system in accordance with the Hückel theory. Heteroaryl includes fused or bridged ring systems. The heteroatom(s) in the heteroaryl radical is optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. The heteroaryl is attached to the rest of the molecule through any atom of the ring(s). Examples of heteroaryls include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzindolyl, 1,3-benzodioxolyl, benzofuranyl, benzooxazolyl, benzo[d]thiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, benzo[b][1,4]oxazinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl), benzothieno[3,2-d]pyrimidinyl, benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, cyclopenta[d]pyrimidinyl, 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, 5,6-dihydrobenzo[h]quinazolinyl, 5,6-dihydrobenzo[h]cinnolinyl, 6,7-dihydro-5H- benzo[6,7]cyclohepta[1,2-c]pyridazinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furanonyl, furo[3,2-c]pyridinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyrimidinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyridazinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyridinyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, 5,8-methano-5,6,7,8-tetrahydroquinazolinyl, naphthyridinyl, 1,6-naphthyridinonyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 5,6,6a,7,8,9,10,10a-octahydrobenzo[h]quinazolinyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyrazolo[3,4-d]pyrimidinyl, pyridinyl, pyrido[3,2-d]pyrimidinyl, pyrido[3,4-d]pyrimidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, 5,6,7,8-tetrahydroquinazolinyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, 6,7,8,9-tetrahydro-5H-cyclohepta[4,5]thieno[2,3-d]pyrimidiny l, 5,6,7,8-tetrahydropyrido[4,5-c]pyridazinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, thieno[2,3-c]pridinyl, and thiophenyl (i.e. thienyl). Unless stated otherwise specifically in the specification, the term "heteroaryl" is meant to include heteroaryl radicals as defined above which are optionally substituted by one or more substituents selected from optionally substituted alkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, optionally substituted alkenyl, optionally substituted alkynyl, halo, optionally substituted fluoroalkyl, optionally substituted haloalkenyl, optionally substituted haloalkynyl, oxo, thioxo, cyano, nitro, -R ^b -OR ^a , -R ^b -OC(O)-R ^a , -R ^b -OC(O)-OR ^a , - R ^b -OC(O)-N(R ^a ) ₂ , -R ^b -N(R ^a ) ₂ , -R ^b -C(O)R ^a , -R ^b -C(O)OR ^a , -R ^b -C(O)N(R ^a ) ₂ , -R ^b -O-R ^c - C(O)N(R ^a ) ₂ , -R ^b -N(R ^a )C(O)OR ^a , -R ^b -N(R ^a )C(O)R ^a , -R ^b -N(R ^a )S(O)tR ^a (where t is 1 or 2), -R ^b - S(O) _t R ^a (where t is 1 or 2), -R ^b -S(O) _t OR ^a (where t is 1 or 2) and -R ^b -S(O) _t N(R ^a ) ₂ (where t is 1 or 2), where each R ^a is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), cycloalkylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), each R ^b is independently a direct bond or a straight or branched alkylene or alkenylene chain, and R ^c is a straight or branched alkylene or alkenylene chain, and where each of the R ^a , R ^b , or R ^c substituents is unsubstituted unless otherwise indicated. [0043] "N-heteroaryl" refers to a heteroaryl radical as defined above containing at least one nitrogen and where the point of attachment of the heteroaryl radical to the rest of the molecule is through a nitrogen atom in the heteroaryl radical. An N-heteroaryl radical is optionally substituted as described above for heteroaryl radicals. [0044] "C-heteroaryl" refers to a heteroaryl radical as defined above and where the point of attachment of the heteroaryl radical to the rest of the molecule is through a carbon atom in the heteroaryl radical. A C-heteroaryl radical is optionally substituted as described above for heteroaryl radicals. [0045] "Heteroarylalkyl" refers to a radical of the formula –R ^c -heteroaryl, where R ^c is an alkylene chain as defined above. If the heteroaryl is a nitrogen-containing heteroaryl, the heteroaryl is optionally attached to the alkyl radical at the nitrogen atom. The alkylene chain of the heteroarylalkyl radical is optionally substituted as defined above for an alkylene chain. The heteroaryl part of the heteroarylalkyl radical is optionally substituted as defined above for a heteroaryl group. [0046] "Heteroarylalkoxy" refers to a radical bonded through an oxygen atom of the formula – O-R ^c -heteroaryl, where R ^c is an alkylene chain as defined above. If the heteroaryl is a nitrogen-containing heteroaryl, the heteroaryl is optionally attached to the alkyl radical at the nitrogen atom. The alkylene chain of the heteroarylalkoxy radical is optionally substituted as defined above for an alkylene chain. The heteroaryl part of the heteroarylalkoxy radical is optionally substituted as defined above for a heteroaryl group. [0047] The compounds disclosed herein, in some embodiments, contain one or more asymmetric centers and thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that are defined, in terms of absolute stereochemistry, as (R)- or (S)-. Unless stated otherwise, it is intended that all stereoisomeric forms of the compounds disclosed herein are contemplated by this disclosure. When the compounds described herein contain alkene double bonds, and unless specified otherwise, it is intended that this disclosure includes both E and Z geometric isomers (e.g., cis or trans.) Likewise, all possible isomers, as well as their racemic and optically pure forms, and all tautomeric forms are also intended to be included. The term “geometric isomer” refers to E or Z geometric isomers (e.g., cis or trans) of an alkene double bond. The term “positional isomer” refers to structural isomers around a central ring, such as ortho-, meta-, and para- isomers around a benzene ring. [0048] As used herein, “carboxylic acid bioisostere” refers to a functional group or moiety that exhibits similar physical, biological and/or chemical properties as a carboxylic acid moiety. Examples of carboxylic acid bioisosteres include, but are not limited to, and the like. [0049] A "tautomer" refers to a molecule wherein a proton shift from one atom of a molecule to another atom of the same molecule is possible. The compounds presented herein, in certain embodiments, exist as tautomers. In circumstances where tautomerization is possible, a chemical equilibrium of the tautomers will exist. The exact ratio of the tautomers depends on several factors, including physical state, temperature, solvent, and pH. Some examples of tautomeric equilibrium include:

[0050] The compounds disclosed herein, in some embodiments, are used in different enriched isotopic forms, e.g., enriched in the content of ² H, ³ H, ¹¹ C, ¹³ C and/or ¹⁴ C. In one particular embodiment, the compound is deuterated in at least one position. Such deuterated forms can be made by the procedure described in U.S. Patent Nos.5,846,514 and 6,334,997. As described in U.S. Patent Nos.5,846,514 and 6,334,997, deuteration can improve the metabolic stability and or efficacy, thus increasing the duration of action of drugs. [0051] Unless otherwise stated, structures depicted herein are intended to include compounds which differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures except for the replacement of a hydrogen by a deuterium or tritium, or the replacement of a carbon by ¹³ C- or ¹⁴ C-enriched carbon are within the scope of the present disclosure. [0052] The compounds of the present disclosure optionally contain unnatural proportions of atomic isotopes at one or more atoms that constitute such compounds. For example, the compounds may be labeled with isotopes, such as for example, deuterium ( ² H), tritium ( ³ H), iodine-125 ( ¹²⁵ I) or carbon-14 ( ¹⁴ C). Isotopic substitution with ² H, ¹¹ C, ¹³ C, ¹⁴ C, ¹⁵ C, ¹² N, ¹³ N, ¹⁵ N, ¹⁶ N, ¹⁶ O, ¹⁷ O, ¹⁴ F, ¹⁵ F, ¹⁶ F, ¹⁷ F, ¹⁸ F, ³³ S, ³⁴ S, ³⁵ S, ³⁶ S, ³⁵ Cl, ³⁷ Cl, ⁷⁹ Br, ⁸¹ Br, ¹²⁵ I are all contemplated. In some embodiments, isotopic substitution with ¹⁸ F is contemplated. All isotopic variations of the compounds of the present invention, whether radioactive or not, are encompassed within the scope of the present invention. [0053] In certain embodiments, the compounds disclosed herein have some or all of the ¹ H atoms replaced with ² H atoms. The methods of synthesis for deuterium-containing compounds are known in the art and include, by way of non-limiting example only, the following synthetic methods. [0054] Deuterium substituted compounds are synthesized using various methods such as described in: Dean, Dennis C.; Editor. Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [Curr., Pharm. Des., 2000; 6(10)] 2000, 110 pp; George W.; Varma, Rajender S. The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21; and Evans, E. Anthony. Synthesis of radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32. [0055] Deuterated starting materials are readily available and are subjected to the synthetic methods described herein to provide for the synthesis of deuterium-containing compounds. Large numbers of deuterium-containing reagents and building blocks are available commercially from chemical vendors, such as Aldrich Chemical Co. [0056] Deuterium-transfer reagents suitable for use in nucleophilic substitution reactions, such as iodomethane-d3 (CD ₃ I), are readily available and may be employed to transfer a deuterium- substituted carbon atom under nucleophilic substitution reaction conditions to the reaction substrate. The use of CD ₃ I is illustrated, by way of example only, in the reaction schemes below. [0057] Deuterium-transfer reagents, such as lithium aluminum deuteride (LiAlD4), are employed to transfer deuterium under reducing conditions to the reaction substrate. The use of LiAlD ₄ is illustrated, by way of example only, in the reaction schemes below. [0058] Deuterium gas and palladium catalyst are employed to reduce unsaturated carbon-carbon linkages and to perform a reductive substitution of aryl carbon-halogen bonds as illustrated, by way of example only, in the reaction schemes below. [0059] In one embodiment, the compounds disclosed herein contain one deuterium atom. In another embodiment, the compounds disclosed herein contain two deuterium atoms. In another embodiment, the compounds disclosed herein contain three deuterium atoms. In another embodiment, the compounds disclosed herein contain four deuterium atoms. In another embodiment, the compounds disclosed herein contain five deuterium atoms. In another embodiment, the compounds disclosed herein contain six deuterium atoms. In another embodiment, the compounds disclosed herein contain more than six deuterium atoms. In another embodiment, the compound disclosed herein is fully substituted with deuterium atoms and contains no non-exchangeable ¹ H hydrogen atoms. In one embodiment, the level of deuterium incorporation is determined by synthetic methods in which a deuterated synthetic building block is used as a starting material. [0060] "Pharmaceutically acceptable salt" includes both acid and base addition salts. A pharmaceutically acceptable salt of any one of the AKT1 inhibitory compounds described herein is intended to encompass any and all pharmaceutically suitable salt forms. Preferred pharmaceutically acceptable salts of the compounds described herein are pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts. [0061] "Pharmaceutically acceptable acid addition salt" refers to those salts which retain the biological effectiveness and properties of the free bases, which are not biologically or otherwise undesirable, and which are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, hydroiodic acid, hydrofluoric acid, phosphorous acid, and the like. Also included are salts that are formed with organic acids such as aliphatic mono- and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxy alkanoic acids, alkanedioic acids, aromatic acids, aliphatic and. aromatic sulfonic acids, etc. and include, for example, acetic acid, trifluoroacetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. Exemplary salts thus include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, nitrates, phosphates, monohydrogenphosphates, dihydrogenphosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, trifluoroacetates, propionates, caprylates, isobutyrates, oxalates, malonates, succinate suberates, sebacates, fumarates, maleates, mandelates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, phthalates, benzenesulfonates, toluenesulfonates, phenylacetates, citrates, lactates, malates, tartrates, methanesulfonates, and the like. Also contemplated are salts of amino acids, such as arginates, gluconates, and galacturonates (see, for example, Berge S.M. etal., "Pharmaceutical Salts," Journal of Pharmaceutical Science, 66:1- 19 (1997)). Acid addition salts of basic compounds are, in some embodiments, prepared by contacting the free base forms with a sufficient amount of the desired acid to produce the salt according to methods and techniques with which a skilled artisan is familiar.

[0062] "Pharmaceutically acceptable base addition salt" refers to those salts that retain the biological effectiveness and properties of the free acids, which are not biologically or otherwise undesirable. These salts are prepared from addition of an inorganic base or an organic base to the free acid. Pharmaceutically acceptable base addition salts are, in some embodiments, formed with metals or amines, such as alkali and alkaline earth metals or organic amines. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts and the like. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, for example, isopropyl amine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, diethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, N,N- dibenzylethylenediamine, chloroprocaine, hydrabamine, choline, betaine, ethylenediamine, ethylenedianiline, N-methylglucamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, polyamine resins and the like. See Berge et al., supra. [0063] "Pharmaceutically acceptable solvate" refers to a composition of matter that is the solvent addition form. In some embodiments, solvates contain either stoichiometric or non- stoichiometric amounts of a solvent, and are formed during the process of making with pharmaceutically acceptable solvents such as water, ethanol, and the like. Hydrates are formed when the solvent is water, or alcoholates are formed when the solvent is alcohol. Solvates of compounds described herein are conveniently prepared or formed during the processes described herein. The compounds provided herein exist in either unsolvated or solvated forms.

[0064] The term “subject” or “patient” encompasses mammals. Examples of mammals include, but are not limited to, any member of the mammalian class: humans, non-human primates such as chimpanzees, and other apes and monkey species; farm animals such as cattle, horses, sheep, goats, swine; domestic animals such as rabbits, dogs, and cats; laboratory animals including rodents, such as rats, mice and guinea pigs, and the like. In one aspect, the mammal is a human. [0065] As used herein, “treatment” or “treating,” or “palliating” or “ameliorating” are used interchangeably. These terms refer to an approach for obtaining beneficial or desired results including but not limited to therapeutic benefit and/or a prophylactic benefit. By “therapeutic benefit” is meant eradication or amelioration of the underlying disorder being treated. Also, a therapeutic benefit is achieved with the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder such that an improvement is observed in the patient, notwithstanding that the patient is still afflicted with the underlying disorder. For prophylactic benefit, the compositions are, in some embodiments, administered to a patient at risk of developing a particular disease, or to a patient reporting one or more of the physiological symptoms of a disease, even though a diagnosis of this disease has not been made. AKT1 Protein and Function [0066] AKT, also known as protein kinase B (PKB), is a serine/threonine protein kinase with three isoforms, AKT1, AKT2, and AKT3. While the isoforms are encoded by different genes, they are highly homologous at the protein level and share a conserved domain structure comprising an N-terminal pleckstrin homology (PH) domain, a kinase domain, and a C-terminal regulatory domain comprising a hydrophobic moiety, which includes the regulatory serine residue (Nitulescu, G. M. et al., Int J Oncol., 2018; 53(6): 2319-2331). [0067] AKT proteins play a crucial role in major cellular functions including cell cycle progression, cell size, regulation of glucose metabolism, transcription, protein synthesis, genome stability, and neovascularization. AKT proteins can block apoptosis by inactivation of pro- apoptotic proteins, and mediate cellular growth factors, promoting cell survival. AKT is a major downstream effector of nuclear factor-kappaB (NfκB), which may link AKT signaling to the nucleus of a cell. [0068] AKT1 is ubiquitously expressed, whereas AKT2 is primarily expressed in insulin- responsive tissues, and AKT3 is primarily expressed in brain and testes. A shared phosphorylation site of AKT in the catalytic domain corresponds to a threonine residue; specifically, Thr308 in AKT1, Thr309 in AKT2, and Thr305 in AKT3. A shared phosphorylation site in the C-terminus of the protein cis a serine residue; specifically, Ser473 in AKT1, Ser474 in AKT2, and Ser472 in AKT3. [0069] AKT is a key downstream mediator of the phosphoinositide-3-kinase (PI3K) signaling patway, PI3Ks are activated by different compounds. For example, PI3Kα, PI3Kβ, and PI3Kδ, are activated by extracellular ligands binding to a transmembrane glycoprotein with enzymatic activity, receptor tyrosine kinases (RTKs). In contrast, PI3Kγ is activated by G-protein- compound receptors (GPCRs) and by RAS family of GTPases.

[0070] The AKT cascade can be activated by RTKs and G-protein-compound receptors (GPCRs), along with other signals including integrins, B cell receptors, T cell receptors, and cytokine receptors.

AKT1 Mechanism

[0071] AKT is activated by a second phosphorylation at the regulatory serine residue, Ser473. Known phosphorylating agents of AKT at Ser473 include, but are not limited to PDK-1, integrin-linked kinase (ILK), members of the PI3K-related kinase (PIKK) family, and mammalian target of rapamycin (mTOR) (Nitulescu, G. M. et al., Int J Oncol., 2018; 53(6): 2319-2331).

[0072] mTOR is a key component in the AKT signaling pathway, which is a downstream member of AKT and important regulator for cell metabolism and growth. mTOR is also an activator which can directly phosphorylate AKT’s regulatory serine residue, Ser473. mTOR forms a complex with rapamycin-insensitive companion of mTOR (RICTOR) (and other proteins) to form mTOR complex 2 (mTORC2), which can directly phosphorylate AKT Ser473. AKT can affect cell survival and growth because it can influence the tuberous sclerosis complex (TSC) 1/2 along the mTORC signaling pathway and inhibit pro-apoptotic proteins or signals. [0073] AKT is known as a survival kinase and mediates cell survival and proliferation by inhibiting pathways including, but not limited to Bcl2 and MDM2, which promotes apoptosis. Studies have shown that the AKT signaling cascade have frequent malfunctions in various cancers, and may be associated with tumor aggressiveness (Nitulescu, G. M. et al., Int J Oncol., 2018; 53(6): 2319-2331). Malfunctions of AKT typically lead to enhanced proliferation, growth, survival, and resistance to apoptosis (Alwhaibi, A. et al., Pharmacol Res., 2019, 145: 104270). Malfunction and mis-regulation of AKT may lead to cancers such as but not limited to breast cancer, gastric carcinoma, glioblastoma, gliosarcomas, head and neck squamous cell carcinoma, ovarian cancer, pancreatic cancer, and prostate cancer.

[0074] Additionally, AKT1 has been found to be involved in invasion and migration of cancerous cells (Alwhaibi, A. et al., Pharmacol Res., 2019, 145: 104270). Researchers found that silencing the AKT1 isoform can abrogate specific types of cancer cell migration. However, there have been other studies which have demonstrated that activated AKT1 resulted in less metastatic propensity for lung metastatic lesion cells and breast cancer cells. AKT1 has also been identified as a key protein involved in angiogenesis, lung cancer, and tumorigenesis. [0075] Furthermore, overexpression of AKT has been correlated to resistance to chemotherapeutic agents such as cisplatin, methotrexate, and paclitaxel. Thus, there remains a need to find AKT inhibitors given its role in cell survival and cancer proliferation. [0076] Recently, it has been found that the AKT1 gene mutation E17K can affect cell growth, proliferation, survival, and migration of breast cancer cells, colorectal cancer cells, and ovarian cancer cells (Chen, Y. et al., Front Cell Dev Biol., 2020; 8: 573599). These mutations in the PH structural domain increase the binding of AKT1 to Phosphatidylinositol-3,4,5-triphosphate (PIP3) lipid ligand, which accelerates transfer of AKT from the cytoplasm to the cell membrane through formation of hydrogen bonds. Transfer of AKT into the cell membrane allows it to be further phosphorylated. Once fully activated, AKT can return to the cytoplasm, or go to the nucleus or other intracellular sites, and phosphorylate other substrate proteins to regulate cell function. [0077] The E17K mutation enhances migration of breast cancer cells, and also enhances resistance to chemotherapeutic drugs. However, the E17K mutation can also selectively destroy chemo-resistant tumor-promoting AKT1 quiescent cancer cells, suggesting that the AKT1(E17K) mutation is crucial in the oncogenic/anti-tumor mechanism. [0078] A major pathway that activates PI3K-AKT signaling pathway is somatic cell mutations, with the E17K mutation being the highest frequency of AKT1 mutations. It is nearly exclusively present in AKT1. The AKT1(E17K) is a recurrent somatic cell mutation predominantly in breast cancer, ovarian cancer, meningioma, and Proteus syndrome. [0079] AKT1(E17K) mutations mediate the PI3K-AKT signaling cascade by expanding PIP lipid specificity, which causes conformational changes. This also enhances subcellular localization to accelerate localization of the PH structural domain to the plasma membrane. The E17K mutation increases PIP3 binding specificity by 7-fold and phosphatidylinositol-(4,5)- bisphosphate (PIP2) by 100-fold. [0080] The AKT1(E17K) mutation also causes rapid conformational changes in the AKT1 PH structural domain. The conformational changes to this domain result in a 4.5-fold increase in its membrane localization, which can result in excessive phosphorylation. The AKT1(E17K) mutation can also result in enhanced subcellular localization by increasing the transient expression. [0081] Given the conformational and signaling effects of the AKT1(E17K) mutation, this target may be useful for targeted treatment of cancers. Prior Art AKT1 Inhibitors [0082] Most AKT inhibitors targeting the ATP binding site are non-selective against the three isoforms, as well as having poor to no selectivity against other structurally similar kinases. Thus, there remains a need to develop new and novel AKT inhibitors. These ATP targeting inhibitors are classified as aminofurazans, azepane derivatives, isoquinoline-5-sulfonamides, phenylpyrazole derivatives, thiophene carboxamide derivatives, and thiazole carboxamide derivatives. [0083] There are also ATP non-competitive AKT inhibitors which are allosteric modulators which has greater specificity than the ATP targeting inhibitors. Many of these allosteric modulator inhibitors are classified as purine derivatives, thiourea derivatives, alkylphospholipids, sulfonamides, 2,3-diphenylquinoxaline analogs, and indole-3-carbinol derivatives. Novel AKT1 Inhibitory Compounds [0084] In one aspect, provided herein is an AKT1 inhibitory compound. [0085] One embodiment provides a compound having the structure of Formula (I), or a pharmaceutically acceptable salt or solvate thereof: wherein: Z ¹ is N, C-H, or C-R ³ ; Z ² is N, C-H, or C-R ⁴ ; Z ³ is N, C-OH, or C-R ⁹ ; Ar is selected from: X ¹ is N or C-R ⁷ ; X ² is N or C-R ⁷ ; X ³ is N or C-R ⁷ ; X ⁴ is N or C-R ⁷ ; Y is O, S, or N-R ⁹ ; R ¹ is selected from hydrogen, optionally substituted C1-C6 alkyl, optionally substituted aryl, or optionally substituted heteroaryl; R ² is selected from hydrogen, halogen, -OH, -CN, -N(R ⁹ ) ₂ , -OR ⁹ , -SR ⁹ , -SO ₂ R ⁹ , -CO ₂ R ⁹ , -CON(R ⁹ ) ₂ , -SR ⁹ , -S(O)R ⁹ , - S(O) ₂ R ⁹ , optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkoxy, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C3-C7 carbocyclyl, optionally substituted 4-membered to 6-membered heterocyclyl, optionally substituted aryl, aryl substituted with an optionally substituted 4- membered to 6-membered heterocyclyl, optionally substituted heteroaryl or heteroaryl substituted with an optionally substituted 3-membered to 6-membered carbocyclyl; R ³ is selected from optionally substituted C1-C6 alkyl, or optionally substituted aryl; R ⁴ is selected from halogen, -CN, optionally substituted C1-C6 alkyl, or optionally substituted aryl; R ⁵ and R ⁶ are each independently hydrogen, deuterium, halogen, -OH, or optionally substituted C1-C6 alkyl; or R ⁵ and R ⁶ together form an oxo; or R ⁵ and R ⁶ join together to form a carbocycle or heterocycle; each R ⁷ is independently selected from hydrogen, deuterium, halogen, -OH, -SH, optionally substituted C1-C6 alkoxy, -S-(optionally substituted C1-C6 alkyl), -CN, optionally substituted C1-C6 alkyl, and optionally substituted aryl; L is selected from -N(R ⁸ )-, or a divalent radical selected from:

; wherein the asterisk (*) indicates the bond to the -CO-Ar group; R ⁸ is hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C7 cycloalkyl, or optionally substituted heterocyclyl; each R ⁹ is hydrogen, or optionally substituted C1-C6 alkyl; R ¹⁰ is optionally substituted C1-C6 alkyl; m is 0, 1, or 2; n is 1, 2, or 3; and q is 0 or 1. [0086] One embodiment provides a compound having the structure of Formula (Ia), or a pharmaceutically acceptable salt or solvate thereof: wherein: Z ¹ is N, C-H, or C-R ³ ; Z ² is N, C-H, or C-R ⁴ ; Z ³ is N, C-H; Ar is selected from: X ¹ is N or C-R ⁷ ; X ² is N or C-R ⁷ ; X ³ is N or C-R ⁷ ; X ⁴ is N or C-R ⁷ ; Y is O, S, or N-R ⁹ ; R ¹ is selected from hydrogen, optionally substituted C1-C6 alkyl, optionally substituted aryl, or optionally substituted heteroaryl; R ² is selected from hydrogen, halogen, -OH, -CN, -N(R ⁹ ) ₂ , -OR ⁹ , -SR ⁹ , -SO ₂ R ⁹ , -CO ₂ R ⁹ , -CON(R ⁹ ) ₂ , optionally substituted C1-C6 alkyl, optionally substituted C3-C7 carbocyclyl, optionally substituted 4-membered to 6-membered heterocyclyl optionally substituted aryl, or optionally substituted heteroaryl; R ³ is selected from optionally substituted C1-C6 alkyl, or optionally substituted aryl; R ⁴ is selected from halogen, -CN, optionally substituted C1-C6 alkyl, or optionally substituted aryl; R ⁵ and R ⁶ are each independently hydrogen, deuterium, halogen, -OH, or optionally substituted C1-C6 alkyl; or R ⁵ and R ⁶ together form an oxo; or R ⁵ and R ⁶ join together to form a carbocycle or heterocycle; each R ⁷ is independently selected from hydrogen, deuterium, halogen, -OH, -SH, optionally substituted C1-C6 alkoxy, -S-(optionally substituted C1-C6 alkyl), -CN, optionally substituted C1-C6 alkyl, and optionally substituted aryl; L is selected from -N(R ⁸ )-, or a divalent radical selected from:

; wherein the asterisk (*) indicates the bond to the -CO-Ar group; R ⁸ is hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C7 cycloalkyl, or optionally substituted heterocyclyl; each R ⁹ is hydrogen, or optionally substituted C1-C6 alkyl; R ¹⁰ is optionally substituted C1-C6 alkyl; m is 0, 1, or 2; n is 1, 2, or 3; and q is 0 or 1. [0087] One embodiment provides a compound having the structure of Formula (Ib), or a pharmaceutically acceptable salt or solvate thereof: wherein: Z ¹ is N, C-H, or C-R ³ ; Z ² is N, C-H, or C-R ⁴ ; Ar is selected from: X ¹ is N or C-R ⁷ ; X ² is N or C-R ⁷ ; X ³ is N or C-R ⁷ ; X ⁴ is N or C-R ⁷ ; Y is O, S, or N-R ⁹ ; R ¹ is selected from hydrogen, optionally substituted C1-C6 alkyl, optionally substituted aryl, or optionally substituted heteroaryl; R ² is selected from hydrogen, optionally substituted C1-C6 alkyl, optionally substituted aryl, or optionally substituted heteroaryl; R ³ is selected from optionally substituted C1-C6 alkyl, or optionally substituted aryl; R ⁴ is selected from optionally substituted C1-C6 alkyl, or optionally substituted aryl; R ⁵ and R ⁶ are each independently hydrogen, deuterium, halogen, -OH, or optionally substituted C1-C6 alkyl; or R ⁵ and R ⁶ together form an oxo; or R ⁵ and R ⁶ join together to form a carbocycle or heterocycle; each R ⁷ is independently selected from hydrogen, deuterium, halogen, -OH, -SH, optionally substituted C1-C6 alkoxy, -S-(optionally substituted C1-C6 alkyl), -CN, optionally substituted C1-C6 alkyl, and optionally substituted aryl; L is selected from -N(R ⁸ )-, or a divalent radical selected from:

wherein the asterisk (*) indicates the bond to the -CO-Ar group; R ⁸ is hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C7 cycloalkyl, or optionally substituted heterocyclyl; R ⁹ is hydrogen, or optionally substituted C1-C6 alkyl; m is 0, 1, or 2; n is 1, 2, or 3; and q is 0 or 1. [0088] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein Z ¹ is N. [0089] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein Z ² is C-H. [0090] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein Z ² is C-R ⁴ . [0091] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein R ¹ is optionally substituted heteroaryl. Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted heteroaryl is an optionally substituted pyridyl. [0092] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein R ² is optionally substituted aryl. Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted aryl is an optionally substituted phenyl. [0093] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein R ² is optionally substituted heteroaryl. Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted heteroaryl is an optionally substituted pyridyl. [0094] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein R ⁵ is hydrogen. Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein R ⁶ is hydrogen. Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein R ⁵ and R ⁶ together form an oxo. Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein R ⁶ is optionally substituted C1-C6 alkyl. Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein R ⁵ and R ⁶ join together to form a carbocycle or heterocycle. [0095] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein L is -N(R ⁸ )-. [0096] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein L is selected from a divalent radical selected from:

[0097] Another embodiment provides the compound of Formula (I), (la) or (lb), or pharmaceutically acceptable salt or solvate thereof, wherein L is selected from: . [0098] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein L is selected from: . [0099] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein L is selected from: . [00100] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein L is selected from: . [00101] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein L is selected from: . [00102] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein L is selected from: . [00103] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein L is selected from: . [00104] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein R ⁸ is hydrogen. Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein R ⁸ is optionally substituted C1-C6 alkyl. [00105] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein q is 0. [00106] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein q is 1. [00107] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein Ar is . [00108] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein Ar is . [00109] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein Ar is . [00110] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein X ¹ , X ² , and X ³ are C-H. Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein X ¹ is N; and X ² , and X ³ are C-H. Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein X ² is N; and X ¹ , and X ³ are C-H. Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein X ³ is N; and X ¹ , and X ² are C-H. Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein X ¹ is N; and X ² , and X ³ are C-H. [00111] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein Y is O. Another embodiment provides the compound of Formula (I), (Ia) or (Ib),or pharmaceutically acceptable salt or solvate thereof, wherein Y is S. Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein Y is N-R ⁹ . Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein R ⁹ is hydrogen. Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein R ⁹ is optionally substituted C1-C6 alkyl. [00112] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein Ar is . Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein X ¹ is N. Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein X ² is N. Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein X ³ is N. Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein X ⁴ is N. Another embodiment provides the compound of Formula (I), (Ia) or (Ib),or pharmaceutically acceptable salt or solvate thereof, wherein X ¹ is C-H. Another embodiment provides the compound of Formula (I), (Ia) or (Ib),or pharmaceutically acceptable salt or solvate thereof, wherein X ² is C-H. Another embodiment provides the compound of Formula (I), (Ia) or (Ib),or pharmaceutically acceptable salt or solvate thereof, wherein X ³ is C-H. Another embodiment provides the compound of Formula (I), (Ia) or (Ib),or pharmaceutically acceptable salt or solvate thereof, wherein X ⁴ is C-H. [00113] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein Ar is . Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein X ¹ is N. Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein X ² is N. Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein X ³ is N. Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein X ⁴ is N. Another embodiment provides the compound of Formula (I), (Ia) or (Ib),or pharmaceutically acceptable salt or solvate thereof, wherein X ¹ is C-H. Another embodiment provides the compound of Formula (I), (Ia) or (Ib),or pharmaceutically acceptable salt or solvate thereof, wherein X ² is C-H. Another embodiment provides the compound of Formula (I), (Ia) or (Ib),or pharmaceutically acceptable salt or solvate thereof, wherein X ³ is C-H. Another embodiment provides the compound of Formula (I), (Ia) or (Ib),or pharmaceutically acceptable salt or solvate thereof, wherein X ⁴ is C-H. [00114] Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein R ³ is optionally substituted C1-C6 alkyl. Another embodiment provides the compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salt or solvate thereof, wherein R ³ is optionally substituted aryl. Another embodiment provides the compound of Formula (I), (Ia) or (Ib),or pharmaceutically acceptable salt or solvate thereof, wherein R ⁴ is optionally substituted C1-C6 alkyl. Another embodiment provides the compound of Formula (I), (Ia) or (Ib),or pharmaceutically acceptable salt or solvate thereof, wherein R ⁴ is optionally substituted aryl. [00115] One embodiment provides an AKT1 inhibitory compound, or a pharmaceutically acceptable salt or solvate thereof, having a structure presented in Table 1. Table 1

[00116] Another embodiment provides an AKT1 inhibitory compound, or a pharmaceutically acceptable salt or solvate thereof, having a structure presented in Table 2.

Table 2

153

Preparation of Compounds [00117] The compounds used in the synthetic chemistry reactions described herein are made according to organic synthesis techniques known to those skilled in this art, starting from commercially available chemicals and/or from compounds described in the chemical literature. "Commercially available chemicals" are obtained from standard commercial sources including Acros Organics (Pittsburgh, PA), Aldrich Chemical (Milwaukee, WI, including Sigma Chemical and Fluka), Apin Chemicals Ltd. (Milton Park, UK), Avocado Research (Lancashire, U.K.), BDH Inc. (Toronto, Canada), Bionet (Cornwall, U.K.), Chemservice Inc. (West Chester, PA), Crescent Chemical Co. (Hauppauge, NY), Eastman Organic Chemicals, Eastman Kodak Company (Rochester, NY), Fisher Scientific Co. (Pittsburgh, PA), Fisons Chemicals (Leicestershire, UK), Frontier Scientific (Logan, UT), ICN Biomedicals, Inc. (Costa Mesa, CA), Key Organics (Cornwall, U.K.), Lancaster Synthesis (Windham, NH), Maybridge Chemical Co. Ltd. (Cornwall, U.K.), Parish Chemical Co. (Orem, UT), Pfaltz & Bauer, Inc. (Waterbury, CN), Polyorganix (Houston, TX), Pierce Chemical Co. (Rockford, IL), Riedel de Haen AG (Hanover, Germany), Spectrum Quality Product, Inc. (New Brunswick, NJ), TCI America (Portland, OR), Trans World Chemicals, Inc. (Rockville, MD), and Wako Chemicals USA, Inc. (Richmond, VA). [00118] Suitable reference books and treatise that detail the synthesis of reactants useful in the preparation of compounds described herein, or provide references to articles that describe the preparation, include for example, "Synthetic Organic Chemistry", John Wiley & Sons, Inc., New York; S. R. Sandler et al., "Organic Functional Group Preparations," 2nd Ed., Academic Press, New York, 1983; H. O. House, "Modern Synthetic Reactions", 2nd Ed., W. A. Benjamin, Inc. Menlo Park, Calif.1972; T. L. Gilchrist, "Heterocyclic Chemistry", 2nd Ed., John Wiley & Sons, New York, 1992; J. March, "Advanced Organic Chemistry: Reactions, Mechanisms and Structure", 4th Ed., Wiley-Interscience, New York, 1992. Additional suitable reference books and treatise that detail the synthesis of reactants useful in the preparation of compounds described herein, or provide references to articles that describe the preparation, include for example, Fuhrhop, J. and Penzlin G. "Organic Synthesis: Concepts, Methods, Starting Materials", Second, Revised and Enlarged Edition (1994) John Wiley & Sons ISBN: 3-527- 29074-5; Hoffman, R.V. "Organic Chemistry, An Intermediate Text" (1996) Oxford University Press, ISBN 0-19-509618-5; Larock, R. C. "Comprehensive Organic Transformations: A Guide to Functional Group Preparations" 2nd Edition (1999) Wiley-VCH, ISBN: 0-471-19031-4; March, J. "Advanced Organic Chemistry: Reactions, Mechanisms, and Structure" 4th Edition (1992) John Wiley & Sons, ISBN: 0-471-60180-2; Otera, J. (editor) "Modern Carbonyl Chemistry" (2000) Wiley-VCH, ISBN: 3-527-29871-1; Patai, S. "Patai's 1992 Guide to the Chemistry of Functional Groups" (1992) Interscience ISBN: 0-471-93022-9; Solomons, T. W. G. "Organic Chemistry" 7th Edition (2000) John Wiley & Sons, ISBN: 0-471-19095-0; Stowell, J.C., "Intermediate Organic Chemistry" 2nd Edition (1993) Wiley-Interscience, ISBN: 0-471- 57456-2; "Industrial Organic Chemicals: Starting Materials and Intermediates: An Ullmann's Encyclopedia" (1999) John Wiley & Sons, ISBN: 3-527-29645-X, in 8 volumes; "Organic Reactions" (1942-2000) John Wiley & Sons, in over 55 volumes; and "Chemistry of Functional Groups" John Wiley & Sons, in 73 volumes. [00119] Specific and analogous reactants are optionally identified through the indices of known chemicals prepared by the Chemical Abstract Service of the American Chemical Society, which are available in most public and university libraries, as well as through on-line databases (contact the American Chemical Society, Washington, D.C. for more details). Chemicals that are known but not commercially available in catalogs are optionally prepared by custom chemical synthesis houses, where many of the standard chemical supply houses (e.g., those listed above) provide custom synthesis services. A reference useful for the preparation and selection of pharmaceutical salts of the compounds described herein is P. H. Stahl & C. G. Wermuth "Handbook of Pharmaceutical Salts", Verlag Helvetica Chimica Acta, Zurich, 2002. Pharmaceutical Compositions [00120] In certain embodiments, the AKT1 inhibitory compound described herein is administered as a pure chemical. In other embodiments, the AKT1 inhibitory compound described herein is combined with a pharmaceutically suitable or acceptable carrier (also referred to herein as a pharmaceutically suitable (or acceptable) excipient, physiologically suitable (or acceptable) excipient, or physiologically suitable (or acceptable) carrier) selected on the basis of a chosen route of administration and standard pharmaceutical practice as described, for example, in Remington: The Science and Practice of Pharmacy (Gennaro, 21 ^st Ed. Mack Pub. Co., Easton, PA (2005)). [00121] Provided herein is a pharmaceutical composition comprising at least one AKT1 inhibitory compound as described herein, or a stereoisomer, pharmaceutically acceptable salt, hydrate, or solvate thereof, together with one or more pharmaceutically acceptable carriers. The carrier(s) (or excipient(s)) is acceptable or suitable if the carrier is compatible with the other ingredients of the composition and not deleterious to the recipient (i.e., the subject or the patient) of the composition. [00122] One embodiment provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof. [00123] One embodiment provides a method of preparing a pharmaceutical composition comprising mixing a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier. [00124] One embodiment provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of Formula (Ia), or a pharmaceutically acceptable salt or solvate thereof. [00125] One embodiment provides a method of preparing a pharmaceutical composition comprising mixing a compound of Formula (Ia), or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier. [00126] One embodiment provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of Formula (Ib), or a pharmaceutically acceptable salt or solvate thereof. [00127] One embodiment provides a method of preparing a pharmaceutical composition comprising mixing a compound of Formula (Ib), or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier. [00128] In certain embodiments, the AKT1 inhibitory compound as described by Formula (I), (Ia), or (Ib), or a pharmaceutically acceptable salt or solvate thereof, is substantially pure, in that it contains less than about 5%, or less than about 2%, or less than about 1%, or less than about 0.5%, or less than about 0.1%, of other organic small molecules, such as unreacted intermediates or synthesis by-products that are created, for example, in one or more of the steps of a synthesis method. [00129] One embodiment provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of Table 1 or Table 2, or a pharmaceutically acceptable salt or solvate thereof. [00130] One embodiment provides a method of preparing a pharmaceutical composition comprising mixing a compound of Table 1 or Table 2, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier. [00131] In certain embodiments, the AKT1 inhibitory compound as described by Table 1 or Table 2, or a pharmaceutically acceptable salt or solvate thereof, is substantially pure, in that it contains less than about 5%, or less than about 2%, or less than about 1%, or less than about 0.5%, or less than about 0.1%, of other organic small molecules, such as unreacted intermediates or synthesis by-products that are created, for example, in one or more of the steps of a synthesis method. [00132] Suitable oral dosage forms include, for example, tablets, pills, sachets, or capsules of hard or soft gelatin, methylcellulose or of another suitable material easily dissolved in the digestive tract. In some embodiments, suitable nontoxic solid carriers are used which include, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharin, talcum, cellulose, glucose, sucrose, magnesium carbonate, and the like. (See, e.g., Remington: The Science and Practice of Pharmacy (Gennaro, 21 ^st Ed. Mack Pub. Co., Easton, PA (2005)). [00133] In some embodiments, the AKT1 inhibitory compound as described by Formula (I) or Table 1 or Table 2, or pharmaceutically acceptable salt or solvate thereof, is formulated for administration by injection. In some instances, the injection formulation is an aqueous formulation. In some instances, the injection formulation is a non-aqueous formulation. In some instances, the injection formulation is an oil-based formulation, such as sesame oil, or the like. [00134] The dose of the composition comprising at least one AKT1 inhibitory compound as described herein differs depending upon the subject or patient's (e.g., human) condition. In some embodiments, such factors include general health status, age, and other factors. [00135] Pharmaceutical compositions are administered in a manner appropriate to the disease to be treated (or prevented). An appropriate dose and a suitable duration and frequency of administration will be determined by such factors as the condition of the patient, the type and severity of the patient's disease, the particular form of the active ingredient, and the method of administration. In general, an appropriate dose and treatment regimen provides the composition(s) in an amount sufficient to provide therapeutic and/or prophylactic benefit (e.g., an improved clinical outcome, such as more frequent complete or partial remissions, or longer disease-free and/or overall survival, or a lessening of symptom severity. Optimal doses are generally determined using experimental models and/or clinical trials. The optimal dose depends upon the body mass, weight, or blood volume of the patient. [00136] Oral doses typically range from about 1.0 mg to about 1000 mg, one to four times, or more, per day. Methods of Treatment [00137] One embodiment provides a compound of Formula (I), (Ia), or (Ib), or a pharmaceutically acceptable salt or solvate thereof, for use in a method of treatment of the human or animal body. [00138] One embodiment provides a compound of Formula (I), (Ia), or (Ib), or a pharmaceutically acceptable salt or solvate thereof, for use in a method of treatment of cancer or neoplastic disease. [00139] One embodiment provides a pharmaceutical composition comprising a compound of Formula (I), (Ia), or (Ib), or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient for use in a method of treatment of cancer or neoplastic disease. [00140] One embodiment provides a use of a compound of Formula (I), (Ia), or (Ib), or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for the treatment of cancer or neoplastic disease. [00141] In some embodiments is provided a method of treating cancer, in a patient in need thereof, comprising administering to the patient a compound of Formula (I), (Ia), or (Ib), or a pharmaceutically acceptable salt or solvate thereof. In some embodiments is provided a method of treating cancer, in a patient in need thereof, comprising administering to the patient a pharmaceutical composition comprising a compound of Formula (I), (Ia), or (Ib), or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient. [00142] One embodiment provides a compound of Table 1 or Table 2, or a pharmaceutically acceptable salt or solvate thereof, for use in a method of treatment of the human or animal body. [00143] One embodiment provides a compound of Table 1 or Table 2, or a pharmaceutically acceptable salt or solvate thereof, for use in a method of treatment of cancer or neoplastic disease. [00144] One embodiment provides a pharmaceutical composition comprising a compound of Table 1 or Table 2, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient for use in a method of treatment of cancer or neoplastic disease. [00145] One embodiment provides a use of a compound of Table 1 or Table 2, or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for the treatment of cancer or neoplastic disease. [00146] In some embodiments is provided a method of treating cancer, in a patient in need thereof, comprising administering to the patient a compound of Table 1 or Table 2, or a pharmaceutically acceptable salt or solvate thereof. In some embodiments is provided a method of treating cancer, in a patient in need thereof, comprising administering to the patient a pharmaceutical composition comprising a compound of Table 1 or Table 2, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient. [00147] Provided herein is the method wherein the pharmaceutical composition is administered orally. Provided herein is the method wherein the pharmaceutical composition is administered by injection. [00148] One embodiment provides a method of inhibiting a AKT1 enzyme comprising contacting the AKT1 enzyme with a compound of Formula (I), (Ia), or (Ib), or Table 1 or Table 2. Another embodiment provides the method of inhibiting a AKT1 enzyme, wherein the AKT1 enzyme is contacted in an in vivo setting. Another embodiment provides the method of inhibiting a AKT1 enzyme, wherein the AKT1 enzyme is contacted in an in vitro setting. Modification of AKT1 [00149] Without wishing to be bound by any theory, the AKT1 inhibitory compounds described herein interact with AKT1 E17K by nucleophilic addition of the lysine of residue 17 to the nitrile group of the compounds of Formula (I), (Ia), or (Ib), or Table 1 or Table 2 as indicated in the scheme below. [00150] One embodiment provides a modified AKT1 E17K polypeptide wherein the lysine at position 17 of an unmodified AKT1 E17K polypeptide has been modified with a nitrogen substituent having the structure of Formula (X), or a tautomer thereof: wherein: Z ¹ is N, C-H, or C-R ³ ; Z ² is N, C-H, or C-R ⁴ ; Z ³ is N, C-OH, or C-R ⁹ ; Ar is selected from: X ¹ is N or C-R ⁷ ; X ² is N or C-R ⁷ ; X ³ is N or C-R ⁷ ; X ⁴ is N or C-R ⁷ ; Y is O, S, or N-R ⁹ ; R ¹ is selected from hydrogen, optionally substituted C1-C6 alkyl, optionally substituted aryl, or optionally substituted heteroaryl; R ² is selected from hydrogen, halogen, -OH, -CN, -N(R ⁹ ) ₂ , -OR ⁹ , -SR ⁹ , -SO ₂ R ⁹ , -CO ₂ R ⁹ , -CON(R ⁹ ) ₂ , -SR ⁹ , -S(O)R ⁹ , - S(O) ₂ R ⁹ , optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkoxy, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C3-C7 carbocyclyl, optionally substituted 4-membered to 6-membered heterocyclyl, optionally substituted aryl, aryl substituted with an optionally substituted 4- membered to 6-membered heterocyclyl, optionally substituted heteroaryl or heteroaryl substituted with an optionally substituted 3-membered to 6-membered carbocyclyl; R ³ is selected from optionally substituted C1-C6 alkyl, or optionally substituted aryl; R ⁴ is selected from halogen, -CN, optionally substituted C1-C6 alkyl, or optionally substituted aryl; R ⁵ and R ⁶ are each independently hydrogen, deuterium, halogen, -OH, or optionally substituted C1-C6 alkyl; or R ⁵ and R ⁶ together form an oxo; or R ⁵ and R ⁶ join together to form a carbocycle or heterocycle; each R ⁷ is independently selected from hydrogen, deuterium, halogen, -OH, -SH, optionally substituted C1-C6 alkoxy, -S-(optionally substituted C1-C6 alkyl), -CN, optionally substituted C1-C6 alkyl, and optionally substituted aryl; L is selected from -N(R ⁸ )-, or a divalent radical selected from:

wherein the asterisk (*) indicates the bond to the -CO-Ar group; R ⁸ is hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C7 cycloalkyl, or optionally substituted heterocyclyl; each R ⁹ is hydrogen, or optionally substituted C1-C6 alkyl; R ¹⁰ is optionally substituted C1-C6 alkyl; m is 0, 1, or 2; n is 1, 2, or 3; and q is 0 or 1. [00151] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein Z ¹ is N. [00152] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein Z ² is C-H. [00153] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein Z ² is C-R ⁴ . [00154] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein R ¹ is optionally substituted heteroaryl. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein the optionally substituted heteroaryl is an optionally substituted pyridyl. [00155] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein R ² is optionally substituted aryl. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein the optionally substituted aryl is an optionally substituted phenyl. [00156] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein R ² is optionally substituted heteroaryl. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein the optionally substituted heteroaryl is an optionally substituted pyridyl. [00157] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein R ⁵ is hydrogen. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein R ⁶ is hydrogen. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein R ⁵ and R ⁶ together form an oxo. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein R ⁶ is optionally substituted C1-C6 alkyl. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein R ⁵ and R ⁶ join together to form a carbocycle or heterocycle. [00158] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein L is -N(R ⁸ )-. [00159] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein L is selected from: . [00160] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein L is selected from: . [00161] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein L is selected from: . [00162] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein L is selected from: . [00163] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein L is selected from: . [00164] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein L is selected from: . [00165] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein R ⁸ is hydrogen or optionally substituted C1-C6 alkyl. [00166] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein q is 0. [00167] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein q is 1. [00168] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein Ar is [00169] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein Ar is [00170] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein Ar is [00171] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X),wherein X ¹ , X ² , and X ³ are C-H. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein X ¹ is N; and X ² , and X ³ are C-H. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein X ² is N; and X ¹ , and X ³ are C-H. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein X ³ is N; and X ¹ , and X ² are C-H. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein X ¹ is N; and X ² , and X ³ are C-H. [00172] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein Y is O. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein Y is S. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein Y is N-R ⁹ . Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein R ⁹ is hydrogen. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein R ⁹ is optionally substituted C1-C6 alkyl. [00173] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein Ar is Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein X ¹ is N. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein X ² is N. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein X ³ is N. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein X ⁴ is N. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), X ¹ is C-H. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), X ² is C-H. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), X ³ is C-H. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein X ⁴ is C-H. [00174] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein R ³ is optionally substituted C1-C6 alkyl. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein R ³ is optionally substituted aryl. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein R ⁴ is optionally substituted C1-C6 alkyl. Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein R ⁴ is optionally substituted aryl. [00175] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein Ar is and L is selected from: . [00176] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein Ar is [00177] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein Ar is and q is 0. [00178] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein Ar is and L is selected from: . [00179] Another embodiment provides the modified AKT1 E17K polypeptide of Formula (X), wherein Ar is ; and R ¹ is optionally substituted heteroaryl, and R ² is optionally substituted heteroaryl. [00180] Another embodiment provides the modified AKT1 E17K polypeptide wherein the unmodified AKT1 E17K polypeptide is a SEQID selected from a SEQID provided in Table 3. Table 3 [00181] Other embodiments and uses will be apparent to one skilled in the art in light of the present disclosures. The following examples are provided merely as illustrative of various embodiments and shall not be construed to limit the invention in any way. EXAMPLES I. Chemical Synthesis [00182] In some embodiments, the AKT1 inhibitory compounds disclosed herein are synthesized according to the following examples. As used below, and throughout the description of the invention, the following abbreviations, unless otherwise indicated, shall be understood to have the following meanings: ACN acetonitrile ºC degrees Celsius δ _H chemical shift in parts per million downfield from tetramethylsilane DCM dichloromethane (CH ₂ Cl ₂ ) DIAD diisopropyl azodicarboxylate DIEA diisopropylethylamine DMF dimethylformamide DMSO dimethylsulfoxide EA ethyl acetate EtOAc ethyl acetate ESI electrospray ionization Et ethyl g gram(s) h hour(s) HPLC high performance liquid chromatography Hz hertz J coupling constant (in NMR spectrometry) LCMS liquid chromatography mass spectrometry μ micro m multiplet (spectral); meter(s); milli M molar M ⁺ parent molecular ion Me methyl MsCl methanesulfonyl chloride MHz megahertz min minute(s) mol mole(s); molecular (as in mol wt) mL milliliter MS mass spectrometry nm nanometer(s) NMR nuclear magnetic resonance pH potential of hydrogen; a measure of the acidity or basicity of an aqueous solution PE petroleum ether RT room temperature s singlet (spectral) t triplet (spectral) SFC Supercritical fluid chromatography T temperature TFA trifluoroacetic acid THF tetrahydrofuran TPP Triphenylphosphine Experimental Procedures [00183] Intermediate 1: 3-(3-(4-(Aminomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2- yl)pyridin-2-amine Step 1: tert-Butyl 4-((3-nitropyridin-2-yl)amino)benzylcarbamate To a solution of 2-chloro-3-nitro-pyridine (7.0 g, 44.2 mmol) and tert-butyl N-[(4- aminophenyl)methyl]carbamate (9.8 g, 44.2 mmol) in DMSO (100 mL) was added DIEA (11.4 g, 88.3 mmol). The mixture was stirred at 80 °C for 12 hr. The reaction mixture was diluted with H ₂ O (100 mL) at 25 °C and extracted with EtOAc (100 mL x 3). The combined organic layers were washed with brine (150 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. The residue was triturated with petroleum ether: EtOAc (10: 1) to give tert- butyl N-[[4-[(3-nitro-2-pyridyl)amino]phenyl]methyl]carbamate (13.9 g, yield: 91%) as a red solid. MS: m/z = 344.8 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.90 (s, 1H), 8.49 (dd, J = 8.4, 1.6 Hz, 1H), 8.45 (dd, J = 4.4, 1.6 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.35 (t, J = 6.0 Hz, 1H), 7.19 (d, J = 8.4 Hz, 2H), 6.93 (dd, J = 8.4, 4.4 Hz, 1H), 4.07 (d, J = 6.0 Hz, 2H), 1.36 (s, 9H). Step 2: tert-Butyl 4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)ben zylcarbamate To a solution of tert-butyl N-[[4-[(3-nitro-2-pyridyl)amino]phenyl]methyl]carbamate (10 g, 29.0 mmol) in MeOH (70 mL) and DMSO (140 mL) were added 2-aminopyridine-3-carbaldehyde (3.9 g, 31.9 mmol) and Na ₂ S ₂ O ₄ (10.1 g, 58.1 mmol). The mixture was stirred at 100 °C for 12 hr. After cooling to room temperature, the reaction mixture was diluted with H ₂ O (200 mL), and extracted with EtOAc (400 mL x 2). The combined organic layers were washed with brine (400mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel (Eluent of 1~2% MeOH in CH ₂ Cl ₂ ) to give tert-butyl 4-(2-(2-aminopyridin-3-yl)-3H-imidaExazo[4,5-b]pyridin-3- yl)benzylcarbamate (5.7 g, yield: 44%) as a red solid. MS: m/z = 417.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.31 (dd, J = 4.8, 1.2 Hz, 1H), 8.20 (dd, J = 8.0, 1.2 Hz, 1H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.49 (t, J = 6.0 Hz, 1H), 7.41 - 7.36 (m, 5H), 7.21 (dd, J = 7.6, 1.6 Hz, 1H), 6.99 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 4.21 (d, J = 6.0 Hz, 2H), 1.41 (s, 9H). Step 3: 3-(3-(4-(Aminomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)p yridin-2-amine To a solution of tert-butyl N-[[4-[2-(2-amino-3-pyridyl)imidazo[4,5-b]pyridin-3- yl]phenyl]methyl]carbamate (350 mg, 840 µmol) in 1,4-dioxane (3 mL) was added 4 M HCl in concentrated under reduced pressure to give crude product 280 mg (HCl salt, yield: 95%). The crude product was purified by prep-HPLC (Column: Phenomenex luna C18150 x 25 mm x 10 µm; Condition: water (HCl)-ACN; Begin B: 0; End B: 16; Gradient Time (min): 10; 100%B Hold Time (min): 2; Flow Rate (mL/min): 25) to give product (HCl salt). The product was diluted with 10 mL aqueous NaHCO ₃ and extracted with DCM (10 mL x 3). The combined organic layers were washed with 20 mL brine, dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give 3-(3-(4-(Aminomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2- yl)pyridin-2-amine (Intermediate 1, 70.0 mg, yield: 95%) was obtained as a light-yellow solid. MS: m/z = 317.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.31 (dd, J = 4.8, 1.2 Hz, 1H), 8.19 (dd, J = 8.0, 1.2 Hz, 1H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.47 (d, J = 8.4 Hz, 2H), 7.40 - 7.33 (m, 3H), 7.22 (dd, J = 7.6, 2.0 Hz, 1H), 6.98 (br s, 2H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 3.79 (s, 2H), 1.82 (br s, 2H). [00184] Intermediate 2: 3-(3-(4-(Piperazin-1-ylmethyl)phenyl)-3H-imidazo[4,5-b]pyrid in- 2-yl)pyridin-2-amine Step 1: Tert-butyl 4-(4-nitrobenzyl)piperazine-1-carboxylate To a solution of 1-(bromomethyl)-4-nitro-benzene (25 g, 116 mmol) in ACN (250 mL) was added tert-butyl piperazine-1-carboxylate (25.8 g, 139 mmol) and K ₂ CO ₃ (31.9 g, 231 mmol) at 20 °C. The mixture was stirred at 20 °C for 12 hr. The reaction mixture was filtered. The filter liquor was concentrated to dryness to give a crude tert-butyl 4-(4-nitrobenzyl)piperazine-1- carboxylate (37 g, yield: 99%) as a white solid, which was used in the next step without further purification. MS: m/z = 322.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.19 (d, J = 8.8 Hz, 2H), 7.60 (d, J = 8.8 Hz, 2H), 3.62 (s, 2H), 3.32 - 3.36 (m, 4H), 2.38-2.28 (m, 4H), 1.39 (s, 9H). Step 2: Tert-butyl 4-(4-aminobenzyl)piperazine-1-carboxylate To a solution of tert-butyl 4-(4-nitrobenzyl)piperazine-1-carboxylate(20 g, 62.2 mmol) in EtOH (150 mL) and H ₂ O (50 mL) was added Fe (17.3 g, 311 mmol) and NH ₄ Cl (13.3 g, 249 mmol) at 25 °C, the mixture was stirred at 90 °C for 2 hr. The reaction mixture was filtered and concentrated directly to give a crude product tert-butyl 4-(4-aminobenzyl)piperazine-1- carboxylate (17 g, crude) as a yellow oil, which was used in the next step without further purification. MS: m/z = 292.9 [M+ H] ⁺ . Step 3: Tert-butyl 4-(4-((3-nitropyridin-2-yl)amino)benzyl)piperazine-1-carboxy late To a solution of 2-chloro-3-nitro-pyridine (10 g, 63 mmol) in DMSO (200 mL) was added tert- butyl 4-(4-aminobenzyl)piperazine-1-carboxylate(15.3 g, 52.5 mmol) and DIEA (13.5 g, 105 mmol) at 25 °C. The mixture was stirred at 80 °C for 12 hr. The reaction mixture was concentrated to give a residue. The residue was diluted with H ₂ O (200 mL) and extracted with CH ₂ Cl ₂ (200 mL x 2). The combined organic layers were washed with brine (200 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The residue was purified by flash chromatography on silica gel (Eluent of 10~30% EtOAc in petroleum ether) to give tert-butyl 4-(4-((3-nitropyridin-2-yl)amino)benzyl)piperazine-1-carboxy late (11g, yield: 45%) as a red solid. MS: m/z = 413.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide- d ₆ ) δ 9.95 (s, 1H), 8.48-8.58 (m, 2H), 7.60 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 6.98 (dd, J = 8.4, 4.8 Hz, 1H), 3.46 (s, 2H), 3.29 - 3.32 (m, 4H), 2.29 - 2.35 (m, 4H), 1.39 (s, 9H). Step 4: Tert-butyl 4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazine-1-carboxylate To a solution of tert-butyl 4-(4-((3-nitropyridin-2-yl)amino)benzyl)piperazine-1-carboxy late (10 g, 24.1 mmol) in DMSO (200 mL), added 2-aminopyridine-3-carbaldehyde (3.54 g, 29.0 mmol) and Na ₂ S ₂ O ₄ (12.6 g, 72.5 mmol) at 25 °C. The mixture was stirred at 100 °C for 14 hr. The reaction mixture was poured into 500 mL of H ₂ O. The mixture was extracted with CH ₂ Cl ₂ (200 mL x 2). The combined organic layers were washed with brine (400 mL), dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated to dryness. The residue was purified by flash chromatography on silica gel (Eluent of 10~30% MeOH in CH ₂ Cl ₂ ) to give 4-(4-(2-(2- Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)pipe razine-1-carboxyla (4.9 g, yield: 42%) as a red solid. MS: m/z = 486.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.33 (dd, J = 4.8, 1.2 Hz, 1 H), 8.20 (dd, J = 8.0, 1.2 Hz, 1 H), 7.99 (dd, J = 4.8, 2.0 Hz, 1 H), 7.43 - 7.48 (m, 2 H), 7.36 - 7.42 (m, 3 H), 7.16 (dd, J = 7.6, 1.6 Hz, 1 H), 7.00 (br s, 2 H), 6.38 (dd, J = 7.6, 4.8 Hz, 1 H), 3.56 (s, 2 H), 3.33 - 3.37 (m, 4 H), 2.32 - 2.38 (m, 4 H), 1.40 (s, 9 H). Step 5: 3-(3-(4-(Piperazin-1-ylmethyl)phenyl)-3H-imidazo[4,5-b]pyrid in-2-yl)pyridin-2-amine To a solution of tert-butyl 4-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazine-1-carboxylate (2 g, 4.12 mmol) in CH ₂ Cl ₂ (10 mL) was added dropwise TFA (4.62 g, 40.5 mmol) at 25 °C, the mixture was stirred at 25 °C for 3hr. The reaction mixture was concentrated to a residue. The residue was poured into water (50 mL), then adjusted pH to about 8 by saturated NaHCO ₃ (aq). The resulting mixture was extracted with CH ₂ Cl ₂ (100 mL x 3). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated to give 3-(3-(4-(Piperazin-1-ylmethyl)phenyl)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (1.43 g, yield: 90%) as an off-white solid.100 mg of solid was triturated with EtOAc (3 mL) at 25 °C for 1 hr and filtered. The filter cake was collected to give 3-(3-(4-(Piperazin-1-ylmethyl)phenyl)-3H-imidazo[4,5-b]pyrid in-2-yl)pyridin-2-amine (Intermediate 2, 24.5 mg, yield: 90%). MS: m/z = 386.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.33 (d, J = 4.0 Hz, 1H), 8.22 (d, J = 8.0 Hz, 1H), 8.00 (d, J = 3.2 Hz, 1H), 7.35 - 7.52 (m, 5H), 7.18 (d, J = 7.2 Hz, 1H), 7.00 (br s, 2H), 6.40 (dd, d, J = 7.8, 4.8 Hz, 1H), 3.63 (s, 2H), 3.16-3.01 (m, 4H), 2.63-2.48 (ms, 4H). [00185] Intermediate 3: 3-(3-(4-((4-aminopiperidin-1-yl)methyl)phenyl)-3H-imidazo[4, 5- b]pyridin-2-yl)pyridin-2-amine Step 1: tert-Butyl (1-(4-nitrobenzyl) piperidin-4-yl) carbamate To a solution of 1-(bromomethyl)-4-nitro-benzene (108 g, 499 mmol) in ACN (1.5 L) was added K ₂ CO ₃ (149 g, 1.1 mol) and tert-butyl N-(4-piperidyl)carbamate (100 g, 499 mmol). The mixture was stirred at 25 °C for 16 hr. The reaction mixture was filtered. The filtrate was concentrated under reduced pressure to give tert-butyl (1-(4-nitrobenzyl) piperidin-4- yl)carbamate (167 g, crude) as a yellow solid, which was used to the next step without further purification. MS: m/z = 335.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.16 (d, J = 8.8 Hz, 2H), 7.49 (d, J = 8.8 Hz, 2H), 4.44 (br s, 1H), 3.56 (s, 2H), 3.52 - 3.42 (m, 1H), 2.77 - 2.74 (m, 2H), 2.16 - 2.10 (m, 2H), 1.93 - 1.90 (m, 2H), 1.43 (s, 9H), 1.42 - 1.36 (m, 2H). Step 2: Tert-butyl (1-(4-aminobenzyl) piperidin-4-yl) carbamate To a solution of tert-butyl (1-(4-nitrobenzyl) piperidin-4-yl)carbamate (109 g, 325 mmol) in EtOH (500 mL) and H ₂ O (150 mL) was added Fe (91 g, 1.6 mol) and NH ₄ Cl (174 g, 3.3 mol). The mixture was stirred at 85°C for 2 hr. The reaction mixture was filtered. The filtrate was concentrated under pressure to remove most of the EtOH. The residue was diluted with 500 mL of H ₂ O and extracted with CH ₂ Cl ₂ (500 mL × 2). The combined organic layers were washed with 500 mL of brine, dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give tert-butyl (1-(4-aminobenzyl) piperidin-4-yl) carbamate (80 g crude) as a yellow solid. MS: m/z = 306.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 7.14 (d, J = 8.0 Hz, 2H), 6.64 (d, J = 8.0 Hz, 2H), 4.51 (br d, J = 6.0 Hz, 1H), 3.80 - 3.59 (m, 2H), 3.55 (s, 2H), 3.51 - 3.39 (m, 1H), 2.95 - 2.93 (m, 2H), 2.25 - 2.20 (m, 2H), 1.96 - 1.93 (m, 2H), 1.72 - 1.54 (m, 2H), 1.42 (s, 9H). Step 3: tert-Butyl (1-(4-((3-nitropyridin-2-yl) amino)benzyl)piperidin-4-yl)carbamate To a solution of tert-butyl (1-(4-aminobenzyl) piperidin-4-yl) carbamate (30 g, 98.2 mmol) in DMSO (500 mL) was added DIEA (38.1 g, 295 mmol) and 2-chloro-3-nitro-pyridine (18.7 g, 118 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched by addition 500 mL of H ₂ O at 20 °C and extracted with EtOAc (300 mL × 2). The combined organic layers were washed with 300 mL of brine, dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The crude product was purified by flash chromatography on silica gel (Eluent of 0~10% MeOH in CH ₂ Cl ₂ ) to give tert-butyl (1-(4-((3- nitropyridin-2-yl) amino) benzyl) piperidin-4-yl) carbamate (30 g, yield: 71%) as a yellow solid. MS: m/z = 428.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 10.10 (s, 1H), 8.51 (dd, J = 8.0, 1.6 Hz, 1H), 8.47 (dd, J = 8.4, 1.6 Hz, 1H), 7.58 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 6.81 (dd, J = 8.4, 4.4 Hz, 1H), 4.44 (br s, 1H), 3.47 (s, 2H), 3.44 - 3.34 (m, 1H), 2.82 - 2.79 (m, 2H), 2.13 - 2.05 (m, 2H), 1.93 - 1.89 (m, 2H), 1.43 (s, 9H), 1.39 - 1.37 (m, 2H). Step 4: tert-Butyl (1-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)carbamate To a solution of (12.5 g, 29.2 mmol) in DMSO (500 mL) was added Na ₂ S ₂ O ₄ (15.3 g, 87.7 mmol) and 2-aminopyridine-3-carbaldehyde (4.3 g, 35.1 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched by addition 1000 mL of H ₂ O at 20 °C and extracted with EtOAc (1000 mL × 2). The combined organic layers were washed with 500 mL of brine, dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The crude product was purified by flash chromatography on silica gel (Eluent of 0~10% MeOH in CH ₂ Cl ₂ ) to give tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)carbamate (5.5 g, yield: 38%) as a yellow solid. MS: m/z = 500.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.46-8.37 (m, 1H), 8.12 - 8.02 (m, 2H), 7.48 (d, J = 8.0 Hz, 2H), 7.34 - 7.28 (m, 3H), 7.07 (dd, J = 8.0, 4.0 Hz, 1H), 6.62 (br s, 2H), 6.33 (dd, J = 7.6, 4.8 Hz, 1H), 4.46 (br d, J = 6.0 Hz, 1H), 3.56 (s, 2H), 3.49 - 3.47(m, 1H), 2.84 (br d, J = 11.2 Hz, 2H), 2.14 (t, J = 12.0 Hz, 2H), 1.93 (br d, J = 11.2 Hz, 2H), 1.45 (s, 9H), 1.51-1.38 (m, 2H). Step 5.3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-3H-imidazo[ 4,5-b]pyridin-2-yl)pyridin- 2-amine A solution of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)carbamate (2.0 g, 4.0 mmol) in HCl/1,4-dioxane (4M, 20 mL) was stirred at 25 °C for 1 hr. The reaction mixture was concentrated under reduced pressure to remove solvent. Then residue was quenched by addition 30 mL NaHCO ₃ at 20°C, then MeOH was added, filtered, and the filtrate after freeze-dried to give 3-(3-(4-((4-aminopiperidin-1- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-am ine (Intermediate 3, 1.45 g, yield: 91%) as a yellow solid. MS: m/z = 400.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.37 - 8.28 (m, 1H), 8.19 (dd, J = 8.0, 4.0 Hz, 1H), 7.99 – 7.97 (m, 1H), 7.47 - 7.32 (m, 5H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.36 (dd, J = 6.8, 4.0 Hz, 1H), 3.50 (s, 2H), 3.27 – 3.23(m, 1H), 2.75 (br d, J = 10.8 Hz, 2H), 2.00 (t, J = 10.8 Hz, 2H), 1.72 (d, J = 10.8 Hz, 2H), 1.39 -1.31 (m, 2H). [00186] Intermediate 4: 3-(3-(4-(Aminomethyl)phenyl)-5-phenyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine Step 1: tert-Butyl 4-((6-chloro-3-nitropyridin-2-yl)amino)benzylcarbamate To a solution of 2,6-dichloro-3-nitro-pyridine (2.0 g, 10.4 mmol) and tert-butyl N-[(4- aminophenyl)methyl]carbamate (2.3 g, 10.4 mmol) in DMSO (25 mL) was added DIEA (4.0 g, 31.1 mmol). The mixture was stirred at 80 °C for 12 hr. The reaction mixture was quenched by addition 50 mL of H ₂ O at 25 °C and extracted with EtOAc (50 mL x 3). The combined organic layers were washed with brine (50 mL x 2), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give crude product. The crude product was purified by flash chromatography on silica gel (Eluent of 0~10% MeOH in CH ₂ Cl ₂ ) to give tert-butyl N-[[4-[(6- chloro-3-nitro-2-pyridyl)amino]phenyl]methyl]carbamate (2.4 g, yield: 44%) as a red solid. MS: m/z = 400.9 [M + Na] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.10 (s, 1H), 8.53 (d, J = 8.8 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.40 (t, J = 6.0 Hz, 1H), 7.25 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 8.8 Hz, 1H), 4.13 (d, J = 6.0 Hz, 2H), 1.40 (s, 9H). Step 2: Tert-butyl N-[[4-[2-(2-amino-3-pyridyl)-5-chloro-imidazo[4,5-b]pyridin- 3- yl]phenyl]methyl]carbamate To a solution of tert-butyl N-[[4-[(6-chloro-3-nitro-2-pyridyl)amino]phenyl]methyl]carba mate (2.0 g, 5.3 mmol) in DMSO (30 mL) and MeOH (15 mL) was added 2-aminopyridine-3- carbaldehyde (0.7 g, 5.8 mmol) and Na ₂ S ₂ O ₄ (1.8 g, 10.6 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched by addition 50 mL of H ₂ O at 25°C, and extracted with EtOAc (100 mL x 3). The combined organic layers were washed with brine (100 mL x 2), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a crude product. The crude product was purified by flash chromatography on silica gel (Eluent of 0~10% MeOH in CH ₂ Cl ₂ ) to give tert-butyl N-[[4-[2-(2-amino-3-pyridyl)-5-chloro-imidazo[4,5- b]pyridin-3-yl]phenyl]methyl]carbamate (1.4 g, yield: 51%) as a yellow solid. MS: m/z = 451.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.26 (d, J = 8.4 Hz, 1H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.50 - 7.43 (m, 2H), 7.38 (s, 4H), 7.21 (dd, J = 7.6, 1.6 Hz, 1H), 6.91 (br s, 2H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 4.22 (d, J = 6.0 Hz, 2H), 1.41 (s, 9H). Step 3: Tert-butyl N-[[4-[2-(2-amino-3-pyridyl)-5-phenyl-imidazo[4,5-b]pyridin- 3- yl]phenyl]methyl]carbamate To a solution of tert-butyl N-[[4-[2-(2-amino-3-pyridyl)-5-chloro-imidazo[4,5-b]pyridin- 3- yl]phenyl]methyl]carbamate (500 mg, 1.1 mmol) and phenylboronic acid (270 mg, 2.2 mmol,) in 1,4-dioxane (5 mL) and H ₂ O (1 mL) was added Pd(dppf)Cl ₂ (81.1 mg, 111 µmol) and Cs ₂ CO ₃ (1.1 g, 3.3 mmol). The mixture was was degassed and purged with N ₂ three times and then stirred at 80 °C for 16 hr under N ₂ atmosphere. After cooling to 20 °C, the reaction was diluted with 10 mL of EtOAc, and the mixture filtered through celite and extracted with H ₂ O (10 mL x 3), the combined organic layers were washed with brine (15 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a residue. The crude product was purified by flash chromatography on silica gel (Eluent of 10~35% EtOAc in petroleum ether) to give tert- butyl N-[[4-[2-(2-amino-3-pyridyl)-5-phenyl-imidazo[4,5-b]pyridin- 3- yl]phenyl]methyl]carbamate (126 mg, yield: 21%) as a brown solid. MS: m/z = 493.2 [M + H] ⁺ . Step 4: 3-(3-(4-(Aminomethyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyrid in-2-yl)pyridin-2- amine To a solution of tert-butyl N-[[4-[2-(2-amino-3-pyridyl)-5-phenyl-imidazo[4,5-b]pyridin- 3- yl]phenyl]methyl]carbamate (126 mg, 256 µmol) in HCl/1,4-dioxane (4 M, 1 mL). The mixture was stirred at 25 °C for 2 hr. The solvent was removed under reduced pressure to give a crude product (84 mg, yield: 84%). The crude product was purified by prep-HPLC (column: Welch Xtimate C18150 x 25mm x 5 µm; mobile phase: [water (HCl) - ACN]; B%: 5% - 35%, 8min) to give the desired product (HCl salt). The product was diluted with aqueous NaHCO ₃ (10 mL) and extracted with DCM (10 mL x 3). The combined organic layers were washed with brine (10 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give 3-(3-(4- (aminomethyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl) pyridin-2-amine (Intermediate 4, 32.2 mg, yield: 84%) as a light-yellow solid. MS: m/z = 393.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.26 (d, J = 8.4 Hz, 1H), 8.04 - 7.96 (m, 4H), 7.54 - 7.49 (m, 2H), 7.49 - 7.43 (m, 2H), 7.43 - 7.35 (m, 3H), 7.21 (dd, J = 7.6, 1.6 Hz, 1H), 6.98 (br s, 2H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 3.82 (s, 2H). [00187] Intermediate 5: N-(3-(3-(4-(aminomethyl)phenyl)-2-(2-aminopyridin-3-yl)-3H- imidazo[4,5-b]pyridin-5-yl)phenyl)acetamide Step 1: Tert-butyl 4-(5-(3-acetamidophenyl)-2-(2-aminopyridin-3-yl)-3H-imidazo[ 4,5-b]pyridin- 3-yl)benzylcarbamate To a solution of tert-butyl N-[[4-[2-(2-amino-3-pyridyl)-5-chloro-imidazo[4,5-b]pyridin- 3- yl]phenyl]methyl]carbamate (3.5 g, 7.8 mmol) and (3-acetamidophenyl)boronic acid (2.8 g, 15.5 mmol) in 1,4-dioxane (30 mL) and H ₂ O (6 mL) was added Pd(dppf)Cl ₂ (568 mg, 776 µmol) and Cs ₂ CO ₃ (7.6 g, 23.3 mmol). The mixture was was degassed and purged with N ₂ three times and then stirred at 80 °C for 16 hr under N ₂ atmosphere. The reaction mixture was quenched by addition of H ₂ O (50 mL) at 25 °C and extracted with EtOAc (50 mL x 3). The combined organic layers were washed with brine (50 mL x 2), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give tert-butyl N-[[4-[5-(3-acetamidophenyl)-2-(2- amino-3-pyridyl)imidazo[4,5-b]pyridin-3-yl]phenyl]methyl]car bamate (2.43 g, yield: 57%), which was directly used to the next step without further purification. MS: m/z = 550.1 [M + H] ⁺ . Step 2: N-(3-(3-(4-(Aminomethyl)phenyl)-2-(2-aminopyridin-3-yl)-3H-i midazo[4,5-b]pyridin-5- yl)phenyl)acetamide To a solution of tert-butyl N-[[4-[5-(3-acetamidophenyl)-2-(2-amino-3-pyridyl)imidazo[4, 5- b]pyridin-3-yl]phenyl]methyl]carbamate (8.0 g, 14.6 mmol) in HCl/1,4-dioxane (4 M, 20 mL). The mixture was stirred at 25 °C for 2 hr. Then the solvent was removed under reduced pressure to give a crude product (6.4 g, HCl salt, yield: 90%). 250 mg of the HCl salt was diluted with aqueous NaHCO ₃ (10 mL) and extracted with CH ₂ Cl ₂ (10 mL x 3). The combined organic layers were washed with brine (10 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give N-(3-(3-(4-(aminomethyl)phenyl)-2-(2-aminopyridin-3-yl)-3H- imidazo[4,5-b]pyridin-5-yl)phenyl)acetamide (Intermediate 5, 86.7 mg, yield: 90%) as a light- yellow solid. MS: m/z = 450.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.08 (s, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.10 (s, 1H), 8.00 (dd, J = 4.8, 1.6 Hz, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.68 (d, J = 8.0Hz, 1H), 7.65 (d, J = 8.0 Hz, 1H), 7.53 - 7.48 (m, 2H), 7.45 - 7.35 (m, 3H), 7.20 (dd, J = 7.6, 1.6 Hz, 1H), 6.94 (br s, 2H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 3.82 (s, 2H), 2.06 (s, 3H). [00188] Intermediate 6: N-(3-(2-(2-aminopyridin-3-yl)-3-(4-(piperazin-1- ylmethyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)phenyl)acetam ide Step 1: tert-Butyl 4-(4-((6-(3-Acetamidophenyl)-3-nitropyridin-2-yl)amino)benzy l)piperazine-1- carboxylate To a solution of tert-butyl 4-[[4-[(6-chloro-3-nitro-2-pyridyl)amino]phenyl]methyl]piper azine-1- carboxylate (2.78 g, 5.39 mmol,) and (3-acetamidophenyl)boronic acid (1.93 g, 10.78 mmol) in 1,4-dioxane (30 mL) and H ₂ O (6 mL) was added K ₂ CO ₃ (2.24 g, 16.2 mmol) and Pd(dppf)Cl ₂ (789 mg, 1.08 mmol). The mixture was degassed and purged with N ₂ three times and stirred at 60 ºC for 16 hr under N ₂ atmosphere. The reaction mixture was quenched by addition 200 mL of H ₂ O at 25 ºC, and then extracted with CH ₂ Cl ₂ (60 mL x 3). The combined organic layers were washed with brine (100 mL x 2), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (Eluent of 50-100% EtOAc in petroleum ether) to give tert-butyl 4-[[4-[[6-(3-acetamidophenyl)-3-nitro- 2-pyridyl]amino]phenyl]methyl]piperazine-l-carboxylate (2.81 g, yield: 83%) as a red solid. MS: m/z = 547.1 [M+H] ⁺ . ¹ HNMR (400 MHz, Chloroform-d) δ 10.19 (s, 1H), 8.42 (d, J= 8.8 Hz, 1H), 8.19 (br s, 1H), 7.68-7.60 (m, 4H), 7.47 (d, J= 9.2 Hz, 1H), 7.34-7.27 (m, 2H), 7.17- 7.12 (m, 1H), 3.43 (s, 2H), 3.35 (br t, J= 4.8 Hz, 4H), 2.32 (br t, J= 4.8 Hz, 4H), 2.11 (s, 3H), 1.36 (s, 9H).

Step 2: Tert-butyl 4-(4-(5-(3-acetamidophenyl)-2-(2-aminopyridin-3-yl)-3H-imida zo[4,5- b]pyridin-3 -yl)benzyl)piperazine- 1 -carboxylate

To a solution of 2-aminopyridine-3-carbaldehyde (2.3 g, 18.9 mmol) and tert-butyl 4-[[4-[(6- chloro-3-nitro-2-pyridyl)amino]phenyl]methyl]piperazine-l-ca rboxylate (9.5 g, 17.2 mmol) in DMSO (100 mL) was added Na ₂ S ₂ O ₄ (8.97 g, 51.5 mmol). The mixture was degassed and purged with N2 three times and stirred at 60 °C for 16 hr under N ₂ atmosphere. The reaction mixture was quenched by addition 400 mL of H ₂ O at 25 °C, and then extracted with CH ₂ CI ₂ (400 mL x 2). The combined organic layers were washed with brine (300 mL x 2), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give tert-butyl 4-[[4-[5-(3- acetamidophenyl)-2-(2-amino-3-pyridyl)imidazo[4,5-b]pyridin- 3-yl]phenyl]methyl]piperazine- 1 -carboxylate (9.67 g, crude) as a red solid, which was direct used to the next step without further purification. MS: m/z = 619.2 [M+H] ⁺ .

Step 3 : N-(3-(2-(2-aminopyridin-3-yl)-3-(4-(piperazin-l-ylmethyl)phe nyl)-3H-imidazo[4,5- b]pyridin-5-yl)phenyl)acetamide

To a solution of tert-butyl 4-[[4-[5-(3-acetamidophenyl)-2-(2-amino-3-pyridyl)imidazo[4, 5- b]pyridin-3-yl]phenyl]methyl]piperazine-l -carboxylate (0.4 g, 370 μmol, crude) in HCl/1,4- dioxane (4M, 5 mL) and 1,4-di oxane (1 mL). The mixture was degassed and purged with N ₂ three times and stirred at 25 °C for 4 hr under N ₂ atmosphere. The reaction mixture was filtered and the filtered cake was washed with 1,4-dioxane (10 mL x 2) and then concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Phenomenex Luna C18 200*40mm*10um; mobile phase: [water (HCl)-ACN]; B%: l%-30%, 10min) to give N-(3-(2-(2-aminopyridin-3-yl)-3-(4-(piperazin-l-ylmethyl)phe nyl)-3H- imidazo[4,5-b]pyridin-5-yl)phenyl)acetamide (Intermediate 6, 244 mg HC1 salt, yield: 68%) as a yellow solid. MS: m/z = 519.2 [M+H] ⁺ . ¹ HNMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.05 (s, 1H), 8.27 (d, J= 8.4 Hz, 1H), 8.15 (s, 1H), 7.99 (dd, J= 4.8, 1.6 Hz, 1H), 7.86 (d, J= 8.4 Hz, 1H), 7.66 (d, J = 8.0 Hz, 2H), 7.50 - 7.33 (m, 5H), 7.14 (dd, J = 7.6, 1.2 Hz, 1H), 7.00 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.52 (s, 2H), 2.77-2.67 (m, 4H), 2.41-2.27 (m, 4H), 2.05 (s, 3H). [00189] Intermediate 7: 3-[3-[4-(aminomethyl)phenyl]-6-phenyl-imidazo[4,5-b]pyridin- 2- yl]pyridin-2-amine Step 1: Tert-butyl N-[[4-[(5-bromo-3-nitro-2-pyridyl)amino]phenyl]methyl]carbam ate To a solution of 5-bromo-2-chloro-3-nitro-pyridine (2.1 g, 9.0 mmol) and tert-butyl N-[(4- aminophenyl)methyl]carbamate (2 g, 9.0 mmol) in DMSO (20 mL) was added DIEA (3.5 g, 27.0 mmol). The mixture was stirred at 80 °C for 12 hr. After cooling to 20 °C, H ₂ O (50 mL) was added to the reaction mixture, then extracted with EtOAc (50 mL x 2). The combined organic layers were washed with brine (50 mL x 2), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give tert-butyl N-[[4-[(5-bromo-3-nitro-2- pyridyl)amino]phenyl]methyl]carbamate (3.5 g crude, yield: 92%) as a red solid. MS: m/z = 367.6, 368.6 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d)) δ 10.02 (s, 1H), 8.65 (d, J = 2.0 Hz, 1H), 8.49 (d, J = 2.0 Hz, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 4.84 (br s, 1H), 4.32 (d, J = 5.2 Hz, 2H), 1.47 (s, 9H). Step 2: tert-Butyl N-[[4-[2-(2-amino-3-pyridyl)-6-bromo-imidazo[4,5-b]pyridin-3 - yl]phenyl]methyl]carbamate To a solution of tert-butyl N-[[4-[(5-bromo-3-nitro-2-pyridyl)amino]phenyl]methyl]carbam ate (3 g, 7.1 mmol) and 2-aminopyridine-3-carbaldehyde (952 mg, 7.8 mmol) in DMSO (30 mL) and MeOH (15 mL) was added Na ₂ S ₂ O ₄ (2.5 g, 14.2 mmol). The mixture was stirred at 100 °C for 12 hr. After cooling to 20 °C, H ₂ O (50 mL)was added to the reaction mixture, then the resulting mixture extracted with EtOAc (50 mL x 2). The combined organic layers were washed with brine (50 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (Eluent of 0~1% MeOH in CH ₂ Cl ₂ ) to give tert-butyl-N-[[4-[2-(2-amino-3-pyridyl)-6-bromo-imidazo[4,5- b]pyridin-3- yl]phenyl]methyl]carbamate (1.7 g, yield: 36%) as a yellow solid. MS: m/z = 495.9, 496.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d)) δ 8.40 (d, J = 2.0 Hz, 1H), 8.22 (d, J = 2.0 Hz, 1H), 8.08 (dd, J = 4.8, 2.0 Hz, 1H), 7.46 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 7.10 (dd, J = 8.0, 2.0 Hz, 1H), 6.63 (br s, 2H), 6.41 - 6.34 (m, 1H), 4.93 (br s, 1H), 4.42 (d, J = 5.6 Hz, 2H), 1.48 (s, 9H). Step 3: tert-Butyl N-[[4-[2-(2-amino-3-pyridyl)-6-phenyl-imidazo[4,5-b]pyridin- 3- yl]phenyl]methyl]carbamate To a solution of tert-butyl N-[[4-[2-(2-amino-3-pyridyl)-6-bromo-imidazo[4,5-b]pyridin-3 - yl]phenyl]methyl]carbamate (500 mg, 1.0 mmol) and phenylboronic acid (246 mg, 2.0 mmol) in toluene (5 mL) and EtOH (5 mL) was added NaHCO ₃ (254 mg, 3.0 mmol) and Pd(PPh ₃ ) ₄ (233 mg, 202 µmol). The mixture degassed and purged with N ₂ three times, and then the mixture was stirred at 100 °C for 12 hr under N ₂ atmosphere. After cooling to 20 °C, H ₂ O (20 mL) was added to the reaction mixture, then extracted with EtOAc (20 mL x 2). The combined organic layers were washed with saturated NaHCO ₃ solution (20 mL x 2), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (Eluent of 0~1% MeOH in CH ₂ Cl ₂ ) to give tert-butyl N-[[4-[2-(2- amino-3-pyridyl)-6-phenyl-imidazo[4,5-b]pyridin-3-yl]phenyl] methyl]carbamate (340 mg, 62% yield) as a brown solid. MS: m/z = 493.1 [M + H] ⁺ . 1H NMR (400 MHz, Dimethylsulfoxide- d ₆ )) δ 8.61 (d, J = 2.0 Hz, 1H), 8.45 (d, J = 2.0 Hz, 1H), 8.01 - 7.99 (m, 1H), 7.77 (d, J = 7.2 Hz, 2H), 7.63 - 7.59 (m, 4H), 7.54 - 7.52 (m, 2H), 7.39 (d, J = 5.2 Hz, 2H), 7.23 (dd, J = 7.6, 2.0 Hz, 1H), 7.04 (br s, 2H), 6.40 (dd, J = 7.6, 5.2Hz, 1H), 4.21 (d, J = 6.0 Hz, 2H), 1.40 (s, 9H). Step 4.3-[3-[4-(aminomethyl)phenyl]-6-phenyl-imidazo[4,5-b]pyridi n-2-yl]pyridin-2-amine To a solution of tert-butyl N-[[4-[2-(2-amino-3-pyridyl)-6-phenyl-imidazo[4,5-b]pyridin- 3- yl]phenyl]methyl]carbamate (340 mg, 690 µmol, 1.0 eq) in 1,4-dioxane (5 mL) was added HCl/dioxane (5 mL). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was concentrated under reduced pressure to give the crude product (297 mg, HCl salt, yield: 96%). The residue was purified by prep-HPLC (column: Welch Xtimate C ₁ 8150 x 25mm x 5µm; mobile phase: [water (HCl)-ACN]; B%: 3%-33%, 8min) and dissociated with NaHCO ₃ to give 3-[3-[4-(aminomethyl)phenyl]-6-phenyl-imidazo[4,5-b]pyridin- 2-yl]pyridin-2-amine (Intermediate 7, 83.8 mg, yield: 96%) as an off-white solid. MS: m/z = 393.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ )) δ 8.62 (d, J = 2.0 Hz, 1H), 8.46 (d, J = 2.0 Hz, 1H), 8.00 (dd, J = 4.8, 2.0 Hz, 1H), 7.78 (d, J = 7.2 Hz, 2H), 7.56 - 7.46 (m, 5H), 7.45 - 7.35 (m, 4H), 7.26 (dd, J = 8.0, 2.0 Hz, 1H), 7.04 (s, 2H), 6.44 - 6.39 (m, 1H), 3.80 (s, 2H). [00190] Intermediate 8: 3-(6-Phenyl-3-(4-(piperazin-1-ylmethyl)phenyl)-3H-imidazo[4, 5- b]pyridin-2-yl)pyridin-2-amine Intermediate 8 was prepared in a manner similar to Intermediate 7. MS: m/z = 462.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.63 (d, J = 2.0 Hz, 1H), 8.46 (d, J = 2.0 Hz, 1H), 8.00 (dd, J = 4.8, 1.6 Hz, 1H), 7.81 - 7.75 (m, 2H), 7.52 (dd, J = 7.6, 7.6 Hz, 2H), 7.47 - 7.38 (m, 5H), 7.19 (dd, J = 7.6, 1.6 Hz, 1H), 7.06 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.51 (s, 2H), 3.33 - 3.27 (m, 1H), 2.71 (br t, J = 4.4 Hz, 4H), 2.32 (s, 4H). [00191] Intermediate 9: 3-[3-[4-[(4-Amino-1-piperidyl)methyl]phenyl]-6-phenyl- imidazo[4,5-b]pyridin-2-yl]pyridin-2-amine Intermediate 9 was prepared in a manner similar to Intermediate 7. MS: m/z = 476.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.63 (d, J = 2.0 Hz, 1H), 8.47 (d, J = 2.0 Hz, 1H), 8.34 (s, 2H), 8.00 (dd, J = 4.8, 1.6 Hz, 1H), 7.78 (d, J = 7.6 Hz, 2H), 7.53 (dd, J = 7.6, 7.6 Hz, 2H), 7.47 - 7.39 (m, 5H), 7.20 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.55 (s, 2H), 2.98-2.88 (m, 1H), 2.87-2.80 (m, 2H), 2.09-1.97 (m, 2H), 1.90 - 1.80 (m, 2H), 1.57 - 1.44 (m, 2H). [00192] Intermediate 10: 3-[5-Phenyl-3-[4-(piperazin-1-ylmethyl)phenyl]imidazo[4,5- b]pyridin-2-yl]pyridin-2-amine Step 1: tert-Butyl 4-[[4-[(6-chloro-3-nitro-2-pyridyl)amino]phenyl]methyl]piper azine-1- carboxylate To a solution of 2,6-dichloro-3-nitro-pyridine (5.0 g, 25.9 mmol) in 1,4-dioxane (50 mL) was added DIEA (6.7 g, 51.8 mmol) and tert-butyl 4-[(4-aminophenyl)methyl]piperazine-1- carboxylate (10.8 g, 25.9 mmol). The mixture was stirred at 60 °C for 12 hr. The reaction mixture was diluted 50 mL of H ₂ O, and the aqueous phase extracted with EtOAc (100 mL x 3). The combined organic layers were washed with brine (50 mL x 2), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (Eluent of 0~50% EtOAc in petroleum ether) to give tert-butyl 4-[[4- [(6-chloro-3-nitro-2-pyridyl)amino]phenyl]methyl]piperazine- 1-carboxylate (6.1 g, yield: 53%) as a yellow solid. MS: m/z = 447.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 10.27 (s, 1H), 8.46 (d, J = 8.8 Hz, 1H), 7.61 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 6.80 (d, J = 8.4 Hz, 1H), 3.52 (s, 2H), 3.48-3.37 (m, 4H), 2.45-2.32 (m, 4H), 1.46 (s, 9H). Step 2. Tert-butyl 4-[[4-[(3-nitro-6-phenyl-2-pyridyl)amino]phenyl]methyl]piper azine-1- carboxylate To a solution of tert-butyl 4-[[4-[(6-chloro-3-nitro-2-pyridyl)amino]phenyl]methyl]piper azine-1- carboxylate (1.0 g, 2.23 mmol) and phenylboronic acid (544 mg, 4.47 mmol) in 1,4-dioxane (10 mL) and H ₂ O (2 mL) was added Pd(dppf)Cl ₂ (327 mg, 0.446 mmol) and K ₂ CO ₃ (926 mg, 6.7 mmol). The mixture was stirred at 60 °C for 4 hr. The reaction mixture was added with 50 mL of H ₂ O, and the aqueous phase extracted with EtOAc (100 mL x 3). The combined organic layers were washed with brine (50 mL x 2), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (Eluent of 0~50% EtOAc in petroleum ether) to give tert-butyl 4-[[4-[(3-nitro-6-phenyl-2- pyridyl)amino]phenyl]methyl]piperazine-1-carboxylate (1.0 g, yield: 92%) as a red solid. MS: m/z = 490.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 10.31 (s, 1H), 8.59 (d, J = 8.8 Hz, 1H), 8.06-8.04 (m, 2H), 7.73 (d, J = 8.4 Hz, 2H), 7.52-7.44 (m, 3H), 7.37 (d, J = 8.4 Hz, 2H), 7.3 (d, J = 8.4 Hz, 1H), 3.54 (s, 2H), 3.52-3.37 (m, 4H), 2.49-2.37 (m, 4H), 1.46 (s, 9H). Step 3: Tert-butyl 4-[[4-[2-(2-amino-3-pyridyl)-5-phenyl-imidazo[4,5-b]pyridin- 3- yl]phenyl]methyl]piperazine-1-carboxylate To a solution of 2-aminopyridine-3-carbaldehyde (269 mg, 2.21 mmol) and tert-butyl 4-[[4-[(3- nitro-6-phenyl-2-pyridyl)amino]phenyl]methyl]piperazine-1-ca rboxylate (900 mg, 1.84 mmol) in DMSO (10 mL) was added Na ₂ S ₂ O ₄ (960 mg, 5.52 mmol) at 15 °C. The mixture was stirred at 100 °C for 20 hr. The reaction mixture was diluted with H ₂ O (50 mL), and the aqueous phase extracted with DCM (80 mL x 3). The combined organic layers were washed with brine (80 mL x 3), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (Eluent of 0~10% MeOH in CH ₂ Cl ₂ ) to give tert-butyl 4-[[4-[2-(2-amino-3-pyridyl)-5-phenyl-imidazo[4,5-b]pyridin- 3- yl]phenyl]methyl]piperazine-1-carboxylate (600 mg, yield: 58%) as a yellow solid. MS: m/z = 562.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.13 (d, J = 8.4 Hz, 1H), 8.06 (dd, J = 5.2, 2.0 Hz, 1H), 8.03-8.01 (m, 2H), 7.81 (d, J = 8.4 Hz, 1H), 7.51-7.49 (m, 2H), 7.48-7.35 (m, 5H), 7.10 (dd, J = 9.6, 2.0 Hz, 1H), 6.66 (br s, 2H), 6.36 (dd, J = 8.0, 4.0 Hz, 1H), 3.64 (s, 2H), 3.53-3.42 (m, 4H), 2.55-2.42 (m, 4H), 1.47 (s, 9H). Step 4: 3-[5-Phenyl-3-[4-(piperazin-1-ylmethyl)phenyl]imidazo[4,5-b] pyridin-2-yl]pyridin-2- amine A solution of tert-butyl 4-[[4-[2-(2-amino-3-pyridyl)-5-phenyl-imidazo[4,5-b]pyridin- 3- yl]phenyl]methyl]piperazine-1-carboxylate (400 mg, 712 µmol) in HCl/1,4-dioxane (4M, 8 mL) was stirred at 25 °C for 4 hr. The reaction was filtered and concentrated under reduced pressure to give 3-[5-phenyl-3-[4-(piperazin-1-ylmethyl)phenyl]imidazo[4,5-b] pyridin-2-yl]pyridin-2- amine (450 mg, HCl) as a yellow solid, which was used in the next step without further purification. 200 mg of the residue was purified by prep-HPLC (column: Waters xbridge 150*25mm 10um;mobile phase: [water(NH ₄ HCO ₃ )-ACN];B%: 19%-49%, 9min) to give 3-[5- Phenyl-3-[4-(piperazin-1-ylmethyl)phenyl]imidazo[4,5-b]pyrid in-2-yl]pyridin-2-amine (Intermediate 10, 49.7 mg) as a yellow solid. MS: m/z = 462.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.04-7.97 (m, 4H), 7.48-7.39 (m, 8H), 7.15 (dd, J = 8.0, 2.0 Hz, 1H), 7.03 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.53 (s, 2H), 2.74-2.66 (m, 4H), 2.38-2.27 (m, 4H). [00193] Intermediate 11: 3-[3-[4-[(4-amino-1-piperidyl)methyl]phenyl]-5-phenyl- imidazo[4,5-b]pyridin-2-yl]pyridin-2-amine Step 1: tert-Butyl (1-(4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl)piperidin- 4-yl)carbamate To a solution of 2,6-dichloro-3-nitro-pyridine (3.0 g, 15.5 mmol) and tert-butyl N-[1-[(4- aminophenyl)methyl]-4-piperidyl]carbamate (4.8 g, 15.6 mmol) in 1,4-dioxane (100 mL) was added DIEA (6.0 g, 46.6 mmol). The mixture was stirred at 50 °C for 12 hr. The reaction mixture was diluted with H ₂ O (50 mL) and extracted with EtOAc (30 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (Eluent of 0~5% MeOH in CH ₂ Cl ₂ ) to give tert-butyl N-[1-[[4-[(6-chloro-3- nitro-2-pyridyl)amino]phenyl]methyl]-4-piperidyl]carbamate (4.6 g, yield: 64%) as an orange solid. MS: m/z = 462.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 10.26 (s, 1H), 8.46 (d, J = 8.8 Hz, 1H), 7.60 (d, J = 8.8 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 6.79 (d, J = 8.4 Hz, 1H), 4.42 (br s, 1H), 3.48 (s, 2H), 3.48 - 3.39 (m, 1H), 2.82 (br d, J = 10.8 Hz, 2H), 2.10 (br t, J = 10.8 Hz, 2H), 1.92 (br d, J = 10.8 Hz, 2H), 1.50-1.40 (m, 2H).1.44 (s, 9H). Step 2: Tert-butyl (1-(4-((3-nitro-6-phenylpyridin-2-yl)amino)benzyl)piperidin- 4-yl)carbamate A mixture of tert-butyl N-[1-[[4-[(6-chloro-3-nitro-2-pyridyl)amino]phenyl]methyl]-4 - piperidyl]carbamate (1.0 g, 2.20 mmol), phenylboronic acid (528 mg, 4.30 mmol), Pd(dppf)Cl ₂ (158 mg, 0.216 mmol) and K ₂ CO ₃ (898 mg, 6.50 mmol) in 1,4-dioxane (10 mL) and H ₂ O (2 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 100 °C for 12 hr under N ₂ atmosphere. After cooling to 25 °C, the reaction mixture was diluted with H ₂ O and extracted with DCM (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (Eluent of 0~7% MeOH in CH ₂ Cl ₂ ) to give tert-butyl N-[1-[[4-[(3-nitro-6-phenyl-2-pyridyl)amino]phenyl]methyl]-4 - piperidyl]carbamate (1.1 g, yield: 96%) as a yellow solid MS: m/z = 504.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 10.31 (s, 1H), 8.59 (d, J = 8.8 Hz, 1H), 8.09 - 8.02 (m, 2H), 7.72 (d, J = 8.4 Hz, 2H), 7.51 - 7.47 (m, 3H), 7.36 (d, J = 8.8 Hz, 1H), 7.30 (d, J = 8.8 Hz, 1H), 4.52 - 4.37 (m, 1H), 3.52 (s, 2H), 3.51 - 3.42 (m, 1H), 2.85 (br d, J = 11.2 Hz, 2H), 2.12 (br t, J = 10.8 Hz, 2H), 1.93 (br d, J = 11.0 Hz, 2H), 1.50 - 1.40 (m, 2H).1.44 (s, 9H). Step 3: tert-Butyl (1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyr idin-3- yl)benzyl)piperidin-4-yl) carbamate To a solution of tert-butyl N-[1-[[4-[(3-nitro-6-phenyl-2-pyridyl)amino]phenyl]methyl]-4 - piperidyl]carbamate (200 mg, 0.397 mmol), 2-aminopyridine-3-carbaldehyde (53.4 mg, 0.437 mmol) and Na ₂ S ₂ O ₄ (207 mg, 1.2 mmol) in DMSO (6 mL). The mixture was stirred at 100 °C for 18 hr. After cooling to 25 °C, the reaction mixture was diluted with DCM (40 mL). The organic layers were washed with H ₂ O (20 mL) and brine (20 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (IEluent of 0~7% MeOH in CH ₂ Cl ₂ ) to give tert-butyl N-[1-[[4-[2-(2- amino-3-pyridyl)-5-phenyl-imidazo[4,5-b]pyridin-3-yl]phenyl] methyl]-4-piperidyl]carbamate (100 mg, yield: 40%) as a yellow solid. MS: m/z = 576.2 [M + H] ⁺ . Step 4: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-phenyl-3H-i midazo[4,5-b]pyridin-2- yl)pyridin-2-amine To a solution of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyr idin-3- yl)benzyl)piperidin-4-yl)carbamate (200 mg, 0.347 mmol) in HCl in 1,4-dioxane (4 M, 2 mL). The mixture was stirred at 25 °C for 2 hr. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Waters xbridge 150*25mm 10um; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 24% - 54%, 8 min) to give 3- [3-[4-[(4-amino-1-piperidyl)methyl]phenyl]-5-phenyl-imidazo[ 4,5-b]pyridin-2-yl]pyridin-2- amine (Intermediate 11, 120 mg, yield: 72 %) as a light-yellow solid. MS: m/z = 476.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.12 (d, J = 8.4 Hz, 1H), 8.05 (dd, J = 5.2, 1.6 Hz, 1H), 8.01 (d, J = 7.2 Hz, 2H), 7.79 (d, J = 8.4 Hz, 1H), 7.50 - 7.35 (m, 7H), 7.09 (dd, J = 7.6, 1.2 Hz, 1H), 6.61 (br s, 2H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 3.58 (s, 2H), 2.88 (br d, J = 11.6 Hz, 2H), 2.75 - 2.65 (m, 1H), 2.09 (br t, J = 11.6 Hz, 2H), 1.83 (br d, J = 11.6 Hz, 2H), 1.49 - 1.38 (m, 2H). [00194] Intermediate 12: N-(3-(3-(4-((4-aminopiperidin-1-yl)methyl)phenyl)-2-(2- aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-5-yl)phenyl)acet amide

Step 1: tert-Butyl (1-(4-((6-(3-acetamidophenyl)-3-nitropyridin-2-yl)amino)benz yl)piperidin-4- yl)carbamate A mixture of tert-butyl N-[1-[[4-[(6-chloro-3-nitro-2-pyridyl)amino]phenyl]methyl]-4 - piperidyl]carbamate (1.0 g, 2.16 mmol), (3-acetamidophenyl)boronic acid (773 mg, 4.32 mmol), Pd(dppf)Cl ₂ (158 mg, 0.216 mmol) and K ₂ CO ₃ (895 mg, 6.48 mmol) in H ₂ O (2 mL) and 1,4- dioxane (10 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 100°C for 12 hr under N ₂ atmosphere. The reaction mixture was diluted with H ₂ O (50 mL) and extracted with CH ₂ Cl ₂ (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (Eluent of 0~5% MeOH in CH ₂ Cl ₂ ) to give tert-butyl N-[1-[[4-[[6-(3-acetamidophenyl)-3-nitro-2-pyridyl]amino]phe nyl]methyl]-4- piperidyl]carbamate (1.04 g, yield: 86%) as an orange solid. MS: m/z = 561.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 10.30 (s, 1H), 8.57 (d, J = 8.8 Hz, 1H), 8.26 (br s, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.72 (d, J = 8.4 Hz, 2H), 7.63 - 7.57 (m, 1H), 7.47 - 7.35 (m, 4H), 7.28 (d, J = 8.8 Hz, 1H), 4.44 (br s, 1H), 3.51 (s, 2H), 3.44 - 3.48 (m, 1H), 2.93 - 2.78 (m, 2H), 2.23 (s, 3H), 2.13 (br t, J = 10.4 Hz, 2H), 1.93 (br d, J = 11.2 Hz, 2H), 1.52 - 1.45 (m, 2H), 1.44 (s, 9H). Step 2: Tert-butyl (1-(4-((3-nitro-6-phenylpyridin-2-yl)amino)benzyl)piperidin- 4-yl)carbamate To a solution of tert-butyl N-[1-[[4-[[6-(3-acetamidophenyl)-3-nitro-2- pyridyl]amino]phenyl]methyl]-4-piperidyl]carbamate (950 mg, 1.69 mmol), 2-aminopyridine-3- carbaldehyde (228 mg, 1.9 mmol) and Na ₂ SO ₄ (590 mg, 3.4 mmol) in DMSO (12 mL).The mixture was stirred at 100 °C for 18 hr. After cooling to 25 °C, the reaction mixture was diluted with CH ₂ Cl ₂ (50 mL). The organic layers were washed with H ₂ O (50 mL) and brine (50 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (Eluent of 0~7% MeOH in CH ₂ Cl ₂ ) to give tert-butyl N-[1-[[4-[5-(3-acetamidophenyl)-2-(2-amino-3-pyridyl)imidazo [4,5-b]pyridin-3- yl]phenyl]methyl]-4-piperidyl]carbamate (536 mg, yield: 50%) as a yellow solid. MS: m/z = 633.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.11 (d, J = 8.4 Hz, 1H), 8.06 (dd, J = 4.8, 2.0 Hz, 1H), 8.00 (br s, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.73 (d, J = 8.0 Hz, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.49 (br s, 1H), 7.45 (d, J =8.4 Hz, 2H), 7.40 - 7.34 (m, 3H), 7.05 (dd, J = 8.0, 1.6 Hz, 1H), 6.60 (br s, 2H), 6.33 (dd, J = 7.6, 4.8 Hz, 1H), 4.47 (br s, 1H), 3.58 (s, 2H), 3.51 – 3.48 (m, 1H), 2.85 (br d, J = 11.2 Hz, 2H), 2.18 - 2.16 (m, 2H), 2.14 (s, 3H), 1.94 (br d, J = 10.8 Hz, 2H), 1.49 - 1.47 (m, 2H), 1.45 (s, 9H). Step 3: N-(3-(3-(4-((4-aminopiperidin-1-yl)methyl)phenyl)-2-(2-amino pyridin-3-yl)-3H- imidazo[4,5-b]pyridin-5-yl)phenyl)acetamide A solution of tert-butyl N-[1-[[4-[5-(3-acetamidophenyl)-2-(2-amino-3-pyridyl)imidazo [4,5- b]pyridin-3-yl]phenyl]methyl]-4-piperidyl]carbamate (300 mg, 474 mmol) in HCl/1,4-dioxane (4 M, 2 mL) was stirred at 25 °C for 2 hr. The reaction mixture was added NaHCO ₃ to adjust the pH abount 8 and extracted with DCM (15 mL x 3). The combined organic layers were washed with brine (10 mL x 2), dried by Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give N-[3-[3-[4-[(4-amino-1-piperidyl)methyl]phenyl]-2-(2-amino-3 - pyridyl)imidazo[4,5-b]pyridin-5-yl]phenyl]acetamide (Intermediate 12, 134 mg, yield: 53%) as a yellow solid. MS: m/z = 533.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.13 (d, J = 8.4 Hz, 1H), 8.07 (dd, J = 4.8, 1.6 Hz, 1H), 8.02 (s, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.69 (d, J = 8.0 Hz, 1H), 7.48 (d, J = 8.4 Hz, 2H), 7.42 - 7.37 (m, 4H), 7.08 (d, J = 6.8 Hz, 1H), 6.61 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.59 (s, 2H), 2.90 (br d, J = 11.2 Hz, 2H), 2.77 - 2.67 (m, 1H), 2.20 (s, 3H), 2.12 (br t, J = 11.2 Hz, 2H), 1.85 (br d, J = 11.2 Hz, 2H), 1.49 - 1.41 (m, 2H). [00195] Intermediate 13: Methyl 4-[2-(2-amino-3-pyridyl)-5-phenyl-imidazo[4,5- b]pyridin-3-yl]benzoate Step 1: Methyl 4-((6-chloro-3-nitropyridin-2-yl)amino)benzoate To a solution of methyl 4-aminobenzoate (5 g, 33.1 mmol) in DMSO (50 mL) was added 2,6- dichloro-3-nitro-pyridine (7.66 g, 39.7 mmol) and DIEA (12.82 g, 99.2 mmol). The mixture was stirred at 80 °C for 16 hr. After cooling to 20 °C, the reaction mixture was poured into H ₂ O (100 mL)and extracted with CH ₂ Cl ₂ (100 mL x 3). The combined organic layers were washed with brine (100 mL x 2), dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated to dryness. The crude product was triturated with EtOAc at 25 ºC for 30 min to give methyl 4-[(6-chloro-3- nitro-2-pyridyl)amino]benzoate (8 g, yield: 51%) as a yellow solid. MS: m/z = 307.8 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.25 (s, 1H), 8.57 (d, J = 8.4 Hz, 1H), 7.97 (d, J = 8.8 Hz, 2H), 7.79 (d, J = 8.8 Hz, 2H), 7.12 (d, J = 8.4 Hz, 1H), 3.85 (s, 3H). Step 2: Methyl 4-((3-nitro-6-phenylpyridin-2-yl)amino)benzoate To a solution of methyl 4-[(6-chloro-3-nitro-2-pyridyl)amino]benzoate (45 g, 146 mmol)and phenylboronic acid (21.4 g, 176 mmol) in 1,4-dioxane (500 mL) and H ₂ O (100 mL) were added Pd(dppf)Cl ₂ (10.7 g, 14.6 mmol) and Cs ₂ CO ₃ (143 g, 439 mmol). The mixture was degassed and purged with N ₂ three times, and then the mixture was stirred at 80 °C for 16 hr under N ₂ atmosphere. The reaction mixture was poured into H ₂ O (500 mL) and extracted with CH ₂ Cl ₂ (500 mL x 3). The combined organic layers were washed with brine (500 mL x 3), dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated to dryness. The crude product was triturated with EtOAc at 25 ºC for 30 min to give methyl 4-[(3-nitro-6-phenyl-2-pyridyl)amino]benzoate (35.2 g, yield: 69%) as a red solid. MS: m/z = 350.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.25 (s, 1H), 8.62 (d, J = 8.8 Hz, 1H), 8.15 - 8.10 (m, 2H), 8.00 (d, J = 8.4 Hz, 2H), 7.92 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 8.8 Hz, 1H), 7.59 - 7.54 (m, 3H), 3.86 (s, 3H) Step 3: Methyl 4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin -3-yl)benzoate To a solution of methyl 4-[(3-nitro-6-phenyl-2-pyridyl)amino]benzoate (15 g, 42.9 mmol) in DMSO (150 mL) was added 2-aminopyridine-3-carbaldehyde (6.29 g, 51.5 mmol) and Na ₂ S ₂ O ₄ (15 g, 85.9 mmol). Then the reaction mixture was heated to 100°C for 16 hr. After cooling to 25 °C, the reaction mixture was diluted with H ₂ O (200 mL) and extracted with CH ₂ Cl ₂ (200ml x 3), the combined organic layers were washed with brine brine (200ml x 2), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The crude product was triturated with CH ₂ Cl ₂ at 25ºC for 30 min to give methyl 4-[2-(2-amino-3-pyridyl)-5-phenyl- imidazo[4,5-b]pyridin-3-yl]benzoate (Intermediate 13, 12 g, yield: 66%) as a yellow solid. MS: m/z = 422.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.29 (d, J = 8.0 Hz, 1H), 8.12 (d, J = 8.4 Hz, 2H), 8.07 - 8.00 (m, 4H), 7.67 (d, J = 8.8 Hz, 2H), 7.49 - 7.44 (m, 2H), 7.42 - 7.38 (m, 1H), 7.23 (dd, J = 7.6, 1.6Hz, 1H), 6.89 (br s, 2H), 6.46 (dd, J = 7.6, 4.8 Hz, 1H), 3.90 (s, 3H). [00196] Intermediate 14: 3-(3-(4-(Chloromethyl)phenyl)-5-phenyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine Step 1: (4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridi n-3-yl)phenyl)methanol To a solution of Intermediate 13 (2.5 g, 5.9 mmol) in THF (25 mL) was added LiAlH ₄ (450 mg, 11.9 mmol) at 0 °C. After addition, the resulting mixture was stirred at 25 °C for 2 hr. After the reaction mixture was cooled to 0 °C, the reaction mixture was quenched by addition of H ₂ O (100 mL), followed by 15% aqueous NaOH (30 mL). Then the reaction mixture was filtered. The filter liquor was concentrated to dryness to give [4-[2-(2-amino-3-pyridyl)-5-phenyl- imidazo[4,5-b]pyridin-3-yl]phenyl]methanol (1.87 g, yield: 80%) as a yellow solid, which was directly used to the next step without further purification. MS: m/z = 394.1 [M + H] ⁺ . Step 2: 3-(3-(4-(Chloromethyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyri din-2-yl)pyridin-2- amine To a solution of [4-[2-(2-amino-3-pyridyl)-5-phenyl-imidazo[4,5-b]pyridin-3- yl]phenyl]methanol (2.3 g, 5.9 mmol) in CH ₂ Cl ₂ (25 mL) was added SOCl ₂ (2.1 g, 17.5 mmol). The mixture was stirred at 40°C for 1 hr. The reaction mixture was filtered. The filter liquor was concentrated to dryness to give 3-(3-(4-(chloromethyl)phenyl)-5-phenyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (Intermediate 14, 1.71 g, yield: 71%) as a yellow solid. MS: m/z = 412.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.29 (d, J = 8.4 Hz, 1H), 8.12 (d, J = 8.4 Hz, 2H), 8.07 - 8.00 (m, 4H), 7.67 (d, J = 8.4 Hz, 2H), 7.50 - 7.44 (m, 2H), 7.42 - 7.37 (m, 1H), 7.24 (d, J = 7.2 Hz, 1H), 6.88 (br s, 2H), 6.46 (dd, J = 4.8, 7.6 Hz, 1H), 3.90 (s, 2H). [00197] Intermediate 15: 3-(3-(4-(Chloromethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2- yl)pyridin-2-amine Step 1: (4-((3-Nitropyridin-2-yl)amino)phenyl)methanol To a solution of (4-aminophenyl)methanol (10 g, 81.2 mmol) in 1,4-dioxane (150 mL) was added DIEA (31.5 g, 244 mmol) and 2-chloro-3-nitro-pyridine (15.5 g, 97.4 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was concentrated under reduced pressure to remove solvent. The residue was diluted with H ₂ O (200 mL) and extracted with EtOAc (200 mL × 2). The combined organic layers were washed with brine (500 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a residue. The crude product was purified by flash chromatography on silica gel (Eluent of 0 ~ 82% EtOAc in petroleum ether) to give (4-((3-nitropyridin-2-yl)amino)phenyl)methanol (15.3 g, yield: 77%) as a yellow solid. MS: m/z = 245.8 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 10.12 (s, 1H), 8.53 (dd, J = 8.4, 2.0 Hz, 1H), 8.48 (dd, J = 4.4, 1.6 Hz, 1H), 7.64 (d, J = 8.0 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 6.84 (dd, J = 8.4, 4.8 Hz, 1H), 4.70 (s, 2H). Step 2: (4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)ph enyl)methanol To a solution of 4-((3-nitropyridin-2-yl)amino)phenyl)methanol (10 g, 40.8mmol) in DMSO (500 mL) was added Na ₂ S ₂ O ₄ (21.3 g, 122 mmol) and 2-aminopyridine-3-carbaldehyde (5.98 g, 48.9 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched by H ₂ O (500 mL) at 20 °C and extracted with EtOAc (500 mL × 2). The combined organic layers were washed with brine (500 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The crude product was purified by flash chromatography on silica gel (Eluent of 0 ~ 100% EtOAc in petroleum ether) to give (4-(2-(2-aminopyridin-3-yl)- 3H-imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (3.1 g, yield: 24%) as a yellow solid. MS: m/z = 318.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.39 - 8.32 (m, 1H), 8.08 (dd, J = 8.0, 1.2 Hz, 1H), 8.02 (dd, J = 4.8, 1.6 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.30 - 7.27 (m, 1H), 7.12 (dd, J = 7.6, 1.6 Hz, 1H), 6.65 (br s, 2H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 4.76 (s, 2H). Step 3: 3-(3-(4-(Chloromethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl) pyridin-2-amine To a solution of [4-[2-(2-amino-3-pyridyl)imidazo[4,5-b]pyridin-3-yl]phenyl]m ethanol (1.0 g, 3.15 mmol) in CH ₂ Cl ₂ (10 mL) was added SOCl ₂ (3.3 g, 27.6 mmol). The mixture was stirred at 40 °C for 1 hr. The reaction mixture was concentrated under reduced pressure to remove solvent to give 3-(3-(4-(chloromethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl) pyridin-2-amine (Intermediate 15, 1.2 g HCl salt) as a gray solid, which was used to the next step without further purification. MS: m/z = 336.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 9.35 ( br s, 1H), 8.55 (d, J = 8.0 Hz, 1H), 8.28 (d, J = 7.6 Hz, 1H), 7.91 - 7.83 (m, 1H), 7.68 (d, J = 8.0 Hz, 2H), 7.64 – 7.59 (m, 1H), 7.54 - 7.50 (m, 1H), 7.46 (d, J = 8.0 Hz, 2H), 7.30 – 7.27 (m, 2H), 6.70 – 6.60 (m, 1H), 4.70 (s, 2H). [00198] Intermediate 16: 6-(Piperidin-4-yloxy) nicotinonitrile Step 1: tert-Butyl 4-((5-cyanopyridin-2-yl)oxy)piperidine-1-carboxylate To a solution of 6-oxo-1H-pyridine-3-carbonitrile (1.0 g, 8.33 mmol) inTHF (30 mL) was added PPh ₃ (4.4 g, 16.7 mmol), then the mixture was degassed and purged with N ₂ three times, DEAD (2.9 g, 16.7 mmol) and tert-butyl 4-hydroxypiperidine-1-carboxylate (1.8 g, 9.16 mmol) was added dropwise at 0 °C. The resulting mixtuer was stirred at 25 °C for 16 hr. The mixture was 3diluted with H ₂ O (50 mL)and extracted with EtOAc (50 mL × 2). The combined organic layers were washed with 50 mL brine, dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a residue. The crude product was purified by flash chromatography on silica gel (Eluent of 0~25% EtOAc in petroleum ether) to give tert-butyl 4-((5-cyanopyridin-2- yl)oxy)piperidine-1-carboxylate (2.5 g, yield: 99%) as a pink solid. ¹ H NMR (400 MHz, Chloroform-d) δ 8.44 (d, J = 2.4 Hz, 1H), 7.77 (dd, J = 8.8, 2.4 Hz, 1H), 6.78 (d, J = 8.4 Hz, 1H), 5.30 - 5.26 (m, 1H), 3.79 - 3.74 (m, 2H), 3.30 - 3.25 (m, 2H), 1.99 - 1.95 (m, 2H), 1.74 - 1.70 (m, 2H), 1.46 (s, 9H). Step 2: 6-(Piperidin-4-yloxy) nicotinonitrile To a solution of tert-butyl 4-[(5-cyano-2-pyridyl)oxy]piperidine-1-carboxylate (200 mg, 659 µmol) in HCl in 1,4-dioxane (4M, 2 mL). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was concentrated under reduced pressure to remove solvent to give 6- (piperidin-4-yloxy) nicotinonitrile (Intermediate 16, 150 mg, HCl salt) as a pink solid, which was directly used to the next step without further purification. ¹ H NMR (400 MHz, Chloroform- d) δ 9.64 (br s, 2H), 8.45 (d, J = 1.6 Hz, 1H), 7.82 (dd, J = 8.4, 1.6 Hz, 1H), 6.83 (d, J = 8.4 Hz, 1H), 5.43 (br s, 1H), 4.28 - 4.14 (m, 1H), 3.44 - 3.24 (m, 4H), 2.40 - 2.16 (m, 4H). [00199] Intermediate 17: 6-(Piperidin-4-yloxy)picolinonitrile Intermediate 17 was prepared in a manner similar to Intermediate 16. [00200] Intermediate 18: 2-(Piperidin-4-yloxy)isonicotinonitrile Intermediate 18 was prepared in a manner similar to Intermediate 16. [00201] Intermediate 19: 2-(Piperidin-4-yloxy)nicotinonitrile Intermediate 19 was prepared in a manner similar to Intermediate 16. [00202] Intermeidate 20: 3-(3-(4-(Chloromethyl)phenyl)-6-phenyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine Step 1: (4-((5-Bromo-3-nitropyridin-2-yl)amino)phenyl)methanol To a solution of 5-bromo-2-chloro-3-nitro-pyridine (10 g, 42 mmol) and (4- aminophenyl)methanol (5.2 g, 42 mmol) in DMSO (100 mL) was added DIEA (16.3 g, 126 mmol). The mixture was stirred at 25 °C for 16 hr. Then the reaction mixture was poured into H ₂ O (200 mL) and extracted with EtOAc (300 mL x 2). The combined organic layers were washed with brine (200 mL x 2), dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated to dryness. The residue was purified by flash silica gel chromatography (Eluent of 10~50% EtOAc in petroleum ether) to give (4-((5-bromo-3-nitropyridin-2-yl)amino)phenyl)methanol (6.28 g, yield: 46%) as a red solid. MS: m/z = 324.0, 325.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform- d-) δ 10.05 (br s, 1H), 8.65 (d, J = 2.4 Hz, 1H), 8.50 (d, J = 2.4 Hz, 1H), 7.59 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 4.71 (s, 2H). Step 2: (4-((3-Nitro-5-phenylpyridin-2-yl)amino)phenyl)methanol A mixture of [4-[(5-bromo-3-nitro-2-pyridyl)amino]phenyl]methanol (5.4 g, 16.7 mmol), phenylboronic acid (6.1 g, 50 mmol), K ₂ CO ₃ (4.62 g, 33.44 mmol), Pd(dppf)Cl ₂ (1.22 g, 1.67 mmol) in 1,4-dioxane (60 mL) and H ₂ O (12 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 100 °C for 8 hr under N ₂ atmosphere. The reaction mixture was poured into H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (100 mL x 3). The combined organic layers were washed with brine (100 mL x 2), dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated to dryness. The residue was purified by flash silica gel chromatography (Eluent of 0~50% EtOAc in petroleum ether) to give [4-[(3-nitro-5-phenyl-2- pyridyl)amino]phenyl]methanol (4.6 g, yield: 86%) as a red solid. MS: m/z = 322.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 10.15 (s, 1H), 8.78 - 8.72 (m, 2H), 8.25 (d, J = 8.0 Hz 1H), 7.70 - 7.65 (m, 2H), 7.59 - 7.56 (m, 2H), 7.51 - 7.49 (m, 2H), 7.44 - 7.41 (m, 2H), 4.72 (s, 2H). Step 3: (4-(2-(2-Aminopyridin-3-yl)-6-phenyl-3H-imidazo[4,5-b]pyridi n-3-yl)phenyl)methanol To a solution of [4-[(3-nitro-5-phenyl-2-pyridyl)amino]phenyl]methanol (15 g, 46.7 mmol) in DMSO (600 mL) was added Na ₂ S ₂ O ₄ (16 g, 93 mmol) and 2-aminopyridine-3-carbaldehyde (6.8 g, 56 mmol). The mixture was stirred at 100 °C for 12 hr. After cooling to 25 °C, the reaction mixture was diluted with H ₂ O (200 mL) and extracted with CH ₂ Cl ₂ (200ml x 3), the combined organic layers were washed with brine (200ml x 2), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (Eluent of 0~100% EtOAc in petroleum ether) to give [4-[2-(2-amino-3- pyridyl)-6-phenyl-imidazo[4,5-b]pyridin-3-yl]phenyl]methanol (5.15 g crude, yield: 28%) as a yellow solid. MS: m/z = 394.0 [M + H] ⁺ . Step 4: 3-(3-(4-(Chloromethyl)phenyl)-6-phenyl-3H-imidazo[4,5-b]pyri din-2-yl)pyridin-2- amine To a solution of [4-[2-(2-amino-3-pyridyl)-6-phenyl-imidazo[4,5-b]pyridin-3- yl]phenyl]methanol (500 mg, 1.3 mmol) in CH ₂ Cl ₂ (10 mL) was added SOCl ₂ (771 mg, 6.5 mmol). The mixture was stirred at 40 °C for 2 hr. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (Eluent of 0~100% EtOAc in petroleum ether) to give 3-[3-[4-(chloromethyl)phenyl]-6-phenyl- imidazo[4,5-b]pyridin-2-yl]pyridin-2-amine (Intermediate 20, 267 mg, yield: 51%) as a yellow solid. MS: m/z = 411.8 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.63 (d, J = 2.0 Hz, 1H), 8.47 (d, J = 2.0 Hz, 1H), 8.01 (dd, J = 8.8, 3.2 Hz, 1H), 7.79 (d, J = 7.2 Hz, 2H), 7.61 (d, J = 8.4 Hz, 2H), 7.55 - 7.47 (m, 4H), 7.45 - 7.40 (m, 1H), 7.25 (dd, J = 7.6, 1.8 Hz, 1H), 6.96 (br s, 2H), 6.44 (dd, J = 7.6, 4.8 Hz, 1H), 4.86 (s, 2H). [00203] Intermediate 21: 6-Chloropyridazine-4-carbonitrile Step 1: 6-Chloropyridazine-4-carboxamide A solution of methyl 6-chloropyridazine-4-carboxylate (9.0 g, 52 mmol) and ammonia in MeOH (7 M, 90 mL) was stirred at 80 °C for 3 hr. The residue was purified by flash silica gel chromatography (Eluent of 0~98% EtOAc in petroleum ether), 6-chloropyridazine-4- carboxamide (6.4 g, yield: 78%) was obtained as a yellow solid. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.52 (s, 1H), 8.38 (br s, 1H), 8.21 (s, 1H), 8.09 (br s, 1H). Step 2: 6-Chloropyridazine-4-carbonitrile To a solution of 6-chloropyridazine-4-carboxamide (3.0 g, 19.0 mmol) in Py (30 mL) was added POCl ₃ (14.6 g, 95.0 mmol). The mixture was stirred at 25 °C for 12 hr. The residue was purified by column chromatography (0~30% EtOAc in petroleum ether), 6-chloropyridazine-4- carbonitrile (Intermediate 21, 1.48 g, yield: 56%) was obtained as a yellow solid. MS: m/z = 140.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.67 (s, 1H), 8.64 (s, 1H). [00204] Intermediate 22: 5-(Piperidin-4-ylamino)nicotinonitrile Step 1: tert-Butyl 4-((5-cyanopyridin-3-yl)amino)piperidine-1-carboxylate A mixture of tert-butyl 4-aminopiperidine-1-carboxylate (1.3 g, 6.6 mmol), 5- bromonicotinonitrile (1.0 g, 5.5 mmol), BINAP (170 mg, 273 µmol), Pd(OAc) ₂ (25 mg, 109 mmol) and Cs ₂ CO ₃ (3.56 g, 10.9 mmol) in 1,4-dioxane (20 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 100 °C for 16 hr under N ₂ atmosphere. The mixture was diluted with H ₂ O (50 mL) and extracted with EtOAc (50 mL × 2). The combined organic layers were washed with 50 mL brine, dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The crude product was purified by flash chromatography on silica gel (Eluent of 0~30% EtOAc in petroleum ether), tert-butyl 4-((5- cyanopyridin-3-yl)amino)piperidine-1-carboxylate (1.2 g, yield: 72%) was obtained as a light yellow solid. ¹ H NMR (400 MHz, Chloroform-d) δ 8.16 (s, 2H), 7.06 - 6.97 (m, 1H), 4.17 - 3.98 (m, 3H), 3.41 (br s, 1H), 2.99 - 2.87 (m, 2H), 2.05 - 1.97 (m, 2H), 1.46 (s, 9H), 1.43 - 1.32 (m, 2H). Step 2: 5-(Piperidin-4-ylamino)nicotinonitrile To a solution of tert-butyl 4-((5-cyanopyridin-3-yl)amino)piperidine-1-carboxylate (150 mg, 496 mol) in HCl in 1,4-dioxane (4M, 2 mL). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was concentrated under reduced pressure to give 5-(piperidin-4- ylamino)nicotinonitrile (110 mg, HCl salt, yield: 93%) as a light-yellow solid, which was used to the next step without further purification. [00205] Intermediate 23: 3-Cyanopyridazine-4-carboxylic acid Step 1: Methyl 3-cyanopyridazine-4-carboxylate To a solution of methyl pyridazine-4-carboxylate (600 mg, 4.34 mmol) in CHCl ₃ (25 mL) was added Tf ₂ O (1.47 g, 5.21 mmol). The mixture was stirred at 25 °C for 1 hr. And then TMSCN (2.15 g, 21.7 mmol) was added dropwise at 25 °C. The reaction mixture was stirred at 60 °C for 3 hr. And then 4-methylmorpholine (571 mg, 5.65 mmol) was added dropwise at 60 °C. The mixture was stirred at 60 °C for another 12 hr. The reaction mixture was quenched by addition of NaHCO ₃ (aq) (10 mL) at 25 °C and extracted with CH ₂ Cl ₂ (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (Eluent of 0 – 40% EtOAc in petroleum ether), methyl 3-cyanopyridazine-4- carboxylate (400 mg, yield: 56%) was obtained as a brown solid. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.71 (d, J=5.6 Hz, 1H), 8.31 (d, J=5.6 Hz, 1H), 3.98 (s, 3H). Step 2: 3-Cyanopyridazine-4-carboxylic acid To a solution of methyl 3-cyanopyridazine-4-carboxylate (400 mg, 2.45 mmol) in THF (5 mL) was added the mixture of LiOH.H ₂ O (205 mg, 4.90 mmol) in H ₂ O (5 mL) at 0 °C. The reaction mixture was stirred at 0 °C for 0.5 hr. The reaction mixture was then adjusted to pH = 5 by aq. HCl (1 N). The resulting mixture was extracted with CH ₂ Cl ₂ (20 mL x 3). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated to give a residue 3- cyanopyridazine-4-carboxylic acid (Intermediate 23, 350 mg, yield: 96%) as a brown solid. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.68 (d, J=5.6 Hz, 1H), 8.26 (d, J=5.6 Hz, 1H). [00206] Intermediate 24: 5-Cyanopyrimidine-4-carboxylic acid Step 1: Methyl 5-cyanopyrimidine-4-carboxylate To a solution of methyl 5-bromopyrimidine-4-carboxylate (400 mg, 1.84 mmol) and Zn(CN) ₂ (216 mg, 1.84 mmol) in DMF (10 mL) was added DPPF (102 mg, 184 µmol) and Pd ₂ (dba) ₃ (84 mg, 92.2 µmol) at 25 °C. After addition the reaction mixture was stirred at 90 °C under N ₂ atmosphere for 12hr. The reaction mixture was poured into H ₂ O (50 mL). The resulting mixture was extracted with EtOAc (30 mL x 2). The combined organic phase was washed with water (50 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. The residue was purified by flash silica gel chromatography (Eluent of 0 – 40% EtOAc in petroleum ether), methyl 5-cyanopyrimidine-4-carboxylate (130 mg, yield: 42%) was obtained as a yellow solid. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.58 (s, 1 H), 9.54 (s, 1 H), 3.98 (s, 3 H). Step 2: 5-Cyanopyrimidine-4-carboxylic acid To a solution of methyl 5-cyanopyrimidine-4-carboxylate (400 mg, 2.45 mmol) in THF (4 mL) was added the mixture of LiOH.H ₂ O (205 mg, 4.90 mmol) in H ₂ O (4 mL) at 0 °C. The reaction mixture was stirred at 0 °C for 0.5 hr. The reaction mixture was then adjusted to pH = 5 by aq. HCl (1 N). The resulting mixture was extracted with CH ₂ Cl ₂ (20 mL x 3). The combined organic phase was dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated to give a residue 5- cyanopyrimidine-4-carboxylic acid (Intermediate 24, 350 mg, yield: 96%) as a brown solid. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.22 (s, 1H), 9.08 (s, 1H). [00207] Intermediate 25: 2-Carbamoylbenzo[d]thiazole-5-carboxylic acid Step 1: Methyl (Z)-4-bromo-3-((4-chloro-5H-1,2,3-dithiazol-5-ylidene)amino) benzoate To a solution of methyl 3-amino-4-bromo-benzoate (5.0 g, 22 mmol) in 50 mL DCM was added 4,5-dichlorodithiazol-2-ium;chloride (5.9 g, 28 mmol). The mixture was stirred at 25 °C for 3 hr. Then pyridine (3.4 g, 43 mmol) was added to the mixture, the resulting mixture was stirred at 25 °C for 2 hr. The mixture was concentrated under reduced pressure. The residue was purified by column chromatography (Eluent of 0~10% EtOAc in petroleum ether), methyl methyl (Z)-4-bromo-3-((4-chloro-5H-1,2,3-dithiazol-5-ylidene)amino) benzoate (2.27 g, yield: 27%) was obtained as a yellow solid. MS: m/z = 366.6 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 7.80 (d, J = 1.6 Hz, 1H), 7.76 (s, 1H), 7.76 (d, J = 2.0 Hz, 1H), 3.92 - 3.92 (m, 3H). Step 2: (4-((3-Nitro-5-phenylpyridin-2-yl)amino)phenyl)methanol Methyl 4-bromo-3-[(Z)-(4-chlorodithiazol-5-ylidene)amino]benzoate (1.13 g, 3.0 mmol) and CuI (588 mg, 3.0 mmol) were taken up into a microwave tube in pyridine (20 mL). The sealed tube was heated at 115 °C for 0.5 hr under microwave. The reaction mixture was diluted with EtOAc (50 mL) and quenched by addition of Na ₂ SO ₃ (50 mL) at 25 °C. The combined organic layers were washed with brine (50 mL), dried over, filtered, and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (Eluent of 0~5% EtOAc in petroleum ether), (4-((3-nitro-5-phenylpyridin-2-yl)amino)phenyl)methanol (1.0 g, yield: 70%) was obtained as a yellow solid. MS: m/z = 218.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.89 (d, J = 2.0 Hz, 1H), 8.33 - 8.26 (m, 1H), 8.05 (d, J = 8.4 Hz,1H), 4.01 (s, 3H). Step 3: 2-Carbamoylbenzo[d]thiazole-5-carboxylic acid To a solution of methyl 2-cyano-1,3-benzothiazole-5-carboxylate (200 mg, 916 µmol) in THF (2 mL) was added LiOH.H ₂ O in H ₂ O (1 M, 1.37 mL). The mixture was stirred at 0 °C for 3 hr. The mixture was concentrated under pressure at 20 °C, 2-Carbamoylbenzo[d]thiazole-5- carboxylic acid (Intermediate 25, 200 mg, used directly) was obtained as a yellow solid. MS: m/z = 223.0 [M + H] ⁺ . [00208] Intermediate 26: 2-carbamoyl-5-fluorobenzo[d]thiazole-7-carboxylic acid Intermediate 26 was prepared in a manner similar to Intermediate 25. MS: m/z = 240.8 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.30 (s, 1H), 7.91 (s, 1H), 7.83 - 7.72 (m, 1H), 7.65 - 7.62 (m, 1H). ¹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ - 116.1. [00209] Intermediate 27: 2-Carbamoyl-6-fluorobenzo[d]thiazole-4-carboxylic acid Step 1: Methyl 2-amino-3-bromo-5-fluorobenzoate To a solution of 2-amino-3-bromo-5-fluoro-benzoic acid (2.0 g, 8.55 mmol) in MeOH (50 mL) was added SOCl ₂ (3.05 g, 25.64 mmol) dropwise. The mixture was stirred at 70 °C for 2 hr. The reaction mixture was concentrated under reduced pressure to give methyl 2-amino-3-bromo- 5-fluorobenzoate (2.0 g, yield: 73%) was obtained as a black solid, which was directly used to the next step without further purification. MS: m/z = 249.8, 250.8 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 7.68 - 7.53 (m, 1H), 7.42 - 7.40 (m, 1H), 5.34 (br s, 2H), 3.90 (s, 3H). ¹ F NMR (400 MHz, Chloroform-d 127.5. Step 2: Methyl (Z)-3-bromo-2-((4-chloro-5H-1,2,3-dithiazol-5-ylidene)amino) -5-fluorobenzoate A mixture of 4,5-dichlorodithiazol-2-ium;chloride (168.1 mg, 806µmol) and methyl 2-amino-3- bromo-5-fluorobenzoate (200 mg, 806 µmol) in DCM (3 mL) was stirred at 25 °C for 3 hr, and then pyridine (128 mg, 1.61 mmol) was added dropwise to the solution, the reaction mixture was stirred for another 2 hr. The reaction mixture was concentrated under reduced pressure to give a residue. Methyl (Z)-3-bromo-2-((4-chloro-5H-1,2,3-dithiazol-5-ylidene)amino) -5- fluorobenzoate (300 mg, yield: 63%) was obtained as light-green oil, which was used directly used to the next step without further purification. MS: m/z = 384.4 [M + H] ⁺ . Step 3: Methyl 2-cyano-6-fluorobenzo[d]thiazole-4-carboxylate To a solution of methyl methyl (Z)-3-bromo-2-((4-chloro-5H-1,2,3-dithiazol-5-ylidene)amino) - 5-fluorobenzoate(200 mg, 521 µmol) in pyridine (4 mL) was added CuI (99 mg, 521 mol). The mixture was stirred under microwave irradiation (400 W) 115 °C for 0.5 hr. The reaction was diluted with H ₂ O (20 mL) and extracted with EtOAc (10 mL x 3). The combined organic layers were washed with 0.5 M HCl (5 mL x 3) and brine (10 mL x 5), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (Eluent of 6~8% Ethyl acetate in petroleum ether), Methyl 2- cyano-6-fluorobenzo[d]thiazole-4-carboxylate (65 mg, yield: 51%) was obtained as white solid, which was used directly used to the next step. MS: m/z = 236.7 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.01 (dd, J = 9.2, 2.8 Hz, 1H), 7.87 (dd, J = 7.2, 2.8 Hz, 1H), 4.08 (s, 3H). ¹ F NMR (400 MHz, Chloroform-d) δ - 108.7. Step 4: 2-Carbamoyl-6-fluorobenzo[d]thiazole-4-carboxylic acid A mixture of methyl 2-cyano-6-fluorobenzo[d]thiazole-4-carboxylate (20 mg, 85 µmol), LiOH.H ₂ O (3 mg, 85 µmol) in THF (1 mL) and H ₂ O (1 mL) was stirred at 60 °C for 0.5 hr. The reaction was concentrated under reduced pressure to give 2-carbamoyl-6- fluorobenzo[d]thiazole-4-carboxylic acid (Intermediate 27, 15 mg, yield: 68%) was obtained as white solid, which was used directly used to the next step without further purification. MS: m/z = 240.6 [M + H] ⁺ .1H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.37 (br s, 1H), 8.07 (br s, 1H), 7.90 (dd, J = 8.4, 3.2 Hz, 1H), 7.41 - 7.34 (m, 1H). ¹ F NMR (400 MHz, Chloroform-d) δ - 114.2. [00210] Intermediate 28: 3-(3-(4-(((3S,5S)-3,5-Dimethylpiperazin-1-yl)methyl)phenyl)- 5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: tert-Butyl (2S,6S)-4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4, 5-b]pyridin-3- yl)benzyl)-2,6-dimethylpiperazine-1-carboxylate To a solution of Intermediate 14 (1.0 g, 2.43 mmol) in DMF (4 mL) were added K ₂ CO ₃ (671 mg, 4.86 mmol) and tert-butyl (2R,6R)-2,6-dimethylpiperazine-1-carboxylate (624 mg, 2.91 mmol). The mixture was stirred at 25 °C for 16 hr. The reaction mixture was quenched with H ₂ O (10 mL) at 25 °C, diluted with CH ₂ Cl ₂ (6 mL), and extracted with H ₂ O (20 mL x 3). The combined organic layers were washed with brine (20 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0-10% MeOH in CH ₂ Cl ₂ ), tert-butyl (2S,6S)-4-(4-(2-(2- aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)be nzyl)-2,6-dimethylpiperazine-1- carboxylate (750 mg, yield: 52%) was obtained as a yellow solid. MS: m/z = 590.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.26 (d, J = 8.4 Hz, 1H), 8.04 - 7.95 (m, 4H), 7.51 - 7.38 (m, 7H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (br s, 2H), 6.38 (dd, J = 8.0, 4.8 Hz, 1H),3.82 - 3.75 (m, 2H), 3.64 (d, J = 13.6 Hz, 1H), 3.47 (d, J = 13.6 Hz, 1H), 2.90 - 2.86 (m, 1H), 2.76 - 2.70 (m, 1H),2.26 - 2.18 (m, 2H), 1.40 (s, 9H), 1.22 (d, J = 6.4 Hz, 6H). Step 2: 3-(3-(4-(((3S,5S)-3,5-Dimethylpiperazin-1-yl)methyl)phenyl)- 5-phenyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine A solution of tert-butyl (2S,6S)-4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl)-2,6-dimethylpiperazine-1-carboxylate (700 mg, 1.19 mmol) in HCl/1,4- dioxane (10 mL) was stirred at 25 °C for 2 hr. The reaction was filtered and concentrated under reduced pressure to give 3-(3-(4-(((3S,5S)-3,5-dimethylpiperazin-1-yl)methyl)phenyl)- 5-phenyl- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (Intermediate 28, 540 mg, HCl salt, yield: 86%) as a white solid MS: m/z = 490.6 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.08 - 7.95 (m, 4H), 7.52 - 7.35 (m, 7H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (br s, 2H), 6.40 - 6.34 (m, 1H), 3.54 (d, J = 14.0 Hz, 1H), 3.45 – 3.40 (m, 1H), 3.10 – 3.04 (m, 2H), 2.41 - 2.33 (m, 2H), 2.06 – 2.00 (m, 2H), 1.04 (d, J = 6.4 Hz, 6H). [00211] Intermediate 29: 3-(3-(4-(((3R,5R)-3,5-dimethylpiperazin-1-yl)methyl)phenyl)- 5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: tert-Butyl (2R,6R)-4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4, 5-b]pyridin-3- yl)benzyl)-2,6-dimethylpiperazine-1-carboxylate To a solution of Intermediate 14 (1.06 g, 2.57 mmol), tert-butyl (2R,6R)-2,6-dimethylpiperazine- 1-carboxylate (500 mg, 2.33 mmol) in DMF (10 mL) was added DIEA (905 mg, 7.0 mmol). The mixture was stirred at 80 °C for 16 hr. The mixture was quenched with H ₂ O (40 mL) and extracted with EtOAc (40 mL x 3), the combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated to give a residue. The residue was purified by flash silica gel chromatography (Eluent of 0~9% MeOH in CH ₂ Cl ₂ ), tert-butyl (2R,6R)-4-(4-(2-(2- aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)be nzyl)-2,6-dimethylpiperazine-1- carboxylate (Intermediate 29, 1 g, yield: 69.4%) was obtained as a yellow solid. MS: m/z = 590.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.05 - 7.98 (m, 4H), 7.52 - 7.43 (m, 6H), 7.42 - 7.36 (m, 1H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.83 - 3.74 (m, 2H), 3.65 (d, J = 13.6 Hz, 1H), 3.48 (d, J = 13.6 Hz, 1H), 3.35 – 3.39 (m, 2H), 2.27-2.19 (m, 2H), 1.42 - 1.41 (m, 1H), 1.40 (s, 9H), 1.23 (d, J = 6.4 Hz, 6H). Step 2: 3-(3-(4-(((3R,5R)-3,5-Dimethylpiperazin-1-yl)methyl)phenyl)- 5-phenyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine A solution of tert-butyl (2R,6R)-4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl)-2,6-dimethylpiperazine-1-carboxylate (100 mg, 169 µmol) in HCl/1,4- dioxane (4M, 1 mL) was stirred at 25 °C for 0.5 hr. The mixture was filtered to give 3-(3-(4- (((3R,5R)-3,5-dimethylpiperazin-1-yl)methyl)phenyl)-5-phenyl -3H-imidazo[4,5-b]pyridin-2- yl)pyridin-2-amine (Intermediate 29, 84 mg HCl salt, yield: 95%) as a yellow solid. MS: m/z = 490.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 12.41 - 11.57 (m, 0.5H), 10.79 - 10.27 (m, 0.5H), 10.07 - 9.71 (m, 1H), 8.65 - 8.51 (m, 1H), 8.38 (d, J = 8.4 Hz, 1H), 8.16 (d, J = 6.0 Hz, 1H), 8.11 - 7.95 (m, 4H), 7.93 - 7.82 (m, 3H), 7.68 (d, J = 8.0 Hz, 2H), 7.51 - 7.42 (m, 3H), 7.04 (t, J = 6.8 Hz, 1H), 4.50 - 4.25 (m, 2H), 3.44-3.32 (m, 2H), 3.20-3.01 (m, 2H), 2.91 – 2.87 (m, 1H), 2.75 – 2.71 (m, 1H), 1.60 - 1.31 (m, 6H). [00212] Intermediate 30: 3-[3-[4-(4,7-Diazaspiro[2.5]octan-7-ylmethyl)phenyl]-5-pheny l- imidazo[4,5-b]pyridin-2-yl]pyridin-2-amine Intermediate 30 was prepared in a manner similar to Intermediate 28. MS: m/z = 488.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.26 (d, J = 8.4 Hz, 1H), 8.09 - 7.92 (m, 4H), 7.56 - 7.33 (m, 7H), 7.14 (dd, J = 7.8, 1.8 Hz, 1H), 7.05 (br s, 2H), 6.34 (dd, J = 7.6, 4.8 Hz, 1H), 3.52 (s, 2H), 2.76 (t, J = 4.8 Hz, 2H), 2.44 - 2.32 (m, 2H), 2.18 (s, 2H), 0.47 - 0.38 (m, 2H), 0.35 - 0.25 (m, 2H). [00213] Intermediate 31: 3-(3-(4-((3,8-Diazabicyclo[3.2.1]octan-3-yl)methyl)phenyl)-5 - phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 31 was prepared in a manner similar to Intermediate 28. MS: m/z = 488.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.34 – 8.28 (m, 1H), 8.05 - 7.95 (m, 4H), 7.90-7.85 (m, 3H), 7.65 (d, J = 8.0 Hz, 2H), 7.48 – 7.37 (m, 3H), 6.90 (t, J = 6.8 Hz, 1H), 4.35 – 4.25 (m, 4H),3.50 – 3.40 (m, 4H),2.41 (d, J = 8.4 Hz, 2H), 2.25 – 2.16 (m, 2H). [00214] Intermediate 32: 3-(3-(4-((3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)phenyl)-5 - phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 32 was prepared in a manner similar to Intermediate 28. MS: m/z = 488.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 12.42 (br s, 1H), 10.4 - 10.0 (m, 2H), 8.55 (br s, 1H), 8.38 (d, J = 8.0 Hz, 1H), 8.13 – 8.07 (m, 1H), 8.06 – 8.00 (m, 5H), 7.98 – 7.94 (m, 1H), 7.69 (d, J = 8.0 Hz, 2H), 7.50 – 7.40 (m, 3H), 6.94 (t, J = 7.2 Hz, 1H), 4.39 - 4.33 (m, 2H), 4.01 (s, 2H), 3.95 – 3.89 (m, 3H), 3.42 – 3.39 (m, 3H), 2.47 – 2.38 (m, 2H). [00215] Intermediate 33: 3-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-3-azabicyclo[3.2.1]octan-8-amine Intermediate 33 was prepared in a manner similar to Intermediate 28. MS: m/z = 502.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ )) δ 8.17 (d, J = 8.4 Hz, 1H), 8.02 (d, J = 7.2 Hz, 2H), 7.97 (dd, J = 5.2, 1.6 Hz, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.43 - 7.35 (m, 5H), 7.29 (dd, J = 7.6, 1.6 Hz, 1H), 6.44 (dd, J = 7.6, 4.8 Hz, 1H), 3.62 (s, 2H), 2.96 (t, J = 4.4 Hz, 1H), 2.57 - 2.49 (m, 4H), 1.93 - 1.88 (m, 2H), 1.85 - 1.79 (m, 2H), 1.75 - 1.68 (m, 2H) [00216] Intermediate 34: (S)-3-(3-(4-((3-methylpiperazin-1-yl)methyl)phenyl)-5-phenyl - 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 34 was prepared in a manner similar to Intermediate 28. MS: m/z = 476.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.32 (d, J = 8.4 Hz, 1H), 8.07 - 7.99 (m, 4H), 7.94 - 7.84 (m, 3H), 7.73 (d, J = 8.4 Hz, 2H), 7.50 - 7.37 (m, 3H), 6.96 - 6.88 (m, 1H), 4.57 (s, 1H), 4.60 - 4.53 (s, 2H), 3.94 - 3.83 (m, 1H), 3.81 - 3.69 (m, 3H), 3.68 - 3.56 (m, 1H), 3.54 - 3.41 (m, 1H), 3.39 - 3.31 (m, 1H), 1.45 (d, J = 6.8 Hz, 3H). [00217] Intermediate 35: 3-(3-(4-((1,4-Diazepan-1-yl)methyl)phenyl)-5-phenyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: tert-Butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din-3- yl)benzyl)-1,4-diazepane-1-carboxylate To a solution of Intermediate 14 (1 g, 2.43 mmol), tert-butyl 1,4-diazepane-1-carboxylate (584 mg, 2.92 mmol) in ACN (20 mL) was added NaI (36.4 mg, 243 µmol) and K ₂ CO ₃ (671 mg, 4.86 mmol). The mixture was stirred at 80 °C for 2 hr. The reaction mixture was concentrated directly. The residue was purified by flash silica gel chromatography (Eluent of 0~10% MeOH in CH ₂ Cl ₂ ) to give tert-butyl 4-[[4-[2-(2-amino-3-pyridyl)-5-phenyl-imidazo[4,5-b]pyridin- 3- yl]phenyl]methyl]-1,4-diazepane-1-carboxylate (520 mg, yield: 33%) as a light-yellow solid, which was used directly in the next step without further purification. MS: m/z = 576.4 [M + H] ⁺ . Step 2: 3-(3-(4-((1,4-Diazepan-1-yl)methyl)phenyl)-5-phenyl-3H-imida zo[4,5-b]pyridin-2- yl)pyridin-2-amine To a solution of tert-butyl 4-[[4-[2-(2-amino-3-pyridyl)-5-phenyl-imidazo[4,5-b]pyridin- 3- yl]phenyl]methyl]-1,4-diazepane-1-carboxylate (520 mg, 0.903 mmol) in HCl/1,4-dioxane (4M, 10 mL). The mixture was stirred at 25 C for 1 hr. The reaction mixture was concentrated directly to give the crude product (310 mg HCl salt, yield: 67%). The 100 mg was purified by prep-HPLC (column: Phenomenex C18150 x 25mm x 10um; mobile phase: [water (NH ₄ HCO ₃ )-ACN]; B%: 28% - 58%, 8 min) to give 3-[3-[4-(1,4-diazepan-1-ylmethyl)phenyl]- 5-phenyl-imidazo[4,5-b]pyridin-2-yl]pyridin-2-amine (Intermediate 35, 9 mg) as light-yellow solid. MS: m/z = 476.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.4 (d, J = 8.4 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.52 - 7.39 (m, 7H), 7.14 (dd, J = 7.6, 1.8 Hz, 1H), 7.05 (br s, 2H), 6.39 - 6.34 (m, 1H), 3.72 (s, 2H), 2.82 (t, J = 6.4 Hz, 2H), 2.78 - 2.74 (m, 2H), 2.67 (t, J = 6.4 Hz, 2H), 2.66 - 2.57 (m, 2H), 1.78 - 1.64 (m, 2H). [00218] Intermediate 36: 3-(3-(4-((4-(Methylamino)piperidin-1-yl)methyl)phenyl)-5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 36 was prepared in a manner similar to Intermediate 35. MS: m/z = 490.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.07 - 7.94 (m, 4H), 7.53 - 7.43 (m, 6H), 7.41 -7.39 (m, 1H), 7.16 (dd, J = 7.8, 1.2 Hz, 1H), 7.02 (br s, 2H), 6.37 (dd, J = 7.4, 4.8 Hz, 1H), 3.55 (s, 2H), 3.47-3.37 (m, 1H), 2.80 (br d, J = 12.0 Hz, 2H), 2.31 (s, 3H), 2.01 (dd, J = 11.4, 9.8 Hz, 2H), 1.85 - 1.77 (m, 2H), 1.36 - 1.22 (m, 2H). [00219] Intermediate 37: 3-(3-(4-(((1R,4R)-2,5-Diazabicyclo[2.2.1]heptan-2- yl)methyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyr idin-2-amine Intermediate 37 was prepared in a manner similar to Intermediate 28. MS: m/z = 474.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.33 (d, J = 8.4 Hz, 1H), 8.06 - 8.00 (m, 6H), 7.88 (dd, J = 7.6, 1.6 Hz, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.46 - 7.40 (m, 3H), 6.92 (dd, J = 7.6, 6.4 Hz, 1H), 4.84 - 4.81 (m, 1H), 4.75 - 4.65 (m, 2H), 4.14 (d, J = 12.8 Hz, 1H), 3.96 - 3.92 (m, 1H), 3.74 - 3.71 (m, 1H), 3.62 - 3.60 (m, 1H), 3.38 - 3.32 (m, 1H), 2.87 - 2.82 (m, 1H), 2.39 - 2.36 (m, 1H). [00220] Intermediate 38: 3-(3-(4-((2,5-Diazabicyclo[2.2.2]octan-2-yl)methyl)phenyl)-5 - phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 38 was prepared in a manner similar to Intermediate 35. MS: m/z = 488.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 12.11 -11.44 (m, 1H), 10.27 - 9.61 (m, 2H), 8.56 - 8.40 (m, 1H), 8.38 (d, J = 8.4 Hz, 1H), 8.15 (dd, J = 6.0, 1.2 Hz, 1H), 8.10 - 7.99 (m, 5H), 7.86 (dd, J = 7.2, 1.2 Hz, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.51 - 7.46 (m, 2H), 7.46 - 7.40 (m, 1H), 6.91 (dd, J = 7.6, 6.4 Hz, 1H), 4.62 (br s, 2H), 4.01 - 3.79 (m, 4H), 3.76 - 3.70 (m, 2H), 2.21 (m, 2H), 1.97 - 1.80 (m, 2H). [00221] Intermediate 39: 2-(4-Piperidylamino)pyridine-4-carbonitrile Step 1: tert-Butyl 4-[(4-cyano-2-pyridyl)amino]piperidine-1-carboxylate A mixture of tert-butyl 4-aminopiperidine-1-carboxylate (1.20 g, 6.01 mmol), 2-bromopyridine- 4-carbonitrile (1.0 g, 5.46 mmol), BINAP (136 mg, 219 µmol), Pd ₂ (dba) ₃ (100 mg, 109 µmol) and t-BuONa (1.05 g, 10.9 mmol) in toluene (20 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 100 °C for 2 hr under N ₂ atmosphere. The mixture was diluted with H ₂ O (50 mL) and extracted with EtOAc (50 mL × 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a residue. The crude product was purified by silica gel flash chromatography (Eluent of 0~25% EtOAc in petroleum ether), tert-butyl 4-[(4-cyano-2- pyridyl)amino]piperidine-1-carboxylate (350 mg, yield: 20%) was obtained as a yellow solid. ¹ H NMR (400 MHz, Chloroform-d) δ 8.18 (d, J = 5.2 Hz, 1H), 6.71 (dd, J = 5.2, 1.2 Hz, 1H), 6.56 (s, 1H), 4.72 (d, J = 7.6 Hz, 1H), 4.14 - 4.00 (m, 2H), 3.90 - 3.76 (m, 1H), 2.96 – 2.90 (m, 2H), 2.05 - 1.99 (m, 2H), 1.46 (s, 9H), 1.43 - 1.33 (m, 2H). Step 2: 2-(4-Piperidylamino)pyridine-4-carbonitrile A solution of tert-butyl 4-[(4-cyano-2-pyridyl)amino]piperidine-1-carboxylate (350 mg, 1.16 mmol) in HCl in 1,4-dioxane (4M, 5 mL). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was concentrated under reduced pressure to give 2-(4-piperidylamino)pyridine- 4-carbonitrile (Intermediate 39, 200 mg, HCl salt, yield: 72%) as a yellow solid, which was used in the next step without further purification. [00222] Intermediate 40: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl-d2)phenyl)-5-phenyl- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine hydrochloride Step 1: (4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridi n-3-yl)phenyl)methan- d2-ol To a solution of Intermediate 13 (500 mg, 1.19 mmol) in THF (50 mL) at 0°C was added LiAlD ₄ (99.6 mg, 2.37 mmol) in portions under N ₂ atmosphere. The mixture was stirred at 0 °C for 1 hr. The reaction mixture was quenched with Na ₂ SO ₄ ·10 H ₂ O at 0 °C, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0~100% EtOAc in petroleum ether) to give (4-(2-(2-aminopyridin-3- yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)methan-d2- ol (190 mg, yield: 41%) as a yellow solid. MS: m/z = 396.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.15 (d, J = 8.4 Hz, 1H), 8.03 - 7.97 (m, 3H), 7.83 (d, J = 8.4 Hz, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.47 - 7.37 (m, 6H), 6.44 (dd, J = 7.6, 5.2 Hz, 1H). Step 2: 3-(3-(4-(Chloromethyl-d2)phenyl)-5-phenyl-3H-imidazo[4,5-b]p yridin-2-yl)pyridin-2- amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridi n-3- yl)phenyl)methan-d2-ol (190 mg, 480 μmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (171 mg, 1.44 mmol) in portions under N ₂ atmosphere. The mixture was stirred at 40 °C for 1 hr. The reaction mixture was filtered. The filter liquor was concentrated to dryness. The crude was used in the next step without further purification. 3-(3-(4-(chloromethyl-d2)phenyl)-5-phenyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (198 mg, crude) was obtained as a yellow solid. MS: m/z = 414.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.36 (d, J = 8.4 Hz, 1H), 8.12 (dd, J = 6.4, 1.6 Hz, 1H), 8.09 - 8.04 (m, 3H), 7.90 - 7.87 (m, 1H), 7.68 - 7.56 (m, 4H), 7.51 - 7.41 (m, 3H), 6.90 (dd, J = 7.2, 6.4 Hz, 1H). Step 3: tert-Butyl(1-((4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidaz o[4,5-b]pyridin-3- yl)phenyl)methyl-d2)piperidin-4-yl)carbamate A solution of 3-(3-(4-(chloromethyl-d2)phenyl)-5-phenyl-3H-imidazo[4,5-b]p yridin-2- yl)pyridin-2-amine (248 mg, 599 μmol), tert-butyl N-(4-piperidyl)carbamate (132 mg, 659 μmol), K ₂ CO ₃ (166 mg, 1.20 mmol) and NaI (89.8 mg, 599.2 μmol) in DMF (3 mL) was stirred at 80°C for 2 h under N ₂ atmosphere. The water (10 mL) was added to the mixture, and the mixture was extracted with EtOAc (3 x 5 mL). The combined organic layers were washed with brine (10 mL), dried over Na ₂ SO ₄ , filtered, and concentrated. The residue was purified by silica gel flash chromatography (Eluent of 0~100% EtOAc in petroleum ether) and prep-HPLC (column: Xtimate C18100*30 mm*3 μm; mobile phase: [water (FA) - ACN]; B%: 20% - 60%, 9 min). tert-Butyl(1-((4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidaz o[4,5-b]pyridin-3- yl)phenyl)methyl-d2)piperidin-4-yl)carbamate (180 mg, yield: 52%) was obtained as a yellow solid. MS: m/z = 578.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.13 (d, J = 8.4 Hz, 1H), 8.07 (dd, J = 4.8, 1.6 Hz, 1H), 8.03 - 8.00 (m, 2H), 7.81 (d, J = 8.4 Hz, 1H), 7.63 - 7.52 (m, 2H), 7.46 - 7.42 (m, 4H), 7.40 - 7.36 (m, 1H), 7.08 (dd, J = 7.6, 1.6 Hz, 1H), 6.59 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 4.52 - 4.39 (br s, 1H), 3.57 - 3.59 (m, 1H), 3.01 - 2.98 (m, 1H), 2.33 - 2.28 (m, 2H), 2.00 - 1.98 (m, 2H), 1.68 - 1.65 (m, 2H), 1.47 - 1.46 (m, 1H), 1.44 (s, 9H). Step 4: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl-d2)phenyl)-5-phenyl-3 H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine hydrochloride To a solution of tert-butyl (1-((4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]py ridin- 3-yl)phenyl)methyl-d2)piperidin-4-yl)carbamate (90.0 mg, 156 μmol) in CH ₂ Cl ₂ (3 mL) was added HCl in 1,4-dioxane (4 M, 974 μL) under N ₂ atmosphere. The mixture was stirred at 20 °C for1 hr. The mixture was filtered, washed with CH ₂ Cl ₂ (2 x 10 mL). The filter liquor was concentrated to dryness. Filter cake was dried to remove solvent. The crude product was used in the next step without further purification.3-(3-(4-((4-Aminopiperidin-1-yl)methyl- d2)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2- amine hydrochloride (Intermediate 40, 70 mg, HCl salt, yield: 93%) was obtained as a yellow solid. MS: m/z = 478.2 [M + H] ⁺ . ¹ H NMR (400MHz, Methanol-d ₄ ) δ 8.33 (d, J = 8.4 Hz, 1H), 8.08 - 8.00 (m, 4H), 7.91 (d, J = 8.0 Hz, 3H), 7.73 (d, J = 9.2 Hz, 2H), 7.50 - 7.38 (m, 3H), 6.91 (t, J = 6.6 Hz, 1H), 3.70 (d, J = 12.0 Hz, 2H), 3.61 - 3.52 (m, 1H), 3.35 - 3.29 (m, 1H), 3.28 - 3.17 (m, 1H), 2.31 (d, J = 10.8 Hz, 2H), 2.23 - 2.04 (m, 2H). [00223] Intermediate 41: 3-(3-(4-((4-((Methyl-d3)amino)piperidin-1-yl)methyl)phenyl)- 5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: Benzyl 4-((tert-butoxycarbonyl)amino)piperidine-1-carboxylate To a solution of tert-butyl N-(4-piperidyl)carbamate (12 g, 59.9 mmol) in CH ₂ Cl ₂ (100 mL) was added TEA (18.2 g, 179 mmol), and then the CbzCl (11.2 g, 65.9 mmol) was added into the mixture at 0 °C. The mixture was stirred at 25 °C for 2 hr. The mixture was concentrated under reduced pressure. The crude was purified by silica gel flash chromatography (Eluent of 10~50% EtOAc in petroleum ether) to give benzyl 4-((tert-butoxycarbonyl)amino)piperidine-1- carboxylate (16 g, yield: 71%) as an off-white solid. ¹ H NMR (400 MHz, Dimethylsulfoxide- d ₆ ) δ 7.40 - 7.28 (m, 5H), 5.06 (s, 2H), 3.90 (d, J = 13.6 Hz, 2H), 3.50 - 3.34 (m, 2H), 2.89 (s, 2H), 1.71 (d, J = 10.8 Hz, 2H), 1.37 (s, 9H), 1.30 - 1.18 (m, 2H). Step 2: Benzyl 4-((tert-butoxycarbonyl)(methyl-d3)amino)piperidine-1-carbox ylate To a solution of benzyl 4-(tert-butoxycarbonylamino)piperidine-1-carboxylate (13 g, 38.9 mmol) in THF (200 mL) was added NaH (4.66 g, 117 mmol) at 0 °C. After stirring at 0 °C for 30 min, CD ₃ I (16.5 g, 117 mmol) was added to the mixture. The mixture was stirred at 25 °C for 16 hr. The mixture was quenched with NH ₄ Cl (aq) (100 mL) at 0 °C. The mixture was duilted with H ₂ O (100 mL) and extrated with CH ₂ Cl ₂ (200 mL x 2). The combined organic layers were washed with brine (200 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0~20% EtOAc in petroleum ether) to give benzyl 4-((tert-butoxycarbonyl)(methyl-d ₃ )amino)piperidine-1- carboxylate (8.6 g, yield: 56%) as a colorless oil. MS: m/z = 252.3 [M + H - 100] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 7.42 - 7.28 (m, 5H), 5.07 (s, 2H), 4.14 - 3.89 (m, 3H), 2.82 (s, 2H), 1.58 – 1.48 (m, 4H), 1.39 (s, 9H). Step 3: tert-Butyl (methyl-d ₃ )(piperidin-4-yl)carbamate To a solution of benzyl 4-[tert-butoxycarbonyl(trideuteriomethyl)amino]piperidine-1- carboxylate (8.6 g, 24.5 mmol) in MeOH (90 mL) was added Pd/C (900 mg, 24.5 mmol). The mixture was stirred at 25 °C for 16 hr under H ₂ (15 psi). The mixture was filtered, and the filter cake was washed with MeOH (30 mL). The filtrate was concentrated under reduced pressure to give a tert-butyl (methyl-d ₃ )(piperidin-4-yl)carbamate (5 g, yield: 80%) as a colorless oil. MS: m/z = 218.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 3.93 - 3.62 (m, 1H), 3.26 - 3.16 (m, 1H), 2.95 (d, J = 12.0 Hz, 2H), 2.47 - 2.38 (m, 2H), 1.54 - 1.42 (m, 4H), 1.39 (s, 9H). Step 4: tert-Butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyr idin-3- yl)benzyl)piperidin-4-yl)(methyl-d3)carbamate To a solution of Intermediate 14 (1 g, 2.43 mmol) in DMF (10 mL) were added tert-butyl (methyl-d ₃ )(piperidin-4-yl)carbamate (527 mg, 2.43 mmol), NaI (182 mg, 1.21 mmol) and K ₂ CO ₃ (1.0 g, 7.28 mmol). The mixture was stirred at 80 °C for 18 hr. The reaction mixture was diluted with H ₂ O (20 mL) and extracted with CH ₂ Cl ₂ (20 mL x 3). The combined organic layers were washed with brine (20 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0~6% MeOH in CH ₂ Cl ₂ ) to give tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)(methyl-d ₃ )carbamate (750 mg, yield: 49%) as a yellow solid. MS: m/z = 593.3 [M + H] ⁺ . Step 5: 3-(3-(4-((4-((Methyl-d3)amino)piperidin-1-yl)methyl)phenyl)- 5-phenyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine To a solution of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyr idin-3- yl)benzyl)piperidin-4-yl)(methyl-d3)carbamate (430 mg, 725 µmol) in CH ₂ Cl ₂ (5 mL) was added TFA (165 mg, 1.45 mmol). The mixture was stirred at 25 °C for 1 hr. The mixture was diluted with H ₂ O (10 mL), and pH was adjusted to about 8 by NaHCO ₃ (aq.). The mixture was extracted with CH ₂ Cl ₂ (10 mL x 2). The combined organic layers were washed with brine (10 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-TLC (CH ₂ Cl ₂ : MeOH = 5 : 1), 3-(3-(4-((4-((methyl-d3)amino)piperidin-1- yl)methyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyr idin-2-amine (Intermediate 41, 350 mg crude, yield: 50%) was obtained as a light-yellow solid. MS: m/z = 493.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.19 (d, J = 8.4 Hz, 1H), 8.03 (d, J = 7.2 Hz, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.47 - 7.35 (m, 5H), 7.32 (dd, J = 7.6, 1.6 Hz, 1H), 6.47 (dd, J = 7.6, 4.8 Hz, 1H), 3.65 (s, 2H), 3.08 - 3.03 (m, 2H), 3.02 - 2.95 (m, 1H), 2.21 - 2.15 (m, 2H), 2.08 - 2.05 (m, 2H), 1.67 - 1.61 (m, 2H). [00224] Intermediate 42: tert-Butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-chloro-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazine-1-carboxylate To a solution of tert-butyl 4-(4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl)piperazine- 1- carboxylate (refer to Intermediate 10 for detail procedures, 21 g, 46.9 mmol) in DMSO (300 mL) were added 2-aminonicotinaldehyde (6.87 g, 56.4 mmol) and Na ₂ S ₂ O ₄ (28.8 g, 141 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched with H ₂ O (300 mL) at 25°C, and extracted with CH ₂ Cl ₂ (500 mL x 2). The combined organic layers were washed with H ₂ O (1000 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a crude product. After purified by silica gel flash chromatography (Eluent of 1 ~ 8% MeOH in CH ₂ Cl ₂ ), tert-butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carboxylate (Intermediate 42, 6.3 g, yield: 25%) was obtained as a yellow solid. MS: m/z = 520.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.05 (dd, J = 4.8, 2.0 Hz, 1H), 8.02 (d, J = 8.4 Hz, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.31 (dd, J = 8.4, 2.8 Hz, 3H), 7.02 (dd, J = 8.0, 2.0 Hz, 1H), 6.62 (br s, 2H), 6.33 (dd, J = 8.0, 4.8 Hz, 1H), 3.61 (s, 2H), 3.50 - 3.45 (m, 4H), 2.49 - 2.43 (m, 4H), 1.47 (s, 9H). [00225] Intermediate 43: 3-(5-(4-Chlorophenyl)-3-(4-(piperazin-1-ylmethyl)phenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine hydrochloride

Step 1: Methyl 4-((6-(4-chlorophenyl)-3-nitropyridin-2-yl)amino)benzoate A mixture of methyl 4-((6-chloro-3-nitropyridin-2-yl)amino)benzoate (refer to Intermediate 13 for detail procedures, 5 g, 16.3 mmol), (4-chlorophenyl)boronic acid (2.54 g,16.3 mmol), Cs ₂ CO ₃ (15.9 g, 48.8 mmol), and Pd(dppf)Cl ₂ (2.38 g, 3.25 mmol) in 1,4-dioxane (100 mL) and H ₂ O (20 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 80 °C for 16 hr under N ₂ atmosphere. The reaction mixture was diluted with H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (50 mL x 4). The combined organic layers were washed with brine (30 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 35 ~ 45% EtOAc in petroleum ether) to give methyl 4-((6-(4-chlorophenyl)-3-nitropyridin-2-yl)amino)benzoate (5 g, yield: 80%) as a yellow solid. MS: m/z = 383.9 [M + H] ⁺ . Step 2: Methyl 4-(2-(2-aminopyridin-3-yl)-5-(4-chlorophenyl)-3H-imidazo[4,5 -b]pyridin-3- yl)benzoate To a solution of methyl 4-((6-(4-chlorophenyl)-3-nitropyridin-2-yl)amino)benzoate (5 g, 13.0 mmol) and 2-aminonicotinaldehyde (1.75 g, 14.3 mmol) in DMSO (150 mL) was added Na ₂ S ₂ O ₄ (9.07 g, 52.1 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was diluted with H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (500 mL x 6). The combined organic layers were washed with brine (250 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 25 ~ 30% EtOAc in CH ₂ Cl ₂ ) to give methyl 4-(2-(2-aminopyridin-3- yl)-5-(4-chlorophenyl)-3H-imidazo[4,5-b]pyridin-3-yl)benzoat e (2.3 g, yield: 34%) as a yellow solid. MS: m/z = 456.0 [M + H] ⁺ . Step 3: (4-(2-(2-Aminopyridin-3-yl)-5-(4-chlorophenyl)-3H-imidazo[4, 5-b]pyridin-3- yl)phenyl)methanol To a solution of 4-(2-(2-aminopyridin-3-yl)-5-(4-chlorophenyl)-3H-imidazo[4,5 -b]pyridin-3- yl)benzoate (2.3 g, 5.05 mmol) in THF (30 mL) was added LiAlH ₄ (2.5 M, 2.42 mL) at 0 °C, then the mixture was stirred at 25°C for 2 hr. The reaction mixture was quenched with Na ₂ SO ₄ ·H ₂ O (4 g) at 0 °C, and the mixture was filtered, the filter cake was washed by CH ₂ Cl ₂ (30 mL x 3). The filtrate was concentrated under reduced pressure to give (4-(2-(2- aminopyridin-3-yl)-5-(4-chlorophenyl)-3H-imidazo[4,5-b]pyrid in-3-yl)phenyl)methanol (2.1 g, yield: 97%) as a yellow solid, which was directly used in the next step without purification. MS: m/z = 428.1 [M + H] ⁺ . Step 4: 3-(3-(4-(Chloromethyl)phenyl)-5-(4-chlorophenyl)-3H-imidazo[ 4,5-b]pyridin-2- yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(4-chlorophenyl)-3H-imidazo[4, 5-b]pyridin-3- yl)phenyl)methanol (1.85 g, 4.32 mmol) in CH ₂ Cl ₂ (40 mL) was added SOCl ₂ (1.54 g, 13.0 mmol) at 0 °C. The mixture was stirred at 40 °C for 3 hr. The reaction mixture was quenched with H ₂ O (5 mL) at 0 °C, and then filtered and concentrated under reduced pressure to give 3-(3- (4-(chloromethyl)phenyl)-5-(4-chlorophenyl)-3H-imidazo[4,5-b ]pyridin-2-yl)pyridin-2-amine (1.9 g, yield: 98%) as a black brown solid. MS: m/z = 455.9, 447.8 [M + H] ⁺ . Step 5: tert-Butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-(4-chlorophenyl)-3H-imidazo[ 4,5-b]pyridin- 3-yl)benzyl)piperazine-1-carboxylate To a solution of 3-(3-(4-(chloromethyl)phenyl)-5-(4-chlorophenyl)-3H-imidazo[ 4,5-b]pyridin-2- yl)pyridin-2-amine (1 g, 2.24 mmol), tert-butyl piperazine-1-carboxylate (417 mg, 2.24 mmol) in DMF (10 mL) were added NaI (67.2 mg, 448 μmol) and K ₂ CO ₃ (929 mg, 6.72 mmol). The mixture was stirred at 25 °C for 16 hr. The residue was diluted with H ₂ O (30 mL) and extracted with EtOAc (30 mL x 3). The combined organic layers were washed with brine (20 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0 ~ 4% MeOH in CH ₂ Cl ₂ ) to give tert-butyl 4-(4- (2-(2-aminopyridin-3-yl)-5-(4-chlorophenyl)-3H-imidazo[4,5-b ]pyridin-3-yl)benzyl)piperazine- 1-carboxylate(550 mg, yield: 40%) as a yellow solid. MS: m/z = 596.1 [M + H] ⁺ . Step 6: 3-(5-(4-Chlorophenyl)-3-(4-(piperazin-1-ylmethyl)phenyl)-3H- imidazo[4,5-b]pyridin-2- yl)pyridin-2-amine To a solution of tert-butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-(4-chlorophenyl)-3H-imidazo[ 4,5- b]pyridin-3-yl)benzyl)piperazine-1-carboxylate (550 mg, 923 µmol) in 1,4-dioxane (5 mL) was added 4.0 M HCl in 1,4-dioxane (3 mL) at 25 ºC. The mixture was stirred at 25 ºC for 1 hr. The reaction was concentrated under reduced pressure to give 3-(5-(4-chlorophenyl)-3-(4- (piperazin-1-ylmethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl) pyridin-2-amine (Intermediate 43, 550 mg, HCl salt, yield: 98%) as a yellow solid. MS: m/z = 496.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.33 (d, J = 8.4 Hz, 1H), 8.08 - 8.02 (m, 4H), 7.95 (d, J = 8.4 Hz, 2H), 7.90 (d, J = 7.6 Hz, 1H), 7.74 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 8.8 Hz, 2H), 6.94 (t, J = 7.2 Hz, 1H), 4.67 (s, 2H), 3.80 - 3.64 (m, 8H). [00226] Intermediate 44: tert-Butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-chloro-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)carbamate A mixture of tert-butyl (1-(4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl)piperidin- 4- yl)carbamate (refer to Intermediate 11 for detail procedures, 13.0 g, 28.0 mmol), 2- aminopyridine-3-carbaldehyde (4.12 g, 33.8 mmol), and Na ₂ S ₂ O ₄ (23.1 g, 112 mmol) in DMSO (500 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 100 °C for 16 hr under N ₂ atmosphere. The reaction mixture was diluted with water (500 mL) and extracted with EtOAc (500 mL × 3). The combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0 ~ 8% MeOH in CH ₂ Cl ₂ ) to give tert-butyl (1-(4-(2-(2- aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5-b]pyridin-3-yl)be nzyl)piperidin-4-yl)carbamate (Intermediate 44, 4.8 g, yield: 28%) as a yellow solid. MS: m/z = 534.3 [M + H] ⁺ . [00227] Intermediate 45: 3-(2-(2-Aminopyridin-3-yl)-3-(4-(piperazin-1-ylmethyl)phenyl )- 3H-imidazo[4,5-b]pyridin-5-yl)pyridin-2(1H)-one Step 1: tert-Butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-(2-oxo-1,2-dihydropyridin-3- yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazine-1-carboxylate A mixture of Intermediate 42 (250 mg, 481 μmol), (2-oxo-1,2-dihydropyridin-3-yl)boronic acid (80.1 mg, 577 μmol), Cs ₂ CO ₃ (470 mg, 1.44 mmol), and Pd(dppf)Cl ₂ (70,4 mg, 96.2 μmol) in 1,4-dioxane (5 mL) and H ₂ O (1 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 80 °C for 16 hr under N ₂ atmosphere. The reaction mixture was filtered at 25°C, and then diluted with H ₂ O (20 mL) and extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 1 ~ 100% EtOAc in petroleum ether and eluent of 1 ~ 10% MeOH in CH ₂ Cl ₂ ), tert-butyl 4- (4-(2-(2-aminopyridin-3-yl)-5-(2-oxo-1,2-dihydropyridin-3-yl )-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazine-1-carboxylate (200 mg, yield: 58%) was obtained as a brown solid. MS: m/z = 579.3 [M + H] ⁺ . Step 2: 3-(2-(2-Aminopyridin-3-yl)-3-(4-(piperazin-1-ylmethyl)phenyl )-3H-imidazo[4,5- b]pyridin-5-yl)pyridin-2(1H)-one To a solution of tert-butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-(2-oxo-1,2-dihydropyridin-3- yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazine-1-carboxylate (200 mg, 346 µmol) in 1,4-dioxane (3 mL) was added 4 M HCl in 1,4-dioxane (3 mL) at 25 ºC. The mixture was stirred at 25 ºC for 16 hr. The pH of the mixture was adjusted to ~ 8 with NaHCO ₃ . Then the mixture was extracted with CH ₂ Cl ₂ (20 mL x 3). The combined organic layers were washed with brine (20 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give 3-(2-(2- aminopyridin-3-yl)-3-(4-(piperazin-1-ylmethyl)phenyl)-3H-imi dazo[4,5-b]pyridin-5-yl)pyridin- 2(1H)-one (Intermediate 45, 200 mg, yield: 85%) as a yellow solid. MS: m/z = 479.2 [M + H] ⁺ . [00228] Intermediate 46: 3-(5-Morpholino-3-(4-(piperazin-1-ylmethyl)phenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: tert-Butyl 4-(4-((6-morpholino-3-nitropyridin-2-yl)amino)benzyl)piperaz ine-1- carboxylate To a solution of tert-butyl 4-(4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl)piperazine- 1- carboxylate (refer to Intermediate 10 for detail procedures, 300 mg, 670 µmol) and morpholine (117 mg, 1.34 mmol) in CH ₃ CN (4 mL) was added DIEA (173 mg, 1.34 mmol). The mixture was stirred at 90 °C for 2 hr. The reaction mixture was quenched with H ₂ O (10 mL) at 25 °C, and then extracted with CH ₂ Cl ₂ (15 mL x 2). The combined organic layers were washed with brine (15 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give tert- butyl 4-(4-((6-morpholino-3-nitropyridin-2-yl)amino)benzyl)piperaz ine-1-carboxylate (330 mg, yield: 93%) as a yellow solid. MS: m/z = 499.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 10.71 (s, 1H), 8.32 (d, J = 9.2 Hz, 1H), 7.53 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 6.13 (d, J = 9.6 Hz, 1H), 3.79 - 3.75 (m, 4H), 3.73 - 3.67 (m, 4H), 3.50 (s, 2H), 3.46 - 3.40 (m, 4H), 2.44 - 2.35 (m, 4H), 1.45 (s, 9H). Step 2: tert-Butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5-b] pyridin-3- yl)benzyl)piperazine-1-carboxylate To a solution of tert-butyl 4-(4-((6-morpholino-3-nitropyridin-2-yl)amino)benzyl)piperaz ine-1- carboxylate (330 mg, 662 µmol) in DMSO (10 mL) were added 2-aminonicotinaldehyde (97 mg, 794 µmol) and Na ₂ S ₂ O ₄ (542 mg, 2.65 mmol). The mixture was stirred at 100 °C for 2 hr. The reaction mixture was quenched with H ₂ O (20 mL) at 25 °C, and extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give the crude product. The crude was purified by silica gel flash chromatography (Eluent of 1 ~ 5% MeOH in CH ₂ Cl ₂ ) to give tert- butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5-b] pyridin-3- yl)benzyl)piperazine-1-carboxylate (270 mg, yield: 68%) as a yellow solid. MS: m/z = 571.2 [M + H] ⁺ . Step 3: 3-(5-Morpholino-3-(4-(piperazin-1-ylmethyl)phenyl)-3H-imidaz o[4,5-b]pyridin-2- yl)pyridin-2-amine To a solution of tert-butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carboxylate (270 mg, 473 µmol) in 1,4-dioxane (2 mL) was added 4 M HCl in 1,4-dioxane (2 mL) at 25 ºC. The mixture was stirred at 25 ºC for 16 hr. The reaction was concentrated under reduced pressure to give 3-(5-morpholino-3-(4-(piperazin-1- ylmethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-ami ne (Intermediate 46, 240 mg, HCl salt, yield: 93%) as a yellow solid. MS: m/z = 471.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.13 - 7.99 (m, 2H), 7.96 - 7.82 (m, 3H), 7.66 (dd, J =8.4, 3.2 Hz, 2H), 7.14 - 7.02 (m, 1H), 7.01 - 6.90 (m, 1H), 4.66 - 4.59 (m, 2H), 3.82 - 3.77 (m, 4H), 3.73 - 3.69 (m, 6H), 3.68 (s, 2H), 3.60 - 3.55 (m, 4H). [00229] Intermediate 47: 6-(2-(2-Aminopyridin-3-yl)-3-(4-(piperazin-1-ylmethyl)phenyl )- 3H-imidazo[4,5-b]pyridin-5-yl)pyridin-2(1H)-one Intermediate 47 was prepared in a manner similar to Intermediate 45. MS: m/z = 479.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.33 (d, J = 8.4 Hz, 1H), 8.16 (d, J = 8.4 Hz, 1H), 8.01 (dd, J = 4.8, 2.0 Hz, 1H), 7.60 (dd, J = 8.8, 6.8 Hz, 1H), 7.52 - 7.41 (m, 5H), 7.20 - 7.14 (m, 2H), 7.02 (br s, 2H), 6.46 (d, J = 8.8 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.53 (s, 2H), 2.73 - 2.69 (m, 4H), 2.36 - 2.30 (m, 4H). [00230] Intermediate 48: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-morpholino- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: tert-Butyl (1-(4-((6-morpholino-3-nitropyridin-2-yl)amino)benzyl)piperi din-4- yl)carbamate A mixture of tert-butyl (1-(4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl)piperidin- 4- yl)carbamate (refer to Intermediate 11 for detail procedures, 3 g, 6.49 mmol), morpholine (678 mg, 7.79 mmol), DIEA (1.68 g, 12.9 mmol) in MeCN (40 mL) was stirred at 90 °C for 2 hr. The reaction mixture was diluted with H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (100 mL x 3). The combined organic layers were washed with H ₂ O (50 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated to give tert-butyl (1-(4-((6-morpholino-3-nitropyridin-2- yl)amino)benzyl)piperidin-4-yl)carbamate (3.24 g, yield: 97%) as a yellow solid, which was directly used in the next step. MS: m/z = 513.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) 10.70 (s, 1H), 8.32 (d, J = 9.2 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 6.12 (d, J = 9.6 Hz, 1H), 4.53 - 4.34 (m, 1H), 3.79 - 3.75 (m, 4H), 3.75 - 3.55 (m, 4H), 3.48 (s, 3H), 2.90 - 2.75 (m, 2H), 2.15 - 2.05 (m, 2H), 1.95 - 1.75 (m, 2H), 1.76 - 1.53 (m, 2H), 1.44 (s, 9H). Step 2: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-morpholino- 3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine A mixture of tert-butyl (1-(4-((6-morpholino-3-nitropyridin-2-yl)amino)benzyl)piperi din-4- yl)carbamate (3.24 g, 6.32 mmol), 2-aminopyridine-3-carbaldehyde (926 mg, 7.58 mmol), and Na ₂ S ₂ O ₄ (3.88 g, 18.9 mmol) in DMSO (90 mL) was stirred at 100 °C for 24 hr. The reaction mixture was diluted with H ₂ O (200 mL) and extracted with CH ₂ Cl ₂ (50 mL x 3). Then sat. aq. Na ₂ CO ₃ (100 mL) was added to aqueous phase to adjust pH about 8~9. The aqueous phase was extracted with EtOAc (50 mL x 6), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0 ~ 7% MeOH in CH ₂ Cl ₂ ) to give 3-(3-(4-((4-aminopiperidin-1-yl)methyl)phenyl)-5-morpholino- 3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (1.2 g, yield: 29%) as a yellow solid. The product (80 mg) was purified by prep-HPLC (column: Phenomenex C18150 * 25 mm * μm ; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient:7% - 37% B over 10 min) to give 3-(3-(4-((4- aminopiperidin-1-yl)methyl)phenyl)-5-morpholino-3H-imidazo[4 ,5-b]pyridin-2-yl)pyridin-2- amine (Intermediate 48, 36.5 mg) as a light-yellow powder. MS: m/z = 485.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide- d ₆ ) δ 7.98 (d, J = 8.8 Hz, 1H), 7.96 (dd, J = 4.8, 2.0 Hz, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 7.03 (br s, 2H), 6.98 (dd, J = 8.0, 1.6 Hz, 1H), 6.89 (d, J = 8.8 Hz, 1H), 6.30 (dd, J = 8.0, 4.8 Hz, 1H), 3.69 - 3.65 (m, 4H), 3.50 (s, 2H), 3.41 - 3.38 (m, 5H), 2.78 - 2.70 (m, 2H), 2.02 - 1.92 (m, 2H), 1.70 - 1.64 (m, 2H), 1.35 - 1.16 (m, 2H). [00231] Intermediate 49: 3-(5-(4-fluorophenyl)-3-(4-(piperazin-1-ylmethyl)phenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine hydrochloride Intermediate 49 was prepared in a manner similar to Intermediate 45. MS: m/z = 480.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 13.00 - 12.05 (m, 1H), 10.26 - 9.46 (m, 2H), 8.60 - 8.48 (m, 1H), 8.38 (d, J = 8.4 Hz, 1H), 8.19 - 8.06 (m, 4H), 7.90 - 7.82 (m, 3H), 7.68 (d, J = 8.4 Hz, 2H), 7.32 (t, J = 9.2 Hz, 2H), 7.03 - 6.93 (m, 1H), 4.51 (br s, 2H), 3.55 - 3.50 (m, 4H), 2.59 - 2.51 (m, 4H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -113.04. [00232] Intermediate 50: 3-(3-(4-(Chloromethyl)phenyl)-5-cyclopropyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine

Step 1: Methyl 4-((6-cyclopropyl-3-nitropyridin-2-yl)amino)benzoate To a solution of methyl 4-((6-chloro-3-nitropyridin-2-yl)amino)benzoate (refer to Intermediate 13 for detail procedures, 30 g, 97.5 mmol) in 1,4-dioxane (300 mL) were added cyclopropylboronic acid (12.6 g, 146 mmol), Cs ₂ CO ₃ (95.3 g, 292 mmol) and H ₂ O (50 mL) at 25 °C. The mixture was stirred at 100°C for 12 hr under N ₂ . The reaction mixture was poured into H ₂ O (500 mL) and extracted with CH ₂ Cl ₂ (200 mL x 2). The combined organic layers were washed with brine (400 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. The residue was purified by silica gel flash chromatography (Eluent of 0~50% EtOAc in petroleum ether, and then use CH ₂ Cl ₂ directly) to give methyl 4-((6-cyclopropyl-3-nitropyridin-2- yl)amino)benzoate (25 g, yield: 74%) as an off-white solid. MS: m/z = 314.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.20 (s, 1H), 8.42 (d, J = 8.4 Hz, 1H), 7.94 (d, J = 8.4 Hz, 2H), 7.80 (d, J = 8.8 Hz, 2H), 7.05 (d, J = 8.4 Hz, 1H), 3.84 (s, 3H), 2.28 - 2.18 (m, 1H), 1.15 - 1.08 (m, 2H), 1.07 - 1.01 (m, 2H). Step 2: Methyl 4-(2-(2-aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4,5-b]py ridin-3- yl)benzoate To a solution of methyl 4-((6-cyclopropyl-3-nitropyridin-2-yl)amino)benzoate (20 g, 63.8 mmol) in DMSO (500 mL) were added 2-aminopyridine-3-carbaldehyde (9.4 g, 76.6 mmol) and Na ₂ S ₂ O ₄ (44.5 g, 255 mmol) at 25 °C. The mixture was stirred at 100 °C for 12 hr. The reaction mixture was poured into H ₂ O (500 mL) and then extracted with CH ₂ Cl ₂ (200 mL x 2). The combined organic layers were washed with brine (400 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated to dryness. The residue was purified by silica gel flash chromatography (Eluent of 1~3% MeOH in CH ₂ Cl ₂ ) to give methyl 4-(2-(2-aminopyridin-3-yl)- 5-cyclopropyl-3H-imidazo[4,5-b]pyridin-3-yl)benzoate (10 g, yield: 37%) as a red solid. MS: m/z = 386.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.11 - 8.06 (m, 3H), 8.02 (dd, J = 5.6, 1.6 Hz, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.41 - 7.27 (m, 4H), 6.59 (dd, J = 7.6, 5.2 Hz, 1H), 3.89 (s, 3H), 2.24 - 2.17 (m, 1H), 0.98 - 0.92 (m, 2H), 0.87 - 0.82 (m, 2H). Step 3: (4-(2-(2-Aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4,5-b]p yridin-3- yl)phenyl)methanol To a solution of methyl 4-(2-(2-aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4,5-b]py ridin-3- yl)benzoate (2 g, 5.2 mmol) in THF (50 mL) was added LiAlH ₄ (3.1 mL, 2.5M) at 0 °C. The mixture was stirred at 0 °C for 1.5 hr, and then was quenched with Na ₂ SO ₄ ·10H ₂ O (8 g) at 0 °C. The mixture was filtered, and the filter cake was washed by CH ₂ Cl ₂ (30 mL x 2). The filtrate was concentrated under reduced pressure to give (4-(2-(2-aminopyridin-3-yl)-5-cyclopropyl-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (1.8 g, crude) as a yellow solid, which was used in the next step without further purification. MS: m/z = 358.0 [M ] ⁺ . Step 4: 3-(3-(4-(Chloromethyl)phenyl)-5-cyclopropyl-3H-imidazo[4,5-b ]pyridin-2-yl)pyridin-2- amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4,5-b]p yridin-3- yl)phenyl)methanol (1.4 g, 3.9 mmol) in CH ₂ Cl ₂ (20 mL) was added SOCl ₂ (2.8 g, 23.5 mmol) dropwise at 25 °C. The mixture was stirred at 40 °C for 1 hr. The reaction mixture was concentrated to give 3-(3-(4-(chloromethyl)phenyl)-5-cyclopropyl-3H-imidazo[4,5-b ]pyridin-2- yl)pyridin-2-amine (Intermediate 50, 1.43 g, yield: 93%) as an off-white solid. MS: m/z = 376.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.59 - 8.24 (m, 2H), 8.17 - 8.08 (m, 2H), 7.81 (dd, J = 7.2, 1.6 Hz, 1H), 7.60 (d, J = 8.0 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 1H), 6.87 (dd, J = 7.6, 6.0 Hz, 1H), 4.85 (s, 2H), 2.27 - 2.17 (m, 1H), 1.00 - 0.92 (m, 2H), 0.88 - 0.81 (m, 2H). [00233] Intermediate 51: 4-(Piperidin-4-ylamino)pyrimidine-2-carbonitrile Step 1: tert-Butyl 4-((2-cyanopyrimidin-4-yl)amino)piperidine-1-carboxylate To a solution of tert-butyl 4-aminopiperidine-1-carboxylate (600 mg, 3.0 mmol) and 2- chloropyrimidine-4-carbonitrile (418 mg, 3.0 mmol) in DMF (5 mL) were added K ₂ CO ₃ (1.24 g, 8.99 mmol) and NaI (89.8 mg, 599 μmol). The mixture was stirred at 80 ºC for 1hr. The reaction mixture was diluted with H ₂ O (20 mL), and then extracted with EtOAc (30 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0 ~ 50% EtOAc in petroleum ether) to give tert-butyl 4-[(2- cyanopyrimidin-4-yl)amino]piperidine-1-carboxylate (860 mg, yield: 92%) as a white solid. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.13 - 8.01 (m, 2H), 6.66 (d, J = 5.6 Hz, 1H), 4.05 - 3.95 (m, 1H), 3.87 – 3.84 (m, 2H), 2.99 – 2.86 (m, 2H), 1.86 – 1.83 (m, 2H), 1.40 (s, 9H), 1.34 - 1.26 (m, 2H). Step 2: 4-(Piperidin-4-ylamino)pyrimidine-2-carbonitrile To a solution of tert-butyl 4-[(2-cyanopyrimidin-4-yl)amino]piperidine-1-carboxylate (110 mg, 362 μmol) in DCM (3 mL) was added TFA (767 mg, 6.73 mmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude 4- (piperidin-4-ylamino)pyrimidine-2-carbonitrile (Intermediate 51, 120 mg, yield: 100%, TFA salt) was used in the next step without further purification. MS: m/z = 204.0 [M + H] ⁺ . [00234] Intermediate 52: 6-(Piperidin-4-ylamino)pyrimidine-4-carbonitrile Step 1: tert-Butyl 4-((6-cyanopyrimidin-4-yl)amino)piperidine-1-carboxylate) To a solution of tert-butyl 4-aminopiperidine-1-carboxylate (700 mg, 3.50 mmol) and 6- chloropyrimidine-4-carbonitrile (487 mg, 3.50 mmol) in DMF (5 mL) were added K ₂ CO ₃ (1.45 reaction mixture was diluted with H ₂ O (20 mL), and then extracted with EtOAc (30 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0 ~ 45% EtOAc in petroleum ether) to give tert-butyl 4-[(6- cyanopyrimidin-4-yl)amino]piperidine-1-carboxylate (1.0 g, yield: 94%) as a white solid. MS: m/z = 304.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.50 (s, 1H), 8.07 (d, J = 7.6 Hz, 1H), 6.92 (s, 1H), 4.08 - 4.01 (m, 1H), 3.88 – 3.85 (m, 2H), 2.95 – 2.75 (m, 2H), 1.86 – 1.8.3 (m, 2H), 1.40 (s, 9H), 1.34 - 1.27 (m, 2H). Step 2: 6-(Piperidin-4-ylamino)pyrimidine-4-carbonitrile To a solution of tert-butyl 4-[(6-cyanopyrimidin-4-yl)amino]piperidine-1-carboxylate (285 mg, 939 μmol) in CH ₂ Cl ₂ (5 mL) was added TFA (535 mg, 4.7 mol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude product 6-(piperidin-4-ylamino)pyrimidine-4-carbonitrile (Intermediate 52, 298 mg TFA salt, yield: 100%), which was used in the next step without further purification. MS: m/z = 204.0 [M + H] ⁺ . [00235] Intermediate 53: 4-(Piperazin-1-yl)pyrimidine-2-carbonitrile Step 1: Tert-butyl 4-(2-cyanopyrimidin-4-yl)piperazine-1-carboxylate To a solution of tert-butyl piperazine-1-carboxylate (550 mg, 2.95 mmol) and 2- chloropyrimidine-4-carbonitrile (412 mg, 2.95 mmol) in DMF (5 mL) were added K ₂ CO ₃ (1.22 g, 8.86 mmol) and NaI (88.5 mg, 590 μmol). Themixture was stirred at 80 ºC for 1 hr. The reaction mixture was diluted with H ₂ O (20 mL), and then extracted with EtOAc (30 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0 ~ 10% EtOAc in petroleum ether) to give tert-butyl 4-(2- cyanopyrimidin-4-yl)piperazine-1-carboxylate (780 mg, yield: 92%) as a white solid. MS: m/z = 290.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.29 (d, J = 6.4 Hz, 1H), 7.10 (d, J = 6.4 Hz, 1H), 3.73 – 3.60 (m, 4H), 3.46 - 3.41 (m, 4H), 1.42 (s, 9H). Step 2: 4-(Piperazin-1-yl)pyrimidine-2-carbonitrile To a solution of tert-butyl 4-(2-cyanopyrimidin-4-yl)piperazine-1-carboxylate (140 mg, 483 μmol) in CH ₂ Cl ₂ (3 mL) was added TFA (767 mg, 6.73 mmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude 4- (piperazin-1-yl)pyrimidine-2-carbonitrile (Intermediate 53, 146 mg TFA salt, yield: 100%) was used in the next step without further purification. MS: m/z = 190.0 [M + H] ⁺ . [00236] Intermediate 54: 6-(Piperazin-1-yl)pyrimidine-4-carbonitrile Intermediate 54 was prepared in a manner similar to Intermediate 53. [00237] Intermediate 55: 4-(Piperazin-1-yl)-1,3,5-triazine-2-carbonitrile Step 1: tert-Butyl 4-(4-chloro-1,3,5-triazin-2-yl)piperazine-1-carboxylate To a solution of tert-butyl piperazine-1-carboxylate (3 g, 1.11 mmol) in THF (70 mL) was added DIEA (3.12 g, 24.2 mmol). The mixture was stirred at 0 °C for 10 min. Then 2,4-dichloro- 1,3,5-triazine (2.42 g, 16.1 mmol) in THF (30 mL) was added to the mixture. The mixture was stirred at 25 °C for 16 hr. The mixture was partitioned between EtOAc (600 mL) and H ₂ O (200 mL). The combined organic layers were washed with H ₂ O (60 mL) and dried over Na ₂ SO ₄ , filtered and concentrated. The residue was purified by silica gel flash chromatography (Eluent of 0 ~ 27% EtOAc in petroleum ether) to give tert-butyl 4-(4-chloro-1,3,5-triazin-2- yl)piperazine-1-carboxylate (3.45 g, yield: 70%) as a light-yellow solid. MS: m/z = 300.1 [M + H]+.1H NMR (400 MHz, Chloroform-d) δ 8.36 (s, 1H), 3.87 - 3.83 (m, 4H), 3.51 - 3.48 (m, 4H), 1.48 (s, 9H). Step 2: tert-Butyl 4-(4-cyano-1,3,5-triazin-2-yl)piperazine-1-carboxylate To a solution of tert-butyl 4-(4-chloro-1,3,5-triazin-2-yl)piperazine-1-carboxylate (3.45 g, 11.5 mmol) in DMSO (110 mL) were added KCN (1.64 g, 25.2 mmol) and DABCO (258 mg, 2.30 mmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was poured into H ₂ O (1 L). The resulting mixture was extracted with EtOAc (500 mL x 2). The combined organic layers were washed with brine (100 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0~30% EtOAc in petroleum ether), tert-butyl 4-(4-cyano-1,3,5-triazin-2-yl)piperazine-1-carboxylate (1.5 g, yield: 44%) was obtained as a light-yellow solid. MS: m/z = 291.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.57 (s, 1H), 3.89 - 3.82 (m, 4H), 3.53 - 3.50 (m, 4H), 1.48 (s, 9H). Step 3: 4-(Piperazin-1-yl)-1,3,5-triazine-2-carbonitrile To a solution of tert-butyl 4-(4-cyano-1,3,5-triazin-2-yl)piperazine-1-carboxylate (200 mg, 689 μmol) in CH ₂ Cl ₂ (3 mL) was added TFA (1.02 g, 8.07 mmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude 4- (piperazin-1-yl)-1,3,5-triazine-2-carbonitrile (Intermediate 55, 209 mg TFA salt, yield: 100%) was used in the next step without further purification. [00238] Intermediate 56: 3-(3-(4-(Chloromethyl)phenyl)-5-morpholino-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine Step 1: Methyl 4-((6-morpholino-3-nitropyridin-2-yl)amino)benzoate A mixture of methyl 4-((6-chloro-3-nitropyridin-2-yl)amino)benzoate (refer to Intermediate 13 for detail procedures, 2.5 g, 8.13 mmol), morpholine (849 mg, 9.75 mmol), DIEA (2.10 g, 16.2 mmol) in CH ₃ CN (30 mL) was stirred at 90 °C for 2 hr. The reaction mixture was filtered and the filter cake was dried under reduced pressure to give methyl 4-((6-morpholino-3-nitropyridin- 2-yl)amino)benzoate (2.94 g, yield: 92%) as a yellow solid. MS: m/z = 359.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 10.74 (s, 1H), 8.27 (d, J = 9.6 Hz, 1H), 7.98 - 7.94 (m, 2H), 7.83 - 7.79 (m, 2H), 6.58 (d, J = 9.6 Hz, 1H), 3.84 (s, 3H), 3.75 - 3.65 (m, 8H). Step 2: Methyl 4-(2-(2-aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5-b]pyr idin-3- yl)benzoate A mixture of methyl 4-((6-morpholino-3-nitropyridin-2-yl)amino)benzoate (2.94 g, 8.20 mmol), 2-aminonicotinaldehyde (1.10 g, 9.02 mmol), and Na ₂ S ₂ O ₄ (5.71 g, 32.8 mmol) in DMSO (30 mL) was stirred at 100 °C for 16 hr. The reaction mixture was cooled to room temperature and the pH was adjusted to about 9 with sat. NaHCO ₃ . Then the mixture was diluted with H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (100 mL x 3). The combined organic layers were washed with brine (100 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. The crude was triturated with EtOAc (100 mL) at 20 °C for 30 min to give methyl 4-(2-(2- aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5-b]pyridin-3-y l)benzoate (3.5 g, yield: 83%) as a green solid.. MS: m/z = 431.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide- d ₆ ) δ 8.07 (d, J = 8.4 Hz, 2H), 8.03 - 7.97 (m, 2H), 7.55 (d, J = 8.8 Hz, 2H), 7.32 - 7.13 (m, 3H), 6.93 (d, J = 8.8 Hz, 1H), 6.51 - 6.44 (m, 1H), 3.88 (s, 3H), 3.70 - 3.65 (m, 4H), 3.44 - 3.38 (m, 4H). Step 3: (4-(2-(2-Aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5-b]py ridin-3- yl)phenyl)methanol A mixture of methyl 4-(2-(2-aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5-b]pyr idin-3- yl)benzoate (3.5 g, 8.13 mmol) in THF (100 mL) was added LiAlH ₄ (2.5 M, 3.90 mL) dropwise at 0 °C, then the mixture was stirred at 20 °C for 1 hr. The reaction mixture was quenched with Na ₂ SO ₄ ·10H ₂ O (5 g) at 0 °C, filtered and concentrated under reduced pressure to give (4-(2-(2- aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5-b]pyridin-3-y l)phenyl)methanol (2.4 g, yield: 63%) as a green solid. MS: m/z = 403.1 [M + H] ⁺ . Step 4: 3-(3-(4-(Chloromethyl)phenyl)-5-morpholino-3H-imidazo[4,5-b] pyridin-2-yl)pyridin-2- amine To a mixture of (4-(2-(2-aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5-b]py ridin- 3yl)phenyl)methanol (2.4 g, 5.96 mmol) in CH ₂ Cl ₂ (16 mL) was added SOCl ₂ (4.26 g, 35.7 mmol,). The mixture was stirred at 40 °C for 1 hr. The reaction mixture was concentrated under reduced pressure to give 3-(3-(4-(chloromethyl)phenyl)-5-morpholino-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (Intermediate 56, 2.6 g, yield: 64%) as a green solid. MS: m/z = 421.0 [M + H] ⁺ . [00239] Intermediate 57: 3-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)-1-methylpyridin-2(1H)-one Step 1: Methyl 4-((3-nitro-6-(trimethylstannyl)pyridin-2-yl)amino)benzoate To a solution of methyl 4-((6-chloro-3-nitropyridin-2-yl)amino)benzoate (refer to Intermediate 13 for detail procedure, 5 g, 16.3 mmol), Pd(PPh ₃ ) ₄ (939 mg, 813 μmol) and 1,1,1,2,2,2- hexamethyldistannane (11.1 g, 33.7 mmol) in 1,4-dioxane (100 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 90 °C for 16 hr under N ₂ atmosphere. The reaction was concentrated under reduced pressure to give methyl 4-((3-nitro-6- (trimethylstannyl)pyridin-2-yl)amino)benzoate (7.09 g, yield: 34%) as a black solid, which was directly used in the next step. Step 2: Methyl 4-((1'-methyl-5-nitro-2'-oxo-1',2'-dihydro-[2,3'-bipyridin]- 6-yl)amino)benzoate A mixture of methyl 4-((3-nitro-6-(trimethylstannyl)pyridin-2-yl)amino)benzoate (7.09 g, 16.3 mmol), 3-bromo-1-methylpyridin-2(1H)-one (3.06 g, 16.3 mmol), and Pd(PPh ₃ ) ₄ (939 mg, 813 μmol) in 1,4-dioxane (100 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 125 °C for 1 hr under N ₂ atmosphere. The reaction was concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 1~5% MeOH in CH ₂ Cl ₂ ), methyl 4-((1'-methyl-5-nitro-2'-oxo-1',2'-dihydro-[2,3'-bipyridin]- 6- yl)amino)benzoate (3.6 g, purity: 58%) was obtained as a black solid. MS: m/z = 351.1 [M + H] ⁺ . Step 3: Methyl 4-(2-(2-aminopyridin-3-yl)-5-(1-methyl-2-oxo-1,2-dihydropyri din-3-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzoate To a solution of methyl 4-((5-amino-1'-methyl-2'-oxo-1',2'-dihydro-[2,3'-bipyridin]- 6- yl)amino)benzoate (2.6 g, 7.42 mmol) in DMSO (30 mL) were added Na ₂ S ₂ O ₄ (5.94 g, 29.7 mmol, 87% purity) and 2-aminonicotinaldehyde (1.09 g, 8.9 mmol). The mixture was stirred at 100 °C for 2 hr. The reaction mixture was quenched with H ₂ O (50 mL) at 25°C, and then diluted with CH ₂ Cl ₂ (100 mL) and extracted with H ₂ O (100 mL x 3). The combined organic layers were washed with brine (100 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 1~5% MeOH in CH ₂ Cl ₂ ), methyl 4-(2-(2-aminopyridin-3-yl)-5-(1-methyl-2-oxo-1,2-dihydropyri din-3-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzoate (750 mg, yield: 24%) was obtained as a brown solid. MS: m/z = 453.1 [M + H] ⁺ . Step 4: 3-(2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5-b]pyridin-5- yl)-1-methylpyridin-2(1H)-one To a solution of methyl 4-(2-(2-aminopyridin-3-yl)-5-(1-methyl-2-oxo-1,2-dihydropyri din-3-yl)- 3H-imidazo[4,5-b]pyridin-3-yl)benzoate (1.0 g, 2.21 mmol) in THF (15 mL) was added LiAlH ₄ (1.33 mL, 2.5 M in THF). The mixture was stirred at 0 °C for 1 hr. The reaction mixture was quenched with Na ₂ SO ₄ ·10H ₂ O (2 g) at 0 °C, filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 1~5% MeOH in CH ₂ Cl ₂ ), 3-(2-(2- aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imidazo[4, 5-b]pyridin-5-yl)-1- methylpyridin-2(1H)-one (200 mg, yield: 16%) was obtained as a yellow solid, which was used to the next step directly. Step 5: 3-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imi dazo[4,5-b]pyridin-5- yl)-1-methylpyridin-2(1H)-one To a solution of 3-(2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5- b]pyridin-5-yl)-1-methylpyridin-2(1H)-one (160 mg, 377 μmol) in CH ₂ Cl ₂ (20 mL) was added SOCl ₂ (135 mg, 1.13 mmol) at 0 °C. The mixture was stirred at 25 °C for 1 hr. The reaction mixture was quenched with H ₂ O (3 mL) at 0 °C, and then filtered and concentrated under reduced pressure to give 3-(2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)-1-methylpyridin-2(1H)-one (Intermediate 57, 150 mg, yield: 66%) as a yellow solid. MS: m/z = 443.0 [M + H] ⁺ . [00240] Intermediate 58: 3-(3-(4-(Chloromethyl)phenyl)-5-cyclobutyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine

Step 1: (E)-1-Cyclobutyl-3-(dimethylamino)prop-2-en-1-one To a solution of 1-cyclobutylethan-1-one (8 g, 81.5 mmol) in DMF (20 mL) were added CH ₃ ONa (220 mg, 4.08 mmol) and DMF-DMA (19.4 g, 163 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched with H ₂ O (50 mL) at 25 °C, and then extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give (E)-1- cyclobutyl-3-(dimethylamino)prop-2-en-1-one (10 g, yield: 74%) as a yellow oil. MS: m/z = 154.2 [M + H] ⁺ . Step 2: 6-Cyclobutyl-3-nitropyridin-2-ol To a solution of (E)-1-cyclobutyl-3-(dimethylamino)prop-2-en-1-one (10 g, 65.3 mmol) in H ₂ O (100 mL) were added piperidinium acetate(4.74 g, 32.6 mmol) and 2-nitroacetamide (10.2 g, 97.9 mmol). The mixture was stirred at 25 °C for 16 hr. The reaction mixture was extracted with CH ₂ Cl ₂ (150 mL x 2). The combined organic layers were washed with brine (150 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. The crude was triturated with EtOAc : petroleum ether = 1 : 10 at 25 °C for 10 min to give 6-cyclobutyl-3-nitropyridin-2- ol (6.5 g, yield: 51%) as a yellow solid. MS: m/z = 195.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 12.85 - 12.40 (m, 1H), 8.42 (d, J = 8.0 Hz, 1H), 6.34 (d, J = 8.0 Hz, 1H), 3.55 - 3.44 (m, 1H), 2.30 - 2.13 (m, 4H), 2.00 - 1.94 (m, 1H), 1.86 - 1.77 (m, 1H). Step 3: 2-Chloro-6-cyclobutyl-3-nitropyridine A solution of 6-cyclobutyl-3-nitropyridin-2-ol (6.5 g, 33.5 mmol) in POCl ₃ (50 mL) was stirred at 100 °C for 1.5 hr. The reaction mixture was filtered and concentrated under reduced pressure. The crude was quenched with aqueous NaHCO ₃ (50 mL) at 10 °C, and then extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (100 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give 2-chloro-6-cyclobutyl-3- nitropyridine (5.5 g, yield: 76%) as a black oil. MS: m/z = 213.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.48 (d, J = 8.0 Hz, 1H), 7.56 (d, J = 8.4 Hz, 1H), 3.83 - 3.71 (m, 1H), 2.34 - 2.22 (m, 4H), 2.07 - 1.96 (m, 1H), 1.92 - 1.79 (m, 1H). Step 4: (4-((6-Cyclobutyl-3-nitropyridin-2-yl)amino)phenyl)methanol To a solution of 2-chloro-6-cyclobutyl-3-nitropyridine (5.5 g, 25.9 mmol) in DMSO (60 mL) were added DIEA (10 g, 77.6 mmol) and (4-aminophenyl)methanol (3.19 g, 25.9 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched with H ₂ O (200 mL) at 25°C and extracted with CH ₂ Cl ₂ (500 mL x 3). The combined organic layers were washed with brine (500 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give (4-((6-cyclobutyl-3-nitropyridin-2-yl)amino)phenyl)methanol (7.74 g, yield: 83%) as a brown solid. MS: m/z = 300.1 [M + H] ⁺ . Step 5: 4-((6-Cyclobutyl-3-nitropyridin-2-yl)amino)benzyl acetate To a solution of (4-((6-cyclobutyl-3-nitropyridin-2-yl)amino)phenyl)methanol (7.7 g, 25.7 mmol) in CH ₂ Cl ₂ (100 mL) were added TEA (7.81 g, 77.2 mmol), Ac ₂ O (3.94 g, 38.6 mmol) and DMAP (314 mg, 2.57 mmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was quenched with H ₂ O (100 mL) at 25 °C, and then extracted with CH ₂ Cl ₂ (100 mL x 3). The combined organic layers were washed with brine (100 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 1~5% EtOAc in petroleum ether), 4-((6-cyclobutyl-3-nitropyridin-2-yl)amino)benzyl acetate (5.65 g, yield: 64%) was obtained as a yellow oil. MS: m/z = 342.0 [M + H] ⁺ . Step 6: 4-(2-(2-Aminopyridin-3-yl)-5-cyclobutyl-3H-imidazo[4,5-b]pyr idin-3-yl)benzyl acetate acetate To a solution of 4-((6-cyclobutyl-3-nitropyridin-2-yl)amino)benzyl acetate (5.6 g, 16.4 mmol) in DMSO (60 mL) were added Na ₂ S ₂ O ₄ (13.1 g, 65.6 mmol, 87% purity) and 2- aminonicotinaldehyde (2.4 g, 19.7 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched with H ₂ O (100 mL) at 25 °C, and then extracted with CH ₂ Cl ₂ (150 mL x 2). The combined organic layers were washed with brine (150 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 1 ~ 50% CH ₂ Cl ₂ in EtOAc), 4-(2-(2-aminopyridin-3-yl)-5- cyclobutyl-3H-imidazo[4,5-b]pyridin-3-yl)benzyl acetate acetate (2.1 g, yield: 31%) was obtained as a yellow solid. MS: m/z = 414.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide- d ₆ ) δ 8.10 (d, J = 8.4 Hz, 1H), 7.98 (d, J = 4.4 Hz, 1H), 7.52 (d, J = 8.0 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.4 Hz, 1H), 7.16 (d, J = 7.2 Hz, 1H), 6.85 (br s, 2H), 6.41 (dd, J = 7.6, 5.2 Hz, 1H), 5.16 (s, 2H), 3.74 - 3.64 (m, 1H), 2.27 - 2.20 (m, 4H), 2.11 (s, 3H), 1.99 - 1.92 (m, 1H), 1.84 - 1.75 (m, 1H). Step 7: (4-(2-(2-Aminopyridin-3-yl)-5-cyclobutyl-3H-imidazo[4,5-b]py ridin-3- yl)phenyl)methanol To a solution of 4-(2-(2-aminopyridin-3-yl)-5-cyclobutyl-3H-imidazo[4,5-b]pyr idin-3-yl)benzyl acetate acetate (500 mg, 1.21 mmol) in MeOH (5 mL), THF (5 mL) and H ₂ O (2 mL) was added K ₂ CO ₃ (501 mg, 3.63 mmol). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was diluted with H ₂ O (10 mL) and extracted with CH ₂ Cl ₂ (15 mL x 2). The combined organic layers were washed with brine (15 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give (4-(2-(2-aminopyridin-3-yl)-5-cyclobutyl-3H-imidazo[4,5-b]py ridin-3- yl)phenyl)methanol (450 mg, yield: 86%) as a yellow solid. MS: m/z = 372.0 [M + H] ⁺ . Step 8: 3-(3-(4-(Chloromethyl)phenyl)-5-cyclobutyl-3H-imidazo[4,5-b] pyridin-2-yl)pyridin-2- amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-cyclobutyl-3H-imidazo[4,5-b]py ridin-3- yl)phenyl)methanol (449 mg, 1.21 mmol) in CH ₂ Cl ₂ (10 mL) was added SOCl ₂ (288 mg, 2.42 mmol) at 0 °C. The mixture was stirred at 25 °C for 0.3 hr. The reaction was concentrated under reduced pressure to give 3-(3-(4-(chloromethyl)phenyl)-5-cyclobutyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (Intermediate 58, 560 mg, HCl salt, yield: 90%) as a yellow solid. MS: m/z = 390.1[M + H] ⁺ . [00241] Intermediate 59: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-(cyclohex-1 - en-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 59 was prepared in a manner similar to Intermediate 45. MS: m/z = 480.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.10 (d, J = 8.4 Hz, 1H), 7.98 (dd, J =4.8, 1.2 Hz, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.45 - 7.40 (m, 2H), 7.38 - 7.32 (m, 2H), 7.14 - 7.07 (m, 1H), 7.01 (br s, 2H), 6.67 - 6.60 (m, 1H), 6.34 (dd, J = 7.6, 4.8Hz, 1H), 3.52 (br s, 2H), 3.49 - 3.48 (m, 1H), 2.76 - 2.73 (m, 2H), 2.44 - 2.43 (m, 2H), 2.20 -2.19 (m, 2H), 2.02 - 1.96 (m, 2H), 1.72 - 1.65 (m, 4H), 1.61 - 1.54 (m, 2H), 1.27 - 1.23 (m, 2H). [00242] Intermediate 60: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-cyclohexyl- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: tert-Butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-cyclohexyl-3H-imidazo[4,5-b ]pyridin-3- yl)benzyl)piperidin-4-yl)carbamate To a solution of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-(cyclohex-1-en-1-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)carbamate (refer to Intermediate 59 for detail procedures, 242 mg, 417 µmol) in MeOH (10 mL) was added Pd/C (50 mg, 834 µmol, 10% w/w). The suspension was degassed under reduced pressure and purged with H ₂ several times. The mixture was stirred under H ₂ (50 psi) at 50 °C for 24 hr under H ₂ . The reaction mixture was cooled to 25 °C, then filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0 ~ 82% EtOAc in petroleum ether) to give tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-cyclohexyl-3H-imidazo[4,5-b ]pyridin-3- yl)benzyl)piperidin-4-yl)carbamate (182 mg, yield: 75%) as a yellow solid. MS: m/z = 582.3 [M + H] ⁺ . Step 2: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-cyclohexyl- 3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine To a solution of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-cyclohexyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)carbamate (182 mg, 345 µmol) in 1,4-dioxane (2 mL) was added 4 M HCl in 1,4-dioxane (2.0 mL). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was filtered to give 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5- cyclohexyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (Intermediate 60, 162 mg HCl salt , yield: 91%) was obtained as a yellow solid. MS: m/z = 482.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.25 - 8.11 (m, 1H), 7.99 -7.92 (m, 1H), 7.93 - 7.77 (m, 3H), 7.65 (d, J = 8.0 Hz, 2H), 7.50 - 7.35 (m, 1H), 6.95 - 6.73 (m, 1H), 3.70 (d, J = 12.0 Hz, 2H), 3.64 - 3.40 (m, 2H), 3.33 - 3.31 (m, 3H), 2.88 - 2.70 (m, 1H), 2.30 (d, J = 12.8 Hz, 2H), 2.21 - 2.02 (m, 2H), 1.95 - 1.81 (m, 4H), 1.79 - 1.71 (m, 1H), 1.63 - 1.49 (m, 2H), 1.39 (m, 2H), 1.35 - 1.24 (m, 1H). [00243] Intermediate 61: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-2-(2- aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-5-yl)benzonitril e Step 1: Tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-(3-cyanophenyl)-3H-imidazo[ 4,5-b]pyridin- 3-yl)benzyl)piperidin-4-yl)carbamate A mixture of Intermediate 44 (350 mg, 655 µmol), (3-cyanophenyl)boronic acid (116 mg, 786 µmol), K ₂ CO ₃ (181 mg, 1.31 mmol), and Pd(dppf)Cl ₂ (24 mg, 33 µmol) in 1,4-dioxane (10 mL) and H ₂ O (2 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 100 °C for 16 hr under N ₂ atmosphere. The reaction mixture was poured into H ₂ O (3 mL), extracted with EtOAc (15 mL). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0 ~ 9% MeOH in CH ₂ Cl ₂ ) to give tert-butyl (1-(4-(2-(2- aminopyridin-3-yl)-5-(3-cyanophenyl)-3H-imidazo[4,5-b]pyridi n-3-yl)benzyl)piperidin-4- yl)carbamate (150 mg, yield: 38%) as a yellow solid. MS: m/z = 601.4 [M + H] ⁺ . Step 2: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-2-(2-aminopyr idin-3-yl)-3H- imidazo[4,5-b]pyridin-5-yl)benzonitrile To a solution of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-(3-cyanophenyl)-3H-imidazo[ 4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)carbamate (50 mg, 73 µmol) in 1,4-dioxane (2 mL) was added 4M HCl in 1,4-dioxane (2 mL). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was filtered to give the filter cake. 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-2- (2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-5-yl)benzonit rile (Intermediate 61, 32 mg HCl salt, yield: 87%) was obtained as a yellow solid. MS: m/z = 501.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.48 - 8.32 (m, 3H), 8.14 (d, J = 8.8 Hz, 1H), 8.06 (d, J = 5.6 Hz, 1H), 7.99 - 7.87 (m, 3H), 7.83 - 7.73 (m, 3H), 7.71 - 7.64 (m, 1H), 6.93 - 6.89 (m, 1H), 3.79 - 3.68 (m, 2H), 3.67 - 3.45 (m, 3H), 3.37 (s, 2H), 2.35 - 2.33 (m, 2H), 2.23 - 2.05 (m, 2H). [00244] Intermediate 62: 5-(3-(4-((4-aminopiperidin-1-yl)methyl)phenyl)-2-(2- aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-5-yl)pyridin-2(1 H)-one Intermediate 62 was prepared in a manner similar to Intermediate 59. MS: m/z = 493.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.59 - 8.52 (m, 1H), 8.45 - 8.39 (m, 1H), 8.33 (d, J = 8.4 Hz, 1H), 8.05 - 8.01 (m, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.92 - 7.86 (m, 3H), 7.73 - 7.69 (m, 2H), 6.92 - 6.84 (m, 2H), 3.73 - 3.67 (m, 2H), 3.67 – 3.65 (m, 1H), 3.62 - 3.57 (m, 2H), 3.38 – 3.34 (m, 2H), 2.35 – 2.30 (m, 2H), 2.21 - 2.13 (m, 2H). [00245] Intermediate 63: 6-(3-(4-((4-aminopiperidin-1-yl)methyl)phenyl)-2-(2- aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-5-yl)pyridin-2(1 H)-one Intermediate 63 was prepared in a manner similar to Intermediate 59. MS: m/z = 493.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.47 (d, J = 8.4 Hz, 1H), 8.25 (d, J = 8.0 Hz, 1H), 8.08 - 7.98 (m, 2H), 7.96 - 7.89 (m, 3H), 7.78 – 7.72 (m, 2H), 7.50 – 7.58 (m, 1H), 6.94 - 6.82 (m, 2H), 3.76 - 3.68 (m, 2H), 3.66 (s, 2H), 3.61 - 3.56 (m, 1H), 3.38 – 3.32 (m, 2H), 2.36 – 2.29 (m, 2H), 2.21 - 2.08 (m, 2H). [00246] Intermediate 64: 4-(2,7-Diazaspiro[3.5]nonan-7-yl)-1,3,5-triazine-2-carbonitr ile Intermediate 64 was prepared in a manner similar to Intermediate 55. MS: m/z = 231.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.74 - 8.68 (m, 3H), 3.82 - 3.76 (m, 6H), 3.75 - 3.71 (m, 2H), 1.86 - 1.80 (m, 4H). [00247] Intermediate 65: 4-(7-Azaspiro[3.5]nonan-2-ylamino)-1,3,5-triazine-2- carbonitrile Intermediate 65 was prepared in a manner similar to Intermediate 55. MS: m/z = 245.1 [M + H] ⁺ . [00248] Intermediate 66: Methyl 4-(2-(2-aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5- b]pyridin-3-yl)benzoate To a solution of methyl 4-((6-chloro-3-nitropyridin-2-yl)amino)benzoate (refer to Intermediate 13 for detail procedures, 5.0 g, 16.3 mmol) and 2-aminonicotinaldehyde (2.18 g, 81.8 mmol) in DMSO (150 mL) was added Na ₂ S ₂ O ₄ (5.66 g, 32.5 mmol). The mixture was stirred at 105 °C for 12 hr. The reaction mixture was diluted with water (300 mL) and extracted with EtOAc (300 mL × 3). The combined organic layers were washed with brine (100 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0~100% EtOAc in petroleum ether) to give methyl 4-(2-(2- aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5-b]pyridin-3-yl)be nzoate (Intermediate 66, 700 mg, yield: 11.3%) as a yellow solid. MS: m/z = 380.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.28 (d, J = 8.4 Hz, 1H), 8.09 (d, J = 8.4 Hz, 2H), 8.01 (dd, J = 4.4, 1.6 Hz, 1H), 7.60 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.4 Hz, 1H), 7.23 (dd, J = 7.6, 1.6 Hz, 1H), 6.78 (br s, 2H), 6.45 (dd, J = 7.6, 4.8 Hz, 1H), 3.89 (s, 3H). [00249] Intermediate 67: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-methyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 67 was prepared in a manner similar to Intermediate 59. MS: m/z = 414.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.17 (d, J = 8.4 Hz, 1H), 7.99 (d, J = 5.6 Hz, 1H), 7.88 (d, J = 7.6 Hz, 2H), 7.81 (d, J = 7.2 Hz, 1H), 7.63 (d, J = 7.6 Hz, 2H), 7.38 (d, J = 8.4 Hz, 1H), 6.88 - 6.82 (m, 1H), 3.70 -3.64 (m, 2H), 3.59 - 3.54 (m, 1H), 3.29 - 3.17 (m, 2H), 2.61 (s, 3H), 2.32 - 2.29 (m, 2H), 2.20 - 2.06 (m, 2H), 1.33 - 1.27 (m, 2H). [00250] Intermediate 68: 3-(5-(2-Fluorophenyl)-3-(4-(piperazin-1-ylmethyl)phenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine hydrochloride Intermediate 68 was prepared in a manner similar to Intermediate 45. MS: m/z = 480.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 12.82 - 11.99 (m, 1H), 12.20 - 9.62 (m, 2H), 8.53 - 8.43 (m, 1H), 8.40 (d, J = 8.0 Hz, 1H), 8.15 (dd, J = 6.0, 1.6 Hz, 1H), 7.91 - 7.81 (m, 5H), 7.67 (d, J = 8.4 Hz, 2H), 7.52 - 7.46 (m, 1H), 7.39 - 7.30 (m, 2H), 6.98 (dd, J = 7.6, 6.4 Hz, 1H), 4.48 (s, 2H), 3.53 - 3.48 (m, 4H), 2.50 (m, 4H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ 117.18. [00251] Intermediate 69: 2-(2-(2-Aminopyridin-3-yl)-3-(4-(piperazin-1-ylmethyl)phenyl )- 3H-imidazo[4,5-b]pyridin-5-yl)benzonitrile Step 1: tert-Butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-(2-cyanophenyl)-3H-imidazo[4 ,5-b]pyridin- 3-yl)benzyl)piperazine-1-carboxylate A mixture of Intermediate 42 (400 mg, 770 μmol), (2-cyanophenyl)boronic acid (124 mg, 846 μmol), K ₃ PO ₄ (327 mg, 1.54 mmol), cataCXiumAPdG ₃ (280 mg, 385 μmol), and tricyclohexylphosphane (22 mg, 76.9 μmol) inDMF (5 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 120 °C for 16 hr under N ₂ atmosphere. The reaction mixture was filtered at 25 °C, and then diluted with H ₂ O (20 mL) and extracted with CH ₂ Cl ₂ (20 mL x 3). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 20 ~ 80% EtOAc in Petroleum ether), tert-butyl 4-(4-(2-(2- aminopyridin-3-yl)-5-(2-cyanophenyl)-3H-imidazo[4,5-b]pyridi n-3-yl)benzyl)piperazine-1- carboxylate (400 mg, yield: 80%) was obtained as a yellow solid. MS: m/z = 587.2 [M + H] ⁺ . Step 2: 2-(2-(2-Aminopyridin-3-yl)-3-(4-(piperazin-1-ylmethyl)phenyl )-3H-imidazo[4,5- b]pyridin-5-yl)benzonitrile To a solution of tert-butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-(2-cyanophenyl)-3H-imidazo[4 ,5- b]pyridin-3-yl)benzyl)piperazine-1-carboxylate (400 mg, 682 µmol) in 1,4-dioxane (5 mL) was added 4 M HCl in 1,4-dioxane (3 mL) at 25 ºC. The mixture was stirred at 25 ºC for 1 hr. The reaction mixture was then filtered and the collected solid was washed with 1,4-dioxane (5 mL x 2) and dried in vacuo to give 2-(2-(2-aminopyridin-3-yl)-3-(4-(piperazin-1-ylmethyl)phenyl )- 3H-imidazo[4,5-b]pyridin-5-yl)benzonitrile (Intermediate 69, 268 mg HCl salt, yield: 75%) as a yellow solid. MS: m/z = 487.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.38 (d, J = 8.0 Hz, 1H), 8.03 - 7.99 (m, 1H), 7.97 - 7.92 (m, 1H), 7.90 - 7.77 (m, 3H), 7.64 - 7.58 (m, 1H), 7.50 - 7.37 (m, 5H), 7.19 (dd, J = 7.6, 2.0 Hz, 1H), 6.98 (br s, 2H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 3.50 (s, 2H), 2.80 - 2.70 (m, 4H), 2.37 - 2.32 (m, 4H). [00252] Intermediate 70: 4-(2-(2-aminopyridin-3-yl)-3-(4-(piperazin-1-ylmethyl)phenyl )- 3H-imidazo[4,5-b]pyridin-5-yl)-1,4-diazepan-2-one Step 1: tert-Butyl 4-(4-((3-nitro-6-(3-oxo-1,4-diazepan-1-yl)pyridin-2- yl)amino)benzyl)piperazine-1-carboxylate To a solution of tert-butyl 4-(4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl)piperazine- 1- carboxylate (refer to Intermediate 10 for detail procedures, 1.5 g, 3.35 mmol) and 1,4-diazepan- 2-one (382 mg, 3.35 mmol) in ACN (20 mL) was added DIEA (866 mg, 6.7 mmol). The mixture was stirred at 90 °C for 4 hr. The reaction was concentrated under reduced pressure to give tert-butyl 4-(4-((3-nitro-6-(3-oxo-1,4-diazepan-1-yl)pyridin-2-yl)amino )benzyl)piperazine- 1-carboxylate (1.8 g, yield: 92%) as a yellow solid MS: m/z = 526.1 [M + H] ⁺ . Step 2: tert -Butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-(3-oxo-1,4-diazepan-1-yl)-3H -imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carboxylate To a solution of tert-butyl 4-(4-((3-nitro-6-(3-oxo-1,4-diazepan-1-yl)pyridin-2- yl)amino)benzyl)piperazine-1-carboxylate (1.8 g, 3.42 mmol) in DMSO (20 mL) was added 2- aminonicotinaldehyde (502 mg, 4.11 mmol) and Na ₂ S ₂ O ₄ (2.74 g, 13.7 mmol, 87% purity). The mixture was stirred at 100 °C for 8 hr. The reaction mixture was quenched with H ₂ O (30 mL) at 25 °C, and extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give tert- butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-(3-oxo-1,4-diazepan-1-yl)-3H -imidazo[4,5-b]pyridin-3- yl)benzyl)piperazine-1-carboxylate (1.3 g, purity: 49%, yield: 30%) as a yellow solid. MS: m/z = 598.3 [M + H] ⁺ , 498.2 [M - Boc + H] ⁺ Step 3: 4-(2-(2-Aminopyridin-3-yl)-3-(4-(piperazin-1-ylmethyl)phenyl )-3H-imidazo[4,5- b]pyridin-5-yl)-1,4-diazepan-2-one To a solution of tert-butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-(3-oxo-1,4-diazepan-1-yl)-3H - imidazo[4,5-b]pyridin-3-yl)benzyl)piperazine-1-carboxylate (1.2 g, 2.01 mmol) in 4 M HCl in 1,4-dioxane (10 mL) at 25 ºC. The mixture was stirred at 25 ºC for 0.5 hr. The reaction was concentrated under reduced pressure to give crude product (1 g, yield: 54%). The crude (100 mg) was purified by prep-HPLC (column: Phenomenex C18150 * 25 mm * 10 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: B: 9% - 39%, 10 min) to give 4-(2-(2- aminopyridin-3-yl)-3-(4-(piperazin-1-ylmethyl)phenyl)-3H-imi dazo[4,5-b]pyridin-5-yl)-1,4- diazepan-2-one (Intermediate 70, 25.1 mg) as a yellow solid. MS: m/z = 498.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ.8.01 - 7.89 (m, 2H), 7.52 - 7.42 (m, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 7.00 (dd, J = 7.6, 1.6 Hz, 1H), 6.98 (br s, 1H), 6.80 (d, J = 8.8 Hz, 1H), 6.32 (dd, J = 7.6, 4.8 Hz, 1H), 4.17 (s, 2H), 3.85 - 3.77 (m, 2H), 3.49 (s, 2H), 3.19 - 3.15 (m, 2H), 2.70 (t, J = 4.8 Hz, 4H), 2.35 - 2.27 (m, 4H), 1.68 - 1.61 (m, 2H). [00253] Intermediate 71: 4-(3,8-Diazabicyclo[3.2.1]octan-3-yl)-1,3,5-triazine-2- carbonitrile [00254] Intermediate 71 was prepared in a manner similar to Intermediate 55. MS: m/z = 217.1 [M + H] ⁺ . [00255] Intermediate 72: 3-(3-(4-(Chloromethyl)phenyl)-5-isopropyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine

Step 1: Methyl 4-(2-(2-aminopyridin-3-yl)-5-(prop-1-en-2-yl)-3H-imidazo[4,5 -b]pyridin-3- yl)benzoate A mixture of Intermediate 66 (660 mg, 1.74 mmol), 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)- 1,3,2-dioxaborolane (321 mg, 1.91 mmol), Pd(dppf)Cl ₂ (127 mg, 173 μmol) and Cs ₂ CO ₃ (1.13 g, 3.48 mmol) in 1,4-dioxane (10 mL) and H ₂ O (1 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 100 °C for 3hr. The reaction mixture was diluted with H ₂ O (50 mL) and extracted with CH ₂ Cl ₂ (50 mL x 2). The combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (eluent of 50% EtOAc in petroleum ether), methyl 4-(2-(2-aminopyridin-3-yl)- 5-(prop-1-en-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzoate (530 mg, yield: 72%) was obtained as a yellow solid. MS: m/z = 386.0 [M + H] ⁺ . Step 2: Methyl 4-(2-(2-aminopyridin-3-yl)-5-isopropyl-3H-imidazo[4,5-b]pyri din-3-yl)benzoate A mixture of methyl 4-(2-(2-aminopyridin-3-yl)-5-(prop-1-en-2-yl)-3H-imidazo[4,5 -b]pyridin- 3-yl)benzoate (530 mg, 1.38 mmol) in MeOH (20 mL) was added Pd/C (150 mg, 2.75 mmol, 10% purity), the mixture was stirred at 50 °C and 50 psi under H ₂ atmosphere for 24 hr. The reaction mixture was cooled to 25 °C, then filtered to get the liquor and concentrated under reduced pressure to give methyl 4-(2-(2-aminopyridin-3-yl)-5-isopropyl-3H-imidazo[4,5- b]pyridin-3-yl)benzoate (500 mg, yield: 94%) as a green solid. MS: m/z = 388.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide- d ₆ ) δ 8.13 (d, J = 8.4 Hz, 1H), 8.08 (d, J = 8.4 Hz, 2H), 8.00 (dd, J = 4.8, 1.6 Hz, 1H), 7.58 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.0 Hz, 1H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 6.78 (br s, 2H), 6.43 (dd, J = 7.6, 4.8 Hz, 1H), 3.88 (s, 3H), 3.12 - 3.04 (m, 1H), 1.23 (d, J = 6.8 Hz, 6H). Step 3: (4-(2-(2-Aminopyridin-3-yl)-5-isopropyl-3H-imidazo[4,5-b]pyr idin-3- yl)phenyl)methanol A mixture of methyl methyl 4-(2-(2-aminopyridin-3-yl)-5-isopropyl-3H-imidazo[4,5-b]pyri din- 3-yl)benzoate (500 mg, 1.29 mmol) in THF (20 mL) was added LiAlH ₄ (2.5 M, 800 μL) at 0 ºC dropwise, the mixture was stirred at 25 °C for 1 hr. The reaction mixture was quenched with Na ₂ SO ₄ ·10H ₂ O (3 g) at 0 °C, and then filtered and concentrated under reduced pressure to give (4-(2-(2-aminopyridin-3-yl)-5-isopropyl-3H-imidazo[4,5-b]pyr idin-3-yl)phenyl)methanol (480 mg, crude) as a yellow solid. MS: m/z = 360.0 [M + H] ⁺ . Step 4: 3-(3-(4-(Chloromethyl)phenyl)-5-isopropyl-3H-imidazo[4,5-b]p yridin-2-yl)pyridin-2- amine A mixture of (4-(2-(2-aminopyridin-3-yl)-5-isopropyl-3H-imidazo[4,5-b]pyr idin-3- yl)phenyl)methanol (480 mg, 1.34 mmol) in CH ₂ Cl ₂ (10 mL) was added SOCl ₂ (953 mg, 8.0 mmol), the mixture was stirred at 40 °C for 1 hr. The reaction mixture was filtered and the filter cake was washed with CH ₂ Cl ₂ (5 mL) to give 3-(3-(4-(chloromethyl)phenyl)-5-isopropyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (Intermediate 72, 220 mg, yield: 41%) as a yellow solid. MS: m/z = 378.0 [M + H] ⁺ . [00256] Intermediate 73: 3-(3-(4-(Chloromethyl)phenyl)-5-methoxy-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine Step 1: Methyl 4-((6-methoxy-3-nitropyridin-2-yl)amino)benzoate To a solution of 2-chloro-6-methoxy-3-nitropyridine (10 g, 53.0 mmol) and methyl 4- aminobenzoate (7.62 g, 50.4 mmol) in DIEA (50 mL). The mixture was stirred at 130 °C for 4 hr. The mixture was diluted with EtOAc (50 mL) and H ₂ O (30 mL). The separated organic layer was washed with H ₂ O (60 mL) and dried over Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0 ~ 10% EtOAc in petroleum ether), methyl 4-((6-methoxy-3-nitropyridin-2-yl)amino)benzoate (5.12 g, yield: 26%) was obtained as a light-yellow solid. MS: m/z = 304.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d 1H), 8.48 - 8.41 (m, 1H), 8.06 (d, J = 8.4 Hz, 2H), 7.78 (d, J = 8.0 Hz, 2H), 6.31 (dd, J = 9.2, 0.8 Hz, 1H), 4.01 (s, 3H), 3.92 (s, 3H). Step 2: Methyl 4-(2-(2-aminopyridin-3-yl)-5-methoxy-3H-imidazo[4,5-b]pyridi n-3-yl)benzoate To a solution of methyl 4-((6-methoxy-3-nitropyridin-2-yl)amino)benzoate (5.12 g, 16.9 mmol) in DMSO (100 mL) was added Na ₂ S ₂ O ₄ (13.5 g, 67.5 mmol, 87% purity) and 2- aminonicotinaldehyde (2.47g, 20.3 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched with H ₂ O (25 mL) at 25°C, and then extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 35% EtOAc in petroleum ether), methyl 4-(2-(2-aminopyridin-3- yl)-5-methoxy-3H-imidazo[4,5-b]pyridin-3-yl)benzoate (2.0 g, yield: 28%) was obtained as a light-yellow solid. MS: m/z = 376.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.16 (d, J = 8.4 Hz, 2H), 8.04 (dd, J = 5.2, 2.0 Hz, 1H), 7.97 (d, J = 8.8 Hz, 1H), 7.47 (d, J = 8.8 Hz, 2H), 6.99 (dd, J = 7.6, 1.6 Hz, 1H), 6.77 (d, J = 8.4 Hz, 1H), 6.55 (br s, 2H), 6.37 (dd, J = 8.0, 5.2 Hz, 1H), 3.96 (s, 3H), 3.86 (s, 3H). Step 3: (4-(2-(2-Aminopyridin-3-yl)-5-methoxy-3H-imidazo[4,5-b]pyrid in-3- yl)phenyl)methanol A mixture of methyl 4-(2-(2-aminopyridin-3-yl)-5-methoxy-3H-imidazo[4,5-b]pyridi n-3- yl)benzoate (2.0 g, 5.33 mmol) in THF (130 mL) was added LiAlH ₄ (2.5 M, 2.77 mL) at 0 °C dropwise, the mixture was stirred at 25 °C for 2 hr. The reaction mixture was quenched with Na ₂ SO ₄ ·10H ₂ O (3 g) at 0°C, and then filtered and concentrated under reduced pressure to give (4-(2-(2-aminopyridin-3-yl)-5-methoxy-3H-imidazo[4,5-b]pyrid in-3-yl)phenyl)methanol (1.8 g, crude) as a yellow solid. MS: m/z = 348.0 [M + H] ⁺ . Step 4: 3-(3-(4-(Chloromethyl)phenyl)-5-methoxy-3H-imidazo[4,5-b]pyr idin-2-yl)pyridin-2- amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-methoxy-3H-imidazo[4,5-b]pyrid in-3- yl)phenyl)methanol (1.8 g, 5.18 mmol) in CH ₂ Cl ₂ (20 mL) was added SOCl ₂ (1.23 g, 10.4 mmol). The mixture was stirred at 40 °C for 2 hr. The residue was poured into water (200 mL). The resulting mixture was washed with CH ₂ Cl ₂ (10 mL x 2), then aqueous phase was adjusted pH to around 8 by NaHCO ₃ . The resulting mixture was extracted with CH ₂ Cl ₂ (100 mL). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated to dryness. After purified by silica gel flash chromatography (Eluent of 0 ~ 35% EtOAc in petroleum ether), 3-(3-(4-(chloromethyl)phenyl)-5-methoxy-3H-imidazo[4,5-b]pyr idin-2- yl)pyridin-2-amine (Intermediate 73, 1.3 g, yield: 65%) was obtained as a light-yellow solid. MS: m/z = 366.0 [M + H] ⁺ . [00257] Intermediate 74: 2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridine-5-carboxamide Step 1: 6-Chloro-5-nitropicolinoyl chloride A solution of 6-chloro-5-nitropicolinic acid (5 g, 24.7 mmol) in SOCl ₂ (20 mL) was stirred at 80 °C for 16 hr. The reaction mixture was filtered and concentrated under reduced pressure to give 6-chloro-5-nitropicolinoyl chloride (5.4 g, yield: 97%) as a yellow solid, which was directly used to the next step. Step 2: 6-Chloro-5-nitropicolinamide To a solution of 6-chloro-5-nitropicolinoyl chloride (5 g, 22.6 mmol) in THF (50 mL) was added NH _3- H ₂ O (9.51 g, 67.9 mmol) at 0 °C. The mixture was stirred at 0 °C for 1hr. Then the reaction mixture was diluted with H ₂ O (100 mL) and extracted with EtOAc (100 mL x 2). The combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give 6-chloro-5-nitropicolinamide (3.3 g, yield: 65%) as a yellow solid. MS: m/z = 201.9 [M + H] ⁺ . Step 3: 6-((4-(Hydroxymethyl)phenyl)amino)-5-nitropicolinamide To a solution of 6-chloro-5-nitropicolinamide (3.3 g, 16.4 mmol) in DMSO (20 mL) were added (4-aminophenyl)methanol (2.02 g, 16.4 mmol) and DIEA (6.35 g, 49.1 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was diluted with H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (100 mL x 2). The combined organic layers were washed with brine (100 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give 6-((4- (hydroxymethyl)phenyl)amino)-5-nitropicolinamide (3.2 g, yield: 67%) as a yellow solid. MS: m/z = 288.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.96 (s, 1H), 8.67 (d, J = 8.4 Hz, 1H), 7.94 (s, 1H), 7.61 - 7.55 (m, 2H), 7.47 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 8.4 Hz, 2H), 7.27 (s, 1H), 5.18 (t, J = 5.6 Hz, 1H), 4.50 (d, J = 5.6 Hz, 2H). Step 4: 4-((6-Carbamoyl-3-nitropyridin-2-yl)amino)benzyl acetate To a solution of 6-((4-(hydroxymethyl)phenyl)amino)-5-nitropicolinamide (2.4 g, 8.33 mmol) in CH ₂ Cl ₂ (20 mL) were added TEA (2.53 g, 25 mmol), Ac ₂ O (1.27 g, 12.5 mmol) and DMAP (101 mg, 823 μmol). The mixture was stirred at 25 ºC for 1hr. The reaction mixture was quenched with H ₂ O (50 mL) at 25 °C, and then extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give 4-((6-carbamoyl-3-nitropyridin-2-yl)amino)benzyl acetate (2.5 g, yield: 90%) as a red solid. MS: m/z = 353.0 [M + Na] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.98 (s, 1H), 8.67 (d, J = 8.4 Hz, 1H), 7.94 (s, 1H), 7.69 - 7.62 (m, 2H), 7.49 (d, J = 8.4 Hz, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.36 - 7.29 (m, 1H), 5.07 (s, 2H), 2.07 (s, 3H). Step 5: 4-(2-(2-Aminopyridin-3-yl)-5-carbamoyl-3H-imidazo[4,5-b]pyri din-3-yl)benzyl acetate To a solution of 4-((6-(dimethylcarbamoyl)-3-nitropyridin-2-yl)amino)benzyl acetate (2.2 g, 6.66 mmol) in DMSO (20 mL) were added Na ₂ S ₂ O ₄ (2.32 g, 13.3 mmol) and 2- aminonicotinaldehyde (895 mg, 7.33 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched with H ₂ O (50 mL) at 25°C, and then extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 50~80% EtOAc in petroleum ether), 4-(2-(2-aminopyridin-3-yl)-5- carbamoyl-3H-imidazo[4,5-b]pyridin-3-yl)benzyl acetate (900 mg, yield: 30%) was obtained as a yellow solid. MS: m/z = 403.0 [M + H] ⁺ . Step 6: 2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imida zo[4,5-b]pyridine-5- carboxamide To a solution of 4-(2-(2-aminopyridin-3-yl)-5-carbamoyl-3H-imidazo[4,5-b]pyri din-3-yl)benzyl acetate (900 mg, 2.24 mmol) in THF (10 mL) and MeOH (10 mL) was added K ₂ CO ₃ (927 mg, 6.71 mmol). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was diluted with H ₂ O (20 mL) and extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (20 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give 2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imida zo[4,5-b]pyridine-5- carboxamide (700 mg, yield: 46%) as a yellow solid. MS: m/z = 361.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.32 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 8.4 Hz, 1H), 8.03 - 8.00 (m, 1H), 7.65 - 7.51 (m, 2H), 7.50 - 7.43 (m, 4H), 7.25 (dd, J = 7.6, 1.6 Hz, 1H), 6.91 (br s, 2H), 6.44 (dd, J = 7.6, 4.8 Hz, 1H), 4.59 (s, 2H), 3.32 - 3.29 (m, 1H). Step 7: 2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imidaz o[4,5-b]pyridine-5- carboxamide To a solution of 2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imida zo[4,5- b]pyridine-5-carboxamide (400 mg, 1.11 mmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (396 mg, 3.33 mmol). The mixture was stirred at 40 °C for 0.5 hr. The reaction was concentrated under reduced pressure to give 2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imidaz o[4,5- b]pyridine-5-carboxamide (Intermediate 74, 400 mg, yield: 81%) was obtained as a brown solid. MS: m/z = 378.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.42 (d, J = 8.4 Hz, 1H), 8.18 - 8.09 (m, 2H), 7.97 - 7.93 (m, 1H), 7.74 - 7.34 (m, 6H), 6.99 - 6.84 (m, 1H), 4.85 (s, 2H). [00258] Intermediate 75: 2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-N,N- dimethyl-3H-imidazo[4,5-b]pyridine-5-carboxamide Step 1: 6-Chloro-N,N-dimethyl-5-nitropicolinamide To a solution of 6-chloro-5-nitropicolinoyl chloride (2 g, 9.05 mmol) in CH ₂ Cl ₂ (20 mL) were added TEA (2.75 g, 27.2 mmol) and dimethylamine (738 mg, 9.05 mmol, HCl salt). The mixture was stirred at 0 °C for 1 hr. The reaction mixture was quenched with H ₂ O (20 mL) at 25 °C, and then diluted with CH ₂ Cl ₂ (30 mL) and extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give 6-chloro-N,N-dimethyl-5-nitropicolinamide (1.9 g, yield: 70%) as a yellow solid. MS: m/z = 230.0 [M + H]+. Step 2: 6-((4-(Hydroxymethyl)phenyl)amino)-N,N-dimethyl-5-nitropicol inamide To a solution of 6-chloro-N,N-dimethyl-5-nitropicolinamide (1.9 g, 8.27 mmol) in DMSO (20 mL) were added (4-aminophenyl)methanol (815 mg, 6.62 mmol) and DIEA (3.21 g, 24.8 mmol). The mixture was stirred at 110 °C for 16 hr. The reaction mixture was quenched with H ₂ O (20 mL) at 25 °C, and extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give 6-((4-(hydroxymethyl)phenyl)amino)-N,N-dimethyl-5-nitropicol inamide (2.6 g, yield: 79%) as a red solid. MS: m/z = 317.0 [M + H] ⁺ . Step 3: 4-((6-(Dimethylcarbamoyl)-3-nitropyridin-2-yl)amino)benzyl acetate To a solution of 6-((4-(hydroxymethyl)phenyl)amino)-N,N-dimethyl-5-nitropicol inamide (2.6 g, 8.22 mmol) in CH ₂ Cl ₂ (20 mL) were added TEA (2.50 g, 24.7 mmol), Ac ₂ O (1.26 g, 12.3 mmol) and DMAP (100 mg, 822 μmol). The mixture was stirred at 25 ºC for 1 hr. The reaction mixture was quenched with H ₂ O (50 mL) at 25 °C, and extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 1~30% EtOAc in petroleum ether), 4-((6-(dimethylcarbamoyl)-3-nitropyridin-2- yl)amino)benzyl acetate (1.7 g, yield: 55%) was obtained as a red solid. MS: m/z = 380.9 [M + Na] ⁺ . Step 4: 4-(2-(2-Aminopyridin-3-yl)-5-(dimethylcarbamoyl)-3H-imidazo[ 4,5-b]pyridin-3- yl)benzyl acetate To a solution of 4-((6-(dimethylcarbamoyl)-3-nitropyridin-2-yl)amino)benzyl acetate (1.6 g, 4.46 mmol) in DMSO (20 mL) were added Na ₂ S ₂ O ₄ (3.57 g, 17.9 mmol) and 2- aminonicotinaldehyde (654 mg, 5.36 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched with H ₂ O (25 mL) at 25 °C and extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 50% ~ 100% EtOAc in petroleum ether), 4-(2-(2-aminopyridin-3-yl)-5- (dimethylcarbamoyl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl acetate (370 mg, yield: 19%) was obtained as a brown solid. MS: m/z = 431.1 [M + H] ⁺ . Step 5: 2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-N,N-dime thyl-3H-imidazo[4,5- b]pyridine-5-carboxamide To a solution of 4-(2-(2-aminopyridin-3-yl)-5-(dimethylcarbamoyl)-3H-imidazo[ 4,5-b]pyridin- 3-yl)benzyl acetate (370 mg, 860 μmol) in THF (5 mL) and MeOH (5 mL) was added K ₂ CO ₃ (356 mg, 2.58 mmol). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was diluted with H ₂ O (10 mL) and extracted with CH ₂ Cl ₂ (15 mL x 2). The combined organic layers were washed with brine (10 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give 2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-N,N-dime thyl-3H- imidazo[4,5-b]pyridine-5-carboxamide (320 mg, yield: 74%) as a yellow solid. MS: m/z = 389.1 [M + H] ⁺ . Step 6: 2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-N,N-dimet hyl-3H-imidazo[4,5- b]pyridine-5-carboxamide To a solution of 2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-N,N-dime thyl-3H- imidazo[4,5-b]pyridine-5-carboxamide (320 mg, 824 μmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (294 mg, 2.47 mmol). The mixture was stirred at 40 °C for 0.4 hr. The reaction was concentrated under reduced pressure to give 2-(2-aminopyridin-3-yl)-3-(4- (chloromethyl)phenyl)-N,N-dimethyl-3H-imidazo[4,5-b]pyridine -5-carboxamide (Intermediate 75, 330 mg, yield: 91%) as a yellow solid. MS: m/z = 407.0 [M + H] ⁺ . [00259] Intermediate 76: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-chlorophenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: Methyl 4-((6-(2-chlorophenyl)-3-nitropyridin-2-yl)amino)benzoate To a mixture of methyl 4-((6-chloro-3-nitropyridin-2-yl)amino)benzoate (refer to Intermediate 13 for detail procedures, 5 g, 16.2 mmol), (2-chlorophenyl)boronic acid (3.3 g, 21.1 mmol), Pd(dppf)Cl ₂ (1.19 g, 1.63 mmol), Cs ₂ CO ₃ (15.8 g, 48.7 mmol) in dioxane (50 mL) and H ₂ O (5 mL) was degassed and purged with N ₂ three times, and the mixture was stirred at 100 °C for 12 hr under N ₂ atmosphere. The reaction mixture was diluted with water (20 mL) and extracted with CH ₂ Cl ₂ (30 mL × 2). The combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0~10% MeOH in CH ₂ Cl ₂ ) to give methyl 4-((6-(2-chlorophenyl)-3- nitropyridin-2-yl)amino)benzoate (1.5 g, yield: 21%) as a yellow solid. MS: m/z = 384.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 10.49 (br s, 1H), 8.63 (d, J = 8.8 Hz, 1H), 8.04 (d, J = 6.8 Hz, 2H), 7.90 (d, J = 9.2 Hz, 2H), 7.68 - 7.63 (m, 1H), 7.56 - 7.52 (m, 1H), 7.46 - 7.39 (m, 2H), 7.33 (d, J = 8.8 Hz, 1H), 3.91 (s, 3H). Step 2: Methyl 4-(2-(2-aminopyridin-3-yl)-5-(2-chlorophenyl)-3H-imidazo[4,5 -b]pyridin-3- yl)benzoate To a solution of methyl 4-((6-(2-chlorophenyl)-3-nitropyridin-2-yl)amino)benzoate (1.5 g, 3.91 mmol) and 2-aminonicotinaldehyde (525 mg, 4.30 mmol) in DMSO (45 mL) was added Na ₂ S ₂ O ₄ (3.20 g, 15.6 mmol). The mixture was stirred at 100 °C for 12 hr. The reaction mixture was diluted with water (100 mL) and extracted with CH ₂ Cl ₂ (300 mL × 2). The combined organic layers were washed with brine (100 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0~100% EtOAc in petroleum ether) to give methyl 4-(2-(2- aminopyridin-3-yl)-5-(2-chlorophenyl)-3H-imidazo [4, 5-b] pyridin-3-yl) benzoate (800 mg, yield: 41%) as a yellow solid. MS: m/z = 456.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.23 - 8.15 (m, 3H), 8.07 (dd, J = 4.8, 1.6 Hz, 1H), 7.73 (d, J = 8.4 Hz, 1H), 7.60 - 7.52 (m, 3H), 7.50 - 7.46 (m, 1H), 7.36 - 7.31 (m, 2H), 7.10 (dd, J = 7.6, 1.6 Hz, 1H), 6.92 (br s, 2H), 6.43 (dd, J = 8.0, 5.2 Hz, 1H), 3.96 (s, 3H). Step 3: (4-(2-(2-Aminopyridin-3-yl)-5-(2-chlorophenyl)-3H-imidazo[4, 5-b]pyridin-3- yl)phenyl)methanol To a solution of methyl 4-(2-(2-aminopyridin-3-yl)-5-(2-chlorophenyl)-3H-imidazo[4,5 - b]pyridin-3-yl)benzoate (800 mg, 1.75 mmol) in THF (50 mL) was added LiAlH ₄ (2.5 M, 1.05 mL) at 0 °C. The mixture was stirred at 25 °C for 2 hr. The reaction mixture was quenched with Na ₂ SO _{4 2} O (120 mg) at 0 °C and filtered. The filtrate was concentrated under reduced pressure to give (4-(2-(2-aminopyridin-3-yl)-5-(2-chlorophenyl)-3H-imidazo[4, 5-b]pyridin-3- yl)phenyl)methanol (700 mg, crude as a yellow solid. Step 4: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-chlorophenyl)-3H-imidazo[ 4,5-b]pyridin-2- yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(2-chlorophenyl)-3H-imidazo[4, 5-b]pyridin-3- yl)phenyl)methanol (700 mg, 1.64 mmol) in CH ₂ Cl ₂ (10 mL) was added SOCl ₂ (1.17 g, 9.82 mmol). The mixture was stirred at 40 °C for 2 hr. The mixture was concentrated under reduced pressure. 3-(3-(4-(Chloromethyl)phenyl)-5-(2-chlorophenyl)-3H-imidazo[ 4,5-b]pyridin-2- yl)pyridin-2-amine (Intermediate 76, 750 mg HCl salt) was obtained as a yellow solid. MS: m/z = 446.0 [M + H] ⁺ . [00260] Intermediate 77: 3-(5-(2-Chlorophenyl)-3-(4-(piperazin-1-ylmethyl)phenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: tert-Butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-(2-chlorophenyl)-3H-imidazo[ 4,5-b]pyridin- 3-yl)benzyl)piperazine-1-carboxylate To a solution of Intermediate 76 (1 g, 2.24 mmol) and tert-butyl piperazine-1-carboxylate (417 mg, 2.24 mmol) in MeCN (10 mL) were added NaI (67.2 mg, 448 µmol) and K ₂ CO ₃ (929 mg, 6.72 mmol). The mixture was stirred at 25 °C for 16 hr. The residue was diluted with H ₂ O (30 mL) and extracted with EtOAc (30 mL x 3). The combined organic layers were washed with brine (20 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0~3% MeOH in CH ₂ Cl ₂ ) to give tert-butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-(2-chlorophenyl)-3H-imidazo[ 4,5-b]pyridin-3- yl)benzyl)piperazine-1-carboxylate(600 mg, yield: 45%) as a yellow solid. MS: m/z = 596.1 [M + H] ⁺ . Step 6: 3-(5-(2-Chlorophenyl)-3-(4-(piperazin-1-ylmethyl)phenyl)-3H- imidazo[4,5-b]pyridin-2- yl)pyridin-2-amine To a solution of tert-butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-(2-chlorophenyl)-3H-imidazo[ 4,5- b]pyridin-3-yl)benzyl)piperazine-1-carboxylate (600 mg, 1.01 mmol) in MeOH (2 mL) was added HCl in 1,4-dioxane (4 M, 5 mL). The mixture was stirred at 25 °C for 3 hr. The reaction mixture was filtered and concentrated under reduced pressure to give 3-(5-(2-chlorophenyl)-3- (4-(piperazin-1-ylmethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2- yl)pyridin-2-amine (Intermediate 77, HCl salt, 530 mg, yield: 90%). MS: m/z = 496.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol- d ₄ ) δ 8.23 (d, J = 8.4 Hz, 1H), 8.01 - 7.96 (m, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.56 - 7.48 (m, 4H), 7.44 - 7.32 (m, 5H), 6.48 (dd, J = 7.6, 5.6 Hz, 1H), 3.58 (s, 2H), 2.87 - 2.84(m, 4H), 2.52 - 2.44 (m, 4H). [00261] Intermediate 78: 4-(2-(2-Aminopyridin-3-yl)-3-(4-(piperazin-1-ylmethyl)phenyl )- 3H-imidazo[4,5-b]pyridin-5-yl)benzonitrile Intermediate 78 was prepared in a manner similar to Intermediate 45. MS: m/z = 487.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.38 (d, J = 8.4 Hz, 1H), 8.25 (d, J = 8.4 Hz, 2H), 8.13 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 5.6 Hz, 1H), 7.95 (d, J = 7.6 Hz, 2H), 7.89 (d, J = 7.2 Hz, 1H), 7.81 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 7.6 Hz, 2H), 6.93 (t, J = 6.8 Hz, 1H), 3.71 - 3.70 (m, 6H), 3.68 - 3.64 (m, 4H). [00262] Intermediate 79: 3-(5-(3-Fluorophenyl)-3-(4-(piperazin-1-ylmethyl)phenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 79 was prepared in a manner similar to Intermediate 45. MS: m/z = 480.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.34 (d, J = 8.4 Hz, 1H), 8.08 - 8.01 (m, 2H), 7.98 - 7.86 (m, 4H), 7.81 - 7.71 (m, 3H), 7.52 - 7.42 (m, 1H), 7.18 - 7.12 (m, 1H), 6.98 – 6.85 (m, 1H), 3.69 - 3.67 (m, 4H), 3.35 (s, 2H), 3.34 - 3.31 (m, 4H). ¹⁹ F NMR (400 MHz, Methanol-d ₄ ) δ - 115.02. [00263] Intermediate 80: 3-(5-(3-Chlorophenyl)-3-(4-(piperazin-1-ylmethyl)phenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 80 was prepared in a manner similar to Intermediate 45. MS: m/z = 496.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.21 (d, J = 8.4 Hz, 1H), 8.04 (s, 1H), 8.01 - 7.92 (m, 3H), 7.55 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 8.4 Hz, 2H), 7.43 - 7.33 (m, 3H), 6.48 (dd, J = 7.6, 5.2 Hz, 1H), 3.64 (s, 2H), 2.92 (t, J = 5.2 Hz, 4H), 2.50 - 2.58 (m, 4H). [00264] Intermediate 81: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-cyclopropyl - 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: tert-Butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4,5- b]pyridin-3- yl)benzyl)piperidin-4-yl)carbamate A mixture of intermediate 44 (300 mg, 562 μmol), cyclopropylboronic acid (97 mg, 1.1 mmol), t-BuOK (126 mg, 1.1 mmol), cataCXiumAPdG3 (41 mg, 56 μmol) in H ₂ O (2 mL) and 1,4- dioxane (8 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 100 °C for 16 hr under N ₂ atmosphere. The reaction mixture was quenched with H ₂ O (30 mL) at 25 °C, and extracted with EtOAc (30 mL × 2). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. The crude was purified by silica gel flash chromatography (Eluent of 0~100% EtOAc in petroleum ether) to give tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-cyclopropyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)carbamate (120 mg, yield:40%) as a yellow solid. MS: m/z = 540.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d J = 4.8, 1.6 Hz, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.48 - 7.43 (m, 2H), 7.31 – 7.28 (m, 2H), 7.12 (d, J = 8.4 Hz, 1H), 7.02 (dd, J = 7.6, 1.6 Hz, 1H), 6.52 (br s, 2H), 6.33 (dd, J = 7.6, 4.8 Hz, 1H), 4.52 - 4.41 (m, 1H), 3.68 - 3.51 (m, 3H), 2.98 - 2.85 (m, 2H), 2.30 - 2.17 (m, 2H), 2.12 - 2.11 (m, 1H), 2.01 - 1.95 (m, 2H), 1.45 - 1.43 (m, 11H), 0.96 – 0.92 (m, 4H). Step 2: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-cyclopropyl -3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine To a solution of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)carbamate (130 mg, 241 μmol) in HCI in 1,4-dioxane (4M, 3 mL). The mixture was stirred at 25 °C for 1 hr. Then the mixture was concentrated under reduced pressure to give 3-(3-(4-((4-aminopiperidin-1-yl)methyl)phenyl)-5-cyclopropyl -3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (Intermediate 81, 110 mg HCl salt, yield: 96%) was obtained as a light yellow solid. MS: m/z = 440.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.16 - 8.06 (m, 1H), 8.05 - 7.95 (m, 1H), 7.98 - 7.85 (m, 3H), 7.61 (d, J = 7.2 Hz, 2H), 7.41 - 7.30 (m, 1H), 6.96 - 6.79 (m, 1H), 4.48 (s, 2H), 3.68 (d, J = 11.6 Hz, 2H), 3.60 - 3.65 (m, 2H), 3.29 - 3.23 (m, 1H), 2.31 (d, J = 12.8 Hz, 2H), 2.26 - 2.03 (m, 3H), 1.07 - 0.88 (m, 4H). [00265] Intermediate 82: 3-(3-(4-(Chloromethyl)phenyl)-5-(tetrahydro-2H-pyran-4-yl)- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Step 1: (E)-3-(dimethylamino)-1-(tetrahydro-2H-pyran-4-yl)prop-2-en- 1-one To a solution of 1-(tetrahydro-2H-pyran-4-yl)ethan-1-one (10 g, 78 mmol) in DMF (100 mL) was added DMF-DMA (18.6 g, 156 mmol) and CH ₃ ONa (422 mg, 7.8 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched with H ₂ O (500 mL) at 25 °C, and extracted with EtOAc (500 mL × 2). The combined organic layers were washed with brine (500 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a (E)-3- (dimethylamino)-1-(tetrahydro-2H-pyran-4-yl)prop-2-en-1-one (12.56 g, crude) as light yellow oil, which was used to the next step directly. MS: m/z = 184.0 [M + H] ⁺ . Step 2: 3-Nitro-6-(tetrahydro-2H-pyran-4-yl) pyridin-2-ol To a solution of (E)-3-(dimethylamino)-1-(tetrahydro-2H-pyran-4-yl)prop-2-en- 1-one (2.3 g, 13 mmol) in H ₂ O (20 mL) were added piperidine acetic acid salt (911 mg, 6.3 mmol) and 2- nitroacetamide (2.0 g, 18.8 mmol). The mixture was stirred at 25 °C for 16 hr. The reaction mixture was filtered, and the filter cake was washed with H ₂ O (20 mL), dried in reduced pressure to give a 3-nitro-6-(tetrahydro-2H-pyran-4-yl) pyridin-2-ol (1.2 g, yield: 41%) as a light yellow solid. MS: m/z = 225.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 12.78 (br s, 1H), 8.41 (d, J = 8.0 Hz, 1H), 6.30 (d, J = 8.0 Hz, 1H), 3.97 - 3.89 (m, 2H), 3.39 - 3.32 (m, 2H), 2.89 - 2.79 (m,1H), 1.77 - 1.61 (m, 4H). Step 3: 2-Chloro-3-nitro-6-(tetrahydro-2H-pyran-4-yl)pyridine A solution of 3-nitro-6-(tetrahydro-2H-pyran-4-yl) pyridin-2-ol (4.5 g, 20 mmol) in POCl ₃ (40 mL) was stirred at 80 °C for 16 hr. The reaction mixture was quenched with H ₂ O (80 mL) at 25 °C, and then diluted with Na ₂ CO ₃ aqueous solution (80 mL) and extracted with EtOAc (100 mL × 2). The combined organic layers were washed with brine (100 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a 2-chloro-3-nitro-6-(tetrahydro-2H- pyran-4-yl)pyridine (4.1 g, crude) as a brown oil, which was used to the next step directly. MS: m/z = 242.9 [M + H] ⁺ . Step 4: Methyl 4-((3-nitro-6-(tetrahydro-2H-pyran-4-yl)pyridin-2-yl)amino)b enzoate To a solution of 2-chloro-3-nitro-6-(tetrahydro-2H-pyran-4-yl)pyridine (1.1 g, 4.5 mmol) in DIEA (15 mL) was added methyl 4-aminobenzoate (754 mg, 4.9 mmol). The mixture was stirred at 130 °C for 16 hr. The reaction mixture was poured into H ₂ O (100 mL), extracted with EtOAc (100 mL × 2). The organic phase was dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (Eluent of 0~18% EtOAc in petroleum ether) to give methyl 4-((3-nitro-6- (tetrahydro-2H-pyran-4-yl) pyridin-2-yl) amino) benzoate (500 mg, yield: 31%) as a yellow solid. MS: m/z = 358.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.17 (s, 1H), 8.50 (d, J = 8.4 Hz, 1H), 7.95 (d, J = 8.8 Hz, 2H), 7.89 (d, J = 8.8 Hz, 2H), 7.02 (d, J = 8.4 Hz, 1H), 4.01 - 3.93 (m, 2H), 3.84 (s, 3H), 3.47 - 3.40 (m , 2H), 3.06 - 2.95 (m, 1H), 1.83 - 1.65 (m, 4H). Step 5: Methyl 4-(2-(2-aminopyridin-3-yl)-5-(tetrahydro-2H-pyran-4-yl)-3H-i midazo[4,5- b]pyridin-3-yl)benzoate To a solution of methyl 4-((3-nitro-6-(tetrahydro-2H-pyran-4-yl) pyridin-2-yl) amino) benzoate (0.5 g, 1.4 mmol) in DMSO (30 mL) were added Na ₂ S ₂ O ₄ (9741 mg, 5.6 mmol) and 2- aminonicotinaldehyde (205 mg, 1.7 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was poured into H ₂ O (100 mL), extracted with CH ₂ Cl ₂ (100 mL × 2). The organic phase was dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (Eluent of 0~76% EtOAc in petroleum ether) to give methyl 4-(2-(2-aminopyridin-3-yl)-5-(tetrahydro-2H-pyran-4- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzoate (200 mg, yield: 33%) as a yellow solid. MS: m/z = 430.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.20 - 8.17 (m, 2H), 8.06 (dd, J = 4.8, 1.6 Hz, 1H), 8.03 (d, J = 8.4 Hz, 1H), 7.51 - 7.47 (m, 2H), 7.22 (d, J = 8.4 Hz, 1H), 7.04 (dd, J = 7.6, 1.6 Hz, 1H), 6.61 (br s, 2H), 6.39 (dd, J = 8.0, 4.8 Hz, 1H), 4.09 - 4.05 (m, 2H), 3.97 (s, 3H), 3.57 - 3.51 (m, 2H), 3.05 - 2.97 (m, 1H), 1.95 - 1.83 (m, 4H). Step 6: (4-(2-(2-Aminopyridin-3-yl)-5-(tetrahydro-2H-pyran-4-yl)-3H- imidazo[4,5-b]pyridin-3- yl)phenyl)methanol To a solution of methyl 4-(2-(2-aminopyridin-3-yl)-5-(tetrahydro-2H-pyran-4-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzoate (200 mg, 466 μmol) inTHF (10 mL) was added dropwise LiAlH ₄ (2,5 M, 372 μL) at 0 ºC. The resulting mixture was stirred at 25 ºC for 1h. After the reaction mixture cooled to 0 ºC, the reaction mixture was quenched with H ₂ O (15 mL), followed by 15% aqueous NaOH (10 mL). After being stirred at room temperature for 30 min, the mixture was filtered through celite. The filtrate was concentrated to dryness to give (4-(2-(2- aminopyridin-3-yl)-5-(tetrahydro-2H-pyran-4-yl)-3H-imidazo[4 ,5-b]pyridin-3- yl)phenyl)methanol (190 mg, crude) as a light yellow solid, which was used to the next step directly. MS: m/z = 402.2 [M + H] ⁺ Step 7: 3-(3-(4-(Chloromethyl)phenyl)-5-(tetrahydro-2H-pyran-4-yl)-3 H-imidazo[4,5-b]pyridin- 2-yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(tetrahydro-2H-pyran-4-yl)-3H- imidazo[4,5- b]pyridin-3-yl)phenyl)methanol (190 mg, 473 μmo) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (1.6 g, 13.1 mmol). The mixture was stirred at 40 °C for 1 hr. The reaction mixture was concentrated under reduced pressure to give 3-(3-(4-(chloromethyl)phenyl)-5-(tetrahydro-2H-pyran-4-yl)-3 H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (Intermediate 82, 200 mg, crude) as a brown solid, which was used to the next step directly. MS: m/z = 420.0 [M + H] ⁺ [00266] Intermediate 83: 4-(Azetidin-3-ylamino)-1,3,5-triazine-2-carbonitrile Intermediate 83 was prepared in a manner similar to Intermediate 55. [00267] Intermediate 84: 4-(2,6-Diazaspiro[3.4]octan-2-yl)-1,3,5-triazine-2-carbonitr ile Intermediate 84 was prepared in a manner similar to Intermediate 55. [00268] Intermediate 85: 4-(2,6-Diazaspiro[3.3]heptan-2-yl)-1,3,5-triazine-2-carbonit rile Intermediate 85 was prepared in a manner similar to Intermediate 55. [00269] Intermediate 86: 2-(Piperazin-1-yl)pyrimidine-4-carbonitrile Intermediate 86 was prepared in a manner similar to Intermediate 51. [00270] Intermediate 87: 2-(Piperidin-4-ylamino)pyrimidine-4-carbonitrile Intermediate 87 was prepared in a manner similar to Intermediate 51. MS: m/z = 204.0 [M + H] ⁺ . [00271] Intermediate 88: (R)-4-(Piperidin-3-ylamino)-1,3,5-triazine-2-carbonitrile Intermediate 88 was prepared in a manner similar to Intermediate 55. [00272] Intermediate 89: 3-(3-(4-(Chloromethyl)phenyl)-5-(3-fluorophenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 89 was prepared in a manner similar to Intermediate 76. MS: m/z = 430.0 [M + H] ⁺ . [00273] Intermediate 90: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-fluorophenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 90 was prepared in a manner similar to Intermediate 76. MS: m/z = 430.1 [M + H] ⁺ . [00274] Intermediate 91: 4-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)-1,4-diazepan-2-one Step 1: Methyl 4-((3-nitro-6-(3-oxo-1,4-diazepan-1-yl)pyridin-2-yl)amino)be nzoate To a solution of methyl 4-[(6-chloro-3-nitro-2-pyridyl)amino]benzoate (refer to Intermediate 13 for detail procedures, 1 g, 3.25 mmol) in CH ₃ CN (10 mL) were added DIEA (1.26 g, 9.75 mmol, 1.70 mL) and 1,4-diazepan-2-one (556 mg, HCl salt, 3.69 mmol). The mixture was stirred at 90 °C for 12 hr. Water (10 mL) was added to the mixture and the mixture was filtrated and the filter cake was dried under reduced pressure to give methyl 4-((3-nitro-6-(3-oxo-1,4-diazepan-1- yl)pyridin-2-yl)amino)benzoate (900 mg, yield: 72%) as a yellow solid. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.85 - 10.68 (m, 1H), 8.30 (d, J = 8.4 Hz, 1H), 8.31 - 7.64 (m, 5H), 6.60 - 6.45 (m, 1H), 4.46 - 4.27 (m, 2H), 3.99 (s, 2H), 3.84 (s, 3H), 3.31 - 3.24 (m, 2H), 1.85 - 1.65 (m, 2H)). Step 2: Methyl 4-(2-(2-aminopyridin-3-yl)-5-(3-oxo-1,4-diazepan-1-yl)-3H-im idazo[4,5- b]pyridin-3-yl)benzoate To a solution of methyl 4-((3-nitro-6-(3-oxo-1,4-diazepan-1-yl)pyridin-2-yl)amino)be nzoate (900 mg, 2.34 mmol) in DMSO (10 mL) were added Na ₂ S ₂ O ₄ (1.22 g, 7.01 mmol) and 2- aminopyridine-3-carbaldehyde (342 mg, 2.80 mmol). The mixture was stirred at 100 °C for 12 hr. Water (10 mL) was added to the mixture and the mixture was extracted with CH ₂ Cl ₂ (10 mL x 2). The combined organic phases were washed with brine (10 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated to give methyl 4-(2-(2-aminopyridin-3-yl)-5-(3-oxo-1,4- diazepan-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzoate (1 g, yield: 94%) as a yellow solid. MS: m/z = 458.2 [M + H] ⁺ . Step 3: 4-(2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5-b]pyridin-5- yl)-1,4-diazepan-2-one To a solution of methyl 4-(2-(2-aminopyridin-3-yl)-5-(3-oxo-1,4-diazepan-1-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzoate (1 g, 2.19 mmol) in THF (50 mL) was added LiAlH ₄ (166 mg, 109 ul) at 0 ºC under N ₂ . The reaction mixture was stirred at 20 °C for 12 hr. Na ₂ SO ₄ ·10H ₂ O was added in portions at 0 °C until no bubbles formed, and the resulting mixture was stirred for 10 min. Then filtered and the filter cake was washed with THF (10 mL x 2). The filtrate was concentrated under reduced pressure to give 4-(2-(2-aminopyridin-3-yl)-3-(4- (hydroxymethyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)-1,4-di azepan-2-one (939 mg, yield: 100%) as a brown oil, which was used in the next step directly. MS: m/z = 430.0 [M + H] ⁺ . Step 4; 4-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imi dazo[4,5-b]pyridin-5- yl)-1,4-diazepan-2-one To a solution of 4-(2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5- b]pyridin-5-yl)-1,4-diazepan-2-one (939 mg, 2.19 mmol) in CH ₂ Cl ₂ (20 mL) was added SOCl ₂ (780 mg, 476 μL) at 20 ºC. The reaction mixture was stirred at 40 ºC for 2 hr. The reaction mixture was concentrated to dryness to give 4-(2-(2-aminopyridin-3-yl)-3-(4- (chloromethyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)-1,4-dia zepan-2-one (Intermediate 91, 760 mg, yield: 78%) as a brown solid, which was used in the next step directly. MS: m/z = 448.1 [M + H] ⁺ . [00275] Intermediate 92: 4-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)benzonitrile Intermediate 92 was prepared in a manner similar to Intermediate 76. MS: m/z = 437.0 [M + H] ⁺ . [00276] Intermediate 93: 2-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)benzonitrile Intermediate 93 was prepared in a manner similar to Intermediate 76. MS: m/z = 437.0 [00277] Intermediate 94: 1-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)-1,4-diazepan-5-one Intermediate 94 was prepared in a manner similar to Intermediate 91. MS: m/z = 448.3 [M+H] ⁺ . [00278] Intermediate 95: 1-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)-4-methyl-1,4-diazepan-5-one

Step 1: tert-Butyl 4-methyl-5-oxo-1,4-diazepane-1-carboxylate To a solution of tert-butyl 5-oxo-1,4-diazepane-1-carboxylate (5 g, 23.3 mmol) in THF (50 mL) were added MeI (4.97 g, 35.0 mmol, 2.18 mL) and NaH (1.87 g, 46.7 mmol, 60% purity) at 0 °C under N ₂ . This mixture was stirred at 25 °C for 3 h. The mixture was quenched with water (10 mL) at 0 °C and then phase was extracted with CH ₂ Cl ₂ (20 mL x 3). The combined organic phase was washed with brine (30 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated to give Tert-butyl 4-methyl-5-oxo-1,4-diazepane-1-carboxylate (5.33 g, yield :100%) as light- yellow oil, which was used next step without purification. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 3.51 - 3.39 (m, 6H), 2.84 (s, 3H), 2.56 - 2.52 (m, 2H), 1.39 (s, Step 2: 4-Methyl-1,4-diazepan-5-one To a solution of tert-butyl 4-methyl-5-oxo-1,4-diazepane-1-carboxylate (5.33 g, 23.4 mmol) in 1,4-dioxane (10 mL) was added HCl/1,4-dioxane (4 M, 40 mL) at 25 °C under N ₂ . This mixture was stirred at 25 °C for 3 hr. The reaction was concentrated. 4-Methyl-1,4-diazepan-5-one (3.84 g, HCl salt, yield:100%) was obtained as a light-yellow solid, which was used next step without purification. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.63 - 9.39 (m, 1H), 3.71 - 3.63 (m, 2H), 3.22 - 3.09 (m, 4H), 2.87 (s, 3H), 2.81 - 2.73 (m, 2H). Step 3: Methyl 4-((6-(4-methyl-5-oxo-1,4-diazepan-1-yl)-3-nitropyridin-2-yl )amino)benzoate To a solution methyl 4-((6-chloro-3-nitropyridin-2-yl)amino)benzoate (refer to Intermediate 13 for detail procedures, 6.2 g, 20.2 mmol) in DMSO (50 mL) were added DIEA (7.81 g, 10.53 mL) and 4-methyl-1,4-diazepan-5-one (3.65 g, HCl salt, 22.2 mmol). The mixture was stirred at 80 °C for 12 hr. Water (50 mL) was added to the mixture and the mixture was extracted with EtOAc (50 mL x 2). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. Methyl 4-((6-(4-methyl-5-oxo-1,4-diazepan-1- yl)-3-nitropyridin-2-yl)amino)benzoate (8.05 g, yield :100%) was obtained as a light-yellow solid. MS: m/z = 400.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 10.78 (s, 1H), 8.32 (d, J = 9.2 Hz, 1H), 8.03 (d, J = 8.8 Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 6.21 (d, J = 9.6 Hz, 1H), 3.99 - 3.94 (m, 2H), 3.92 (s, 3H), 3.88 - 3.82 (m, 2H), 3.58 - 3.507 (m, 2H), 3.04 (s, 3H), 2.82 - 2.76 (m, 2H). Step 4: Methyl 4-(2-(2-aminopyridin-3-yl)-5-(4-methyl-5-oxo-1,4-diazepan-1- yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzoate To a solution of methyl 4-((6-(4-methyl-5-oxo-1,4-diazepan-1-yl)-3-nitropyridin-2- yl)amino)benzoate (7.99 g, 20 mmol) in DMSO (80 mL) were added Na ₂ S ₂ O ₄ (10.5 g, 60 mmol) and 2-aminopyridine-3-carbaldehyde (2.44 g, 20 mmol). The mixture was stirred at 100 °C for 12 hr. The reaction was concentrated. Water (100 mL) was added and the aqueous was extracted with CH ₂ Cl ₂ (200 mL x 2). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. Methyl 4-(2-(2-aminopyridin-3-yl)-5-(4-methyl-5-oxo-1,4- diazepan-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzoate (7 g, yield: 74%) was obtained as a yellow solid, which was used in next step without purification. MS: m/z = 472.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.09 (d, J = 8.8 Hz, 2H), 8.04 - 7.95 (m, 2H), 7.57 (d, J = 8.8 Hz, 2H), 7.30 (d, J = 6.8 Hz, 1H), 6.95 (d, J = 9.2 Hz, 1H), 6.57 (dd, J = 7.6, 5.6 Hz, 1H), 3.89 (s, 3H), 3.80 - 3.74 (m, 2H), 3.73 - 3.68 (m, 2H), 3.54 - 3.44 (m, 2H), 2.82 (s, 3H), 2.64 - 2.60 (m, 2H). Step 5: 1-(2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5-b]pyridin-5- yl)-4-methyl-1,4-diazepan-5-one To a solution of methyl methyl 4-(2-(2-aminopyridin-3-yl)-5-(4-methyl-5-oxo-1,4-diazepan-1- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzoate (100 mg, 212 μmol) in THF (1 mL) was added LiAlH ₄ (24.2 mg, 636 µmol) at 0 ºC for 30 min .The mixture was stirred at 0 ºC for 1.5 hr. The mixture was diluted with THF (20 mL). Na ₂ SO ₄ 10H ₂ O was added in portions until no bubbles were formed. The resulting mixture was stirred at 25 °C for 20 min and filtered. The filter cake was washed with THF (20 mL x 2), the combined filtrate was concentrated. 1-(2-(2- Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imidazo[4, 5-b]pyridin-5-yl)-4-methyl- 1,4-diazepan-5-one (82 mg, yield :87%) was obtained as light-yellow oil, which was used next step without further purification. MS: m/z = 444.1 [M + H] ⁺ . Step 6: 1-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imi dazo[4,5-b]pyridin-5- yl)-4-methyl-1,4-diazepan-5-one To a solution of 1-(2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5- b]pyridin-5-yl)-4-methyl-1,4-diazepan-5-one (82 mg, 185 μmol) in CH ₂ Cl ₂ (1 mL) were added SOCl ₂ (110 mg, 924 μmol). The mixture was stirred at 25 °C for 12 hr. The reaction was concentrated. l-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imi dazo[4,5- b]pyridin-5-yl)-4-methyl-l,4-diazepan-5-one (Intermediate 95, 85.4 mg, yield: 100%) was obtained as a light-yellow solid, which was used for next step without purification. MS: m/z = 462.1 [M + H] ⁺ .

[00279] Intermediate 96: 3 -(5 -(Cyclohex- 1 -en- 1 -y 1 ) - 3 -(4-(piperazin- 1 -ylmethyl)pheny 1)- 3H-imidazo[4,5-b]pyri din-2 -yl)pyridin-2-amine

Step 1 : Tert-butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-(cyclohex-l-en-l-yl)-3H-imid azo[4,5- b]pyridin-3-yl)benzyl)piperazine-l-carboxylate

To a solution of Intermediate 42 (200 mg, 385 μmol) in 1,4-dioxane (5 mL) and H ₂ O (1 mL) were added cyclohex- 1-en-l-ylboronic acid (72.7 mg, 577 μmol), K ₂ CO ₃ (159 mg, 1.15 mmol) and Pd(dppf)C12 (28.1 mg, 38.5 μmol) at 25 °C under N ₂ . This mixture was stirred at 100 °C for 5 hr. H ₂ O (5 mL) was added to the mixture. The aqueous phase was extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. The residue was purified by prep-TLC (EtOAc : petroleum ether = 2 : 1) to give tert-butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-(cyclohex-l-en-l-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazine-l-carboxylate (100 mg, yield: 83%) as a yellow oil. MS: m/z = 566.4 [M + H] ⁺ .

Step 2 : 3 -(5 -(Cyclohex- 1 -en- 1 -y 1 ) - 3 -(4-(piperazin- 1 -ylmethyl)pheny l)-3H-imidazo[4, 5 - b]pyri din-2 -yl)pyridin-2-amine

To a solution of tert-butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-(cyclohex-l-en-l-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazine-l-carboxylate (79.7 mg, 141 μmol) in 1,4-dioxane (1 mL) was added HCl/l,4-dioxane (4 M, 35.2 μL) at 25 °C. This mixture was stirred at 25 °C for 3 hr. The mixture was filtrated and concentrated. 3-(5-(Cyclohex-l-en-l-yl)-3-(4- (piperazin-l-ylmethyl)phenyl)-3H-imidazo[4,5-b]pyri din-2 -yl)pyridin-2-amine (Intermediate 96, 60 mg, HC1 salt, yield: 84%) was obtained as a yellow solid, which was used in the next step directly without purification. MS: m/z = 466.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol -d ₄ ) δ 8.16 (d, J= 8.4 Hz, 1H), 8.01 (dd, J= 6.4, 1.6 Hz, 1H), 7.90 (d, J= 8.4 Hz, 2H), 7.85 (dd, J = 7.6, 1.4 Hz, 1H), 7.70 - 7.62 (m, 3H), 6.92 (dd, J= 7.6, 6.4 Hz, 1H), 6.75 - 6.69 (m, 1H), 4.62 (s, 2H), 3.69 - 3.68 (m, 7H), 3.60 - 3.59 (m, 1H), 2.56 - 2.47 (m, 2H), 2.30 - 2.21 (m, 2H), 1.81 - 1.64 (m, 4H). [00280] Intermediate 97: 3-(5-(3,6-Dihydro-2H-pyran-4-yl)-3-(4-(piperazin-1- ylmethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-ami ne Step 1: Tert-butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-(3,6-dihydro-2H-pyran-4-yl)- 3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazine-1-carboxylate To a solution of Intermediate 42 (200 mg, 385 μmol) in 1,4-dioxane (5 mL) and H ₂ O (1 mL) were added 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-diox aborolane (121 mg, 577 μmol), K ₂ CO ₃ (159 mg, 1.15 mmol) and Pd(dppf)Cl ₂ (28.1 mg, 38.5 μmol) at 25 ºC under N ₂ . This mixture was stirred at 100 °C for 5 hr. The water (5 mL) was added to the mixture. The aqueous phase was extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. The residue was purified by prep-TLC (EtOAc : petroleum ether = 2 : 1) to give tert-butyl 4-(4-(2- (2-aminopyridin-3-yl)-5-(3,6-dihydro-2H-pyran-4-yl)-3H-imida zo[4,5-b]pyridin-3- yl)benzyl)piperazine-1-carboxylate (45 mg, yield: 50%) as an off-white solid. MS: m/z = 568.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.08 (d, J = 8.4 Hz, 1H), 7.97 (dd, J = 4.8, 1.6 Hz, 1H), 7.62 (d, J = 8.4 Hz, 1H), 7.51 (d, J = 8.0 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H), 7.29 (dd, J = 8.0, 2.0 Hz, 1H), 6.72-6.65 (m, 1H), 6.47 (dd, J = 8.0, 5.2 Hz, 1H), 4.36 - 4.28 (m, 2H), 3.90 (t, J = 5.6 Hz, 2H), 3.62 (s, 2H), 3.46 - 3.45 (m, 4H), 2.67 - 2.60 (m, 2H), 2.46 (t, J = 4.8 Hz, 4H), 1.46 (s, 9H). Step 2: 3-(5-(3,6-Dihydro-2H-pyran-4-yl)-3-(4-(piperazin-1-ylmethyl) phenyl)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine To a solution of tert-butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-(3,6-dihydro-2H-pyran-4-yl)- 3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazine-1-carboxylate (45.0 mg, 79.3 μmol) in 1,4- dioxane (1 mL) was added HCl/1,4-dioxane (4 M, 19.8 μL) at 25 ºC. This mixture was stirred at 25 °C for 3 hr. The mixture was filtrated and concentrated. 3-(5-(3,6-Dihydro-2H-pyran-4- yl)-3-(4-(piperazin-1-ylmethyl)phenyl)-3H-imidazo[4,5-b]pyri din-2-yl)pyridin-2-amine (Intermediate 97, 20.8 mg, HCl salt, yield: 52%) was obtained as a yellow solid, which was used in the next step directly without purification. MS: m/z = 468.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.21 (d, J = 8.4 Hz, 1H), 8.01 (dd, J = 6.4, 1.2 Hz, 1H), 7.93 - 7.83 (m, 3H), 7.75 - 7.62 (m, 3H), 6.96 - 6.87 (m, 1H), 6.75 - 6.74 (m, 1H), 4.62 (s, 2H), 4.39 - 4.29 (m, 2H), 3.90 (t, J = 5.2 Hz, 2H), 3.69 - 3.68 (m, 8H), 2.68-2.57 (m, 2H). [00281] Intermediate 98: 3-(2-(2-Aminopyridin-3-yl)-3-(4-(piperazin-1-ylmethyl)phenyl )- 3H-imidazo[4,5-b]pyridin-5-yl)benzonitrile Intermediate 98 was prepared in a manner similar to Intermediate 45. MS: m/z = 487.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.43 - 8.34 (m, 3H), 8.11 (d, J = 8.4 Hz, 1H), 8.03 (d, J = 5.6 Hz, 1H), 7.96 (d, J = 8.4 Hz, 2H), 7.90 (d, J = 7.6 Hz, 1H), 7.79 - 7.73 (m, 3H), 7.68 - 7.63 (m, 1H), 6.96 - 6.90 (m, 1H), 3.70 - 3.68 (m, 6H), 3.67 – 3.65 (m, 4H). [00282] Intermediate 99: 5-(2-(2-aminopyridin-3-yl)-3-(4-(piperazin-1-ylmethyl)phenyl )- 3H-imidazo[4,5-b]pyridin-5-yl)pyridin-2(1H)-one Intermediate 99 was prepared in a manner similar to Intermediate 45. MS: m/z = 479.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.76 (d, J = 9.2 Hz, 1H), 8.61 (s, 1H), 8.37 (d, J = 8.4 Hz, 1H), 8.01 - 8.07 (m, 2H), 7.95 (d, J = 8.0 Hz, 2H), 7.90 (d, J = 7.2 Hz, 1H), 7.73 (d, J = 7.6 Hz, 2H), 7.08 (d, J = 9.2 Hz, 1H), 6.94 (t, J = 6.8 Hz, 1H), 4.67 (s, 2H), 3.82 - 3.64 (m, 8H). [00283] Intermediate 100: 2-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-2-(2- aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-5-yl)benzonitril e Intermediate 100 was prepared in a manner similar to Intermediate 81. MS: m/z = 501.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.42 (d, J = 8.0 Hz, 1H), 8.06 - 8.01 (m, 1H), 7.96 - 7.90 (m, 3H), 7.85 - 7.83 (m, 3H), 7.80 - 7.75 (m, 3H), 7.62 - 7.55 (m, 1H), 6.88 (t, J = 7.2 Hz, 1H), 3.69 - 3.65 (m, 2H), 3.62 - 3.35 (m, 2H), 3.29 - 3.21 (m, 3H), 2.30 - 2.26 (m, 2H), 2.12 - 2.01 (m, 2H). [00284] Intermediate 101: 3-(3-(4-(((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)- yl)methyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyr idin-2-amine Intermediate 101 was prepared in a manner similar to Intermediate 35. MS: m/z = 488.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.27 (d, J = 8.0 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.49 - 7.44 (m, 5H), 7.43 - 7.37 (m, 2H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.60 (s, 2H), 2.85 - 2.76 (m, 2H), 2.58 - 2.51 (m, 7H), 2.31 - 2.26 (m, 2H). [00285] Intermediate 102: 3-(3-(4-(((3aR,6aR)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)- yl)methyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyr idin-2-amine Intermediate 102 was prepared in a manner similar to Intermediate 35. MS: m/z = 488.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 12.14 - 11.98 (m, 1H), 9.92 - 9.78 (m, 1H), 9.73 - 9.54 (m, 1H), 8.37 (d, J = 8.8 Hz, 1H), 8.33 - 8.19 (m, 1H), 8.13 (dd, J = 6.0, 1.2 Hz, 1H), 8.09 - 8.04 (m, 3H), 7.86 (d, J = 8.4 Hz, 2H), 7.81 - 7.76 (m, 1H), 7.66 (d, J = 8.0 Hz, 2H), 7.51 - 7.41 (m, 3H), 6.89 - 6.83 (m, 1H), 4.66 - 4.51 (m, 2H), 3.72 - 3.63 (m, 2H), 3.20 - 3.10 (m, 2H), 3.04 - 2.93 (m, 2H), 2.85 - 2.76 (m, 1H), 2.64 - 2.57 (m, 1H), 2.46 - 2.33 (m, 2H). [00286] Intermediate 103: 4-((3aR,6aR)-Hexahydropyrrolo[3,4-c]pyrrol-2(1H)- yl)pyrimidine-2-carbonitrile Step 1: tert-Butyl (3aS,6aS)-5-(2-cyanopyrimidin-4-yl)hexahydropyrrolo[3,4-c]py rrole-2(1H)- carboxylate To a mixture of tert-butyl (3aS,6aS)-hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (300 mg, 1.41 mmol) and 4-chloropyrimidine-2-carbonitrile (197 mg, 1.41 mmol) in NMP (4 mL) was added DIEA (547 mg, 4.24 mmol, 738 μL). The mixture was stirred at 60 ºC fo 1 hr. H ₂ O (10 mL) was added and the reaction mixture was filtrated. The filtration cake was dried to give tert-butyl (3aS,6aS)-5-(2-cyanopyrimidin-4-yl)hexahydropyrrolo[3,4-c]py rrole-2(1H)- carboxylate (230 mg, yield: 52%) as a white solid. MS: m/z = 316.0 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.24 (d, J = 6.4 Hz, 1H), 6.76 (d, J = 6.4 Hz, 1H), 3.91 - 3.80 (m, 1H), 3.70 - 3.60 (m, 1H), 3.57 - 3.49 (m, 2H), 3.18 - 3.10 (m, 2H), 3.08 - 2.96 (m, 2H), 2.43 - 2.22 (m, 2H), 1.41 (s, 9H). Step 2: 4-((3aR,6aR)-Hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyrimidi ne-2-carbonitrile To a mixture of tert-butyl (3aS,6aS)-5-(2-cyanopyrimidin-4-yl)hexahydropyrrolo[3,4-c]py rrole- 2(1H)-carboxylate (100 mg, 317 μmol) in CH ₂ Cl ₂ (3 mL) was added TFA (767 mg, 0.5 mL), the mixture was stirred at 20 °C for 1 hr. The mixture was concentrated to give 4-((3aR,6aR)- hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyrimidine-2-carbonit rile (Intermediate 103, 104 mg, TFA salt, yield: 100%) as yellow oil. MS: m/z = 215.8 [M+H] ⁺ . [00287] Intermediate 105: 5-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)-1-methylpyridin-2(1H)-one Step 1: (4-((6-Chloro-3-nitropyridin-2-yl)amino)phenyl)methanol To a mixture of (4-aminophenyl)methanol (5 g, 40.6 mmol) and 2,6-dichloro-3-nitro-pyridine (7.84 g, 40.6 mmol) in THF (70 mL) was added DIEA (10.5 g, 81.2 mmol, 14.1 mL). The mixture was stirred at 80 °C for 1 hr. The mixture was concentrated to give (4-((6-chloro-3- nitropyridin-2-yl)amino)phenyl)methanol (11.36 g, yield: 100%) as yellow oil. MS: m/z = 279.8 [M+H] ⁺ . Step 2: N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-6-chloro- 3-nitropyridin-2-amine To a mixture of (4-((6-chloro-3-nitropyridin-2-yl)amino)phenyl)methanol (1 g, 3.58 mmol) in CH ₂ Cl ₂ (10 mL) were added imidazole (365 mg, 5.36 mmol) and TBSCl (701 mg, 4.65 mmol). The mixture was stirred at 20 °C for 1 hr. H ₂ O (50 mL) was added and extracted with CH ₂ Cl ₂ (50 mL x 2). The combined organic layers were washed with brine (20 mL), dried over Na ₂ SO ₄ , filtered and concentrated to give N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-6-chloro- 3- nitropyridin-2-amine (1.1 g, yield: 78%) as a yellow solid. MS: m/z = 394.0 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.12 *s, 1H(, 8.54 *d, J = 8.8 Hz, 1H), 7.59 - 7.52 (m, 2H), 7.36 - 7.30 (m, 2H), 7.00 (d, J = 8.4 Hz, 1H), 4.71 (s, 2H), 0.91 (s, 9H), 0.09 (s, 6H). Step 3: 6-((4-(((Tert-butyldimethylsilyl)oxy)methyl)phenyl)amino)-1' -methyl-5-nitro-[2,3'- bipyridin]-6'(1'H)-one To a mixture of N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-6-chloro- 3-nitropyridin-2- amine (900 mg, 2.28 mmol) and (1-methyl-6-oxo-1,6-dihydropyridin-3-yl)boronic acid (591 mg, 2.51 mmol) in 1,4-dioxane (10 mL) and H ₂ O (2 mL) were added Cs ₂ CO ₃ (2.23 g, 6.85 mmol) and Pd(dppf)Cl ₂ (167 mg, 228 μmol). The mixture was stirred at 100 ºC for 12 hr under N ₂ atmophere. EtOAc (100 mL) and H ₂ O (100 mL) were added into the mixture and filtered. The filtration cake was concentrated to give 6-((4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)amino)-1'-methyl-5-nitr o-[2,3'-bipyridin]-6'(1'H)-one (600 mg, yield: 56%) as a brown solid. MS: m/z = 467.1 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.13 (s, 1H), 8.66 (s, 1H), 8.54 (d, J = 8.8 Hz, 1H), 8.06 (d, J = 8.4 Hz, 1H), 7.64 (d, J = 8.0 Hz, 2H), 7.45 - 7.32 (m, 3H), 6.47 (d, J = 9.6 Hz, 1H), 4.72 (s, 2 H), 3.52 (s, 3H), 0.91 (s, 9H), 0.10 (s, 6H). Step 4: 5-(2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5-b]pyridin-5- yl)-1-methylpyridin-2(1H)-one To a mixture of 6-((4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)amino)-1' -methyl-5-nitro- 2,3'-bipyridin]-6'(1'H)-one (300 mg, 643 μmol) and 2-aminopyridine-3-carbaldehyde (86.4 mg, 707 μmol) in DMSO (3 mL) was added Na ₂ S ₂ O ₄ (280 mg, 1.61 mmol). The mixture was stirred at 100 °C for 12 hr. H ₂ O (50 mL) was added and extracted with CH ₂ Cl ₂ /MeOH (10/1) (30 mL x 3). The combined organic layers were washed with brine (20 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated. The mixture was purified by silica gel flash chromatography (Eluent of 0-60% EtOAc/EtOH (3/1) in petroleum ether) to give 5-(2-(2-aminopyridin-3-yl)-3-(4- (hydroxymethyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)-1-meth ylpyridin-2(1H)-one (100 mg, yield: 37%) as a yellow solid. MS: m/z = 425.0 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.49 (d, J = 2.4 Hz, 1H), 8.24 (d, J = 8.8 Hz, 1H), 8.08 (dd, J = 9.6, 2.4 Hz, 1H), 8.00 (dd, J = 4.8, 2.0 Hz, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.50 - 7.42(m, 4H), 7.19 (dd, J = 8.0, 2.0 Hz, 1H), 6.98 (br s, 2H), 6.50 (d, J = 9.6 Hz, 1H), 6.44 - 6.37(m, 1H), 5.37 (t, J = 6.0 Hz, 1H), 4.61 (d, J = 6.0 Hz, 2H), 3.53 (s, 3H). Step 5: 5-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imi dazo[4,5-b]pyridin-5- yl)-1-methylpyridin-2(1H)-one To a mixture of 5-(2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5- b]pyridin-5-yl)-1-methylpyridin-2(1H)-one (100 mg, 236 μmol) in CH ₂ Cl ₂ (2 mL) was added SOCl ₂ (84.1 mg, 51.3 μL). The mixture was stirred at 40 ºC for 1 hr. The mixture was concentrated to give 5-(2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imi dazo[4,5- b]pyridin-5-yl)-1-methylpyridin-2(1H)-one (Intermediate 105, 80 mg, yield: 77%) as a yellow solid. MS: m/z = 443.0 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.59 - 8.51 (m, 2H), 8.33 (d, J = 8.4 Hz, 1H), 8.17 - 8.05 (m, 2H), 7.96 - 7.80 (m, 2H), 7.74 - 7.48 (m, 3H), 6.94 - 6.84 (m, 1H), 6.56 - 6.47 (m, 1H), 4.86 (s, 2H), 3.53 (s, 3H). [00288] Intermediate 106: 4-(2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)-1-methylpyridin-2(1H)-one Step 1: 6-((4-(((Tert-butyldimethylsilyl)oxy)methyl)phenyl)amino)-1' -methyl-5-nitro-[2,4'- bipyridin]-2'(1'H)-one To a mixture of N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-6-chloro- 3-nitropyridin-2- amine (refer to Intermediate 105 for detail procedures, 6 g, 15.2 mmol) and (1-methyl-2-oxo-4- pyridyl)boronic acid (2.56 g, 16.8 mmol) in H ₂ O (12 mL) and dioxane (60 mL) were added Pd(dppf)Cl ₂ (1.11 g, 1.52 mmol) and Cs ₂ CO ₃ (14.9 g, 45.7 mmol). The mixture was stirred at 100 °C for 2 hr under N ₂ . H ₂ O (200 mL) was added and extracted with EtOAc (300 mL x 2). The combined organic layers were washed with brine (200 mL), dried over Na ₂ SO ₄ , filtered and concentrated. The mixture was purified by silica gel flash chromatography (Eluent 0 - 50% EtOAc in petroleum ether) to give 6-((4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)amino)- 1'-methyl-5-nitro-[2,4'-bipyridin]-2'(1'H)-one (3.2 g, yield: 45%) as a yellow solid. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.02 (s, 1H), 8.61 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 7.2 Hz, 1H), 7.64 (d, J = 8.4 Hz, 2H), 7.58 (d, J = 8.8 Hz, 1H), 7.34 (d, J = 8.4 Hz, 2H), 7.06 (s, 1H), 6.77 (dd, J = 6.8, 1.6 Hz, 1H), 4.73 (s, 2H), 3.45 (s, 3H), 0.92 (s, 9H), 0.10 (s, 6H). Step 2: 4-(2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5-b]pyridin-5- yl)-1-methylpyridin-2(1H)-one To a mixture of 6-((4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)amino)-1' -methyl-5-nitro- [2,4'-bipyridin]-2'(1'H)-one (3.1 g, 6.64 mmol) and 2-aminopyridine-3-carbaldehyde (892 mg, 7.31 mmol) in DMSO (3 mL) was added Na ₂ S ₂ O ₄ (2.89 g, 16.6 mmol). The mixture was stirred at 100 °C for 12 hr. Sat.NaHCO ₃ (500 mL) was added and extracted with CH ₂ Cl ₂ /MeOH (10/1) (300 mL x 3). The combined organic layers were washed with brine (200 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated. The mixture was purified by silica gel flash chromatography (Eluent of 0 - 100% EtOAc / EtOH (3/1) in petroleum ether) to give 4-(2-(2-aminopyridin-3-yl)- 3-(4-(hydroxymethyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)-1 -methylpyridin-2(1H)-one (1.4 g, yield: 50%) as a yellow solid. MS: m/z = 425.1 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.28 (d, J = 8.0 Hz, 1H), 8.08 - 7.98 (m, 2H), 7.75 (d, J = 7.2 Hz, 1H), 7.54 - 7.41 (m, 4H), 7.27 - 7.20 (m, 1H), 7.04 (d, J = 1.6 Hz, 1H), 6.97 (d, J = 4.4 Hz, 1H), 6.86 (dd, J = 7.2, 2.0 Hz, 1H), 6.42 (dd, J = 7.6, 4.8 Hz, 1H), 4.64 - 4.56 (m, 2H), 3.44 (s, 3H). Step 3: 4-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imi dazo[4,5-b]pyridin-5- yl)-1-methylpyridin-2(1H)-one To a mixture of 4-(2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5- b]pyridin-5-yl)-1-methylpyridin-2(1H)-one (400 mg, 942 μmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (336 mg, 205 μL), the mixture was stirred at 40 ºC for 1 hr. The mixture was concentrated to give 4-(2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imi dazo[4,5- b]pyridin-5-yl)-1-methylpyridin-2(1H)-one (Intermediate 106, 400 mg, yield: 96%) as a yellow solid. MS: m/z = 443.1 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.50 - 8.36 (m, 2H), 8.17 - 8.10 (m, 2H), 7.95 (dd, J = 7.6, 1.6 Hz, 1H), 7.81 (d, J = 7.2 Hz, 1H), 7.71 - 7.56 (m, 4H), 7.13 - 7.07 (m, 1H), 6.97 - 6.86 (m, 2H), 4.88 (s, 2H), 3.46 (s, 3H). [00289] Intermediate 107: 3-(3-(4-(Chloromethyl)phenyl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Step 1: Methyl 4-((6-(4-fluorophenyl)-3-nitropyridin-2-yl)amino)benzoate A mixture of methyl 4-((6-chloro-3-nitropyridin-2-yl)amino)benzoate (refer to Intermediate 13 for detail procedures, 5.0 g, 16.3 mmol), (4-fluorophenyl)boronic acid (3.0 g, 21.1 mmol), Pd(dppf)Cl ₂ (1.2 g, 1.63 mmol), Cs ₂ CO ₃ (15.9 g, 48.8 mmol) in 1,4-dioxane (50 mL) and H ₂ O (5 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 100 °C for 16 hr under N ₂ atmosphere. The reaction mixture was diluted with water (200 mL) and extracted with EtOAc (300 mL × 3). The combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0 ~ 10% MeOH in CH ₂ Cl ₂ ) to give methyl 4-((6-(4-fluorophenyl)-3- nitropyridin-2-yl)amino)benzoate (2.5 g, yield: 34%) as a yellow solid. MS: m/z = 340.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.45 (s, 1H), 8.62 (d, J = 8.6 Hz, 1H), 8.15 - 8.04 (m, 4H), 7.85 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.6 Hz, 1H), 7.24 - 7.18 (m, 2H), 3.95 (s, 3H). Step 2: Methyl 4-(2-(2-aminopyridin-3-yl)-5-(4-fluorophenyl)-3H-imidazo[4,5 -b]pyridin-3- yl)benzoate To a solution of methyl 4-((6-(4-fluorophenyl)-3-nitropyridin-2-yl)amino)benzoate (2.5 g, 6.81 mmol) and 2-aminopyridine-3-carbaldehyde (914 mg, 7.49 mmol) in DMSO (100 mL) was added Na ₂ S ₂ O ₄ (4.74 g, 7.49 mmol). The mixture was stirred at 100 °C for 12 hr. The reaction mixture was diluted with water (100 mL) and extracted with CH ₂ Cl ₂ (300 mL × 2). The combined organic layers were washed with brine (100 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0 ~ 100% EtOAc in petroleum ether) to give methyl 4-(2-(2- aminopyridin-3-yl)-5-(4-fluorophenyl)-3H-imidazo[4,5-b]pyrid in-3-yl)benzoate (1.3 g, yield: 40%) as yellow solid. MS: m/z = 440.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.26 - 8.21 (m, 2H), 8.15 (d, J = 8.4 Hz, 1H), 8.08 (dd, J = 5.2, 1.6 Hz, 1H), 8.03 - 7.98 (m, 2H), 7.79 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 8.4 Hz, 2H), 7.17 - 7.08 (m, 3H), 6.82 (br s, 2H), 6.42 (dd, J = 7.6, 4.8 Hz, 1H), 3.99 (s, 3H). Step 3: (4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H-imidazo[4, 5-b]pyridin-3- yl)phenyl)methanol To a solution of methyl 4-(2-(2-aminopyridin-3-yl)-5-(4-fluorophenyl)-3H-imidazo[4,5 - b]pyridin-3-yl)benzoate (1.3 g, 2.92mmol) in THF (100 mL) was added LiAlH ₄ (2.5 M, 4.44 mmol) at 0 °C. The mixture was stirred at 0 °C for 2 hr. The reaction mixture was quenched with Na ₂ SO ₄ ^. 10H ₂ O (203 mg) at 0 °C and filtered. The filtrate was concentrated under reduced pressure. The crude (4-(2-(2-aminopyridin-3-yl)-5-(4-fluorophenyl)-3H-imidazo[4, 5-b]pyridin- 3-yl)phenyl)methanol (1.2 g) was used in the next step without further purification. MS: m/z = 412.0 [M + H] ⁺ . Step 4: 3-(3-(4-(Chloromethyl)phenyl)-5-(4-fluorophenyl)-3H-imidazo[ 4,5-b]pyridin-2- yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(4-fluorophenyl)-3H-imidazo[4, 5-b]pyridin-3- yl)phenyl)methanol (1.2 g, 2.91mmol) in CH ₂ Cl ₂ (20 mL) was added SOCl ₂ (2.1 g, 17.5 mmol). The mixture was stirred at 40 °C for 2 hr. The mixture was concentrated under reduced pressure.3-(3-(4-(Chloromethyl)phenyl)-5-(4-fluorophenyl)-3H -imidazo[4,5-b]pyridin-2- yl)pyridin-2-amine (Intermediate 107, 1.25 g HCl salt, yield: 89%) was obtained as yellow solid. MS: m/z = 429.9 [M + H] ⁺ . [00290] Intermediate 108: 3-(3-(4-(Chloromethyl)phenyl)-5-(3-chlorophenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 108 was prepared in a manner similar to Intermediate 76. MS: m/z = 446.0 [M + H] ⁺ . [00291] Intermediate 109: 3-(3-(4-(((1S,4S)-2,5-Diazabicyclo[2.2.1]heptan-2- yl)methyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyr idin-2-amine Intermediate 109 was prepared in a manner similar to Intermediate 29. MS: m/z = 474.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 12.42 - 11.57 (m, 1H), 10.39 - 9.51 (m, 2H), 8.55 – 8.39 (m, 1H), 8.38 (d, J = 8.4 Hz, 1H), 8.14 (d, J = 5.2 Hz, 1H), 8.11 - 8.01 (m, 3H), 7.94 (d, J = 8.0 Hz, 2H), 7.84 (d, J = 7.2 Hz, 1H), 7.69 (d, J = 8.4 Hz, 2H), 7.54 - 7.40 (m, 3H), 6.91 - 6.87 (m, 1H), 4.68 - 4.40 (m, 4H), 3.99 - 3.94 (m, 1H), 3.80 - 3.75 (m, 2H), 3.42 - 3.40 (m, 1H), 2.60 - 2.52 (m, 1H), 2.20 - 2.06 (m, 1H). [00292] Intermediate 110: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-2-(2- aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-5-yl)pyridin-2(1 H)-one Intermediate 110 was prepared in a manner similar to Intermediate 59. MS: m/z = 493.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.67 - 8.62 (m, 1H), 8.55 (d, J = 8.4 Hz, 1H), 8.43 (d, J = 8.0 Hz, 1H), 8.05 - 8.03 (m, 1H), 7.96 - 7.88 (m, 3H), 7.80 (d, J = 5.2 Hz, 1H), 7.75 - 7.74 (m, 2H), 6.94 - 6.84 (m, 2H), 4.52 (s, 2H), 3.78 - 3.62 (m, 3H), 3.61 - 3.49 (m, 2H), 2.35 - 2.28 (m, 2H), 2.20 - 2.10 (m, 2H). [00293] Intermediate 111: 4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-amine hydrochloride Intermediate 111 was prepared in a manner similar to Intermediate 35. MS: m/z = 477.3 [M + H]+. [00294] Intermediate 112: 3-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)isonicotinonitrile Step 1: 6-((4-(Hydroxymethyl)phenyl)amino)-5-nitro-[2,3'-bipyridine] -4'-carbonitrile A mixture of (4-((6-chloro-3-nitropyridin-2-yl)amino)phenyl)methanol (refer to Intermediate 105 for detail procedures, 2.0 g, 7.0 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)pyridine-4-carbonitrile (1.8 g, 7.9 mmol), cataCXiumAPdG3 (2.6 g, 3.6 mmol), PCy3 (200 mg, 715 μmol), and K ₃ PO ₄ (3.0 g, 14.0 mmol) in DMF (20 mL) was degassed and purged with N ₂ three times, and then mixture was stirred at 120 °C for 2 hr under N ₂ atmosphere. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (150 mL x 2). The combined organic layers were washed with brine (100 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 26% EtOAc in petroleum ether), 6-((4-(hydroxymethyl)phenyl)amino)-5-nitro-[2,3'- bipyridine]-4'-carbonitrile (1.9 g, yield: 58%) was obtained as an orange solid. MS: m/z = 348.0 [M + H] ⁺ , ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.07 (s, 1H), 9.10 (s, 1H), 8.93 (d, J = 5.2 Hz, 1H), 8.74 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 5.2 Hz, 1H), 7.67 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.4 Hz, 1H), 7.29 (d, J = 8.4 Hz, 2H), 5.16 (t, J = 6.0 Hz, 1H), 4.47 (d, J = 6.4 Hz, 2H). Step 2: 6-((4-(((tert-Butyldimethylsilyl)oxy)methyl)phenyl)amino)-5- nitro-[2,3'-bipyridine]-4'- carbonitrile A mixture of 6-((4-(hydroxymethyl)phenyl)amino)-5-nitro-[2,3'-bipyridine] -4'-carbonitrile (1.9 g, 5.5 mmol), TBSCl (1.65 g, 11 mmol) and imidazole (931 mg, 14 mmol) in CH ₂ Cl ₂ (20 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 25 °C for 2 hr under N ₂ atmosphere. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (150 mL x 2). The combined organic layers were washed with brine (100 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 5% MeOH in CH ₂ Cl ₂ ), 6-((4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)amino)-5-nitro-[2,3'-bi pyridine]-4'-carbonitrile (1.2 g, yield: 34%) was obtained as an orange solid. MS: m/z = 462.1 [M + H] ⁺ , ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.08 (s, 1h), 9.11 (s, 1H), 8.93 (d, J = 5.2 Hz, 1H), 8.74 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 5.4 Hz, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.4 Hz, 1H), 7.28 (d, J = 8.4 Hz, 2H), 4.69 (s, 2H), 0.89 (s, 9H), 0.07 (s, 6H). Step 3: 3-(2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5-b]pyridin-5- yl)isonicotinonitrile A mixture of 6-((4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)amino)-5- nitro-[2,3'- bipyridine]-4'-carbonitrile (1.2 g, 2.6 mmol), 2-aminopyridine-3-carbaldehyde (349 mg, 2.9 mmol), Na ₂ S ₂ O ₄ (1.8 g, 10 mmol) in DMSO (50 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 100 °C for 16hr under N ₂ atmosphere. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (300 mL x 2). The combined organic layers were washed with brine (200 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 5% MeOH in CH ₂ Cl ₂ ), 3-(2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)isonicotinonitrile (600 mg, yield: 22%) was obtained as a red solid. MS: m/z = 420.0 [M + H] ⁺ . Step 4: 3-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imi dazo[4,5-b]pyridin-5- yl)isonicotinonitrile To a solution of 3-(2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5- b]pyridin-5-yl)isonicotinonitrile (600 mg, 715 μmol) in CH ₂ Cl ₂ (20 mL) was added SOCl ₂ (511 mg, 4.3 mmol). The mixture was stirred at 40 °C for 2 hr. The reaction mixture was diluted with water (20 mL) and adjusted the pH to about 7~8 by saturated NaHCO ₃ solution, then extracted with EtOAc (50 mL x 2). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 26% EtOAc in petroleum ether), 3-(2-(2- aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imidazo[4,5 -b]pyridin-5- yl)isonicotinonitrile (Intermediate 112, 202 mg, yield: 55%) was obtained as a yellow solid. MS: m/z = 437.9 [M + H] ⁺ . [00295] Intermediate 113: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-(3- chlorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 113 was prepared in a manner similar to Intermediate 59. MS: m/z = 510.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.21 (d, J = 8.4 Hz, 1H), 8.07 - 8.03 (m, 1H), 7.99 - 7.96 (m, 2H), 7.55(d, J = 8.4 Hz, 2H), 7.48 - 7.31 (m, 6H), 6.47 (dd, J = 7.6, 4.8 Hz, 1H), 3.64 (s, 2H), 2.98 - 2.93 (m, 2H), 2.80 - 2.72 (m, 1H), 2.18 - 2.12 (m, 2H), 1.91 - 1.85 (m, 2H), 1.55 - 1.48 (m, 2H). [00296] Intermediate 114: 4-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)-1-methyl-1,4-diazepan-2-one Step 1: Methyl 4-((6-(4-methyl-3-oxo-1,4-diazepan-1-yl)-3-nitropyridin-2-yl )amino)benzoate To a solution of methyl 4-((6-chloro-3-nitropyridin-2-yl)amino)benzoate (refer to Intermediate 13 for detail procedures, 5 g, 16.3 mmol), 1-methyl-1,4-diazepan-2-one (4.01 g HCl salt, 24.4 mmol) in ACN (50 mL) was added DIEA (6.30 g, 48.8 mmol). The mixture was stirred at 80 °C for 16 hr under N ₂ . Water (50 mL) was added, and the mixture was extracted with EtOAc (50 mL x 2). The combined organic layers were filtered and concentrated. The filter cake was washed with ACN (10 mL). Methyl 4-((6-(4-methyl-3-oxo-1,4-diazepan-1-yl)-3-nitropyridin-2- yl)amino)benzoate (4.6 g, yield: 71%) was obtained as yellow solid, which was used in the next step without further purification. MS: m/z = 400.0 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.90 - 10.65 (m, 1H), 8.28 (d, J = 8.8 Hz, 1H), 8.12 - 7.98 (m, 1H), 7.95 (d, J = 8.4 Hz, 2H), 7.88 - 7.75 (m, 1H), 6.65 - 6.37 (m, 1H), 4.63 - 4.30 (m, 2H), 3.84 (s, 3H) 3.62 – 3.47 (m, 2H), 3.40 – 3.25 (m, 2H), 2.83 (s, 3H), 1.97 - 1.793 (m, 2H). Step 2: Methyl 4-(2-(2-aminopyridin-3-yl)-5-(4-methyl-3-oxo-1,4-diazepan-1- yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzoate To a solution of methyl 4-((6-(4-methyl-3-oxo-1,4-diazepan-1-yl)-3-nitropyridin-2- yl)amino)benzoate (4.60 g, 11.5 mmol) in DMSO (15 mL) and MeOH (1.5 mL) were added 2- aminopyridine-3-carbaldehyde (1.55 g, 12.7 mmol) and Na ₂ S ₂ O ₄ (6.02 g, 34.6 mmol). The mixture was stirred at 100 °C for 48 hr. Water (300 mL) was added to the mixture and the mixture was extracted with CH ₂ Cl ₂ (50 mL × 2). The combined organic layers were washed with brine (20 mL), dried over Na ₂ SO ₄ , filtered and concentrated. Methyl 4-(2-(2-aminopyridin- 3-yl)-5-(4-methyl-3-oxo-1,4-diazepan-1-yl)-3H-imidazo[4,5-b] pyridin-3-yl)benzoate (4.7 g, yield: 87%) was obtained as yellow oil, which was used in next step without further purification. MS: m/z = 472.3 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.06 (d, J = 8.4 Hz, 2H), 8.02 - 7.97 (m, 2H), 7.58 (d, J = 8.4 Hz, 2H),7.45 (br s, 2H), 7.31 (d, J = 7.8 Hz, 1H), 6.86 (d, J = 8.8 Hz, 1H), 6.57 (dd, J = 7.2, 5.6 Hz, 1H), 4.28 (s, 2H), 3.87 (s, 3H), 3.84 - 3.78 (m, 2H), 3.48 - 3.44 (m, 2H), 2.76 (s, 3H), 1.76 - 1.66 (m, 2H). Step 3: 4-(2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5-b]pyridin-5- yl)-1-methyl-1,4-diazepan-2-one To a solution of methyl 4-(2-(2-aminopyridin-3-yl)-5-(4-methyl-3-oxo-1,4-diazepan-1- yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzoate (1.0 g, 2.12 mmol) in THF (20 mL) was added LiAlH ₄ (121 mg, 3.18 mmol) in portions under N ₂ at 0 °C. The mixture was stirred at 0 °C for 2 hr under N ₂ . The mixture was diluted with THF (20 mL). Na ₂ SO ₄ ·10H ₂ O was added in portions until no bubbles were formed. The resulting mixture was stirred at 25 °C for 20 min and filtered. The filter cake was washed with THF (20 mL × 2), the combined filtrate was concentrated. 4-(2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5- b]pyridin-5-yl)-1-methyl-1,4-diazepan-2-one (941 mg) as brown oli, which was used in the next step directly. MS: m/z = 444.3 [M+H] ⁺ . Step 4: 4-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imi dazo[4,5-b]pyridin-5- yl)-1-methyl-1,4-diazepan-2-one To a solution of 4-(2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5- b]pyridin-5-yl)-1-methyl-1,4-diazepan-2-one (941 mg, 2.12 mmol) in CH ₂ Cl ₂ (10 mL) was added SOCl ₂ (757 mg, 6.36 mmol) at 25 °C. The mixture was stirred at 40 °C for 1 hr under N ₂ . The mixture was concentrated. 4-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)-1-methyl-1,4-diazepan-2-one (Intermediate 114, 980 mg) as brown solid, which was used in the next step directly. MS: m/z = 462.2 [M+H] ⁺ . [00297] Intermediate 115: 3-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)benzonitrile Intermediate 115 was prepared in a manner similar to Intermediate 76. MS: m/z = 437.0 [M + H] ⁺ . [00298] Intermediate 116: 4-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)morpholin-3-one hydrochloride Step 1: 3-(3-(4-(((Tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-morp holino-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine A mixture of (4-(2-(2-aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5-b]py ridin-3- yl)phenyl)methanol (refer to Intermediate 56 for detail procedures, 5.1 g, 13 mmol), TBSCl (3.8 g, 25 mmol) and imidazole (2.2 g, 32 mmol) in CH ₂ Cl ₂ (70 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 25 °C for 2 hr under N ₂ atmosphere. The reaction mixture was diluted with water (40 mL) and extracted with EtOAc (100 mL x 2). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 16%, EtOAc in petroleum ether), 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)- 5-morpholino-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (3.5 g, yield: 53%) was obtained as yellow solid. MS: m/z = 517.6 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.00 (dd, J = 5.2, 1.6 Hz, 1H), 7.90 (d, J = 8.8 Hz, 1H), 7.43 (d, J = 8.4 Hz, 2H), 7.34 - 7.28 (m, 2H), 7.04 (dd, J = 7.6, 1.6 Hz, 1H), 6.69 (d, J = 8.8 Hz, 1H), 6.60 (br s, 2H), 6.34 (dd, J = 7.6, 4.8 Hz, 1H), 4.69 (s, 2H), 3.83 - 3.77 (m, 4H), 3.51 - 3.43 (m, 4H), 0.96 (s, 9H), 0.13 (s, 6H). Step 2: 4-(2-(2-Aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)o xy)methyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)morpholin-3-one To a solution of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-morp holino-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (1.0 g, 1.9 mmol) in MeCN (30 mL) was added dropwise NaClO ₂ (1.4 g, 15 mmol) in H ₂ O (5 mL) at 50 °C over 10 min. The resulting mixture was stirred at 50 °C for 12 hr under CO ₂ atmosphere. The reaction mixture was concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 100% EtOAc in petroleum ether), 4-(2-(2-aminopyridin-3-yl)-3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-3H-imidazo[4,5-b]pyrid in-5-yl)morpholin-3-one (200 mg, yield: 16%) was obtained as a yellow solid. MS: m/z = 531.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.11 - 8.02 (m, 3H), 7.48 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 7.14 - 7.11 (m, 1H), 6.99 (br s, 2H), 6.38 (dd, J = 7.6, 5.2 Hz, 1H), 4.85 (s, 2H), 4.35 (s, 2H), 3.99 (br s, 4H), 0.97 (s, 9H), 0.14 (s, 6H). Step 3: 4-(2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5-b]pyridin-5- yl)morpholin-3-one To a solution of 4-(2-(2-aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)o xy)methyl)phenyl)- 3H-imidazo[4,5-b]pyridin-5-yl)morpholin-3-one (200 mg, 377 μmol) in TBAF (1 M, 5 mL). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was diluted with H ₂ O (30 mL) and extracted with EtOAc (30 mL x 2). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The crude 4-(2- (2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imidazo [4,5-b]pyridin-5-yl)morpholin- 3-one (157 mg, yield: 100%) was used in the next step without further purification. MS: m/z = 417.1 [M + H] ⁺ . Step 4: 4-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imi dazo[4,5-b]pyridin-5- yl)morpholin-3-one hydrochloride To a solution of 4-(2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5- b]pyridin-5-yl)morpholin-3-one (150 mg, 360 μmol) in CH ₂ Cl ₂ (2 mL) was added SOCl ₂ (129 mg, 1 mmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude 4-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)morpholin-3-one hydrochloride (Intermediate 116, 170 mg HCl salt, yield: 100%) was used in the next step without further purification. MS: m/z = 435.2 [M + H] ⁺ . [00299] Intermediate 117: 3-(5-Chloro-3-(4-(chloromethyl)phenyl)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine Step 1: N ² -(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-6-ch loropyridine-2,3-diamine To a solution of N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-6-chloro- 3-nitropyridin-2- amine (refer to Intermediate 105 for detail procedures, 5 g, 12.7 mmol) in EtOH (50 mL) and H ₂ O (10 mL) was added Fe (1.42 g, 25.4 mmol) and NH ₄ Cl (3.39 g, 63.5 mmol). The mixture was degassed and purged with N ₂ three times and stirred at 80 ºC for 2 hr under N ₂ . The reaction mixture was filtered and concentrated under reduced pressure to give N ² -(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-6-chloropyridine-2,3-d iamine (4.62 g, crude) as a black solid, which was used in the next step directly. MS: m/z = 364.2 [M+H] ⁺ . Step 2: 3-(3-(4-(((tert-Butyldimethylsilyl)oxy)methyl)phenyl)-5-chlo ro-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine To a solution of N ² -(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-6-ch loropyridine-2,3- diamine (13.9 g, 38.1 mmol), 2-aminonicotinaldehyde (4.65 g, 38.1 mmol) in EtOH (150 mL) was added InCl ₃ (842 mg, 3.81 mmol). The mixture was degassed and purged with N ₂ three times and stirred at 80 oC for 2 hr under N ₂ . Then MnO ₂ (19.9 g, 228 mmol) was added. The mixture was degassed and purged with N ₂ three times and stirred at 80 ºC for 2 hr under N ₂ . The reaction mixture was filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 1 ~ 50% EtOAc in petroleum ether), 3-(3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-5-chloro-3H-imidazo[4, 5-b]pyridin-2-yl)pyridin-2- amine (6.02 g, 11.8 mmol) was obtained as a gray solid. MS: m/z = 466.3 [M+H]+. ¹ H NMR (400 MHz, Chloroform-d) δ 8.06 - 8.00 (m,, 2H), 7.49 (d, J = 8.0 Hz, 2H), 7.31 (dd, J = 1.8, 8.4 Hz, 3H), 7.09 (dd, J = 7.6, 1.2 Hz, 1H), 6.80 (br s, 2H), 6.36 (dd, J = 7.6, 5.2 Hz, 1H), 4.83 (s, 2H), 0.97 (s, 9H), 0.14 (s, 6H). Step 3: (4-(2-(2-Aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5-b]pyridi n-3-yl)phenyl)methanol To a solution of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-chlo ro-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (500 mg, 1.07 mmol) in CH ₂ Cl ₂ (5 mL) was added TBAF (1 M, 1.61 mL). The mixture was degassed and purged with N ₂ three times and stirred at 25 ºC for 2 hr under N ₂ . The reaction mixture was quenched with Sat.NH ₄ Cl (20 mL) at 25 ºC, and then extracted with CH ₂ Cl ₂ (10 mL × 3). The combined organic layers were washed with brine (20 mL × 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. (4-(2- (2-aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5-b]pyridin-3-yl )phenyl)methanol (377 mg, crude) was obtained as a yellow solid. MS: m/z = 352.2 [M+H] ⁺ . Step 4: 3-(5-Chloro-3-(4-(chloromethyl)phenyl)-3H-imidazo[4,5-b]pyri din-2-yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5-b]pyridi n-3- yl)phenyl)methanol (377 mg, 1.07 mmol) in CH2Cl2 (5 mL) was added SOCl2 (1.28 g, 10.7 mmol). The mixture was degassed and purged with N ₂ three times and stirred at 25 ºC for 4 hr under N ₂ . The reaction mixture was concentrated under reduced pressure to give 3-(5-chloro-3- (4-(chloromethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrid in-2-amine (Intermediate 117, 430 mg, crude) as a gray solid. MS: m/z = 370.1 [M+H] ⁺ . [00300] Intermediate 118: 3-(3-(4-(Chloromethyl)phenyl)-5-cyclopentyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine

Step 1: 3-(3-(4-(((Tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-(cyc lopent-1-en-1-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine A mixture of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-chlo ro-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (refer to Intermediate 117 for detail procedures, 1 g, 2.15 mmol), cyclopenten-1-ylboronic acid (288 mg, 2.57 mmol), Cs ₂ CO ₃ (2.1 g, 6.4 mmol), Pd(dppf)Cl ₂ (157 mg, 215 µmol) in 1,4-dioxane (10 mL) and H ₂ O (2 mL) was degassed and purged with N ₂ three times, then the mixture was stirred at 100 °C for 16 hr under N ₂ atmosphere. The reaction mixture was poured into H ₂ O (15 mL), extracted with EtOAc (15 mL × 3). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 35% EtOAc in petroleum ether), 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-(cyc lopent-1-en-1-yl)- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (930 mg, yield: 84%) was obtained as a gray solid. MS: m/z = 498.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d J = 4.8, 1.6 Hz, 1H), 7.98 (d, J = 8.4 Hz, 1H), 7.50 - 7.32 (m, 5H), 7.12 (dd, J = 7.6, 1.6 Hz, 1H), 6.67 (br s, 2H), 6.56 (t, J = 2.0 Hz, 1H), 6.36 (dd, J = 7.6, 5.2 Hz, 1H), 4.84 (s, 2H), 2.88 - 2.72 (m, 2H), 2.59 - 2.50 (m, 2H), 2.01 (d, J = 7.6 Hz, 1H), 1.86 - 1.74 (m, 1H), 0.97 (s, 9H), 0.14 (s, 6H) Step 2: 3-(3-(4-(((Tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-cycl opentyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine To a solution of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-(cyc lopent-1-en-1-yl)- 3H-imidazol[4,5-b]pyridin-2-yl)pyridin-2-amine (160 mg, 322 µmol) in MeOH (10 mL) was added Pd/C (230 mg, 216 μmol, 10% purity) under N ₂ . The suspension was degassed under reduced pressure and purged with H ₂ several times. The mixture was stirred under H ₂ (15psi) at 25 °C for 4 hr. The reaction mixture was filtered and concentrated under reduced pressure. The crude 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-cycl opentyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (150 mg, yield: 94%) was obtained as a yellow solid. MS: m/z = 500.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.07 (d, J = 8.0 Hz, 1H), 7.97 (dd, J = 4.4, 1.6 Hz, 1H), 7.46 - 7.43 (m, 2H), 7.40 - 7.36 (m, 2H), 7.29 (d, J = 8.4 Hz, 1H), 7.13 (dd, J = 7.2, 1.6 Hz, 1H), 6.93 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 4.80 (s, 2H), 4.10 - 4.08 (m, 1H), 1.98 - 1.94 (m, 2H), 1.75 - 1.67 (m, 4H), 1.64 - 1.58 (m, 2H), 0.92 (s, 9H), 0.10 (s, 6H). Step 3: (4-(2-(2-Aminopyridin-3-yl)-5-cyclopentyl-3H-imidazo[4,5-b]p yridin-3- yl)phenyl)methanol To a solution of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-cycl opentyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (150 mg, 300 µmol) in THF (2 mL) was added TBAF (157 mg, 600 μmol). The mixture was stirred at 25 ºC for 0.3 hr. The reaction mixture was poured into H ₂ O (15 mL), extracted with EtOAc (15 mL × 3). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure., (4-(2-(2- aminopyridin-3-yl)-5-cyclopentyl-3H-imidazo[4,5-b]pyridin-3- yl)phenyl)methanol (110 mg, crude) as a yellow oil. MS: m/z = 386.1 [M + H] ⁺ . Step 4: 3-(3-(4-(Chloromethyl)phenyl)-5-cyclopentyl-3H-imidazo[4,5-b ]pyridin-2-yl)pyridin-2- amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-cyclopentyl-3H-imidazo[4,5-b]p yridin-3- yl)phenyl)methanol (110 mg, 285 μmol) in CH ₂ Cl ₂ (2 mL) was added SOCl ₂ (68 mg, 571 μmol). The mixture was stirred at 40 °C for 0.5 hr. The mixture was concentrated under reduced pressure to give the crude 3-(3-(4-(chloromethyl)phenyl)-5-cyclopentyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (Intermediate 118, 100 mg) as a yellow solid. MS: m/z = 404.1 [M + H] ⁺ . [00301] Intermediate 119: 2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-N,N- dimethyl-3H-imidazo[4,5-b]pyridin-5-amine Intermediate 119 was prepared in a manner similar to Intermediate 114. MS: m/z = 379.0 [M + H] ⁺ . [00302] Intermediate 120: 4-(Methyl(piperidin-4-yl)amino)pyrimidine-2-carbonitrile Step 1: tert-Butyl 4-((2-cyanopyrimidin-4-yl)(methyl)amino)piperidine-1-carboxy late To a solution of tert-butyl 4-(methylamino)piperidine-1-carboxylate (500 mg, 2.3 mmol) and 4- chloropyrimidine-2-carbonitrile (326 mg, 2.3 mmol) in DMF (5 mL) were added NaI (35 mg, 233 μmol) and K ₂ CO ₃ (645 mg, 4.7 mmol). The mixture was stirred at 80 °C for 2 hr. The reaction mixture was quenched with H ₂ O (10 mL) at 25 °C, and extracted with EtOAc (10 mL × 2). The combined organic layers were washed with brine (10 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 50%, EtOAc in petroleum ether), tert-butyl 4-((2-cyanopyrimidin-4- yl)(methyl)amino)piperidine-1-carboxylate (700 mg, yield: 95%) was obtained as a light yellow solid. MS: m/z = 318.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.19 (d, J = 6.4 Hz, 1H), 6.51 (d, J = 6.0 Hz, 1H), 5.29 - 4.62 (m, 1H), 4.25 (s, 2H), 2.93 - 2.81 (m, 5H), 1.68 - 1.62 (m, 4H), 1.47 (s, 9H). Step 2: 4-(Methyl(piperidin-4-yl)amino)pyrimidine-2-carbonitrile To a solution of tert-butyl 4-((2-cyanopyrimidin-4-yl)(methyl)amino)piperidine-1-carboxy late (150 mg, 473 μmol) in CH ₂ Cl ₂ (3 mL) was added TFA (1.5 g, 13 mmol). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was concentrated under reduced pressure to give 4-(methyl(piperidin-4-yl)amino)pyrimidine-2-carbonitrile (Intermediate 120, 156 mg) as a light yellow oil, which was used in the next step without further purification. MS: m/z = 218.0 [M + H] ⁺ . [00303] Intermediate 121: 4-((4-Methylpiperidin-4-yl)amino)pyrimidine-2-carbonitrile Intermediate 121 was prepared in a manner similar to Intermediate 120. MS: m/z = 218.0 [M + H] ⁺ . [00304] Intermediate 122: 3-(3-(4-(Chloromethyl)phenyl)-5-(3-methoxyphenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Intermediate 122 was prepared in a manner similar to Intermediate 76. MS: m/z = 442.1 [M + H] ⁺ . [00305] Intermediate 123: 3-(5-(Tert-butyl)-3-(4-(chloromethyl)phenyl)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine Step 1: (E)-1-(dimethylamino)-4,4-dimethylpent-1-en-3-one To a solution of 3,3-dimethylbutan-2-one (10 g, 100 mmol) in DMF (100 mL) was added DMF- DMA (23.8 g, 200 mmol) and CH ₃ ONa (539 mg, 9.98 mmol). The mixture was stirred at 100 °C for 16 hr. The mixture was diluted with H ₂ O (500 mL) and extracted with CH ₂ Cl ₂ (500 mL × 2). The combined organic layers were washed with brine (500 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give (E)-1-(dimethylamino)-4,4- dimethylpent-1-en-3-one (10.6 g, yield: 68%) as a brown oil. MS: m/z = 156.2 [M + H] ⁺ . Step 2: 6-(Tert-butyl)-3-nitropyridin-2-ol To a solution of (E)-1-(dimethylamino)-4,4-dimethylpent-1-en-3-one (10.6 g, 68.3 mmol) in H ₂ O (100 mL) were added piperdinium acetate (5 g, 34 mmol) and 2-nitroacetamide (10.6 g, 102 mmol). The mixture was stirred at 25 °C for 16 hr. The reaction mixture was filtered and the filter cake was dried to give 6-(tert-butyl)-3-nitropyridin-2-ol (3.1 g, yield: 23%) as a light- yellow solid. MS: m/z = 197.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.41 (d, J = 8.0 Hz, 1H), 6.34 (d, J = 7.6 Hz, 1H), 1.44 (s, 9H). Step 3: 6-(Tert-butyl)-3-nitropyridin-2-ol A solution of 6-(tert-butyl)-3-nitropyridin-2-ol (3.1 g, 15.8 mmol) in POCl ₃ (5 mL) was stirred at 100 °C for 16 hr. The reaction mixture was concentrated under reduced pressure to remove POCl ₃ . The reaction mixture was poured into H ₂ O (20 mL), extracted with CH ₂ Cl ₂ (60 mL). The organic phase was dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. 6-(tert-Butyl)-3-nitropyridin-2-ol (2.3 g, crude) was obtained as a black brown oil. MS: m/z = 214.9 [M + Na] ⁺ . Step 4: (4-((6-(tert-Butyl)-3-nitropyridin-2-yl)amino)phenyl)methano l To a solution of 6-(tert-butyl)-3-nitropyridin-2-ol (1 g, 4.7 mmol) in DMSO (10 mL) were added DIEA (1.8 g, 14 mmol) and (4-aminophenyl)methanol (574 mg, 4.7 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was poured into H ₂ O (50 mL) and was extracted with EtOAc (300 mL). The organic phase was dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. to give (4-((6-(tert-butyl)-3-nitropyridin-2- yl)amino)phenyl)methanol (1.5 g) as a yellow oil. MS: m/z = 302.1 [M + H] ⁺ . Step 5: 4-((6-(Tert-butyl)-3-nitropyridin-2-yl)amino)benzyl acetate To a solution of (4-((6-(tert-butyl)-3-nitropyridin-2-yl)amino)phenyl)methano l (1.5 g, 5 mmol) in CH ₂ Cl ₂ (20 mL) were added TEA (1.51 g, 1.9 mmol) and DMAP (61, mg, 498 μmol). The mixture was stirred at 0 °C for 5 min, and Ac ₂ O (508 mg, 5 mmol) was added dropwise at 0 °C. The mixture was stirred at 0 °C for 1 hr, Na ₂ CO ₃ (aq.15 mL) was added to adjust the pH about 8 and extracted with CH ₂ Cl ₂ (60 mL). The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 5%, EtOAc in petroleum ether), 4-((6-(tert-butyl)-3-nitropyridin-2-yl)amino)benzyl acetate (877 mg, yield: 52%) was obtained as a yellow solid. MS: m/z = 344.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 10.39 - 10.22 (m, 1H), 8.4 (d, J = 8.4 Hz, 1H), 7.77 (d, J = 8.0 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 6.89 (d, J = 8.4 Hz, 1H), 5.11 (s, 2H), 2.12 (s, 3H), 1.36 (s, 9H). Step 6: 4-(2-(2-Aminopyridin-3-yl)-5-(tert-butyl)-3H-imidazo[4,5-b]p yridin-3-yl)benzyl acetate To a solution of 4-((6-(tert-butyl)-3-nitropyridin-2-yl)amino)benzyl acetate in DMSO (30 mL) were added Na ₂ S ₂ O ₄ (1.85 g, 9 mmol) and 2-aminopyridine-3-carbaldehyde (311 mg, 2.6 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was poured into H ₂ O (10 mL), extracted with CH ₂ Cl ₂ (90 mL). The organic phase was dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 72% EtOAc in petroleum ether), 4-(2-(2-aminopyridin-3-yl)-5- (tert-butyl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl acetate (285 mg, yield: 30%) was obtained as a yellow solid. MS: m/z = 416.1 [M + H] ⁺ . Step 7: (4-(2-(2-Aminopyridin-3-yl)-5-(tert-butyl)-3H-imidazo[4,5-b] pyridin-3- yl)phenyl)methanol To a solution of 4-(2-(2-aminopyridin-3-yl)-5-(tert-butyl)-3H-imidazo[4,5-b]p yridin-3-yl)benzyl acetate (285 mg, 686 μmol) in MeOH (2 mL) and THF (2 mL) were added K ₂ CO ₃ (190 mg, 1.4 mmol) in H ₂ O (1 mL). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was concentrated under reduced pressure to remove MeOH. The residue was diluted with H ₂ O (5 mL) and extracted with EtOAc (30 mL). The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give (4-(2-(2-Aminopyridin-3-yl)-5-(tert-butyl)-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (216 mg, crude) as a yellow solid. MS: m/z = 374.1 [M + H] ⁺ . Step 8: 3-(5-(Tert-butyl)-3-(4-(chloromethyl)phenyl)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2- amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(tert-butyl)-3H-imidazo[4,5-b] pyridin-3- yl)phenyl)methanol (216 mg, 578 μmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (206 mg, 1.7 mmol). The mixture was stirred at 40 °C for 0.3 hr. The reaction was concentrated under reduced pressure to give 3-(5-(tert-butyl)-3-(4-(chloromethyl)phenyl)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (Intermediate 123, 200 mg, crude) as a yellow solid. MS: m/z = 392.1 [M + H] ⁺ . [00306] Intermediate 124: 3-(3-(4-(Chloromethyl)phenyl)-5-ethyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine

Intermediate 124 was prepared in a manner similar to Intermediate 118. MS: m/z = 364.1 [M + H] ⁺ . [00307] Intermediate 125: 2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-N- methyl-3H-imidazo[4,5-b]pyridine-5-carboxamide Step 1: 6-Chloro-5-nitropicolinoyl chloride A solution of 6-chloro-5-nitropicolinic acid (10 g, 49 mmol) in SOCl ₂ (50 mL) was stirred at 80 °C for 16 hr. The reaction mixture was concentrated to give 6-chloro-5-nitropicolinoyl chloride (9.5 g, crude) as a light-green solid. Step 2: 6-Chloro-N-methyl-5-nitropicolinamide To a solution of methylamine (183 mg, 2.71 mmol) in CH ₂ Cl ₂ (5 mL) was added TEA (687 mg, 6.8 mmol) dropwise at 25 C. The mixture was stirred at 25 C for 5 min, then 6-chloro-5- nitropicolinoyl chloride (500 mg, 2.26 mmol) in CH ₂ Cl ₂ (5 mL) was added dropwise at 0 °C. The resulting mixture was stirred at 0 °C for 1 hr. The residue was purified by silica gel flash chromatography (Eluent of 0 ~ 10% EtOAc in petroleum ether) to give 6-chloro-N-methyl-5- nitropicolinamide (308 mg, yield: 63%) as a yellow solid. MS: m/z = 215.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.36-8.30 (m, 2H), 7.76 (br s, 1H), 3.07 (d, J = 5.2 Hz 3H). Step 3: 6-((4-(Hydroxymethyl)phenyl)amino)-N-methyl-5-nitropicolinam ide To a solution of 6-chloro-N-methyl-5-nitropicolinamide (2.3 g, 11 mmol) and (4- aminophenyl)methanol (1.3 g, 11 mmol) in 1,4-dioxane (30 mL) was added DIEA (4.1 g, 32 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was poured into H ₂ O (30 mL), extracted with EtOAc (100 mL). The organic phase was dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The crude 6-((4- (hydroxymethyl)phenyl)amino)-N-methyl-5-nitropicolinamide (3.6 g, crude) was obtained as a red solid. MS: m/z = 302.9 [M + H] ⁺ . Step 4: 4-((6-(Methylcarbamoyl)-3-nitropyridin-2-yl)amino)benzyl acetate To a solution of 6-((4-(hydroxymethyl)phenyl)amino)-N-methyl-5-nitropicolinam ide (1.7 g, 5.6 mmol) in CH ₂ Cl ₂ (10 mL) were added TEA (1.7 g, 17 mmol) and DMAP (69 mg, 562 μmol). The mixture was stirred at 0 °C for 5 min, and then Ac ₂ O (574 mg, 5.6 mmol) was added dropwise at 0 °C. The mixture was stirred at 0 °C for 1 hr. Then sat. Na ₂ CO ₃ (5 mL) was added to adjust pH about 8 and extracted with CH ₂ Cl ₂ (15mL). The combined layer was dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 50% EtOAc in petroleum ether), 4-((6-(methylcarbamoyl)-3- nitropyridin-2-yl)amino)benzyl acetate (1.4 g, yield: 72%) was obtained as an orange solid. MS: m/z = 345.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 9.92 (s, 1H), 8.68 (d, J = 8.4 Hz, 1H), 7.71(d, J = 8.8 Hz, 1H), 7.54 - 7.37 (m, 5H), 5.15 (s, 2H), 2.98 (d, J = 5.2 Hz, 3H), 2.14 (s, 3H). Step 5: 4-(2-(2-Aminopyridin-3-yl)-5-(methylcarbamoyl)-3H-imidazo[4, 5-b]pyridin-3-yl)benzyl acetate To a solution of 4-((6-(methylcarbamoyl)-3-nitropyridin-2-yl)amino)benzyl acetate (1.4 g, 4 mmol) and 2-aminopyridine-3-carbaldehyde (546 mg, 4.5 mmol) in DMSO (15 mL) was added Na ₂ S ₂ O ₄ (3.3 g, 16 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was poured into H ₂ O (30 mL), extracted with CH ₂ Cl ₂ (150 mL). The organic phase was dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 82% EtOAc in petroleum ether), 4-(2-(2- aminopyridin-3-yl)-5-(methylcarbamoyl)-3H-imidazo[4,5-b]pyri din-3-yl)benzyl acetate (650 mg, yield: 38%) was obtained as a yellow oil. MS: m/z = 417.1 [M + H] ⁺ . Step 6: 2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-N-methyl -3H-imidazo[4,5- b]pyridine-5-carboxamide To a solution of 4-(2-(2-aminopyridin-3-yl)-5-(methylcarbamoyl)-3H-imidazo[4, 5-b]pyridin-3- yl)benzyl acetate (420 mg, 1 mmol) in MeOH (8 mL) and THF (8 mL) was added K ₂ CO ₃ (279 mg, 2 mmol) in H ₂ O (2 mL). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was concentrated under reduced pressure to move MeOH. Then the residue was diluted with H ₂ O (20 mL) and extracted with EtOAc (30 mL). The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give 2-(2-aminopyridin-3-yl)-3-(4- (hydroxymethyl)phenyl)-N-methyl-3H-imidazo[4,5-b]pyridine-5- carboxamide (350 mg, crude) as a yellow solid. MS: m/z = 375.1 [M + H] ⁺ . Step 7: 2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-N-methyl- 3H-imidazo[4,5- b]pyridine-5-carboxamide To a solution of 2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-N-methyl -3H- imidazo[4,5-b]pyridine-5-carboxamide (350 mg, 935 μmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (334 mg, 2.8 mmol). The mixture was stirred at 40 °C for 0.3 hr. The reaction was concentrated under reduced pressure to give 2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-N-methyl- 3H-imidazo[4,5-b]pyridine-5-carboxamide (Intermediate 125, 200 mg, HCl salt, crude) as a yellow solid. MS: m/z = 393.0 [M + H] ⁺ . [00308] Intermediate 126: 4-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)nicotinonitrile Step 1: 4-(2-(2-Aminopyridin-3-yl)-5-(3-cyanopyridin-4-yl)-3H-imidaz o[4,5-b]pyridin-3- yl)benzyl acetate A mixture of Intermediate 178 (400 mg, 1.02 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2-yl)nicotinonitrile (257 mg, 1.12 mmol), cataCXiumAPdG3 (369 mg, 507 μmol), K ₃ PO ₄ (431 mg, 2.03 mmol) and PCy ₃ (28.4 mg, 101 µmol) in DMF (10 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 120 °C for 12 hr under N ₂ atmosphere. The reaction mixture was diluted with water (20 mL) and extracted with EtOAc (2 × 30 mL). The combined organic layers were washed with brine (10 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0~8% MeOH in CH ₂ Cl ₂ ), 4-(2-(2-aminopyridin-3-yl)-5-(3-cyanopyridin-4-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl acetate (450 mg, yield: 76%) was obtained as a red solid. MS: m/z = 462.1 [M + H] ⁺ . Step 2: 4-(2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5-b]pyridin-5- yl)nicotinonitrile To a solution of 4-(2-(2-aminopyridin-3-yl)-5-(3-cyanopyridin-4-yl)-3H-imidaz o[4,5-b]pyridin- 3-yl)benzyl acetate (450 mg, 975 μmol) in MeOH (3 mL) and THF (3 mL) was added a solution of K ₂ CO ₃ (134 mg, 975 μmol) in H ₂ O (1 mL). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (2 × 10 mL). The combined organic layers were washed with brine (10 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give 4-(2-(2-aminopyridin-3-yl)-3-(4- (hydroxymethyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)nicotin onitrile (300 mg, yield: 73%) as a yellow solid. MS: m/z = 420.1 [M + H] ⁺ . Step 3: 4-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imi dazo[4,5-b]pyridin-5- yl)nicotinonitrile To a solution of 4-(2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5- b]pyridin-5-yl)nicotinonitrile (300 mg, 715 μmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (340 mg, 2.86 mmol). The mixture was stirred at 40 °C for 0.5 hr. The mixture was concentrated under reduced pressure to give 4-(2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)nicotinonitrile (Intermediate 126, 300 mg, HCl salt) as a yellow solid. MS: m/z = 437.9 [M + H] ⁺ . [00309] Intermediate 127: 3-(3-(4-(Chloromethyl)phenyl)-5-fluoro-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine Step 1: Methyl 4-((6-fluoro-3-nitropyridin-2-yl)amino)benzoate To a solution of methyl 4-aminobenzoate (10 g, 66.1 mmol) and 2,6-difluoro-3-nitropyridine (10.5 g, 66 mmol) in dioxane (175 mL) was added DIEA (17.1 g, 132 mmol). The mixture was stirred at 80 °C for 12 hr. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (2 × 200 mL). The combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After triturated with EtOAc (100 mL) and filtered, methyl 4-((6-fluoro-3-nitropyridin-2-yl)amino)benzoate (13.4 g, yield: 60%) was obtained as a yellow solid. MS: m/z = 292.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 10.53 (br s, 1H), 8.74 - 8.62 (m, 1H), 8.07 (d, J = 8.4 Hz, 2H), 7.76 (d, J = 8.8 Hz, 2H), 6.49 (dd, J = 8.8, 3.6 Hz, 1H), 3.92 (s, 3H), ¹⁹ F NMR (400 MHz, Chloroform-d Step 2: Methyl 4-(2-(2-aminopyridin-3-yl)-5-fluoro-3H-imidazo[4,5-b]pyridin -3-yl)benzoate To a solution of methyl 4-((6-fluoro-3-nitropyridin-2-yl)amino)benzoate (6.2 g, 21.2 mmol) and 2-aminonicotinaldehyde (2.86 g, 23.4 mmol) in DMSO (186 mL) was added Na ₂ S ₂ O ₄ (17 g, 85.1 mmol, 87% purity). The mixture was stirred at 100 °C for 12 hr. The reaction mixture was diluted with water (50 mL) and extracted with CH ₂ Cl ₂ (2 × 250 mL). The combined organic layers were washed with brine (100 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0~100% EtOAc in petroleum ether), methyl 4-(2-(2-aminopyridin-3-yl)-5-fluoro-3H-imidazo[4,5-b]pyridin -3- yl)benzoate (1.5 g, yield: 18%) was obtained as a yellow solid. MS: m/z = 364.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.22 - 8.14 (m, 3H), 8.08 (dd, J = 4.8, 1.6 Hz, 1H), 7.48 - 7.42 (m, 2H), 7.01 (dd, J = 8.0, 1.6 Hz, 1H), 6.96 (d, J = 8.4 Hz, 1H), 6.56 (br s, 2H), 6.37 (dd, J = 8.0, 4.8 Hz, 1H), 3.97 (s, 3H), ¹⁹ F NMR (400 MHz, Chloroform-d) δ -71.619. Step 3: (4-(2-(2-Aminopyridin-3-yl)-5-fluoro-3H-imidazo[4,5-b]pyridi n-3-yl)phenyl)methanol To a solution of methyl 4-(2-(2-aminopyridin-3-yl)-5-fluoro-3H-imidazo[4,5-b]pyridin -3- yl)benzoate (1.5 g, 4.13 mmol) in THF (30 mL) was added LiAlH ₄ (2.5 M, 2.48 mL). The mixture was stirred at 0 °C for 2 hr. The reaction mixture was quenched with Na ₂ SO ₄ ·10H ₂ O (282 mg) at 0 °C and filtered. The filtrate was concentrated under reduced pressure to give (4- (2-(2-aminopyridin-3-yl)-5-fluoro-3H-imidazo[4,5-b]pyridin-3 -yl)phenyl)methanol (1.3 g) as a yellow solid. Step 4: 3-(3-(4-(Chloromethyl)phenyl)-5-fluoro-3H-imidazo[4,5-b]pyri din-2-yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-fluoro-3H-imidazo[4,5-b]pyridi n-3- yl)phenyl)methanol (1.3 g, 3.88 mmol) in CH ₂ Cl ₂ (10 mL) was added SOCl ₂ (2.77 g, 23.3 mmol). The mixture was stirred at 40 °C for 0.5 hr. The mixture was concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0~6% MeOH in CH ₂ Cl ₂ ), 3-(3-(4-(chloromethyl)phenyl)-5-fluoro-3H-imidazo[4,5-b]pyri din-2- yl)pyridin-2-amine (Intermediate 127, 400 mg, yield: 27%) was obtained as a yellow solid. MS: m/z = 353.9 [M + H] ⁺ . [00310] Intermediate 128: 3-(3-(4-(Chloromethyl)phenyl)-6-fluoro-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine Step 1: (4-((5-Fluoro-3-nitropyridin-2-yl)amino)phenyl)methanol To a solution of 2-chloro-5-fluoro-3-nitro-pyridine (4 g, 23 mmol) in 1,4-dioxane (40 mL) were added DIEA (7.3 g, 57 mmol) and (4-aminophenyl)methanol (2.8 g, 23 mmol). The mixture was stirred at 110 °C for 16 hr. The reaction mixture was diluted with H ₂ O (200 mL) and extracted with EtOAc (400 mL). The organic layer was washed with brine (130 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give (4-((5-fluoro-3-nitropyridin-2- yl)amino)phenyl)methanol (3.8 g, crude) as a yellow solid. MS: m/z = 263.9 [M + H] ⁺ . Step 2: 4-((5-Fluoro-3-nitropyridin-2-yl)amino)benzyl acetate To a solution of (4-((5-fluoro-3-nitropyridin-2-yl)amino)phenyl)methanol (3.8 g, 14 mmol) and Ac ₂ O (1.5 g, 14 mmol) in CH ₂ Cl ₂ (38 mL) was added TEA (4.4 g, 43 mmol) and DMAP (176 mg, 1.4 mmol) at 0 °C. The mixture was stirred at 0 °C for 1 hr. The reaction mixture was diluted with H ₂ O (150 mL) and extracted with CH ₂ Cl ₂ (400 mL). The organic layer was washed with brine (150 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 10 ~ 30%, EtOAc in petroleum ether), 4-((5-fluoro-3-nitropyridin-2-yl)amino)benzyl acetate (1.4 g, yield: 30%) was obtained as a yellow solid. MS: m/z = 305.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 10.02 (br s, 1H), 8.44 (d, J = 2.4 Hz, 1H), 8.30 (dd, J = 7.6, 2.8 Hz, 1H), 7.61 (d, J = 8.4 Hz, 2H), 7.39 (d, J = 8.0 Hz, 2H), 5.11 (s, 2H), 2.11 (s, 3H). Step 3: 4-(2-(2-Aminopyridin-3-yl)-6-fluoro-3H-imidazo[4,5-b]pyridin -3-yl)benzyl acetate A mixture of 4-((5-fluoro-3-nitropyridin-2-yl)amino)benzyl acetate (1.4 g, 4.6 mmol), 2- aminopyridine-3-carbaldehyde (616 mg, 5 mmol), Na ₂ S ₂ O ₄ (3.2 g, 18 mmol) in DMSO (40 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 100 °C for 16 hr under N ₂ atmosphere. The reaction mixture was diluted with H ₂ O (200 mL) and extracted with CH ₂ Cl ₂ (200 mL x 3). The combined organic layers were washed with brine (150 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 10 ~20% EtOAc in petroleum ether), 4-(2-(2-aminopyridin-3- yl)-6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)benzyl acetate (285 mg, yield: 11%) was obtained as a brown solid. MS: m/z = 378.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.35 - 8.23 (m, 1H), 8.06 (dd, J = 5.2, 1.6 Hz, 1H), 7.82 (dd, J = 5.2, 1.6 Hz, 1H), 7.54 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 7.13 (dd, J = 8.0, 1.6 Hz, 1H), 6.89 (br s, 2H), 6.41 (dd, J = 8.0, 5.2 Hz, 1H), 5.20 (s, 2H), 2.15 (s, 3H). Step 4: (4-(2-(2-Aminopyridin-3-yl)-6-fluoro-3H-imidazo[4,5-b]pyridi n-3-yl)phenyl)methanol To a solution of 4-(2-(2-aminopyridin-3-yl)-6-fluoro-3H-imidazo[4,5-b]pyridin -3-yl)benzyl acetate (285 mg, 755 μmol) in THF (2 mL) and MeOH (2 mL) was added K ₂ CO ₃ (313 mg, 2.3 mmol) in H ₂ O (1 mL). The mixture was stirred at 25 °C for 0.5 hr. The mixture was concentrated under reduced pressure. The residue was diluted with H ₂ O (10 mL) and extracted with CH ₂ Cl ₂ (20 mL). The organic layer was washed with brine (10 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. (4-(2-(2-Aminopyridin-3-yl)-6-fluoro-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (230 mg, crude) was obtained as a brown solid. MS: m/z = 336.0 [M + H] ⁺ . Step 5: 3-(3-(4-(Chloromethyl)phenyl)-6-fluoro-3H-imidazo[4,5-b]pyri din-2-yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-6-fluoro-3H-imidazo[4,5-b]pyridi n-3- yl)phenyl)methanol (230 mg, 686 µmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (163 mg, 1 mmol). The mixture was stirred at 40 °C for 0.5 hr. The mixture was concentrated under reduced pressure. 3-(3-(4-(Chloromethyl)phenyl)-6-fluoro-3H-imidazo[4,5-b]pyri din-2-yl)pyridin-2- amine (Intermediate 128, 284 mg, crude) was obtained as a yellow solid. MS: m/z = 353.9 [M + H] ⁺ . [00311] Intermediate 129: 3-(5-Bromo-3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-3H-imidazo[4,5-b]pyrid in-2-yl)pyridin-2-amine Step 1: 4-(((tert-Butyldimethylsilyl)oxy)methyl)aniline To a solution of (4-aminophenyl)methanol (5 g, 40.6 mmol) in CH ₂ Cl ₂ (50 mL) were added TBSCl (8.34 g, 55.4 mmol), TEA (10.3 mL, 73.8 mmol), and DMAP (225 mg, 1.85 mmol). The mixture was degassed and purged with N ₂ three times and stirred at 25 ºC for 2 hr under N ₂ . The reaction mixture was filtered and concentrated under reduced pressure to give 4-(((tert- butyldimethylsilyl)oxy)methyl)aniline (8.76 g, crude) as a white oil, which was used in the next step without further purficition. Step 2: 6-Bromo-N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-3 -nitropyridin-2-amine To a solution of 4-[[tert-butyl(dimethyl)silyl]oxymethyl]aniline (8.76 g, 36.9 mmol) in 1,4- dioxane (100 mL) were added DIEA (19.3 mL, 111 mmol) and 2,6-dibromo-3-nitropyridine (10.4 g, 36.9 mmol). The mixture was degassed and purged with N ₂ three times and stirred at 45 ºC for 16 hr under N ₂ . The reaction mixture was concentrated under reduced pressure and purified by silica gel flash chromatography (Eluent of 1~10% EtOAc in Petroleum ether) to give 6-bromo-N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-3 -nitropyridin-2-amine (13.7 g, yield: 72%) as a red solid. MS: m/z = 440.2 [M+H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 10.23 (s, 1H), 8.32 (d, J = 8.4 Hz, 1H), 7.61 (d, J = 8.4 Hz, 2H), 6.95 (d, J = 8.4 Hz, 1H), 4.75 (s, 2H), 0.96 (s, 9H), 0.12 (s, 6H). Step 3: 6-Bromo-N ² -(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)pyrid ine-2,3-diamine To a solution of 6-bromo-N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-3 -nitropyridin-2- amine (46 g, 105 mmol) in EtOH (500 mL) and H ₂ O (100 mL) were added Fe (17.6 g, 315 mmol) and NH ₄ Cl (39.3 g, 735 mmol). The mixture was degassed and purged with N ₂ three times and stirred at 80 ºC for 2 hr under N ₂ . The reaction mixture was filtered and concentrated under reduced pressure. 6-Bromo-N ² -(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)pyrid ine- 2,3-diamine (42.9 g, crude) was obtained as a yellow solid, which was used in the next step without further purification. MS: m/z = 408.9, 409.9 [M+H] ⁺ . Step 4: 3-(5-Bromo-3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl )-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine To a solution of 6-bromo-N ² -(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)pyrid ine-2,3- diamine (41 g, 100 mmol), 2-aminonicotinaldehyde (9.81 g, 80.3 mmol) in EtOH (500 mL) was added InCl ₃ (2.22 g, 10.0 mmol). The mixture was degassed and purged with N ₂ three times and stirred at 80 ºC for 2 hr under N ₂ . Then MnO ₂ (52.4 g, 602 mmol) was added. The mixture was stirred at 80 ºC for 2 hr under N ₂ . The reaction mixture was filtered and concentrated under reduced pressure. The crude was purified by silica gel flash chromatography (Eluent of 1~50% EtOAc in petroleum ether) to give 3-(5-bromo-3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-3H-imidazo[4,5-b]pyrid in-2-yl)pyridin-2-amine (Intermediate 129, 19.5 g, yield: 32%) as a brown solid. MS: m/z = 509.9, 511.9 [M+H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.10 - 8.01 (m, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.54 - 7.40 (m, 3H), 7.31 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 7.6 Hz, 1H), 6.64 (br s, 2H), 6.41 - 6.27 (m, 1H), 4.83 (s, 2H), 0.97 (s, 9H), 0.14 (s, 6H). [00312] Intermediate 130: 3-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)oxazolidin-2-one Step 1: 3-(2-(2-Aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)o xy)methyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)oxazolidin-2-one A mixture of Intermediate 129 (800 mg, 783 µmol), oxazolidin-2-one (82 mg, 940 µmol), Cul (8 mg, 39 µmol), K ₂ CO ₃ (216 mg, 1.57 mmol), and dimethylaminoactic acid (8 mg, 78.3 µmol) in DMF (8 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 120 °C for 16 hr under N ₂ atmosphere. The reaction mixture was diluted with H ₂ O (100 mL) and extracted with EtOAc (30 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0 ~ 7% MeOH in CH ₂ Cl ₂ ) to give 3-(2-(2- aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)oxy)methy l)phenyl)-3H-imidazo[4,5- b]pyridin-5-yl)oxazolidin-2-one (300 mg, yield: 33%) as a brown solid. MS: m/z = 517.1 [M + H] ⁺ . Step 2: 3-(2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5-b]pyridin-5- yl)oxazolidin-2-one A solution of 3-(2-(2-aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)o xy)methyl)phenyl)- 3H-imidazol[4,5-b]pyridin-5-yl)oxazolidin-2-one (300 mg, 580 µmol) in TBAF (1 M, 4.69 mL) was stirred at 25 °C for 1hr. The reaction mixture was diluted with H ₂ O (30 mL) and extracted with CH ₂ Cl ₂ (30 mL x 2). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0 ~ 7% MeOH in CH ₂ Cl ₂ ) to give 3-(2-(2- aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imidazo[4, 5-b]pyridin-5-yl)oxazolidin-2- one (90 mg, yield: 38%) as a yellow solid. MS: m/z = 403.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.27 (d, J = 8.8 Hz, 1H), 8.10 (d, J = 8.8 Hz, 1H), 8.05 (dd, J = 5.2, 1.6 Hz, 1H), 7.50 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.07 (dd, J = 7.6, 1.6 Hz, 1H), 6.57 (br s, 2H), 6.37 (dd, J = 7.6, 5.2 Hz, 1H), 4.82 (s, 2H), 4.48 - 4.40 (m, 2H), 4.25 - 4.16 (m, 2H). Step 3: 3-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imi dazo[4,5-b]pyridin-5- yl)oxazolidin-2-one To a solution of 3-(2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5- b]pyridin-5-yl)oxazolidin-2-one (80 mg, 198 µmol) in CH ₂ Cl ₂ (2 mL) was added SOCl ₂ (142 mg, 1.19 mmol). The mixture was stirred at 40 °C for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude 3-(2-(2-aminopyridin-3-yl)-3-(4- (chloromethyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)oxazolid in-2-one (Intermediate 130, 90 mg, HCl salt, yield: 100 %) was used in the next step without further purification. MS: m/z = 420.9 [M + H] ⁺ . [00313] Intermediate 131: 3-(3-(4-(Chloromethyl)phenyl)-5-(6-fluoropyridin-3-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: (ES245Methyl 4-((6'-fluoro-5-nitro-[2,3'-bipyridin]-6-yl)amino)benzoate A mixture of methyl 4-((6-chloro-3-nitropyridin-2-yl)amino)benzoate (refer to Intermediate 13 for detail procedures, 10 g, 33 mmol), (6-fluoro-3-pyridyl)boronic acid (5 g, 36 mmol), Pd(dppf)Cl ₂ (2.4 g, 3.3 mmol), and Cs ₂ CO ₃ (31.8 g, 97.5 mmol) in 1,4-dioxane (100 mL) and H ₂ O (10 mL) was degassed and purged with N ₂ three times, then the mixture was stirred at 100 °C for 16 hr under N ₂ atmosphere. The reaction mixture was diluted with water (200 mL) and extracted with EtOAc (3 x 300 mL). The combined organic layers were washed with brine (300 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 100% EtOAc in petroleum ether), methyl 4-((6'- fluoro-5-nitro-[2,3'-bipyridin]-6-yl)amino)benzoate (6.6 g, yield: 33%) was obtained as a yellow solid. MS: m/z = 369.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 10.41 (s, 1H), 8.90 (d, J = 2.4 Hz, 1H), 8.67 (d, J = 8.4 Hz, 1H), 8.48 - 8.43 (m, 1H), 8.12 (d, J = 8.8 Hz, 2H), 7.80 (d, J = 8.8 Hz, 2H), 7.36 (d, J = 8.8 Hz, 1H), 7.09 (dd, J =8.4, 2.8 Hz, 1H), 3.94 (s, 3H) Step 2: Methyl 4-(2-(2-aminopyridin-3-yl)-5-(6-fluoropyridin-3-yl)-3H-imida zo[4,5-b]pyridin- 3-yl)benzoate A mixture of methyl 4-((6'-fluoro-5-nitro-[2,3'-bipyridin]-6-yl)amino)benzoate (6.6 g, 18 mmol), 2-aminopyridine-3-carbaldehyde (2.41 g, 19.7 mmol), and Na ₂ S ₂ O ₄ (12.5 g, 71.7 mmol) in DMSO (180 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 100 °C for 16 hr under N ₂ atmosphere. The reaction mixture was diluted with water (200 mL) and extracted with EtOAc (3 x 300mL). The combined organic layers were washed with brine (300 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 100%, EtOAc in petroleum ether), methyl 4-(2- (2-aminopyridin-3-yl)-5-(6-fluoropyridin-3-yl)-3H-imidazo[4, 5-b]pyridin-3-yl)benzoate (5 g, yield: 62%) was obtained as a yellow solid. MS: m/z = 441.0 [M + H] ⁺ . Step 3: (4-(2-(2-Aminopyridin-3-yl)-5-(6-fluoropyridin-3-yl)-3H-imid azo[4,5-b]pyridin-3- yl)phenyl)methanol To a mixture of methyl 4-(2-(2-aminopyridin-3-yl)-5-(6-fluoropyridin-3-yl)-3H-imida zo[4,5- b]pyridin-3-yl)benzoate (2.6 g, 5.9 mmol) in THF (100 mL) was added LiAlH ₄ (2.5 M in THF, 3.54 mL), then the mixture was degassed and purged with N ₂ three times. The mixture was stirred at 0 °C for 2 hr under N ₂ atmosphere. The reaction mixture was quenched with Na ₂ SO ₄ ·10H ₂ O (600 mg) at 0 °C and filtered. The filtrate was concentrated under reduced pressure to give the crude (4-(2-(2-aminopyridin-3-yl)-5-(6-fluoropyridin-3-yl)-3H-imid azo[4,5- b]pyridin-3-yl)phenyl)methanol 2.3 g, yield: 85%) as a yellow solid. MS: m/z = 413.0 [M + H] ⁺ . Step 4: 3-(3-(4-(Chloromethyl)phenyl)-5-(6-fluoropyridin-3-yl)-3H-im idazo[4,5-b]pyridin-2- yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(6-fluoropyridin-3-yl)-3H-imid azo[4,5-b]pyridin- 3-yl)phenyl)methanol (2.3 g, 5.58 mmol) in CH ₂ Cl ₂ (50 mL) was added SOCl ₂ (3.98 g, 33.5 mmol). The mixture was stirred at 40 °C for 1 hr. The mixture was concentrated under reduced pressure, 3-(3-(4-(chloromethyl)phenyl)-5-(6-fluoropyridin-3-yl)-3H-im idazo[4,5-b]pyridin-2- yl)pyridin-2-amine (Intermediate 131, 2.2 g, yield: 86%) was obtained as a yellow solid. MS: m/z = 430.9 [M + H] ⁺ . [00314] Intermediate 132: 2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridine-5-carbonitrile Step 1: 4-(2-(2-Aminopyridin-3-yl)-5-cyano-3H-imidazo[4,5-b]pyridin- 3-yl)benzyl acetate A solution of 4-(2-(2-aminopyridin-3-yl)-5-carbamoyl-3H-imidazo[4,5-b]pyri din-3-yl)benzyl acetate (refer to Inetermediate 74 for detail procedures, 250 mg, 621 µmol) in POCl ₃ (3 mL) was stirred at 100 °C for 1 hr. The reaction mixture was filtered and concentrated under reduced pressure to give 4-(2-(2-aminopyridin-3-yl)-5-cyano-3H-imidazo[4,5-b]pyridin- 3-yl)benzyl acetate (230 mg, yield: 71%) as a brown solid. MS: m/z = 385.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.52 (d, J = 8.0 Hz, 1H), 8.14 - 8.07 (m, 2H), 7.95 - 7.90 (m, 1H), 7.66 - 7.61 (m, 1H), 7.58 - 7.44 (m, 5H), 6.91 - 6.80 (m, 1H), 5.16 (s, 2H), 2.11 (s, 3H). Step 2: 2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imida zo[4,5-b]pyridine-5- carbonitrile To a solution of 4-(2-(2-aminopyridin-3-yl)-5-cyano-3H-imidazo[4,5-b]pyridin- 3-yl)benzyl aceate (230 mg, 598 µmol) in THF (5 mL) and MeOH (5 mL) was added K ₂ CO ₃ (248 mg, 1.8 mmol). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was diluted with H ₂ O (20 mL) and extracted with CH ₂ Cl ₂ (20 mL × 2). The combined organic layers were washed with brine (20 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give 2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imida zo[4,5-b]pyridine-5-carbonitrile (200 mg, yield: 68%) as a yellow solid. MS: m/z = 343.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.41 (d, J = 8.4 Hz, 1H), 8.04 - 7.96 (m, 2H), 7.51 - 7.41 (m, 4H), 7.29 (dd, J = 7.6, 1.6 Hz, 1H), 6.96 (s, 2H), 6.43 (dd, J = 7.6, 4.8 Hz, 1H), 4.59 (s, 2H). Step 3: 2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imidaz o[4,5-b]pyridine-5- carbonitrile To a solution of 2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imida zo[4,5- b]pyridine-5-carbonitrile (230 mg, 672 µmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (240 mg, 2.02 mmol). The mixture was stirred at 40 °C for 0.5 hr. The reaction was concentrated under reduced pressure to give 2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imidaz o[4,5- b]pyridine-5-carbonitrile (Intermediate 132, 240 mg, yield: 42%) as a brown solid. MS: m/z = 360.9 [M + H] ⁺ . [00315] Intermediate 133: 3-(3-(4-(Chloromethyl)phenyl)-5-(methylthio)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: Methyl 4-((6-(methylthio)-3-nitropyridin-2-yl)amino)benzoate To a solution of methyl 4-[(6-chloro-3-nitro-2-pyridyl)amino]benzoate (refer to Intermediate 13 for detail procedures, 5 g, 16.3 mmol) in THF (50 mL) was added NaSMe (1.09 g, 15.6 mmol). The mixture was stirred at 25 °C for 2 hr. The mixture was diluted with H ₂ O (50 mL) and extracted with CH ₂ Cl ₂ (100 mL x 3). The combined organic layers were washed with brine (50 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give methyl 4- ((6-(methylthio)-3-nitropyridin-2-yl)amino)benzoate (5 g, yield: 94%), which was used in the next step without further purification. MS: m/z = 320.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) R 10.63 (s, 1H), 8.31 (d, J = 9.2 Hz, 1H), 8.10 - 8.04 (m, 2H), 7.81 - 7.73 (m, 2H), 6.76 (d, J = 8.8 Hz, 1H), 3.94 (s, 3H), 2.59 (s, 3H). Step 2: Methyl 4-(2-(2-aminopyridin-3-yl)-5-(methylthio)-3H-imidazo[4,5-b]p yridin-3- yl)benzoate To a solution of methyl 4-((6-(methylthio)-3-nitropyridin-2-yl)amino)benzoate (5 g, 15.7 mmol), 2-aminonicotinaldehyde (1.51 g, 15.7 mmol) in DMSO (100 mL) was added Na ₂ S ₂ O ₄ (10.9 g, 62.6 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was diluted with H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (500 mL x 6). The combined organic layers were washed with brine (250 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 20 ~ 30% EtOAc in CH ₂ Cl ₂ ), methyl 4-(2-(2-aminopyridin-3-yl)-5-(methylthio)-3H-imidazo[4,5-b]p yridin-3- yl)benzoate (3 g, yield: 44%) was obtained as an orange solid. MS: m/z = 392.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) R 8.25 - 8.20 (m, 2H), 7.94 - 7.92 (m, 2H), 7.51 (d, J = 8.4 Hz, 2H), 7.26 - 7.23 (m, 1H), 7.21 - 7.11 (m, 1H), 6.49 - 6.43 (m, 1H), 4.00 (s, 3H), 2.49 (s, 3H). Step 3: (4-(2-(2-Aminopyridin-3-yl)-5-(methylthio)-3H-imidazo[4,5-b] pyridin-3- yl)phenyl)methanol To a solution of methyl 4-(2-(2-aminopyridin-3-yl)-5-(methylthio)-3H-imidazo[4,5-b]p yridin-3- yl)benzoate (1.5 g, 3.83 mmol) in THF (30 mL) was added LiAlH ₄ (2.5 M, 1.53 mL) at 0 °C, then the mixture was stried at 25 °C for 2 hr. The reaction mixture was quenched with Na ₂ SO _{4 2} O (about 1 g) at 0 °C, and the mixture was filtered, the filter cake was washed by CH ₂ Cl ₂ (10 mL x 3). The filtrate was concentrated under reduced pressure to give (4-(2-(2- aminopyridin-3-yl)-5-(methylthio)-3H-imidazo[4,5-b]pyridin-3 -yl)phenyl)methanol (1.2 g, yield: 86%) as a yellow solid, which was used in the next step without purification. MS: m/z = 364.1 [M + H]+. ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 7.86 (dd, J = 5.2 Hz,1.6 Hz, 1H), 7.53 - 7.49 (m, 3H), 7.30 - 7.23 (m, 2H), 6.84 (d, J = 8.4 Hz,1.6 Hz, 1H), 6.67 - 6.65 (m, 1H), 6.64 - 6.62 (m, 1H), 4.19 (s, 3H), 2.49 (s, 3H). Step 4: 3-(3-(4-(Chloromethyl)phenyl)-5-(methylthio)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2- amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(methylthio)-3H-imidazo[4,5-b] pyridin-3- yl)phenyl)methanol (1.2 g, 3.30 mmol) in CH ₂ Cl ₂ (15 mL) was added SOCl ₂ (1.18 g, 9.91 mmol) at 0 °C. The mixture was stirred at 40 °C for 2 hr. The reaction mixture was quenched with H ₂ O (0.5 mL) at 0 °C, filtered and concentrated under reduced pressure to give 3-(3-(4- (chloromethyl)phenyl)-5-(methylthio)-3H-imidazo[4,5-b]pyridi n-2-yl)pyridin-2-amine (Intermediate 133, 500 mg, yield: 42%) as a yellow solid. MS: m/z = 382.2 [M + H] ⁺ . [00316] Intermediate 134: 2-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)nicotinonitrile

Step 1: (4-((3-Nitro-6-(trimethylstannyl)pyridin-2-yl)amino)phenyl)m ethanol A mixture of methyl 4-((6-chloro-3-nitropyridin-2-yl)amino)benzoate (refer to Intermediate 13 for detail procedures, 4 g, 12.4 mmol), 1,1,1,2,2,2-hexamethyldistannane (8.15 g, 24.9 mmol) and Pd(PPh ₃ ) ₄ (229 mg, 622 µmol) in 1,4-dioxane (50 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 90 °C for 4 hr under N ₂ atmosphere. The reaction mixture was concentrated under reduced pressure to give (4-((3-nitro-6- (trimethylstannyl)pyridin-2-yl)amino)phenyl)methanol (5 g, crude) as a black brown solid, which was used in the next step without further purification. MS: m/z = 348.0 [M + H] ⁺ . Step 2: 6'-((4-(hydroxymethyl)phenyl)amino)-5'-nitro-[2,2'-bipyridin e]-3-carbonitrile A mixture of (4-((3-nitro-6-(trimethylstannyl)pyridin-2-yl)amino)phenyl)m ethanol (5 g, 12.3 mmol), 2-bromonicotinonitrile (2.24 g, 12.3 mmol), and Pd(PPh ₃ ) ₄ (226 mg, 613 µmol) in 1,4- dioxane (60 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 100 °C for 16 hr under N ₂ atmosphere. The residue was diluted with H ₂ O (50 mL) and extracted with CH ₂ Cl ₂ (40 mL x 3). The combined organic layers were washed with brine (30 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give 6'-((4- (hydroxymethyl)phenyl)amino)-5'-nitro-[2,2'-bipyridine]-3-ca rbonitrile (4.6 g, crude) as an orange red solid, which was directly used in the next step without further purification. MS: m/z = 348.0 [M + H] ⁺ . Step 3: 4-((3'-Cyano-5-nitro-[2,2'-bipyridin]-6-yl)amino)benzyl acetate To a solution of 2-[6-[4-(hydroxymethyl)anilino]-5-nitro-2-pyridyl]pyridine-3 -carbonitrile (4 g, 11.5 mmol) and Ac ₂ O (1.76 g, 17.3 mmol) in CH ₂ Cl ₂ (60 mL) were added DMAP (141 mg, 1.15 mmol) and TEA (3.50 g, 34.6 mmol). The reaction mixture was diluted with H ₂ O (50 mL) and extracted with CH ₂ Cl ₂ (50 mL x 4). The organic layers were washed with brine (50 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 35% EtOAc in CH ₂ Cl ₂ ), 4-((3'-cyano-5-nitro-[2,2'- bipyridin]-6-yl)amino)benzyl acetate (1.0 g, yield: 11%) was obtained as a light-yellow solid. MS: m/z = 390.0 [M + H] ⁺ . Step 4: 4-(2-(2-Aminopyridin-3-yl)-5-(3-cyanopyridin-2-yl)-3H-imidaz o[4,5-b]pyridin-3- yl)benzyl acetate To a solution of 4-((3'-cyano-5-nitro-[2,2'-bipyridin]-6-yl)amino)benzyl acetate (500 mg, 1.28 mmol) in DMSO (20 mL) were added Na ₂ S ₂ O ₄ (894 mg, 5.14 mmol, 87% purity) and 2- aminonicotinaldehyde (188 mg, 1.54 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched with H ₂ O (25 mL) at 25 °C, and then diluted with H ₂ O (50 mL) and extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 45% EtOAc in petroleum ether), 4-(2-(2- aminopyridin-3-yl)-5-(3-cyanopyridin-2-yl)-3H-imidazo[4,5-b] pyridin-3-yl)benzyl acetate (300 mg, yield: 42%) was obtained as a light-yellow solid. MS: m/z = 462.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.82 - 8.78 (m, 1H), 8.29 - 8.23 (m, 2H), 8.07 - 8.04 (m, 2H), 7.60 - 7.55 (m, 2H), 7.53 - 7.49 (m, 2H), 7.40 – 7.36 (m, 1H), 7.22 - 7.18 (m, 1H), 6.93 (br s, 2H), 6.48 - 6.37 (m, 1H), 5.18 (s, 2H), 2.13 (s, 3H). Step 5: 2-(2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5-b]pyridin-5- yl)nicotinonitrile To a solution of 4-(2-(2-aminopyridin-3-yl)-5-(3-cyanopyridin-2-yl)-3H-imidaz o[4,5-b]pyridin- 3-yl)benzyl acetate (300 mg, 650 µmol) in THF (2 mL) and MeOH (2 mL) was added K ₂ CO ₃ (89.9 mg, 650 µmol). The mixture was stirred at 25 ºC for 0.5 hr. The reaction mixture was diluted with H ₂ O (20 mL) and extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (10 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give 2-(2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5- b]pyridin-5-yl)nicotinonitrile (280 mg, yield: 82%) as a light-yellow solid. MS: m/z = 420.0 [M + H] ⁺ . Step 6: 2-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imi dazo[4,5-b]pyridin-5- yl)nicotinonitrile To a solution of 2-(2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5- b]pyridin-5-yl)nicotinonitrile (280 mg, 668 µmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (159 mg, 1.34 mmol). The mixture was stirred at 40 °C for 0.5 hr. The reaction was concentrated under reduced pressure to give 2-(2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)nicotinonitrile (Intermediate 134, 260 mg, yield: 89%) as a yellow solid. MS: m/z = 438.1 [M + H] ⁺ . [00317] Intermediate 135: 3-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)picolinonitrile Intermediate 135 was prepared in a manner similar to Intermediate 112.MS: m/z = 438.0 [M + H] ⁺ . [00318] Intermediate 136: 3-(3-(4-(Chloromethyl)phenyl)-5-(trifluoromethyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: Methyl 4-((3-nitro-6-(trifluoromethyl)pyridin-2-yl)amino)benzoate To a solution of methyl 2-chloro-3-nitro-6-(trifluoromethyl)pyridine (5 g, 22.1 mmol) in 1,4- dioxane (50 mL) were added DIEA (8.56 g, 66.2 mmol) and methyl 4-aminobenzoate (3.34 g, 22.1 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched with H ₂ O (50 mL) at 25 °C, and then diluted with H ₂ O (500 mL) and extracted EtOAc with (200 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The crude product was triturated with EtOAc at 25 ºC for 30 min to give methyl 4-((3-nitro-6-(trifluoromethyl)pyridin-2-yl)amino)benzoate (3.7 g, yield: 49%) as a yellow solid. MS: m/z = 341.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 19.17 (s, 1H), 8.78 (d, J = 8.4 Hz, 1H), 7.96 (d, J = 8.8 Hz, 2H), 7.87 - 7.80 (m, 2H), 7.51 (d, J = 8.4 Hz, 1H), 3.84 (s, 3H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -67.72. Step 2: Methyl 4-(2-(2-aminopyridin-3-yl)-5-(trifluoromethyl)-3H-imidazo[4, 5-b]pyridin-3- yl)benzoate To a solution of methyl 4-((3-nitro-6-(trifluoromethyl)pyridin-2-yl)amino)benzoate (2.2 g, 6.45 mmol) in DMSO (50 mL) were added Na ₂ S ₂ O ₄ (4.5 g, 25.8 mmol, 87% purity) and 2- aminonicotinaldehyde (866 mg, 7.1 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched with H ₂ O (100 mL) at 25 °C, and then diluted with H ₂ O (300 mL) and extracted with CH ₂ Cl ₂ (100 mL x 4). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The crude was triturated with EtOAc at 25 ºC for 30 min to give methyl 4-(2-(2-aminopyridin-3-yl)-5- (trifluoromethyl)-3H-imidazo[4,5-b]pyridin-3-yl)benzoate (1.3 g, yield: 49%) as a yellow solid. MS: m/z = 414.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.47 (d, J = 8.4 Hz, 1H), 8.11 (d, J = 8.4 Hz, 2H), 8.03 (dd, J = 4.8, 2.0 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 8.4 Hz, 2H), 7.30 (dd, J = 7.2, 1.2 Hz, 1H), 6.77 (s, 2H), 6.47 (dd, J = 7.6, 4.8 Hz, 1H), 3.89 (s, 3H). 19F NMR (400 Hz, Dimethylsulfoxide-d6) δ -64.28. Step 3: (4-(2-(2-Aminopyridin-3-yl)-5-(trifluoromethyl)-3H-imidazo[4 ,5-b]pyridin-3- yl)phenyl)methanol To a solution of methyl 4-(2-(2-aminopyridin-3-yl)-5-(trifluoromethyl)-3H-imidazo[4, 5- b]pyridin-3-yl)benzoate (500 mg, 1.21 mmol) in THF (5 mL) was added LiAlH ₄ (91.8 mg, 2.5 mmol) at 0 °C. The resulting mixture was stirred at 25 °C for 1 hr. The reaction mixture was filtered and concentrated to give (4-(2-(2-aminopyridin-3-yl)-5-(trifluoromethyl)-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (450 mg, yield: 84%) as a brown solid . MS: m/z = 388.0 [M + 3] ⁺ . Step 4: 3-(3-(4-(Chloromethyl)phenyl)-5-(trifluoromethyl)-3H-imidazo [4,5-b]pyridin-2- yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(trifluoromethyl)-3H-imidazo[4 ,5-b]pyridin-3- yl)phenyl)methanol (450 mg, 1.17 mmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (417 mg, 3.5 mmol). The mixture was stirred at 40 °C for 0.5 hr. The reaction was concentrated under reduced pressure to give 3-(3-(4-(chloromethyl)phenyl)-5-(trifluoromethyl)-3H-imidazo [4,5- b]pyridin-2-yl)pyridin-2-amine (Intermediate 136, 450 mg, yield: 68%) was obtained as a brown solid. MS: m/z = 404.0 [M + H] ⁺ . [00319] Intermediate 137: 2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridine-6-carboxamide Step 1: 6-Chloro-5-nitronicotinoyl chloride To a solution of 6-chloro-5-nitronicotinic acid (5 g, 24.7 mmol) in SOCl ₂ (50 mL) was stirred at 80 °C for 16 hr. The reaction mixture was filtered and concentrated under reduced pressure to give 6-chloro-5-nitronicotinoyl chloride (5.4 g, yield: 91%) as a yellow solid. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.12 (s, 1H), 8.87 (s, 1H). Step 2: 6-Chloro-5-nitronicotinamide To a solution of 6-chloro-5-nitronicotinoyl chloride (5.4 g, 24.4 mmol) in THF (50 mL) was added NH ₃ ·H ₂ O (10.3 g, 73.3 mmol) at 0 °C. The mixture was stirred at 0 °C for 1 hr. Then the reaction mixture was diluted with H ₂ O (100 mL) and extracted with EtOAc (100 mL × 2). The combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give 6-chloro-5-nitronicotinamide (2.3 g, yield: 41%) as a yellow solid. MS: m/z = 201.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.11 (d, J = 2.0 Hz, 1H), 8.92 (d, J = 2.0 Hz, 1H), 8.45 (s, 1H), 7.97 (s, 1H). Step 3: 6-((4-(Hydroxymethyl)phenyl)amino)-5-nitronicotinamide To a solution of 6-chloro-5-nitronicotinamide (2.3 g, 11.4 mmol) in DMSO (40 mL) were added (4-aminophenyl)methanol (1.41 g, 11.4 mmol) and DIEA (4.42 g, 34.2 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was diluted with H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (100 mL × 2). The combined organic layers were washed with brine (100 mL × 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give 6-((4- (hydroxymethyl)phenyl)amino)-5-nitronicotinamide (3.2 g, yield: 78%) as a yellow solid. MS: m/z = 289.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.17 (s, 1H), 9.63 - 9.24 (m, 1H), 8.94 (d, J = 11.6 Hz, 2H), 8.21 (s, 1H), 7.58 - 7.55 (m, 2H), 7.33 (d, J = 8.0 Hz, 2H), 5.28 - 5.16 (m, 1H), 4.49 (d, J = 4.4 Hz, 2H). Step 4: 4-((5-Carbamoyl-3-nitropyridin-2-yl)amino)benzyl acetate To a solution of 6-((4-(hydroxymethyl)phenyl)amino)-5-nitronicotinamide (3.2 g, 11.1 mmol) in CH ₂ Cl ₂ (20 mL) were added TEA (3.37 g, 33.3 mmol), Ac ₂ O (1.27 g, 12.5 mmol) and DMAP (1.7 g, 16.7 mmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was quenched with H ₂ O (50 mL) at 25 °C, and then diluted with CH ₂ Cl ₂ (200 mL) and washed with H ₂ O (200 mL × 3). The combined organic layers were washed with brine (200 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give 4-((5-carbamoyl-3- nitropyridin-2-yl)amino)benzyl acetate (2.5 g, yield: 84%) as a red solid. MS: m/z = 331.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.19 (s, 1H), 8.94 (d, J = 17.6 Hz, 2H), 8.19 (s, 1H), 7.66 - 7.53 (m, 3H), 7.39 (d, J = 8.0 Hz, 2H), 5.07 (s, 2H), 2.07 (s, 3H). Step 5: 4-(2-(2-Aminopyridin-3-yl)-6-carbamoyl-3H-imidazo[4,5-b]pyri din-3-yl)benzyl acetate To a solution of 4-((5-carbamoyl-3-nitropyridin-2-yl)amino)benzyl acetate (2 g, 6.06 mmol) in DMSO (10 mL) were added Na ₂ S ₂ O ₄ (2.11 g, 12.1 mmol, 87% purity) and 2- aminonicotinaldehyde (813 mg, 6.66 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched with H ₂ O (100 mL) at 25 °C, and then diluted with water (200 mL) and extracted with CH ₂ Cl ₂ (100 mL × 3). The combined organic layers were washed with brine (200 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 5% ~ 15% MeOH in CH ₂ Cl ₂ ), 4-(2-(2- aminopyridin-3-yl)-6-carbamoyl-3H-imidazo[4,5-b]pyridin-3-yl )benzyl acetate (400 mg, yield: 12%) was obtained as a brown oil. MS: m/z = 403.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.86 (d, J = 2.0 Hz, 1H), 8.67 (d, J = 2.0 Hz, 1H), 8.14 (s, 1H), 8.04 - 8.01 (m, 1H), 7.59 - 7.45 (m, 5H), 7.39 - 7.33 (m, 1H), 7.05 (br s, 2H), 6.51 (dd, J = 7.6, 4.8 Hz, 1H), 5.16 (s, 2H), 2.13 (s, 3H). Step 6: 2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imida zo[4,5-b]pyridine-6- carboxamide To a solution of 4-(2-(2-aminopyridin-3-yl)-6-carbamoyl-3H-imidazo[4,5-b]pyri din-3-yl)benzyl acetate (300 mg, 746 µmol) in THF (10 mL) and MeOH (10 mL) was addde K ₂ CO ₃ (309 mg, 2.24 mmol). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was diluted with H ₂ O (50 mL) and extracted with CH ₂ Cl ₂ (50 mL × 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give 2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imida zo[4,5-b]pyridine-6- carboxamide (260 mg, yield: 83%) as a yellow solid. MS: m/z = 361.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.93 (d, J = 2.0 Hz, 1H), 8.75 (d, J = 2.0 Hz, 1H), 8.58 - 8.28 (m, 2H), 8.20 - 8.07 (m, 1H), 7.95 (dd, J = 7.6, 1.6 Hz, 1H), 7.60 (s, 1H), 7.47 - 7.46 (m, 4H), 6.96 - 6.82 (m, 1H), 4.57 (s, 2H). Step 7: 2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imidaz o[4,5-b]pyridine-6- carboxamide To a solution of 2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imida zo[4,5- b]pyridine-6-carboxamide (260 mg, 721 µmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (258 mg, 2.16 mmol). The mixture was stirred at 40 °C for 0.5 hr. The reaction mixture was concentrated under reduced pressure to give 2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridine-6-carboxamide (Intermediate 137, 270 mg, yield: 74%) as a yellow solid. MS: m/z = 379.2 [M + H] ⁺ . [00320] Intermediate 138: 3-(3-(4-(Chloromethyl)phenyl)-5,6-dimethyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine Step 1: Methyl 4-((5-bromo-6-methyl-3-nitropyridin-2-yl)amino)benzoate To a solution of 3-bromo-6-chloro-2-methyl-5-nitropyridine (8 g, 31.8 mmol) and methyl 4- aminobenzoate (5.29 g, 35 mmol) in DMSO (200 mL) was added DIEA (4.93 g, 38.2 mmol). The mixture was stirred at 100 °C for 16 hr. The mixture was added into H ₂ O (500 mL), the mixture was filtered and the filter cake was concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 50% EtOAc in petroleum ether (adding 50% CH ₂ Cl ₂ )) and purified again by triturated with EtOAc (20 mL) at 25 °C for 0.5 hr, methyl 4-((5- bromo-6-methyl-3-nitropyridin-2-yl)amino)benzoate (2.2 g, yield: 17%) was obtained as a red solid. MS: m/z = 365.8, 367.8 [M + H] ^{+ 1} H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.11 (s, 1H), 8.66 (s, 1H), 7.95 (d, J = 8.8 Hz, 2H), 7.87 (d, J = 8.8 Hz, 2H), 3.84 (s, 3H), 2.59 (s, 3H). Step 2: Methyl 4-((5,6-dimethyl-3-nitropyridin-2-yl)amino)benzoate To a solution of methyl 4-((5-bromo-6-methyl-3-nitropyridin-2-yl)amino)benzoate (2.1 g, 5.74 mmol) and methylboronic acid (412 mg, 6.88 mmol) in H ₂ O (2 mL) and 1,4-dioxane (20 mL) were added Pd(dppf)Cl ₂ (41.9 mg, 57.4 µmol) and Cs ₂ CO ₃ (3.74 g, 11.5 mmol). The mixture was stirred at 100 °C for 16 hr under N ₂ atmosphere. The mixture was concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 10% EtOAc in petroleum ether (adding 20% CH ₂ Cl ₂ )), methyl 4-((5,6-dimethyl-3-nitropyridin-2- yl)amino)benzoate (1.6 g, yield: 81%) was obtained as a red solid. MS: m/z = 302.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.10 (s, 1H), 8.34 (s, 1H), 7.93 (br s, 4H), 3.83 (s, 3H), 2.48 (s, 3H), 2.27 (s, 3H). Step 3: Methyl 4-(2-(2-aminopyridin-3-yl)-5,6-dimethyl-3H-imidazo[4,5-b]pyr idin-3- yl)benzoate To a solution of methyl 4-((5,6-dimethyl-3-nitropyridin-2-yl)amino)benzoate (1.5 g, 4.98 mmol) and 2-aminonicotinaldehyde (669 mg, 5.48 mmol) in DMSO (30 mL) was added Na ₂ S ₂ O ₄ (3.47 g, 19.9 mmol). The mixture was stirred at 100 °C for 16 hr. H ₂ O (50 mL) was added to the mixture. The mixture was filtered. The filter cake was dissolved in CH ₂ Cl ₂ (200 mL). The organic layer was washed with brine (100 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a yellow solid. The yellow solid was triturated with EtOAc (10 mL) at 25 °C for 30 min to give methyl 4-(2-(2-aminopyridin-3-yl)-5,6-dimethyl-3H- imidazo[4,5-b]pyridin-3-yl)benzoate (950 mg, yield: 66%) as a light-yellow solid. MS: m/z = 374.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ 8.08 (d, J = 8.4 Hz, 2H), 7.99 - 7.96 (m, 2H), 7.55 (d, J = 8.8 Hz, 2H), 7.12 (dd, J = 7.6, 1.6 Hz, 1H), 6.91 (s, 2H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 3.89 (s, 3H), 2.45 (s, 3H), 2.39 (s, 3H). Step 4: (4-(2-(2-Aminopyridin-3-yl)-5,6-dimethyl-3H-imidazo[4,5-b]py ridin-3- yl)phenyl)methanol To a solution of methyl 4-(2-(2-aminopyridin-3-yl)-5,6-dimethyl-3H-imidazo[4,5-b]pyr idin-3- yl)benzoate (950 mg, 2.54 mmol) in THF (10 mL) was added LiAlH ₄ (2.5 M, 2.04 mL) at 0 °C. The mixture was stirred at 25 °C for 0.5 hr under N ₂ atmosphere. The Na ₂ SO ₄ ·10H ₂ O (1 g) was added into the mixture slowly at 0 °C. The mixture was stirred at 25 °C for 20 min. The mixture was filtered, concentrated under reduced pressure to give (4-(2-(2-aminopyridin-3-yl)- 5,6-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (870 mg, yield: 55%) as a light- yellow solid. MS: m/z = 346.0 [M + H] ⁺ . Step 5: 3-(3-(4-(Chloromethyl)phenyl)-5,6-dimethyl-3H-imidazo[4,5-b] pyridin-2-yl)pyridin-2- amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5,6-dimethyl-3H-imidazo[4,5-b]py ridin-3- yl)phenyl)methanol (870 mg, 2.52 mmol) in CH ₂ Cl ₂ (10 mL) was added SOCl ₂ (819 mg, 6.88 mmol). The mixture was stirred at 40 °C for 2 hr. The mixture was concentrated under reduced pressure to give 3-(3-(4-(chloromethyl)phenyl)-5,6-dimethyl-3H-imidazo[4,5-b] pyridin-2- yl)pyridin-2-amine (Intermediate 138, 1 g, yield: 87%) as a yellow solid. MS: m/z = 364.0 [M + H] ⁺ . [00321] Intermediate 139: 3-(1-(4-(Chloromethyl)phenyl)-1H-imidazo[4,5-b]pyrazin-2- yl)pyridin-2-amine Step 1: Methyl 4-((3-aminopyrazin-2-yl)amino)benzoate To a mixture of 3-chloropyrazin-2-amine (5 g, 38.6 mmol) in H ₂ O (100 mL) were added TsOH·H ₂ O (7.34 g, 38.6 mmol) and methyl 4-aminobenzoate (5.83 g, 38.6 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was filtered and concentrated under reduced pressure. The crude was triturated with EtOAc/MeOH (1:1) (50 mL) to give methyl 4- ((3-aminopyrazin-2-yl)amino)benzoate (10 g, yield: 77%) as an off-white solid. MS: m/z = 245.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide - d ₆ ) δ 9.31 (s, 1H), 7.58 (d, J = 3.6 Hz, 1H), 7.49 (d, J = 8.0 Hz, 2H), 7.44 (d, J = 4.0 Hz, 1H), 7.12 (d, J = 8.0 Hz, 2H), 3.83 (s, 3H). Step 2: Methyl 4-(2-(2-aminopyridin-3-yl)-1H-imidazo[4,5-b]pyrazin-1-yl)ben zoate A mixture of methyl 4-((3-aminopyrazin-2-yl)amino)benzoate (5 g, 20.4 mmol), 2- aminonicotinaldehyde (2.75 g, 22.5 mmol), and Cu(OAc) ₂ (743 mg, 4.09 mmol) in AcOH (300 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 70 °C for 24 hr under N ₂ atmosphere. The reaction mixture was diluted with H ₂ O (100 mL) and pH was adjusted to about 7 with sat. Na ₂ CO ₃ (1500 mL). The mixture was extracted with EtOAc (300 mL). The combined organic layers were washed with H ₂ O (100 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 50% EtOAc in petroleum ether), methyl 4-(2-(2-aminopyridin-3- yl)-1H-imidazo[4,5-b]pyrazin-1-yl)benzoate (1.6 g, yield: 22%) was obtained as a yellow solid. MS: m/z = 347.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide - d ₆ ) δ 8.61 (d, J = 2.8 Hz, 1H), 8.40 (d, J = 2.8 Hz, 1H), 8.12 - 8.07 (m, 2H), 8.05 (dd, J = 4.8, 2.0 Hz, 1H), 7.66 - 7.59 (m, 2H), 7.34 (dd, J = 8.0, 2.0 Hz, 1H), 6.80 (s, 2H), 6.48 (dd, J = 8.0, 5.2 Hz, 1H), 3.89 (s, 3H). Step 3: (4-(2-(2-Aminopyridin-3-yl)-1H-imidazo[4,5-b]pyrazin-1-yl)ph enyl)methanol A mixture of methyl 4-(2-(2-aminopyridin-3-yl)-1H-imidazo[4,5-b]pyrazin-1-yl)ben zoate (1 g, 2.89 mmol) in THF (100 mL) was added LiAlH ₄ (2.5 M, 1.73 mL) dropwise at 0 °C. The mixture was stirred at 25 °C for 1 hr under N ₂ atmosphere. The reaction mixture was quenched with 1.7 g Na ₂ SO ₄ ·10H ₂ O at 0 °C, filtered and concentrated under reduced pressure to give (4- (2-(2-aminopyridin-3-yl)-1H-imidazo[4,5-b]pyrazin-1-yl)pheny l)methanol (750 mg, crude) as a yellow solid. MS: m/z = 318.9 [M + H] ⁺ . Step 4: 3-(1-(4-(Chloromethyl)phenyl)-1H-imidazo[4,5-b]pyrazin-2-yl) pyridin-2-amine A mixture of (4-(2-(2-aminopyridin-3-yl)-1H-imidazo[4,5-b]pyrazin-1-yl)ph enyl)methanol (745 mg, 2.34 mmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (1.67 g, 14.0 mmol), and then the mixture was stirred at 40 °C for 1 hr. The reaction mixture was filtered and concentrated under reduced pressure to give 3-(1-(4-(chloromethyl)phenyl)-1H-imidazo[4,5-b]pyrazin-2-yl) pyridin-2-amine (Intermediate 139, 100 mg, yield: 10% for 2 steps) as a brown solid. MS: m/z = 337.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide - d ₆ ) δ 8.69 (d, J = 2.8 Hz, 1H), 8.50 (d, J = 2.8 Hz, 1H), 8.15 (dd, J = 6.0, 1.2 Hz, 1H), 7.96 (dd, J = 7.6, 1.2 Hz, 1H), 7.62 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 8.4 Hz, 2H), 6.90 (dd, J = 7.2, 6.0 Hz, 1H), 4.84 (s, 2H). [00322] Intermediate 140: Methyl 2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)- 3H-imidazo[4,5-b]pyridine-5-carboxylate Step 1: Methyl 6-((4-(hydroxymethyl)phenyl)amino)-5-nitropicolinate To a solution of 6-chloro-5-nitropyridin-2-yl acetate (4.8 g, 22.2 mmol) in DMSO (40 mL) were added (4-aminophenyl)methanol (2.73 g, 22.2 mmol) and DIEA (8.59 g, 66.5 mmol). The mixture was stirred at 100 °C for 1 hr. The reaction mixture was diluted with H ₂ O (200 mL) and extracted with CH ₂ Cl ₂ (200 mL x 2). The combined organic layers were washed with brine (200 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give methyl 6- ((4-(hydroxymethyl)phenyl)amino)-5-nitropicolinate (6 g, yield: 74%) as a yellow solid. MS: m/z = 304.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.95 (s, 1H), 9.32 (br s, 1H), 8.68 (d, J = 8.4 Hz, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.52 (d, J = 8.4 Hz, 1H), 7.31 (d, J = 8.0 Hz, 2H), 5.18 (t, J = 5.6 Hz, 2H), 4.49 (d, J = 5.2 Hz, 2H), 3.90 (s, 3H). Step 2: Methyl 6-((4-(acetoxymethyl)phenyl)amino)-5-nitropicolinate To a solution of methyl 6-((4-(hydroxymethyl)phenyl)amino)-5-nitropicolinate (6 g, 19.8 mmol) in CH ₂ Cl ₂ (20 mL) were added TEA (6.01 g, 59.4 mmol), Ac ₂ O (3.03g, 29.7 mmol) and DMAP (242 mg, 1.98 mmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was quenched with H ₂ O (100 mL) at 25 °C, diluted with water (200 mL) and extracted with CH ₂ Cl ₂ (200 mL x 3). The combined organic layers were washed with brine (200 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give methyl 6-((4- (acetoxymethyl)phenyl)amino)-5-nitropicolinate (6.5 g, yield: 59%) as a red solid. MS: m/z = 346.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.97 (s, 1H), 8.68 (d, J = 8.4 Hz, 1H), 7.84 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 8.4 Hz, 1H), 7.37 (d, J = 8.4 Hz, 2H), 5.06 (s, 2H), 3.91 (s, 3H), 2.07 (s, 3H). Step 3: Methyl 3-(4-(acetoxymethyl)phenyl)-2-(2-aminopyridin-3-yl)-3H-imida zo[4,5- b]pyridine-5-carboxylate To a solution of methyl 6-((4-(acetoxymethyl)phenyl)amino)-5-nitropicolinate (4 g, 11.6 mmol) in DMSO (20 mL) were added Na ₂ S ₂ O ₄ (4.03 g, 23.2 mmol, 87% purity) and 2- aminonicotinaldehyde (1.56 g, 12.7 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched with H ₂ O (100 mL) at 25°C, and then diluted with H ₂ O (200 mL) and extracted with CH ₂ Cl ₂ (100 mL x 2). The combined organic layers were washed with brine (200 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 30 ~ 50%, EtOAc in petroleum ether), methyl 3-(4-(acetoxymethyl)phenyl)-2-(2-aminopyridin-3-yl)-3H-imida zo[4,5-b]pyridine-5- carboxylate (560 mg, yield: 10%) was obtained as a yellow solid. MS: m/z = 418.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.34 (d, J = 8.0 Hz, 1H), 8.12 (d, J = 8.0 Hz, 1H), 8.03 - 7.98 (m, 1H), 7.57 - 7.44 (m, 4H), 7.25 (dd, J = 7.6, 1.6 Hz, 1H), 6.87 (s, 2H), 6.51 - 6.34 (m, 1H), 5.17 (s, 2H), 3.85 (s, 3H), 2.12 (s, 3H). Step 4: Methyl 2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imida zo[4,5- b]pyridine-5-carboxylate To a solution of methyl 3-(4-(acetoxymethyl)phenyl)-2-(2-aminopyridin-3-yl)-3H-imida zo[4,5- b]pyridine-5-carboxylate (560 mg, 1.34 mmol) in THF (10 mL) and MeOH (10 mL) was added K ₂ CO ₃ (556 mg, 4.02 mmol). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was diluted with H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (100 mL x 2). The combined organic layers were washed with brine (100 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give methyl 2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)- 3H-imidazo[4,5-b]pyridine-5-carboxylate (330 mg, yield: 57%) was obtained as a yellow solid. MS: m/z = 376.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.33 (d, J = 8.0 Hz, 1H), 8.12 (d, J = 8.4 Hz, 1H), 8.03 - 7.98 (m, 1H), 7.51 - 7.39 (m, 4H), 7.28 - 7.20 (m, 1H), 6.94 (s, 2H), 6.42 (dd, J = 7.2, 4.8 Hz, 1H), 5.46 - 5.29 (m, 1H), 4.59 (d, J = 4.4 Hz, 2H), 3.85 (s, 3H). Step 5: Methyl 2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imidaz o[4,5-b]pyridine- 5-carboxylate To a solution of methyl 2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imida zo[4,5- b]pyridine-5-carboxylate (330 mg, 879 μmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (314 mg, 2.64 mmol). The mixture was stirred at 40 °C for 0.5 hr. The reaction was concentrated under reduced pressure to give methyl 2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridine-5-carboxylate (Intermediate 140, 340 mg, yield: 98%) as a yellow solid. MS: m/z = 394.1 [M + H] ⁺ . [00323] Intermediate 141: 3-(3-(4-(Chloromethyl)phenyl)-5-(fluoromethoxy)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: 6-Bromo-5-nitropyridin-2-ol A solution of 2-bromo-6-methoxy-3-nitropyridine (9.9 g, 42.5 mmol) in hydrogen bromide (186g, 759 mmol, 33% purity) was stirred at 80 °C for 12 hr. The reaction mixture was filtered and washed with petroleum ether. The filter cake was concentrated under reduced pressure to give 6-bromo-5-nitropyridin-2-ol (7.4 g, yield: 71%) as a brown solid. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 14.90 - 11-14 (m, 1), 8.35 (d, J = 8.8 Hz, 1H), 6.79 (d, J = 8.8 Hz, 1H). Step 2: 2-Bromo-6-(fluoromethoxy)-3-nitropyridine To a solution of 6-bromo-5-nitropyridin-2-ol (4 g, 18.3mmol) in DMF (30 mL) were added K ₂ CO ₃ (5.05 g, 36.5 mmol) and CH ₂ FI (4.38 g, 27.4 mmol). The mixture was stirred at 20 °C for 2 hr. The reaction mixture was diluted with water (50 mL) and extracted with EtOAc (2 × 30 mL). The combined organic layers were washed with brine (130 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. 2-bromo-6-(fluoromethoxy)-3-nitropyridine (3.1 g, yield: 64%) was obtained as a yellow solid. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.55 (d, J = 8.8 Hz, 1H), 7.28 (d, J = 8.8 Hz, 1H), 6.11 (d, J = 51.6 Hz, 2H), ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -156.386. Step 3: (4-((6-(Fluoromethoxy)-3-nitropyridin-2-yl)amino)phenyl)meth anol To a solution of 2-bromo-6-(fluoromethoxy)-3-nitropyridine (3.1 g, 12.3 mmol) and (4- aminophenyl)methanol (1.67 g, 13.6 mmol) in DMSO (30 mL) was added DIEA (4.79 g, 37.1 mmol). The mixture was stirred at 100 °C for 2 hr. The reaction mixture was diluted with water (50 mL), filtered and concentrated under reduced pressure to give (4-((6-(fluoromethoxy)-3- nitropyridin-2-yl)amino)phenyl)methanol (3.6 g, crude) as yellow a solid. MS: m/z = 294.1 [M + H] ⁺ . Step 4: 4-((6-(Fluoromethoxy)-3-nitropyridin-2-yl)amino)benzyl acetate To a solution of 4-((6-(fluoromethoxy)-3-nitropyridin-2-yl)amino)benzyl acetate (3.5 g, 11.9 mmol) in CH ₂ Cl ₂ (30 mL) were added Ac ₂ O (1.22 g, 11.9 mmol), DMAP (145 mg, 1.19 mmol) and TEA (3.62 g, 35.8 mmol). The mixture was stirred at 0 °C for 2 hr. The reaction mixture was diluted with water (20 mL) and extracted with CH ₂ Cl ₂ (3 × 30 mL). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0~100% EtOAc in petroleum ether), 4-((6-(fluoromethoxy)-3-nitropyridin-2-yl)amino)benzyl acetate (3.2 g, yield: 79%) was obtained as yellow solid. MS: m/z = 336.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.35 (s, 1H), 8.58 (d, J = 8.8 Hz, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 6.53 (d, J = 9.2 Hz, 1H), 6.01 (d, J = 51.6 Hz, 2H), 5.07 (s, 2H), 2.07 (s, 3H), ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -156.402. Step 5: 4-(2-(2-Aminopyridin-3-yl)-5-(fluoromethoxy)-3H-imidazo[4,5- b]pyridin-3-yl)benzyl acetate To a solution of 4-((6-(fluoromethoxy)-3-nitropyridin-2-yl)amino)benzyl acetate (3.2 g, 9.54 mmol) and 2-aminonicotinaldehyde (1.28 g, 10.5 mmol) in DMSO (100 mL) was added Na ₂ S ₂ O ₄ (7.64 g, 38.2 mmol, 85% purity). The mixture was stirred at 100 °C for 12 hr. The reaction mixture was diluted with water (100 mL) and extracted with CH ₂ Cl ₂ (300 mL × 2). The combined organic layers were washed with brine (100 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0 ~ 100% EtOAc in petroleum ether) to give 4-(2-(2-aminopyridin- 3-yl)-5-(fluoromethoxy)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl acetate (300 mg, yield: 6.8%) as a yellow solid. MS: m/z = 408.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.25 (d, J = 8.4 Hz, 1H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.53 - 7.48 (m, 2H), 7.45 - 7.42 (m, 2H), 7.17 (dd, J = 7.6, 2.0 Hz, 1H), 6.98 (d, J = 8.4 Hz, 1H), 6.78 (br s, 2H), 6.42 (dd, J = 7.6, 4.8 Hz, 1H), 6.10 - 6.05 (m, 1H), 5.96 - 5.92 (m, 1H), 5.15 (s, 2H), 2.11 (s, 3H), ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -153.980. Step 6: (4-(2-(2-Aminopyridin-3-yl)-5-(fluoromethoxy)-3H-imidazo[4,5 -b]pyridin-3- yl)phenyl)methanol To a solution of 4-(2-(2-aminopyridin-3-yl)-5-(fluoromethoxy)-3H-imidazo[4,5- b]pyridin-3- yl)benzyl acetate (300 mg, 736 µmol) IN MeOH (3 mL) and THF (3 mL) was added a solution of K ₂ CO ₃ (101 mg, 736 umol) in H ₂ O (1 mL). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (2 × 10 mL). The combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give (4-(2-(2-aminopyridin-3-yl)-5-(fluoromethoxy)-3H-imidazo[4,5 -b]pyridin-3- yl)phenyl)methanol (260 mg, yield: 83%) as a pink solid. MS: m/z = 366.1 [M + H] ⁺ . Step 7: 3-(3-(4-(Chloromethyl)phenyl)-5-(fluoromethoxy)-3H-imidazo[4 ,5-b]pyridin-2- yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(fluoromethoxy)-3H-imidazo[4,5 -b]pyridin-3- yl)phenyl)methanol (260 mg, 711 µmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (338 mg, 2.85 mmol). The mixture was stirred at 40 °C for 0.5 hr. The mixture was concentrated under reduced pressure, 3-(3-(4-(chloromethyl)phenyl)-5-(fluoromethoxy)-3H-imidazo[4 ,5-b]pyridin- 2-yl)pyridin-2-amine (Intermediate 141, 290 mg, yield: 89%, HCl salt) was obtained as green solid. MS: m/z = 384.1 [M + H] ⁺ . [00324] Intermediate 142: 3-(3-(4-(Chloromethyl)phenyl)-5-(tetrahydrofuran-3-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Step 1: 4-(2-(2-Aminopyridin-3-yl)-5-(2,5-dihydrofuran-3-yl)-3H-imid azo[4,5-b]pyridin-3- yl)benzyl acetate To a solution of Intermediate 178 (1 g, 2.54 mmol) and 2-(2,5-dihydrofuran-3-yl)-4,4,5,5- tetramethyl-1,3,2-dioxaborolane (547 mg, 2.79 mmol) in DMF (15 mL) were added cataCXiumAPdG3 (71.2 mg, 253 µmol), PCy ₃ (185 mg, 254 µmol) and K ₃ PO ₄ (1.08 g, 5.08 mmol). The mixture was stirred at 120 °C for 12 hr. The reaction mixture was diluted with H ₂ O (30 mL) and extracted with EtOAc (2 x 40 mL). The combined organic layers were washed with brine (10 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 70% EtOAc in petroleum ether), 4-(2- (2-aminopyridin-3-yl)-5-(2,5-dihydrofuran-3-yl)-3H-imidazo[4 ,5-b]pyridin-3-yl)benzyl acetate (900 mg, yield: 77 %) was obtained as a yellow solid. MS: m/z = 428.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.07 (dd, J = 4.8, 1.6 Hz, 1H), 8.03 (d, J = 8.4 Hz, 1H), 7.48 (d, J = 8.4 Hz, 2H), 7.43 - 7.37 (m, 3H), 7.09 (dd, J = 8.01.6 Hz, 1H), 6.60 (br s, 2H), 6.53 (t, J = 2.0 Hz, 1H), 6.40 (dd, J = 8.0, 4.8 Hz, 1H), 5.21 (s, 2H), 5.07 - 5.03 (m, 2H), 4.90 - 4.86 (m, 2H), 2.17 (s, 3H). Step 2: 4-(2-(2-Aminopyridin-3-yl)-5-(tetrahydrofuran-3-yl)-3H-imida zo[4,5-b]pyridin-3- yl)benzyl acetate To a solution of 4-(2-(2-aminopyridin-3-yl)-5-(2,5-dihydrofuran-3-yl)-3H-imid azo[4,5- b]pyridin-3-yl)benzyl acetate (550 mg, 1.29 mmol) in MeOH (10 mL) was added Pd/C (68.4 mg, 64.3 µmol, 10% purity). The mixture was degassed and purged with H ₂ three times. The mixture was stirred at 40 °C for 16 hr under H ₂ . The reaction mixture was filtered and concentrated under reduced pressure to give 4-(2-(2-aminopyridin-3-yl)-5-(tetrahydrofuran-3- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl acetate (240 mg, yield: 35 %) as a yellow solid. MS: m/z = 430.1 [M + H] ⁺ . Step 3: (4-(2-(2-Aminopyridin-3-yl)-5-(tetrahydrofuran-3-yl)-3H-imid azo[4,5-b]pyridin-3- yl)phenyl)methanol To a solution of 4-(2-(2-aminopyridin-3-yl)-5-(tetrahydrofuran-3-yl)-3H-imida zo[4,5-b]pyridin- 3-yl)benzyl acetate (240 mg, 558 μmoTl)H iFn (7 mL) and MeOH (7 mL) was added a solution of K ₂ CO ₃ (77.2 mg, 558 µmol) in H ₂ O (3.5 mL). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was diluted with H ₂ O (20 mL) and extracted with EtOAc (3 x 30 mL). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure, (4-(2-(2-aminopyridin-3-yl)-5-(tetrahydrofuran-3-yl)-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (220 mg, crude) was obtained as a yellow solid. MS: m/z = 388.0 [M + H] ⁺ . Step 4: 3-(3-(4-(Chloromethyl)phenyl)-5-(tetrahydrofuran-3-yl)-3H-im idazo[4,5-b]pyridin-2- yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(tetrahydrofuran-3-yl)-3H-imid azo[4,5- b]pyridin-3-yl)phenyl)methanol (220 mg, 567 µmol) in CH ₂ Cl ₂ (10 mL) was added SOCl ₂ (405 mg, 3.41 mmol). The mixture was stirred at 40 °C for 0.5 hr. The mixture was concentrated under reduced pressure to give 3-(3-(4-(chloromethyl)phenyl)-5-(tetrahydrofuran-3-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (Intermediate 142, 230 mg, crude) as a yellow solid. MS: m/z = 406.0 [M + H] ⁺ . [00325] Intermediate 143: 6-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)nicotinonitrile Step 1: Methyl 4-((3-nitro-6-(trimethylstannyl)pyridin-2-yl)amino)benzoate A mixture of 4-((6-chloro-3-nitropyridin-2-yl)amino)benzoate (refer to Intermediate 13 for detail procedures, 2 g, 6.5 mmol), Pd(PPh ₃ ) ₄ (751 mg, 650 µmol), and 1,1,1,2,2,2- hexamethyldistannane (5.06 g, 15.4 mmol) in 1,4-dioxane (20 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 125 °C for 2 hr under N ₂ atmosphere. The reaction mixture was used for next step directly without work-up and purification. Methyl 4-((3-nitro-6-(trimethylstannyl)pyridin-2-yl)amino)benzoate (2.83 g) was obtained as a black oil. MS: m/z = 438.1 [M + H] ⁺ . Step 2: Methyl 4-((5-amino-5'-cyano-[2,2'-bipyridin]-6-yl)amino)benzoate A mixture of methyl 4-((3-nitro-6-(trimethylstannyl)pyridin-2-yl)amino)benzoate (2.83 g, 6.49 mmol), 6-bromonicotinonitrile (594 mg, 3.25 mmol), and Pd(PPh ₃ ) ₄ (375 mg, 325 µmol) in 1,4- dioxane (30 mL) was degassed and purged with N ₂ three times, then the mixture was stirred at 100 °C for 2 hr under N ₂ atmosphere. The reaction was concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 1 ~ 33%, EtOAc in petroleum ether), methyl 4-((5-amino-5'-cyano-[2,2'-bipyridin]-6-yl)amino)benzoate (380 mg, yield: 17% for two steps) was obtained as a yellow solid. MS: m/z = 346.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.95 (d, J = 1.2 Hz, 1H), 8.51 (s, 1H), 8.29 (dd, J = 8.4, 2.0 Hz, 1H), 8.22 - 8.19 (m, 1H), 7.95 - 7.89 (m, 3H), 7.82 - 7.79 (m, 2H), 7.08 (d, J = 8.4 Hz, 1H), 3.82 (s, 3H). Step 3: Methyl 4-(2-(2-aminopyridin-3-yl)-5-(5-cyanopyridin-2-yl)-3H-imidaz o[4,5-b]pyridin- 3-yl)benzoate To a solution of methyl 4-((5-amino-5'-cyano-[2,2'-bipyridin]-6-yl)amino)benzoate (160 mg, 426 µmol) in DMSO (5 mL) were added Na ₂ S ₂ O ₄ (349 mg, 1.71 mmol 85% purity) and 2- aminonicotinaldehyde (62.5 mg, 512 µmol). The mixture was stirred at 100 ºC for 16 hr. The reaction mixture was quenched with H ₂ O (10 mL) at 25 °C, and then diluted with water (30 mL) and extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 1 ~ 50% EtOAc in petroleum ether), methyl 4-(2-(2- aminopyridin-3-yl)-5-(5-cyanopyridin-2-yl)-3H-imidazo[4,5-b] pyridin-3-yl)benzoate (100 mg, yield: 47%) was obtained as a yellow solid. MS: m/z = 448.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.93 (s, 1H), 8.73 - 8.65 (8m, 1H), 8.40 (d, J = 7.6 Hz, 1H), 8.34 - 8.28 (m, 3H), 8.27 - 8.09 (m, 2H), 8.00 - 7.96 (m, 2H), 7.58 (d, J = 7.2 Hz, 2H), 7.32 (d, J = 7.6 Hz, 1H), 6.56 - 6.46 (m, 1H), 4.03 (s, 3H). Step 4: 6-(2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5-b]pyridin-5- yl)nicotinonitrile To a solution of methyl 4-(2-(2-aminopyridin-3-yl)-5-(5-cyanopyridin-2-yl)-3H-imidaz o[4,5- b]pyridin-3-yl)benzoate (100 mg, 223 µmol) in THF (2 mL) was added LiAlH ₄ (12.7 mg, 335 µmol). The mixture was stirred at 0 ºC for 1 hr. The reaction mixture was quanched with Na ₂ SO ₄ ·10H ₂ O (100 mg) at 0 °C, filtered and concentrated under reduced pressure to give 6-(2- (2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imidazo [4,5-b]pyridin-5- yl)nicotinonitrile (60 mg, yield: 15%) as a yellow solid. MS: m/z = 420.2 [M + H] ⁺ . Step 5: 6-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imi dazo[4,5-b]pyridin-5- yl)nicotinonitrile To a solution of 6-(2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5- b]pyridin-5-yl)nicotinonitrile (60 mg, 143 umol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (34 mg, 286 umol) at 0 ºC. Then the mixture was stirred at 40 ºC for 1 hr. Th reaction mixture was concentrated under reduced pressure to give 6-(2-(2-aminopyridin-3-yl)-3-(4- (chloromethyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)nicotino nitrile (Intermediate 143, 70 mg, yield: 45%, HCl salt) as a yellow solid. MS: m/z = 438.2 [M + H] ⁺ . [00326] Intermediate 144: 5-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)picolinonitrile Step 1: 5-(2-(2-Aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)o xy)methyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)picolinonitrile A mixture of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-chlo ro-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (refer to Intermediate 117 for detail procedures, 700 mg, 1.50 mmol), (6-cyanopyridin-3-yl)boronic acid (267 mg, 1.80 mmol), Cs ₂ CO ₃ (1.47 g, 4.51 mmol), and Pd(dppf)Cl ₂ (220 mg, 300 µmol) IN 1,4-dioxane (10 mL) and H ₂ O (2 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 80 °C for 2 hr under N ₂ atmosphere. The reaction mixture was diluted with CH ₂ Cl ₂ (50 mL) and extracted with H ₂ O (50 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 50 ~ 100% EtOAc in petroleum ether), 5-(2-(2-aminopyridin-3-yl)-3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-3H-imidazo[4,5-b]pyrid in-5-yl)picolinonitrile (700 mg, yield: 74%) was obtained as a yellow solid. MS: m/z = 534.1 [M + H] ⁺ . Step 2: 5-(2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5-b]pyridin-5- yl)picolinonitrile To a solution of 5-(2-(2-aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)o xy)methyl)phenyl)- 3H-imidazo[4,5-b]pyridin-5-yl)picolinonitrile (100 mg, 187 µmol) in THF (5 mL) was added TBAF (73.5 mg, 281 µmol, 1 M). The mixture was stirred at 25 ºC for 0.5 hr. The reaction mixture was quenched with H ₂ O (20 mL) at 25 °C and extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give 5-(2-(2-aminopyridin-3-yl)-3-(4- (hydroxymethyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)picolin onitrile (100 mg, yield: 96%) as a yellow solid. MS: m/z = 420.0 [M + H] ⁺ . Step 3: 5-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imi dazo[4,5-b]pyridin-5- yl)picolinonitrile To a solution of 5-(2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5- b]pyridin-5-yl)picolinonitrile (10 mg, 238 µmol) in CH ₂ Cl ₂ (3 mL) was added SOCl ₂ (56.7 mg, 477 µmol) at 0 ºC, Then the mixture was stirred at 40 ºC for 1 hr. The reaction mixture was quenched with H ₂ O (1 mL) at 25 °C, and concentrated under reduced pressure to give 5-(2-(2- aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imidazo[4,5 -b]pyridin-5-yl)picolinonitrile (Intermediate 144, 120 mg, HCl salt, yield: 82%) as a yellow solid. MS: m/z = 438.2 [M + H] ⁺ . [00327] Intermediate 145: 4-(2-(2-Aminopyridin-3-yl)-5-(oxetan-3-yl)-3H-imidazo[4,5- b]pyridin-3-yl)benzyl methanesulfonate Step 1: Methyl 4-((6-bromo-3-nitropyridin-2-yl)amino)benzoate To a solution of 2,6-dibromo-3-nitropyridine (5 g, 17.7 mmol) and methyl 4-aminobenzoate (2.68 g, 17.7 mmol) in 1,4-dioxane (50 mL) was added DIEA (4.58 g, 35.5 mmol). The mixture was stirred at 50 °C for 12 hr under N ₂ . The mixture was concentrated under reduced pressure. The crude was triturated with EtOAc (100 mL) at 25 ºC for 30 min to give methyl 4-((6-bromo- 3-nitropyridin-2-yl)amino)benzoate (4.4 g, yield: 70%) as a red solid. MS: m/z = 351.9, 353.9 [M+H] ⁺ . Step 2: Methyl 4-(2-(2-aminopyridin-3-yl)-5-bromo-3H-imidazo[4,5-b]pyridin- 3-yl)benzoate To a solution of methyl 4-((6-bromo-3-nitropyridin-2-yl)amino)benzoate (2 g, 5.68 mmol) and 2-aminopyridine-3-carbaldehyde (763 mg, 6.25 mmol) in DMSO (20 mL) was added Na ₂ S ₂ O ₄ (2.47 g, 14.2 mmol). The mixture was stirred at 100 °C for 12 hr under N ₂ . Sat. aq. NaHCO ₃ (50 mL) was added and the mixture was extracted with CH ₂ Cl ₂ /MeOH (10/1, 50 mL x 3). The combined organic layers were washed with brine (50 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0 ~ 100% EtOAc in petroleum ether), methyl 4-(2-(2-aminopyridin-3-yl)-5-bromo-3H-imidazo[4,5-b]pyridin- 3- yl)benzoate (1.3 g, yield: 54%) was obtained as a black brown solid. MS: m/z = 423.9, 425.9 [M+H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.25 - 8.15 (m, 2H), 8.10 - 8.00 (m, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.55-7.40 (m, 3H), 7.05 - 7.00 (m, 1H), 6.83 (br s, 2H), 6.45-6.30 (m, 1H), 3.97 (s, 3H). Step 3: Methyl 4-(2-(2-aminopyridin-3-yl)-5-(oxetan-3-yl)-3H-imidazo[4,5-b] pyridin-3- yl)benzoate To a solution of methyl 4-(2-(2-aminopyridin-3-yl)-5-bromo-3H-imidazo[4,5-b]pyridin- 3- yl)benzoate (500 mg, 1.18 mmol) and 3-bromooxetane (242 mg, 1.77 mmol) in DME (8 mL) were added bis(trimethylsilyl)silyl-trimethyl-silane (293 mg, 1.18 mmol), Na ₂ CO ₃ (250 mg, 2.36 mmol), 4-tert-butyl-2-(4-tert-butyl-2-pyridyl)pyridine (15.8 mg, 59.0 µmol), (Ir[df(CF ₃ )ppy] ₂ (dtbpy))PF ₆ (13.2 mg, 11.8 umol), and NiCl ₂ .glyme (12.9 mg, 58.9 µmol). The mixture was stirred at 25 °C for 16 hr under 450 nm blue-light with fan cooling at 5000 rpm. H ₂ O (50 mL) was added and the mixture was extracted with CH ₂ Cl ₂ /MeOH (10/1, 30 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0 ~ 100% EtOAc in petroleum ether), methyl 4-(2-(2-aminopyridin-3-yl)-5-(oxetan-3-yl)-3H-imidazo[4,5-b] pyridin- 3-yl)benzoate (170 mg, yield: 36%) was obtained as a black brown oil. MS: m/z = 402.2 [M+H] ⁺ . Step 4: (4-(2-(2-Aminopyridin-3-yl)-5-(oxetan-3-yl)-3H-imidazo[4,5-b ]pyridin-3- yl)phenyl)methanol To a solution of methyl 4-(2-(2-aminopyridin-3-yl)-5-bromo-3H-imidazo[4,5-b]pyridin- 3- yl)benzoate (170 mg, 424 µmol) in THF (4 mL) was added LiAlH ₄ (32.2 mg, 847 µmol) in portions under N ₂ at 0 °C. The mixture was stirred at 0 °C for 1 hr under N ₂ . The mixture was diluted with THF (20 mL). Na ₂ SO ₄ 10H ₂ O was added in portions until no bubbles were formed. The resulting mixture was stirred at 25 °C for 20 min and filtered. The filter cake was washed with THF (20mL x 2), the combined filtrate was concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 100% EtOAc in petroleum ether), (4- (2-(2-aminopyridin-3-yl)-5-(oxetan-3-yl)-3H-imidazo[4,5-b]py ridin-3-yl)phenyl)methanol (50 mg, yield: 32%) was obtained as yellow oil. MS: m/z = 374.2 [M+H] ⁺ . Step 5: 4-(2-(2-Aminopyridin-3-yl)-5-(oxetan-3-yl)-3H-imidazo[4,5-b] pyridin-3-yl)benzyl methanesulfonate To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(oxetan-3-yl)-3H-imidazo[4,5-b ]pyridin-3- yl)phenyl)methanol (50 mg, 134 umol) in CH ₂ Cl ₂ (1 mL) were added TEA (40.7 mg, 402 µmol) and MsCl (100 mg, 873 umol) at 0 ºC. The Mixture was stirred at 0 ºC for 2 hr under N ₂ . The mixture was added dropwise into H ₂ O (20ml) at 0 °C. The mixture was extracted with CH ₂ Cl ₂ (10 mL x 2). The combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated. 4-(2-(2-Aminopyridin-3-yl)-5-(oxetan-3-yl)-3H-imidazo[4,5-b] pyridin-3-yl)benzyl methanesulfonate (Intermediate 145, 60.5 mg) was obtained as yellow oil, which was used in the next step directly. MS: m/z = 452.1 [M+H] ⁺ . [00328] Intermediate 146: 3-(3-(4-(Chloromethyl)phenyl)-5-(4-methoxyphenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 146 was prepared in a manner similar to Intermediate 144. MS: m/z = 442.3 [M+H] ⁺ . [00329] Intermediate 147: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-methoxyphenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Intermediate 47 was prepared in a manner similar to Intermediate 76. MS: m/z = 442.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ )) δ 8.31 (d, J = 8.8 Hz, 1H), 8.09 (d, J = 4.8 Hz, 1H), 8.05 (dd, J = 6.4, 1.2 Hz, 1H), 7.95 (dd, J = 7.6, 1.2 Hz, 1H), 7.71 - 7.65 (m, 3H), 7.60 - 7.56 (m, 2H), 7.43 - 7.38 (m, 1H), 7.13 (d, J = 8.0 Hz, 1H), 7.04 - 6.99 (m, 1H), 6.91 - 6.88 (m, 1H), 4.76 (s, 2H), 3.88 (s, 3H). [00330] Intermediate 148: 3-(3-(4-(Chloromethyl)phenyl)-5-(trifluoromethoxy)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: 2-Chloro-3-nitro-6-(trifluoromethoxy)pyridine To a solution of 2-chloro-6-(trifluoromethoxy)pyridine (2.0 g, 10.1 mmol) in H ₂ SO ₄ (25 mL) at 0 °C was added HNO ₃ (18.9 g, 300 mmol) dropwise and stirred for 1 hr . This mixture was stirred at 40 °C for 12 hr. This mixture was poured into ice water (30 mL) and extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (50 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated to give 2-chloro-3-nitro-6-(trifluoromethoxy)pyridinee (2.40 g, yield: 97%) as yellow oil, which was used in the next step without purification. Step 2: (4-((3-Nitro-6-(trifluoromethoxy)pyridin-2-yl)amino)phenyl)m ethanol To a mixture of 2-chloro-3-nitro-6-(trifluoromethoxy)pyridinee (1.80 g, 7.42 mmol) in THF (25 mL) were added DIEA (2.88 g, 22.3 mmol) and (4-aminophenyl)methanol (1.01 g, 8.16 mmol) at 25 °C, the mixture was stirred at 80 °C for 1 hr. The mixture was quenched with water (30 mL) and then extracted with EtOAc (30 mL x 3). The combined organic layers were filtered and concentrated to give the crude. After purified by silica gel flash chromatography (Eluent of 0 ~ 30% EtOAc in petroleum ether), (4-((3-nitro-6-(trifluoromethoxy)pyridin-2- yl)amino)phenyl)methanol (900 mg, yield: 36%) was obtained as a yellow solid. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.26 (s, 1H), 8.70 (d, J = 8.8 Hz, 1H), 7.54 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.8 Hz, 2H), 6.70 (d, J = 8.8 Hz, 1H), 5.18 (t, J = 5.6 Hz, 1H), 4.50 (d, J = 5.6 Hz, 2H). ¹⁹ F NMR (376.5 MHz, Dimethylsulfoxide-d ₆ ) δ -55.544. Step 3: N-(4-(((Tert-butyldimethylsilyl)oxy)methyl)phenyl)-3-nitro-6 - (trifluoromethoxy)pyridin-2-amine To a solution of (4-((3-Nitro-6-(trifluoromethoxy)pyridin-2-yl)amino)phenyl)m ethanol (900 mg, 2.73 mmol) in CH ₂ Cl ₂ (8 mL) were added imidazole (279 mg, 4.10 mmol) and TBSCl (536 mg, 3.55 mmol) at 25 °C. This mixture was stirred at 25 °C for 1 hr. The mixture was filtered and concentrated to give N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-3-nitro-6 - (trifluoromethoxy)pyridin-2-amine (1.20 g, yield: 99%) as a yellow solid, which was used in the next step without further purification. MS: m/z = 444.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.25 (s, 1H), 8.69 (d, J = 8.8 Hz, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 6.69 (d, J = 8.8 Hz, 1H), 4.71 (s, 2H), 0.89 (s, 9H), 0.07 (s, 6H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -55.611. Step 4: (4-(2-(2-Aminopyridin-3-yl)-5-(trifluoromethoxy)-3H-imidazo[ 4,5-b]pyridin-3- yl)phenyl)methanol To a solution of N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-3-nitro-6 - (trifluoromethoxy)pyridin-2-amine (1.20 g, 2.71 mmol) in DMSO (10 mL) were added Na ₂ S ₂ O ₄ (1.18 g, 6.76 mmol) and 2-aminopyridine-3-carbaldehyde (363 mg, 2.98 mmol) at 25 °C. The mixture was stirred at 100 °C for 12 hr. NaHCO ₃ (sat, 50 mL) was added and the mixture was extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (50 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated to give the crude. After purified by silica gel flash chromatography (Eluent of 0 ~ 100% EtOAc/ EtOH (3 / 1) in petroleum ether), (4-(2- (2-aminopyridin-3-yl)-5-(trifluoromethoxy)-3H-imidazo[4,5-b] pyridin-3-yl)phenyl)methanol (400 mg, yield: 37%) was obtained as a brown oil. MS: m/z = 402.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.41 (d, J = 8.0 Hz, 1H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.45 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 7.31-7.21 (m, 2H), 6.79 (s, 2H), 6.43 (dd, J = 7.6, 4.8 Hz, 1H), 5.34 (t, J = 6.0 Hz, 1H), 4.57 (d, J = 5.2 Hz, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -55.482. Step 5: 3-(3-(4-(Chloromethyl)phenyl)-5-(trifluoromethoxy)-3H-imidaz o[4,5-b]pyridin-2- yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(trifluoromethoxy)-3H-imidazo[ 4,5-b]pyridin-3- yl)phenyl)methanol (400 mg, 997 µmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (356 mg, 2.99 mmol) at 25 °C. This mixture was stirred at 25 °C for 1 hr. The reaction mixture was concentrated to give 3-(3-(4-(chloromethyl)phenyl)-5-(trifluoromethoxy)-3H-imidaz o[4,5- b]pyridin-2-yl)pyridin-2-amine (Intermediate 148, 220 mg) as a brown solid, which was used in the next step without purification. MS: m/z = 420.1 [M + H] ⁺ . [00331] Intermediate 149: 3-(3-(4-(Chloromethyl)phenyl)-5-isopropoxy-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine Step 1: N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-6-isoprop oxy-3-nitropyridin-2- amine To a mixture of N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-6-chloro- 3-nitropyridin-2- amine (refer to Intermediate 105 for detail procedures, 1 g, 2.54 mmol) in i-PrOH (10 mL) was added NaH (203 mg, 5.08 mmol, 60% purity). The mixture was stirred at 20 °C for 12 hr. H ₂ O (50 mL) was added, and the mixture was extracted with EtOAc (100 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0 ~ 30% EtOAc in petroleum ether), N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-6-isoprop oxy-3-nitropyridin-2-amine (710 mg, yield: 67%) was obtained as a yellow solid. MS: m/z = 418.1 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.40 (s, 1H), 8.39 (d, J = 8.8 Hz, 1H), 7.58 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 6.27 (d, J = 9.2 Hz, 1H), 5.17 - 5.00 (m, 1H), 4.71 (s, 2H), 1.25 (d, J = 6.2 Hz, 6H), 0.89 (s, 9H), 0.07 (s, 6H). Step 2: (4-(2-(2-Aminopyridin-3-yl)-5-isopropoxy-3H-imidazo[4,5-b]py ridin-3- yl)phenyl)methanol To a mixture of N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-6-isoprop oxy-3- nitropyridin-2-amine (700 mg, 1.68 mmol) and 2-aminopyridine-3-carbaldehyde (225 mg, 1.84 mmol) in DMSO (10 mL) was added Na ₂ S ₂ O ₄ (730 mg, 4.19 mmol). The mixture was stirred at 100 °C for 12 hr. H ₂ O (50 mL) was added. The mixture was filtered and concentrated to give (4-(2-(2-aminopyridin-3-yl)-5-isopropoxy-3H-imidazo[4,5-b]py ridin-3-yl)phenyl)methanol (500 mg, yield: 79%) as a brown solid. MS: m/z = 376.0 [M+H] ⁺ . Step 3: 3-(3-(4-(Chloromethyl)phenyl)-5-isopropoxy-3H-imidazo[4,5-b] pyridin-2-yl)pyridin-2- amine To a mixture of (4-(2-(2-aminopyridin-3-yl)-5-isopropoxy-3H-imidazo[4,5-b]py ridin-3- yl)phenyl)methanol (450 mg, 1.20 mmol) in CH ₂ Cl ₂ (4 mL) was added SOCl ₂ (174 μL, 2.40 mmol), the mixture was stirred at 40 °C for 1 hr. The mixture was concentrated to give 3-(3-(4- (chloromethyl)phenyl)-5-isopropoxy-3H-imidazo[4,5-b]pyridin- 2-yl)pyridin-2-amine (Intermediate 149, 450 mg, yield: 95 %) as a yellow solid. MS: m/z = 394.0 [M+H] ⁺ . Intermediate 150: 3-(3-(4-(Chloromethyl)phenyl)-5-(methoxy-d ₃ )-3H-imidazo[4,5-b]pyridin-2- yl)pyridin-2-amine Step 1: N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-6-(methox y-d ₃ )-3-nitropyridin-2- amine To a mixture of N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-6-chloro- 3-nitropyridin-2- amine (refer to Intermediate 105 for detail procedures, 2 g, 5.08 mmol) in CD ₃ OD (30 mL) was added NaH (406 mg, 10.2 mmol, 60% purity) at 0 °C. The mixture was stirred at 20 °C for 2 hr. H ₂ O (30 mL) was added slowly, and the mixture was extracted with EtOAc (30 mL x 2). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-6-(methox y-d ₃ )- 3-nitropyridin-2-amine (1.77 g, yield: 89%) was obtained as a brown oil, which was used in the next step directly. MS: m/z = 393.1 [M + H] ⁺ . Step 2: (4-(2-(2-Aminopyridin-3-yl)-5-(methoxy-d3)-3H-imidazo[4,5-b] pyridin-3- yl)phenyl)methanol To a solution of N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-6-(methox y-d3)-3- nitropyridin-2-amine (870 mg, 2.22 mmol) in DMSO (15 mL) were added Na ₂ S ₂ O ₄ (1.16 g, 6.65 mmol) and 2-aminopyridine-3-carbaldehyde (298 mg, 2.44 mmol). The mixture was stirred at 100 °C for 12 hr. Sat. NaHCO ₃ (50 mL) was added to the mixture and the mixture was extracted with CH ₂ Cl ₂ (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by prep-HPLC (column: Xtimate C18 150 x 40 mm x 10 μm; mobile phase: [water (NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN]; gradient: 26% - 56% B over 8 min), (4-(2-(2-aminopyridin-3-yl)-5-(methoxy-d3)-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (200 mg, yield: 13%) was obtained as a yellow solid. MS: m/z = 351.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.11 (d, J = 8.8 Hz, 1H), 7.95 (d, J = 2.8 Hz, 1H), 7.88 (d, J = 4.0 Hz, 1H), 7.47 - 7.42 (m, 2H), 7.38 - 7.36 (m, 1H), 7.10 (dd, J = 7.6, 2.0 Hz, 1H), 6.90 - 6.89 (m, 1H), 6.81 (d, J = 8.8 Hz, 1H), 6.57 (dd, J = 7.2, 4.8 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 5.67 - 5.60 (m, 1H), 5.35 (t, J = 5.6 Hz, 1H), 4.58 (d, J = 6.0 Hz, 2H). Step 3: 3-(3-(4-(Chloromethyl)phenyl)-5-(methoxy-d3)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin- 2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(methoxy-d3)-3H-imidazo[4,5-b] pyridin-3- yl)phenyl)methanol (100 mg, 285 µmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (102 mg, 856 µmol) at 20 oC. The reaction mixture was stirred at 20 ºC for 2 hr. The reaction mixture was concentrated to give 3-(3-(4-(Chloromethyl)phenyl)-5-(methoxy-d3)-3H-imidazo[4,5- b]pyridin- 2-yl)pyridin-2-amine (Intermediate 150, 105mg, yield: 100%) as a yellow solid, which was used in the next step without further purification. MS: m/z = 369.1 [M + H] ⁺ . [00332] Intermediate 151: 6-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)picolinonitrile Intermediate 151 was prepared in a manner similar to Intermediate 144. MS: m/z = 438.0 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.78 - 8.25 (m, 5H), 8.25 - 8.13 (m, 2 H), 8.12 - 8.06 (m, 1 H), 7.95 (dd, J = 7.6, 1.6 Hz, 1H), 7.68 - 7.60 (m, 4H), 6.93 (dd, J = 7.6, 5.2 Hz, 1H), 4.88 (s, 2H). [00333] Intermediate 152: 4-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)picolinonitrile Intermediate 152 was prepared in a manner similar to Intermediate 144. MS: m/z = 438.2 [M + 1] ⁺ . [00334] Intermediate 153: 5-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)nicotinonitrile Intermediate 153 was prepared in a manner similar to Intermediate 144. MS: m/z = 438.1 [M + H] ⁺ . [00335] Intermediate 154: 3-(3-(4-(Chloromethyl)phenyl)-5-(pyridin-3-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: N-(4-(((Tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-nitro-[ 2,3'-bipyridin]-6-amine To a solution of N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-6-chloro- 3-nitropyridin-2- amine (refer to Intermediate 105 for detail procedures, 2 g, 5.08 mmol) and 3-pyridylboronic acid (749 mg, 6.09 mmol) in 1,4-dioxane (20 mL) and H ₂ O (4 mL) were added Pd(dppf)Cl ₂ (371 mg, 508 µmol) and Cs ₂ CO ₃ (4.96 g, 15.2 mmol). The mixture was degassed and purged with N ₂ three times, and then was stirred at 100 °C for 12 hr under N ₂ . H ₂ O (50 mL) was added, and the mixture was extracted with EtOAc (30 mL x 2). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. N-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-5-nitro-[2,3'-bipyridi n]-6-amine (2.22 g) was obtained as a black brown oil, which was used in the next step directly. MS: m/z = 437.2 [M+H] ⁺ . Step 2: (4-(2-(2-Aminopyridin-3-yl)-5-(pyridin-3-yl)-3H-imidazo[4,5- b]pyridin-3- yl)phenyl)methanol To a solution of N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-nitro-[ 2,3'-bipyridin]-6- amine (2 g, 4.58 mmol) and 2-aminopyridine-3-carbaldehyde (615 mg, 5.04 mmol) in DMSO (20 mL) was added Na ₂ S ₂ O ₄ (1.99 g, 11.5 mmol). The mixture was stirred at 100 °C for 12 hr under N ₂ . Sat. NaHCO ₃ (50 mL) was added and the mixture was extracted with CH ₂ Cl ₂ /MeOH (10/1, 50 mL x 3). The combined organic layers were washed with brine (50 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0 ~ 100% EtOAc /EtOH (3/1) in petroleum ether), (4-(2-(2-aminopyridin-3-yl)-5- (pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (500 mg, yield: 28% for 2 steps) was obtained as brown oil. MS: m/z = 395.2 [M+H] ⁺ . Step 3: 3-(3-(4-(Chloromethyl)phenyl)-5-(pyridin-3-yl)-3H-imidazo[4, 5-b]pyridin-2-yl)pyridin- 2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(pyridin-3-yl)-3H-imidazo[4,5- b]pyridin-3- yl)phenyl)methanol (500 mg, 1.27 mmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (452 mg, 3.80 mmol). The mixture was stirred at 40 °C for 1 hr under N ₂ . The solution was consentrated. 3- (3-(4-(Chloromethyl)phenyl)-5-(pyridin-3-yl)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (Intermediate 154, 400 mg, yield: 76%) was obtained as yellow solid, which was used in the next step directly. MS: m/z = 413.2 [M+H] ⁺ . [00336] Intermediate 155: 3-(3-(4-(Chloromethyl)phenyl)-5-(pyridin-4-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: N-(4-(((tert-Butyldimethylsilyl)oxy)methyl)phenyl)-5-nitro-[ 2,4'-bipyridin]-6-amine To a solution of N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-6-chloro- 3-nitropyridin-2- amine (refer to Intermediate 105 for detail procedures, 2 g, 5.08 mmol) in 1,4-dioxane (20 mL) and H ₂ O (4 mL) were added 4-pyridylboronic acid (686 mg, 5.58 mmol), Pd(dppf)Cl ₂ (371 mg, 507 µmol), and Cs ₂ CO ₃ (4.96 g, 15.2 mmol). The mixture was degassed and purged with N ₂ three times and was stirred at 100 °C for 2 hr under N ₂ atmosphere. The crude was extracted with CH ₂ Cl ₂ (30 mL x 3). The combined organic layers were washed with brine (40 mL), dried over Na ₂ SO ₄ , filtered and concentrated. N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5- nitro-[2,4'-bipyridin]-6-amine (2.22 g, crude) was obtained as a brown solid and was used for the next step without further purification. MS: m/z = 437.3 [M+H] ⁺ . Step 2: (4-(2-(2-Aminopyridin-3-yl)-5-(pyridin-4-yl)-3H-imidazo[4,5- b]pyridin-3- yl)phenyl)methanol To a solution of N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-nitro-[ 2,4'-bipyridin]-6- amine (2.12 g, 4.86 mmol), 2-aminopyridine-3-carbaldehyde (711 mg, 5.83 mmol) in DMSO (20 mL) was added Na ₂ S ₂ O ₄ (2.11 g, 12.1 mmol). The mixture was stirred at 100 °C for 12 hr. Sat. Na ₂ CO ₃ (15 mL) was added to adjust pH about 8 and the mixture was extracted with CH ₂ Cl ₂ (15 mL x 3). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0 ~ 78% EtOAc/EtOH (3:1) in petroleum ether), (4-(2-(2-aminopyridin-3-yl)-5-(pyridin-4-yl)-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (100 mg, yield: 5% for 2 steps) was obtained as a yellow solid. MS: m/z = 395.3 [M+H] ⁺ . Step 3: 3-(3-(4-(Chloromethyl)phenyl)-5-(pyridin-4-yl)-3H-imidazo[4, 5-b]pyridin-2-yl)pyridin- 2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(pyridin-4-yl)-3H-imidazo[4,5- b]pyridin-3- yl)phenyl)methanol (100 mg, 253 umol) in CH ₂ Cl ₂ (2 mL) was added SOCl ₂ (60.3 mg, 507 µmol). The mixture was stirred at 25 ºC for 2 hr. The residue was concentrated. 3-(3-(4- (Chloromethyl)phenyl)-5-(pyridin-4-yl)-3H-imidazo[4,5-b]pyri din-2-yl)pyridin-2-amine (Intermediate 155, 104 mg, crude) was obtained a brown solid and used for the next step without further purification. MS: m/z = 413.2 [M+H] ⁺ . [00337] Intermediate 156: 7-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-7-azaspiro[3.5]nonan-2-amine Intermediate 156 was prepared in a manner similar to Intermediate 35. MS: m/z = 516.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.0 Hz, 1H), 8.06 - 7.95 (m, 4H), 7.55 - 7.35 (m, 7H), 7.18 - 7.12 (m, 1H), 7.01 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.71 - 3.58 (m, 1H), 3.52 (s, 2H), 3.01 - 2.98 (m, 4H), 2.41 - 2.20 (m, 2H), 2.14 - 2.05 (m, 2H), 1.90 - 1.80 (m, 2H), 1.67 - 1.53 (m, 2H). [00338] Intermediate 157: 3-(3-(4-((2,7-Diazaspiro[4.4]nonan-2-yl)methyl)phenyl)-5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 157 was prepared in a manner similar to Intermediate 35. MS: m/z = 502.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 11.93 (br s, 1H), 9.88 - 9.48 (m, 2H), 8.60 - 8.35 (m, 2H), 8.38 (d, J = 8.4 Hz, 1H), 8.16 (dd, J = 6.4, 1.6 Hz, 1H), 8.08 - 8.05 (m, 3H), 7.98 - 7.83 (m, 3H), 7.66 (d, J = 8.4 Hz, 2H), 7.52 - 7.40 (m, 3H), 7.02 - 6.92 (m, 1H), 4.54 - 4.43 (m, 2H), 3.64 - 3.47 (m, 2H), 3.43 - 3.27 (m, 3H), 3.25 - 3.18 (m, 3H), 2.31 - 2.14 (m, 2H), 2.11 - 1.96 (m, 2H). [00339] Intermediate 158: 3-(3-(4-((2,7-Diazaspiro[3.5]nonan-7-yl)methyl)phenyl)-5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 158 was prepared in a manner similar to Intermediate 35. MS: m/z = 502.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.26 (d, J = 8.4 Hz, 1H), 8.05 - 7.97 (m, 4H), 7.49 - 7.39 (m, 7H), 7.18 - 7.12 (dd, J = 7.6, 1.6 Hz, 1H), 7.02 (br s, 2H), 6.36 (dd, J = 7.6, 5.2 Hz, 1H), 3.58 - 3.41 (m, 6H), 2.38 - 2.26 (m, 4H), 1.71 – 1.68 (m, 4H). [00340] Intermediate 159: 3-(3-(4-((2,7-Diazaspiro[4.5]decan-2-yl)methyl)phenyl)-5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 159 was prepared in a manner similar to Intermediate 35. MS: m/z = 516.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.32 (d, J = 8.4 Hz, 1H), 8.09 - 8.00 (m, 4H), 7.93 (d, J = 8.4 Hz, 2H), 7.89 (d, J = 7.2 Hz, 1H), 7.72 (d, J = 8.0 Hz, 2H), 7.49 - 7.37 (m, 3H), 6.99 - 6.85 (m, 1H), 4.62 (d, J = 11.6 Hz, 2H), 3.78 - 3.72 (m, 1H), 3.65 - 3.47 (m, 2H), 3.44 - 3.38 (m, 1H), 3.35 (s, 2H), 3.18 - 3.13 (m, 2H), 2.26 - 2.13 (m, 1H), 2.11 - 2.01 (m, 1H), 1.95 - 1.86 (m, 4H). [00341] Intermediate 160: 3-(3-(4-((2,8-diazaspiro[4.5]decan-2-yl)methyl)phenyl)-5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 160 was prepared in a manner similar to Intermediate 35. MS: m/z = 516.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.33 (d, J = 8.8 Hz, 1H), 8.10 - 8.01 (m, 4H), 7.96 - 7.87 (m, 3H), 7.72 (d, J = 8.0 Hz, 2H), 7.49 - 7.40 (m, 3H), 6.96 - 6.87 (m, 1H), 4.67 - 4.54 (m, 2H), 3.75 - 3.65 (m, 2H), 3.51 (d, J = 10.0 Hz, 1H), 3.35 (s, 2H), 3.32 - 3.20 (m, 3H), 2.32 - 2.23 (m, 1H), 2.15 - 2.05 (m, 2H), 2.04 - 1.96 (m, 3H). [00342] Intermediate 161: (R)-3-(3-(4-((2,7-Diazaspiro[4.4]nonan-2-yl)methyl)phenyl)-5 - phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 161 was prepared in a manner similar to Intermediate 28. MS: m/z = 502.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 12.00 - 11.77 (m, 1H), 9.73 - 9.52 (m, 2H), 8.58 - 8.44 (m, 1H), 8.38 (d, J = 8.4 Hz, 1H), 8.16 (dd, J =6.0, 1.6 Hz, 1H), 8.04 – 8.09 (m, 3H), 7.92 - 7.85 (m, 3H), 7.66 (d, J = 8.4 Hz, 2H), 7.52 - 7.46 (m, 2H), 7.45 - 7.40 (m, 1H), 7.00 - 6.92 (m, 1H), 4.57 - 4.41 (m, 2H), 3.50-3.58 (m, 4H), 3.41 - 3.33 (m, 2H), 3.25 - 3.22 (m, 2H), 2.28 - 2.13 (m, 2H), 2.10 - 1.97 (m, 2H). [00343] Intermediate 162: 3-(3-(4-(2,9-Diazaspiro[5.5]undecan-9-ylmethyl)phenyl)-5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 162 was prepared in a manner similar to Intermediate 28. MS: m/z = 530.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 11.24 - 10.95 (m, 1H), 9.45 - 8.99 (m, 2H), 8.52 (br s, 1H), 8.38 (d, J = 8.4 Hz, 1H), 8.16 (d, J = 6.0 Hz, 1H), 8.12 - 8.02 (m, 3H), 7.91 - 7.81 (m, 3H), 7.73 - 7.62 (m, 2H), 7.52 - 7.40 (m, 3H), 6.93 - 6.84 (m, 1H), 4.41 (d, J = 5.2 Hz, 2H), 3.21 - 3.09 (m, 5H), 2.99 - 2.90 (m, 2H), 2.87 - 2.75 (m, 1H), 2.13 - 2.09 (m, 1H), 2.00 - 1.88 (m, 1H), 1.86 - 1.73 (m, 2H), 1.72 - 1.56 (m, 3H), 1.45 - 1.40 (m, 1H). [00344] Intermediate 163: (S)-3-(3-(4-((2,7-Diazaspiro[4.4]nonan-2-yl)methyl)phenyl)-5 - phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 163 was prepared in a manner similar to Intermediate 28. MS: m/z = 502.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 11.9 (br s, 1H), 9.80 - 9.66 (m, 2H), 8.66 - 8.50 (m, 2H), 8.38 (d, J = 8.4 Hz, 1H), 8.17 (dd, J = 6.4, 1.6 Hz, 1H), 8.08 - 8.05 (m, 3H), 7.93 - 7.86 (M, 3H), 7.66 (d, J = 8.4 Hz, 2H), 7.54 - 7.40 (m, 3H), 7.00 - 6.95 (m, 1H), 3.55 - 3.50 (m, 1H), 3.40 - 3.17 (m, 8H), 2.33 - 1.95 (m, 5H). [00345] Intermediate 164: (R)-3-(3-(4-((3-Methylpiperazin-1-yl)methyl)phenyl)-5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 164 was prepared in a manner similar to Intermediate 28. MS: m/z = 476.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.08 - 7.95 (m, 4H), 7.52 - 7.35 (m, 7H), 7.15 (d, J = 6.0 Hz, 1H), 7.04 (br s, 2H), 6.40 - 6.34 (m, 1H), 3.53 (s, 2H), 2.87 - 2.77 (m, 1H), 2.75 - 2.62 (m, 4H), 2.02 - 1.91 (m, 1H), 1.68 - 1.58 (m, 1H), 0.92 (d, J = 6.0 Hz, 3H). [00346] Intermediate 165: 3-(3-(4-(((3S,5R)-3,5-Dimethylpiperazin-1-yl)methyl)phenyl)- 5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 165 was prepared in a manner similar to Intermediate 28. MS: m/z = 490.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 7.97 - 8.04 (m, 4H), 7.42 - 7.48 (m, 6H), 7.37 - 7.42 (m, 1H), 7.15 (dd, J = 7.6, 2.0 Hz, 1H), 7.05 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.52 (s, 2H), 2.73 - 2.79 (m, 2H), 2.64 - 2.67 (m, 2H), 1.56 - 1.50 (m, 2H), 0.91 (d, J = 6.0 Hz, 6H). [00347] Intermediate 166: 4-(Azepan-4-ylamino)-1,3,5-triazine-2-carbonitrile Intermediate 166 was prepared in a manner similar to Intermediate 55. [00348] Intermediate 167: 4-((1,4-Oxazepan-6-yl)amino)-1,3,5-triazine-2-carbonitrile Intermediate 167 was prepared in a manner similar to Intermediate 55. [00349] Intermediate 168: 3-(3-(4-((2,8-Diazaspiro[4.5]decan-8-yl)methyl)phenyl)-5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 168 was prepared in a manner similar to Intermediate 35. MS: m/z = 516.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.18 (d, J = 8.4 Hz, 1H), 8.02 (d, J = 7.2 Hz, 2H), 7.97 (dd, J = 4.8, 1.6 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.45 - 7.34 (m, 5H), 7.31 (dd, J = 6.8, 1.6 Hz, 1H), 6.45 (dd, J = 7.6, 4.8 Hz, 1H), 3.62 (s, 2H), 3.10 (t, J = 7.2 Hz, 2H), 2.85 (s, 2H), 2.50 (m, 4H), 1.75 (t, J = 7.2 Hz, 2H), 1.65 (t, J = 5.6 Hz, 4H). [00350] Intermediate 169: 3-(3-(4-((3,9-diazaspiro[5.5]undecan-3-yl)methyl)phenyl)-5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 169 was prepared in a manner similar to Intermediate 35. MS: m/z = 530.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.81 - 10.50 (m, 1H), 8.79 - 8.66 (m, 2H), 8.38 (dd, J = 8.4 Hz, 1H), 8.13 - 8.11 (m, 1H), 8.08 - 8.05 (m, 4H), 7.86 - 7.77 (m, 3H), 7.67 (d, J = 8.0 Hz, 2H), 7.51 - 7.46 (m, 2H), 7.45 - 7.41 (m, 1H), 6.86 - 6.78 (m, 1H), 4.41 (d, J = 4.4 Hz, 2H), 3.21 - 3.15 (m, 2H), 3.09 - 3.01 (m, 6H), 1.91 - 1.85 (m, 2H), 1.82 - 1.71 (m, 4H), 1.54 – 1.53 (m, 2H). [00351] Intermediate 170: 3-(3-(4-((2,6-Diazaspiro[3.3]heptan-2-yl)methyl)phenyl)-5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 170 was prepared in a manner similar to Intermediate 28. MS: m/z = 474.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.26 (d, J = 8.4 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.49 - 7.44 (m, 2H), 7.42 - 7.37 (m, 5H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 6.99 (br s, 2H), 6.39 (dd, J = 8.0, 5.2 Hz, 1H), 3.58 (s, 2H), 3.56 (s, 4H), 3.25 (s, 4H), 1.23 (s, 1H). [00352] Intermediate 171: 2-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2-azaspiro[3.3]heptan-6-amine Intermediate 171 was prepared in a manner similar to Intermediate 35. MS: m/z = 488.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ 8.20 (d, J = 8.8 Hz, 1H), 8.05 - 8.01 (m, 2H), 7.99 (dd, J = 5.2, 1.6 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.58 - 7.50 (m, 2H), 7.43 - 7.39 (m, 2H), 7.34 (dd, J = 7.6, 2.0 Hz, 1H), 6.49 (dd, J = 7.6, 4.8 Hz, 1H), 6.21 - 6.17 (m, 2H), 5.65 (dd, J = 7.6, 4.4 Hz, 1H), 4.26 - 4.18 (m, 1H), 4.00 (s, 2H), 3.77 (s, 2H), 3.66 (s, 2H), 2.65 – 2.60 (m, 2H), 2.22 - 2.17 (m, 2H). [00353] Intermediate 172: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-(3- fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 172 was prepared in a manner similar to Intermediate 61. MS: m/z = 494.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 11.38 - 11.04 (m, 1H), 8.45 - 8.36 (m, 4H), 8.18 - 8.10 (m, 2H), 7.94 (d, J = 8.0 Hz, 1H), 7.91 - 7.81 (m, 4H), 7.72 - 7.64 (m, 2H), 7.57 - 7.51 (m, 1H), 7.31 - 7.20 (m, 2H), 7.18 - 7.12 (m, 1H), 6.94 - 6.85 (m, 1H), 4.37 - 4.34 (m, 2H), 3.57 (s, 2H), 3.33 - 3.30 m, 1H), 3.12 - 3.02 (m, 2H), 2.22 - 2.14 (m, 2H), 2.09 - 1.95 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -112.71. [00354] Intermediate 173: (S)-3-(3-(4-((3-Aminopiperidin-1-yl)methyl)phenyl)-5-phenyl- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 173 was prepared in a manner similar to Intermediate 35. MS: m/z = 476.2 [M + H] ⁺ .1H NMR (400 MHz, Methanol-d ₄ 8.32 (d, J = 8.4 Hz, 1H), 8.10 - 7.98 (m, 4H), 7.94 (d, J = 8.4 Hz, 2H), 7.89 (dd, J = 7.6, 1.2 Hz, 1H), 7.74 (d, J = 8.4 Hz, 2H), 7.49 - 7.34 (m, 3H), 6.93 (dd, J = 7.6, 6.4 Hz, 1H), 4.62 (s, 2H), 3.89 - 3.56 (m, 3H), 3.28 - 3.12 (m, 2H), 2.26 - 1.99 (m, 3H), 1.90 - 1.66 (m, 1H). [00355] Intermediate 174: 6-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)-1-methylpyridin-2(1H)-one Step 1: Methyl 4-((3-nitro-6-(trimethylstannyl)pyridin-2-yl)amino)benzoate A mixture of methyl 4-((6-chloro-3-nitropyridin-2-yl)amino)benzoate (refer to Intermediate 13 for detail procedures, 5 g, 16.3 mmol), (Me ₃ Sn) ₂ (9.43 g, 28.8 mmol), and Pd(PPh ₃ ) ₄ (300 mg, 813 μmol) in 1,4-dioxane (50 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 90 °C for 4 hr under N ₂ atmosphere. The reaction mixture was concentrated under reduced pressure to give methyl 4-((3-nitro-6-(trimethylstannyl)pyridin-2- yl)amino)benzoate (7 g, crude) as a black brown solid, which was directly used in the next step. Step 2: Methyl 4-((1'-methyl-5-nitro-6'-oxo-1',6'-dihydro-[2,2'-bipyridin]- 6-yl)amino)benzoate A mixture of methyl 4-((3-nitro-6-(trimethylstannyl)pyridin-2-yl)amino)benzoate (7 g, 16.1 mmol), 6-bromo-1-methylpyridin-2(1H)-one (3.62 g, 19.3 mmol), and Pd(PPh ₃ ) ₄ (296 mg, 803 μmol) in 1,4-dioxane (60 mL) was degassed and purged with N ₂ three times, then the mixture was stirred at 100 °C for 16 hr under N ₂ atmosphere. The residue was diluted with CH ₂ Cl ₂ (50 mL) and extracted with H ₂ O (40 mL x 3). The combined organic layers were washed with brine (30 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 20 ~ 25% EtOAc in CH ₂ Cl ₂ ), methyl 4- ((1'-methyl-5-nitro-6'-oxo-1',6'-dihydro-[2,2'-bipyridin]-6- yl)amino)benzoate (9.4 g, purity: 29%) was obtained as an orange red solid. MS: m/z = 381.0 [M + H] ⁺ . Step 3: Methyl 4-(2-(2-aminopyridin-3-yl)-5-(1-methyl-6-oxo-1,6-dihydropyri din-2-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzoate To a solution of methyl 4-((1'-methyl-5-nitro-6'-oxo-1',6'-dihydro-[2,2'-bipyridin]- 6- yl)amino)benzoate (225 mg, 1.84 mmol) in DMSO (15 mL) was added Na ₂ S ₂ O ₄ (1.28 g, 7.36 mmol). The mixture was stirred at 100 °C for 16 hr. The residue was diluted with H ₂ O (20 mL) and extracted with CH ₂ Cl ₂ (20 mL x 3). The combined organic layers were washed with brine (20 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 2 ~ 3%, MeOH in CH ₂ Cl ₂ ), methyl 4-(2- (2-aminopyridin-3-yl)-5-(1-methyl-6-oxo-1,6-dihydropyridin-2 -yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzoate (300 mg, yield: 31%) was obtained as a black brown solid. MS: m/z = 453.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chlororm-d) R 8.28 - 8.23 (m, 3H), 7.94 (dd, J = 5.2 Hz, 1.2 Hz, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.50 - 7.44 (m, 3H), 7.38 - 7.34 (m, 1H), 7.29 (d, J = 7.6 Hz, 1H), 6.67 - 6.63 (m, 1H), 6.50 (dd, J = 7.6, 5.2 Hz, 1H), 6.27 (dd, J = 5.6 Hz, 1.2 Hz, 1H), 3.99 (s, 3H), 3.45 (s, 3H). Step 4: 6-(2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5-b]pyridin-5- yl)-1-methylpyridin-2(1H)-one To a solution of methyl 4-(2-(2-aminopyridin-3-yl)-5-(1-methyl-6-oxo-1,6-dihydropyri din-2-yl)- 3H-imidazo[4,5-b]pyridin-3-yl)benzoate (100 mg, 221 µmol) in THF (3 mL) was added LiAlH ₄ (2.5 M, 177 μL) at 0 ºC. The mixture was stirred at 2 - 5ºC for 2 hr. The reaction mixture was quenched by Na ₂ SO ₄ ·10H ₂ O (about 0.5 g) at 0 °C, and the mixture was filtered. The filter cake was washed by CH ₂ Cl ₂ (5 mL x 3), and the filtrate was concentrated under reduced pressure to give 6-(2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5-b]pyridin-5-yl)- 1-methylpyridin-2(1H)-one (82 mg, yield: 89%) as a yellow solid. Compound 6 was directly used to the next step without purification. MS: m/z = 425.3 [M + H] ⁺ . Step 5: 6-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imi dazo[4,5-b]pyridin-5- yl)-1-methylpyridin-2(1H)-one To a solution of 6-(2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5- b]pyridin-5-yl)-1-methylpyridin-2(1H)-one (300 mg, 707 umol) in CH ₂ Cl ₂ (3 mL) was added SOCl ₂ (168 mg, 1.41 mmol) at 0 °C. The mixture was stirred at 40 °C for 2 hr. The reaction mixture was quenched by addition H ₂ O (0.5 mL) at 0 °C, then filtered and concentrated under reduced pressure to give 6-(2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)-1-methylpyridin-2(1H)-one (Intermediate 174, 300 mg, yield: 89%) as a yellow solid. MS: m/z = 443.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ )) δ 8.43 (d, J = 8.4 Hz, 1H), 8.05 - 8.01 (m, 1H), 7.92 - 7.88 (m, 1H), 7.76 (d, J = 8.4Hz, 1H), 7.70 - 7.62 (m, 3H), 7.53 (d, J = 8.0 Hz, 2H), 6.90 - 6.85 (m, 1H), 6.71 - 6.66 (m, 1H), 6.62 - 6.57 (m, 1H), 4.75 (s, 2H), 3.46 (s, 3H). [00356] Intermediate 175: 4-(Piperidin-4-ylamino)-1,3,5-triazine-2-carbonitrile Intermediate 175 was prepared in a manner similar to Intermediate 55. [00357] Intermediate 176: Methyl 4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin- 3-yl)benzoate Step 1: Methyl 4-((3-nitropyridin-2-yl)amino)benzoate To a solution of methyl 4-aminobenzoate (10 g, 66 mmol) were added DIEA (111g, 861 mmol) and 2-chloro-3-nitropyridine (12.6 g, 79 mmol). The mixture was stirred at 130 °C for 16 hr. The mixture was diluted with H ₂ O (500 mL) and extracted with EtOAc (500 mL × 2). The combined organic layers were washed with brine (1000 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a residue. After purified by column chromatography (Eluent of 0 ~ 10% EtOAc in petroleum ether), methyl 4-((3-nitropyridin-2- yl)amino)benzoate (7.2 g, yield: 40%) was obtained as a yellow solid. MS: m/z = 274.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 10.32 (br s, 1H), 8.58 - 8.53 (m, 2H), 8.05 (d, J = 8.8 Hz, 2H), 7.81 (d, J = 8.8 Hz, 2H), 6.93 (dd, J = 8.0, 4.8 Hz, 1H), 3.91 (s, 3H). Step 2: Methyl 4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)ben zoate To a solution of methyl 4-((3-nitropyridin-2-yl)amino)benzoate (7 g, 26 mmol) in DMSO (300 mL) were added Na ₂ S ₂ O ₄ (18 g, 102 mmol) and 2-aminonicotinaldehyde (3.8 g, 31 mmol). The mixture was stirred at 110 °C for 16 hr. The mixture was diluted with H ₂ O (1000 mL) and extracted with CH ₂ Cl ₂ (1000 mL × 2). The combined organic layers were washed with brine (1000 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by column chromatography (Eluent of 0 ~ 43% EtOAc in petroleum ether), methyl 4-(2-(2- aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzoate (Intermediate 176, 4.1 g, yield: 45%) was obtained as a yellowe solid. MS: m/z = 346.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.43 - 8.36 (m, 1H), 8.21 (d, J = 8.4 Hz, 2H), 8.14 - 8.06 (m, 2H), 7.49 (d, J = 8.4 Hz, 2H), 7.33 (dd, J = 8.0, 4.8 Hz, 1H), 7.04 (dd, J = 7.6, 1.2 Hz, 1H), 6.59 (br s, 2H), 6.37 (dd, J = 8.0, 4.8 Hz, 1H), 3.96 (s, 3H). [00358] Intermediate 177: 3-(3-(4-(Chloromethyl-d ₂ ) phenyl)-3H-imidazo [4,5-b]pyridin- 2-yl)pyridin-2-amine Step 1: (4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)ph enyl)methan-d2-ol To a solution of Intermediate 176 (400 mg, 1.2 mmol) in THF (10 mL) was added LiAlD4 (88 mg, 2.3 mmol) at 0 °C. The resulting mixture was stirred at 25 °C for 1 hr. The reaction mixture was quenched by Na ₂ SO ₄ ·10H ₂ O (2 g) at 0 °C, filtered and concentrated under reduced pressure to give a (4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)ph enyl)methan- d ₂ -ol (370 mg) as a yellow solid, which was used for next step directly. MS: m/z = 320.0 [M + H] ⁺ . Step 2: 3-(3-(4-(Chloromethyl-d ₂ ) phenyl)-3H-imidazo [4,5-b]pyridin-2-yl)pyridin-2-amine To a solution of 4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)phe nyl)methan-d ₂ -ol (370 mg, 1.2 mmol) in CH ₂ Cl ₂ (5 mL) was added dropwise SOCl ₂ (1.6 g, 14 mmol). The resulting mixture was stirred at 40 °C for 1 hr. The reaction mixture was quenched by Na ₂ CO ₃ (5 mL) at 25 °C, diluted with H ₂ O (10 mL) and extracted with EtOAc (10 mL x 2). The combined organic layers were washed with brine (10 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by flash chromatography on silica gel (Eluent of 0 ~ 50% EtOAc in petroleum ether), 3-(3-(4-(chloromethyl-d ₂ ) phenyl)-3H-imidazo [4,5-b]pyridin-2-yl)pyridin-2-amine (Intermediate 177, 90 mg, yield: 23% for 2 steps) was obtained as a yellow solid. MS: m/z = 337.9 [M + H] ⁺ . [00359] Intermediate 178: 4-(2-(2-Aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5- b]pyridin-3-yl)benzyl acetate Step 1: (4-((6-Chloro-3-nitropyridin-2-yl)amino)phenyl)methanol To a solution of 2,6-dichloro-3-nitropyridine (50 g, 259 mmol) and (4-aminophenyl)methanol (32 g, 259 mmol) in 1,4-dioxane (500 mL) was added DIEA (100 g, 777 mmol). The mixture was stirred at 70 °C for 1 hr. The reaction mixture was diluted with H ₂ O (500 mL) and extracted with CH ₂ Cl ₂ (300 mL x 2). The combined organic layers were washed with brine (200 mL), dried over Na ₂ SO ₄ , filtered and concentrated to give (4-((6-chloro-3-nitropyridin-2- yl)amino)phenyl)methanol (67 g, yield: 92%) as an orange solid, which was used in the next step without purification. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.11 (br s, 1H), 8.53 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 6.98 (d, J = 8.8 Hz, 1H), 5.20 (br s, 1H), 4.49 (s, 2H). Step 2: 4-((6-Chloro-3-nitropyridin-2-yl)amino)benzyl acetate To a solution of (4-((6-chloro-3-nitropyridin-2-yl)amino)phenyl)methanol (67 g, 239 mmol) in CH ₂ Cl ₂ (600 mL) was added Et3N (72.7 g, 718 mmol) and DMAP (2.93 g, 23.9 mmol) at 0 °C. The mixture was stirred at 0 °C for 10 min, and then Ac ₂ O (24.5 g, 239 mmol) in CH ₂ Cl ₂ (50 mL) was added dropwise at 0 °C. The resulting mixture was stirred at 25 °C for 16 hr. The reaction mixture was diluted with H ₂ O (500 mL) and extracted with CH ₂ Cl ₂ (500 mL x 2). The combined organic layers were washed with brine (500 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 1% MeOH in CH ₂ Cl ₂ ), 4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl acetate (36 g, yield: 45%) was obtained as an orange solid. MS: m/z = 321.8 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.14 (s, 1H), 8.55 (d, J = 8.4 Hz, 1H), 7.61 - 7.58 (m, 2H), 7.39 - 7.37 (m, 1H), 7.08 - 6.97 (m, 2H), 5.07 (s, 2H), 2.07 (s, 3H). Step 3: 4-(2-(2-Aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5-b]pyridin -3-yl)benzyl acetate To a solution of 4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl acetate (24 g, 74.6 mmol) and 2- aminonicotinaldehyde (10 g, 82 mmol) in DMSO (600 mL) was added Na ₂ S ₂ O ₄ (52 g, 298 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was diluted with H ₂ O (1500 mL) and extracted with CH ₂ Cl ₂ (150 mL x 3). The combined organic layers were washed with brine (500 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a residue. After purified by column chromatography (Eluent of 0 ~ 50% EtOAc in petroleum ether), 4-(2-(2-aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5-b]pyridin -3-yl)benzyl acetate (Intermediate 178, 5 g, yield: 14%) was obtained as a black brown solid. MS: m/z = 394.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.10 - 7.99 (m, 2H), 7.52 (d, J = 8.0 Hz, 2H), 7.41 - 7.32 (m, 3H), 7.08 (d, J = 7.2 Hz, 1H), 6.80 (br s, 2H), 6.40 (dd, J = 7.6, 5.2 Hz, 1H), 5.20 (s, 2H), 2.16 (s, 3H). [00360] Intermediate 179: 4-((7-Azaspiro[3.5]nonan-2-yl)amino)pyrimidine-2- carbonitrile Intermediate 179 was prepared in a manner similar to Intermediate 120. MS: m/z = 244.0 [M + H] ⁺ [00361] Intermediate 180: 4-((2-Azaspiro[3.3]heptan-6-yl)amino)pyrimidine-2- carbonitrile Intermediate 180 was prepared in a manner similar to Intermediate 120. [00362] Intermediate 181: 4-(Azetidin-3-ylamino)pyrimidine-2-carbonitrile Intermediate 181 was prepared in a manner similar to Intermediate 120. [00363] Intermediate 182: 4-((2-azaspiro[3.5]nonan-7-yl)amino)pyrimidine-2-carbonitril e Intermediate 182 was prepared in a manner similar to Intermediate 120. [00364] Intermediate: 183: 4-(2,6-diazaspiro[3.3]heptan-2-yl)pyrimidine-2-carbonitrile Intermediate 183 was prepared in a manner similar to Intermediate 120. [00365] Intermediate 184: 4-(3,8-Diazabicyclo[3.2.1]octan-3-yl)pyrimidine-2-carbonitri le Intermediate 184 was prepared in a manner similar to Intermediate 120. MS: m/z = 216.0 [M + H] ⁺ . [00366] Intermediate 185: 4-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)- yl)pyrimidine-2-carbonitrile Intermediate 185 was prepared in a manner similar to Intermediate 120. MS: m/z = 216.1 [M + H] ⁺ . [00367] Intermediate 186: 4-((Piperidin-4-yl-4-d)amino)pyrimidine-2-carbonitrile Step 1: Benzyl 4-((tert-butylsulfinyl)imino)piperidine-1-carboxylate A mixture of benzyl 4-oxopiperidine-1-carboxylate (5 g, 21.4 mmol), 2-methylpropane-2- sulfinamide (2.86 g, 23.6 mmol), tetraethoxytitanium (8.31 g, 36.4 mmol) in THF (100 mL) was degassed and purged with N ₂ three times, and then was stirred at 70 °C for 1 hr under N ₂ atmosphere. The reaction mixture was concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 30 % EtOAc in petroleum ether), benzyl 4-((tert- butylsulfinyl)imino)piperidine-1-carboxylate (4.3 g, yield: 60%) was obtained as a light-yellow oil. MS: m/z = 337.0 [M + H] ⁺ . ¹ H NMR (400MHz, Chloroform-d) δ 7.38 - 7.35 (m, 5H), 5.17 (s, 1H), 5.15 (s, 1H), 3.83 - 3.73 (m, 4H), 3.16 - 3.11 (m, 1H), 2.90 - 2.79 (m, 1H), 2.55 - 2.51 (m, 1H), 2.46 - 2.43 (m, 1H), 1.23 (s, 9H). Step 2: Benzyl 4-((tert-butylsulfinyl)amino)piperidine-1-carboxylate-4-d To a solution of benzyl 4-((tert-butylsulfinyl)imino)piperidine-1-carboxylate (3 g, 8.92 mmol) in THF (40 mL) was added LiAlD4 (675 mg, 17.8 mmol) at 0 °C. The mixture was stirred at 25 °C for 1 hr. The mixture was diluted with H ₂ O (60 mL) and extracted with EtOAc (40 mL x 3). The combined organic layers were washed with brine (30 mL x 3), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 50 ~ 60% EtOAc in CH ₂ Cl ₂ ), benzyl 4-((tert-butylsulfinyl)amino)piperidine-1- carboxylate-4-d (1.4 g, yield: 39%) was obtained as a colorless oil. MS: m/z = 340.1 [M + H] ⁺ . ¹ H NMR (400MHz, Chloroform-d) δ 7.41 - 7.30 (m, 5H), 5.13 (s, 2H), 4.14 - 4.06 (m, 2H), 3.05 - 2.90 (m, 2H), 2.01 - 1.93 (m, 2H), 1.52 - 1.40 (m, 2H), 1.21 (s, 9H). Step 3: Benzyl 4-aminopiperidine-1-carboxylate-4-d To a solution of benzyl 4-((tert-butylsulfinyl)amino)piperidine-1-carboxylate-4-d (1.31 g, 3.86 mmol) in 1,4-dioxane (10 mL) was added HCl/1,4-dioxane (4 M, 1.93 mL). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was filtered and concentrated under reduced pressure to give benzyl 4-aminopiperidine-1-carboxylate-4-d (900 mg, yield: 99%) as a colorless oil. MS: m/z = 236.1 [M + H] ⁺ . ¹ H NMR (400MHz, Methanol-d ₄ ) δ 7.41 - 7.28 (m, 5H), 5.12 (s, 2H), 4.25 - 4.21 (m, 2H), 3.37 - 3.33 (m, 2H), 2.02 (d, J = 12.8 Hz, 2H), 1.56 - 1.45 (m, 2H). Step 4: Benzyl 4-((2-cyanopyrimidin-4-yl)amino)piperidine-1-carboxylate-4-d To a solution of benzyl 4-aminopiperidine-1-carboxylate-4-d (500 mg, 2.12 mmol), 4- chloropyrimidine-2-carbonitrile (297 mg, 2.12 mmol) in DMF (10 mL) were added NaI (63.7 mg, 425 umol) and K ₂ CO ₃ (881 mg, 6.37 mmol). The mixture was stirred at 50 °C for 1 hr. The mixture was diluted with H ₂ O (10 mL) and extracted with CH ₂ Cl ₂ (20 mL x 3). The combined organic layers were washed with brine (20 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 40 ~ 50% EtOAc in petroleum ether), benzyl 4-((2-cyanopyrimidin-4-yl)amino)piperidine-1- carboxylate-4-d (330 mg, yield: 45%) was obtained as a colorless oil. MS: m/z = 339.1 [M + H] ⁺ . ¹ H NMR (400MHz, Chloroform-d) δ 8.26 - 8.12 (m, 1H), 7.39 - 7.34 (m, 5H), 6.44 (d, J = 5.6 Hz, 1H), 5.15 (s, 2H), 4.30 - 4.08 (m, 2H), 3.11 - 2.95 (m, 2H), 2.09 - 2.00 (m, 2H), 1.66 (br s, 2H). Step 5: 4-((Piperidin-4-yl-4-d)amino)pyrimidine-2-carbonitrile To a solution of benzyl 4-((2-cyanopyrimidin-4-yl)amino)piperidine-1-carboxylate-4-d (300 mg, 887 µmol) in CH ₂ Cl ₂ (10 mL) was added TMSI (887 mg, 4.43 mmol). The mixture was stirred at 25 °C for 1 hr. The mixture was filtered to give 4-((piperidin-4-yl-4-d)amino)pyrimidine-2- carbonitrile (Intermediate 186, 330 mg, yield: 45%) as a yellow solid. MS: m/z = 205.0 [M + H] ⁺ . ¹ H NMR (400MHz, Dimethylsulfoxide-d ₆ - 6.63 (m, 1H), 3.35 - 3.27 (m, 2H), 3.13 - 3.03 (m, 2H), 2.08 - 2.00 (m, 2H), 1.64 - 1.56 (m, 2H). [00368] Intermediate 187: N-(3-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)- 3H-imidazo[4,5-b]pyridin-5-yl)phenyl)acetamide Step 1: N-(3-(2-(2-Aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsily l)oxy)methyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)phenyl)acetamide A mixture of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-chlo ro-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (refer to Intermediate 117 for detail procedures, 500 mg, 1.07 mmol), (3-acetamidophenyl)boronic acid (288 mg, 1.61 mmol), Pd(dppf)Cl ₂ (78.5 mg, 107 µmol), K ₂ CO ₃ (444 mg, 3.22 mmol) in 1,4-dioxane (10 mL) and H ₂ O (2 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 100 °C for 16 hr under N ₂ atmosphere. The reaction mixture was diluted with H ₂ O (50 mL) and extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (eluent of 0~50% EtOAc in petroleum ether), N-(3-(2-(2-aminopyridin-3-yl)-3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-3H-imidazo[4,5-b]pyrid in-5-yl)phenyl)acetamide (500 mg, yield: 81%) was obtained as a gray solid. MS: m/z = 565.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.05 (s, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.12 (s, 1H), 8.01 (dd, J = 4.8, 1.6 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.67 (t, J = 8.8 Hz, 2H), 7.54 - 7.42 (m, 4H), 7.37 (t, J = 8.0 Hz, 1H), 7.19 (dd, J = 7.6, 1.6 Hz, 1H), 6.99 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 4.82 (s, 2H), 2.05 (s, 3H), 0.93 (s, 9H), 0.11 (s, 6H). Step 2: N-(3-(2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H -imidazo[4,5-b]pyridin- 5-yl)phenyl)acetamide A mixture of N-(3-(2-(2-aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsily l)oxy)methyl)phenyl)- 3H-imidazo[4,5-b]pyridin-5-yl)phenyl)acetamide (500 mg, 885 μmol) in TBAF (1 M, 5 mL) was stirred at 25 °C for 1 hr. The reaction mixture was diluted with H ₂ O (50 mL) and extracted with EtOAc (50 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. N-(3-(2-(2-aminopyridin-3-yl)- 3-(4-(hydroxymethyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)ph enyl)acetamide (400 mg, yield: 89%) was obtained as a gray solid. MS: m/z = 451.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.17 (s, 1H), 8.38 (d, J = 8.4 Hz, 2H), 8.19 (s, 1H), 8.14 (dd, J = 6.0, 1.2 Hz, 2H), 7.96 - 7.90 (m, 3H), 7.70 - 7.60 (m, 5H), 7.40 (t, J = 7.6 Hz, 2H), 6.91 (d, J = 7.6, 6.4 Hz, 1H), 4.87 (s, 2H), 2.06 (s, 3H). Step 3: N-(3-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5- yl)phenyl)acetamide To a mixture of N-(3-(2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H -imidazo[4,5- b]pyridin-5-yl)phenyl)acetamide (200 mg, 443 μmol) in CH ₂ Cl ₂ (4 mL) was added SOCl ₂ (3.28 g, 27.5 mmol). The mixture was stirred at 40 °C for 1 hr. The reaction mixture was filtered, and the filter cake was concentrated under reduced pressure. N-(3-(2-(2-Aminopyridin-3-yl)-3-(4- (chloromethyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)phenyl)a cetamide (Intermediate 187, 220 mg, yield: 86%) was obtained as a gray solid. MS: m/z = 469.0 [M + H] ⁺ . [00369] Intermediate 188: 3-(3-(4-(Chloromethyl)phenyl)-5-vinyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine Step 1: (4-(2-(2-Aminopyridin-3-yl)-5-vinyl-3H-imidazo[4,5-b]pyridin -3-yl)phenyl)methanol To a solution of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-viny l-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (refer to Intermediate 124 for detail procedures, 320 mg, 699 µmol) in THF (4 mL) was added TBAF (1 M, 2.80 mL). The mixture was stirred at 25 ºC for 0.5 hr. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (2 × 20 mL). The combined organic layers were dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. (4-(2-(2-Aminopyridin-3-yl)-5-vinyl-3H-imidazo[4,5-b]pyridin -3- yl)phenyl)methanol (240 mg, crude) was obtained as a brown oil. MS: m/z = 344.1 [M + H] ⁺ . Step 2: 3-(3-(4-(Chloromethyl)phenyl)-5-vinyl-3H-imidazo[4,5-b]pyrid in-2-yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-vinyl-3H-imidazo[4,5-b]pyridin -3- yl)phenyl)methanol (240 mg, 698 µmol) in CH ₂ Cl ₂ (2 mL) was added SOCl ₂ (332 mg, 2.80 mmol). The mixture was stirred at 40 °C for 0.5 hr. The mixture was concentrated under reduced pressure to give 3-(3-(4-(chloromethyl)phenyl)-5-vinyl-3H-imidazo[4,5-b]pyrid in-2- yl)pyridin-2-amine (Intermediate 188, 240 mg, yield: 86 %, HCl salt) as a yellow solid. MS: m/z = 361.9 [M + H] ⁺ . [00370] Intermediate 189: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-fluoropyridin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: 3-(3-(4-(((Tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-(5-f luoropyridin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine To a solution of Intermediate 129 (500 mg, 979 µmol) in 1,4-dioxane (16.5 mL) were added CuBr (105 mg, 734 µmol), Cs2CO3 (105 mg, 957 µmol), (5-fluoropyridin-2-yl)boronic acid (690 mg, 957 mmol) and cataCXium A Pd G3 (71 mg, 98 µmol) at 25 °C. The reaction mixture was degassed and purged with N ₂ three times. The mixture was stirred at 100 °C for 4 hr under N ₂ . The reaction mixture was then poured into H ₂ O (50 mL) and extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (40 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0~40% EtOAc in petroleum ether), 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-(5- fluoropyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2- amine (450 mg, yield: 85%) was obtained as a brown solid. MS: m/z = 527.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide- d ₆ ) δ 8.67 (d, J = 3.2 Hz, 1H), 8.40 (d, J = 8.4 Hz, 1H), 8.32 (d, J = 8.0 Hz, 1H), 8.25 - 8.17 (m, 1H), 8.04 - 7.98 (m, 1H), 7.87 - 7.78 (m, 1H), 7.55 – 7.45 (m, 4H), 7.25 - 7.16 (m, 1H), 7.11 - 6.88 (m, 2H), 6.43 - 6.35 (m, 1H), 4.83 (s, 2H), 0.95 - 0.92 (m, 9H), 0.13 - 0.11 (m, 6H). Step 2: (4-(2-(2-Aminopyridin-3-yl)-5-(5-fluoropyridin-2-yl)-3H-imid azo[4,5-b]pyridin-3- yl)phenyl)methanol To a solution of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-(5-f luoropyridin-2-yl)- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (450 mg, 854 µmol) in THF (5 mL) was added TBAF (670 mg, 2.5ml, 1M) at 25 °C. The mixture was stirred at 25 °C for 1 hr. The reaction mixture was poured into H ₂ O (20 mL). The mixture was extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (40 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. (4-(2-(2-Aminopyridin-3-yl)-5-(5-fluoropyridin-2-yl)-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (300 mg, crude) was obtained as a yellow solid. MS: m/z = 413.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.66 (d, J = 2.4 Hz, 1H), 8.40 (d, J = 6.4 Hz, 1H), 8.31 (d, J = 8.4 Hz, 1H), 8.22 (dd, J = 8.8, 4.8 Hz, 1H), 8.01 (dd, J = 4.8, 2.0 Hz, 1H), 7.87 - 7.80 (m, 1H), 7.53 - 7.44 (m, 4H), 7.23 (dd, J = 7.6, 1.6 Hz, 1H), 6.98 (br s, 2H), 6.42 (dd, J = 7.6, 4.8 Hz, 1H), 5.36 (br s, 1H), 4.61 (s, 2H). Step 3: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-fluoropyridin-2-yl)-3H-im idazo[4,5-b]pyridin-2- yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(5-fluoropyridin-2-yl)-3H-imid azo[4,5-b]pyridin- 3-yl)phenyl)methanol (300 mg, 727 µmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (433 mg, 3.6 mmol) at 25 °C. The mixture was stirred at 40 °C for 0.5 hr. The reaction mixture was concentrated under reduced pressure to give 3-(3-(4-(chloromethyl)phenyl)-5-(5-fluoropyridin- 2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (Intermediate 189, 300 mg, crude) as a yellow solid, which was used for the next step without further purification. MS: m/z = 431.0 [M ]+. 1H NMR (400 MHz, Dimethylsulfoxide-d6) δ 8.67 (d, J = 2.8 Hz, 1H), 8.41 (d, J = 8.4 Hz, 1H), 8.30 (d, J = 8.4 Hz, 1H), 8.24 (dd, J = 8.8, 4.8 Hz, 1H), 8.01 (dd, J = 4.8,1.6 Hz, 1H), 7.87 - 7.82 (m, 1H), 7.63 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 8.4 Hz, 2H), 7.25 - 7.21 (m, 1H), 6.90 (br s, 2H), 6.44 (dd, J = 7.6, 4.8 Hz, 1H), 4.88 (s, 2H). 19F NMR (400 MHz, Dimethylsulfoxide-d6) δ -127.227 [00371] Intermediate 190: 2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-N- methyl-3H-imidazo[4,5-b]pyridin-5-amine Intermediate 190 was prepared in a manner similar to Intermediate 114. MS: m/z = 364.9 [M + H] ⁺ . [00372] Intermediate 191: 4-(2,7-Diazaspiro[3.5]nonan-2-yl)pyrimidine-2-carbonitrile Intermediate 191 was prepared in a manner similar to Intermediate 120. MS: m/z = 230.0 [M + H] ⁺ . [00373] Intermediate 192: 4-(2,7-Diazaspiro[3.5]nonan-7-yl)pyrimidine-2-carbonitrile Intermediate 192 was prepared in a manner similar to Intermediate 120. MS: m/z = 230.0 [M + H] ⁺ . [00374] Intermediate 193: 3-(5-Bromo-3-(4-(chloromethyl)phenyl)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine Step 1: (4-(2-(2-Aminopyridin-3-yl)-5-bromo-3H-imidazo[4,5-b]pyridin -3-yl)phenyl)methanol To a solution of Intermediate 129 (5 g, 9.79 mmol) in THF (50 mL) was added TBAF (1 M, 14.7 mL). The mixture was degassed and purged with N ₂ three times and stirred at 25 ºC under N ₂ for 2 hr. The reaction mixture was quenched with saturated NH ₄ Cl (100 mL), then extracted with EtOAc (100 mL x 2). The combined organic layers were washed with brine (200 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure, (4-(2-(2-aminopyridin-3- yl)-5-bromo-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (3.88 g, crude) was obtained as a yellow solid which was used directly into the next step. MS: m/z = 395.9, 397.9 [M+H] ⁺ . Step 2: 3-(5-Bromo-3-(4-(chloromethyl)phenyl)-3H-imidazo[4,5-b]pyrid in-2-yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-bromo-3H-imidazo[4,5-b]pyridin -3- yl)phenyl)methanol (3.88 g, 9.79 mmol) in CH ₂ Cl ₂ (50 mL) was added SOCl ₂ (7.11 mL, 97.9 mmol). The mixture was degassed and purged with N ₂ three times and stirred at 25 ºC for 2 hr under N ₂ . The reaction mixture was concentrated under reduced pressure. 3-(5-Bromo-3-(4- (chloromethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin- 2-amine (Intermediate 193, 4.06 g, crude) was obtained as a gray solid which was used directly into the next step. MS: m/z = 414.0, 416.0 [M+H] ⁺ . [00375] Intermediate 194: 3-(5-Bromo-3-(4-(chloromethyl-d2)phenyl)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine Step 1: Methyl 4-((6-bromo-3-nitropyridin-2-yl)amino)benzoate To a solution of 2,6-dibromo-3-nitropyridine (10 g, 35.5 mmol) and methyl 4-aminobenzoate (5.36 g, 35.5 mmol) in 1,4-dioxane (100 mL) was added DIEA (18.5 mL, 106 mmol). The mixture was degassed and purged with N ₂ three times and stirred at 40 ºC for 16 hr under N ₂ . The reaction mixture was concentrated under reduced pressure. The crude product was triturated with EtOAc at 25 ºC for 30 mins. Methyl 4-((6-bromo-3-nitropyridin-2- yl)amino)benzoate (9.2 g, yield: 67%) was obtained as a red solid. MS: m/z = 351.7, 353.7 [M+H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 10.38 (s, 1H), 8.35 (d, J = 8.8 Hz, 1H), 8.07 (d, J = 8.8 Hz, 2H), 7.77 (d, J = 8.8 Hz, 2H), 7.05 (d, J = 8.8 Hz, 1H), 3.91 (s, 3H). Step 2: 4-(2-(2-Aminopyridin-3-yl)-5-bromo-3H-imidazo[4,5-b]pyridin- 3-yl)benzoate To a solution of methyl 4-((6-bromo-3-nitropyridin-2-yl)amino)benzoate (4.5 g, 12.8 mmol) and 2-aminonicotinaldehyde (1.72 g, 14.1 mmol) in DMSO (50 mL) was added Na ₂ S ₂ O ₄ (4.45 g, 25.6 mmol). The mixture was degassed and purged with N ₂ three times and stirred at 100 ºC for 16 hr under N ₂ . The reaction mixture was quenched with H ₂ O (200 mL) and then extracted with CH ₂ Cl ₂ (100 mL x 3). The combined organic layers were washed with brine (200 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (EtOAc in petroleum ether = 1 to 50%). 4-(2-(2-Aminopyridin-3-yl)-5- bromo-3H-imidazo[4,5-b]pyridin-3-yl)benzoate (2.2 g, yield: 36.5%) was obtained as a yellow solid. MS: m/z = 423.8, 425.8 [M+H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.20 (d, J = 8.4 Hz, 2H), 8.06 (dd, J = 4.4, 1.2 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.50 - 7.43 (m, 3H), 7.02 (dd, J = 8.0, 1.6 Hz, 1H), 6.69 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.97 (s, 3H). Step 3: (4-(2-(2-Aminopyridin-3-yl)-5-bromo-3H-imidazo[4,5-b]pyridin -3-yl)phenyl)methan-d ₂ - ol To a solution of methyl 4-(2-(2-aminopyridin-3-yl)-5-bromo-3H-imidazo[4,5-b]pyridin- 3- yl)benzoate (300 mg, 707 umol) in THF (30 mL) was added LiAlD ₄ (65.1 mg, 1.41 mmol). The mixture was degassed and purged with N ₂ three times and stirred at 0 °C for 1 hr under N ₂ . The reaction mixture was quenched with Na ₂ SO ₄ ·10H ₂ O (1 g) at 0 °C, and then filtered and concentrated under reduced pressure. (4-(2-(2-Aminopyridin-3-yl)-5-bromo-3H-imidazo[4,5- b]pyridin-3-yl)phenyl)methan-d ₂ -ol (190 mg, crude) was obtained as a yellow solid which was used directly into the next step. MS: m/z = 397.9, 399.9 [M + H] ⁺ . Step 4: 3-(5-Bromo-3-(4-(chloromethyl-d ₂ )phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2- amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-bromo-3H-imidazo[4,5-b]pyridin -3- yl)phenyl)methan-d ₂ -ol (190 mg, 477 µmol) in CH ₂ Cl ₂ (2 mL) was added SOCl ₂ (347 μl), 4.77 mmol). The mixture was degassed and purged with N ₂ three times and stirred at 25 ºC for 2 hr under N ₂ . The reaction mixture was concentrated under reduced pressure.3-(5-Bromo-3-(4- (chloromethyl-d ₂ )phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (Intermediate 194, 199 mg, crude) was obtained as a gray solid, which was used directly into the next step. MS: m/z = 416.0, 418.0 [M + H] ⁺ . [00376] Intermediate 195: 3-(3-(4-(Chloromethyl-d2)phenyl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: (4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H-imidazo[4, 5-b]pyridin-3- yl)phenyl)methan-d2-ol To a solution of methyl 4-(2-(2-aminopyridin-3-yl)-5-(4-fluorophenyl)-3H-imidazo[4,5 - b]pyridin-3-yl)benzoate (refer to Intermediate 107 for detail procedures, 900 mg, 2.0 mmol) in THF (3 mL) was added LiAlD4 (155 mg, 4.1 mmol) at 0 °C. The reaction mixture was stirred at 25 °C for 1 hr. The reaction mixture was quenched with Na ₂ SO ₄ ·10H ₂ O (203 mg) at 0 °C and filtered, concentrated under reduced pressure. The crude product (4-(2-(2-aminopyridin-3-yl)-5- (4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)methan -d2-ol (830 mg) was used into the next step without further purification. MS: m/z = 414.1 [M + H] ⁺ . ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -113.60 Step 2: 3-(3-(4-(Chloromethyl-d2)phenyl)-5-(4-fluorophenyl)-3H-imida zo[4,5-b]pyridin-2- yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(4-fluorophenyl)-3H-imidazo[4, 5-b]pyridin-3- yl)phenyl)methan-d2-ol (500 mg, 1.2 mmol) in CH ₂ Cl ₂ (10 mL) was added SOCl ₂ (719 mg, 6.0 mmol) at 25 °C. The reaction mixture was stirred at 40 °C for 0.5 hr. The reaction mixture was concentrated under reduced pressure. The crude product 3-(3-(4-(chloromethyl-d2)phenyl)-5- (4-fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-ami ne (Intermediate 195, 500 mg, yield: 74%) was used into the next step without further purification. MS: m/z = 432.0 [M + H] ⁺ . ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -113.05. [00377] Intermediate 196 : 3-(3-(4-(Chloromethyl)phenyl)-5,7-dimethyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine

Step 1: 4,6-Dimethyl-3-nitropyridin-2-ol To a solution of 2-nitroacetamide (12.3 g, 118 mmol) in H ₂ O (120 mL) were added pentane-2,4- dione (14.4 g, 143 mmol), Py (3.09 g, 39.1 mmol), AcOH (2.35 g, 39.2 mmol). The mixture was stirred at 25 °C for 7 days. The mixture was filtered and the filter cake was concentrated under reduced pressure to give 4,6-dimethyl-3-nitropyridin-2-ol (4.5 g, yield: 20%) as a light- yellow solid. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 12.14 (s, 1H), 6.08 (s, 1H), 2.20 (s, 3H), 2.14 (s, 3H). Step 2: 2-Chloro-4,6-dimethyl-3-nitropyridine To a solution of 4,6-dimethyl-3-nitropyridin-2-ol (4 g, 23.8 mmol) in POCl ₃ (65.8 g, 429 mmol) was stirred at 100 °C for 2 hr under N ₂ atmosphere. The reaction mixture was quenched with H ₂ O (300 mL) at 25 °C, and then extracted with EtOAc (500 mL x 2). The combined organic layers were washed with brine (300 mL x 2), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 6% EtOAc in petroleum ether), 2-chloro-4,6-dimethyl-3-nitropyridine (3.8 g, yield: 85%) was obtained as a light-yellow solid. MS: m/z = 186.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ 7.49 (s, 1H), 2.50 (s, 3H), 2.32 (s, 3H). Step 3: (4-((4,6-Dimethyl-3-nitropyridin-2-yl)amino)phenyl)methanol To a solution of 2-chloro-4,6-dimethyl-3-nitropyridine (2.4 g, 12.8 mmol) and (4- aminophenyl)methanol (1.74 g, 14.1 mmol) in 1,4-dioxane (30 mL) and was added DIEA (4.99 g, 38.6 mmol). The mixture was stirred at 110 °C for 48 hr. The reaction mixture was diluted H ₂ O (300 mL) and extrated with EtOAc (500 mL x 2). The combined organic layers were washed with brine (300 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give (4-((4,6-dimethyl-3-nitropyridin-2-yl)amino)phenyl)methanol (3.3 g, yield: 78%) was obtained as a red solid. MS: m/z = 274.0 [M + H] ⁺ . Step 4: 4-((4,6-Dimethyl-3-nitropyridin-2-yl)amino)benzyl acetate To a mixture of (4-((4,6-dimethyl-3-nitropyridin-2-yl)amino)phenyl)methanol (3 g, 10.9 mmol), DMAP (134 mg, 1.10 mmol) and TEA (3.33 g, 32.9 mmol) in CH ₂ Cl ₂ (50 mL) was added acetic anhydride (1.12 g, 10.9 mmol), then degassed and purged with N ₂ three times and stirred at 0 °C for 2 hr under N ₂ atmosphere. The reaction mixture was diluted with H ₂ O (200 mL) and extracted with EtOAc (200 mL x 3). The combined organic layers were washed with brine (200 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 50% EtOAc in petroleum ether), 4-((4,6- dimethyl-3-nitropyridin-2-yl)amino)benzyl acetate (970 mg, yield: 28%) was obtained as a yellow solid. MS: m/z = 316.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 9.59 (s, 1H), 7.64 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 6.56 (s, 1H), 5.09 (s, 2H), 2.55 (s, 3H), 2.44 (s, 3H), 2.10 (s, 3H). Step 5: 4-(2-(2-Aminopyridin-3-yl)-5,7-dimethyl-3H-imidazo[4,5-b]pyr idin-3-yl)benzyl acetate A mixture of 4-((4,6-dimethyl-3-nitropyridin-2-yl)amino)benzyl acetate (970 mg, 3.08 mmol), 2-aminonicotinaldehyde (413 mg, 3.38 mmol) and Na ₂ S ₂ O ₄ (2.14 g, 12.3 mmol) in DMSO (100 mL) was degassed and purged with N ₂ three times, and then was stirred at 100 °C for 16 hr under N ₂ atmosphere. The reaction mixture was diluted with H ₂ O (100 mL) and extracted with EtOAc (100 mL x 3). The combined organic layers were washed with brine (200 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 50% EtOAc in petroleum ether), 4-(2-(2-aminopyridin-3-yl)-5,7- dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)benzyl acetate (550 mg, yield: 44%) was obtained as a yellow solid. MS: m/z = 388.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 7.97 (dd, J = 4.8, 2.0 Hz, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.10 (s, 1H), 6.93 (s, 2H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 5.16 (s, 2H), 2.62 (s, 3H), 2.47 (s, 3H), 2.11 (s, 3H). Step 6: (4-(2-(2-Aminopyridin-3-yl)-5,7-dimethyl-3H-imidazo[4,5-b]py ridin-3- yl)phenyl)methanol To a mixture of 4-(2-(2-aminopyridin-3-yl)-5,7-dimethyl-3H-imidazo[4,5-b]pyr idin-3-yl)benzyl acetate (500 mg, 1.29 mmol) in MeOH (15 mL), THF (15 mL) and H ₂ O (7 mL) was added K ₂ CO ₃ (178 mg, 1.29 mmol). The mixture was stirred at 25 °C for 0.5 hr. The mixture was filtered, concentrated under reduced pressure, (4-(2-(2-aminopyridin-3-yl)-5,7-dimethyl-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (400 mg, yield: 80%) was obtained as a yellow solid. MS: m/z = 346.1 [M + H] ⁺ . Step 7: 3-(3-(4-(Chloromethyl)phenyl)-5,7-dimethyl-3H-imidazo[4,5-b] pyridin-2-yl)pyridin-2- amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5,7-dimethyl-3H-imidazo[4,5-b]py ridin-3- yl)phenyl)methanol (400 mg, 1.16 mmol) in CH ₂ Cl ₂ (15 mL) was added SOCl ₂ (827 mg, 6.95 mmol). The mixture was stirred at 40 °C for 1 hr. The mixture was concentrated to give 3-(3- (4-(chloromethyl)phenyl)-5,7-dimethyl-3H-imidazo[4,5-b]pyrid in-2-yl)pyridin-2-amine (Intermediate 196, 350 mg, yield: 88%) as a yellow solid, which was used in the next step without further purification. MS: m/z = 364.0 [M + H] ⁺ . [00378] Intermediate 197: 3-(3-(4-(chloromethyl)phenyl)-5-(pyridin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: 4-((5-Nitro-[2,2'-bipyridin]-6-yl)amino)benzyl acetate To a solution of 4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl acetate (refer to Intermediate 178 for detail procedures, 500 mg, 1.6 mmol) in 1,4-dioxane (10 mL) were added CuBr (167 mg, 1.2 mmol), Cs ₂ CO ₃ (1.5 g, 4.7 µmol), pyridin-2-ylboronic acid (573 mg, 4.7 mmol) and cataCXium A PdG3 (113 mg, 155 µmol) at 25 °C, the reaction mixture was degassed and purged with N ₂ three times. The mixture was stirred at 100 °C for 4 hr under N ₂ . The reaction mixture was poured into H ₂ O (50 mL), then extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (40 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0~45% EtOAc in petroleum ether), 4-((5-nitro-[2,2'-bipyridin]-6-yl)amino)benzyl acetate (300 mg, yield: 43%) was obtained as a yellow solid. MS: m/z = 365.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.11 (s, 1H), 8.76 (d, J = 4.0 Hz, 1H), 8.70 (d, J = 8.8 Hz, 1H), 8.20 (d, J = 8.0 Hz, 1H), 8.05 - 7.95 (m, 2H), 7.81 - 7.75 (m, 2H), 7.56 (dd, J = 7.2, 4.8 Hz, 1H), 7.45 (d, J = 8.4 Hz, 2H), 5.10 (s, 2H), 2.09 (s, 3H). Step 2: 4-(2-(2-Aminopyridin-3-yl)-5-(pyridin-2-yl)-3H-imidazo[4,5-b ]pyridin-3-yl)benzyl acetate To a solution of 4-((5-nitro-[2,2'-bipyridin]-6-yl)amino)benzyl acetate (300 mg, 823 µmol) in DMSO (10 mL) were added 2-aminonicotinaldehyde (121 mg, 988 µmol) and Na ₂ S ₂ O ₄ (573 mg, 3.3 mmol) at 25 °C. The mixture was stirred at 100 °C for 12 hr. The reaction mixture was poured into H ₂ O (100 mL). The mixture was extracted with CH ₂ Cl ₂ (50 mL x 2). The combined organic layers were washed with 400 mL brine, dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0~3% MeOH in CH ₂ Cl ₂ ), 4-(2-(2-aminopyridin-3-yl)-5-(pyridin-2-yl)-3H-imidazo[4,5-b ]pyridin-3-yl)benzyl acetate (200 mg, yield: 56%) was obtained as a yellow solid. MS: m/z = 437.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.67 (d, J = 4.0 Hz, 1H), 8.47 (d, J = 8.4 Hz, 1H), 8.32 (d, J = 8.4 Hz, 1H), 8.19 (d, J = 8.0 Hz, 1H), 8.02 (dd, J = 4.8, 2.0 Hz, 1H), 7.94 - 7.87 (m, 1H), 7.59 - 7.51 (m, 4H), 7.40 (dd, J = 7.2, 5.6 Hz, 1H), 7.25 (dd, J = 7.6, 2.0 Hz, 1H), 6.90 (s, 2H), 6.44 (dd, J = 7.6, 4.8 Hz, 1H), 5.19 (s, 2H), 2.12 (s, 3H). Step 3: (4-(2-(2-Aminopyridin-3-yl)-5-(pyridin-2-yl)-3H-imidazo[4,5- b]pyridin-3- yl)phenyl)methanol To a solution of 4-(2-(2-aminopyridin-3-yl)-5-(pyridin-2-yl)-3H-imidazo[4,5-b ]pyridin-3- yl)benzyl acetate (200 mg, 458 µmol) in H ₂ O (1 mL) and MeOH (2 mL) THF (2 mL) was added K ₂ CO ₃ (63 mg, 458 µmol) at 25 °C. The mixture was stirred at 25 °C for 1 hr. The reaction mixture was poured into H ₂ O (20 mL). The mixture was extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (40 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated, (4-(2-(2-aminopyridin-3-yl)-5-(5-fluoropyridin-2-yl)-3H-imid azo[4,5- b]pyridin-3-yl)phenyl)methanol (300 mg, crude) was obtained as a yellow solid. MS: m/z = 395.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.64 - 8.58 (m, 1H), 8.44 (d, J = 8.4 Hz, 1H), 8.30 - 8.20 (m, 2H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.87 - 7.80 (m, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.40 - 7.32 (m, 2H), 6.48 (dd, J = 7.6, 5.2 Hz, 1H), 4.72 (s, 2H). Step 4: 3-(3-(4-(Chloromethyl)phenyl)-5-(pyridin-2-yl)-3H-imidazo[4, 5-b]pyridin-2-yl)pyridin- 2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(5-fluoropyridin-2-yl)-3H-imid azo[4,5-b]pyridin- 3-yl)phenyl)methanol (180 mg, 456 µmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (271 mg, 2.3 mmol) at 25 °C. The mixture was stirred at 40 °C for 0.5 hr. The reaction mixture was concentrated under reduced pressure to give 3-(3-(4-(chloromethyl)phenyl)-5-(pyridin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (Intermediate 197, 188 mg, crude) as a yellow solid, which was used for the next step without further purification. MS: m/z = 413.0 [M + H] ⁺ . [00379] Intermediate 198: 3-(3-(4-(Chloromethyl)phenyl)-5-(pyrrolidin-1-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: N-(4-(((tert-Butyldimethylsilyl)oxy)methyl)phenyl)-3-nitro-6 -(pyrrolidin-1-yl)pyridin-2- amine To a solution of N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-6-chloro- 3-nitropyridin-2- amine (refer to Intermediate 105 for detail procedures, 3 g, 7.62 mmol) in MeCN (50 mL) were added DIEA (2.95 g, 22.9 mmol) and pyrrolidine (1.23 g, 11.4 mmol, HCl). The mixture was stirred at 90 °C for 12 hr. The reaction mixture was concentrated. The residue was dissolved in EtOAc (50 mL), washed with brine (50 mL x 2), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. N-(4-(((Tert-butyldimethylsilyl)oxy)methyl)phenyl)-3-nitro-6 -(pyrrolidin-1- yl)pyridin-2-amine (3 g, yield: 92%) was obtained as a brown solid, which was used directly into the next step. MS: m/z = 429.1 [M + H] ⁺ . Step 2: (4-(2-(2-Aminopyridin-3-yl)-5-(pyrrolidin-1-yl)-3H-imidazo[4 ,5-b]pyridin-3- yl)phenyl)methanol To a solution of N-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-3-nitro-6 -(pyrrolidin-1- yl)pyridin-2-amine (1.5 g, 3.50 mmol) in DMSO (30 mL) were added Na ₂ S ₂ O ₄ (1.83 g, 10.5 mmol) and 2-aminonicotinaldehyde (470 mg, 3.85 mmol). The mixture was stirred at 100 °C for 12 hr. Saturated NaHCO ₃ (50 mL) was added to the mixture and the mixture was extracted with CH ₂ Cl ₂ (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by prep-HPLC (column: Xtimate C18150 x 40 mm x 10 μm; mobile phase: [water (NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN]; gradient: 35% - 65% B over 8 min), (4-(2-(2-aminopyridin-3-yl)-5-(pyrrolidin-1-yl)-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (200 mg, yield:15%) was obtained as a yellow solid. MS: m/z = 387.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 7.96 - 7.86 (m, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.35 - 7.28 (m, 2H), 7.11 - 6.98 (m, 3H), 6.49 (d, J = 8.8 Hz, 1H), 6.33 (dd, J = 7.6, 4.8 Hz, 1H), 5.38 - 5.30 (m, 1H), 4.57 (d, J = 5.6 Hz, 2H), 2.59 - 2.52 (m, 2H), 2.49 - 2.47 (m, 2H), 1.96 - 1.87 (m, 4H). Step 3: 3-(3-(4-(Chloromethyl)phenyl)-5-(pyrrolidin-1-yl)-3H-imidazo [4,5-b]pyridin-2- yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(pyrrolidin-l-yl)-3H-imidazo[4 ,5-b]pyridin-3- yl)phenyl)methanol (100 mg, 259 μmol) in CH2Cl2 (3 mL) was added SOCl2 (92.4 mg, 776 μmol) at 20 °C. The mixture was stirred at 20 °C for 2 hr. The reaction mixture was concentrated. 3-(3-(4-(Chloromethyl)phenyl)-5-(pyrrolidin-l-yl)-3H-imidazo [4,5-b]pyridin-2- yl)pyridin-2-amine (Intermediate 198, 105 mg, yield: 100%) was obtained as a yellow solid, which was used directly into the next step. MS: m/z = 405.1 [M + H] ⁺ .

[00380] Intermediate 199: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-methoxypyridin-4-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Step 1 : 3-(3-(4-(((Tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-(2-m ethoxypyridin-4-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

To a solution of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-chlo ro-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (refer to Intermediate 117 for detail procedures, 0.5 g, 1.07 mmol) in 1,4-dioxane (5 mL), H ₂ O (1 mL) were added (2-methoxypyridin-4-yl)boronic acid (230 mg, 1.50 mmol), Pd(dppf)Cl ₂ (78.5 mg, 107 μmol), and CS ₂ CO ₃ (445 mg, 1.37 mmol). The mixture was degassed and purged with N2 three times and stirred at 100 °C for 2 hr under N2 atmosphere. The mixture was quenched with H ₂ O (20 mL) and extrcted with EtOAc (8 mL x 3). The combined organic layers were washed with brine (20 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 62% EtOAc in petroleum ether), 3-(3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-5-(2-methoxypyridin-4- yl)-3H-imidazo[4,5-b]pyri din-2- yl)pyridin-2-amine (323 mg, yield: 88%) was obtained as a black brown solid. MS: m/z = 539.2 [M+H] ⁺ .

Step 2: (4-(2-(2-Aminopyridin-3-yl)-5-(2-methoxypyridin-4-yl)-3H-imi dazo[4,5-b]pyridin-3- yl)phenyl)methanol

To a solution of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-(2-m ethoxypyridin-4- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (323 mg, 600 μmol) in THF (5 mL) was added TBAF (1 M in THF, 959 μL). The mixture was stirred at 25 °C for 1 hr. The reaction was quenched with H ₂ O (10 mL) and extracted with EtOAc (8 mL x 2), then concentrated. (4- (2-(2-Aminopyridin-3-yl)-5-(2-methoxypyridin-4-yl)-3H-imidaz o[4,5-b]pyridin-3- yl)phenyl)methanol (254 mg, yield :97%) was obtained as a brown solid. MS: m/z = 425.1 [M+H] ⁺ . Step 3: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-methoxypyridin-4-yl)-3H-i midazo[4,5-b]pyridin-2- yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(2-methoxypyridin-4-yl)-3H-imi dazo[4,5- b]pyridin-3-yl)phenyl)methanol (500 mg, 1.18 mmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (257 μL, 3.53 mmol). The mixture was stirred at 25 ºC for 1 hr. The reaction mixture was concentrated. 3-(3-(4-(Chloromethyl)phenyl)-5-(2-methoxypyridin-4-yl)-3H-i midazo[4,5- b]pyridin-2-yl)pyridin-2-amine (Intermediate 199, 500 mg, yield: 94%) was obtained as a black solid and used for the next step without further purification. MS: m/z = 443.2 [M+H] ⁺ . [00381] Intermediate 200: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-methoxypyridin-3-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 200 was prepared in a manner similar to Intermediate 144. MS: m/z = 443.2 [M+H] ⁺ . [00382] Intermediate 201: N-Methyl-N-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl)acetamide Step 1: N-(3-Bromophenyl)-N-methylacetamide To a solution of 3-bromo-N-methyl-aniline (500 mg, 2.69 mmol) in CH ₂ Cl ₂ (10 mL) were added TEA (816 mg, 8.06 mmol) and AcCl (316 mg, 4.03 mmol) at 25 °C. This mixture was stirred at 25 °C for 1 hr. The mixture was quenched with H ₂ O (30 mL) and extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated. N-(3-bromophenyl)-N-methylacetamide (600 mg, yield: 97.9%) was obtained as a yellow oil, which was used directly without purification. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 7.64 (s, 1H), 7.53 (s, 1H), 7.42 - 7.32 (m, 2 H), 3.40 - 3.19 (m, 3 H), 1.88 - 1.68 (m, 3 H). Step 2: N-Methyl-N-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)p henyl)acetamide To a solution of N-(3-bromophenyl)-N-methyl-acetamide (500 mg, 2.19 mmol) and 4,4,5,5- tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)- 1,3,2-dioxaborolane (835 mg, 3.29 mmol) in 1,4-dioxane (20 mL) were added AcOK (861 mg, 8.77 mmol) and Pd(dppf)Cl ₂ (160 mg, 219 µmol) at 25 ºC. This mixture was stirred at 100 ºC for 12 hr under N ₂ . The mixture was quenched with H ₂ O (30 mL) and extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated. N- methyl-N-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phe nyl)acetamide (Intermediate 201, 600 mg, yield: 99.5%) was obtained as a black solid, which was used directly without purification. MS: m/z = 275.8 [M + H] ⁺ . [00383] Intermediate 202: 3-(3-(4-(Chloromethyl)phenyl)-5-(3-methoxypyridin-4-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 202 was prepared in a manner similar to Intermediate 144. MS: m/z = 443.1 [M+H] ⁺ . [00384] Intermediate 203: 3-(3-(4-(Chloromethyl)phenyl)-5-(6-methoxypyridin-3-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: 3-(3-(4-(((Tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-(6-m ethoxypyridin-3-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine To a solution of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-chlo ro-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (refer to Intermediate 117 for detail procedures, 500 mg, 1.07 mmol) in 1,4-dioxane (5 mL) and H ₂ O (1 mL) were added Pd(dppf)Cl ₂ (78.5 mg, 107 µmol), (6-methoxy-3-pyridyl)boronic acid (213 mg, 1.39 mmol) and Cs ₂ CO ₃ (1.05 g, 3.22 mmol), the mixture was degassed and purged with N ₂ three times and stirred at 100 °C for 2 hr under N ₂ atmosphere. The mixture was diluted with H ₂ O (50 mL) and extracted with EtOAc (30 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0 ~ 80% EtOAc in petroleum ether), 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-(6- methoxypyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2 -amine (450 mg, yield: 77.9%) was obtained as a brown solid. MS: m/z = 539.2 [M+H] ⁺ . Step 2: (4-(2-(2-Aminopyridin-3-yl)-5-(6-methoxypyridin-3-yl)-3H-imi dazo[4,5-b]pyridin-3- yl)phenyl)methanol To a solution of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-(6-m ethoxypyridin-3- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (440 mg, 817 µmol) in THF (4 mL) was added TBAF (1 M in THF, 1 mL). The mixture was stirred at 25 °C for 2 hr. The mixture was diluted with H ₂ O (50 mL) and extracted with EtOAc (2 x 20 mL). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. (4-(2-(2-Aminopyridin-3-yl)-5- (6-methoxypyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)phenyl )methanol (250 mg, yield: 72.1%) was obtained as a brown solid, which was used in the next step directly. MS: m/z = 425.2 [M+H] ⁺ . Step 3: 3-(3-(4-(Chloromethyl)phenyl)-5-(6-methoxypyridin-3-yl)-3H-i midazo[4,5-b]pyridin-2- yl)pyridin-2-amine To a solution of (4-(2(2-aminopyridin-3-yl)-5-(6-methoxypyridin-3-yl)-3H-imid azo[4,5- b]pyridin-3-yl)phenyl)methanol (240 mg, 565 µmol) in CH ₂ Cl ₂ (3 mL) was added SOCl ₂ (202 mg, 1.70 mmol). The mixture was stirred at 25 °C for 2 hr, then was concentrated. 3-(3-(4- (Chloromethyl)phenyl)-5-(6-methoxypyridin-3-yl)-3H-imidazo[4 ,5-b]pyridin-2-yl)pyridin-2- amine (Intermediate 203, 250 mg, yield: 99.8%) was obtained as a brown solid, which was used in the next step directly. MS: m/z = 443.1 [M+H] ⁺ . [00385] Intermediate 204: N-Methyl-N-(1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl)piperidin-4-yl)acetamide Step 1: N-(1-(3-Bromophenyl)piperidin-4-yl)acetamide A mixture of 1,3-dibromobenzene (5 g, 21.2 mmol), N-(piperidin-4-yl)acetamide (3.01 g, 21.2 mmol), Pd ₂ (dba) ₃ (970 mg, 1.06 mmol), BINAP (990 mg, 1.59 mmol) and t-BuONa (2.44 g, 25.4 mmol) in toluene (120 mL) was stirred at 80 °C for 16 hr under N ₂ . After cooling to 25 °C, the mixture was diluted with EtOAc (50 mL) and filtered, concentrated. After purified by silica gel flash chromatography (EtOAc in petroleum ether = 50% - 100%), N-(1-(3- bromophenyl)piperidin-4-yl)acetamide (4.02 g, yield: 63.8%) was obtained as an off-white solid. MS: m/z = 297.0, 299.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 7.81 (d, J = 7.6 Hz, 1H), 7.14 - 7.09 (m, 1H), 7.07 - 7.04 (m, 1H), 6.93 (dd, J = 8.4, 2.0 Hz, 1H), 6.87 (dd, J = 7.6, 0.8 Hz, 1H), 3.78 - 3.62 (m, 3H), 2.86 - 2.77 (m, 2H), 1.81 - 1.73 (m, 5H), 1.46 - 1.35 (m, 2H). Step 2: N-(1-(3-Bromophenyl)piperidin-4-yl)-N-methylacetamide To a solution of N-(1-(3-bromophenyl)piperidin-4-yl)acetamide (2 g, 6.73 mmol) in THF (50 mL) was added NaH (1.08 g, 26.9 mmol, 60% in mineral oil) in portions at 0 °C and stirred at 20 °C for 10 min under N ₂ , then added the MeI (2.87 g, 20.2 mmol) at 0 °C and stirred at 20 °C for 12 hr. The reaction mixture was slowly quenched with water (50 mL) at 0° C and extracted with EtOAc (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na ₂ SO ₄ and filtered, concentrated. After purified by silica gel flash chromatography (EtOAc in petroleum ether = 20% - 100%), N-(1-(3-bromophenyl)piperidin-4- yl)-N-methylacetamide (1.8 g, yield: 85.9%) was obtained as a brown oil. MS: m/z = 310.9, 312.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 7.16 - 7.08 (m, 1H), 7.07 (d, J = 2.4 Hz,, 1H), 6.94 (d, J = 8.0 Hz, 1H), 6.88 (d, J = 7.6 Hz, 1H), 4.51 - 4.37 (m, 0.5H), 3.83 - 3.73 (m, 2.5H), 2.88 - 2.78 (m, 4H), 2.65 (s, 1H), 2.07 (s, 1H), 1.99 (s, 2H), 1.84 - 1.62 (m, 3H), 1.53 - 1.47 (m, 1H). Step 3: N-Methyl-N-(1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-y l)phenyl)piperidin-4- yl)acetamide A mixture of N-(1-(3-bromophenyl)piperidin-4-yl)-N-methylacetamide (1.8 g, 5.78 mmol), 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborola n-2-yl)-1,3,2-dioxaborolane (1.76 g, 6.94 mmol), Pd(dppf)Cl ₂ (212 mg, 289 µmol) and K ₂ CO ₃ (2.40 g, 17.4 mmol) in 1,4-dioxane (50 mL) was stirred at 80 °C for 12 hr under N ₂ . The mixture was diluted with water (50 mL) at 20 °C and extracted with EtOAc (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated. N-Methyl-N-(1-(3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidi n-4-yl)acetamide (Intermediate 204, 2 g, 5.58 mmol, yield: 96.5%) was obtained as a gray solid, which was used directly into the next step. MS: m/z = 359.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 7.39 (s, 1H), 7.36 - 7.26 (m, 2H), 7.05 (d, J = 6.4 Hz, 1H), 4.69 - 4.61 (m, 1H), 3.84 - 3.74 (m, 2H), 2.90 - 2.75 (m, 5H), 2.16 (s, 1H), 2.11 (s, 2H), 2.05 - 2.01 (m, 1H), 1.79 - 1.68 (m, 3H), 1.34 (s, 12H). [00386] Intermediate 205: 3-(3-(4-(Chloromethyl)phenyl)-5-(4-fluoro-2- (trifluoromethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrid in-2-amine Intermediate 205 was prepared in a manner similar to Intermediate 144. MS: m/z = 498.1 [M + H] ⁺ . [00387] Intermediate 206: 3-(3-(4-(Chloromethyl)phenyl)-5-(p-tolyl)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine Intermediate 206 was prepared in a manner similar to Intermediate 144. MS: m/z = 426.3 [M + H] ⁺ [00388] Intermediate 207: 3-(3-(4-(Chloromethyl)phenyl)-5-(3-(trifluoromethyl)phenyl)- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 207 was prepared in a manner similar to Intermediate 144. MS: m/z = 480.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.52 (br s, 1H), 8.42 (d, J = 8.4 Hz, 1H), 8.34 - 8.40 (m, 2H), 8.22 (d, J = 8.4 Hz, 1H), 8.17 (dd, J = 6.0, 1.6 Hz, 1H), 7.93 (dd, J = 7.6, 1.6 Hz, 1H), 7.71 - 7.81 (m, 2H), 7.64 - 7.60 (m, 4H), 6.92 (t, J = 7.2 Hz, 1H), 4.88 (s, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -61.094. [00389] Intermediate 208: 3-(1-(4-(Chloromethyl)phenyl)-1H-benzo[d]imidazol-2- yl)pyridin-2-amine

Step 1: (4-((2-Nitrophenyl)amino)phenyl)methanol To a solution of 1-fluoro-2-nitrobenzene (5 g, 35.4 mmol) and (4-aminophenyl)methanol (4.36 g, 35.4 mmol) in DMSO (50 mL) was added DIPEA (13.7 g, 106 mmol) at 20 °C. The reaction mixture was stirred at 100 °C for 12 hr. The mixture was diluted with H2O (100 mL) and the mixture was extracted with EtOAc (100 mL x 3). The combined organic layers were washed with brine (100 mL x 2), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. (4-((2-Nitrophenyl)amino)phenyl)methanol (8.66 g, crude) was obtained as brown oil, which was used directly into the next step. Step 2: 4-((2-Nitrophenyl)amino)benzyl acetate To a solution of (4-((2-nitrophenyl)amino)phenyl)methanol (2.8 g, 11.5 mmol) in CH ₂ Cl ₂ (30 mL) were added DMAP (140 mg, 1.15 mmol), TEA (3.48 g, 34.4 mmol) and Ac ₂ O (1.76 g, 17.2 mmol). The mixture was stirred at 20 °C for 1 hr. H ₂ O (30 mL) was added and the mixture was extracted with CH ₂ Cl ₂ (30 mL x 3). The combined organic layers were washed with brine (30 mL x 2), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (EtOAc in petroleum ether = 0 ~ 20 %), 4-((2- nitrophenyl)amino)benzyl acetate (1.97 g, yield: 60%) was obtained as a brown oil. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.34 (s, 1H), 8.11 (dd, J = 8.4, 1.6 Hz, 1H), 7.54 - 7.48 (m, 1H), 7.42 - 7.38 (m, 2H), 7.33 - 7.29 (m, 2H), 7.23 (d, J = 8.0 Hz, 1H), 6.92 - 6.87 (m, 1H), 5.06 (s, 2H), 2.07 (s, 3H). Step 3: 4-(2-(2-Aminopyridin-3-yl)-1H-benzo[d]imidazol-1-yl)benzyl acetate To a solution of 4-((2-nitrophenyl)amino)benzyl acetate (950 mg, 3.32 mmol) in DMSO (30 mL) were added Na ₂ S ₂ O ₄ (1.73 g, 9.96 mmol) and 2-aminopyridine-3-carbaldehyde (446 mg, 3.65 mmol). The mixture was stirred at 100 °C for 12 hr. Brine (30 mL) was added to the mixture, and it was extracted with CH ₂ Cl ₂ (30 mL x 2). The combined organic phase was washed with brine (30 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (EtOAc in petroleum ether = 55 - 100%), 4-(2-(2- aminopyridin-3-yl)-1H-benzo[d]imidazol-1-yl)benzyl acetate (230 mg, yield: 19.3%) was obtained as an off-white solid. MS: m/z = 359.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 7.97 (dd, J = 4.4, 1.6 Hz, 1H), 7.80 (d, J = 7.6 Hz, 1H), 7.56 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.4 Hz, 2H), 7.36 - 7.26 (m, 2H), 7.19 (d, J = 7.6 Hz, 1H), 7.14 (dd, J = 1.6, 7.6 Hz, 1H), 6.98 (s, 2H), 6.39 (dd, J = 4.8, 7.6 Hz, 1H), 5.17 (s, 2H), 2.11 (s, 3H). Step 4: (4-(2-(2-Aminopyridin-3-yl)-1H-benzo[d]imidazol-1-yl)phenyl) methanol To a mixture of 4-(2-(2-aminopyridin-3-yl)-1H-benzo[d]imidazol-1-yl)benzyl acetate (220 mg, 614 umol) in THF (3 mL), MeOH (3 mL) and H ₂ O (1 mL) was added K ₂ CO ₃ (255 mg, 1.84 mmol) at 20 °C. The reaction mixture was stirred at 20 °C for 0.5 hr. Then it was diluted with water (10 mL) and extracted with EtOAc (10 mL x 2). The combined organic layers were washed with brine (10 mL x 2), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. (4-(2- (2-Aminopyridin-3-yl)-1H-benzo[d]imidazol-1-yl)phenyl)methan ol (180 mg, yield: 92.7%) was obtained as a yellow solid, which was used directly into the next step. MS: m/z = 317.2 [M + H] ⁺ . Step 5: 3-(1-(4-(Chloromethyl)phenyl)-1H-benzo[d]imidazol-2-yl)pyrid in-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-1H-benzo[d]imidazol-1-yl)phenyl) methanol (170 mg, 537 µmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (192 mg, 1.61 mmol). The reaction mixture was stirred at 20 °C for 2 hr. The reaction mixture was concentrated. 3-(1-(4- (Chloromethyl)phenyl)-1H-benzo[d]imidazol-2-yl)pyridin-2-ami ne (Intermediate 208, 180 mg, crude) was obtained as a yellow solid, which was used directly into the next step. MS: m/z = 335.1 [M + H] ⁺ . [00390] Intermediate 209: 3-(1-(4-(Chloromethyl)phenyl)-1H-imidazo[4,5-b]pyridin-2- yl)pyridin-2-amine Step 1: (4-((2-Nitropyridin-3-yl)amino)phenyl)methanol To a solution of 3-fluoro-2-nitro-pyridine (5 g, 35.2 mmol) and (4-aminophenyl)methanol (4.33 g, 35.2 mmol) in DMF (50 mL) was added TEA (10.7 g, 106 mmol) at 20 °C. The reaction mixture was stirred at 100 °C for 12 hr. H ₂ O (100 mL) was added, and the mixture was extracted with EtOAc (100 mL x 3). The combined organic layers were washed with brine (100 mL x 2), dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. (4- ((2-Nitropyridin-3-yl)amino)phenyl)methanol (8.63 g, crude) was obtained as brown oil, which was used directly into the next step. MS: m/z = 246.0 [M + H] ⁺ . Step 2: 4-((2-Nitropyridin-3-yl)amino)benzyl acetate To a solution of (4-((2-nitropyridin-3-yl)amino)phenyl)methanol (2.8 g, 11.4 mmol) in CH ₂ Cl ₂ (30 mL) were added DMAP (139 mg, 1.14 mmol), TEA (3.47 g, 34.3 mmol), and Ac ₂ O (1.75 g, 17.1 mmol). The mixture was stirred at 20 °C for 1 hr. H ₂ O (30 mL) was added, and the resulting mixture was extracted with CH ₂ Cl ₂ (30 mL x 3). The combined organic layers were washed with brine (30 mL x 2), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (EtOAc in petroleum ether = 0 - 50 %), 4-((2-nitropyridin-3-yl)amino)benzyl acetate (2.23 g, yield: 68%) was obtained as an orange solid. MS: m/z = 288.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.13 (s, 1H), 7.99 (dd, J = 4.0, 1.2 Hz, 1H), 7.77 - 7.72 (m, 1H), 7.57 (dd, J = 8.4, 4.0 Hz, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 5.06 (s, 2H), 2.07 (s, 3H). Step 3: 4-(2-(2-Aminopyridin-3-yl)-1H-imidazo[4,5-b]pyridin-1-yl)ben zyl acetate To a solution of 4-((2-nitropyridin-3-yl)amino)benzyl acetate (1.10 g, 3.84 mmol) in DMSO (30 mL) were added Na ₂ S ₂ O ₄ (2.01 g, 11.5 mmol) and 2-aminopyridine-3-carbaldehyde (516 mg, 4.23 mmol). The mixture was stirred at 100 °C for 12 hr. Brine (30 mL) was added to the mixture and the mixture was extracted with CH ₂ Cl ₂ in MeOH (10:1) (30 mL x 2). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (MeOH in CH ₂ Cl ₂ = 0 - 30%), 4-(2-(2-aminopyridin-3-yl)-1H-imidazo[4,5-b]pyridin-1-yl)ben zyl acetate (300 mg, yield: 21.7%) was obtained as brown oil. MS: m/z = 360.2 [M + H] ⁺ . Step 4: (4-(2-(2-Aminopyridin-3-yl)-1H-imidazo[4,5-b]pyridin-1-yl)ph enyl)methanol To a mixture of 4-(2-(2-aminopyridin-3-yl)-1H-imidazo[4,5-b]pyridin-1-yl)ben zyl acetate (290 mg, 807 µmol) in THF (3 mL), MeOH (3 mL) and H ₂ O (1 mL) was added K ₂ CO ₃ (335 mg, 2.42 mmol) at 20 °C. The reaction mixture was stirred at 20 °C for 0.5 hr. The resulting mixture was diluted with brine (10 mL) and extracted with EtOAc (10 mL x 2). The combined organic layers were washed with brine (10 mL x 2), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. (4-(2-(2-Aminopyridin-3-yl)-1H-imidazo[4,5-b]pyridin-1-yl)ph enyl)methanol (110 mg, yield:43%) was obtained as a brown solid, which was used directly into the next step. MS: m/z = 318.1 [M + H] ⁺ . Step 5: 3-(1-(4-(Chloromethyl)phenyl)-1H-imidazo[4,5-b]pyridin-2-yl) pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-1H-imidazo[4,5-b]pyridin-1-yl)ph enyl)methanol (100 mg, 315 µmol) in CH ₂ Cl ₂ (3 mL) was added SOCl ₂ (112 mg, 945 µmol). The reaction mixture was stirred at 20 °C for 1 hr. The reaction mixture was concentrated. 3-(1-(4- (chloromethyl)phenyl)-1H-imidazo[4,5-b]pyridin-2-yl)pyridin- 2-amine (Intermediate 209, 106 mg, crude) was obtained as a yellow solid, which was used directly into the next step. MS: m/z = 336.0 [M + H] ⁺ . [00391] Intermediate 210: 3-(3-(4-(Chloromethyl)phenyl)-5-(difluoromethoxy)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: 2-Chloro-6-(difluoromethoxy)-3-nitropyridine To a solution of 2-chloro-6-(difluoromethoxy)pyridine (1.4 g, 7.80 mmol) in H ₂ SO ₄ (14 mL) was added dropwise HNO ₃ (9.80 g, 156 mmol, 7 mL) slowly at 0 °C for 1 hr. The reaction mixture was stirred at 40 °C for 12 hr. The reaction mixture was poured into ice water (60 mL) and extracted with EtOAc (60 mL x 3). The combined organic layers were washed with brine (60 mL x 3), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (EtOAc in petroleum ether = 0 - 20%), 2-chloro-6-(difluoromethoxy)- 3-nitropyridine (0.9 g, yield: 51%) was obtained as a yellow oil. ¹ H NMR (400 MHz, Chloroform-d) δ 9.11 (s, 1H), 7.55 (t, J = 69.6 Hz, 1H). ¹⁹ F NMR (400 MHz, Chloroform-d 89.627. Step 2: (4-((6-(Difluoromethoxy)-3-nitropyridin-2-yl)amino)phenyl)me thanol To a solution of 2-chloro-6-(difluoromethoxy)-3-nitropyridine (0.9 g, 4.01 mmol) in 1,4-dioxane (15 mL) were added (4-aminophenyl)methanol (543 mg, 4.41 mmol) and DIEA (1.55 g, 12.0 mmol) at 20 °C. The reaction mixture was stirred at 80 °C for 2 hr. The reaction mixture was concentrated to give (4-((6-(difluoromethoxy)-3-nitropyridin-2-yl)amino)phenyl)me thanol (1.25 g, crude) as a brown oil, which was used directly into the next step. Step 3: 4-((6-(Difluoromethoxy)-3-nitropyridin-2-yl)amino)benzyl acetate

To a solution of (4-((6-(difluoromethoxy)-3-nitropyridin-2-yl)amino)phenyl)me thanol (0.65 g, 2.09 mmol) in CH2Cl ₂ (6 mL) were added Ac ₂ O (320 mg, 3.13 mmol), DMAP (25.5 mg, 209 umol) and TEA (634 mg, 6.27 mmol). The mixture was stirred at 20 °C for 12 hr. The reaction was diluted with H ₂ O (10 mL) and extracted with CH2Cl ₂ (10 mL x 3). The combined organic layers were washed with brine (10 mL x 2), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 10-20% EtOAc in petroleum ether), 4-((6-(difluoromethoxy)-3-nitropyridin-2- yl)amino)benzyl acetate (290 mg, yield: 39% for 2 steps) was obtained as an orange solid. ¹ H NMR (400 MHz, Dimethylsulfoxide-d6) δ 10.32 (s, 1H), 8.64 (d, J= 9.2 Hz, 1H), 7.74 - 7.53 (m, 3H), 7.41 - 7.36 (m, 2H), 6.59 (d, J= 8.8 Hz, 1H), 5.07 (s, 2H), 2.07 (s, 3H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d6) δ -88.486.

Step 4 : 4-(2-(2-Aminopyridin-3 -yl)-5-(difluoromethoxy)-3H-imidazo[4,5 -b]pyridin-3 -yl)benzyl acetate

To a solution of 4-((6-(difluoromethoxy)-3-nitropyridin-2-yl)amino)benzyl acetate (290 mg, 821 umol) in DMSO (10 mL) were added Na ₂ S ₂ O ₄ (429 mg, 2.46 mmol) and 2- aminonicotinaldehyde (110 mg, 903 umol). The mixture was stirred at 100 °C for 12 hr. Aqueous NaHCO ₃ (30 mL) was added and the mixture was extracted with CH ₂ CI ₂ (30 mL x 2). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (EtOAc in petroleum ether = 40 - 100%), 4-(2-(2-aminopyridin-3-yl)-5-(difluoromethoxy)-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl acetate (130 mg, yield: 43%) was obtained as a brown solid. MS: m/z = 426.2 [M + H] ⁺ .

Step 5 : (4-(2-(2-Aminopyridin-3-yl)-5-(difluoromethoxy)-3H-imidazo[4 ,5-b]pyridin-3- yl)phenyl)methanol

To a mixture of 4-(2-(2-aminopyridin-3-yl)-5-(difluoromethoxy)-3H-imidazo[4, 5-b]pyridin-3- yl)benzyl acetate (130 mg, 306 umol) in THF (3 mL), MeOH (3 mL), and H ₂ O (1 mL) was added K ₂ CO ₃ (127 mg, 917 umol) at 20 °C. The reaction mixture was stirred at 20 °C for 0.5 hr. The resulting mixture was quenched with water (10 ml) and extracted with CH ₂ CI ₂ (10 mL x 3). The combined organic layers were washed with brine (10 mL x 2), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. (4-(2-(2-Aminopyridin-3-yl)-5-(difluoromethoxy)-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (117 mg, crude) was obtained as a brown solid, which was used directly into the next step. MS: m/z = 384.1 [M + H] ⁺ . Step 6: 3-(3-(4-(Chloromethyl)phenyl)-5-(difluoromethoxy)-3H-imidazo [4,5-b]pyridin-2- yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(difluoromethoxy)-3H-imidazo[4 ,5-b]pyridin-3- yl)phenyl)methanol (117 mg, 306 µmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (109 mg, 917 µmol). The reaction mixture was stirred at 20 ºC for 2 hr. The reaction mixture was concentrated to give 3-(3-(4-(chloromethyl)phenyl)-5-(difluoromethoxy)-3H-imidazo [4,5- b]pyridin-2-yl)pyridin-2-amine (Intermediate 210, 123 mg, crude) as a gray solid, which was used directly into the next step. MS: m/z = 402.1 [M + H] ⁺ . [00392] Intermediate 211: 3-(3-(4-(Chloromethyl)phenyl)-5-(4-methoxypyridin-3-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 211 was prepared in a manner similar to Intermediate 144. MS: m/z = 443.1 [M+H] ⁺ . [00393] Intermediate 212: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-methoxypyridin-3-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 212 was prepared in a manner similar to Intermediate 144. MS: m/z = 443.1 [M + H] ⁺ . [00394] Intermediate 213: 3-(3-(4-(Chloromethyl)phenyl)-5-(1,3-dimethyl-1H-pyrazol-4- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 213 was prepared in a manner similar to Intermediate 144. ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.69 (s, 1H), 8.36 (d, J = 7.6 Hz, 1H), 8.06 (d, J = 4.4 Hz, 1H), 7.98 - 7.87 (m, 1H), 7.76 - 7.58 (m, 5H), 6.90 (s, 1H), 4.78 (s, 2H), 4.11 (s, 3H), 2.61 (s, 3H). [00395] Intermediate 214: 3-(1-(4-(Chloromethyl)phenyl)-1H-imidazo[4,5-c]pyridin-2- yl)pyridin-2-amine Step 1: (4-((3-Nitropyridin-4-yl)amino)phenyl)methanol To a mixture of 4-chloro-3-nitropyridine (2 g, 12.6 mmol) and (4-aminophenyl)methanol (1.71 g, 13.9 mmol) in THF (20 mL) was added DIEA (3.3 g, 25.2 mmol). The mixture was stirred at 80 °C for 12 hr. H ₂ O (50 mL) was added and the mixture was extracted with EtOAc (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. (4-((3-nitropyridin-4-yl)amino)phenyl)methanol (3 g, yield: 97%) was obtained as a yellow solid. MS: m/z = 246.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.82 (s, 1H), 9.09 (s, 1H), 8.23 (d, J = 6.0 Hz, 1H), 7.42 (d, J = 8.4 Hz, 2H) 7.31 (d, J = 8.0 Hz, 2H), 6.84 (d, J = 6.0 Hz, 1H), 5.28 (t, J = 6.0 Hz, 1H), 4.53 (d, J = 5.4 Hz, 2H). Step 2: (4-(2-(2-Aminopyridin-3-yl)-1H-imidazo[4,5-c]pyridin-1-yl)ph enyl)methanol To a mixture of (4-((3-nitropyridin-4-yl)amino)phenyl)methanol (1.5 g, 6.1 mmol) and 2- aminonicotinaldehyde (821.7 mg, 6.7 mmol) in DMSO (10 mL) was added Na ₂ S ₂ O ₄ (2.7 g, 15.3 mmol). Then it was stirred at 100 °C for 12 hr. The mixture was quenched with H ₂ O (200 mL) and extracted with CH ₂ Cl ₂ (200 mL x 2). The combined organic layers were washed with brine (100 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (EtOAc / EtOH (3/1) in petroleum ether = 0 - 80%), (4-(2-(2- aminopyridin-3-yl)-1H-imidazo[4,5-c]pyridin-1-yl)phenyl)meth anol (100 mg, yield: 5%) was obtained as a yellow oil. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.09 (s, 1 H), 8.37 (d, J = 5.6 Hz, 1 H), 8.00 (dd, J = 4.8, 1.6 Hz, 1 H), 7.50 (d, J = 8.0 Hz, 2 H), 7.44 (d, J = 8.0 Hz, 2 H), 7.25 - 7.19 (m, 2 H), 6.90 (s, 2 H), 6.41 (dd, J = 7.6, 4.8 Hz, 1 H), 5.38 (t, J = 5.6 Hz, 1 H), 4.59 (d, J = 5.6 Hz, 2 H). Step 3: 3-(1-(4-(Chloromethyl)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl) pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-1H-imidazo[4,5-c]pyridin-1-yl)ph enyl)methanol (100 mg, 315 µmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ mixture was stirred at 25 °C for 2 hr. The reaction mixture was concentrated to give 3-(l-(4- (chloromethyl)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)pyridin- 2-amine (Intermediate 214, 102 mg, yield: 96%) as a yellow solid, which was used directly without purification. MS: m/z = 335.9 [M + H] ⁺ .

[00396] Intermediate 215: 3-(3-(4-(Chloromethyl)phenyl)-5-(3-methoxypyridin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Step 1 : (2-(2-Aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)oxy )methyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)boronic acid

A mixture of Intermediate 129 (500 mg, 979 umol), 4,4,4',4 ^, ,5,5,5',5 ^, -octamethyl-2,2 ^, -bi(l,3,2- dioxaborolane) (497 mg, 1.96 mmol), KOAc (288 mg, 2.94 mmol) and Pd(dppf)Cl ₂ (71.7 mg, 97.9 uuol) in 1,4-dioxane (2 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 80 °C for 16 hr under N2 atmosphere. (2-(2-Aminopyridin-3-yl)-3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-3H-imidazo[4,5-b]pyrid in-5-yl)boronic acid was obtained as a black liquid, which was used in the next step without work-up and purification. MS: m/z = 476.2 [M + H] ⁺ .

Step 2 : 3 -(3 -(4-(((tert-Buty Idimethy 1 sily l)oxy)methy l)pheny l)-5 -(3 -methoxy pyridin-2-y 1)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

A mixture of (2-(2-aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)oxy )methyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)boronic acid (470 mg, 989 umol), 2-bromo-3-methoxypyridine (186 mg, 989 umol), Pd(dppf)Cl ₂ (72.3 mg, 98.9 umol) and CS ₂ CO ₃ (966 mg, 2.97 mmol) in 1,4- dioxane (5 mL) and H ₂ O (1 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 90 °C for 16 hr under N2 atmosphere. The reaction mixture was quenched with H ₂ O (5 mL), diluted with CH ₂ CI ₂ (10 mL), and extracted with CH ₂ CI ₂ (15 mL x 2). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 30% ~ 61% EtOAc in petroleum ether), 3-(3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-5-(3-methoxypyridin-2- yl)-3H-imidazo[4,5-b]pyridin-2- yl)pyridin-2-amine (280 mg, yield: 47% for two steps) was obtained as a black solid. MS: m/z = 539.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.32 (dd, J = 4.4, 1.6 Hz, 1H), 8.15 (d, J = 8.4 Hz, 1H), 8.04 (dd, J = 4.8, 1.6 Hz, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.46 - 7.40 (m, 4H), 7.34 - 7.27 (m, 2H), 7.10 (dd, J = 7.6, 1.6 Hz, 1H), 6.69 (br s, 2H), 6.36 (dd, J = 8.0, 4.8 Hz, 1H), 4.80 (s, 2H), 3.83 (s, 3H), 0.95 (s, 9H), 0.12 (s, 6H). Step 3: (4-(2-(2-Aminopyridin-3-yl)-5-(3-methoxypyridin-2-yl)-3H-imi dazo[4,5-b]pyridin-3- yl)phenyl)methanol To a solution of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-(3-m ethoxypyridin-2- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (250 mg, 464 µmol) in THF (5 mL) was added TBAF (1.4 mL, 1.4 mmol, 1 M in THF). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was quenched with H ₂ O (5 mL) at 25 °C, diluted with CH ₂ Cl ₂ (10 mL), and extracted with CH ₂ Cl ₂ (15 mL x 3). The combined organic layers were washed with brine (50 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After triturated with EtOAc : petroleum ether = 1 : 10 (10 mL) at 25 °C for 10 min, (4-(2-(2-aminopyridin-3-yl)- 5-(3-methoxypyridin-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl)phen yl)methanol (175 mg, yield: 84%) was obtained as a brown solid. MS: m/z = 425.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.26 - 8.20 (m, 2H), 7.99 (dd, J = 4.8, 2.0 Hz, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.61 - 7.53 (m, 1H), 7.46 - 7.38 (m, 5H), 7.23 (dd, J = 7.6, 1.6 Hz, 1H), 6.96 (br s, 2H), 6.42 (dd, J = 7.6, 5.2 Hz, 1H), 5.34 (t, J = 6.0 Hz, 1H), 4.56 (d, J = 6.0 Hz, 2H), 3.77 (s, 3H). Step 4: 3-(3-(4-(Chloromethyl)phenyl)-5-(3-methoxypyridin-2-yl)-3H-i midazo[4,5-b]pyridin-2- yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(3-methoxypyridin-2-yl)-3H-imi dazo[4,5- b]pyridin-3-yl)phenyl)methanol (175 mg,412 µmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (245 mg, 2.06 mmol). The mixture was stirred at 25 °C for 0.5 hr. The reaction was concentrated under reduced pressure to give 3-(3-(4-(chloromethyl)phenyl)-5-(3-methoxypyridin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (Intermediate 215, 198 mg, HCl salt) as a brown solid. MS: m/z = 443.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.62 (d, J = 8.4 Hz, 1H), 8.54 - 8.45 (m, 3H), 8.09 - 8.04 (m, 2H), 7.86 (d, J = 7.2 Hz, 1H), 7.74 - 7.69 (m, 2H), 7.66 - 7.62 (m, 2H), 6.91 - 6.83 (m, 1H), 4.79 (s, 2H), 4.26 (s, 3H). [00397] Intermediate 216: 3-(3-(4-(Chloromethyl)phenyl)-5-(1-methyl-1H-1,2,3-triazol- 5-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Intermediate 216 was prepared in a manner similar to Intermediate 215. MS: m/z = 417.1 [M + H] ⁺ . [00398] Intermediate 217: 2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-6- methyl-3H-imidazo[4,5-b]pyridine-5-carbonitrile Step 1: (4-((6-Chloro-5-methyl-3-nitropyridin-2-yl)amino)phenyl)meth anol To a solution of 2,6-dichloro-3-methyl-5-nitropyridine (10 g, 48.3 mmol) and (4- aminophenyl)methanol (5.35 g, 43.5 mmol) in 1,4-dioxane (100 mL) was added DIEA (12.5 g, 96.6 mmol). The mixture was stirred at 60 °C for 16 hr. The reaction mixture was diluted with H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (100 mL x 3). The combined organic layers were washed with brine (100 mL x 4), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. (4-((6-Chloro-5-methyl-3-nitropyridin-2-yl)amino)phenyl)meth anol (14 g, crude) was obtained as a red solid. MS: m/z = 294.0 [M + H] ⁺ . Step 2: 4-((6-Chloro-5-methyl-3-nitropyridin-2-yl)amino)benzyl acetate To a solution of (4-((6-chloro-5-methyl-3-nitropyridin-2-yl)amino)phenyl)meth anol (14 g, 47.7 mmol) and TEA (14.5 g, 143 mmol) in CH ₂ Cl ₂ (200 mL) were added Ac ₂ O (7.3 g, 71.5 mmol) and DMAP (582 mg, 4.77 mmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was diluted with H ₂ O (200 mL) and extracted with CH ₂ Cl ₂ (200 mL x 3). The combined organic layers were washed with brine (300 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 10% EtOAc in petroleum ether), 4-((6-chloro-5-methyl-3-nitropyridin-2-yl)amino)benzyl acetate (7 g, yield: 44% for two steps) was obtained as a red solid. MS: m/z = 336.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.98 (s, 1H), 8.56 (s, 1H), 7.60 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.8 Hz, 2H), 5.06 (s, 2H), 2.29 (s, 3H), 2.07 (s, 3H). Step 3: 4-((6-Cyano-5-methyl-3-nitropyridin-2-yl)amino)benzyl acetate To a solution of 4-((6-chloro-5-methyl-3-nitropyridin-2-yl)amino)benzyl acetate (2.4 g, 7.15 mmol) in DMF (30 mL) was added CuCN (3.2 g, 35.7 mmol). The mixture was stirred at 180 °C for 8 hr. The reaction mixture was quenched with H ₂ O (50 mL) at 25 °C and extracted with CH ₂ Cl ₂ (100 mL x 3). The combined organic layers were washed with brine (100 mL x 5), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 5% EtOAc in petroleum ether), 4-((6-cyano-5-methyl-3- nitropyridin-2-yl)amino)benzyl acetate (150 mg, yield: 6.4%) was obtained as a red solid. MS: m/z = 326.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ 9.80 (s, 1H), 8.66 (s, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 5.06 (s, 2H), 2.44 (s, 3H), 2.07 (s, 3H). Step 4: 4-(2-(2-Aminopyridin-3-yl)-5-cyano-6-methyl-3H-imidazo[4,5-b ]pyridin-3-yl)benzyl acetate A mixture of 4-((6-cyano-5-methyl-3-nitropyridin-2-yl)amino)benzyl acetate (140 mg, 429 µmol) and 2-aminonicotinaldehyde (63 mg, 515 µmol) in DMSO (2 mL) was added Na2S2O4 (352 mg, 1.72 mmol) at 25 °C. The mixture was stirred at 80 °C for 16 hr. The reaction mixture was quenched with H ₂ O (10 mL) at 25 °C, diluted with CH ₂ Cl ₂ (10 mL), and extracted with CH ₂ Cl ₂ (10 mL x 3). The combined organic layers were washed with brine (10 mL x 3), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by prep-TLC (100% EtOAc), 4-(2-(2-aminopyridin-3-yl)-5-cyano-6-methyl-3H-imidazo[4,5-b ]pyridin-3- yl)benzyl acetate (30 mg, yield: 18%) was obtained as a yellow solid. MS: m/z = 399.4 [M + H] ⁺ . Step 5: 2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-6-methyl -3H-imidazo[4,5- b]pyridine-5-carbonitrile To a solution of 4-(2-(2-aminopyridin-3-yl)-5-cyano-6-methyl-3H-imidazo[4,5-b ]pyridin-3- yl)benzyl acetate (30 mg, 75.3 µmol) in THF (1 mL) were added K ₂ CO ₃ (31.2 mg, 226 mmol), MeOH (1 mL) and H ₂ O (1 mL). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was diluted with H ₂ O (20 mL) and extracted with CH ₂ Cl ₂ (20 mL x 3). The combined organic layers were washed with brine (40 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give 2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-6-methyl - 3H-imidazo[4,5-b]pyridine-5-carbonitrile (27 mg, crude) as a yellow solid. MS: m/z = 357.2 [M + H] ⁺ . Step 6: 2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-6-methyl- 3H-imidazo[4,5- b]pyridine-5-carbonitrile To a solution of 2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-6-methyl -3H- imidazo[4,5-b]pyridine-5-carbonitrile (27 mg, 75.8 µmol) in CH ₂ Cl ₂ (2 mL) was added SOCl ₂ (0.3 mL). The mixture was stirred at 40 °C for 1 hr. The mixture was concentrated under reduced pressure to give 2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-6-methyl- 3H- imidazo[4,5-b]pyridine-5-carbonitrile (Intermediate 217, 28 mg, crude) was obtained as a yellow solid. MS: m/z = 375.0 [M + H] ⁺ . [00399] Intermediate 218: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-methyl-1,3,4-oxadiazol-2- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 218 was prepared in a manner similar to Intermediate 215. MS: m/z = 418.0 [M + H] ⁺ . [00400] Intermediate 219: 3-(3-(4-(chloromethyl)phenyl)-5-(1-methyl-1H-1,2,4-triazol-5 - yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Intermediate 219 was prepared in a manner similar to Intermediate 215. MS: m/z = 417.0 [M + H] ⁺ . [00401] Intermediate 220: 3-(3-(4-(Chloromethyl)phenyl)-5-(4-methyl-2H-1,2,3-triazol- 2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: 4-((6-(4-Methyl-2H-1,2,3-triazol-2-yl)-3-nitropyridin-2-yl)a mino)benzyl acetate To a solution of 4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl acetate (refer to Intermediate 178 for detail procedures, 3 g, 9.33 mmol) and 4-methyl-1H-1,2,3-triazole (775 mg, 9.33 mmol) in DMF (30 mL) were added K ₂ CO ₃ (6.44 g, 46.6 mmol) and NaI (140 mg, 933 µmol). mixture was stirred at 80 °C for 1 hr. The reaction mixture was quenched with H ₂ O (100 mL) at 25°C and extracted with CH ₂ Cl ₂ (100 mL x 2). The combined organic layers were washed with brine (100 mL x3), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 10% ~ 20% EtOAc in petroleum ether), 4- ((6-(4-methyl-2H-1,2,3-triazol-2-yl)-3-nitropyridin-2-yl)ami no)benzyl acetate (1.4 g, yield: 40%) was obtained as a red solid. MS: m/z = 369.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.33 (s, 1H), 8.76 (d, J = 9.2 Hz, 1H), 8.13 (s, 1H), 8.03 - 7.95 (m, 2H), 7.50 (d, J = 9.2 Hz, 1H), 7.41 (d, J = 8.4 Hz, 2H), 5.08 (s, 2H), 2.42 (s, 3H), 2.08 (s, 3H). Step 2: 4-(2-(2-Aminopyridin-3-yl)-5-(4-methyl-2H-1,2,3-triazol-2-yl )-3H-imidazo[4,5- b]pyridin-3-yl)benzyl acetate To a solution of 4-((6-(4-methyl-2H-1,2,3-triazol-2-yl)-3-nitropyridin-2-yl)a mino)benzyl acetate (1.4 g, 3.8 mmol) in DMSO (10 mL) were added Na ₂ S ₂ O ₄ (2.65 g, 15.2 mmol, 87% purity) and 2-aminonicotinaldehyde (511 mg, 4.18 mmol). The mixture was stirred at 100 °C for 4 hr. The reaction mixture was quenched with H ₂ O (100 mL) at 25°C and extracted with CH ₂ Cl ₂ (100 mL x 2). The combined organic layers were washed with brine (100 mL x 2), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 20% ~ 70% EtOAc in petroleum ether), 4-(2-(2-aminopyridin-3-yl)- 5-(4-methyl-2H-1,2,3-triazol-2-yl)-3H-imidazo[4,5-b]pyridin- 3-yl)benzyl acetate (240 mg, yield: 14%) was obtained as a red solid. MS: m/z = 441.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.40 (d, J = 8.8 Hz, 1H), 8.03 - 7.88 (m, 3H), 7.58 - 7.47 (m, 4H), 7.23 (dd, J = 7.6, 1.6 Hz, 1H), 6.84 (s, 2H), 6.43 (dd, J = 7.6, 4.8 Hz, 1H), 5.17 (s, 2H), 2.35 (s, 3H), 2.12 (s, 3H). Step 3: (4-(2-(2-Aminopyridin-3-yl)-5-(4-methyl-2H-1,2,3-triazol-2-y l)-3H-imidazo[4,5- b]pyridin-3-yl)phenyl)methanol To a solution of 4-(2-(2-aminopyridin-3-yl)-5-(4-methyl-2H-1,2,3-triazol-2-yl )-3H-imidazo[4,5- b]pyridin-3-yl)benzyl acetate (240 mg, 545 µmol) in THF (5 mL) and MeOH (5 mL) was added K ₂ CO ₃ (226 mg, 1.63 mmol). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was quenched with H ₂ O (50 mL) at 25 °C and extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (50 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. (4-(2-(2-Aminopyridin-3-yl)-5-(4-methyl-2H-1,2,3- triazol-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (150 mg, yield: 68%) was obtained as a red solid. MS: m/z = 399.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.39 (d, J = 8.4 Hz, 1H), 8.02 - 7.84 (m, 3H), 7.52 - 7.41 (m, 4H), 7.22 (dd, J = 7.6, 2.0 Hz, 1H), 6.91 (s, 2H), 6.44 - 6.37 (m, 1H), 5.35 (t, J = 5.6 Hz, 1H), 4.60 (d, J = 6.0 Hz, 2H), 2.35 (s, 3H). Step 4: 3-(3-(4-(Chloromethyl)phenyl)-5-(4-methyl-2H-1,2,3-triazol-2 -yl)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(4-methyl-2H-1,2,3-triazol-2-y l)-3H- imidazo[4.5-b]pyridin-3-yl)phenyl)methanol (150 mg, 376 µmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (134 mg, 1.13 mmol). The mixture was stirred at 40 °C for 0.5 hr. The reaction was concentrated under reduced pressure to give 3-(3-(4-(chloromethyl)phenyl)-5-(4-methyl-2H- 1,2,3-triazol-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2- amine (Intermediate 220, 170 mg, HCl salt) as a green solid. MS: m/z = 417.1 [M + H] ⁺ . [00402] Intermediate 221: 3-(3-(4-(Chloromethyl)phenyl)-5-(4-methyl-4H-1,2,4-triazol- 3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 221 was prepared in a manner similar to Intermediate 215. MS: m/z = 417.1 [M + H] ⁺ . [00403] Intermediate 222: 3-(3-(4-(Chloromethyl)phenyl)-5-(3-fluoropyridin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 222 was prepared in a manner similar to Intermediate 215. MS: m/z = 431.1 [M + H] ⁺ . [00404] Intermediate 223: 3-(3-(4-(Chloromethyl)phenyl)-5-(6-methylpyridin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Intermediate 223 was prepared in a manner similar to Intermediate 215. MS: m/z = 427.2 [M + H] ⁺ . [00405] Intermediate 224: 3-(3-(4-(Chloromethyl)phenyl)-5-(1-(difluoromethyl)-1H- 1,2,4-triazol-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2- amine Intermediate 224 was prepared in a manner similar to Intermediate 215. MS: m/z = 453.0 [M + H] ⁺ . [00406] Intermediate 225: 4-((5'-Fluoro-5-nitro-[2,2'-bipyridin]-6-yl)amino)benzyl acetate A mixture of 4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl acetate (refer to Intermediate 178 for detail procedures, 10 g, 31 mmol), (5-fluoropyridin-2-yl)boronic acid (13 g, 93 mmol), Cata CXium A Pd G3 (2.3 g, 3.1 mmol), CuBr (3.34 g, 23.3 mmol) and Cs ₂ CO ₃ (30 g, 93 mmol) in 1,4-dioxane (350 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 125 °C for 2.5 hr under N ₂ atmosphere. The reaction mixture was poured into H ₂ O (500 mL) and extracted with CH ₂ Cl ₂ (200 mL x 2). The combined organic layers were washed with brine (500 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After triturated (10% EtOAc in petroleum ether, 100 mL) at 25 °C for 1 hr, 4-((5'-fluoro-5-nitro-[2,2'-bipyridin]- 6-yl)amino)benzyl acetate (Intermediate 225, 10 g, yield: 72%) was obtained as a yellow solid. MS: m/z = 383.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.10 (s, 1H), 8.77 - 8.74 (m, 1H), 8.69 (d, J = 8.8 Hz, 1H), 8.25 - 8.21 (m, 1H), 7.97 - 7.92 (m, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.48 -7.44 (m, 2H), 5.10 (s, 2H), 2.09 (s, 3H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -124.159. [00407] Intermediate 226: 5-(3-(4-(Chloromethyl)phenyl)-5-(5-fluoropyridin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyrimidin-4-amine Step 1: 4-(2-(4-Aminopyrimidin-5-yl)-5-(5-fluoropyridin-2-yl)-3H-imi dazo[4,5-b]pyridin-3- yl)benzyl acetate To a solution of Intermediate 225 (2 g, 5.23 mmol) in DMSO (10 mL) were added Na ₂ S ₂ O ₄ (3.64 g, 20.9 mmol, 87% purity) and 4-aminopyrimidine-5-carbaldehyde (708 mg, 5.75 mmol). The mixture was stirred at 100 °C for 2 hr. The reaction mixture was quenched with H ₂ O (100 mL) at 25°C and extracted with CH ₂ Cl ₂ (100 mL x 2). The combined organic layers were washed with brine (100 mL x 2), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 20% ~ 70% EtOAc in petroleum ether), 4-(2-(4-aminopyrimidin-5-yl)-5-(5-fluoropyridin-2-yl)-3H-imi dazo[4,5- b]pyridin-3-yl)benzyl acetate (500 mg, yield: 21%) was obtained as a yellow solid. MS: m/z = 456.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.67 (d, J = 2.8 Hz, 1H), 8.46 - 8.30 (m, 3H), 8.26 - 8.20 (m, 1H), 8.02 (s, 1H), 7.87 - 7.80 (m, 1H), 7.69 (s, 2H), 7.59 (s, 4H), 5.20 (s, 2H), 2.13 (s, 3H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -127.656. Step 2: (4-(2-(4-Aminopyrimidin-5-yl)-5-(5-fluoropyridin-2-yl)-3H-im idazo[4,5-b]pyridin-3- yl)phenyl)methanol To a solution of 4-(2-(4-aminopyrimidin-5-yl)-5-(5-fluoropyridin-2-yl)-3H-imi dazo[4,5- b]pyridin-3-yl)benzyl acetate (500 mg, 1.1 mmol) in THF (5 mL) and MeOH (5 mL) was added K ₂ CO ₃ (455 mg, 3.29 mmol). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was quenched with H ₂ O (50 mL) at 25 °C and extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (50 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. (4-(2-(4-Aminopyrimidin-5-yl)-5-(5-fluoropyridin-2-yl)- 3H-imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (450 mg, yield: 95%) was obtained as a yellow solid. MS: m/z = 414.1 [M + H] ⁺ . Step 3: 5-(3-(4-(Chloromethyl)phenyl)-5-(5-fluoropyridin-2-yl)-3H-im idazo[4,5-b]pyridin-2- yl)pyrimidin-4-amine To a solution of (4-(2-(4-aminopyrimidin-5-yl)-5-(5-fluoropyridin-2-yl)-3H-im idazo[4,5- b]pyridin-3-yl)phenyl)methanol (450 mg, 1.09 mmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (389 mg, 3.27 mmol). The mixture was stirred at 25 °C for 0.5 hr. The reaction was concentrated under reduced pressure to give 5-(3-(4-(chloromethyl)phenyl)-5-(5-fluoropyridin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyrimidin-4-amine (Intermediate 226, 509 mg, HCl salt) as a yellow solid. MS: m/z = 432.0 [M + H] ⁺ . [00408] Intermediate 227: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-fluoropyridin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyrazin-2-amine Intermediate 227 was prepared in a manner similar to Intermediate 226. MS: m/z = 432.0 [M + H] ⁺ . [00409] Intermediate 228: 3-(4-(Chloromethyl)phenyl)-5-(5-fluoropyridin-2-yl)-2- (pyridin-3-yl)-3H-imidazo[4,5-b]pyridine

Step 1: 4-(5-Chloro-2-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)b enzyl acetate A mixture of 4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl acetate (refer to Intermediate 178 for detail procedures, 2 g, 6.22 mmol) and nicotinaldehyde (799 mg, 7.46 mmol) in DMSO (20 mL) was added Na ₂ S ₂ O ₄ (5.1 g, 24.9 mmol) at 25 °C. The mixture was stirred at 80 °C for 12 hr. The reaction mixture was poured into H ₂ O (50 mL) and extracted with CH ₂ Cl ₂ (30 mL x 3). The combined organic layers were washed with brine (30 mL x 3), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 20% ~ 50% EtOAc in petroleum ether), 4-(5-chloro-2-(pyridin-3-yl)-3H-imidazo[4,5- b]pyridin-3-yl)benzyl acetate (1.2 g, yield: 51%) was obtained as a yellow solid. MS: m/z = 379.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.70 (d, J = 1.6 Hz, 1H), 8.63 (d, J = 4.8 Hz, 1H), 8.33 (d, J = 8.4 Hz, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.59 - 7.54 (m, 2H), 7.53 - 7.46 (m, 4H), 5.18 (s, 2H), 2.12 (s, 3H) Step 2: 4-(5-(5-Fluoropyridin-2-yl)-2-(pyridin-3-yl)-3H-imidazo[4,5- b]pyridin-3-yl)benzyl acetate A mixture of 4-(5-chloro-2-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)b enzyl acetate (640 mg, 1.69 mmol) and (5-fluoropyridin-2-yl)boronic acid (714 mg, 5.07 mmol) in 1,4-dioxane (10 mL) were added cataCXium A Pd G ₃ (123 mg, 169 µmol), CuBr (182 mg, 1.27 mmol) and Cs ₂ CO ₃ (1.65 g, 5.07 mmol) was degassed and purged with N ₂ three times. The mixture was stirred at 90 °C for 2 hr under N ₂ atmosphere. The reaction mixture was poured into H ₂ O (30 mL) and extracted with CH ₂ Cl ₂ (30 mL x 3). The combined organic layers were washed with brine (30 mL x 5), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After triturated with EtOAc (5 mL) at 25 °C for 30 min, 4-(5-(5-fluoropyridin-2-yl)-2-(pyridin-3-yl)- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl acetate (700 mg, yield: 94%) was obtained as a yellow solid. MS: m/z = 440.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.76 - 8.59 (m, 3H), 8.47 - 8.33 (m, 2H), 8.24 (dd, J = 8.8, 4.4 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.88 - 7.80 (m, 1H), 7.59 (br s, 4H), 7.52 - 7.45 (m, 1H), 5.21 (s, 2H), 2.12 (s, 3H). Step 3: (4-(5-(5-Fluoropyridin-2-yl)-2-(pyridin-3-yl)-3H-imidazo[4,5 -b]pyridin-3- yl)phenyl)methanol To a solution of 4-(5-(5-fluoropyridin-2-yl)-2-(pyridin-3-yl)-3H-imidazo[4,5- b]pyridin-3- yl)benzyl acetate (700 mg, 1.59 mmol) in THF (5 mL) were added K ₂ CO ₃ (661 mg, 4.78 mmol), MeOH (5 mL) and H ₂ O (5 mL). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was diluted with H ₂ O (30 mL) and extracted with CH ₂ Cl ₂ (20 mL x 3). The combined organic layers were washed with brine (60 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. (4-(5-(5-Fluoropyridin-2-yl)-2-(pyridin-3-yl)-3H-imidazo[4,5 -b]pyridin-3- yl)phenyl)methanol (360 mg, crude) was obtained as a yellow solid. MS: m/z = 398.1 [M + H] ⁺ . Step 4: 3-(4-(Chloromethyl)phenyl)-5-(5-fluoropyridin-2-yl)-2-(pyrid in-3-yl)-3H-imidazo[4,5- b]pyridine To a solution of (4-(5-(5-fluoropyridin-2-yl)-2-(pyridin-3-yl)-3H-imidazo[4,5 -b]pyridin-3- yl)phenyl)methanol (360 mg, 508 µmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (1 mL). The mixture was stirred at 40 °C for 1 hr. The mixture was concentrated under reduced pressure to give 3-(4-(chloromethyl)phenyl)-5-(5-fluoropyridin-2-yl)-2-(pyrid in-3-yl)-3H-imidazo[4,5- b]pyridine (Intermediate 228, 410 mg, HCl salt, crude) as a yellow solid. MS: m/z = 416.0 [M + H] ⁺ . [00410] Intermediate 229: 2-(3-(4-(Chloromethyl)phenyl)-5-(5-fluoropyridin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)aniline Intermediate 229 was prepared in a manner similar to Intermediate 226. MS: m/z = 430.0 [M + H] ⁺ . [00411] Intermediate 230: 3-(4-(Chloromethyl)phenyl)-5-(5-fluoropyridin-2-yl)-2-phenyl - 3H-imidazo[4,5-b]pyridine

Intermediate 230 was prepared in a manner similar to Intermediate 228. MS: m/z = 415.1 [M + H] ⁺ . [00412] Intermediate 231: 2-Bromo-5-(methoxy-d3)pyridine To a solution of 6-bromopyridin-3-ol (1 g, 5.8 mmol), CD ₃ OD (1.2 g, 34.5 mmol) and PPh ₃ (1.7 g, 6.3 mmol) in 1,4-dioxane (10 mL) was added DIAD (1.4 mg, 6.9 mmol) at 0 °C. The mixture was stirred at 25 °C for 4 hr. The mixture was quenched with H ₂ O (50 mL) and extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (50 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0% ~ 15% EtOAc in petroleum ether), 2-bromo-5-(methoxy-d ₃ )pyridine (Intermediate 231, 1 g, yield: 84%) was obtained as a light yellow oil. MS: m/z = 190.7, 192.7 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.12 (d, J = 3.2 Hz, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.39 (dd, J = 8.8, 3.2 Hz, 1H). [00413] Intermediate 232: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-(methoxy-d3)pyridin-2- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Intermediate 232 was prepared in a manner similar to Intermediate 215. MS: m/z = 446.0 [M + H] ⁺ . D% : 3D = 99.7%. [00414] Intermediate 233: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-(difluoromethoxy)pyridin- 2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: (2-(2-Aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)oxy )methyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)boronic acid A mixture of Intermediate 129 (1 g, 1.96 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2- dioxaborolane) (995 mg, 3.92 mmol), KOAc (577 mg, 5.88 mmol) and Pd(dppf)Cl ₂ (143 mg, 196 mmol) in 1,4-dioxane (5 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 90 °C for 16 hr under N ₂ atmosphere. (2-(2-Aminopyridin-3-yl)-3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-3H-imidazo[4,5-b]pyrid in-5-yl)boronic acid was obtained as a black liquid, which was used in the next step without work-up and purification. MS: m/z = 476.2 [M + H] ⁺ . Step 2: 3-(3-(4-(((tert-Butyldimethylsilyl)oxy)methyl)phenyl)-5-(5-( difluoromethoxy)pyridin-2- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine A mixture of (2-(2-aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)oxy )methyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)boronic acid (470 mg, 989 µmol), 2-bromo-5- (difluoromethoxy)pyridine (266 mg, 1.19 mmol), Pd(dppf)Cl ₂ (72.3 mg, 98.9 µmol) and Cs ₂ CO ₃ (966 mg, 2.97 mmol) in 1,4-dioxane (4 mL) and H ₂ O (1 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 90 °C for 16 hr under N ₂ atmosphere. The reaction mixture was poured into H ₂ O (15 mL) and extracted with EtOAc (15 mL x 3). The combined organic phases were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 56% EtOAc in petroleum ether), 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-(5- (difluoromethoxy)pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl )pyridin-2-amine (210 mg, yield: 37% for two steps) was obtained as a brown solid. MS: m/z = 575.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ 8.57 (d, J = 8.4 Hz, 1H), 8.40 (d, J = 8.4 Hz, 1H), 8.31 (d, J = 8.4 Hz, 1H), 8.21 (d, J = 8.8 Hz, 1H), 8.00 (dd, J = 4.8, 2.0 Hz, 1H), 7.76 (dd, J = 8.4, 2.4 Hz, 1H), 7.54 - 7.45 (m, 4H), 7.41 - 7.27 (m, 1H), 7.22 - 7.16 (m, 1H), 7.00 (s, 2H), 6.34 (dd, J = 7.6, 4.8 Hz, 1H), 4.82 (s, 2H), 0.93 (s, 9H), 0.12 (s, 6H). ¹⁹ F NMR (400 MHz, Dimethysulfoxide-d ₆ 82.487. Step 3: (4-(2-(2-Aminopyridin-3-yl)-5-(5-(difluoromethoxy)pyridin-2- yl)-3H-imidazo[4,5- b]pyridin-3-yl)phenyl)methanol To a solution of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-(5- (difluoromethoxy)pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl )pyridin-2-amine (210 mg, 365 µmol) in THF (3 mL) was added TBAF (1 mL, 1 M inTHF). The mixture was stirred at 25 ºC for 0.3 hr. The reaction mixture was poured into H ₂ O (15 mL) and extracted with EtOAc (15 mL x 3). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. (4-(2-(2-Aminopyridin-3-yl)-5-(5- (difluoromethoxy)pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl )phenyl)methanol (101 mg, crude) was obtained as a brown solid. MS: m/z =461.1 [M + H] ⁺ . Step 4: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-(difluoromethoxy)pyridin- 2-yl)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(5-(difluoromethoxy)pyridin-2- yl)-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (101 mg, 219 µmol) in CH ₂ Cl ₂ (4 mL) was added SOCl ₂ (1 mL). The mixture was stirred at 25 °C for 1 hr. The reaction was concentrated under reduced pressure to give 3-(3-(4-(chloromethyl)phenyl)-5-(5-(difluoromethoxy)pyridin- 2-yl)- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (Intermediate 233, 115 mg, HCl salt) as a brown solid. MS: m/z = 479.1 [M + H] ⁺ . [00415] Intermediate 234: 2-Bromo-5-(fluoromethoxy)pyridine To a solution of 6-bromopyridin-3-ol (1 g, 5.8 mmol) and K ₂ CO ₃ (2.4 g, 17.2 mmol) in DMF (10 mL) was added bromofluoromethane (974 mg, 8.6 mmol) at 0 °C. The mixture was stirred at 0 °C for 2 hr. The mixture was quenched with H ₂ O (50 mL) and extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (50 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0% ~ 15% EtOAc in petroleum ether), 2-bromo-5-(fluoromethoxy)pyridine (Intermediate 234, 1 g, yield: 84%) was obtained as a light yellow oil. MS: m/z = 205.7, 207.7 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 3.0 Hz, 1H), 7.66 (d, J = 8.8 Hz, 1H), 7.61 - 7.55 (m, 1H), 5.93 (d, J = 53.6 Hz, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -152.277. [00416] Intermediate 235: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-(fluoromethoxy)pyridin-2- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 235 was prepared in a manner similar to Intermediate 215. MS: m/z = 460.9 [M + H] ⁺ . [00417] Intermediate 236: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-methoxypyrimidin-2-yl)- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Intermediate 236 was prepared in a manner similar to Intermediate 215. MS: m/z = 444.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.96 (s, 2H), 8.75 (d, J = 8.4 Hz, 1H), 8.54 (d, J = 8.4 Hz, 1H), 8.05 (dd, J = 6.0, 1.2 Hz, 1H), 7.85 (dd, J = 7.6, 1.2 Hz, 1H), 7.74 - 7.70 (m, 2H), 7.64 - 7.60 (m, 2H), 6.87 (dd, J = 7.2, 6.4 Hz, 1H), 4.80 (s, 2H), 4.16 (s, 3H). [00418] Intermediate 237: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-methylpyrazin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 237 was prepared in a manner similar to Intermediate 215. MS: m/z = 428.1 [M + H] ⁺ . [00419] Intermediate 238: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-methoxypyrazin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Intermediate 238 was prepared in a manner similar to Intermediate 215. MS: m/z = 444.1 [M + H] ⁺ . [00420] Intermediate 239: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-ethoxypyridin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 239 was prepared in a manner similar to Intermediate 215. MS: m/z = 457.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.73 (d, J = 9.6 Hz, 1H), 8.55 (d, J = 8.4 Hz, 1H), 8.45 (d, J = 2.8 Hz, 1H), 8.39 (d, J = 8.4 Hz, 1H), 8.32 (dd, J = 9.2, 2.8 Hz, 1H), 8.05 (dd, J = 6.4, 1.6 Hz, 1H), 7.84 (dd, J = 7.6, 1.2 Hz, 1H), 7.76 - 7.71 (m, 2H), 7.66 - 7.60 (m, 2H), 6.90 - 6.84 (m, 1H), 4.80 (s, 2H), 4.37 (q, J = 7.2 Hz, 2H), 1.52 (t, J = 7.2 Hz, 3H). [00421] Intermediate 240: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-methyl-2H-1,2,3-triazol- 4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrazin-2-amine

Intermediate 240 was prepared in a manner similar to Intermediate 197. MS: m/z = 418.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.32 (d, J = 8.4 Hz, 1H), 8.10 (d, J = 8.4 Hz, 1H), 7.98 (s, 1H), 7.90 (d, J = 2.8 Hz, 1H), 7.69 (d, J = 2.8 Hz, 1H), 7.61 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 8.4 Hz, 2H), 4.79 (s, 2H), 4.22 (s, 3H). [00422] Intermediate 241: 2-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)isonicotinonitrile Step 1: (4-((3-Nitro-6-(trimethylstannyl)pyridin-2-yl)amino)phenyl)m ethanol To a solution of 4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl acetate (refer to Intermediate 178 for detail procedures, 5 g, 15.5 mmol), Pd(PPh ₃ ) ₄ (1.8 g, 1.55 mmol) and 1,1,1,2,2,2- hexamethyldistannane (14.4 g, 44 mmol) in 1,4-dioxane (50 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 125 °C for 2 hr under N ₂ atmosphere. (4-((3-Nitro-6- (trimethylstannyl)pyridin-2-yl)amino)phenyl)methanol was obtained as a black liquid, which was used in the next step without work-up and purification. MS: m/z = 409.9 [M + H] ⁺ . Step 2: 6'-((4-(Hydroxymethyl)phenyl)amino)-5'-nitro-[2,2'-bipyridin e]-4-carbonitrile A mixture of (4-((3-nitro-6-(trimethylstannyl)pyridin-2-yl)amino)phenyl)m ethanol (6.34 g, 15.5 mmol), 2-bromoisonicotinonitrile (2.84 g, 15.5 mmol), Pd(PPh ₃ ) ₄ (1.79 g, 1.55 mmol) in 1,4- dioxane (100 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 100 °C for 16 hr under N ₂ atmosphere. The reaction was concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 5 ~ 100% EtOAc in petroleum ether), 6'-((4-(hydroxymethyl)phenyl)amino)-5'-nitro-[2,2'-bipyridin e]-4-carbonitrile (1.4 g, yield: 28% for two steps) was obtained as a black solid. MS: m/z = 348.0 [M + H] ⁺ . Step 3: 4-((4'-Cyano-5-nitro-[2,2'-bipyridin]-6-yl)amino)benzyl acetate To a solution of 6'-((4-(hydroxymethyl)phenyl)amino)-5'-nitro-[2,2'-bipyridin e]-4-carbonitrile (1.3 g, 3.74 mmol) in CH ₂ Cl ₂ (15 mL) were added TEA (1.14 g, 11.2 mmol), DMAP (45.7 mg, 374 µmol), and Ac ₂ O (573 mg, 5.61 mmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was quenched with H ₂ O (30 mL) at 25°C, diluted with CH ₂ Cl ₂ (30 mL) and extracted with CH ₂ Cl ₂ (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 10 ~ 30% EtOAc in petroleum ether), 4-((4'-cyano-5- nitro-[2,2'-bipyridin]-6-yl)amino)benzyl acetate (1.4 g, yield: 40%) was obtained as a black solid. MS: m/z = 390.0 [M + H] ⁺ . Step 4: 4-(2-(2-Aminopyridin-3-yl)-5-(4-cyanopyridin-2-yl)-3H-imidaz o[4,5-b]pyridin-3- yl)benzyl acetate To a solution of 4-((4'-cyano-5-nitro-[2,2'-bipyridin]-6-yl)amino)benzyl acetate (1.2 g, 3.08 mmol) in DMSO (10 mL) were added Na ₂ S ₂ O ₄ (2.38 g, 12.3 mmol, 90% purity) and 2- aminonicotinaldehyde (452 mg, 3.70 mmol). The mixture was stirred at 100 °C for 2 hr. The reaction mixture was quenched with H ₂ O (50 mL) at 25 °C, diluted with CH ₂ Cl ₂ (30 mL) and extracted with CH ₂ Cl ₂ (30 mL x 3). The combined organic layers were washed with brine (50 mL x 3), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 10% ~ 70% EtOAc in petroleum ether), 4-(2-(2- aminopyridin-3-yl)-5-(4-cyanopyridin-2-yl)-3H-imidazo[4,5-b] pyridin-3-yl)benzyl acetate (80 mg, yield: 5.6%) was obtained as a yellow solid. MS: m/z = 462.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.81 (d, J = 4.8 Hz, 1H), 8.55 - 8.52 (m, 2H), 8.21 (d, J = 8.4 Hz, 1H), 8.10 (dd, J = 4.8, 1.6 Hz, 1H), 7.60 - 7.56 (m, 2H), 7.47 - 7.44 (m, 3H), 7.12 (dd, J = 7.6, 1.6 Hz, 1H), 6.66 (br s, 2H), 6.41 (dd, J = 8.0, 4.8 Hz, 1H), 5.27 (s, 2H), 2.20 (s, 3H). Step 5: 2-(2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5-b]pyridin-5- yl)isonicotinonitrile To a solution of 4-(2-(2-aminopyridin-3-yl)-5-(4-cyanopyridin-2-yl)-3H-imidaz o[4,5-b]pyridin- 3-yl)benzyl acetate (80 mg, 173 µmol) in THF (2 mL), MeOH (2 mL) and H ₂ O (1 mL) was added the K ₂ CO ₃ (71.9 mg, 520 µmol). The mixture was stirred at 25 ºC for 2 hr. The reaction mixture was diluted with H ₂ O (10 mL) and extracted with CH2Cl ₂ (15 mL x 2). The combined organic layers were washed with brine (15 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. 2-(2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)isonicotinonitrile (60 mg) was obtained as a yellow solid. MS: m/z = 420.0 [M + H] ⁺ .

Step 6 : 2-(2-(2-Aminopyridin-3 -yl)-3 -(4-(chloromethy l)phenyl)-3H-imidazo[4, 5-b]pyridin-5- yl)isonicotinonitrile

To a solution of 2-(2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5- b]pyridin-5-yl)isonicotinonitrile (60 mg, 143 umol) in CH ₂ CI ₂ (5 mL) was added SOCl ₂ (51.1 mg, 429 umol). The mixture was stirred at 40 °C for 0.4 hr. The reaction was concentrated under reduced pressure to give 2-(2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)isonicotinonitrile (Intermediate 241, 67.9 mg, HC1 salt) was obtained as a yellow solid. MS: m/z = 437.9 [M + H] ⁺ .

[00423] Intermediate 242: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-methoxypyridin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Step 1: 4-((3-Nitro-6-(trimethylstannyl)pyridin-2-yl)amino)benzyl acetate

A mixture of 4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl acetate (refer to Intermediate 178 for detail procedures, 5 g, 15.5 mmol), (Me ₃ Sn)2 (10.8 g, 33.0 mmol), Pd(PPh ₃ ) ₄ (287 mg, 777 umol) in 1,4-dioxane (50 mL) was degassed and purged with N2 three times, and then the mixture was stirred at 90 °C for 3 hr under N2 atmosphere. 4-((3-Nitro-6- (trimethylstannyl)pyridin-2-yl)amino)benzyl acetate was obtained as a black brown liquid. The liquid was directly used in the next step. MS: m/z = 451.9 [M + H] ⁺ .

Step 2: 4-((5'-Methoxy-5-nitro-[2,2'-bipyridin]-6-yl)amino)benzyl acetate A mixture of 4-((3-nitro-6-(trimethylstannyl)pyridin-2-yl)amino)benzyl acetate (6.99 g, 15.5 mmol), 2-bromo-5-methoxypyridine (2.92 g, 15.5 mmol), Pd(PPh ₃ ) ₄ (115 mg, 311 µmol) in 1,4- dioxane (50 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 100 °C for 50 hr under N ₂ atmosphere. The mixture was diluted with H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (100 mL x 3). The combined organic layers were washed with brine (50 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 19% EtOAc in petroleum ether), 4-((5'-methoxy-5-nitro- [2,2'-bipyridin]-6-yl)amino)benzyl acetate (560 mg, yield: 5.8% for two steps) was obtained as an orange red solid. MS: m/z = 395.1 [M + H] ⁺ . Step 3: 4-(2-(2-Aminopyridin-3-yl)-5-(5-methoxypyridin-2-yl)-3H-imid azo[4,5-b]pyridin-3- yl)benzyl acetate A mixture of 4-((5'-methoxy-5-nitro-[2,2'-bipyridin]-6-yl)amino)benzyl acetate (560 mg, 1.42 mmol), 2-aminonicotinaldehyde (208 mg, 1.70 mmol), Na ₂ S ₂ O ₄ (989 mg, 5.68 mmol) in DMSO (5 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 100 °C for 3 hr under N ₂ atmosphere. The reaction mixture was diluted with H ₂ O (500 mL) and extracted with EtOAc (500 mL x 2). The combined organic layers were washed with brine (200 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 43% EtOAc in petroleum ether), 4-(2-(2-aminopyridin-3-yl)-5- (5-methoxypyridin-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl acetate (200 mg, yield: 21%) was obtained as a light yellow solid. MS: m/z = 467.1 [M + H] ⁺ . Step 4: (4-(2-(2-Aminopyridin-3-yl)-5-(5-methoxypyridin-2-yl)-3H-imi dazo[4,5-b]pyridin-3- yl)phenyl)methanol To a solution of 4-(2-(2-aminopyridin-3-yl)-5-(5-methoxypyridin-2-yl)-3H-imid azo[4,5- b]pyridin-3-yl)benzyl acetate (200 mg, 429 µmol) in THF (1 mL), MeOH (1 mL) and H ₂ O (0.5 mL) were added the K ₂ CO ₃ (178 mg, 1.29 mmol). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was diluted with H ₂ O (50 mL) and extracted with EtOAc (50 mL x 2). The combined organic layers were washed with brine (15 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. (4-(2-(2-Aminopyridin-3-yl)-5-(5-methoxypyridin-2-yl)- 3H-imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (160 mg) was obtained as a light yellow solid. MS: m/z = 425.1 [M + H] ⁺ . ¹ H NMR (400MHz, Chloroform-d) δ 8.85 (d, J = 7.6 Hz, 1H), 8.73 - 8.54 (m, 1H), 8.43 (d, J = 7.2 Hz, 2H), 7.95 - 7.83 (m, 2H), 7.72 (s, 2H), 7.65 - 7.53 (m, 3H), 7.22 - 7.11 (m, 1H), 6.62 (d, J = 2.0 Hz, 1H), 4.73 (s, 2H), 4.08 (s, 3H). Step 5: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-methoxypyridin-2-yl)-3H-i midazo[4,5-b]pyridin-2- yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(5-methoxypyridin-2-yl)-3H-imi dazo[4,5- b]pyridin-3-yl)phenyl)methanol (160 mg, 377 umol) in CH2Cl ₂ (2 mL) was added SOCI ₂ (51.1 mg, 429 umol). The mixture was stirred at 40 °C for 0.5 hr and concentrated under reduced pressure to give 3-(3-(4-(chloromethyl)phenyl)-5-(5-methoxypyridin-2-yl)-3H-i midazo[4,5- b]pyridin-2-yl)pyridin-2-amine (Intermediate 242, 160 mg, HC1 salt) as a light yellow solid. MS: m/z = 443.1 [M + H] ⁺ .

[00424] Intermediate 243: 2-(2 -Aminopyri din-3 -yl)-l -(4-(chl oromethyl)pheny 1)- 1H- imidazo[4,5-b]pyrazine-5,6-dicarbonitrile

Step 1: 5-Chloro-6-((4-(hydroxymethyl)phenyl)amino)pyrazine-2,3-dica rbonitrile

To a solution of 5, 6-dichloropyrazine-2, 3 -dicarbonitrile (10 g, 50.3 mmol) in THF (100 mL) was added (4-aminophenyl)methanol (12.4 g, 101 mmol) in THF (100 mL) dropwise slowly under ice bath. The mixture was degassed and purged with N2 three times and stirred at 0 °C for 3 hr under N2. The reaction mixture was filtered and concentrated under reduced pressure. 5- Chloro-6-((4-(hydroxymethyl)phenyl)amino)pyrazine-2,3-dicarb onitrile (13.2 g, yield: 90%) was obtained as a yellow solid. ¹ H NMR (400 MHz, Dimethylsulfoxide-d6) δ 10.27 (br s, 1H), 7.55 (d, J= 8.4 Hz, 2H), 7.44 (d, J= 8.4 Hz, 2H), 4.57 (s, 2H)o

Step 2: 5-Amino-6-((4-(hydroxymethyl)phenyl)amino)pyrazine-2,3-dicar bonitrile

To a solution of 5-chloro-6-((4-(hydroxymethyl)phenyl)amino)pyrazine-2,3-dica rbonitrile (13 g, 45.5 mmol) in DMF (150 mL) was stirred at 0 °C under NH ₃ atmosphere for 0.5 hr. The reaction mixture was quenched with H ₂ O (500 mL) and filtered. The filtered cake was dried under reduced pressure to give 5-amino-6-((4-(hydroxymethyl)phenyl)amino)pyrazine-2,3- dicarbonitrile (10.7 g, yield: 85%) as a yellow solid. MS: m/z = 267.0 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.22 (br s, 1H), 8.02 - 7.81 (m, 2H), 7.59 (d, J= 8.4 Hz, 2H), 7.34 (d, J= 8.4 Hz, 2H), 5.17 (t, J= 5.6 Hz, 1H), 4.48 (d, J= 5.6 Hz, 2H).

Step 3 : 5-Amino-6-((4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)a mino)pyrazine-2,3- dicarbonitrile To a solution of 5-amino-6-((4-(hydroxymethyl)phenyl)amino)pyrazine-2,3-dicar bonitrile (1 g, 3.76 mmol) in CH2Cl ₂ (10 mL) were added TBSC1 (679 mg, 4.51 mmol), TEA (1.57 mL, 11.3 mmol) and DMAP (45.9 mg, 376 umol). The mixture was degassed and purged with N ₂ three times and stirred at 25 °C for 1 hr under N2. The reaction mixture was diluted with CH ₂ CI ₂ (100 mL), washed with brine (100 mL x 2), separated, dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (MeOH in CH ₂ CI ₂ = 1 to 10%), 5-amino-6-((4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)a mino)pyrazine-2,3- dicarbonitrile (680 mg, yield: 47%) was obtained as a red solid. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 9.33 (br s, 1H), 7.99 (br s, 2H), 7.64 (d, J= 8.4 Hz, 2H), 7.33 (d, J= 8.4 Hz, 2H), 4.69 (s, 2H), 0.90 (s, 9H), 0.08 (s, 6H).

Step 4: 2-(2-Aminopyridin-3-yl)-l-(4-(hydroxymethyl)phenyl)-1H-imida zo[4,5-b]pyrazine-5,6- dicarbonitrile

To a solution of 5-amino-6-((4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)a mino)pyrazine- 2,3-dicarbonitrile (1.5 g, 3.94 mmol) in DMSO (100 mL) were added Na ₂ S ₂ O ₄ (2.06 g, 11.8 mmol) and 2-aminonicotinaldehyde (481 mg, 3.94 mmol). The mixture was degassed, purged with N ₂ three times, and stirred at 100 °C for 2 hr under N2. The reaction mixture was diluted with CH ₂ CI ₂ (500 mL) and filtered. The filtrate was washed with brine (300 mL x 3), separated, dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Ethyl acetate in petroleum ether = 1% to 100%), 2-(2-aminopyridin-3- yl)-l-(4-(hydroxymethyl)phenyl)-1H-imidazo[4,5-b]pyrazine-5, 6-dicarbonitrile (366 mg, yield: 23%) was obtained as a yellow solid. MS: m/z = 369.0 [M+H| ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6) δ 8.13 (dd, J= 4.8, 2.0 Hz, 1H), 7.56 - 7.51 (m, 2H), 7.48 - 7.43 (m, 2H), 7.36 (dd, J= 8.0, 2.0 Hz, 1H), 7.18 (br s, 2H), 6.49 (dd, J= 8.0, 4.8 Hz, 1H), 5.39 (t, J= 5.6 Hz, 1H), 4.60 (d, J= 5.4 Hz, 2H).

Step 5: 2-(2-Aminopyridin-3-yl)-l-(4-(chloromethyl)phenyl)-1H-imidaz o[4,5-b]pyrazine-5,6- dicarbonitrile

To a solution of 2-(2-aminopyridin-3-yl)-l-(4-(hydroxymethyl)phenyl)-1H-imida zo[4,5- b]pyrazine-5,6-dicarbonitrile (366 mg, 894 nmol) in CH ₂ CI ₂ (5 mL) was added SOCI ₂ (649 μL, 8.94 mmol) dropwise. The mixture was degassed and purged with N2 three times and stirred at 25 °C for 1 hr under N2. The reaction mixture was concentrated under reduced pressure to give 2-(2-aminopyridin-3-yl)-l-(4-(chloromethyl)phenyl)-1H-imidaz o[4,5-b]pyrazine-5,6- dicarbonitrile (Intermediate 243, 379 mg, crude, HC1 salt) as a yellow solid, which was used in the next step without further purification. MS: m/z = 387.1 [M+H| ⁺ . [00425] Intermediate 244: 2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-5-(4- fluorophenyl)-3H-imidazo[4,5-b]pyridine-6-carbonitrile Step 1: 4-((6-(4-Fluorophenyl)-3-nitropyridin-2-yl)amino)benzyl acetate A mixture of 4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl acetate (refer to Intermediate 178 for detail procedures, 500 mg, 1.55 mmol), (4-fluorophenyl)boronic acid (217 mg, 1.55 mmol), Cs ₂ CO ₃ (1.52 g, 4.66 mmol) and Pd(dppf)Cl ₂ (114 mg, 155 µmol) in 1,4-dioxane (10 mL) and H ₂ O (2 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 80 °C for 16 hr under N ₂ atmosphere. The mixture was filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 10% ~ 20% EtOAc in petroleum ether), 4-((6-(4- fluorophenyl)-3-nitropyridin-2-yl)amino)benzyl acetate (300 mg, yield: 48%) was obtained as a yellow solid. MS: m/z = 381.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.12 (s, 1H), 8.61 (d, J = 8.8 Hz, 1H), 8.20 - 8.13 (m, 2H), 7.74 (d, J = 8.4 Hz, 2H), 7.59 (d, J = 8.8 Hz, 1H), 7.44 - 7.34 (m, 4H), 5.09 (s, 2H), 2.08 (s, 3H). Step 2: 4-((5-Bromo-6-(4-fluorophenyl)-3-nitropyridin-2-yl)amino)ben zyl acetate To a solution of 4-((6-(4-fluorophenyl)-3-nitropyridin-2-yl)amino)benzyl acetate (100 mg, 262 µmol) in DMF (2 mL) was added NBS (51.3 mg, 288 µmol). The mixture was stirred at 25 ºC for 2 hr. The mixture was poured into water (10 mL) at 0 °C and filtrated. The solid was dried and purified by prep-HPLC (column: Phenomenex C18150 x 25 mm x 10 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 65% - 85% B over 11 min) to give 4-((5-bromo-6-(4- fluorophenyl)-3-nitropyridin-2-yl)amino)benzyl acetate (100 mg, yield: 41%) as a red solid. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.02 (s, 1H), 8.80 (s, 1H), 7.80 - 7.75 (m, 2H), 7.67 (d, J = 8.4 Hz, 2H), 7.38 - 7.31 (m, 4H), 5.03 (s, 2H), 2.05 (s, 3H). Step 3: 4-((5-Cyano-6-(4-fluorophenyl)-3-nitropyridin-2-yl)amino)ben zyl acetate A mixture of 4-((5-bromo-6-(4-fluorophenyl)-3-nitropyridin-2-yl)amino)ben zyl acetate (1.7 g, 3.69 mmol) and CuCN (1.65 g, 18.5 mmol) in DMF (20 mL) was degassed and purged with N2 three times. The mixture was stirred at 140 °C for 3 hr under N ₂ atmosphere. The reaction mixture was quenched with H ₂ O (50 mL) at 25 °C and extracted with EtOAc (50 mL x 3). The combined organic layers were washed with brine (100 mL x 3), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 5% ~ 15% EtOAc in petroleum ether), 4-((5-cyano-6-(4-fluorophenyl)-3-nitropyridin-2- yl)amino)benzyl acetate (1.02 g, yield: 68%) was obtained as a yellow solid. MS: m/z = 406.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.41 (s, 1H), 9.10 (s, 1H), 7.98 -7.89 (m, 2H), 7.68 (d, J = 8.8 Hz, 2H), 7.49 - 7.37 (m, 4H), 5.08 (s, 2H), 2.08 (s, 3H). Step 4: 4-(2-(2-Aminopyridin-3-yl)-6-cyano-5-(4-fluorophenyl)-3H-imi dazo[4,5-b]pyridin-3- yl)benzyl acetate To a solution of 4-((5-cyano-6-(4-fluorophenyl)-3-nitropyridin-2-yl)amino)ben zyl acetate (950 mg, 2.34 mmol) in DMSO (10 mL) were added Na ₂ S ₂ O ₄ (1.85 g, 9.35 mmol, 88% purity) and 2- aminonicotinaldehyde (343 mg, 2.81 mmol). The mixture was stirred at 100 °C for 4 hr. The reaction mixture was quenched with H ₂ O (30 mL) at 25 °C, diluted with CH ₂ Cl ₂ (30 mL), and extracted with CH ₂ Cl ₂ (50 mL x 2). The combined organic layers were washed with brine (100 mL x 3), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 20% ~ 40% EtOAc in petroleum ether), 4-(2-(2- aminopyridin-3-yl)-6-cyano-5-(4-fluorophenyl)-3H-imidazo[4,5 -b]pyridin-3-yl)benzyl acetate (300 mg, yield: 27%) was obtained as a yellow solid. MS: m/z = 479.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.44 (s, 1H), 8.14 - 8.08 (m, 1H), 7.89 (dd, J = 8.4, 5.2 Hz, 2H), 7.52 (d, J = 8.0 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.17 (t, J = 8.4 Hz, 2H), 7.09 (d, J = 7.6 Hz, 1H), 6.68 (br s, 2H), 6.40 (dd, J = 8.0, 4.8 Hz, 1H), 5.21 (s, 2H), 2.16 (s, 3H). Step 5: 2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3-(4-(hydroxymeth yl)phenyl)-3H- imidazo[4,5-b]pyridine-6-carbonitrile To a solution of 4-(2-(2-aminopyridin-3-yl)-6-cyano-5-(4-fluorophenyl)-3H-imi dazo[4,5- b]pyridin-3-yl)benzyl acetate (290 mg, 606 μmol) in THF (5 mL), MeOH (5 mL) and H ₂ O (5 mL) was added K ₂ CO ₃ (251 mg, 1.82 mmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was quenched with H ₂ O (10 mL) at 25 °C, diluted with CH ₂ Cl ₂ (10 mL), and extracted with CH ₂ Cl ₂ (15 mL x 2). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. 2-(2-Aminopyridin- 3-yl)-5-(4-fluorophenyl)-3-(4-(hydroxymethyl)phenyl)-3H-imid azo[4,5-b]pyridine-6- carbonitrile (270 mg) was obtained as a yellow solid. MS: m/z = 437.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.90 (s, 1H), 8.02 (dd, J = 4.8, 1.6 Hz, 1H), 7.85 - 7.80 (m, 2H), 7.48 - 7.43 (m, 4H), 7.40 - 7.36 (m, 2H), 7.27 (dd, J = 7.6, 1.6 Hz, 1H), 6.90 (br s, 2H), 6.44 (dd, J = 7.6, 4.8 Hz, 1H), 5.34 (t, J = 5.6 Hz, 1H), 4.57 (d, J = 5.6 Hz, 2H). Step 6: 2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-5-(4-fluo rophenyl)-3H- imidazo[4,5-b]pyridine-6-carbonitrile To a solution of 2-(2-aminopyridin-3-yl)-5-(4-fluorophenyl)-3-(4-(hydroxymeth yl)phenyl)-3H- imidazol[4,5-b]pyridine-6-carbonitrile (270 mg, 619 µmol) in CH ₂ Cl ₂ (10 mL) was added SOCl ₂ (221 mg, 1.86 mmol) at 0 °C. The mixture was stirred at 40 °C for 0.3 hr. The reaction was concentrated under reduced pressure to give 2-(2-aminopyridin-3-yl)-3-(4- (chloromethyl)phenyl)-5-(4-fluorophenyl)-3H-imidazo[4,5-b]py ridine-6-carbonitrile (Intermediate 244, 304 mg, HCl salt) as a yellow solid. MS: m/z = 455.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.76 (s, 1H), 8.04 (dd, J = 6.4, 1.2 Hz, 1H), 7.93 - 7.85 (m, 3H), 7.67 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 8.4 Hz, 2H), 7.24 - 7.22 (m, 2H), 6.92 - 6.84 (m, 1H), 4.76 (s, 2H). [00426] Intermediate 245: 3-(6-Bromo-3-(4-(chloromethyl)phenyl)-5-(4-fluorophenyl)- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: 4-(2-(2-Aminopyridin-3-yl)-6-bromo-5-(4-fluorophenyl)-3H-imi dazo[4,5-b]pyridin-3- yl)benzyl acetate To a solution of 4-((5-bromo-6-(4-fluorophenyl)-3-nitropyridin-2-yl)amino)ben zyl acetate (refer to Intermediate 244 for detail procedures, 1 g, 2.17 mmol) in DMSO (10 mL) was added Na ₂ S ₂ O ₄ (1.72 g, 8.69 mmol, 88% purity) and 2-aminonicotinaldehyde (318 mg, 2.61 mmol). The mixture was stirred at 100 °C for 4 hr. The reaction mixture was quenched with H ₂ O (50 mL) at 25 °C, diluted with CH ₂ Cl ₂ (50 mL), and extracted with CH ₂ Cl ₂ (25 mL x 2). The combined organic layers were washed with brine (100 mL x 3), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 30% ~ 50% EtOAc in petroleum ether), 4-(2-(2-aminopyridin-3-yl)-6-bromo-5-(4- fluorophenyl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl acetate (280 mg, yield: 24%) was obtained as a yellow solid. MS: m/z = 531.9, 533.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.65 (s, 1H), 8.02 (dd, J = 4.8, 1.6 Hz, 1H), 7.60 (dd, J = 8.4, 5.6 Hz, 2H), 7.52 - 7.45 (m, 4H), 7.32 - 7.27 (m, 2H), 7.24 (dd, J = 7.6, 1.6 Hz, 1H), 6.86 (br s, 2H), 6.44 (dd, J = 7.6, 5.2 Hz, 1H), 5.13 (s, 2H), 2.09 (s, 3H). Step 2: (4-(2-(2-Aminopyridin-3-yl)-6-bromo-5-(4-fluorophenyl)-3H-im idazo[4,5-b]pyridin-3- yl)phenyl)methanol To a solution of 4-(2-(2-aminopyridin-3-yl)-6-bromo-5-(4-fluorophenyl)-3H-imi dazo[4,5- b]pyridin-3-yl)benzyl acetate (20 mg,451 µmol) inTHF (2 mL), MeOH (2 mL) and H ₂ O (2 mL) was added K ₂ CO ₃ (187 mg, 1.35 mmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was quenched with H ₂ O (20 mL) at 25 °C, diluted with CH ₂ Cl ₂ (20 mL) and extracted with CH ₂ Cl ₂ (25 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. (4-(2-(2- Aminopyridin-3-yl)-6-bromo-5-(4-fluorophenyl)-3H-imidazo[4,5 -b]pyridin-3- yl)phenyl)methanol (240 mg) was obtained as a yellow solid. MS: m/z = 490.0, 492.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.63 (s, 1H), 8.00 (dd, J =4.8, 1.6 Hz, 1H), 7.62 - 7.57 (m, 2H), 7.44 - 7.38 (m, 4H), 7.28 - 7.26 (m, 2H), 7.21 (dd, J = 7.6, 2.0 Hz, 1H), 6.93 (br s, 2H), 6.42 (dd, J = 7.6, 4.4 Hz, 1H), 5.32 (t, J = 5.2 Hz, 1H), 4.55 (d, J = 5.2 Hz, 2H). Step 3: 3-(6-Bromo-3-(4-(chloromethyl)phenyl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin- 2-yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-6-bromo-5-(4-fluorophenyl)-3H-im idazo[4,5- b]pyridin-3-yl)phenyl)methanol (240 mg, 489.µmol) in CH ₂ Cl ₂ (10 mL) was added SOCl ₂ (175 mg, 1.47 mmol) at 0 °C. The mixture was stirred at 40 °C for 0.3 hr. The reaction was concentrated under reduced pressure to give 3-(6-bromo-3-(4-(chloromethyl)phenyl)-5-(4- fluorophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (Intermediate 245, 266 mg, HCl salt) as a yellow solid. MS: m/z = 508.0, 509.8 [M + H] ⁺ . Intermediate 246: 2-(2-Aminopyridin-3-yl)-1-(4-(chloromethyl)phenyl)-1H-imidaz o[4,5- c]pyridine-6-carbonitrile Step 1: (4-((2-Bromo-5-nitropyridin-4-yl)amino)phenyl)methanol To a solution of 2,4-dibromo-5-nitropyridine (4 g, 14.2 mmol) in DMSO (50 mL) were added DIEA (5.50 g, 42.6 mmol) and (4-aminophenyl)methanol (1.75 g, 14.2 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched with H ₂ O (500 mL) at 25 °C, diluted with EtOAc (500 mL), and extracted with EtOAc (500 mL x 2). The combined organic layers were washed with brine (500 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give (4-((2-bromo-5-nitropyridin-4-yl)amino)phenyl)methanol (4.6 g, yield: 88%) as a light yellow solid. MS: m/z = 323.9, 325.9 [M + H] ⁺ . ¹ H NMR (400MHz, Chloroform-d) δ 9.80 (s, 1H), 9.22 (s, 1H), 7.70 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 8.4 Hz, 3H), 4.96 (s, 2H). Step 2: 4-((2-Bromo-5-nitropyridin-4-yl)amino)benzyl acetate To a solution of (4-((2-bromo-5-nitropyridin-4-yl)amino)phenyl)methanol (4.5 g, 13.9 mmol) in CH ₂ Cl ₂ (50 mL) were added DMAP (170 mg, 1.39 mmol), Ac ₂ O (1.42 g, 13.9 mmol) and TEA (4.21 g, 41.7 mmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was quenched with H ₂ O (100 mL) at 25 °C, diluted with CH ₂ Cl ₂ (50 mL), and extracted with CH ₂ Cl ₂ (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 19% EtOAc in petroleum ether), 4-((2-bromo-5-nitropyridin-4- yl)amino)benzyl acetate (1.5 g, yield: 29%) was obtained as a yellow solid. MS: m/z = 365.9, 367.9 [M + H] ⁺ . ¹ H NMR (400MHz, Chloroform-d) δ 9.62 (s, 1H), 9.03 (s, 1H), 7.50 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.4 Hz, 2H), 7.10 (s, 1H), 5.15 (s, 2H), 2.14 (s, 3H). Step 3: 4-((2-Cyano-5-nitropyridin-4-yl)amino)benzyl acetate A mixture of 4-((2-bromo-5-nitropyridin-4-yl)amino)benzyl acetate (1.5 g, 4.10 mmol), dicyanozinc (2.28 g, 19.4 mmol), Pd(PPh ₃ ) ₄ (473 mg, 410 µmol) in DMF (15 mL) was degassed and purged with N ₂ three times, then stirred at 80 °C for 3 hr under N ₂ atmosphere. The reaction mixture was quenched with H ₂ O (500 mL) at 25 °C and extracted with CH ₂ Cl ₂ (500 mL x 3). The combined organic layers were washed with brine (100 mL x 3), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 5% ~ 15% EtOAc in petroleum ether), 4-((2-cyano-5-nitropyridin-4-yl)amino)benzyl acetate (1.1 g, yield: 86%) was obtained as a light yellow solid. MS: m/z = 312.9 [M + H] ⁺ . Step 4: 4-(2-(2-Aminopyridin-3-yl)-6-cyano-1H-imidazo[4,5-c]pyridin- 1-yl)benzyl acetate To a solution of 4-((2-cyano-5-nitropyridin-4-yl)amino)benzyl acetate (1 g, 3.20 mmol) in DMSO (20 mL) were added Na ₂ S ₂ O ₄ (2.23 g, 12.8 mmol, 88% purity) and 2- aminonicotinaldehyde (469 mg, 3.84 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched with H ₂ O (300 mL) at 25°C, diluted with CH ₂ Cl ₂ (300 mL) and extracted with CH ₂ Cl ₂ (300 mL x 2). The combined organic layers were washed with brine (500 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 27% EtOAc in petroleum ether), 4-(2-(2- aminopyridin-3-yl)-6-cyano-1H-imidazo[4,5-c]pyridin-1-yl)ben zyl acetate (160 mg, yield: 11%) was obtained as a light yellow solid. MS: m/z = 385.1 [M + H] ⁺ . Step 5: 2-(2-Aminopyridin-3-yl)-1-(4-(hydroxymethyl)phenyl)-1H-imida zo[4,5-c]pyridine-6- carbonitrile To a solution of 4-(2-(2-aminopyridin-3-yl)-6-cyano-1H-imidazo[4,5-c]pyridin- 1-yl)benzyl acetate (160 mg, 416 µmol) in THF (2 mL), MeOH (2 mL) and H ₂ O (1 mL) was added K ₂ CO ₃ (173 mg, 1.25 mmol). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was diluted with H ₂ O (50 mL) and extracted with CH ₂ Cl ₂ (50 mL x 2). The combined organic layers were washed with brine (100 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. 2-(2-Aminopyridin-3-yl)-1-(4-(hydroxymethyl)phenyl)-1H-imida zo[4,5-c]pyridine-6- carbonitrile (160 mg crude) was obtained as a light yellow solid. MS: m/z = 343.1 [M + H] ⁺ . Step 6: 2-(2-Aminopyridin-3-yl)-1-(4-(chloromethyl)phenyl)-1H-imidaz o[4,5-c]pyridine-6- carbonitrile To a solution of 2-(2-aminopyridin-3-yl)-1-(4-(hydroxymethyl)phenyl)-1H-imida zo[4,5- c]pyridine-6-carbonitrile (160 mg, 467 µmol) in CH ₂ Cl ₂ (2 mL) was added SOCl ₂ (167 mg, 1.40 mmol). The mixture was stirred at 40 °C for 0.5 hr. The reaction was concentrated under reduced pressure to give 2-(2-aminopyridin-3-yl)-1-(4-(chloromethyl)phenyl)-1H-imidaz o[4,5- c]pyridine-6-carbonitrile (Intermediate 246, 160 mg, HCl salt) as a light yellow solid. MS: m/z = 361.0 [M + H] ⁺ . [00427] Intermediate 247: 3-(3-(4-(Chloromethyl)phenyl)-5-(1-methyl-1H-1,2,4-triazol- 3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 247 was prepared in a manner similar to Intermediate 215. MS: m/z = 417.1 [M + H] ⁺ . [00428] Intermediate 248: 2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-5- methyl-3H-imidazo[4,5-b]pyridine-6-carbonitrile

Step 1: (4-((5-Bromo-6-methyl-3-nitropyridin-2-yl)amino)phenyl)metha nol To a solution of 3-bromo-6-chloro-2-methyl-5-nitropyridine (1 g, 3.98 mmol) in DMSO (10 mL) were added DIEA (1.54 g, 11.9 mmol) and (4-aminophenyl)methanol (490 mg, 3.98 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched with H ₂ O (50 mL) at 25 °C, diluted with CH ₂ Cl ₂ (50 mL), and extracted with CH ₂ Cl ₂ (50 mL x 2). The combined organic layers were washed with brine (50 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. (4-((5-Bromo-6-methyl-3-nitropyridin-2- yl)amino)phenyl)methanol (1.3 g) was obtained as a black solid. MS: m/z = 337.8, 339.8 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.96 (s, 1H), 8.60 (s, 1H), 7.60 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 5.16 (t, J = 6.0 Hz, 1H), 4.48 (d, J = 5.2 Hz, 2H), 2.52 (s, 3H). Step 2: 4-((5-Bromo-6-methyl-3-nitropyridin-2-yl)amino)benzyl acetate To a solution of (4-((5-bromo-6-methyl-3-nitropyridin-2-yl)amino)phenyl)metha nol (1.3 g, 3.84 mmol) in CH ₂ Cl ₂ (15 mL) were added DMAP (93.9 mg, 769 µmol), Ac ₂ O (589 mg, 5.77 mmol) and TEA (1.17 g, 11.5 mmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was quenched with H ₂ O (25 mL) at 25 °C, diluted with CH ₂ Cl ₂ (50 mL) and extracted with CH ₂ Cl ₂ (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 1% ~ 10% EtOAc in petroleum ether), 4-((5-bromo-6-methyl-3- nitropyridin-2-yl)amino)benzyl acetate (850 mg, yield: 58% for two steps) was obtained as a red solid. MS: m/z = 377.8, 379.8 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.98 (s, 1H), 8.62 (s, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 5.05 (s, 2H), 2.54 (s, 3H), 2.07 (s, 3H). Step 3: 4-((5-Cyano-6-methyl-3-nitropyridin-2-yl)amino)benzyl acetate A mixture of 4-((5-bromo-6-methyl-3-nitropyridin-2-yl)amino)benzyl acetate (1 g, 2.63 mmol) and CuCN (471 mg, 5.26 mmol) in DMF (10 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 140 °C for 3 hr under N ₂ atmosphere. The reaction mixture was quenched with H ₂ O (50 mL) at 25 °C and extracted with EtOAc (50 mL x 3). The combined organic layers were washed with brine (100 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 5% ~ 15% EtOAc in petroleum ether), 4-((5-cyano-6-methyl-3-nitropyridin-2- yl)amino)benzyl acetate (480 mg, yield: 56%) was obtained as a yellow solid. MS: m/z = 326.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.32 (s, 1H), 8.94 (s, 1H), 7.65 (d, J = 8.8 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H), 5.08 (s, 2H), 2.56 (s, 3H), 2.07 (s, 3H). Step 4: 4-(2-(2-Aminopyridin-3-yl)-6-cyano-5-methyl-3H-imidazo[4,5-b ]pyridin-3-yl)benzyl acetate To a solution of 4-((5-cyano-6-methyl-3-nitropyridin-2-yl)amino)benzyl acetate (700 mg, 2.15 mmol) in DMSO (1 mL) were added Na ₂ S ₂ O ₄ (1.70 g, 8.58 mmol, 88% purity) and 2- aminonicotinaldehyde (314 mg, 2.57 mmol). The mixture was stirred at 100 °C for 6 hr. The reaction mixture was quenched with H ₂ O (30 mL) at 25 °C, diluted with CH ₂ Cl ₂ (30 mL) and extracted with CH ₂ Cl ₂ (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 20% ~ 50% EtOAc in petroleum ether), 4-(2-(2- aminopyridin-3-yl)-6-cyano-5-methyl-3H-imidazo[4,5-b]pyridin -3-yl)benzyl acetate (200 mg, yield: 23%) was obtained as a light yellow solid. MS: m/z = 399.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.72 (s, 1H), 8.00 (dd, J = 4.8, 2.0 Hz, 1H), 7.54 - 7.50 (m, 2H), 7.48 - 7.43 (m, 2H), 7.25 (dd, J = 7.6, 1.6 Hz, 1H), 6.82 (br s, 2H), 6.43 (dd, J = 7.6, 4.8 Hz, 1H), 5.15 (s, 2H), 2.70 (s, 3H), 2.11 (s, 3H). Step 5: 2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-5-methyl -3H-imidazo[4,5- b]pyridine-6-carbonitrile To a solution of 4-(2-(2-aminopyridin-3-yl)-6-cyano-5-methyl-3H-imidazo[4,5-b ]pyridin-3- yl)benzyl acetate (180 mg, 452 µmol) in THF (2 mL) and MeOH (2 mL) was added K ₂ CO ₃ (187 mg, 1.36 mmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was diluted with H ₂ O (30 mL) and extracted with CH ₂ Cl ₂ (50 mL x 2). The combined organic layers were washed with brine (100 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. 2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-5-methyl -3H-imidazo[4,5- b]pyridine-6-carbonitrile (170 mg) was obtained as a yellow solid. MS: m/z = 357.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.71 (s, 1H), 8.00 (dd, J = 4.8, 1.6 Hz, 1H), 7.48 - 7.44 (m, 2H), 7.42 - 7.37 (m, 2H), 7.24 (dd, J = 7.6, 1.6 Hz, 1H), 6.90 (br s, 2H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 5.35 (t, J = 5.6 Hz, 1H), 4.58 (d, J = 5.6 Hz, 2H), 2.69 (s, 3H). Step 6: 2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-5-methyl- 3H-imidazo[4,5- b]pyridine-6-carbonitrile To a solution of 2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-5-methyl -3H- imidazo[4,5-b]pyridine-6-carbonitrile (170 mg, 477 µmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (170 mg, 1.43 mmol). The mixture was stirred at 25 °C for 1 hr. The reaction was concentrated under reduced pressure, 2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-5-methyl- 3H- imidazo[4,5-b]pyridine-6-carbonitrile (Intermediate 248, 196 mg, HCl salt) was obtained as a yellow solid. MS: m/z = 375.0 [M + H] ⁺ . [00429] Intermediate 249 & 250: 4-((6-(3-Methyl-4H-1,2,4-triazol-4-yl)-3-nitropyridin-2- yl)amino)benzyl acetate & 4-((6-(3-Methyl-1H-1,2,4-triazol-1-yl)-3-nitropyridin-2- yl)amino)benzyl acetate To a solution of 4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl acetate (Refer to Intermediate 178 for detail procedures, 3 g, 9.33 mmol) and 3-methyl-4H-1,2,4-triazole (929 mg, 11.19 mmol) in DMSO (30 mL) was added DIEA (4.87 mL). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was diluted with H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (200 mL). The combined organic layers were washed with brine (100 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-HPLC (column: Phenomenex luna C18 (250 x 70mm, 10 μm); mobile phase: [water (HCI) _ ACN]; gradient: 32% - 72% B over 28 min), 4-((6-(3-methyl-4H-1,2,4-triazol-4-yl)-3-nitropyridin-2- yl)amino)benzyl acetate (Intermediate 249, 475 mg, yield: 14%) was obtained as a yellow solid. MS: m/z = 369.1 [M + H]+ 1H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.20 (br s, 1H), 8.72 (d, J = 8.8 Hz, 1H), 8.11 (s, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.41(d, J = 8.4 Hz, 2H), 7.34 (d, J = 9.2 Hz, 1H), 5.09 (s, 2H), 2.27 (s, 3H), 2.08 (s, 3H). 4-((6-(3-Methyl-1H-1,2,4-triazol-1-yl)-3- nitropyridin-2-yl)amino)benzyl acetate (Intermediate 250, 1.1 g, yield: 32%) was obtained as a yellow solid. MS: m/z = 369.2 [M + H] ^{+ 1} H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.25 (br s, 1H), 8.88 (s, 1H), 8.75 (d, J = 8.4, 1H), 7.71 (d, J = 7.2 Hz, 2H), 7.44(d, J = 7.2 Hz, 2H), 7.30 (d, J = 8.4 Hz, 1H), 5.09 (s, 2H), 2.27 (s, 3H), 2.08 (s, 3H). [00430] Intermediate 251: 3-(3-(4-(Chloromethyl)phenyl)-5-(3-methyl-4H-1,2,4-triazol- 4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: 4-(2-(2-Aminopyridin-3-yl)-5-(3-methyl-4H-1,2,4-triazol-4-yl )-3H-imidazo[4,5- b]pyridin-3-yl)benzyl acetate To a solution of Intermediate 249 (400 mg, 1.09 mmol), 2-aminonicotinaldehyde (146 mg, 1.19 mmol) in DMSO (20 mL) was added Na ₂ S ₂ O ₄ (869 mg, 4.34 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was poured into H ₂ O (20 mL), extracted with EtOAc (15 mL x 3). The combined organic phases were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 69% EtOAc in petroleum ether), 4-(2-(2-aminopyridin-3-yl)-5-(3-methyl-4H-1,2,4- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl acetate (150 mg, yield: 31%) was obtained as a gray solid. MS: m/z =441.3 [M + H] ⁺ . Step 2: (4-(2-(2-Aminopyridin-3-yl)-5-(3-methyl-4H-1,2,4-triazol-4-y l)-3H-imidazo[4,5- b]pyridin-3-yl)phenyl)methanol To mixture of 4-(2-(2-aminopyridin-3-yl)-5-(3-methyl-4H-1,2,4-triazol-4-yl )-3H-imidazo[4,5- b]pyridin-3-yl)benzyl acetate (15 mg, 341 µmol) inTHF (1.5 mL) and MeOH (1.5 mL) was added K ₂ CO ₃ (94.1 mg, 681 µmol) in H ₂ O (1 mL). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was concentrated under reduced pressure. The residue was diluted with H ₂ O (5mL) and extracted with EtOAc (10mL x 3). The organic phase was dried over anhydrous Na ₂ SO _4, filtered and concentrated under reduced pressure. (4-(2-(2-Aminopyridin-3-yl)-5-(3- methyl-4H-1,2,4-triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl) phenyl)methanol (145 mg) was obtained as a gray solid. MS: m/z = 399.2 [M + H] ⁺ . Step 3: 3-(3-(4-(Chloromethyl)phenyl)-5-(3-methyl-4H-1,2,4-triazol-4 -yl)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(3-methyl-4H-1,2,4-triazol-4-y l)-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (145 mg, 364 umol) in CH ₂ Cl ₂ (2 mL) was added SOCl ₂ (1 mL). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was concentrated under reduced pressure. 3-(3-(4-(Chloromethyl)phenyl)-5-(3-methyl-4H-1,2,4- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (Intermediate 251, 166 mg) was obtained as a gray solid. MS: m/z = 417.1, 419.1 [M + H] ⁺ . [00431] Intermediate 252: 3-(3-(4-(Chloromethyl)phenyl)-5-(3-methyl-1H-1,2,4-triazol- 1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 252 was prepared in a manner similar to Intermediate 251. MS: m/z = 417.2, 419.2 [M + H] ⁺ . [00432] Intermediate 253: 3-(3-(4-(Chloromethyl)phenyl)-5-(1H-1,2,4-triazol-1-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 253 was prepared in a manner similar to Intermediate 220. MS: m/z = 403.2, 405.1 [M + H] ⁺ . [00433] Intermediate 254 & 255: 4-((3-Nitro-6-(1H-1,2,3-triazol-1-yl)pyridin-2- yl)amino)benzyl acetate & 4-((3-Nitro-6-(2H-1,2,3-triazol-2-yl)pyridin-2-yl)amino)benz yl acetate To a solution of 4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl acetate (3 g, 9.33 mmol) 1H- 1,2,3-triazole (644 mg, 9.33 mmol) in DMSO (30 mL) was added DIEA (4.87 mL, 28.0 mmol). The mixture was degassed and purged with N ₂ for 3 times and stirred at 100 ºC for 2 hr under N ₂ . The reaction mixture was quenched with H ₂ O (100 mL) at 25 °C and extracted with CH ₂ Cl ₂ (100 mL x 2). The combined organic layers were washed with brine (100 mL x3), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by prep-HPLC (column: Phenomenex luna C18 (250 x 70mm, 15 um); mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 35% - 65% B over 22 min), 4-((3-nitro-6-(1H-1,2,3-triazol-1-yl)pyridin-2- yl)amino)benzyl acetate (Intermediate 254, 360 mg, yield 10%) was obtained as a yellow solid. MS: m/z = 355.0 [M+H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) 10.30 (br s, 1H), 8.77 (d, J = 8.8 Hz, 1H), 8.38 - 8.32 (m, 1H), 7.85 - 7.81 (m, 1H), 7.74 (d, J = 8.8 Hz, 1H), 7.58 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H), 5.15 (s, 2H), 2.14 (s, 3H). 4-((3-Nitro-6-(2H-1,2,3-triazol-2- yl)pyridin-2-yl)amino)benzyl acetate (Intermediate 255, 840 mg, yield 24%) was obtained as a red solid. MS: m/z = 355.0 [M+H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) 10.52 (br s, 1H), 8.73 (dd, J = 9.2, 1.6 Hz, 1H), 8.01 - 7.93 (m, 4H), 7.59 (dd, J = 9.2, 2.0 Hz, 1H), 7.50 - 7.40 (m, 2H), 5.12 (s, 2H), 2.11 (s, 3H). [00434] Intermediate 256: 3-(3-(4-(Chloromethyl)phenyl)-5-(1H-1,2,3-triazol-1-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1:4-(2-(2-Aminopyridin-3-yl)-5-(1H-1,2,3-triazol-1-yl)-3H-im idazo[4,5-b]pyridin-3- yl)benzyl acetate To a solution of Intermediate 254 (300 mg, 847 µmol) in DMSO (5 mL) were added Na ₂ S ₂ O ₄ (442 mg, 2.54 mmol) and 2-aminonicotinaldehyde (114 mg, 931 µmol). The mixture was degassed and purged with N ₂ for 3 times and stirred at 100 oC for 16 hr under N ₂ . The reaction mixture was poured into H ₂ O (50 mL). The mixture was extracted with CH ₂ Cl ₂ (200 mL x 2). The combined organic layers were washed with brine (100 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Ethyl acetate in petroleum ether = 50% to 80%), 4-(2-(2-aminopyridin-3-yl)-5-(1H-1,2,3- triazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl acetate (51 mg, yield 13%) was obtained as an orange solid. MS: m/z = 427.1 [M+H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.44 (s, 1H), 8.28 (d, J = 2.8 Hz, 2H), 8.16 - 8.05 (m, 1H), 7.78 (d, J = 1.6 Hz, 1H), 7.58 - 7.48 (m, 2H), 7.45 - 7.36 (m, 2H), 7.09 (d, J = 7.6 Hz, 1H), 6.62 (br s, 2H), 6.45 - 6.35 (m, 1H), 5.24 (s, 2H), 2.18 (s, 3H). Step 2: (4-(2-(2-Aminopyridin-3-yl)-5-(1H-1,2,3-triazol-1-yl)-3H-imi dazo[4,5-b]pyridin-3- yl)phenyl)methanol To a solution of 4-(2-(2-aminopyridin-3-yl)-5-(1H-l,2,3-triazol-l-yl)-3H-imid azo[4,5-b]pyridin- 3-yl)benzyl acetate (51 mg, 120 umol) in THF (0.5 mL), H2O (0.5 mL), and MeOH (0.5 mL) was added K ₂ CO ₃ (33.1 mg, 239 umol). The mixture was degassed and purged with N2 for 3 times and stirred at 25 °C for 0.5 hr under N2. The reaction mixture was filtered and concentrated under reduced pressure. (4-(2-(2-Aminopyridin-3-yl)-5-(1H-l,2,3-triazol-l-yl)- 3H-imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (46.0 mg, crude) was obtained as a yellow solid which was used into the next step directly. MS: m/z = 385.2 [M+H] ⁺ .

Step 3 : 3-(3-(4-(Chloromethyl)phenyl)-5-(1H-l,2,3-triazol-l-yl)-3H-i midazo[4,5-b]pyridin-2- yl)pyridin-2-amine

To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(1H-l,2,3-triazol-l-yl)-3H-imi dazo[4,5- b]pyridin-3-yl)phenyl)methanol (46.0 mg, 120 umol) in CH2Cl ₂ (1 mL) was added SOCI ₂ (142 mg, 1.20 mmol). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was concentrated under reduced pressure to give 3-(3-(4-(chloromethyl)phenyl)-5-(1H-l,2,3-triazol- l-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (Intermediate 256, 48.2 mg, crude, HC1) as a yellow solid, which was used in the next step. MS: m/z = 403.1 [M+H] ⁺ .

[00435] Intermediate 257: 3-(3-(4-(Chloromethyl)phenyl)-5-(2H-l,2,3-triazol-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Intermediate 257 was prepared in a manner similar to Intermediate 256. MS: m/z = 403.1 [M+H] ⁺ .

[00436] Intermediate 258 & 259: 4-((6-(4-Methyl-1H-l,2,3-triazol-l-yl)-3-nitropyridin-2- yl)amino)benzyl acetate & 4-((6-(4-Methyl-2H- 1,2,3 -triazol -2-yl)-3 -nitropyridin-2- yl)amino)benzyl acetate

To a solution of 4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl acetate (refer to Intermediate 178 for detail procedures, 3 g, 9.33 mmol) and 4-methyl-1H-l,2,3-triazole (775 mg, 9.33 mmol) in DMSO (20 mL) was added DIEA (3.62 g, 28 mmol). The mixture was stirred at 80 °C for 16 hr. The reaction mixture was quenched with H ₂ O (100 mL) at 25 °C and extracted with CH ₂ Cl ₂ (100 mL x 2). The combined organic layers were washed with brine (100 mL x3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-HPLC (column: Phenomenex C ₁ 8150 x 25 mm x 10 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 35% - 65% B over 22 min), 4-((6-(4-methyl-1H-1,2,3-triazol-1-yl)-3-nitropyridin-2- yl)amino)benzyl acetate (Intermediate 258, 720 mg, yield: 20%) was obtained as a red solid. MS: m/z = 391.2 [M + Na] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.27 (s, 1H), 8.78 (d, J = 8.8 Hz, 1H), 8.23 - 8.21 (m, 1H), 7.70 (d, J = 8.4 Hz, 2H), 7.58 (d, J = 8.8 Hz, 1H), 7.45 (d, J = 8.4 Hz, 2H), 5.10 (s, 2H), 2.36 (s, 3H), 2.09 (s, 3H). 4-((6-(4-Methyl-2H-1,2,3-triazol-2- yl)-3-nitropyridin-2-yl)amino)benzyl acetate (Intermediate 259, 1.4 g, yield: 39%) was obtained as a red solid. MS: m/z = 369.1 [M + Na] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.30 (s, 1H), 8.71 (d, J = 9.2 Hz, 1H), 8.1 (s, 1H), 7.96 (d, J = 8.4 Hz, 2H), 7.46 (d, J = 8.8 Hz, 1H), 7.38 (d, J = 8.4 Hz, 2H), 5.07 (s, 2H), 2.36 (s, 3H), 2.07 (s, 3H). [00437] Intermediate 260: 3-(3-(4-(Chloromethyl)phenyl)-5-(4-methyl-1H-1,2,3-triazol- 1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 260 was prepared in a manner similar to Intermediate 256. MS: m/z = 417.1, 419.1 [M + H] ⁺ . [00438] Intermediate 261: 3-(3-(4-(Chloromethyl)phenyl)-5-(oxazol-4-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 261 was prepared in a manner similar to Intermediate 215. MS: m/z = 403.0 [M + H] ⁺ . [00439] Intermediate 262: 3-(3-(4-(Chloromethyl)phenyl)-5-(4-fluoropyridin-3-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 262 was prepared in a manner similar to Intermediate 215. MS: m/z = 431.1 [M + H] ⁺ . [00440] Intermediate 263: 3-(3-(4-(Chloromethyl)phenyl)-5-(4-methylpyridin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 263 was prepared in a manner similar to Intermediate 215. MS: m/z = 427.2, 429.2 [M + H] ⁺ . [00441] Intermediate 264: 5-bromo-2-(methoxy-d3)pyridine-6-d To a solution of 2,5-dibromopyridine (1 g, 4.22 mmol) in CD ₃ OD (10 mL) was added NaOH (338 mg, 8.44 mmol). The mixture was stirred at 70 °C for 2 hr. The reaction mixture was quenched with H ₂ O (20 mL) at 25 °C and extracted with CH ₂ Cl ₂ (25 mL x 2). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 1% EtOAc in petroleum ether), 5-bromo-2-(methoxy-d3)pyridine-6-d (Intermediate 264, 600 mg, yield: 74%) was obtained as a colorless oil. MS: m/z = 190.9, 192.9 [M + H] ⁺ . D%: 3D% = 66.6%, 4D% = 33.4%. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.28(s, 1H), 7.89 (dd, J = 9.2, 2.8 Hz, 1H), 6.86 - 6.79 (m, 1H). [00442] Intermediate 265: 3-(3-(4-(Chloromethyl)phenyl)-5-(6-(methoxy-d3)pyridin-3-yl- 2-d)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 265 was prepared in a manner similar to Intermediate 215. MS: m/z = 446.1 [M + H] ⁺ . D%: 3D% = 66.8%, 4D% = 32.9%. ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 9.07 (dd, J = 9.2, 2.4 Hz, 1H), 8.97 (s, 1H), 8.42 (d, J = 8.4 Hz, 1H), 8.16 (d, J = 8.4 Hz, 1H), 8.03 (dd, J = 6.0, 1.2 Hz, 1H), 7.87 (dd, J = 7.6, 1.6 Hz, 1H), 7.71 (d, J = 8.4 Hz, 2H), 7.63 - 7.58 (m, 3H), 6.87 (dd, J = 7.6, 6.4 Hz, 1H), 4.79 (s, 2H). [00443] Intermediate 266: 5-Bromo-2-(methoxy-d ₃ )pyridine To a solution of 5-bromopyridin-2-ol (1 g, 5.75 mmol) and Ag ₂ CO ₃ (1.11 g, 4.02 mmol) in CH ₂ Cl ₂ (10 mL) was added CD ₃ I (979 mg, 6.9 mmol). The mixture was stirred at 50 °C for 16 hr. The reaction mixture was quenched with H ₂ O (50 mL) at 25 °C and extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (50 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 5% EtOAc in petroleum ether), 5-bromo-2-(methoxy- d ₃ )pyridine (Intermediate 266, 480 mg, yield: 43%) was obtained as a colorless oil. MS: m/z = 190.9, 192.9 [M + H] ⁺ .3D% = 100%. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.29 (d, J = 2.4 Hz, 1H), 7.89 (dd, J = 8.8, 2.4 Hz, 1H), 6.84 (d, J = 8.8 Hz, 1H). [00444] Intermediate 267: 3-(3-(4-(Chloromethyl)phenyl)-5-(6-(methoxy-d ₃ )pyridin-3- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 267 was prepared in a manner similar to Intermediate 215 MS: m/z = 446.1 [M + H] ⁺ . [00445] Intermediate 268: 2-(2-Aminopyridin-3-yl)-3-(4-(bromomethyl)phenyl)-5- hydroxy-3H-imidazo[4,5-b]pyridine-6-carbonitrile Step 1: (4-((6-Methoxy-3-nitropyridin-2-yl)amino)phenyl)methanol To a solution of 2-chloro-6-methoxy-3-nitropyridine (12 g, 64 mmol), and DIEA (25 g, 191 mmol) in DMSO (100 mL) was added (4-aminophenyl)methanol (7.8 g, 64 mmol) at 25 °C. The mixture was stirred at 80 °C for 12 hr. The mixture was quenched with H ₂ O (300 mL) and extracted with CH ₂ Cl ₂ (100 mL x 2). The combined organic layers were washed with brine (200 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated. (4-((6-Methoxy-3-nitropyridin-2- yl)amino)phenyl)methanol (15 g, yield: 79%) was obtained as a yellow solid. MS: m/z = 275.8 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.45 (s, 1H), 8.43 (d, J = 9.2 Hz, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 6.36 (d, J = 9.2 Hz, 1H), 5.18 (t, J = 5.6 Hz, 1H), 4.49 (d, J = 5.6 Hz, 2H), 3.88 (s, 3H). Step 2: 4-((6-Methoxy-3-nitropyridin-2-yl)amino)benzyl acetate To a solution of (4-((6-methoxy-3-nitropyridin-2-yl)amino)phenyl)methanol (15 g, 54 mmol), TEA (16 g, 163 mmol), and DMAP (666 g, 5.4 mmol) in CH ₂ Cl ₂ (100 mL) was added acetic anhydride (6.7 g, 65 mmol) at 0 °C. The mixture was stirred at 0 °C for 2 hr. The mixture was quenched with H ₂ O (300 mL) and extracted with CH ₂ Cl ₂ (100 mL x 2). The combined organic layers were washed with brine (200 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0% ~ 40% EtOAc in petroleum ether), 4-((6-methoxy-3-nitropyridin-2-yl)amino)benzyl acetate (16.5 g, yield: 88%) was obtained as a yellow solid. MS: m/z = 318.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide- d ₆ ) δ 10.47 (s, 1H), 8.44 (d, J = 9.2 Hz, 1H), 7.73 (d, J = 8.8 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H), 6.38 (d, J = 9.2 Hz, 1H), 5.06 (s, 2H), 3.89 (s, 3H), 2.07 (s, 3H). Step 3: 4-((5-Bromo-6-methoxy-3-nitropyridin-2-yl)amino)benzyl acetate To a solution of 4-((6-methoxy-3-nitropyridin-2-yl)amino)benzyl acetate (12 g, 38 mmol) in DMF (50 mL) was added NBS (8.0 g, 45 mmol) at 25 °C. The mixture was stirred at 90 °C for 2 hr. The mixture was quenched with H ₂ O (300 mL) and extracted with CH ₂ Cl ₂ (100 mL x 2). The combined organic layers were washed with brine (200 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated. 4-((5-Bromo-6-methoxy-3-nitropyridin-2-yl)amino)benzyl acetate (14 g, crude) was obtained as a yellow solid. MS: m/z =396.0, 397.8[M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ 10.37 (s, 1H), 8.65 (s, 1H), 7.70 (d, J = 8.4 Hz, 2H), 7.39 (d, J = 8.8 Hz, 2H), 5.07 (s, 2H), 3.94 (s, 3H), 2.07 (s, 3H). Step 4: 4-((5-Cyano-6-methoxy-3-nitropyridin-2-yl)amino)benzyl acetate A mixture of 4-((5-bromo-6-methoxy-3-notropyridin-2-yl)amino)benzyl acetate (5 g, 12.6 µmol) and CuCN(5.6 g, 63 mmol) in DMF(20 mL) was stirred at 180 °C for 2 hr. The mixture was quenched with H ₂ O (200 mL) and extracted with CH ₂ Cl ₂ (100 mL x 2). The combined organic layers were washed with brine (200 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0% ~ 15% EtOAc in petroleum ether), 4-((5-cyano-6-methoxy-3-nitropyridin-2-yl)amino)benzyl acetate (3.3 g, yield: 69% for two steps) was obtained as a yellow solid. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.61 (s, 1H), 8.99 (s, 1H), 7.68 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 8.4 Hz, 2H), 5.08 (s, 2H), 3.94 (s, 3H), 2.07 (s, 3H). Step 5: 4-(2-(2-Aminopyridin-3-yl)-6-cyano-5-methoxy-3H-imidazo[4,5- b]pyridin-3-yl)benzyl acetate To a solution of 4-((5-cyano-6-methoxy-3-nitropyridin-2-yl)amino)benzyl acetate (1.2 g, 3.5 mmol) in DMSO (50 mL) were added 2-aminonicotinaldehyde (514 mg, 4.2 mmol) and Na ₂ S ₂ O ₄ (2.4 g, 14 mmol) at 25 °C. The mixture was stirred at 100 °C for 12 hr. The reaction mixture was poured into H ₂ O (200 mL) and extracted with CH ₂ Cl ₂ (50 mL x 2). The combined organic layers were washed with brine (200 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 25% EtOAc in petroleum ether), 4-(2-(2-aminopyridin-3-yl)-6-cyano-5-methoxy-3H- imidazo[4,5-b]pyridin-3-yl)benzyl acetate (400 mg, yield: 24%) was obtained as a yellow solid. MS: m/z = 414.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.74 (s, 1H), 8.00 (dd, J = 4.8, 2.0 Hz, 1H), 7.53 - 7.44 (m, 4H), 7.20 (dd, J = 7.6, 2.0 Hz, 1H), 6.72 (s, 2H), 6.43 (dd, J = 7.6, 4.8 Hz, 1H), 5.15 (s, 2H), 3.90 (s, 3H), 2.10 (s, 3H). Step 6: 2-(2-Aminopyridin-3-yl)-3-(4-(bromomethyl)phenyl)-5-hydroxy- 3H-imidazo[4,5- b]pyridine-6-carbonitrile To a solution of 4-(2-(2-aminopyridin-3-yl)-6-cyano-5-methoxy-3H-imidazo[4,5- b]pyridin-3- yl)benzyl acetate (400 mg, 965 µmol) in DCE (10mL) was added BBr ₃ (4.8 mL, 4.8 mmol, 1 M in CH ₂ Cl ₂ ). The mixture was stirred at 80 °C for 12 hr. The reaction mixture was quenched with H ₂ O (20 mL) at 25 °C. The pH of the mixture was adjusted to 8 with saturated aq. NaHCO ₃ . The mixture was extracted with CH ₂ Cl ₂ (15 mL x 2). The combined organic layers were washed with brine (30 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. 2-(2-Aminopyridin-3-yl)-3-(4-(bromomethyl)phenyl)-5-hydroxy- 3H- imidazo[4,5-b]pyridine-6-carbonitrile (Intermediate 268, 350 mg, crude) was obtained as a yellow solid. MS: m/z = 420.8, 422.7 [M + H] ⁺ . [00446] Intermediate 269: 2-Amino-4-fluoronicotinaldehyde Step 1: 4-Fluoro-3-vinylpyridin-2-amine A mixture of 3-bromo-4-fluoropyridin-2-amine (1 g, 5.24 mmol), 4,4,5,5-tetramethyl-2-vinyl- 1,3,2-dioxaborolane (1.21 g, 7.85 mmol), Cs ₂ CO ₃ (5.12 g, 15.7 mmol) and Pd(dppf)Cl ₂ (383 mg, 524 µmol) in 1,4-dioxane (20 mL) and H ₂ O (4 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 80 °C for 16 hr under N ₂ atmosphere. The reaction mixture was quenched with H ₂ O (50 mL) at 25 °C and extracted with EtOAc (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 15% EtOAc in petroleum ether), 4-fluoro-3-vinylpyridin-2- amine (700 mg, yield: 77%) was obtained as a light-yellow oil. MS: m/z = 139.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 7.94 - 7.88 (m, 1H), 6.56 - 6.42 (m, 2H), 5.78 (d, J = 17.6 Hz, 1H), 5.63 (d, J = 11.6 Hz, 1H), 4.80 (br s, 2H). ¹⁹ F NMR (400 MHz, Chloroform-d) δ -106.82. Step 2: 2-Amino-4-fluoronicotinaldehyde To a solution of 4-fluoro-3-vinylpyridin-2-amine (700 mg, 5.07 mmol) in H ₂ O (5 mL) and THF (15 mL) were added NaIO ₄ (3.25 g, 15.2 mmol) and K ₂ OsO ₄ ·2H ₂ O(560 mg, 1.52 mmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was quenched with aqueous Na ₂ SO ₃ (50 mL) at 25°C and extracted with CH ₂ Cl ₂ (30 mL x 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 5% ~ 13% EtOAc in petroleum ether), 2-amino-4-fluoronicotinaldehyde (Intermediate 269, 275 mg, yield: 38%) was obtained as a white solid. MS: m/z = 141.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.19 (s, 1H), 8.26 (dd, J = 8.8, 5.6 Hz, 1H), 7.96 (br s, 2H), 6.56 (dd, J = 10.8, 5.6 Hz, 1H). [00447] Intermediate 270: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-fluoropyridin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)-4-fluoropyridin-2-amine Intermediate 270 was prepared in a manner similar to Intermediate 226. MS: m/z = 449.0 [M + H] ⁺ . [00448] Intermediate 271: 3-(4-(Chloromethyl)phenyl)-5-(5-fluoropyridin-2-yl)-2- (pyrimidin-5-yl)-3H-imidazo[4,5-b]pyridine Intermediate 271 was prepared in a manner similar to Intermediate 226. MS: m/z = 417.1, 419.1 [M + H] ⁺ . [00449] Intermediate 272: 3-(1-(4-(Chloromethyl)phenyl)-6-(5-fluoropyridin-2-yl)-1H- benzo[d]imidazol-2-yl)pyridin-2-amine Step 1: (4-((5-Bromo-2-nitrophenyl)amino)phenyl)methanol To a solution of 4-bromo-2-fluoro-1-nitrobenzene (9 g, 40.91 mmol) in 1,4-dioxane (100 mL) were added DIEA (15.86 g, 122.73 mmol) and (4-aminophenyl)methanol (5.04 g, 40.91 mmol). The mixture was degassed and purged with N ₂ three times and stirred at 80 °C for 16 hr under N ₂ . The reaction mixture was diluted with H ₂ O (500 mL) and extracted with CH ₂ Cl ₂ (500 mL x 3). The combined organic layers were washed with brine (200 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (SiO ₂ , petroleum ether/ethyl acetate = 99/1 to 7/3), (4-((5-bromo-2- nitrophenyl)amino)phenyl)methanol (3.1 g, yield: 23%) was obtained as a yellow solid. ¹ H NMR (400MHz, Dimethylsulfoxide-d ₆ ) δ 9.48 (s, 1H)m 8.04 (d, J = 9.2 Hz, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 7.10 (s, 1H), 7.00 (dd, J = 9.2, 7.2 Hz, 1H), 5.23 - 5.21 (m, 1H), 4.53 - 4.51 (m, 2H). Step 2: 4-((5-Bromo-2-nitrophenyl)amino)benzyl acetate To a solution of (4-((5-bromo-2-nitrophenyl)amino)phenyl)methanol (2.54 g, 7.86 mmol) and TEA (2.39 g, 25.6 mmol) in CH ₂ Cl ₂ (30 mL) were added Ac ₂ O (802 mg, 7.86 mmol) and DMAP (96.0 mg, 786 umol). The mixture was stirred at 0 °C for 1 hr. The reaction mixture was diluted with H ₂ O (500 mL) and extracted with CH ₂ CI ₂ (500 mL x 3). The combined organic layers were washed with brine (200 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 15% EtOAc in petroleum ether), 4-((5-bromo-2-nitrophenyl)amino)benzyl acetate (2.7 g, yield: 92% ) was obtained as a yellow solid. ¹ H NMR (400MHz, Chloroform-d) 59.41 (s, 1H), 7.98 (d, J = 9.2 Hz, 1H), 7.35 (d, J= 8.4 Hz, 2H), 7.17 - 7.15 (m, 3H), 6.80 (dd, J= 9.2, 2.0 Hz, 1H), 5.04 (s, 2H), 2.05 (s, 3H).

Step 3: 4-(2-(2-Aminopyridin-3-yl)-6-bromo-1H-benzo[d]imidazol-l-yl) benzyl acetate

To a solution of 4-((5-bromo-2-nitrophenyl)amino)benzyl acetate (2.7 g, 7.39 mmol) in DMSO (10 mL) were added Na ₂ S ₂ O ₄ (5.12 g, 29.6 mmol, 87% purity) and 2-aminonicotinaldehyde (1.08 g, 8.87 mmol). The mixture was stirred at 100 °C for 3 hr. The reaction mixture was quenched with H ₂ O (500 mL) and extracted with EtOAc (500 mL x 2). The combined organic layers were washed with brine (500 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 40% EtOAc in petroleum ether), 4-(2-(2-aminopyridin-3-yl)-6-bromo-1H-benzo[d]imidazol-l- yl)benzyl acetate (1.1 g, yield: 33%) was obtained as a light yellow solid. MS: m/z = 437.0, 438.9 [M + H]+. ¹ HNMR (400MHz, Chloroform^ 6 8.05 (dd, J= 4.8, 1.6 Hz, 1H), 7.68 (d, J = 8.4Hz, 1H), 7.53 (d, J= 8.4Hz, 2H), 7.44 (dd, J= 8.4, 1.6 Hz, 1H), 7.34 (d, J = 1.6 Hz, 1H), 7.31 (d, J= 8.4 Hz, 2H), 7.02 (dd, J= 7.6, 1.6 Hz, 1H), 6.59 (s, 2H), 6.35 (dd, J= 4.8, 7.8 Hz, 1H), 5.21 (s, 2H), 2.18 (s, 3H).

Step 4 : 4-(2-(2-Aminopyridin-3 -yl)-6-(5-fluoropyridin-2-yl)- 1H-benzo[d]imidazol- 1 -yl)benzyl acetate

A mixture of 4-(2-(2-aminopyridin-3-yl)-6-bromo-1H-benzo[d]imidazol-l-yl) benzyl acetate (500 mg, 1.14 mmol), (5-fluoropyridin-2-yl)boronic acid (483 mg, 3.43 mmol), Pd(dppf)Cl ₂ (83.7 mg, 114 umol), CS ₂ CO ₃ (1.12 g, 3.43 mmol) and CuBr 65.6 mg, 457 umol) in 1,4-dioxane (7.5 mL) and H ₂ O (1.5 mL) was degassed and purged with N2 three times. The mixture was stirred at 100 °C for 16 hr under N2 atmosphere. The reaction mixture was quenched with H ₂ O (100 mL), diluted with CH ₂ CI ₂ (100 mL), and extracted with CH ₂ CI ₂ (100 mL x 2). The combined organic layers were washed with brine (100 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 56% EtOAc in petroleum ether), 4-(2-(2-aminopyridin-3-yl)-6-(5-fluoropyridin-2-yl)- 1H-benzo[d]imidazol-l-yl)benzyl acetate (380 mg, yield: 59%) was obtained as a light yellow solid. MS: m/z = 454.2 [M + H]+. Step 5: (4-(2-(2-Aminopyridin-3-yl)-6-(5-fluoropyridin-2-yl)-1H-benz o[d]imidazol-1- yl)phenyl)methanol To a solution of 4-(2-(2-aminopyridin-3-yl)-6-(5-fluoropyridin-2-yl)-1H-benzo [d]imidazol-1- yl)benzyl acetate (380 mg, 838 µmol) in THF (4 mL) and MeOH (4 mL9 was added K ₂ CO ₃ (347 mg, 2.51 mmol) in H ₂ O(4 mL). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was quenched with H ₂ O (100 mL) at 25 °C and extracted with EtOAc (100 mL x 2). The combined organic layers were washed with brine (100 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. (4-(2-(2-Aminopyridin-3-yl)-6-(5-fluoropyridin-2-yl)-1H- benzo[d]imidazol-1-yl)phenyl)methanol (340 mg, yield: 85%) was obtained as a light yellow solid. MS: m/z = 412.2 [M + H] ⁺ . Step 6: 3-(1-(4-(Chloromethyl)phenyl)-6-(5-fluoropyridin-2-yl)-1H-be nzo[d]imidazol-2- yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-6-(5-fluoropyridin-2-yl)-1H-benz o[d]imidazol-1- yl)phenyl)methanol (400 mg, 972 µmol) in CH ₂ Cl ₂ (6 mL) was added SOCl ₂ (347 mg, 2.92 mmol). The mixture was stirred at 40 °C for 0.5 hr. The reaction was concentrated under reduced pressure to give 3-(1-(4-(chloromethyl)phenyl)-6-(5-fluoropyridin-2-yl)-1H- benzo[d]imidazol-2-yl)pyridin-2-amine (Intermediate 272, 400 mg, HCl salt) as a light yellow solid. MS: m/z = 430.1 [M + H] ⁺ . [00450] Intermediate 273: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-fluoropyrimidin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 273 was prepared in a manner similar to Intermediate 215. MS: m/z = 432.1 [M + H] ⁺ . [00451] Intermediate 274: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-methylpyrimidin-2-yl)- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Intermediate 274 was prepared in a manner similar to Intermediate 215. MS: m/z = 428.2 [M + H]+. [00452] Intermediate 275: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-fluoropyrazin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 275 was prepared in a manner similar to Intermediate 215. MS: m/z = 432.1 [M + H] ⁺ . [00453] Intermediate 276: 5-Bromo-2-(fluoromethoxy)pyridine To a solution of 5-bromopyridin-2-ol (1 g, 5.8 mmol) and K ₂ CO ₃ (2.4 g, 17.2 mmol) in DMF (10 mL) was added fluoromethyl 4-methylbenzenesulfonate (1.2 g, 5.8 mmol) at 25 °C. The mixture was stirred at 50 °C for 2 hr. The mixture was quenched with H ₂ O (50 mL) and extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (50 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0~15% Ethyl acetate in petroleum ether), 5-bromo-2- (fluoromethoxy)pyridine (Intermediate 276, 1 g, yield: 84%) was obtained as a yellow oil. MS: m/z = 205.8, 207.8 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.18 (d, J = 2.8 Hz, 1H), 7.61 (dd, J = 9.6, 2.8 Hz, 1H), 6.47 (d, J = 9.6 Hz, 1H), 5.90 - 5.75 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -172.73. [00454] Intermediate 277: 3-(3-(4-(Chloromethyl)phenyl)-5-(6-(fluoromethoxy)pyridin-3- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 277 was prepared in a manner similar to Intermediate 215. MS: m/z = 461.0 [M + H] ⁺ . [00455] Intermediate 278: 5-Bromo-1-(fluoromethyl)pyridin-2(1H)-one To a solution of 5-bromopyridin-2-ol (3 g, 17.2 mmol), and K ₂ CO ₃ (7.1 g, 52 mmol) in DMF (10 mL) was added bromofluoromethane (2.9 g, 26 mmol) at 0 °C. The mixture was stirred at 0 °C for 2 hr. The mixture was quenched with H ₂ O (50 mL) and extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (50 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0~15% Ethyl acetate in petroleum ether), 5-Bromo-1-(fluoromethyl)pyridin-2(1H)-one (Intermediate 278, 2.7 g, yield: 76%) was obtained as a yellow oil. MS: m/z = 205.7, 207.7 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.19 (d, J = 2.8 Hz, 1H), 7.61 (dd, J = 9.6, 2.8 Hz, 1H), 6.47 (d, J = 9.6 Hz, 1H), 5.88 (d, J = 51.2 Hz, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -172.733. [00456] Intermediate 279: 5-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)-1-(fluoromethyl)pyridin-2(1H)-on e Intermediate 279 was prepared in a manner similar to Intermediate 215. MS: m/z = 461.0, 462.7 [M + H] ⁺ . [00457] Intermediate 280: 4-Bromo-2-(methyl-d ₃ )-2H-1,2,3-triazole Step 1: 4,5-Dibromo-2H-1,2,3-triazole To a solution of 2H-1,2,3-triazole (25 g, 362 mmol) in H ₂ O (300 mL) was added dropwise Br ₂ (75.2 g, 471 mmol) at 0 °C under N ₂ atmosphere. The mixture was stirred at 25 °C for 16 hr under N ₂ atmosphere. The reaction mixture was filtered. After triturated with MeOH (100 mL) at 25 °C for 10 min, 4,5-dibromo-2H-1,2,3-triazole (48 g, yield: 58%) was obtained as a white solid. MS: m/z = 226.0, 228.0, 230.0 [M + H] ⁺ . Step 2: 4,5-Dibromo-2-(methyl-d ₃ )-2H-1,2,3-triazole To a solution of 4,5-dibromo-2H-1,2,3-triazole (20 g, 88.2 mmol) and K ₂ CO ₃ (24.4 g, 176 mmol) in DMF (100 mL) was added dropwise CD ₃ I (25 g, 176 mmol) at 0 °C. The mixture was stirred at 25 °C for 16 hr. The reaction mixture was quenched with H ₂ O (200 mL) at 25 °C and extracted with CH ₂ Cl ₂ (200 mL x 3). The combined organic layers were washed with brine (200 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 30% EtOAc in petroleum ether), 4,5-dibromo- 2-(methyl-d ₃ )-2H-1,2,3-triazole (10 g, yield: 47%) was obtained as a colorless oil. MS: m/z = 243.0, 245.0, 247.0 [M + H] ⁺ . Step 3: 4-Bromo-2-(methyl-d ₃ )-2H-1,2,3-triazole To a solution of 4,5-dibromo-2-(methyl-d ₃ )-2H-1,2,3-triazole (10 g, 41 mmol) in THF (100 mL) was added dropwise n-BuLi (5.25 g, 82 mmol, 2.5 M in THF) at -78 °C. The mixture was stirred at -78 °C for 1 hr. The reaction mixture was quenched with H ₂ O (200 mL) at 25 °C and extracted with CH ₂ Cl ₂ (200 mL x 3). The combined organic layers were washed with brine (200 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. 4-Bromo-2- (methyl-d ₃ )-2H-1,2,3-triazole (Intermediate 280, 3.6 g, yield: 53%) was obtained as a yellow oil. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 7.94 (s, 1H). [00458] Intermediate 281: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-(methyl-d ₃ )-2H-1,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 281 was prepared in a manner similar to Intermediate 215. MS: m/z = 420.2 [M + H] ⁺ . [00459] Intermediate 282 & 283: 4,5-Dibromo-2-ethyl-2H-1,2,3-triazole & 4,5-Dibromo- 1-ethyl-1H-1,2,3-triazole To a solution of 4,5-dibromo-2H-triazole (2 g, 8.82 mmol) in DMF (20 mL) were added K ₂ CO ₃ (1.83 g, 13.2 mmol) and iodoethane (1.38 g, 8.82 mmol, 705 μL) at 20 ºC. The reaction mixture was stirred at 20 °C for 12 hr. The reaction mixture was diluted with H ₂ O (100 mL) and extracted with EtOAc (100 mL). The organic layer was separated, dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under vacuum. After purified by silica gel flash chromatography (EtOAc in petroleum ether = 0 - 5 %), 4,5-dibromo-2-ethyl-2H-1,2,3-triazole (Intermediate 282, 3.1 g, yield: 69%) was obtained as a yellow oil. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 4.45 (q, J = 7.2 Hz, 2H), 1.43 (t, J = 7.2 Hz, 3H). 4,5-Dibromo-1- ethyl-1H-1,2,3-triazole (Intermediate 283, 780 mg, yield: 17%) was obtained as a white solid. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 4.42 (q, J = 7.2 Hz, 2H), 1.41 (t, J = 7.2 Hz, 3H). [00460] Intermediate 284: 4-Bromo-2-ethyl-2H-1,2,3-triazole To a mixture of Intermediate 282 (1 g, 3.92 mmol) in THF (10 mL) was added n-BuLi (2.5M in hexane, 1.73 mL) at -70 °C under N ₂ . The mixture was stirred at -70 °C for 1 hr under N ₂ . The reaction mixture was quenched with H ₂ O (20 mL) at -70 °C under N ₂ and extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. 4-Bromo-2-ethyl-2H- 1,2,3-triazole (Intermediate 284, 600 mg, 3.41 mmol, yield: 87%) was obtained as a yellow oil. MS: m/z = 175.7, 177.7 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 7.95 (s, 4.44 (q, J = 7.2 Hz, 2H), 1.43 (t, J = 7.2 Hz, 3H). [00461] Intermediate 285: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-ethyl-2H-1,2,3-triazol-4- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 285 was prepared in a manner similar to Intermediate 215. MS: m/z = 431.2, 433.1 [M + H] ⁺ . [00462] Intermediate 286 & 287: 4,5-Dibromo-2-isopropyl-2H-1,2,3-triazole & 4,5- Dibromo-1-isopropyl-1H-1,2,3-triazole To a solution of 4,5-dibromo-2H-1,2,3-triazole (2 g, 8.82 mmol, 1 eq) in DMF (10 mL) were added K ₂ CO ₃ (1.83 g, 13.2 mmol) and 2-iodopropane (1.50 g, 8.82 mmol, 880 μL) at 20 ºC. The reaction mixture was stirred at 20 °C for 12 hr. The mixture was diluted with H ₂ O (50 mL) and extracted with EtOAc (50 mL). The organic layer was separated, dried over anhydrous Na ₂ SO ₄ and concentrated under reduced pressure. After purified by silica gel flash chromatography (0-10% EtOAc in petroleum ether), 4,5-dibromo-2-isopropyl-2H-1,2,3-triazole (Intermediate 286, 1.7 g, yield: 71.7%) was obtained as a colorless liquid. ¹ H NMR (400 MHz, Chloroform-d) δ 4.82 - 4.71 (m, 1H), 1.55 (d, J = 6.8 Hz, 6H). 4,5-Dibromo-1-isopropyl-1H- 1,2,3-triazole (Intermediate 287, 320 mg, yield: 13.5%) was obtained as a colorless liquid. ¹ H NMR (400 MHz, Chloroform-d) δ 4.83 - 4.71 (m, 1H), 1.64 (d, J = 6.8 Hz, 6H). [00463] Intermediate 288: 4-Bromo-2-isopropyl-2H-1,2,3-triazole To a solution of Intermediate 286 (1 g, 3.72 mmol) in THF (9 mL) was added n-BuLi (2.5 M in hexane, 1.56 mL) at -70 °C. The reaction mixture was stirred at -70 °C for 0.5 hr under N ₂ . The reaction mixture was quenched with saturated aq. NH ₄ Cl (30 mL) dropwise at -70 °C under N ₂ . The mixture was then diluted with H ₂ O (20 mL) and extracted with EtOAc (30 mL x 2). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. 4-Bromo-2-isopropyl-2H-1,2,3-triazole (Intermediate 288, 590 mg, 3.10 mmol, yield: 83.5%) was obtained as a colorless liquid, which was used in the next step directly. MS: m/z = 190.0, 192.0[M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ = 7.51 (s, 1H), 4.87 - 4.73 (m, 1H), 1.56 (d, J = 6.8 Hz, 6H). [00464] Intermediate 289: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-isopropyl-2H-1,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Step 1 : (2-(2-Aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)oxy )methyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)boronic acid

A mixture of Intermediate 129 (1 g, 1.96 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(l,3,2- dioxaborolane) (995 mg, 3.92 mmol), KOAc (577 mg, 5.88 mmol) and Pd(dppf)Cl ₂ (143 mg, 196 umol) in 1,4-dioxane (10 mL) was degassed and purged with N2 three times. The mixture was stirred at 80 °C for 4 hr under N2 atmosphere. (2-(2-Aminopyridin-3-yl)-3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-3H-imidazo[4,5-b]pyrid in-5-yl)boronic acid was obtained as a black liquid, which was used in the next step without work-up and purification. MS: m/z = 476.1 [M + H] ⁺ .

Step 2 : 3 -(3 -(4-(((tert-Butyldimethylsilyl)oxy)methyl)phenyl)-5-(2-isopr opyl-2H- 1,2,3 -triazol- 4-yl)-3H-imidazo[4,5-b]pyri din-2 -yl)pyridin-2-amine

To a solution of (2-(2-aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)oxy )methyl)phenyl)- 3H-imidazo[4,5-b]pyridin-5-yl)boronic acid (373 mg, 784 umol) and 4-bromo-2-isopropyl- triazole (179 mg, 940 umol) in 1,4-dioxane (12.5 mL) and H ₂ O (2.5 mL) were added Pd(dppf)Cl ₂ (57.3 mg, 78.4 umol) and CS ₂ CO ₃ (766 mg, 2.35 mmol) at 20 °C. The mixture was stirred at 100 °C for 2 hr under N2. The mixture was diluted with H ₂ O (20 mL) and extracted with EtOAc (20 mL x 2). The combined organic layers were washed with brine (20 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (40-80% EtOAc in petroleum ether), 3-(3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-5-(2-isopropyl-2H-l,2, 3-triazol-4-yl)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (180 mg, 333 umol, yield: 42.5% for two steps) was obtained as a yellow oil. MS: m/z = 541.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J= 8.4 Hz, 1H), 8.03 - 7.93 (m, 3H), 7.51 - 7.41 (m, 4H), 7.18 (dd, J= 7.6, 2.0, Hz, 1H), 6.98 (s, 2H), 6.38 (dd, J= 7.6, 4.8 Hz, 1H), 4.93 - 4.79 (m, 3H), 1.53 (d, J= 6.8 Hz, 6H), 0.92 (s, 9H), 0.11 (s, 6H).

Step 3 : (4-(2-(2-Aminopyridin-3-yl)-5-(2-isopropyl-2H-l,2,3-triazol- 4-yl)-3H-imidazo[4,5- b]pyridin-3 -yl)phenyl)methanol

To a solution of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-(2-i sopropyl-2H-l,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (180 mg, 333 umol) was added TBAF (1 M in THF, 533 μL). The reaction mixture was stirred at 20 °C for 0.5 hr. The mixture was diluted with H ₂ O (10 mL) and extracted with EtOAc (10 mL x 2). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. (4-(2-(2-Aminopyridin-3-yl)-5-(2-isopropyl-2H-l,2,3-triazol- 4-yl)-3H-imidazo[4,5-b]pyridin-3- yl)phenyl)methanol (140 mg, 328 umol) was obtained as a brown oil, which was used in the next step directly. MS: m/z = 427.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.26 (d, J= 8.4 Hz, 1H), 8.10 - 7.92 (m, 3H), 7.55 - 7.37 (m, 4H), 7.20 (d, J= 7.6 Hz, 1H), 6.93 (s, 2H), 6.52 - 6.35 (m, 1H), 5.37 (s, 1H), 4.97 - 4.82 (m, 1H), 4.60 (s, 2H), 1.53 (d, J= 6.8 Hz, 6H).

Step 4: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-isopropyl-2H-l,2,3-triazo l-4-yl)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine

To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(2-isopropyl-2H-l,2,3-triazol- 4-yl)-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (140 mg, 328 umol) in CH ₂ CI ₂ (5 mL) was added SOCl ₂ (117 mg, 985 umol, 71.5 μL). The reaction mixture was stirred at 20 °C for 1 hr. The reaction mixture was concentrated to give 3-(3-(4-(chloromethyl)phenyl)-5-(2-isopropyl-2H- l,2,3-triazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2- amine (Intermediate 289, 146 mg, 328 umol) as a brown oil, which was used in the next step directly. MS: m/z = 445.2 [M + H] ⁺ . [00465] Intermediate 290: 4-Bromo-l-isopropyl-1H-l,2,3-triazole

Intermediate 290 was prepared in a manner similar to Intermediate 288. MS: m/z = 188.0, 190.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 7.56 (s, 1H), 4.87 - 4.78 (m, 1H), 1.58 (d, J= 6.8 Hz, 6H).

[00466] Intermediate 291: 3-(3-(4-(Chloromethyl)phenyl)-5-(l-isopropyl- 1H-1,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Intermediate 291 was prepared in a manner similar to Intermediate 289. MS: m/z = 445.2, 447.2 [M + H] ⁺ . [00467] Intermediate 292: 4-Bromo-2-methyl-5-(methyl-d ₃ )-2H-1,2,3-triazole To a solution of 4,5-dibromo-2-methyl-2H-1,2,3-triazole (1 g, 4.2 mmol) in THF (10 mL) was degassed and purged with N ₂ three times. n-BuLi (2.49 mL, 6.2 mmol, 2.5 M in n-hexane) was added at 0 ºC and stirred at 0 ºC for 0.5 hr under N ₂ atmosphere. The mixture was added CD ₃ I (884 mg, 6.2 mmol) at 0 ºC and stirred at 0 ºC for 2 hr under N ₂ atmosphere. The mixture was quenched with H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (50 mL x 2). The combined organic layers were washed with brine (50 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated. 4- Bromo-2-methyl-5-(methyl-d ₃ )-2H-1,2,3-triazole (Intermediate 292, 550 mg, crude) was obtained as a yellow oil, which was used in the next step without purification. [00468] Intermediate 293: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-methyl-5-(methyl-d ₃ )-2H- 1,2,3-triazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2- amine

Intermediate 293 was prepared in a manner similar to Intermediate 289. MS: m/z = 434.2 [M + H]+. [00469] Intermediate 294: 3-(3-(4-(Chloromethyl)phenyl)-5-(2,5-dimethyl-2H-1,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 294 was prepared in a manner similar to Intermediate 289. MS: m/z = 431.2, 433.1 [M + H] ⁺ . [00470] Intermediate 295: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-cyclopropyl-2H-1,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Intermediate 295 was prepared in a manner similar to Intermediate 289. MS: m/z = 443.1, 445.2 [M + H] ⁺ . [00471] Intermediate 296: 4-Bromo-2-methyl-2H-1,2,3-triazole-5-d To a solution of 4,5-dibromo-2-methyl-2H-1,2,3-triazole (1 g, 4.15 mmol) in THF (10 mL) was degassed and purged with N ₂ three times. n-BuLi (2.5 M, 2.49 mL) was added at -78 °C under N ₂ atmosphere. The mixture was stirred at -78 °C for 0.5 hr under N ₂ atmosphere. The reaction mixture was quenched with D ₂ O (166 mg, 8.30 mmol) at -78 °C and stirred at -78 °C for 2 hr under N ₂ atmosphere. The reaction mixture was diluted with H ₂ O (10 mL) and extracted with CH ₂ Cl ₂ 30 mL (15 mL x 2). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. 4-Bromo-2- methyl-2H-1,2,3-triazole-5-d (Intermediate 296, 200 mg, yield: 30%) was obtained as a light- yellow oil. NMR (400 MHz, Chloroform-d) δ 4.18 (s, 3H). [00472] Intermediate 297: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-methyl-2H-1,2,3-triazol- 4-yl-5-d)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Intermediate 297 was prepared in a manner similar to Intermediate 289. MS: m/z = 418.1 [M + H] ⁺ . [00473] Intermediate 298: 4-(2-(3-Aminopyrazin-2-yl)-5-bromo-3H-imidazo[4,5- b]pyridin-3-yl)benzyl acetate Step 1: (4-((6-Bromo-3-nitropyridin-2-yl)amino)phenyl)methanol A mixture of 2,6-dibromo-3-nitropyridine (5 g, 17.7 mmol), (4-aminophenyl)methanol (2.18 g, 17.7 mmol), DIEA (6.88 g, 53.2 mmol) in 1,4-dioxane (50 mL) was degassed and purged with N ₂ three times and stirred at 45 °C for 2 hr under N ₂ atmosphere. The reaction mixture was quenched with H ₂ O (100 mL) at 25 °C and extracted with CH ₂ Cl ₂ (100 mL x 2). The combined organic layers were washed with brine (100 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. (4-((6-Bromo-3-nitropyridin-2-yl)amino)phenyl)methanol (5.75 g) was obtained as a yellow solid. MS: m/z = 324.1, 326.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 10.24 (br s, 1H), 8.33 (d, J = 8.8 Hz, 1H), 7.71 - 7.58 (m, 2H), 7.43 - 7.40 (m, 2H), 6.97 (d, J = 8.4 Hz, 1H), 4.71 (br s, 2H). Step 2: 4-((6-Bromo-3-nitropyridin-2-yl)amino)benzyl acetate To a solution of (4-((6-bromo-3-nitropyridin-2-yl)amino)phenyl)methanol (5.75 g, 17.7 mmol) in CH ₂ Cl ₂ (60 mL) were added DMAP (217 mg, 1.77 mmol), TEA (5.39 g, 53.2 mmol) and Ac ₂ O (2.72 g, 26.6 mmol). The mixture was stirred at 25 °C for 2 hr. The reaction mixture was quenched with H ₂ O (100 mL) at 25 °C and extracted with CH ₂ Cl ₂ (100 mL x 2). The combined organic layers were washed with brine (100 mL), dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 15% EtOAc in petroleum ether), 4-((6-bromo-3-nitropyridin-2-yl)amino)benzyl acetate (4.9 g, yield: 75% for two steps) was obtained as a yellow solid. ¹ H NMR (400 MHz, Chloroform-d) δ 10.25 (br s, IH), 8.33 (d, J= 8.4 Hz, IH), 7.66 (d, J= 8.4 Hz, 2H), 7.40 (d, J= 8.4 Hz, 2H), 6.98 (d, J= 8.4 Hz, IH), 5.11 (s, 2H), 2.11 (s, 3H).

Step 3: 4-(2-(3-Aminopyrazin-2-yl)-5-bromo-3H-imidazo[4,5-b]pyridin- 3-yl)benzyl acetate To a solution of 4-((6-bromo-3-nitropyridin-2-yl)amino)benzyl acetate (1 g, 2.73 mmol) in DMSO (10 mL) were added Na ₂ S ₂ O ₄ (2.16 g, 10.9 mmol, 88% purity) and 3-aminopyrazine-2- carbaldehyde (403 mg, 3.28 mmol). The mixture was stirred at 100 °C for 3 hr. The reaction mixture was quenched with H ₂ O (50 mL) at 25 °C and extracted with CH ₂ CI ₂ (50 mL x 2). The combined organic layers were washed with brine (50 mL x 3), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 22% EtOAc in petroleum ether), 4-(2-(3-aminopyrazin-2-yl)- 5-bromo-3H-imidazo[4,5-b]pyridin-3-yl)benzyl acetate (Intermediate 298, 270 mg, yield: 21%) was obtained as a yellow solid. MS: m/z = 439.1, 441.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 7.99 - 7.93 (m, 2H), 7.56 (d, J= 2.4 Hz, IH), 7.50 - 7.44 (m, 3H), 7.33 - 7.29 (m, 2H), 7.17 - 6.85 (m, 2H), 5.21 (s, 2H), 2.17 (s, 3H).

[00474] Intermediate 299: (l-(Difluoromethyl)-6-oxo-l,6-dihydropyridin-3-yl)boronic acid

A mixture of 5-bromo-l-(difluoromethyl)pyridin-2(1H)-one (50 mg, 223 umol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(l,3,,2-dioxaborolane) (113 mg, 446 umol), Pd(dppf)Cl ₂ (16.3 mg, 22.3 umol) and KOAc (65.7 mg, 670 umol) in 1,4-dioxane (2 mL) was degassed and purged with N2 three times. The mixture was stirred at 80 °C for 2 hr under N ₂ atmosphere. (1- (Difluoromethyl)-6-oxo-l,6-dihydropyridin-3-yl)boronic acid (Intermediate 299) was obtained as a black liquid, the mixture was used for next step directly and without work-up and purification. MS: m/z = 189.7 [M + H] ⁺ .

[00475] Intermediate 300 & 301 : 4-Bromo-2-(fluoromethyl)-2H-l,2,3-triazole & 4- Bromo- 1 -(fluoromethyl)- 1H- 1 ,2,3 -triazole A mixture of 4-bromo-2H-1,2,3-triazole (3 g, 20.3 mmol), bromofluoromethane (4.58 g, 40.6 mmol), DIEA (7.86 g, 60.8 mmol) in DMF (50 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 80 °C for 1 hr under N ₂ atmosphere. The reaction mixture was diluted with H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (50 mL x3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The mixture (3.2 g, crude) of 4-bromo-2-(fluoromethyl)-2H-1,2,3-triazole (Intermediate 300) and 4-bromo-1-(fluoromethyl)-1H-1,2,3-triazole (Intermediate 301) was obtained as a brown solid. ¹ H NMR (400 MHz, Chloroform-d) δ 7.73 (s, 1H), 6.27 - 6.12 (m, 2H). ¹⁹ F NMR (400 MHz, Chloroform-d) δ -166.057. ¹ H NMR (400 MHz, Chloroform-d) 7.87 (s, 1H), 6.35 - 6.20 (m, 2H). ¹⁹ F NMR (400 MHz, Chloroform-d) δ -167.648. [00476] Intermediate 302 & 303: 3-(3-(4-(((tert-Butyldimethylsilyl)oxy)methyl)phenyl)- 5-(2-(fluoromethyl)-2H-1,2,3-triazol-4-yl)-3H-imidazo[4,5-b] pyridin-2-yl)pyridin-2-amine & 3- (3-(4-(((tert-Butyldimethylsilyl)oxy)methyl)phenyl)-5-(1-(fl uoromethyl)-1H-1,2,3-triazol-4-yl)- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: (2-(2-Aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)oxy )methyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)boronic acid A mixture of Intermediate 129 (5 g, 9.79 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2- dioxaborolane) (4.97 g, 19.6 mmol), KOAc (2.88 g, 29.4 mmol) and Pd(dppf)Cl ₂ (717 mg, 979 µmol) in 1,4-dioxane (60 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 90 °C for 2 hr under N ₂ atmosphere. (2-(2-Aminopyridin-3-yl)-3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-3H-imidazo[4,5-b]pyrid in-5-yl)boronic acid was obtained as a black liquid, which was used in the next step without work-up and purification. MS: m/z = 476.4 [M+H] ⁺ . Step 2: 3-(3-(4-(((tert-Butyldimethylsilyl)oxy)methyl)phenyl)-5-(2-( fluoromethyl)-2H-1,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine & 3-(3-(4-(((Tert- butyldimethylsilyl)oxy)methyl)phenyl)-5-(1-(fluoromethyl)-1H -1,2,3-triazol-4-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine A mixture of (2-(2-aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)oxy )methyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)boronic acid (4 g, 8.41 mmol), Intermediate 300 (1.51 g, 8.41 mmol contained Intermediate 301), Pd(dppf)Cl ₂ (616 mg, 841 µmol), Cs ₂ CO ₃ (8.22 g, 25.2 mmol) in 1,4-dioxane (40 mL) and H ₂ O (10 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 100 °C for 4 hr under N ₂ atmosphere. The residue was diluted with H ₂ O (50 mL) and extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (20 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-HPLC (column: Phenomenex luna C18 (250 x 70 mm, 10 μm); mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 60% - 90% B over 5 min), 3-(3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-5-(2-(fluoromethyl)-2H -1,2,3-triazol-4-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine as a yellow solid (Intermediate 302, 2.2 g, yield: 48 % for two steps ) was obtained as a yellow solid. MS: m/z = 531.2 [M+H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.21 (s, 1H), 8.17 - 8.13 (m, 1H), 8.09 - 8.04 (m, 2H), 7.51 (d, J = 8.0 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H), 7.13 (dd, J = 7.6, 1.6 Hz, 1H), 6.67 (br s, 2H), 6.38 (dd, J = 8.0, 5.2 Hz, 1H), 6.28 (d, J = 52.0 Hz, 2H), 4.87 (s, 2H), 0.98 (s, 9H), 0.16 (s, 6H). ¹⁹ F NMR (400 MHz, Chloroform-d) δ -166.057. 3-(3-(4-((( tert-butyldimethylsilyl)oxy)methyl)phenyl)-5- (1-(fluoromethyl)-1H-1,2,3-triazol-4-yl)-3H-imidazo[4,5-b]py ridin-2-yl)pyridin-2-amine (Intermediate 303, 550 mg, yield: 8.9 % for two steps) was obtained as a brown solid. MS: m/z = 531.1 [M+H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.30 - 8.23 (m, 2H), 8.18 - 8.14 (m, 1H), 8.09 - 8.06 (m, 1H), 7.50 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 7.11 (dd, J = 8.0, 1.6 Hz, 1H), 6.67 (br s, 2H), 6.39 - 6.35 (m, 2H), 6.24 - 6.22 (m, 1H), 4.87 (s, 2H), 0.99 (s, 9H), 0.17 (s, 6H). ¹⁹ F NMR (400 MHz, Chloroform-d) δ -167.296. [00477] Intermediate 304: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-(fluoromethyl)-2H-1,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Step 1: (4-(2-(2-Aminopyridin-3-yl)-5-(2-(fluoromethyl)-2H-1,2,3-tri azol-4-yl)-3H-imidazo[4,5- b]pyridin-3-yl)phenyl)methanol To a solution of Intermediate 302 (2.2 g, 4.15 mmol) in THF (20 mL) was added TBAF (6.22 mL, 1 M in THF). The residue was diluted with H ₂ O (50 mL) and extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (20 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. (4-(2-(2-Aminopyridin-3-yl)-5-(2- (fluoromethyl)-2H-1,2,3-triazol-4-yl)-3H-imidazo[4,5-b]pyrid in-3-yl)phenyl)methanol (Intermediate 304, 1.5 g, crude) was obtained as a brown solid which was used into the next step directly. MS: m/z = 417.3 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.38 - 8.27 (m, 2H), 8.07 - 7.95 (m, 2H), 7.51 - 7.42 (m, 4H), 7.23 (dd, J = 7.6, 1.6 Hz, 1H), 6.91 (br s, 2H), 6.55 - 6.53 (m, 1H), 6.44 - 6.40 (m, 2H), 5.37 (br t, J = 5.6 Hz, 1H), 4.60 (d, J = 5.6 Hz, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -166.272. Step 2: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-(fluoromethyl)-2H-1,2,3-t riazol-4-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(2-(fluoromethyl)-2H-1,2,3-tri azol-4-yl)-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (1.5 g, 3.60 mmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (857 mg, 7.20 mmol). The reaction mixture was stirred at 40 °C for 1 hr. The reaction mixture was concentrated. 3-(3-(4-(Chloromethyl)phenyl)-5-(2-(fluoromethyl)-2H-1,2,3-t riazol- 4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (Intermediate 304, 1.6 g, crude, HCl salt) was obtained as a yellow solid, which was used into the next step directly. MS: m/z = 435.0, 437.0 [M+H] ⁺ . [00478] Intermediate 305: 3-(3-(4-(Chloromethyl)phenyl)-5-(1-(fluoromethyl)-1H-1,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 305 was prepared in a manner similar to Intermediate 304. MS: m/z = 435.1, 437.1 [M+H] ⁺ . [00479] Intermediate 306: 4-Bromo-2-(difluoromethyl)-2H-1,2,3-triazole To a solution of 4-bromo-2H-1,2,3-triazole (1 g, 6.76 mmol) and Cs ₂ CO ₃ (6.6 g, 20.3 mmol) in DMSO (30 mL) was added sodium 2-chloro-2,2-difluoroacetate (2.06 g, 13.5 mmol) at 25 °C. The mixture was stirred at 90 °C for 16 hr. The mixture was quenched with H ₂ O (30 mL) and extracted with EtOAc (30 mL x 3). The combined organic layers were washed with brine (30 mL x 5), dried over Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0% ~ 5% EtOAc in petroleum ether), 4-bromo-2-(difluoromethyl)- 2H-1,2,3-triazole (Intermediate 306, 150 mg, yield: 11%) was obtained as a yellow oil. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.11 (s, 1H), 8.43 - 8.09 (m, 1H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -96.77. [00480] Intermediate 307: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-(difluoromethyl)-2H- 1,2,3-triazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2- amine Intermediate 307 was prepared in a manner similar to Intermediate 289. MS: m/z = 453.1, 455.1 [M + H] ⁺ . [00481] Intermediate 308: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-(methyl-d ₃ )-2H-1,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrazin-2-amine Intermediate 308 was prepared in a manner similar to Intermediate 289. MS: m/z = 421.1, 423.1 [M + H] ⁺ . [00482] Intermediate 309: tert-Butyl N-tert-butoxycarbonyl-N-(4-formylisoxazol-3- yl)carbamate Step 1: tert-Butyl N-(4-bromoisoxazol-3-yl)-N-tert-butoxycarbonyl-carbamate To a solution of 4-bromoisoxazol-3-amine (1 g, 6.14 mmol) in CH ₂ Cl ₂ (10 mL) were added Boc ₂ O (3.35 g, 15.3 mmol), DMAP (75.0 mg, 614 µmol) and TEA (3.42 mL, 24.5 mmol). The mixture was degassed and purged with N ₂ three times and stirred at 25 °C for 2 hr under N ₂ atmosphere. The reaction mixture was quenched with CH ₂ Cl ₂ (30 mL), washed with H ₂ O (30 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. tert-Butyl N-(4- bromoisoxazol-3-yl)-N-tert-butoxycarbonyl-carbamate (2.40 g, crude) was obtained as a brown solid, which was used in the next step directly. MS: m/z = 206.9, 208.9 [M-156+H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.43 (s, 1H), 1.44 (s, 18H). Step 2: tert-Butyl N-tert-butoxycarbonyl-N-(4-vinylisoxazol-3-yl)carbamate To a solution of tert-butyl N-(4-bromoisoxazol-3-yl)-N-tert-butoxycarbonyl-carbamate (2.40 g, 6.61 mmol) in 1,4-dioxane (30 mL) and H ₂ O (6 mL) were added Pd(dppf)Cl ₂ (484 mg, 661 µmol), Cs ₂ CO ₃ (6.46 g, 19.8 mmol) and 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (2.24 mL, 13.2 mmol). The mixture was degassed and purged with N ₂ for 3 times and stirred at 90 °C for 2 hr. The reaction mixture was quenched with EtOAc (100 mL), washed with brine (100 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 10% EtOAc in petroleum ether), tert-butyl N- tert-butoxycarbonyl-N-(4-vinylisoxazol-3-yl)carbamate (1.26 g, yield: 58% for two steps) was obtained as a pink oil. MS: m/z = 643.2 [2M + Na] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.42 (s, 1H), 6.33 (dd, J = 18.0, 11.2 Hz, 1H), 5.54 (d, J = 18.0 Hz, 1H), 5.34 (d, J = 11.2 Hz, 1H), 1.42 (s, 18H) Step 3: tert-Butyl N-tert-butoxycarbonyl-N-(4-formylisoxazol-3-yl)carbamate To a solution of tert-butyl N-tert-butoxycarbonyl-N-(4-vinylisoxazol-3-yl)carbamate (1.12 g, 3.61 mmol) in THF (20 mL) were added NaIO ₄ (1.54 g, 7.22 mmol) and K ₂ OsO ₄ ·2H ₂ O (133 mg, 361 µmol). The mixture was degassed andpurged with N ₂ three times and stirred at 0 °C for 2 hr under N ₂ . The reaction mixture was quenched with Sat.Na ₂ SO ₃ (30 mL) at 0 °C and extracted with EtOAc (30 mL x 3). The combined organic layers were washed with brine (50 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 10% EtOAc in petroleum ether), tert-butyl N- tert-butoxycarbonyl-N-(4-formylisoxazol-3-yl)carbamate (Intermediate 309, 178 mg, yield: 16%) was obtained as a white solid. ¹ H NMR (400 MHz, Chloroform-d) δ 9.93 (s, 1H), 8.97 (s, 1H), 1.45 (s, 18H). [00483] Intermediate 310: 4-(3-(4-(Chloromethyl)phenyl)-5-(5-fluoropyridin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)isoxazol-3-amine Intermediate 310 was prepared in a manner similar to Intermediate 226. MS: m/z = 420.8, 422.8 [M+H] ⁺ . [00484] Intermediate 311 & 312: 5-Bromo-2-(fluoromethoxy-d ₂ )pyridine & 5-Bromo-1- (fluoromethyl-d ₂ )pyridin-2(1H)-one Step 1: Methylene-d ₂ bis(4-methylbenzenesulfonate) To a solution of (tosyloxy)silver (52 g, 186 mmol) in MeCN (200 mL) was added dibromomethane-d ₂ (14.9 g, 84.7 mmol). The mixture was stirred at 80 °C for 16 hr. The reaction mixture was filtered to remove all the salts. The filtrate was collected and concentrated under reduced pressure. The crude was triturated with CH ₂ Cl ₂ (150 mL) at 25 °C for 3 hr. The filtrate was collected and concentrated under reduced pressure to give methylene-d ₂ bis(4- methylbenzenesulfonate) (18 g, yield: 59%) was obtained as an off-white solid. MS: m/z = 381.0 [M+Na] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 7.60 (d, J = 8.4 Hz, 4H), 7.40 (d, J = 8.0 Hz, 4H), 2.42 (s, 6H). Step 2: Fluoromethyl-d ₂ 4-methylbenzenesulfonate To a solution of methylene-d ₂ bis(4-methylbenzenesulfonate) (3.2 g, 8.93 mmol) in MeCN (80 mL) were added CsF (2.03 g, 13.4 mmol) and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol (3.78 g, 13.4 mmol). The mixture was stirred at 80 °C for 16 hr. The residue was diluted with H ₂ O (10 mL) and extracted with CH ₂ Cl ₂ (10 mL x 3). The combined organic layers were washed with brine (5 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 5% EtOAc in petroleum ether), fluoromethyl-d ₂ 4-methylbenzenesulfonate (18 g, yield: 48%) was obtained as a colorless oil. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 7.85 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 8.0 Hz, 2H), 2.43 (s, 3H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -154.079. Step 3: 5-Bromo-2-(fluoromethoxy-d ₂ )pyridine & 5-Bromo-1-(fluoromethyl-d ₂ )pyridin-2(1H)- one To a solution of fluoromethyl-d ₂ 4-methylbenzenesulfonate (890 mg, 4.32 mmol), 5- bromopyridin-2-ol (751 mg, 4.32 mmol) in DMF (15 mL) was added K ₂ CO ₃ (1.79 g, 13.0 mmol). The mixture was stirred at 50 °C for 2 hr. The residue was diluted with H ₂ O (10 mL) and extracted with CH ₂ Cl ₂ (10 mL x 3). The combined organic layers were washed with brine (5 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 15% EtOAc in petroleum ether), 5-bromo-2- (fluoromethoxy-d ₂ )pyridine (Intermediate 311, 490 mg, yield: 55%) was obtained as a colorless oil. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.38 (d, J = 2.4 Hz, 1H), 8.06 (dd, J = 8.8, 2.4 Hz, 1H), 7.01 (d, J = 8.8 Hz, 1H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -156.130. 5- Bromo-1-(fluoromethyl-d ₂ )pyridin-2(1H)-one (Intermediate 312, 490 mg, yield: 19%) was obtained as a colorless oil. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.19 (d, J = 2.8 Hz, 1H), 7.62 (dd, J = 10.0, 2.8 Hz, 1H), 6.47 (d, J = 10.0 Hz, 1H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -173.825. [00485] Intermediate 313: 3-(3-(4-(Chloromethyl)phenyl)-5-(6-(fluoromethoxy- d ₂ )pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2 -amine Intermediate 313 was prepared in a manner similar to Intermediate 289. MS: m/z = 463.0, 465.0 [M + H] ⁺ . [00486] Intermediate 314: 5-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)-1-(fluoromethyl-d2)pyridin-2(1H) -one Intermediate 314 was prepared in a manner similar to Intermediate 289. MS: m/z = 463.1, 465.1 [M + H] ⁺ . [00487] Intermediate 315: 4-Bromo-1-ethyl-1H-1,2,3-triazole To a mixture of Intermediate 283 (680 mg, 2.67 mmol) in THF (2 mL) was added n-BuLi (2.5M in hexane, 1.07 mL) at -70 °C under N ₂ , the mixture was stirred at -70 °C for 1 hr. The mixture was diluted with H ₂ O (20 mL) and extracted with EtOAc (20 mL x 2). The combined organic layers were washed with brine (20 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. 4-Bromo-1-ethyl-1H-1,2,3-triazole (Intermediate 315, 440 mg, 2.50 mmol, yield: 94%) was obtained as a yellow oil. MS: m/z = 175.8, 177.8 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.42 (s, 1H), 4,40 (q, J = 7.2 Hz, 2H), 1.42 (t, J = 7.2 Hz, 3H). [00488] Intermediate 316: 3-(3-(4-(Chloromethyl)phenyl)-5-(1-ethyl-1H-1,2,3-triazol-4- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Intermediate 316 was prepared in a manner similar to Intermediate 289. MS: m/z = 431.2, 433.1 [M + H] ⁺ . [00489] Intermediate 317: 2-(4-Bromo-2H-1,2,3-triazol-2-yl)acetonitrile To a solution of 4-bromo-2H-1,2,3-triazole (300 mg, 2.03 mmol) and 2-bromoacetonitrile (121 mg, 1.01 mmol) in DMF (5 mL) was added K ₂ CO ₃ (841 mg, 6.08 mmol). The mixture was stirred at 25 °C for 2 hr under N ₂ . The reaction mixture was quenched with NaHSO ₃ (10 mL), diluted with H ₂ O (10 mL), and extracted with CH ₂ Cl ₂ (5 mL x 2). The combined organic layers were washed with brine (10 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. 2-(4-Bromo-2H-1,2,3-triazol-2-yl)acetonitrile (Intermediate 317, 379 mg ) was obtained as a light yellow oil. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) R 8.18 (s, 1H), 5.94 (s, 2H). [00490] Intermediate 318: 2-(4-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)- 3H-imidazo[4,5-b]pyridin-5-yl)-2H-1,2,3-triazol-2-yl)acetoni trile

Intermediate 318 was prepared in a manner similar to Intermediate 289. MS: m/z = 442.1, 444.1[M + H] ⁺ [00491] Intermediate 319 & 320: 4-(2-(3-Aminopyrazin-2-yl)-5-(2-(fluoromethyl)-2H- 1,2,3-triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl acetate & 4-(2-(3-Aminopyrazin-2-yl)- 5-(1-(fluoromethyl)-1H-1,2,3-triazol-4-yl)-3H-imidazo[4,5-b] pyridin-3-yl)benzyl acetate Step 1: (3-(4-(Acetoxymethyl)phenyl)-2-(3-aminopyrazin-2-yl)-3H-imid azo[4,5-b]pyridin-5- yl)boronic acid A mixture of Intermediate 298 (500 mg, 1.14 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2- dioxaborolane) (578 mg, 2.28 mmol), KOAc (335 mg, 3.41 mmol) and Pd(dppf)Cl ₂ (83.3 mg, 114 µmol) in 1,4-dioxane (5 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 90 °C for 2 hr under N ₂ atmosphere. (3-(4-(Acetoxymethyl)phenyl)-2-(3- aminopyrazin-2-yl)-3H-imidazo[4,5-b]pyridin-5-yl)boronic acid was obtained as a black liquid, which was used in the next step without work-up and purification. MS: m/z = 405.2 [M+H] ⁺ . Step 2: 4-(2-(3-Aminopyrazin-2-yl)-5-(2-(fluoromethyl)-2H-1,2,3-tria zol-4-yl)-3H-imidazo[4,5- b]pyridin-3-yl)benzyl acetate & 4-(2-(3-Aminopyrazin-2-yl)-5-(1-(fluoromethyl)-1H-1,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl acetate A mixture of (3-(4-(acetoxymethyl)phenyl)-2-(3-aminopyrazin-2-yl)-3H-imid azo[4,5-b]pyridin- 5-yl)boronic acid (450 mg, 1.11 mmol), Intermediate 300 (200 mg, 1.11 mmol contained Intermdiate 301), Pd(dppf)Cl ₂ (81.5 mg, 111 μmol), CS ₂ CO ₃ (1.09 g, 3.34 mmol) in 1,4-dioxane (10 mL) and H ₂ O (2.5 mL) was degassed and purged with N2 three times. The mixture was stirred at 100 °C for 16 hr under N2 atmosphere. The residue was diluted with H ₂ O (10 mL) and extracted with CH2Cl ₂ (10 mL x 3). The combined organic layers were washed with brine (5 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-HPLC (column: Waters Xbridge BEH C18250 x 50 mm x 10 μm; mobile phase: [water (NH4HCO3) - ACN]; gradient: 33% - 63% B over 10 min), 4-(2-(3-aminopyrazin-2-yl)-5-(2- (fluoromethyl)-2H- 1,2,3 -triazol-4-yl)-3H-imidazo[4, 5-b]pyri din-3 -yl)benzyl acetate (Intermediate 319, 200 mg, yield: 36 % for two steps ) was obtained as a gray solid. MS: m/z = 460.1 [M+H] ⁺ . ¹ HNMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.41 (d, J= 8.4 Hz, 1H), 8.35 (s, 1H), 8.09 - 7.98 (m, 2H), 7.78 (br s, 2H), 7.56 - 7.41 (m, 5H), 6.49 (d, J= 51.6 Hz, 2H), 5.20 (s, 2H), 2.13 (s, 3H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -166.385. 4-(2-(3- Aminopyrazin-2-yl)-5-(l-(fluoromethyl)-1H-l,2,3-triazol-4-yl )-3H-imidazo[4,5-b]pyridin-3- yl)benzyl acetate (Intermediate 320, 80 mg, yield: 15 % for two steps) was aslo obtained as a gray solid. MS: m/z = 460.1 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.77 (s, 1H), 8.39 (d, J= 8.4 Hz, 1H), 8.16 (d, J= 8.4 Hz, 1H), 8.02 (d, J= 2.0 Hz, 1H), 7.78 (br s, 2H), 7.53 - 7.42 (m, 5H), 6.49 (d, J= 50.4 Hz, 2H), 5.19 (s, 2H), 2.13 (s, 3H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -166.760.

[00492] Intermediate 321: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-(fluoromethyl)-2H-l,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyri din-2 -yl)pyrazin-2-amine

Step 1 : (4-(2-(3-Aminopyrazin-2-yl)-5-(2-(fluoromethyl)-2H-l,2,3-tri azol-4-yl)-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methanol

To a solution of Intermediate 319 (200 mg, 435 μmol) in MeOH (2 mL), THF (2 mL) and H ₂ O (0.5 mL) was added K ₂ CO ₃ (180 mg, 1.31 mmol). The mixture was stirred at 25 °C for 0.5 hr. The residue was diluted with H ₂ O (8 mL) and extracted with CH ₂ CI ₂ (10 mL x 3). The combined organic layers were washed with brine (5 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. (4-(2-(3-Aminopyrazin-2-yl)-5-(2-(fluoromethyl)-2H- l,2,3-triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)met hanol (160 mg, crude) was obtained as a yellow solid which was used into the next step directly. MS: m/z = 417.9 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.40 (d, J = 8.0 Hz, 1H), 8.33 (s, 1H), 8.08 - 7.99 (m, 2H), 7.74 (br s, 2H), 7.55 (d, J = 2.4 Hz, 1H), 7.47 - 7.42 (m, 2H), 7.41 - 7.35 (m, 2H), 6.48 (d, J = 51.6 Hz, 2H), 5.34 (br t, J = 5.6 Hz, 1H), 4.61 (d, J = 5.6 Hz, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -166.387. Step 2: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-(fluoromethyl)-2H-1,2,3-t riazol-4-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyrazin-2-amine To a solution of (4-(2-(3-aminopyrazin-2-yl)-5-(2-(fluoromethyl)-2H-1,2,3-tri azol-4-yl)-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (200 mg, 479 μmol) in CH ₂ Cl ₂ (5 mL) was added SOCl ₂ (114 mg, 958 µmol). The reaction mixture was stirred at 40 ºC for 1 hr. The reaction mixture was concentrated under reduced pressure to give 3-(3-(4-(chloromethyl)phenyl)-5-(2- (fluoromethyl)-2H-1,2,3-triazol-4-yl)-3H-imidazo[4,5-b]pyrid in-2-yl)pyrazin-2-amine (Intermediate 321, 200 mg, crude, HCl salt) as a gray solid, which was used in the next step directly. MS: m/z = 435.8, 437.8 [M+H] ⁺ . [00493] Intermediate 322: 3-(3-(4-(Chloromethyl)phenyl)-5-(1-(fluoromethyl)-1H-1,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrazin-2-amine Intermediate 322 was prepared in a manner similar to Intermediate 321. MS: m/z = 435.8, 437.8 [M+H] ⁺ . [00494] Intermediate 323: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-ethyl-2H-1,2,3-triazol-4- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrazin-2-amine

Step 1 : (3-(4-(Acetoxymethyl)phenyl)-2-(3-aminopyrazin-2-yl)-3H-imid azo[4,5-b]pyridin-5- yl)boronic acid

To a mixture of Intermediate 298 (380 mg, 865 μmol) and 4,4,4 ^, ,4 ^, ,5,5,5*,5 ^, -octamethyl-2,2'- bi(l,3,2-dioxaborolane) (439 mg, 1.73 mmol) in 1,4-dioxane (8 mL) were added Pd(dppf)Cl ₂ (63.3 mg, 86.5 μmol) and KOAc (255 mg, 2.60 mmol). The mixture was stirred at 85 °C for 1 hr. (3-(4-(Acetoxymethyl)phenyl)-2-(3-aminopyrazin-2-yl)-3H-imid azo[4,5-b]pyridin-5- yl)boronic acid was obtained as a black liquid, which was used in the next step without work-up and purification. MS: m/z = 405.1 [M + H] ⁺ .

Step 2 : 4-(2-(3 -Aminopyrazin-2-yl)-5-(2-ethyl-2H- 1,2,3 -triazol -4-yl)-3H-imidazo[4, 5-b]py ridin- 3-yl)benzyl acetate

To a mixture of (3-(4-(acetoxymethyl)phenyl)-2-(3-aminopyrazin-2-yl)-3H-imid azo[4,5- b]pyridin-5-yl)boronic acid (270 mg, 668 μmol) and Intermediate 284 (235 mg, 1.34 mmol) in 1,4-dioxane (10 mL) and H ₂ O (2 mL) were added CS ₂ CO ₃ (653 mg, 2.00 mmol) and Pd(dppf)Cl ₂ (48.9 mg, 66.8 μmol). The mixture was stirred at 100 °C for 1 hr. The reaction mixture was quenched with H ₂ O (50 mL) and extracted with EtOAc (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (EtOAc in petroleum ether = 0 - 50%), 4-(2-(3-aminopyrazin-2-yl)-5-(2-ethyl-2H-l,2,3-triazol-4-yl) -3H- imidazo[4,5-b]pyridin-3-yl)benzyl acetate (250 mg, yield 82% for two steps) was obtained as a yellow solid. MS: m/z = 456.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.35 (d, J= 8.4 Hz, 1H), 8.05 (s, 1H), 8.02 (d, J= 2.4 Hz, 1H), 7.98 (d, J= 8.4 Hz, 1H), 7.77 (br s, 2H), 7.56 - 7.48 (m, 3H), 7.46 - 7.41 (m, 2H), 5.19 (s, 2H), 4.51 (q, J= 7.2 Hz, 2H), 2.13 (s, 3H), 1.49 (t, J= 7.2 Hz, 3H). Step 3 : (4-(2-(3-Aminopyrazin-2-yl)-5-(2-ethyl-2H-l,2,3-triazol-4-yl )-3H-imidazo[4,5- b]pyridin-3 -yl)phenyl)methanol

To a mixture of 4-(2-(3-aminopyrazin-2-yl)-5-(2-ethyl-2H-l,2,3-triazol-4-yl) -3H-imidazo[4,5- b]pyridin-3-yl)benzyl acetate (240 mg, 527 μmol) in THF (1 mL), MeOH (1 mL) and H ₂ O (0.5 mL) was added K ₂ CO ₃ (218 mg, 1.58 mmol). The mixture was stirred at 20 °C for 0.5 hr. The reaction mixture was quenched with H ₂ O (50 mL) and extracted with EtOAc (30 mL x 2). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated, (4-(2-(3-aminopyrazin-2-yl)-5-(2-ethyl-2H-l,2,3-triazol-4-yl )-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (210 mg, yield: 96%) was obtained as a yellow solid. MS: m/z = 414.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.34 (d, J= 8.4 Hz, 1H), 8.03 (s, 1H), 8.01 (d, J= 2.4 Hz, 1H), 7.97 (d, J= 8.4 Hz, 1H), 7.74 (br s, 2H), 7.53 (d, J= 2.4 Hz, 1H), 7. 46 - 7. 42 (m, 2H), 7.40 - 7.34 (m, 2H), 5.34 (t, J= 5.6 Hz, 1H), 4.61 (d, J= 6.0 Hz, 2H), 4.50 (q, J= 7.2 Hz, 2H), 1.49 (t, J= 7.2 Hz, 3H).

Step 4 : 3 -(3 -(4-(Chloromethyl)phenyl)-5-(2-ethyl-2H- 1 ,2,3 -triazol-4-yl)-3H-imidazo[4, 5- b]pyridin-2-yl)pyrazin-2-amine

To a mixture of (4-(2-(3-aminopyrazin-2-yl)-5-(2-ethyl-2H-l,2,3-triazol-4-yl )-3H-imidazo[4,5- b]pyridin-3-yl)phenyl)methanol (200 mg, 484 μmol) in CH2Cl ₂ (0.5 mL) was added SOCl ₂ (105 μL, 1.45 mmol). The mixture was stirred at 20 °C for 0.5 hr. The reaction was concentrated under reduced pressure. 3-(3-(4-(Chloromethyl)phenyl)-5-(2-ethyl-2H-l,2,3-triazol-4- yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyrazin-2-amine (Intermediate 323, 209 mg) was obtained as a yellow solid. MS: m/z = 432.0, 434.0 [M + H] ⁺ .

[00495] Intermediate 324: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-isopropyl-2/f-l,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrazin-2-amine

437 Intermediate 324 was prepared in a manner similar to Intermediate 323. MS: m/z = 446.1, 448.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.35 (d, J = 8.4 Hz, 1H), 8.04 - 8.01 (m, 2H), 7.99 (d, J = 8.4 Hz, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.52 (d, J = 2.4 Hz, 1H), 7.44 (d, J = 8.4 Hz, 2H), 4.93 - 4.84 (m, 3H), 1.53 (d, J = 6.8 Hz, 6H). [00496] Intermediate 325: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-cyclopropyl-2H-1,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrazin-2-amine Intermediate 325 was prepared in a manner similar to Intermediate 323. MS: m/z = 444.1, 446.1 [M + H] ⁺ . [00497] Intermediate 326 & 327: 2-(4-(2-(3-Aminopyrazin-2-yl)-3-(4- (chloromethyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)-2H-1,2, 3-triazol-2-yl)acetonitrile and 2- (4-(2-(3-aminopyrazin-2-yl)-3-(4-(chloromethyl)phenyl)-3H-im idazo[4,5-b]pyridin-5-yl)-2H- 1,2,3-triazol-2-yl)acetamide Step 1 : (3-(4-(Acetoxymethyl)phenyl)-2-(3-aminopyrazin-2-yl)-3H-imid azo[4,5-b]pyridin-5- yl)boronic acid

To a solution of Intermediate 298 (360 mg, 820 μmol) and 4,4,4 ^, ,4 ^, ,5,5,5 ^, ,5 ^, -octamethyl-2,2'- bi(l,3,2-dioxaborolane) (416 mg, 1.64 mmol) in 1,4-dioxane (2 mL) were added Pd(dppf)Cl ₂ (60.0 mg, 82.0 μmol) and KOAc (241 mg, 2.46 mmol). The mixture was stirred at 85 °C for 2 hr under N2 atmosphere. (3 -(4 -(Acetoxy methyl )phenyl)-2 -(3- ami nopyrazin-2-yl )- 3H- imidazo[4,5-b]pyridin-5-yl)boronic acid was obtained as a black liquid, which was used in the next step without work-up and purification. MS: m/z = 405.1 [M + H] ⁺ .

Step 2 : 4-(2-(3 -Aminopyrazin-2-yl)-5-(2-(cyanomethyl)-2H- 1,2,3 -triazol -4-yl)-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl acetate

To a solution of (3-(4-(acetoxymethyl)phenyl)-2-(3-aminopyrazin-2-yl)-3H-imid azo[4,5- b]pyridin-5-yl)boronic acid (331 mg, 819 μmol) and Intermediate 317 (184 mg, 983 μmol) in 1,4-dioxane (4 mL) and H ₂ O (0.8 mL) were added Pd(dppf)Cl ₂ (59.9 mg, 81.9 μmol) and CS ₂ CO ₃ (801 mg, 2.46 mmol). The mixture was stirred at 100 °C for 2 hr under N2 atmosphere. The mixture was diluted with water (20 mL) and extracted with EtOAc (20 mL x 2). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0% ~ 30% EtOAc in petroleum ether), 4- (2-(3-aminopyrazin-2-yl)-5-(2-(cyanomethyl)-2H-l,2,3-triazol -4-yl)-3H-imidazo[4,5-b]pyridin- 3-yl)benzyl acetate (300 mg, yield: 79% for two steps) was obtained as a light yellow solid. MS: m/z = 467.2 [M + H] ⁺ .

Step 3 : 2-(4-(2-(3-Aminopyrazin-2-yl)-3-(4-(hydroxymethyl)phenyl)-3H -imidazo[4,5-b]pyridin- 5-yl)-2H-l,2,3-triazol-2-yl)acetonitrile & 2-(4-(2-(3-aminopyrazin-2-yl)-3-(4- (hydroxymethyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)-2H-l,2 ,3-triazol-2-yl)acetamide To a solution of 4-(2-(3-aminopyrazin-2-yl)-5-(2-(cyanomethyl)-2H-l,2,3-triaz ol-4-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl acetate (200 mg, 429 μmol) in THF (2 mL) and H ₂ O (1 mL) was added LiOH (30.8 mg, 1.29 mmol). The mixture was stirred at 25 °C for 2 hr. The mixture was diluted with water (10 mL) and extracted with EtOAc (10 mL x 2). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. The mixture (100 mg) of 2-(4-(2-(3-aminopyrazin-2-yl)-3-(4-(hydroxymethyl)phenyl)-3H -imidazo[4,5-b]pyridin-5-yl)- 2H- 1, 2, 3 -tri azol -2-yl) acetonitrile and 2-(4-(2-(3-aminopyrazin-2-yl)-3-(4- (hydroxymethyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)-2H-l,2 ,3-triazol-2-yl)acetamide was obtained as a light yellow oil. MS: m/z = 447.0 [M + Na] ⁺ & MS: m/z = 443.1 [M + H] ⁺ . Step 4: 2-(4-(2-(3-Aminopyrazin-2-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5- yl)-2H-1,2,3-triazol-2-yl)acetonitrile & 2-(4-(2-(3-aminopyrazin-2-yl)-3-(4- (chloromethyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)-2H-1,2, 3-triazol-2-yl)acetamide To a solution of 2-(4-(2-(3-aminopyrazin-2-yl)-3-(4-(hydroxymethyl)phenyl)-3H -imidazo[4,5- b]pyridin-5-yl)-2H-1,2,3-triazol-2-yl)acetonitrile (100 mg, 236 µmol, contained 2-(4-(2-(3- aminopyrazin-2-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imidazo[4, 5-b]pyridin-5-yl)-2H-1,2,3- triazol-2-yl)acetamide) in CH ₂ Cl ₂ (1 mL) was added SOCl ₂ (84.1 mg, 707 µmol). The mixture was stirred at 25 °C for 2 hr. The reaction was concentrated to give a mixture (104 mg, HCl salt, crude) of 2-(4-(2-(3-aminopyrazin-2-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin- 5-yl)-2H-1,2,3-triazol-2-yl)acetonitrile (Intermediate 326 ) and 2-(4-(2-(3-aminopyrazin-2-yl)-3- (4-(chloromethyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)-2H-1 ,2,3-triazol-2-yl)acetamide (Intermediate 327) as a light yellow solid, which was used in the next step without purification. MS: m/z = 443.1, 445.1 [M + H] ⁺ . MS: m/z = 483.0, 485.0 [M + Na] ⁺ . [00498] Intermediate 328: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-(trifluoromethyl)pyridin- 2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 328 was prepared in a manner similar to Intermediate 289. MS: m/z = 481.1, 483.1 [M + H] ⁺ . [00499] Intermediate 329: 3-(3-(4-(Chloromethyl)phenyl)-5-(2-methyl-2H-1,2,3-triazol- 4-yl-5-d)-3H-imidazo[4,5-b]pyridin-2-yl)pyrazin-2-amine

Intermediate 329 was prepared in a manner similar to Intermediate 323. MS: m/z = 419.1, 421.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.33 (d, J = 8.8 Hz, 1H), 8.11 (d, J = 8.4 Hz, 1H), 7.89 (d, J = 3.2 Hz, 1H), 7.71 (d, J = 2.8 Hz, 1H), 7.64 - 7.60 (m, 2H), 7.48 - 7.43 (m, 2H), 4.80 (s, 2H), 4.22 (s, 3H). [00500] Intermediate 330: 3-(3-(4-(Chloromethyl)phenyl)-5-(2,5-dimethyl-2H-1,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrazin-2-amine Intermediate 330 was prepared in a manner similar to Intermediate 323. MS: m/z = 432.1, 434.1[M + H] ⁺ . [00501] Intermediate 331: 3-(3-(4-(Chloromethyl)phenyl)-5-(6-methoxypyridin-3-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyrazin-2-amine

Intermediate 331 was prepared in a manner similar to Intermediate 323. MS: m/z = 444.0, 446.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 9.00 - 8.90 (m, 2H), 8.44 (d, J = 8.4 Hz, 1H), 8.14 (d, J = 8.4 Hz, 1H), 7.91 (d, J = 3.2 Hz, 1H), 7.72 (d, J = 3.6 Hz, 1H), 7.65 - 7.61 (m, 2H), 7.56 - 7.46 (m, 3H), 4.80 (s, 2H), 4.23 (s, 3H). [00502] Intermediate 332: 3-(3-(4-(Chloromethyl)phenyl)-5-(6-(methoxy-d ₃ )pyridin-3- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrazin-2-amine Intermediate 332 was prepared in a manner similar to Intermediate 323. MS: m/z = 447.2, 449.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.98 - 8.89 (m, 2H), 8.43 (d, J = 8.4 Hz, 1H), 8.13 (d, J = 8.4 Hz, 1H), 7.91 (d, J = 3.2 Hz, 1H), 7.72 (d, J = 2.8 Hz, 1H), 7.63 (d, J = 8.0 Hz, 2H), 7.54 - 7.44 (m, 3H), 4.80 (s, 2H). [00503] Intermediate 333: 2-Bromo-5-(methoxy-d3)pyridine To a solution of 6-bromopyridin-3-ol (1.0 g, 5.75 mmol) in 1,4-dioxane (3 mL) were added CD ₃ OD (1.24 g, 34.5 mmol), PPh ₃ (1.66 g, 6.32 mmol) and DIAD (1.39 g, 6.90 mmol) at 0 °C. The mixture was stirred at 25 °C for 3 hr. The reaction mixture was diluted with H ₂ O (30 mL) and extracted with CH ₂ Cl ₂ (25 mL x 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 15% EtOAc in petroleum ether), 2- bromo-5-(methoxy-d3)pyridine (Intermediate 333, 1.0 g, yield: 71%) was obtained as a yellow oil. MS: m/z = 190.9, 192.9 [M + H] ⁺ . D%: 3D% = 99.3%. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.12 (d, J = 3.2 Hz, 1H), 7.55 (d, J = 8.4 Hz, 1H), 7.39 (dd, J = 8.8, 3.2 Hz, 1H). [00504] Intermediate 334: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-(methoxy-d3)pyridin-2- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrazin-2-amine Intermediate 334 was prepared in a manner similar to Intermediate 323. MS: m/z = 447.1, 449.1 [M + H] ⁺ . [00505] Intermediate 335: 3-(3-(4-(Chloromethyl)phenyl)-5-(6-(fluoromethoxy)pyridin-3- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrazin-2-amine

Intermediate 335 was prepared in a manner similar to Intermediate 323. MS: m/z = 461.9, 463.7 [M + H] ⁺ . [00506] Intermediate 336: 3-(3-(4-(Chloromethyl)phenyl)-5-(6-(fluoromethoxy- d ₂ )pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrazin-2 -amine Intermediate 336 was prepared in a manner similar to Intermediate 323. MS: m/z = 464.0, 466.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.94 - 8.87 (m, 1H), 8.44 - 8.35 (m, 2H), 8.11 - 8.01 (m, 2H), 7.61 - 7.45 (m, 5H), 7.10 (d, J = 8.8 Hz, 1H), 4.89 (s, 2H). [00507] Intermediate 337: 3-(3-(4-(Chloromethyl)phenyl)-5-(6-cyclopropoxypyridin-3- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Step 1: (2-(2-Aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)oxy )methyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)boronic acid To a mixture of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-chlo ro-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (refer to Intermediate 117 for detail procedures, 500 mg, 1.07 mmol) and 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (545 mg, 2.15 mmol) in 1,4-dioxane (10 mL) were added KOAc (316 mg, 3.22 mmol) and Pd(dppf)Cl ₂ (78.5 mg, 107 µmol). The mixture was stirred at 100 ºC for 1 hr. (2-(2-Aminopyridin-3-yl)-3-(4-((( tert- butyldimethylsilyl)oxy)methyl)phenyl)-3H-imidazo[4,5-b]pyrid in-5-yl)boronic acid was obtained as a black liquid, which was used in the next step directly. MS: m/z = 476.2 [M + H] ⁺ . Step 2: 3-(3-(4-(((tert-Butyldimethylsilyl)oxy)methyl)phenyl)-5-(6-c yclopropoxypyridin-3-yl)- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine To a mixture of (2-(2-aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)oxy )methyl)phenyl)- 3H-imidazo[4,5-b]pyridin-5-yl)boronic acid (510 mg, 1.07 mmol) and 5-bromo-2- cyclopropoxypyridine (230 mg, 1.07 mmol) in 1,4-dioxane (10 mL) and H ₂ O (2 mL) were added Cs ₂ CO ₃ (1.05 g, 3.22 mmol) and Pd(dppf)Cl ₂ (78.5 mg, 107 µmol), The mixture was stirred at 100 °C for 2 hr. The mixture was dilute with H ₂ O (50 mL) and extracted with EtOAc (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (EtOAc in petroleum ether = 0 - 50 %), 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-(6- cyclopropoxypyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyri din-2-amine (250 mg, yield: 41% for 2 steps) was obtained as a yellow solid. MS: m/z = 565.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.86 (d, J = 2.0 Hz, 1H), 8.35 - 8.24 (m, 2H), 8.03 - 7.97 (m, 2H), 7.50 - 7.44 (m, 4H), 7.20 (dd, J = 7.6, 2.0 Hz, 1H), 7.03 (br s, 2H), 6.94 (d, J = 8.8 Hz, 1H), 6.39 (dd, J= 8.0, 4.8 Hz, 1H), 4.82 (s, 2H), 4.28 - 4.21 (m, 1H), 0.92 (s, 9H), 0.81 - 0.75 (m, 2H), 0.71 - 0.66 (m, 2H), 0.11 (s, 6H).

Step 3 : (4-(2-(2-Aminopyridin-3-yl)-5-(6-cyclopropoxypyridin-3-yl)-3 H-imidazo[4,5-b]pyridin- 3 -y l)pheny l)methanol

To a mixture of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-(6- cyclopropoxypyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyri din-2-amine (230 mg, 407 μmol) in THF (3 mL) was added TBAF (IM in THF, 611 μL). The mixture was stirred at 20 °C for 0.5 hr. The mixture was diluted with H ₂ O (50 mL) and extracted with EtOAc (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated to give (4-(2-(2-aminopyridin-3-yl)-5-(6-cyclopropoxypyridin-3-yl)- 3H-imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (184 mg) was obtained as a brown solid. MS: m/z = 451.2 [M + H] ⁺ .

Step 4 : 3 -(3 -(4-(Chloromethyl)phenyl)-5-(6-cy clopropoxypyridin-3 -yl)-3H-imidazo[4, 5- b]pyridin-2-yl)pyridin-2-amine

To a mixture of (4-(2-(2-aminopyridin-3-yl)-5-(6-cyclopropoxypyridin-3-yl)-3 H-imidazo[4,5- b]pyridin-3-yl)phenyl)methanol (183 mg, 407 μmol) in CH ₂ Cl ₂ (2 mL) was added SOCl ₂ (88.7 μL, 1.22 mmol,). The mixture was stirred at 20 °C for 0.5 hr. The mixture was filtered and concentrated to give 3-(3-(4-(chloromethyl)phenyl)-5-(6-cyclopropoxypyridin-3-yl) -3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (Intermediate 337, 191 mg) as a yellow solid. MS: m/z = 469.2, 471.1 [M + H] ⁺ .

[00508] Intermediate 338: 3-(3-(4-(Chloromethyl)phenyl)-5-(6-isopropoxypyridin-3-yl)- 3H-imidazo[4,5-b]pyri din-2 -yl)pyridin-2-amine

Intermediate 338 was prepared in a manner similar to Intermediate 337. MS: m/z = 471.2, 473.1 [M + H] ⁺ . [00509] Intermediate 339: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-cyclopropoxypyridin-2- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 339 was prepared in a manner similar to Intermediate 337. MS: m/z = 469.2, 471.2 [M + H] ⁺ . [00510] Intermediate 340: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-isopropoxypyridin-2-yl)- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 340 was prepared in a manner similar to Intermediate 215. MS: m/z = 471.3, 473.3 [M + H] ⁺ . [00511] Intermediate 341: 3-(3-(4-(Chloromethyl)phenyl)-5-(6-cyclopropylpyridin-3-yl)- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Intermediate 341 was prepared in a manner similar to Intermediate 215. MS: m/z = 453.2, 455.2 [M + H]+. 1H NMR (400 MHz, Dimethylsulfoxide-d6) δ 9.15 (s, IH), 8.90 (d, J = 8.4 Hz, IH), 8.48 (d, J = 8.4 Hz, 2H), 8.31 (d, J = 8.4 Hz, IH), 8.17 (d, J = 5.6 Hz, IH), 7.93 (d, J = 7.2 Hz, IH), 7.72 (d, J = 8.8 Hz, IH), 7.68 - 7.59 (m, 4H), 6.92 (t, J = 6.8 Hz, IH), 4.88 (s, 2H), 1.60 - 1.54 (m, IH), 1.41 - 1.33 (m, 2H), 1.26 - 1.20 (m, 2H).

[00512] Intermediate 342: 3-(3-(4-(Chloromethyl)phenyl)-5-(6-isopropylpyridin-3-yl)- 3H-imidazo[4,5-b]pyri din-2 -yl)pyridin-2-amine

Intermediate 342 was prepared in a manner similar to Intermediate 337. MS: m/z = 455.2, 457.2 [M + H] ⁺ .

[00513] Intermediate 343 : 3-(3-(4-(Chloromethyl)phenyl)-5-(5-cyclopropylpyridin-2-yl)-

3H-imidazo[4,5-b]pyri din-2 -yl)pyridin-2-amine

Intermediate 343 was prepared in a manner similar to Intermediate 337. MS: m/z = 453.2, 455.1[M + H] ⁺ . [00514] Intermediate 344: 3-(3-(4-(Chloromethyl)phenyl)-5-(6-(difluoromethyl)pyridin- 3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 344 was prepared in a manner similar to Intermediate 215. MS: m/z = 463.2, 465.2 [M + H] ⁺ . [00515] Intermediate 345: 3-(3-(4-(Chloromethyl)phenyl)-5-(6-(trifluoromethyl)pyridin- 3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

Intermediate 345 was prepared in a manner similar to Intermediate 215. MS: m/z = 481.1, 483.1 [M + H] ⁺ . [00516] Intermediate 346: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-ethylpyridin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 346 was prepared in a manner similar to Intermediate 215. MS: m/z = 441.1, 443.1[M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.60 (s, 1H), 8.55 - 8.47 (m, 1H), 8.46 - 8.27 (m, 2H), 8.23 (d, J = 8.0 Hz, 1H), 8.13 (d, J = 5.6 Hz, 1H), 7.99 - 7.87 (m, 2H), 7.71 - 7.58 (m, 4H), 6.94 - 6.88 (m, 1H), 4.88 (s, 2H), 2.75 - 2.69 (m, 2H), 1.23 (t, J = 7.6 Hz, 3H). [00517] Intermediate 347: 2-Bromo-5-(fluoromethyl)pyridine To a solution of (6-bromopyridin-3-yl)methanol (1 g, 5.32 mmol) in CH ₂ Cl ₂ (25 mL) was added DAST (857 mg, 5.32 mmol) at 0 °C. The mixture was stirred at 0 °C for 1 hr. The reaction mixture was quenched with NaHCO ₃ (30 mL) at 0 °C and extracted with CH ₂ Cl ₂ (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 5% EtOAc in petroleum ether), 2-bromo-5-(fluoromethyl)pyridine (Intermediate 347, 300 mg, yield: 28%) was obtained as a light yellow oil. MS: m/z = 189.8, 191.8 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.39 (s, 1H), 7.71 - 7.47 (m, 2H), 5.37 (d, J = 47.2 Hz, 2H). ¹⁹ F NMR (400 MHz, Chloroform-d) δ -211.43. [00518] Intermediate 348: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-(fluoromethyl)pyridin-2- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 348 was prepared in a manner similar to Intermediate 215. MS: m/z = 445.1, 447.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.76 (s, 1H), 8.57 (d, J = 8.4 Hz, 1H), 8.46 - 8.35 (m, 2H), 8.28 (d, J = 8.4 Hz, 1H), 8.14 (dd, J = 6.4, 1.6 Hz, 1H), 8.05 - 8.00 (m, 1H), 7.94 (dd, J = 7.6, 1.2 Hz, 1H), 7.68 - 7.61 (m, 4H), 6.93 (dd, J = 7.2, 6.4 Hz, 1H), 5.55 (d, J = 47.6 Hz, 2H), 4.88 (s, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -207.28. [00519] Intermediate 349: 3-(3-(4-(Chloromethyl)phenyl)-5-(5-(difluoromethyl)pyridin- 2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 349 was prepared in a manner similar to Intermediate 215. MS: m/z = 463.1, 465.1 [M + H] ⁺ . [00520] Example 1: 6-((1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3 - yl)benzyl)piperidin-4-yl)oxy)nicotinonitrile To a solution of Intermediate 15 (50 mg, 149 µmol) in DMF (2 mL) were added NaI (3 mg, 14.9 µmol), K ₂ CO ₃ (41 mg, 298 µmol) and Intermediate 16 (36 mg, 179 µmol). The mixture was stirred at 80 °C for 2 hr. The mixture was diluted with H ₂ O (20 mL) and extracted with EtOAc (20 mL × 2). The combined organic layers were washed with brine (20 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The crude product was purified by flash chromatography on silica gel (Eluent of 0~8% MeOH in CH ₂ Cl ₂ ) to give 6-((1- (4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)be nzyl)piperidin-4- yl)oxy)nicotinonitrile (Example 1, 24.1 mg, yield: 32%) as a light yellow solid. MS: m/z = 503.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.68 (d, J = 1.6 Hz, 1H), 8.32 (d, J = 4.0 Hz, 1H), 8.20 (d, J = 7.6 Hz, 1H), 8.13 (dd, J = 8.8, 2.0 Hz, 1H), 7.98 (br d, J = 3.2 Hz, 1H), 7.46 (d, J = 8.0 Hz, 2H), 7.40 - 7.37 (m, 3H), 7.16 (d, J = 6.4 Hz, 1H), 7.01 - 6.96 (m, 3H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 5.15 – 5.09 (m, 1H), 3.58 (s, 2H), 2.76 - 2.70 (m, 2H), 2.32 - 2.25 (m, 2H), 2.03 - 1.98 (m, 2H), 1.77 - 1.68 (m, 2H). [00521] Example 2: 6-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)oxy)nicotinonitrile Example 2 was prepared in a manner similar to Example 1. MS: m/z = 579.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.68 (d, J = 2.4 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.13 (dd, J = 8.4, 2.4 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.50 - 7.44 (m, 6H), 7.43 - 7.35 (m, 1H), 7.15 (dd, J = 8.0, 2.0 Hz, 1H), 7.02 (br s, 2H), 6.98 (d, J = 8.8 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 5.15 - 5.09 (m, 1H), 3.61 (s, 2H), 2.77 - 2.72 (m, 2H), 2.34 - 2.28 (m, 2H), 2.05 - 1.99 (m, 2H), 1.77 - 1.71 (m, 2H). [00522] Example 3: 6-((1-(4-(2-(2-aminopyridin-3-yl)-6-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)oxy)nicotinonitrile Example 3 was prepared in a manner similar to Example 1. MS: m/z = 579.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.67 (s, 1H), 8.50 - 8.46 (m, 1H), 8.34 (s, 1H), 8.08 - 7.98 (m, 2H), 7.91 (d, J = 3.6 Hz, 1H), 7.84 (dd, J = 8.0, 2.0 Hz, 1H), 7.64 (d, J = 7.2 Hz, 2H), 7.57 - 7.49 (m, 6H), 7.46 - 7.36 (m, 2H), 6.85 (d, J = 8.8 Hz, 1H), 6.67 - 6.41 (m, 1H), 5.64 - 5.34 (m, 1H), 4.26 (s, 2H), 3.58 - 3.30 (m, 2H), 3.27 - 2.98 (m, 2H), 2.90 - 2.66 (m, 2H), 2.36 - 2.24 (m, 2H). [00523] Example 4: 6-((1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3 - yl)benzyl)piperidin-4-yl)oxy)picolinonitrile Example 4 was prepared in a manner similar to Example 1. MS: m/z = 503.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.33 (dd, J = 4.8, 1.2 Hz, 1H), 8.20 (dd, J = 8.0, 1.2 Hz, 1H), 7.99 (dd, J = 4.4, 1.6 Hz, 1H), 7.91 (dd, J = 8.4, 7.2 Hz, 1H), 7.62 (d, J = 7.2 Hz, 1H), 7.46 d, J = 8.4 Hz, 2H), 7.41 – 7.37 (m, 3H), 7.18 – 7.15 (m, 2H), 7.01 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 5.08 – 5.00 (m, 1H), 3.59 (s, 2H), 2.76 – 2.69 (m, 2H), 2.36 – 2.28 (m, 2H), 2.05 – 1.97 (m, 2H), 1.77 – 1.68 (m, 2H). [00524] Example 5: 2-((1-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3 - yl)benzyl)piperidin-4-yl)oxy)isonicotinonitrile Example 5 was prepared in a manner similar to Example 1. MS: m/z = 503.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.39 (d, J = 5.2 Hz, 1H), 8.33 (d, J = 4.4 Hz, 1H), 8.20 (d, J = 8.0 Hz, 1H), 7.98 (, J = 3.6 Hz, 1H), 7.45 (d, J = 8.4 Hz, 2H), 7.40 – 7.34 (m, 5H), 7.16 (d, J = 8.0 Hz, 1H), 7.00 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 5.09 – 5.03 (m, 1H), 3.58 (s, 2H), 2.77 – 2.69 (m, 2H), 2.32 – 2.26 (m, 2H), 2.04 – 1.98 (m, 2H), 1.75 – 1.68 (m, 2H). [00525] Example 6: 2-((1-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3 - yl)benzyl)piperidin-4-yl)oxy)nicotinonitrile Example 6 was prepared in a manner similar to Example 1. MS: m/z = 503.4 [M + H] ^{+ 1} H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.45 (d, J = 4.8 Hz, 1H), 8.33 (d, J = 4.8 Hz, 1H), 8.26 (d, J = 7.6 Hz, 1H), 8.20 (d, J = 8.0 Hz, 1H), 7.98 (d, J = 4.0 Hz, 1H), 7.48 (d, J = 8.4 Hz, 2H), 7.41 - 7.36 (m, 3H), 7.18 - 7.14 (m, 2H), 7.00 (br s, 2H), 6.38 (dd, J = 8.0, 4.8 Hz, 1H), 5.25 - 5.16 (m, 1H), 3.59 (s, 2H), 2.73 - 2.66 (m, 2H), 2.40 - 2.32 (m, 2H), 2.05 - 1.98 (m, 2H), 1.82 - 1.74 (m, 2H). [00526] Example 7: 6-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)oxy)picolinonitrile Example 7 was prepared in a manner similar to Example 1. MS: m/z = 579.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.06 - 7.96 (m, 4H), 7.95 - 7.88 (m, 1H), 7.62 (d, J = 7.6 Hz, 1H), 7.52 - 7.43 (m, 6H), 7.41 -7.39 (m, 1H), 7.19 - 7.12 (m, 2H), 7.02 (br s, 2H), 6.38 (dd, J = 8.0, 5.2 Hz, 1H), 5.10 - 4.96 (m, 1H), 3.62 (s, 2H), 2.75 - 2.71 (m, 2H), 2.23 – 2.31 (m, 2H), 2.04 - 1.99 (m, 2H), 1.76 - 1.68 (m, 2H). [00527] Example 8: 2-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)oxy)isonicotinonitrile Example 8 was prepared in a manner similar to Example 1. MS: m/z = 579.1 [M + H]+. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.39 (d, J = 5.2 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.06 - 7.97 (m, 4H), 7.51 - 7.44 (m, 6H), 7.41 - 7.34 (m, 3H), 7.16 (d, J = 7.6 Hz, 1H), 7.02 (br s, 2H), 6.38 (dd, J = 8.0, 4.8 Hz, 1H), 5.10 - 5.03 (m, 1H), 3.61 (s, 2H), 2.77 - 2.73 (m, 2H), 2.34 – 2.24 (m, 2H), 2.05 - 1.99 (m, 2H), 1.77 - 1.68 (m, 2H). [00528] Example 9: 2-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)oxy)nicotinonitrile Example 9 was prepared in a manner similar to Example 1. MS: m/z = 579.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.46 (dd, J = 5.2, 2.0 Hz, 1H), 8.30 - 8.23 (m, 2H), 8.05 - 7.97 (m, 4H), 7.53 - 7.44 (m, 6H), .7.41 - 7.39 (m, 1H), 7.19 - 7.13 (m, 2H), 7.02 (br s, 2H), 6.38 (dd, J = 8.0, 5.2 Hz, 1H), 5.28 - 5.16 (m, 1H), 3.62 (s, 2H), 2.68 - 2.66 (m, 2H), 2.40 - 2.35 (m, 2H), 2.06 - 2.00 (m, 2H), 1.83 - 1.75 (m, 2H). [00529] Example 10: 6-((1-(4-(2-(2-Aminopyridin-3-yl)-6-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)oxy)picolinonitrile Example 10 was prepared in a manner similar to Example 1. MS: m/z = 579.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.64 (d, J = 2.0 Hz, 1H), 8.47 (d, J = 2.0 Hz, 1H), 8.00 (dd, J = 4.8, 1.6 Hz, 1H), 7.92 (dd, J = 8.0, 8.0 Hz, 1H), 7.78 (d, J = 7.6 Hz, 2H), 7.62 (d, J = 7.2 Hz, 1H), 7.54 - 7.47 (m, 4H), 7.45 - 7.40 (m, 3H), 7.25 - 7.13 (m, 2H), 7.05 (br s, 2H), 6.39 (dd, J =7.6, 4.8 Hz, 1H), 5.09 - 5.01 (m, 1H), 3.60 (s, 2H), 2.76 - 2.70 (m, 2H), 2.37 - 2.29 (m, 2H), 2.07 - 1.99 (m, 2H), 1.77 - 1.68 (m, 2H). [00530] Example 11: 2-((1-(4-(2-(2-Aminopyridin-3-yl)-6-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)oxy)isonicotinonitrile Example 11 was prepared in a manner similar to Example 1. MS: m/z = 579.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.63 (d, J = 2.0 Hz, 1H), 8.46 (d, J = 2.0 Hz, 1H), 8.39 (d, J = 5.2 Hz, 1H), 8.03 - 7.94 (m, 1H), 7.78 (d, J = 7.2 Hz, 2H), 7.55 - 7.47 (m, 4H), 7.45 - 7.39 (m, 3H), 7.39 - 7.32 (m, 2H), 7.20 (dd, J = 7.6, 1.2 Hz, 1H), 7.04 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 5.11 - 5.03 (m, 1H), 3.61 (s, 2H), 2.84 - 2.72 (m, 2H), 2.39 - 2.19 (m, 2H), 2.03 - 1.95 (m, 2H), 1.76 - 1.65 (m, 2H). [00531] Example 12: 2-((1-(4-(2-(2-Aminopyridin-3-yl)-6-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)oxy)nicotinonitrile Example 12 was prepared in a manner similar to Example 1. MS: m/z = 579.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.64 (d, J = 1.8 Hz, 1H), 8.49 - 8.43 (m, 2H), 8.26 (dd, J = 7.6, 1.6 Hz, 1H), 8.00 (dd, J = 4.8, 1.6 Hz, 1H), 7.79 (d, J = 7.6 Hz, 2H), 7.54 - 7.48 (m, 4H), 7.44 - 7.40 (m, 3H), 7.21 - 7.14 (m, 2H), 7.05 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 5.26 - 5.16 (m, 1H), 3.60 (s, 2H), 2.75 - 2.63 (m, 2H), 2.39 - 2.30 (m, 2H), 2.09 - 1.97 (m, 2H), 1.83 - 1.74 (m, 2H). [00532] Example 13: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazin-1-yl)picolinonitrile To a solution of Intermediate 2 (200 mg, 519 µmol) in DMF (2 mL) were added DIEA (201 mg, 1.6 mmol), and 4-fluoropyridine-2-carbonitrile (76mg, 623 µmol). The mixture was stirred at 100 °C for 2 hr. The mixture was diluted with H ₂ O (10 mL) and extracted with EtOAc (5 mL × 2). The combined organic layers were washed with brine (10 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. The crude product was purified by prep-HPLC (column: Phenomenex luna C18150*25 mm * 10 µm; mobile phase: [water (FA) - ACN]; B%: 0% - 23%, 9 min), 4-(4-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazin-1-yl)picolinonitrile (Example 13, 9.6 mg, yield: 3.8%) was obtained as a yellow solid. MS: m/z = 488.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.44 (dd, J = 4.8, 4.2 Hz, 1H), 8.30 (d, J = 6.0 Hz, 1H), 8.14 (dd, J = 8.0, 1.2 Hz, 1H), 7.97 - 7.93 (m, 1H), 7.82 (br s, 2H), 7.56 (d, J = 8.4 Hz, 2H), 7.42 - 7.32 (m, 3H), 7.21 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (d, J = 2.8 Hz, 1H), 6.80 - 6.74 (m, 1H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 3.67 (s, 2H), 3.44 - 3.39 (m, 4H), 2.68 - 2.62 (m, 4H). [00533] Example 14: 5-(4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazin-1-yl)picolinonitrile Example 14 was prepared in a manner similar to Example 13. MS: m/z = 488.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.43 (d, J = 2.8 Hz, 1H), 8.34 (dd, J = 4.8, 1.2 Hz, 1H), 8.21 (dd, J = 8.0, 1.2 Hz, 1H), 7.99 (dd, J = 4.8, 1.2 Hz, 1H), 7.75 (d, J = 8.8 Hz, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.42 - 7.34 (m, 4H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.63 (s, 2H), 3.50 - 3.40 (m, 4H), 2.55 - 2.48 (m, 4H). [00534] Example 15: 6-(4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazin-1-yl)picolinonitrile Example 15 was prepared in a manner similar to Example 13. MS: m/z = 488.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.41 (d, J = 4.4 Hz, 1H), 8.02-8.16 (m, 2H), 7.57 - 7.48 (m, 3H), 7.42 - 7.30 (m, 3H), 7.09 (d, J = 7.6 Hz, 1H), 6.97 (d, J = 7.2 Hz, 1H), 6.82 (d, J = 8.8 Hz, 1H), 6.63 (br s, 2H), 6.40 - 6.31 (m, 1H), 3.70 - 3.54 (m, 6H), 2.65 - 2.53 (m, 2H), 2.06 - 1.96 (m, 2 H). [00535] Example 16: 5-(4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazin-1-yl)nicotinonitrile Example 16 was prepared in a manner similar to Example 13. MS: m/z = 488.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.59 (d, J = 2.8 Hz, 1H), 8.40 - 8.28 (m, 2H), 8.21 (dd, J = 8.0, 1.2 Hz, 1H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.77 (s, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.44 - 7.36 (m, 3H), 7.17 (dd, J = 8.0, 2.0 Hz, 1H), 7.01 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.62 (s, 2H), 3.37 - 3.33 (m, 4H), 2.58 - 2.52 (m, 4 H). [00536] Example 17: 2-(4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazin-1-yl)isonicotinonitrile Example 17 was prepared in a manner similar to Example 13. MS: m/z = 488.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.34 (dd, J =4.8, 1.2 Hz, 1H), 8.29 (d, J =5.2 Hz, 1H), 8.21 (dd, J =8.0, 1.2 Hz, 1H), 7.99 (dd, =4.8, 1.6 Hz, 1H), 7.49 (d, J =8.0 Hz, 2H), 7.42 - 7.37 (m, 3H), 7.31 (s, 1H), 7.16 (dd, J =8.0, 2.0 Hz, 1H), 7.01 (br s, 2H), 6.95 (d, J =5.2 Hz, 1H), 6.36 (dd, J =7.6, 4.8 Hz, 1H), 3.63 - 3.57 (m, 6H), 2.49 - 2.43 (m, 4 H). [00537] Example 18: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazin-1-yl)pyrimidine-2-carbonitrile Example 18 was prepared in a manner similar to Example 13. MS: m/z = 489.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.33 (dd, J = 4.8, 1.6 Hz, 1H), 8.26 (d, J = 6.4 Hz, 1H), 8.20 (dd, J = 8.0, 1.2 Hz, 1H), 7.98 (dd, J = 4.8, 2.0 Hz, 1H), 7.48 (d, J = 8.0 Hz, 2H), 7.42 - 7.36 (m, 3H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.10 (d, J = 6.4 Hz, 1H), 7.00 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.76 - 3.63 (m, 4H), 3.62 (s, 2H), 2.49 - 2.43 (m, 4 H). [00538] Example 19: 6-(4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazin-1-yl)pyrazine-2-carbonitrile Example 19 was prepared in a manner similar to Example 13. MS: m/z = 489.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.65 (s, 1H), 8.34 (dd, J = 4.4, 1.2 Hz, 1H), 8.30 (s, 1H), 8.21 (dd, J = 8.0, 1.6 Hz, 1H), 7.99 (dd, J = 5.2, 2.0 Hz, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.43 - 7.37 (m, 3H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.70 - 3.64 (m, 4H), 3.62 (s, 2H), 2.55 - 2.51 (m, 4 H). [00539] Example 20: 2-(4-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazin-1-yl)pyrimidine-4-carbonitrile Example 20 was prepared in a manner similar to Example 13. MS: m/z = 489.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.64 (d, J = 4.8 Hz, 1H), 8.33 (dd, J = 4.8, 1.6 Hz, 1H), 8.21 (dd, J = 8.0, 1.6 Hz, 1H), 7.99 (dd, J = 4.8, 2.0 Hz, 1H), 7.48 (d, J = 8.4 Hz, 2H), 7.42 - 7.36 (m, 3H), 7.20 - 7.12 (m, 2H), 7.00 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.82 - 3.74 (m, 4H), 3.61 (s, 2H), 2.49 - 2.43 (m, 4 H). [00540] Example 21: 6-(4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazin-1-yl)pyrimidine-4-carbonitrile Example 21 was prepared in a manner similar to Example 13. MS: m/z = 489.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.57 (s, 1H), 8.33 (d, J = 4.8 Hz, 1H), 8.20 (d, J = 8.0 Hz, 1H), 8.02 - 7.94 (m, 1H), 7.56 (s, 1H), 7.48 (d, J = 8.0 Hz, 2H), 7.43 - 7.37 (m, 3H), 7.16 (dd, J = 7.6, 1.2 Hz, 1H), 7.01 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.98 - 3.68 (m, 4H), 3.64 (s, 2H), 2.58 - 2.52 (m, 4 H). [00541] Example 22: 6-(4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazin-1-yl)pyridazine-4-carbonitrile Example 22 was prepared in a manner similar to Example 13. MS: m/z = 489.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.83 (d, J = 1.2 Hz, 1H), 8.33 (dd, J = 4.8, 1.2 Hz, 1H), 8.20 (dd, J = 8.0, 1.2 Hz, 1H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.86 (d, J = 1.2 Hz, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.42 - 7.36 (m, 3H), 7.16 (dd, J = 7.8, 1.6 Hz, 1H), 7.00 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.75 - 3.67(m, 4H), 3.62 (s, 2H), 2.55 - 2.52 (m, 4H). [00542] Example 23: N-(1-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)-2-cyanoisonicotinamide To a solution of Intermediate 3 (200 mg, 500 mol) in DMF (3 mL) was added HATU (381 mg, 1.00 mmol), 2-cyanopyridine-4-carboxylic acid (89 mg, 600 mol) and DIEA (324 mg, 2.50 mmol). The mixture was stirred at 25 °C for 16 hr. The reaction mixture was poured into H ₂ O (5 mL) and extracted with EtOAc (10 mL x 2). The combined organic layers were concentrated under reduced pressure to give a residue. The crude product was purified by prep-HPLC (column: Waters xbridge 150*25 mm 10 m; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 21% - 51%, 11 min), N-(1-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)-2-cyanoisonicotinamide (Example 23, 76 mg, yield: 29%) was obtained as a light-yellow solid. MS: m/z = 530.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.90 (d, J = 5.2 Hz, 1H), 8.73 (d, J = 7.6 Hz, 1H), 8.37 (s, 1H), 8.33 (d, J = 4.4 Hz, 1H), 8.20 (d, J = 8.0 Hz, 1H), 8.07 (dd, J = 4.8, 1.2 Hz, 1H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.45 (d, J = 8.0 Hz, 2H), 7.41 - 7.37 (m, 3H), 7.18 – 7.15 (m, 1H), 7.01 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.87 - 3.76 (m, 1H), 3.57 (s, 2H), 2.86 (d, J = 11.6 Hz, 2H), 2.12 -2.07 (m, 2H), 1.88 -1.80 (m, 2H), 1.66 - 1.55 (m, 2H). [00543] Example 24 to 30 were prepared in a manner similar to Example 23. [00544] Example 24: N-(1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)-6-cyanonicotinamide MS: m/z = 530.2 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.10 (s, 1H), 8.72 (d, J = 7.6 Hz, 1H), 8.39 (dd, J = 8.0, 2.0 Hz, 1H), 8.33 (dd, J = 8.4, 1.2 Hz, 1H), 8.21 (dd, J = 8.0, 1.2 Hz, 1H), 8.17 (dd, J = 8.0 Hz, 1H), 7.99 (dd, J = 8.4, 1.6 Hz, 1H), 7.45 (d, J = 8.4 Hz, 2H), 7.42 - 7.36 (m, 3H), 7.16(dd, J = 7.6, 2.0 Hz, 1H), 7.01 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.88 - 3.76 (m, 1H), 3.57 (s, 2H), 2.86 (d, J = 11.6 Hz, 2H), 2.09 (t, J = 11.6 Hz, 2H), 1.85 (d, J = 10.0 Hz, 2H), 1.66 - 1.56 (m, 2H). [00545] Example 25: N-(1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)-5-cyanopicolinamide MS: m/z = 530.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.10 (d, J = 1.6 Hz, 1H), 8.80 (d, J = 8.4 Hz, 1H), 8.51 (dd, J = 8.0, 2.0 Hz, 1H), 8.33 (dd, J = 4.8, 1.2 Hz, 1H), 8.24 - 8.13 (m, 2H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.45 (d, J = 8.4 Hz, 2H), 7.41 - 7.35 (m, 3H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.88 - 3.78 (m, 1H), 3.56 (s, 2H), 2.84 (d, J = 12.0 Hz, 2H), 2.15 - 2.05 (m, 2H), 1.80 - 1.70 (m, 4H). [00546] Example 26: N-(1-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)-5-cyanonicotinamide MS: m/z = 530.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.21 (d, J = 2.0 Hz, 1H), 9.16 (d, J = 2.0 Hz, 1H), 8.70 - 8.58 (m, 2H), 8.33 (dd, J = 4.8, 1.2 Hz, 1H), 8.21 (dd, J = 8.0, 1.2 Hz, 1H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.46 (d, J = 8.4 Hz, 2H), 7.43 - 7.33 (m, 3H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.87 - 3.75 (m, 1H), 3.57 (s, 2H), 2.86 (d, J = 11.6 Hz, 2H), 2.10 (t, J = 11.6 Hz, 2H), 1.89 - 1.80 (m, 2H), 1.67 - 1.54 (m, 2H). [00547] Example 27: N-(1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)-2-cyanonicotinamide MS: m/z = 530.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.88 (s, 1H), 8.92 (dd, J = 4.8, 1.6 Hz, 1H), 8.33 (dd, J = 4.8, 1.2 Hz, 1H), 8.26-8.01 (m, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.73 (dd, J = 7.6, 4.8 Hz, 1H), 7.48 (d, J = 8.0 Hz, 2H), 7.42 - 7.36 (m, 3H), 7.17 (dd, J = 7.6, 1.8 Hz, 1H), 7.02 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 4.36 - 4.24 (m, 1H), 3.59 (s, 2H), 2.99 - 2.89 (m, 2H), 2.61 - 2.56 (m, 2H), 2.14 - 2.03 (m, 2H), 1.67 (d, J = 11.6 Hz, 2H). [00548] Example 28: N-(1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)-3-cyanopicolinamide MS: m/z = 529.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.95 - 8.90 (m, 1H), 8.87 - 8.67 (m, 1H), 8.40 (dd, J = 4.8, 1.2 Hz, 1H), 8.10 (dd, J = 8.0, 1.2 Hz, 1H), 8.06 - 7.85 (m, 2H), 7.63 - 7.50 (m, 3H), 7.34 (d, J = 8.4 Hz, 2H), 7.32 - 7.29 (m, 1H), 7.10 (dd, J = 7.6, 1.6 Hz, 1H), 6.62 (br s, 2H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 4.58 - 4.44 (m, 1H), 3.63 (s, 2H), 3.08 (d, J = 11.2 Hz, 2H), 2.96 - 2.68 (m, 2H), 2.26 - 2.16 (m, 2H), 1.77 - 1.73 (m, 2H). [00549] Example 29: N-(1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)-4-cyanonicotinamide MS: m/z = 530.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.59 (s, 1H), 9.05 - 8.97 (m, 2H), 8.33 (dd, J = 4.8, 1.2 Hz, 1H), 8.21 (dd, J = 8.0, 1.2 Hz, 1H), 8.15 (d, J = 5.2 Hz, 1H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.48 (d, J = 8.4 Hz, 2H), 7.41 - 7.35 (m, 3H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.38 (dd, J = 4.6, 4.8 Hz, 1H), 4.35 - 4.22 (m, 1H), 3.59 (s, 2H), 2.96 (d, J = 11.2 Hz, 2H), 2.64 - 2.53 (m, 2H), 2.08 (t, J = 11.2 Hz, 2H), 1.63 (d, J = 9.6Hz, 2H). [00550] Example 30: N-(1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)-6-cyanopicolinamide MS: m/z = 530.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.71 (d, J = 8.4 Hz, 1H), 8.33 (dd, J = 4.8, 1..2 Hz, 1H), 8.30 - 8.26 (m, 1H), 8.24 - 8.21 (m, 2H), 8.20 - 8.06 (m, 1H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.46 (d, J = 8.4 Hz, 2H), 7.42 - 7.36 (m, 3H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.37 (dd, J = 7.2, 4.8 Hz, 1H), 3.91 - 3.77 (m, 1H), 3.57 (s, 2H), 2.86 (d, J = 11.2 Hz, 2H), 2.16 - 2.05 (m, 2H), 1.81 - 1.70 (m, 4H). [00551] Example 31: N-(1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)-4-cyanopicolinamide Example 31 was prepared in a manner similar to Example 32. MS: m/z = 530.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.74 (d, J = 5.2 Hz, 1H), 8.44 - 8.37 (m, 2H), 8.10 (dd, J = 8.0, 1.2 Hz, 1H), 8.05 (dd, J = 4.8, 1.6 Hz, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.67 (dd, J = 4.8, 1.6 Hz, 1H), 7.56 (d, J = 8.0 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.32 (dd, J = 8.0, 4.8 Hz, 1H), 7.07 (dd, J = 8.01.6 Hz, 1H), 6.64 (br s, 2H), 6.34 (dd, J = 8.0, 4.8 Hz, 1H), 4.12 - 4.03 (m, 1H), 3.70 (s, 2H), 3.07 - 2.97 (m, 2H), 2.39 - 2.30 (m, 2H), 2.10 - 2.05 (m, 2H), 1.84 - 1.78 (m, 2H). [00552] Example 32: N-(1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)-2-cyanopyrimidine-4-carboxamide To a solution of Intermediate 3 (130 mg, 325 µmol), 2-cyanopyrimidine-4-carboxylic acid (64.7 mg, 391 µmol), EDCI (81.1 mg, 423 µmol) and HOBt (57.2 mg, 423 µmol) in CH ₂ Cl ₂ (2 mL) was added DIEA (210 mg, 1.63 mmol). The mixture was stirred at 25 °C for 14 hr. The reaction mixture was diluted with H ₂ O (5 mL) and extracted with CH ₂ Cl ₂ (10 mL x 3). The combined organic layers were washed with brine (10 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The crude product was purified by prep- HPLC (column: Waters xbridge 150 x 25 mm 10 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 25% - 55%, 15 min), N-(1-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin- 3-yl)benzyl)piperidin-4-yl)-2-cyanopyrimidine-4-carboxamide (Example 32, 10.0 mg, yield: 5.8%) was obtained as a light-yellow solid. MS: m/z = 531.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.22 (d, J = 5.2 Hz, 1H), 9.04 (d, J = 8.4 Hz, 1H), 8.36 - 8.30 (m, 1H), 8.26 (d, J = 5.2 Hz, 1H), 8.22 - 8.19 (m, 1H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.48 - 7.36 (m, 5H), 7.19 - 7.15 (m, 1H), 7.01 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.90 - 3.75 (m, 1H), 3.56 (s, 2H), 2.91 - 2.83 (m, 2H), 2.13 - 2.04 (m, 2H), 1.80 - 1.71 (m, 4H). [00553] Example 33: N-(1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)-6-cyanopyrimidine-4-carboxamide Example 33 was prepared in a manner similar to Example 32. MS: m/z = 531.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.53 (d, J = 1.6 Hz, 1H), 9.05 (d, J = 8.4 Hz, 1H), 8.53 (d, J = 1.6 Hz, 1H), 8.33 (dd, J = 4.4, 1.2 Hz, 1H), 8.20 (dd, J = 8.0, 1.6 Hz, 1H), 7.99 (dd, J = 4.8, 2.0 Hz, 1H), 7.45 (d, J = 8.4 Hz, 2H), 7.41 - 7.36 (m, 3H), 7.17 (dd, J = 7.6, 2.0 Hz, 1H), 7.00 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.90 - 3.77 (m, 1H), 3.56 (s, 2H), 2.85 (d, J = 11.6 Hz, 2H), 2.13 - 2.05 (m, 2H), 1.78 - 1.71 (m, 4H). [00554] Example 34: N-(1-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)-2-cyanobenzo[d]thiazole-5-carboxam ide Example 34 was prepared in a manner similar to Example 173. MS: m/z = 586.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chlorform-d) δ 8.55 (s, 1H), 8.40 (d, J = 4.4 Hz, 1H), 8.15 - 8.02 (m, 4H), 7.52 (d, J = 7.6 Hz, 2H), 7.37 - 7.30 (m, 3H), 7.08 (d, J = 8.0 Hz, 1H), 6.66 (br s, 2H), 6.38 - 6.30 (m, 1H), 6.17 (d, J = 8.0 Hz, 1H), 4.17 - 4.03 (m, 1H), 3.63 (s, 2H), 3.01 - 2.87 (m, 2H), 2.28 (t, J = 10.8 Hz, 2H), 2.11 (d, J = 12.4 Hz, 2H), 1.65 - 1.61 (m, 2H). [00555] Example 35: N-(1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)-2-cyano-5-fluorobenzo[d]thiazole-7 -carboxamide Example 35 was prepared in a manner similar to Example 173. MS: m/z = 604.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.96 (d, J = 7.6 Hz, 1H), 8.47 (dd, J = 9.6, 2.4 Hz, 1H), 8.41 (dd, J = 8.8, 2.4 Hz, 1H), 8.33 (dd, J = 4.8, 1.2 Hz, 1H), 8.21 (dd, J = 8.0, 1.2 Hz, 1H), 7.99 (dd, J = 4.8, 1.2 Hz, 1H), 7.47 (d, J = 8.4 Hz, 2H), 7.42 - 7.36 (m, 3H), 7.17 (dd, J = 7.6, 2.0 Hz, 1H), 7.01 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.90 - 3.86 (m, 1H), 3.58 (s, 2H), 2.89 (d, J = 11.2 Hz, 2H), 2.11 (t, J = 11.2 Hz, 2H), 1.89 – 1.85 (m, 2H), 1.72 - 1.60 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -113.1. [00556] Example 36: N-(1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)-3-cyanoisonicotinamide Example 36 was prepared in a manner similar to Example 23. MS: m/z = 530.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.52 (s, 1H), 9.40 (s, 1H), 8.94 (d, J = 4.8 Hz, 1H), 8.38 - 8.28 (m, 1H), 8.20 (d, J = 8.0 Hz, 1H) 8.03 - 7.92 (m, 1H), 7.77 (d, J = 4.8 Hz, 1H), 7.48 (d, J = 8.0 Hz, 2H), 7.44 - 7.36 (m, 3H), 7.22 - 7.14 (m, 1H), 7.01 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 4.42 - 4.17 (m, 1H), 3.59 (s, 2H), 3.04 - 2.90 (m, 2H), 2.54 (br s, 2H), 2.14 - 2.02 (m, 2H), 1.70 - 1.55 (m, 2H). [00557] Example 37: N-(3-(2-(2-Aminopyridin-3-yl)-3-(4-((4-(2-cyanopyridin-4- yl)piperazin-1-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-5- yl)phenyl)acetamide To a solution of Intermediate 6 (150 mg, 289 µmol), 4-fluoropicolinonitrile (38.8 mg, 318 µmol) in DMF (2 mL) was added DIEA (112 mg, 868 µmol). The mixture was degassed and purged with N ₂ three times and stirred at 100 ºC for 16 hr under N ₂ . The reaction mixture was filtered and concentrated under reduced pressure. The residue was purified by prep-HPLC (column: Waters xbridge 150*25mm 10 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 26% - 56%, 8 min), N-(3-(2-(2-aminopyridin-3-yl)-3-(4-((4-(2-cyanopyridin-4-yl) piperazin-1- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)phenyl)aceta mide (Example 37, 155 mg, yield: 86%) was obtained as a yellow solid. MS: m/z = 621.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.30 (d, J = 6.0 Hz, 1H), 8.16 – 8.11 (m, 2H), 8.08 (dd, J = 4.8, 1.2 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.77 (d, J = 7.6 Hz, 1H), 7.56 (d, J = 8.0 Hz, 1H), 7.51 (d, J = 8.0 Hz, 2H), 7.45 - 7.35 (m, 4H), 7.09 (d, J = 8.0 Hz, 1H), 7.04 (d, J = 1.6 Hz, 1H), 6.80 – 5.75 (m, 1H), 6.61 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.65 (s, 2H), 3.49 - 3.42 (m, 4H), 2.59 - 2.52 (m, 4H), 2.05 (s, 3H). [00558] Example 38: N-(3-(2-(2-Aminopyridin-3-yl)-3-(4-((4-(6-cyanopyridin-3- yl)piperazin-1-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-5- yl)phenyl)acetamide Example 38 was prepared in a manner similar to Example 37. MS: m/z = 621.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.05 (s, 1H), 8.43 (d, J = 2.8 Hz, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.16 (s, 1H), 8.00 (dd, J = 4.8 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.75 (d, J = 8.8 Hz, 1H), 7.69 - 7.63 (m, 2H), 7.54 - 7.44 (m, 4H), 7.41 - 7.33 (m, 2H), 7.14 (dd, J = 7.6, 1.6 Hz, 1H), 6.99 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.65 (s, 2H), 3.49 - 3.42 (m, 4H), 2.59 - 2.52 (m, 4H), 2.05 (s, 3H). [00559] Example 39: N-(3-(2-(2-Aminopyridin-3-yl)-3-(4-((4-(6-cyanopyridin-2- yl)piperazin-1-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-5- yl)phenyl)acetamide Example 39 was prepared in a manner similar to Example 37. MS: m/z = 621.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.04 (s, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.8 (s, 1H), 8.00 (dd, J = 4.8, 1.6 Hz, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.73 - 7.61 (m, 3H), 7.55 - 7.43 (m, 4H), 7.38 (dd, J = 8.0, 8.0 Hz, 1H), 7.23 - 7.12 (m, 3H), 7.00 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.64 (s, 2H), 3.61 - 3.56 (m, 4H), 2.54 - 2.51 (m, 4H), 2.07 (s, 3H). [00560] Example 40: N-(3-(2-(2-aminopyridin-3-yl)-3-(4-((4-(6-cyanopyrazin-2- yl)piperazin-1-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-5- yl)phenyl)acetamide Example 40 was prepared in a manner similar to Example 37. MS: m/z = 622.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.04 (s, 1H), 8.65 (s, 1H), 8.31 - 8.25 (m, 2H), (s, 1H), 8.00 (dd, J = 4.8 Hz, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.70 - 7.61 (m, 2H), 7.54 - 7.44 (m, 4H), 7.38 (dd, J = 8.0, 8.0 Hz, 1H), 7.15 (dd, J = 7.6, 2.0 Hz, 1H), 7.00 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.70 - 3.65 (m, 4H), 3.64 (s, 2H), 2.55 - 2.52 (m, 4H), 2.06 (s, 3H). [00561] Example 41: N-(3-(2-(2-Aminopyridin-3-yl)-3-(4-((4-(6-cyanopyrimidin-4- yl)piperazin-1-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-5- yl)phenyl)acetamide Example 41 was prepared in a manner similar to Example 37. MS: m/z = 622.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.04 (s, 1H), 8.56 (d, J = 1.2 Hz, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.17 (s, 1H), 7.99 (dd, J = 4.8, 2.0 Hz, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.70 - 7.61 (m, 2H), 7.56 (s, 1H), 7.53 - 7.44 (m, 4H), 7.38 (dd, J = 8.0, 8.0 Hz, 1H), 7.14 (dd, J = 7.6, 2.0 Hz, 1H), 6.99 (br s, 2H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 3.89 - 3.66 (m, 4H), 3.64 (s, 2H), 2.49 - 2.47 (m, 4H), 2.06 (s, 3H). [00562] Example 42: N-(3-(2-(2-Aminopyridin-3-yl)-3-(4-((4-(2-cyanopyrimidin-5- yl)piperazin-1-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-5- yl)phenyl)acetamide To a solution of Intermediate 6 (200 mg, 386 µmol) and 2-chloropyrimidine-4-carbonitrile (59 mg, 424 µmol) in 1,4-dioxane (4 mL) was added DIEA (199 mg, 1.54 mmol). The mixture was stirred at 80 °C for 12 hr. The reaction was filtered and concentrated under reduced pressure to give a residue. The crude product was purified by prep-HPLC (column: Waters xbridge 150*25 mm 10 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 38% - 68%, 10 min), N-(3-(2-(2- aminopyridin-3-yl)-3-(4-((4-(2-cyanopyrimidin-5-yl)piperazin -1-yl)methyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)phenyl)acetamide (Example 42, 36.8 mg, yield: 14%) was obtained as a light-yellow solid. MS: m/z = 622.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.05 (s, 1H), 8.58 (s, 2H), 8.28 (d, J = 8.4 Hz, 1H), 8.17 (s, 1H), 8.00 (dd, J = 4.8, 1.6 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.66 (d, J = 8.0 Hz, 2H), 7.57 - 7.45 (m, 4H), 7.38 (dd, J = 8.0, 8.0 Hz, 1H), 7.14 (d, J = 7.6 Hz, 1H), 6.99 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.65 (s, 2H), 3.56 - 3.48 (m, 4H), 2.60 - 2.52 (m, 4H), 2.05 (s, 3H). [00563] Example 43: N-(3-(2-(2-Aminopyridin-3-yl)-3-(4-((4-(6-cyanopyridazin-4- yl)piperazin-1-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-5- yl)phenyl)acetamide Example 43 was prepared in a manner similar to Example 47. MS: m/z = 622.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.05 (s, 1H), 9.14 (d, J = 3.2 Hz, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.16 (s, 1H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.71 - 7.59 (m, 4H), 7.54 - 7.44 (m, 5H), 7.41 - 7.35 (m, 1H), 7.14 (dd, J = 7.6, 1.6 Hz, 1H), 7.00 (br s, 2H), 6.35 (dd, J = 8.0, 4.8 Hz, 1H), 3.65 (s, 2H), 3.61 - 3.55 (m, 4H), 2.56 - 2.52 (m, 4H), 2.06 (s, 3H). [00564] Example 44: N-(3-(2-(2-Aminopyridin-3-yl)-3-(4-((4-(2-cyanopyrimidin-4- yl)piperazin-1-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-5- yl)phenyl)acetamide Example 44 was prepared in a manner similar to Example 47. MS: m/z = 622.5 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.05 (s, 1H), 8.34 -8.24 (m, 2H), 8.20 (s, 1H), (dd, J = 4.8, 2.0 Hz, 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.70 - 7.62 (m, 2H), 7.57 - 7.45 (m, 4H), 7.42 - 7.36 (m, 1H), 7.18 - 7.10 (m, 2H), 7.00 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.74 - 3.64 (m, 4H), 3.65 (s, 2H), 2.56 - 2.52 (m, 4H), 2.07 (s, 3H). [00565] Example 45: N-(3-(2-(2-Aminopyridin-3-yl)-3-(4-((4-(5-cyanopyridazin-3- yl)piperazin-1-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-5- yl)phenyl)acetamide Example 45 was prepared in a manner similar to Example 50. MS: m/z = 622.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.68 (s, 1H), 8.25 - 8.16 (m, 2H), 7.99 (dd, J = 5.2, 1.2 Hz, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.67 (s, 1H), 7.64 - 7.56 (m, 3H), 7.47 (d, J = 8.4 Hz, 2H), 7.41 - 7.30 (m, 2H), 6.47 (dd, J = 7.6, 4.8 Hz, 1H), 3.79 - 3.74 (m, 4H), 3.70 (s, 2H), 2.70 - 2.63 (m, 4H), 2.14 (s, 3H). [00566] Example 46: N-(3-(2-(2-Aminopyridin-3-yl)-3-(4-((4-(4-cyanopyrimidin-2- yl)piperazin-1-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-5- yl)phenyl)acetamide To a solution of Intermediate 6 (200 mg, 386 mol) and 2-chloropyrimidine-4-carbonitrile (59 mg, 424 mol) in 1,4-dioxane (4 mL) was added DIEA (199 mg, 1.54 mmol). The mixture was stirred at 80 °C for 12 hr. The reaction was filtered and concentrated under reduced pressure to give a residue. The crude product was purified by prep-HPLC (column: Waters xbridge 150*25 mm 10 m; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 38% - 68%, 10 min), N-(3-(2-(2- aminopyridin-3-yl)-3-(4-((4-(4-cyanopyrimidin-2-yl)piperazin -1-yl)methyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)phenyl)acetamide (Example 46, 36.8 mg, yield: 14%) was obtained as a light-yellow solid. MS: m/z = 622.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.04 (s, 1H), 8.64 (d, J = 4.4 Hz, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.19 (s, 1H), 7.99 (dd, J = 4.8, 2.0 Hz, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.70 - 7.60 (m, 2H), 7.57 - 7.43 (m, 4H), 7.40 - 7.34 (m, 1H), 7.24 - 7.09 (m, 2H), 6.99 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.83 - 3.73 (m, 4H), 3.63 (s, 2H), 3.33 - 3.31 (m, 4H), 2.06 (s, 3H). [00567] Example 47: 4-((4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)amino)pyrimidine-2-carbonitrile A mixture of Intermediate 1 (200 mg, 632 µmol), 4-chloropyrimidine-2-carbonitrile (88 mg, 632 µmol) and DIEA (408 mg, 3.16 mmol) in NMP (3 mL) was stirred at 130 °C for 1 hr under microwave. The reaction mixture was poured into H ₂ O (50 mL). The resulting mixture was extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic dried over anhydrous Na ₂ SO ₄ , filtered and concentrated to dryness. The residue was purified by prep-HPLC (column: Waters xbridge 150*25 mm 10 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 20% - 50%, 10 min), 4-((4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl )benzyl)amino)pyrimidine- 2-carbonitrile (Example 47, 26.3 mg, yield: 10%) as a light-yellow lyophilized powder. MS: m/z = 420.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ )) δ 8.70 - 8.56 (m, 1H), 8.31 (d, J = 4.8 Hz, 1H), 8.26 - 8.13 (m, 2H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.47 (d, J = 8.4 Hz, 2H), 7.45 - 7.37 (m, 3H), 7.22 (d, J = 7.6 Hz, 1H), 6.96 (br s, 2H), 6.81 (d, J = 6.0 Hz, 1H), 6.40 (dd, J = 6.8, 4.8 Hz, 1H), 4.63 (d, J = 5.2 Hz, 2H). [00568] Example 48: 4-((4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)amino)pyrimidine-2-carbonitrile Example 48 was prepared in a manner similar to Example 47. MS: m/z = 496.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 64 (t, J = 5.6 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.17 (d, J = 5.6 Hz, 1H), 8.05 - 7.97 (m, 4H), 7.52 - 7.44 (m, 6H), 7.42 - 7.36 (m, 1H), 7.24 - 7.15 (m, 1H), 6.96 (br s, 2H), 6.82 (d, J = 6.0 Hz, 1H), 6.44 - 6.36 (m, 1H), 4.66 (J = 5.6 Hz, 2H). [00569] Example 49: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine-2-carbonitri le Example 49 was prepared in a manner similar to Example 47. MS: m/z = 565.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.32 - 8.22 (m, 2H), 8.07 - 7.95 (m, 4H), 7.54 - 7.44 (m, 6H), 7.43 - 7.37 (m, 1H), 7.18 - 7.08 (m, 2H), 7.03 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.72 - 3.66 (m, 4H), 3.65 (s, 2H), 2.57 - 2.51 (m, 4H). [00570] Example 50: 6-((4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)amino)pyridazine-4-carbonitrile To a solution of Intermediate 1 in NMP (2 mL) was added Intermediate 21 (106 mg, 759 µmol) and DIEA (408 mg, 3.16 mmol). The mixture was stirred at microwave 160 °C for 1 hr. The mixture was concentrated under reduced pressure. The mixture was purified by prep-HPLC (column: Welch Xtimate C18150 * 25 mm * 5 µm; mobile phase: [water (HCl) - ACN]; B%: 18% - 48%, 10 min) to give 6-((4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)amino)pyridazine-4-carbonitrile (Example 50, 11.3 mg, yield: 4.3%) was a light-gray solid. MS: m/z = 420.1 [M + H]+.1H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 7.75 (d, J = 1.6 Hz, 1H), 8.30 (dd, J = 4.8, 1.2 Hz, 1H), 8.19 (dd, J = 8.0, 1.2 Hz, 1H), 8.08 - 7.92 (m, 2H), 7.49 (d, J = 8.4 Hz, 2H), 7.44 - 7.29 (m, 4H), 7.21 (dd, J = 7.6, 1.6 Hz, 1H), 6.96 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 4.70 (d, J = 5.6 Hz, 2H). [00571] Example 51 to 54 were prepared in a manner similar to Example 50. [00572] Example 51: 6-((1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3 - yl)benzyl)piperidin-4-yl)amino)pyridazine-4-carbonitrile MS: m/z = 503.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.68 (d, J = 1.6 Hz, 1H), 8.33 (dd, J = 4.8, 1.2 Hz, 1H), 8.20 (dd, J = 8.0, 1.2 Hz, 1H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.46 (d, J = 8.4 Hz, 2H), 7.42 - 7.32 (m, 4H), 7.22 (s, 1H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.00 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.96 - 3.76 (m, 1H), 3.57 (s, 2H), 2.83 (d, J = 11.2 Hz, 2H), 2.14 (t, J = 11.2 Hz, 2H), 1.96 (d, J = 10.0 Hz, 2H), 1.58 - 1.44 (m, 2H). [00573] Example 52: 6-((4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)amino)pyridazine-4-carbonitrile MS: m/z = 496.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.77 (d, J = 1.6 Hz, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.05 - 7.95 (m, 5H), 7.56 - 7.50 (m, 2H), 7.50 - 7.44 (m, 4H), 7.41 - 7.38 (m, 1H), 7.35 (d, J = 1.6 Hz, 1H), 7.20 (dd, J = 7.6, 1.6 Hz, 1H), 6.95 (br s, 2H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 4.74 (d, J = 5.6 Hz, 2H). [00574] Example 53: 6-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)pyridazine-4-carbonitri le MS: m/z = 565.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.84 (d, J = 1.2 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.16 - 7.96 (m, 4H), 7.87 (d, J = 1.2 Hz, 1H), 7.56 - 7.51 (m, 2H), 7.51 - 7.44 (m, 4H), 7.43 - 7.37 (m, 1H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.75 - 3.68 (m, 4H), 3.65 (s, 2H), 2.56 - 2.53 (m, 4H). [00575] Example 54: 6-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyridazine-4-carb onitrile MS: m/z = 579.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.68 (d, J = 1.6 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.09 - 7.93 (m, 4H), 7.57 - 7.42 (m, 6H), 7.41 - 7.36 (m, 2H), 7.22 (s, 1H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.95 - 3.75(m, 1H), 3.59 (s, 2H), 2.84 (d, J = 11.2 Hz, 2H), 2.16 (t, J = 11.2 Hz, 2H), 1.97 (d, J = 11.6 Hz, 2H), 1.60 - 1.43 (m, 2H). [00576] Example 55 to 61 were prepared in a manner similar to Example 23. [00577] Example 55: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-2-cyanoisonicotinamide MS: m/z = 606.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.84 (d, J = 4.8 Hz, 1H), 8.13 (d, J = 8.4 Hz, 1H), 8.07 (dd, J = 5.2, 1.6 Hz, 1H), 8.04 - 8.00 (m, 3H), 7.84 - 7.79 (m, 2H), 7.50 (d, J = 8.4 Hz, 2H), 7.45 - 7.37 (m, 5H), 7.09 (dd, J = 8.0, 1.6 Hz, 1H), 6.59 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 6.16 (br s, 1H), 4.14 - 4.01 (m, 1H), 3.65 (s, 2H), 2.97 (d, J = 11.6 Hz, 2H), 2.31 – 2.24 (m, 2H), 2.11 – 2.05 (m, 2H), 1.75 – 1.68 (m, 2H). [00578] Example 56: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-6-cyanopicolinamide MS: m/z = 606.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.42 (d, J = 8.0 Hz, 1H), 8.13 (d, J = 8.4 Hz, 1H), 8.06 (dd, J = 4.8, 1.6 Hz, 1H), 8.05 - 7.99 (m, 3H), 7.85 – 7.79 (m, 3H), 7.57 (d, J = 8.0 Hz, 2H), 7.47 - 7.41 (m, 4H), 7.40 - 7.34 (m, 1H), 7.11 (dd, J = 7.6, 1.2 Hz, 1H), 6.65 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 4.13 - 4.01 (m, 1H), 3.73 (s, 2H), 310 – 2.96 (m, 2H), 2.45 – 2.31 (m, 2H), 2.10 (d, J = 10.8 Hz, 2H), 1.87 - 1.80 (m, 2H). [00579] Example 57: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-5-cyanonicotinamide MS: m/z = 606.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 9.16 (d, J = 2.0 Hz, 1H), 8.96 (d, J = 2.0 Hz, 1H), 8.48 - 8.40 (m, 1H), 8.13 (d, J = 8.4 Hz, 1H), 8.06 (dd, J = 4.8, 1.6 Hz, 1H), 8.03 - 7.99 (m, 2H), 7.80 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.45 - 7.40 (m, 4H), 7.39 - 7.35 (m, 1H), 7.08 (dd, J = 7.6, 1.6 Hz, 1H), 6.59 (br s, 2H), 6.43 (br s, 1H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 4.15 - 4.05 (m, 1H), 3.70 (s, 2H), 3.02 (d, J = 11.2 Hz, 2H), 2.33 (t, J = 11.2 Hz, 2H), 2.10 (d, J = 10.0 Hz, 2H), 1.81 - 1.71 (m, 2H). [00580] Example 58: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-2-cyanonicotinamide MS: m/z = 606.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.89 (s, 1H), 8.92 (d, J = 4.4 Hz, 1H), 8.33 - 8.19 (m, 2H), 8.03 (d, J = 7.6 Hz, 2H), 8.01 - 7.93 (m, 2H), 7.73 (dd, J = 7.6, 5.2 Hz, 1H), 7.57 - 7.50 (m, 2H), 7.50 - 7.42 (m, 4H), 7.41 - 7.34 (m, 1H), 7.17 (d, J = 6.8 Hz, 1H), 7.04 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 4.38 - 4.25 (m, 1H), 3.62 (s, 2H), 2.98 (d, J = 11.2 Hz, 2H), 2.64 - 2.55 (m, 2H), 2.16 - 2.04 (m, 2H), 1.67 (d, J = 10.0 Hz, 2H). [00581] Example 59: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-3-cyanoisonicotinamide MS: m/z = 606.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.54 (s, 1H), 9.40 (s, 1H), 8.94 (d, J = 4.8 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 7.6 Hz, 2H), 8.01 - 7.96 (m, 2H), 7.78 (d, J = 4.8 Hz, 1H), 7.57 - 7.50 (m, 2H), 7.50 - 7.42 (m, 4H), 7.42 - 7.36 (m, 1H), 7.20 - 7.14 (m, 1H), 7.01 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 4.34 - 4.24 (m, 1H), 3.64 (s, 2H), 3.00 (d, J = 10.0 Hz, 2H), 2.63 - 2.56 (m, 2H), 2.21 - 2.06 (m, 2H), 1.65 (d, J = 10.0 Hz, 2H). [00582] Example 60: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-4-cyanonicotinamide MS: m/z = 606.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.60 (s, 1H), 9.10 - 8.93 (m, 2H), 8.27 (d, J = 8.4 Hz, 1H), 8.19 - 8.12 (m, 1H), 8.03 (d, J = 7.2 Hz, 2H), 8.01 - 7.95 (m, 2H), 7.57 - 7.49 (m, 2H), 7.49 - 7.43 (m, 4H), 7.42 - 7.34 (m, 1H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 4.34 - 4.21 (m, 1H), 3.62 (s, 2H), 2.98 (d, J = 11.2 Hz, 2H), 2.64 - 2.52 (m, 2H), 2.09 (t, J = 11.2 Hz, 2H), 1.69 - 1.56 (m, 2H). [00583] Example 61: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-3-cyanopicolinamide MS: m/z = 606.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.45 (s, 1H), 8.87 (dd, J = 4.8, 1.2 Hz, 1H), 8.55 (dd, J = 7.6,1.2 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 7.2 Hz, 2H), 8.01 - 7.97 (m, 2H), 7.76 (dd, J = 7.6, 4.8 Hz, 1H), 7.55 - 7.50 (m, 2H), 7.49 - 7.45 (m, 4H), 7.41 - 7.37 (m, 1H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 4.38 - 4.30 (m, 1H), 3.63 (s, 2H), 2.99 (d, J = 10.8 Hz, 2H), 2.66 - 2.52 (m, 2H), 2.15 - 2.06 (m, 2H), 1.65 (d, J = 10.0 Hz, 2H). [00584] Example 62 to 68 were prepared in a manner similar to Example 13. [00585] Example 62: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3 - yl)benzyl)piperidin-4-yl)amino)picolinonitrile MS: m/z = 502.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.34 (dd, J = 4.8, 1.2 Hz, 1H), 8.21 (dd, J = 8.0, 1.2 Hz, 1H), 8.09 (d, J = 5.6 Hz, 1H), 8.03 - 7.95 (m, 1H), 7.46 (d, J = 8.4 Hz, 2H), 7.44 - 7.36 (m, 3H), 7.17 (dd, J = 8.0, 2.0 Hz, 1H), 7.12 - 7.04 (m, 2H), 7.01 (br s, 2H), 6.75 (dd, J = 6.0, 2.4 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.57 (s, 2H), 2.86 - 2.77 (m, 3H), 2.20 - 2.11 (m, 2H), 1.93 - 1.85 (m, 2H), 1.50 - 1.37 (m, 2H). [00586] Example 63: 6-((1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3 - yl)benzyl)piperidin-4-yl)amino)picolinonitrile MS: m/z = 502.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.34 (d, J = 4.8 Hz, 1H), 8.21 (d, J = 8.0 Hz, 1H), 8.05 - 7.95 (m, 1H), 7.54 - 7.44 (m, 3H), 7.43 - 7.34 (m, 3H), 7.17 (d, J = 7.2 Hz, 1H), 7.11 (d, J = 7.6 Hz, 1H), 7.08 - 6.98 (m, 3H), 6.77 (d, J = 8.4 Hz, 1H), 6.40 - 6.37 (m,1H), 3.72 - 3.67 (m, 1H), 3.57 (br s, 2H), 2.84 - 2.79 (m, 2H), 2.19 - 2.10 (m, 2H), 1.94 - 1.87 (m, 2H), 1.51 - 1.41 (m, 2H). [00587] Example 64: 6-((1-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3 - yl)benzyl)piperidin-4-yl)amino)pyrimidine-4-carbonitrile MS: m/z = 503.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.56 (s, 1H), 8.39 (dd, J = 4.8, 1.2 Hz, 1H), 8.10 (dd, J = 8.0, 1.2 Hz, 1H), 8.04 (dd, J = 4.8, 1.6 Hz, 1H), 7.52 (d, J = 7.8 Hz, 2H), 7.36 - 7.29 (m, 3H), 7.06 (dd, J = 7.6, 1.6 Hz, 1H), 6.68 (s, 1H), 6.62 (br s, 2H), 6.33 (dd, J = 7.6, 4.8 Hz, 1H), 5.56 - 5.27 (m, 1H), 4.33 - 3.84 (m, 1H), 3.66 (s, 2H), 3.01 - 2.91 (m, 2H), 2.35 - 2.26 (m, 2H), 2.06 (d, J = 11.2 Hz, 2H), 1.71 - 1.62 (m, 2H). [00588] Example 65: 5-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)nicotinonitrile MS: m/z = 564.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.48 (d, J = 3.2 Hz, 1H), 8.30 (d, J = 1.6 Hz, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.10 - 8.04 (m, 1H), 8.02 (d, J = 7.2 Hz, 2H), 7.81 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.45 - 7.41 (m, 4H), 7.40 - 7.38 (m, 1H), 7.34 - 7.32 (m, 1H), 7.12 (dd, J = 7.6, 1.6 Hz, 1H), 6.67 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.69 (s, 2H), 3.35 - 3.31 (m, 4H), 2.72 - 2.68 (m, 4H). [00589] Example 66: 2-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)isonicotinonitrile MS: m/z = 564.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.28 (d, J = 5.2 Hz, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.07 (dd, J = 4.8, 1.6 Hz, 1H), 8.02 (d, J = 6.8 Hz, 2H), 7.81 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.49 - 7.41 (m, 4H), 7.40 - 7.35 (m, 1H), 7.10 (dd, J = 7.6, 1.6 Hz, 1H), 6.82 (s, 1H), 6.76 (dd, J = 5.2, 1.2 Hz, 1H), 6.61 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.66 (s, 2H), 3.66 - 3.58 (m, 4H), 2.68 - 2.56 (m, 4H). [00590] Example 67:6-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrazine-2-carbonitrile MS: m/z = 565.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.29 (s, 1H), 8.18 - 8.10 (m, 2H), 8.08 (d, J = 4.8 Hz, 1H), 8.02 (d, J = 8.0 Hz, 2H), 7.81 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 8.0 Hz, 2H), 7.47 - 7.42 (m, 4H), 7.41 - 4.35 (m, 1H), 7.11 (d, J = 7.6 Hz, 1H), 6.66 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.74 - 3.69 (m, 4H), 3.67 (s, 2H), 2.63 (t, J = 4.8 Hz, 4H). [00591] Example 68: 2-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine-4-carbonitri le MS: m/z = 565.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.45 (d, J = 4.8 Hz, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 4.4 Hz, 1H), 8.02 (d, J = 7.6 Hz, 2H), 7.81 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 8.0 Hz, 2H), 7.48 - 7.41 (m, 4H), 7.41 - 7.36 (m, 1H), 7.11 (d, J = 7.6 Hz, 1H), 6.75 (d, J = 4.8 Hz, 1H), 6.67 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.94 - 3.87 (m, 4H), 3.66 (s, 2H), 2.58 (t, J = 4.8 Hz, 4H). [00592] Example 69 to 73 were prepared in a manner similar to Example 23. [00593] Example 69: 6-(4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazine-1-carbonyl)picolinonitrile MS: m/z = 516.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.33 (dd, J = 4.8, 1.6 Hz, 1H), 8.25 - 8.16 (m, 2H), 8.15 - 8.09 (m, 1H), 7.98 (dd, J = 4.8, 2.0 Hz, 1H), 7.90 (dd, J=7.6, 1.2 Hz, 1H), 7.47 (d, J=8.4 Hz, 2H), 7.43 - 7.32 (m, 3H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.00 (br s, 2H), 6.38 (dd, J = 8.0, 5.2 Hz, 1H), 3.73 - 3.65 (m, 2H), 3.62 (s, 2H), 3.41 - 3.36 (m, 2H), 2.47 - 2.36 (m, 4H). [00594] Example 70: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carbonyl)pyridazine-3-car bonitrile MS: m/z = 593.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.61 (d, J = 5.2 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 5.2 Hz, 1H), 8.05 - 8.01 (m, 2H), 8.00 - 7.96 (m, 2H), 7.54 - 7.44 (m, 6H), 7.42 - 7.36 (m, 1H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.76 - 3.70 (m, 2H), 3.65 (s, 2H), 3.37 - 3.31 (m, 2H), 2.58 - 2.52 (m, 2H), 2.46 - 2.40 (m, 2H). [00595] Example 71: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-3-cyanopyridazine-4-ca rboxamide MS: m/z = 607.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.52 (s, 1H), 9.59 (d, J = 5.6 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.14 (d, J = 5.2 Hz, 1H), 8.05 - 7.97 (m, 4H), 7.54 - 7.44 (m, 6H), 7.41 - 7.35 (m, 1H), 7.17 (d, J = 7.6 Hz, 1H), 7.04 (br s, 2H), 6.38 (dd, J = 8.0, 4.4 Hz, 1H), 4.42 - 4.28 (m, 1H), 3.63 (s, 2H), 2.99 (d, J = 9.6 Hz, 2H), 2.64 - 2.56 (m, 2H), 2.14 - 2.08 (m, 2H), 1.70 (d, J = 10.4 Hz, 2H). [00596] Example 72: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carbonyl)pyrimidine-5-car bonitrile MS: m/z = 593.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.48 (d, J = 5.2 Hz, 2H), 8.27 (d, J = 8.4 Hz, 1H), 8.05 - 7.95 (m, 4H), 7.54 - 7.44 (m, 6H), 7.41 - 7.35 (m, 1H), 7.14 (dd, J = 8.0, 1.6 Hz, 1H), 7.02 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.77 - 3.71 (m, 2H), 3.65 (s, 2H), 3.39 - 3.31 (m, 2H), 2.59 - 2.51 (m, 2H), 2.48 - 2.42 (m, 2H). [00597] Example 73: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-5-cyanopyrimidine-4-ca rboxamide MS: m/z = 607.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.62 - 9.43 (m, 2H), 9.09 (d, J = 8.0 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.05 - 7.97 (m, 4H), 7.54-7.42 (m, 6H), 7.41 - 7.35 (m, 1H), 7.17 (d, J = 7.2 Hz, 1H), 7.03 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.90 - 3.76 (m, 1H), 3.59 (s, 2H), 2.95 - 2.79 (m, 2H), 2.16 - 2.06 (m, 2H), 1.85 - 1.62 (m, 4H). [00598] Example 74: 5-((1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3 - yl)benzyl)piperidin-4-yl)amino)nicotinonitrile Example 74 was prepared in a manner similar to Example 1. MS: m/z = 502.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.33 (dd, J = 4.4, 1.2 Hz, 1H), 8.23 - 8.19 (m, 2H), 8.06 (d, J = 1.6 Hz, 1H), 7.98 (dd, J = 4.8, 2.0 Hz, 1H), 7.45 (d, J = 8.0, 2H), 7.43 - 7.35 (m, 4H), 7.33 - 7.31 (m, 1H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.00 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.57 (s, 2H), 2.83 - 2.78 (m, 2H), 2.19 - 2.16 (m, 2H), 1.93 - 1.88 (m, 2H), 1.46 - 1.38 (m, 2H). [00599] Example 75: 2-((1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3 - yl)benzyl)piperidin-4-yl)amino)isonicotinonitrile Example 75 was prepared in a manner similar to Example 1. MS: m/z = 502.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.33 (d, J = 4.8 Hz, 1H), 8.21 (dd, J = 8.0, 1.2 Hz, 1H), 8.15 (d, J = 5.2 Hz, 1H), 7.99 (dd, J = 5.2, 1.6 Hz, 1H), 7.45 (d, J = 8.4 Hz, 2H), 7.42 - 7.35 (m, 3H),7.16 (dd, J = 7.6, 2.0 Hz, 1H), 7.05 (d, J = 7.6 Hz, 1H), 7.01(br s, 2H), 6.80(s, 1H), 6.75 (d, J = 5.2 Hz, 1H), 6.437 (dd, J = 7.6, 4.8 Hz, 1H), 3.79 - 3.66 (m, 1H), 3.55 (s, 2H), 2.86 – 2.76 (m, 2H), 2.18 - 2.05 (m, 2H), 1.91 – 1.81 (m, 2H), 1.53 - 1.39 (m, 2H). [00600] Example 76: 6-((1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3 - yl)benzyl)piperidin-4-yl)amino)pyrazine-2-carbonitrile Example 76 was prepared in a manner similar to Example 47. MS: m/z = 503.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.33 (d, J = 4.8 Hz, 1H), 8.21 (d, J = 8.0 Hz, 1H), 8.09 (d, J = 10.4 Hz, 2H), 7.98 (d, J = 4.8 Hz, 1H), 7.80 - 7.71 (m, 1H), 7.45 (m, J = 7.6 Hz, 2H), 7.42 - 7.36 (m, 3H), 7.16 (d, J = 8.4 Hz, 1H), 7.01 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.71 - 3.68 (m, 1H), 3.57 (s, 2H), 2.83 - 2.79 (m, 2H), 2.18 - 2.12 (m, 2H), 1.94 - 1.88 (m, 2H), 1.53 - 1.44 (m, 2H). [00601] Example 77: 2-((1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3 - yl)benzyl)piperidin-4-yl)amino)pyrimidine-4-carbonitrile Example 77 was prepared in a manner smiliar to Example 47. MS: m/z = 503.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.49 (d, J = 4.8 Hz, 1H), 8.35 (d, J = 4.8 Hz, 1H), 8.24 - 8.16 (m, 4H), 8.02 - 7.95 (m, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 8.0 Hz, 2H), 7.45 (dd, J = 8.0, 4.8 Hz, 1H), 7.39 - 7.33 (m, 1H), 6.96 (d, J = 4.4 Hz, 1H), 6.49 (dd, J = 7.6, 4.8 Hz, 1H), 4.33 (br s, 2H), 4.11 - 4.03 (m, 1H), 3.47 (d, J = 12.4 Hz, 2H), 3.11 (t, J = 11.2 Hz, 2H), 2.24 (d, J = 12.4 Hz, 2H), 1.94 - 1.80 (m, 2H). [00602] Example 78: 6-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine-4-carbonitri le Example 78 was prepared in a manner smiliar to Example 47. MS: m/z = 565.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d ₆ ) δ 8.60 (s, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 4.8 Hz, 1H), 8.02 (d, J = 7.6 Hz, 2H), 7.81 (d, J = 8.4 Hz, 1H), 7.51 (d, J = 8.0 Hz, 1H), 7.47 - 7.42 (m, 4H), 7.41 - 7.36 (m, 1H), 7.11 (d, J = 7.6 Hz, 1H), 6.84 (s, 1H), 6.66 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.88 - 3.68 (m, 4H), 3.67 (s, 2H), 2.61 (t, J = 4.8 Hz, 4H). [00603] Example 79: 5-(4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazine-1-carbonyl)nicotinonitrile Example 79 was prepared in a manner similar to Example 23. MS: m/z = 516.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.93 (d, J = 2.0 Hz, 1H), 8.85 (d, J = 2.0 Hz, 1H), 8.40 (dd, J = 4.8, 1.2 Hz, 1H), 8.11 (dd, J = 8.0, 1.2 Hz, 1H), 8.07 - 8.04 (m, 2H), 7.50 (d, J = 8.0 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.33 - 7.30 (m, 1H), 7.07 (dd, J = 7.6, 1.6 Hz, 1H), 6.62 (br s, 2H), 6.33 (dd, J = 8.0, 4.8 Hz, 1H), 3.89 - 3.79 (m, 2H), 3.64 (s, 2H) 3.50 - 3.39 (m, 2H), 2.64 - 2.57 (m, 2H), 2.54 - 2.46 (m, 2H). [00604] Example 80: 6-(4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazine-1-carbonyl)nicotinonitrile Example 80 was prepared in a manner similar to Example 23. MS: m/z = 516.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.86 (d, J = 1.6 Hz, 1H), 8.40 (dd, J = 4.8, 1.2 Hz, 1H), 8.12 - 8.04 (m, 3H), 7.81 (d, J = 7.6 Hz, 1H), 7.51 (d, J = 8.0 Hz, 2H), 7.38 - 7.30 (m, 3H), 7.08 (dd, J = 7.6, 1.6 Hz, 1H), 6.75 (br s, 2H), 6.34 (dd, J = 7.6, 4.8 Hz, 1H), 3.89 - 3.84 (m, 2H), 3.64 (s, 2H), 3.62 - 3.59 (m, 2H), 2.65 - 2.61 (m, 2H), 2.55 - 2.51 (m, 2H). [00605] Example 81: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-5-cyanopicolinamide Example 81 was prepared in a manner similar to Example 23. MS: m/z = 606.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.16 - 9.05 (m, 1H), 8.80 (d, J = 8.4 Hz, 1H), 8.51 (dd, J = 8.4, 2.0 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.17 (d, J = 8.0 Hz, 1H), 8.07 - 7.95 (m, 4H), 7.51 - 7.43 (m, 6H), 7.42 - 7.36 (m, 1H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.93 - 3.79 (m, 1H), 3.58 (s, 2H), 2.87 - 2.84 (m, 2H), 2.17 - 2.06 (m, 2H), 1.79 - 1.67 (m, 4H). [00606] Example 82: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)picolinonitrile Example 82 was prepared in a manner similar to Example 13. MS: m/z = 564.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.23 (d, J = 6.0 Hz, 1H), 8.07 - 7.96 (m, 4H), 7.56 - 7.44 (m, 7H), 7.43 - 7.37 (m, 1H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.07 (dd, J = 6.4, 2.8 Hz, 1H), 7.03 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.64 (s, 2H), 3.50 - 3.43 (m, 4H), 2.55 - 2.51 (m, 4H). [00607] Example 83 6-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)picolinonitrile Example 83 was prepared in a manner similar to Example 13. MS: m/z = 564.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.09 - 7.96 (m, 4H), 7.70 (dd, J = 8.8, 7.6 Hz, 1H), 7.54 - 7.50 (m, 2H), 7.50 - 7.44 (m, 4H), 7.43 - 7.37 (m, 1H), 7.24 - 7.13 (m, 3H), 7.03 (br s, 2H), 6.37 (dd, J = 8.0, 4.8 Hz, 1H), 3.64 (s, 2H), 3.62 - 3.56 (m, 4H), 2.54 - 2.51 (m, 4H). [00608] Example 84: 5-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)picolinonitrile To a solution of Intermediate 11 (150 mg, 315 µmol) in DMF (2 mL) was added 5- fluoropyridine-2-carbonitrile (46.2 mg, 378 µmol) and DIEA (204 mg, 1.58 mmol). The mixture was stirred at 100 °C for 16 hr. The mixture was concentrated under reduced pressure to give a residue. The mixture was purified by prep-HPLC (column: Waters Xbridge 150 x 25mm x 5 m; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 35% - 75%, 8 min). to give 5- ((1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]py ridin-3-yl)benzyl)piperidin-4- yl)amino)picolinonitrile (Example 84, 24.7 mg, yield: 14%) as a light-yellow lyophilized powder. MS: m/z = 578.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.15 (d, J = 8.4 Hz, 1H), 8.07 (dd, J = 4.8,1.2 Hz, 1H), 8.04 - 8.01 (m, 3H), 7.82 (d, J = 8.4 Hz, 1H), 7.57 - 7.51 (m, 2H), 7.48 - 7.35 (m, 7H), 7.10 (dd, J = 7.8, 1.2 Hz, 1H), 6.82 (dd, J = 8.4, 2.8 Hz, 1H), 6.64 (br s, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 4.29 (br s, 1H), 3.71 (s, 2H), 3.49 - 3.35 (m, 1H), 3.09 - 2.93 (m, 2H), 2.33 – 2.30 (m, 2H), 2.17 - 2.05 (m, 2H), 1.68 - 1.67 (m, 2H). [00609] Example 85: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)picolinonitrile Example 85 was prepared in a manner similar to Example 84. MS: m/z = 578.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.22 (d, J = 5.6 Hz, 1H), 8.15 (d, J = 8.4 Hz, 1H), 8.07 (dd, J = 4.8, 1.6 Hz, 1H), 8.04 - 8.01 (m, 2H), 7.82 (d, J = 8.4 Hz, 1H), 7.58 - 7.53 (m, 2H), 7.47 - 7.43 (m, 4H), 7.41 - 7.36 (m, 1H), 7.11 (dd, J = 7.6, 1.6 Hz, 1H), 6.83 (d, J = 2.4 Hz, 1H), 6.68 (br s, 2H), 6.57 (dd, J = 5.6, 2.4 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 4.52 (br s, 1H), 3.75 (s, 2H), 3.49 - 3.38 (m, 1H), 3.10 - 3.00 (m, 2H), 2.43 - 2.32 (m, 2H), 2.14 - 2.07 (m, 2H), 1.76 - 1.75 (m, 2H) [00610] Example 86: 6-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)picolinonitrile Example 86 was prepared in a manner similar to Example 84. MS: m/z = 578.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.16 (d, J = 8.4 Hz, 1H), 8.08 (dd, J = 4.8, 1.2 Hz, 1H), 8.02 (d, J = 7.2 Hz, 2H), 7.86 - 7.82 (m, 2H), 7.58 - 7.53 (m, 2H), 7.49 - 7.37 (m, 5H), 7.10 (dd, J = 7.6, 1.2 Hz, 1H), 7.02 - 6.96 (m, 1H), 6.74 (br s, 2H), 6.62 (d, J = 8.4 Hz, 1H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 4.90 – 4.88 (m, 1H), 4.26 - 4.06 (m, 3H), 3.51-3.49 (m, 2H), 2.89 - 2.70 (m, 2H), 2.28 – 2.27(m, 2H), 1.37 - 1.23 (m, 2H). [00611] Example 87: 2-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)isonicotinonitril e Example 87 was prepared in a manner similar to Example 84. MS: m/z = 578.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.0 Hz, 1H), 8.15 (d, J = 5.2 Hz, 1H), 8.03 (d, J = 7.6 Hz, 2H), 8.01 - 7.97 (m, 2H), 7.52 - 7.42 (m, 7H), 7.41 - 7.37 (m, 1H), 7.18 - 7.13 (m, 1H), 7.03 (br s, 2H), 6.80 (s, 1H), 6.78 - 6.72 (m, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.79 - 3.65 (m, 1H), 3.58 (s, 2H), 2.88 - 2.80 (m, 2H), 2.16 - 2.10 (m, 2H), 1.94 - 1.87 (m, 2H), 1.52 - 1.42 (m, 2H). [00612] Example 88: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile Following the general procedure of Example 84, the reaction of Intermediate 11 (1 g, 2.0 mmol) in with 4-chloropyrimidine-2-carbonitrile (278 mg, 2.0 mmol) was carried out under microwave at 130 °C for 0.5 hr. After purified by silica gel flash chromatography (Eluent of 0~100% EtOAc in petroleum ether and 8% MeOH in CH ₂ Cl ₂ ), 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5- phenyl-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)a mino)pyrimidine-2-carbonitrile (Example 88, 601 mg, yield: 52%) was obtained as a light-yellow solid. MS: m/z = 579.4 [M + H]+. 1H NMR (400 MHz, Dimethylsulfoxide-d6) δ 8. 27 (d, J = 8.4 Hz, 1H), 8.10 - 7.97 (m, 6H), 7.51 - 7.43 (m, 6H), 7.41 - 7.37 (m, 1H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (br s, 2H), 6.67 (d, J = 5.6 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.84 - 3.79 (m, 1H), 3.59 (s, 2H), 2.87 - 2.80 (m, 2H), 2.15 – 2.13 (m, 2H), 1.90 - 1.89 (m, 2H), 1.55 - 1.44 (m, 2H). [00613] Example 89: 6-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrazine-2-carbon itrile Example 89 was prepared in a manner similar to Example 84. MS: m/z = 579.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.15 (d, J = 8.4 Hz, 1H), 8.11 - 8.05 (m, 3H), 8.04 - 8.00 (m, 2H), 7.82 (d, J = 8.4 Hz, 1H), 7.66 - 7.59 (m, 2H), 7.49 - 7.43 (m, 4H), 7.41 - 7.37 (m, 1H), 7.10 (dd, J = 7.6, 1.6 Hz, 1H), 6.63 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 5.59 - 4.63 (m, 1H), 4.03 - 3.80 (m, 3H), 3.27 - 3.02 (m, 2H), 2.59 - 2.40 (m, 2H), 2.20 - 2.13 (m, 2H), 1.93 - 1.84 (m, 2H). [00614] Example 90: 2-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-4-carb onitrile Example 90 was prepared in a manner similar to Example 84. MS: m/z = 579.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.44 (d, J = 2.4 Hz, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.08 (dd, J = 4.8, 1.6 Hz, 1H), 8.03 (d, J = 7.2 Hz, 2H), 7.82 (d, J = 8.4 Hz, 1H), 7.57 (d, J = 7.6 Hz, 2H), 7.49 - 7.42 (m, 4H), 7.41 - 7.35 (m, 1H), 7.11 (dd, J = 7.6, 1.2 Hz, 1H), 6.83 (d, J = 4.8 Hz, 1H), 6.63 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 5.41 (br s, 1H), 4.00 - 3.90 (m, 1H), 3.74 (s, 2H), 3.18 - 2.90 (m, 2H), 2.39 – 2.37 (m, 2H), 2.14 – 2.11 (m, 2H), 1.79 – 1.78 (m, 2H). [00615] Example 91: 6-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-4-carb onitrile Example 91 was prepared in a manner similar to Example 84. MS: m/z = 579.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.50 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.09 - 7.97 (m, 5H), 7.50 - 7.44 (m, 6H), 7.42 - 7.36 (m, 1H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.02 (br s, 2H), 6.93 (s, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.94 - 3.80 (m, 1H), 3.59 (s, 2H), 2.87 - 2.80 (m, 2H), 2.17 - 2.07 (m, 2H), 1.95 - 1.83 (m, 2H), 1.55 - 1.47 (m, 2H). [00616] Example 92: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3 - yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile Example 92 was prepared in a manner similar to Example 84. MS: m/z = 503.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.33 (dd, J = 4.6, 1.2 Hz, 1H), 8.20 (dd, J = 8.0, 1.2 Hz, 1H), 8.11 - 8.03 (m, 2H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.45 (d, J = 8.4 Hz, 2H), 7.41 - 7.36 (m, 3H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.67 (d, J = 5.6 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.84 – 3.80 (m, 1H), 3.56 (s, 2H), 2.81 (d, J = 11.2 Hz, 2H), 2.18 - 2.11 (m, 2H), 1.89 -1.87 (m, 2H), 1.53 - 1.44 (m, 2H). [00617] Example 93: 5-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)nicotinonitrile To a solution of Intermediate 14 (120 mg, 291 µmol), Intermediate 22 (64.8 mg, 320 µmol) in DMF (1 mL) were added NaI (4.37 mg, 29.1 µmol) and K ₂ CO ₃ (80.5 mg, 582 µmol). The mixture was stirred at 80 °C for 2 hr. The reaction mixture was diluted with H ₂ O (5 mL) and then filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep-TLC (CH ₂ Cl ₂ : MeOH = 10 : 1), 5-((1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)ni cotinonitrile (Example 93, 13.7 mg, yield: 8.2%) was obtained as a light-yellow powder. MS: m/z = 578.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.22 (d, J = 2.8 Hz, 1H), 8.08 - 7.97 (m, 5H), 7.51 - 7.44 (m, 6H), 7.43 - 7.36 (m, 1H), 7.32 (s, 1H), 7.16 (dd, J = 7.6, 2.0 Hz, 1H), 7.02 (br s, 2H), 6.42 - 6.32 (m, 2H), 3.59 (s, 2H), 3.30 – 3.10 (m, 1H), 2.95 – 2.75 (m, 2H), 2.18 (t, J = 9.6 Hz, 2H), 1.92 - 1.85 (m, 2H), 1.46 - 1.38 (m, 2H). [00618] Example 94: 5-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)picolinonitrile Example 94 was prepared in a manner similar to Example 13. MS: m/z = 564.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.44 (d, J = 2.8 Hz, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.06 - 7.98 (m, 4H), 7.75 (d, J = 9.2 Hz, 1H), 7.530 (d, J = 8.4 Hz, 2H), 7.50 - 7.44 (m, 4H), 7.43 - 7.35 (m, 2H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.66 (s, 2H), 3.46 (t, J = 4.8 Hz, 4H), 2.56 (t, J = 4.8 Hz, 4H). [00619] Example 95: 5-((4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)amino)pyrimidine-2-carbonitrile To a solution of Intermediate 1 (200 mg, 0.632 mmol) and 5-fluoropyrimidine-2-carbonitrile (77.8 mg, 0.632 mmol) in DMF (4 mL) was added DIEA (245 mg, 1.90 mmol). The mixture was stirred at 100 °C for 12 hr. The reaction mixture was filtered. Then the filtrate was purified by prep-HPLC (column: Waters xbridge 150*25 mm 10 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 17% - 47%, 10 min), 5-((4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)amino)pyrimidine-2-carbonitrile (Example 95, 52.8 mg, yield: 20%) was obtained as a white solid. MS: m/z = 420.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.31 (dd, J = 4.8, 1.6 Hz, 1H), 8.26 (s, 2H), 8.20 (dd, J = 8.0, 1.2 Hz, 1H), 7.99 (m, dd, J = 8.8, 2.0 Hz, 1H), 7.85 (dd, J = 6.0, 6.0 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.45 - 7.33 (m, 3H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 6.97 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 4.55 (d, J = 6.0 Hz, 2H). [00620] Example 96: 5-((4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)amino)pyrimidine-2-carbonitrile Example 96 was prepared in a manner similar to Example 95. MS: m/z = 496.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.36 - 8.20 (m, 3H), 8.09 - 7.95 (m, 4H), 7.87 - 7.77 (m, 1H), 7.60 - 7.36 (m, 7H), 7.21 - 7.14 (m, 1H), 6.99 (br s, 2H), 6.44 - 6.31 (m, 1H), 4.57 (d, J = 5.2 Hz, 2H). [00621] Example 97: 5-(4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine-2-carbonitri le Example 97 was prepared in a manner similar to Example 95. MS: m/z = 565.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.58 (s, 2H), 8.27 (d, J = 8.4 Hz, 1H), 8.10 - 7.95 (m, 4H), 7.56 - 7.44 (m, 6H), 7.43 - 7.34 (m, 1H), 7.15 (d, J = 6.0 Hz, 1H), 7.03 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz,1H), 3.65 (s, 2H), 3.58 - 3.46 (m, 4H), 2.63 - 2.39 (m, 4H). [00622] Example 98 to 111 were prepared in a manner similar to Example 23. [00623] Example 98: N-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)-2-cyanonicotinamide MS: m/z = 447.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.01 (s, 1H), 8.96 (d, J = 4.8 Hz, 1H), 8.32 - 8.27 (m, 2H), 8.18 (d, J = 8.0 Hz, 1H), 7.98 (d, J = 4.8 Hz, 1H), 7.76 (dd, J = 6.4 Hz, 5.2 Hz, 1H), 7.48 (d, J = 8.0 Hz, 2H), 7.39 - 7.35 (m, 3H), 7.20 (d, J = 7.6 Hz, 1H), 6.95 (br s, 2H), 6.41 (dd, J = 8.0 Hz, 4.8 Hz,1H), 5.05 (s, 2H). [00624] Example 99: N-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)-3-cyanoisonicotinamide MS: m/z = 447.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 9.12 (s, 1H), 9.07 - 8.92 (m, 2H), 8.46 - 8.39 (m, 1H), 8.19 - 8.10 (m, 1H), 7.94 - 7.83 (m, 1H), 7.80 (d, J = 4.8 Hz, 1H), 7.77 - 7.56 (m, 2H), 7.39 - 7.31 (m, 4H), 7.23 (br s, 2H), 6.54 - 6.43 (m, 1H), 5.15 (s, 2H). [00625] Example 100: N-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)-4-cyanonicotinamide MS: m/z = 447.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 9.20 (s, 1H), 9.05 (m, 2H), 8.40 (d, J = 4.8 Hz, 1H), 8.15 - 8.02 (m, 2H), 8.01 - 7.87 (m, 2H), 7.73 - 7.59 (m, 3H), 7.41 - 7.30 (m, 4H), 6.48 - 6.43 (m, 1H), 5.13 (br s, 2H). [00626] Example 101: N-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)-3-cyanopicolinamide MS: m/z = 447.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.90 (dd, J = 4.8, 1.2 Hz, 1H), 8.48 (dd, J = 8.0, 1.2 Hz, 1H), 8.29 (dd, J = 4.8, 1.6 Hz, 1H), 8.18 (dd, J = 8.0, 1.6 Hz, 1H), 7.96 (d, J = 5.2 Hz, 1H), 7.77 (dd, J = 8.0, 5.2 Hz, 1H), 7.61 (d, J = 8.0 Hz, 2H), 7.43 - 7.37 (m, 3H), 7.31 (dd, J = 8.0, 2.0 Hz, 1H), 6.46 (dd, J = 7.6, 5.2Hz, 1H), 5.16 (s, 2H). [00627] Example 102: 5-(4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazine-1-carbonyl)picolinonitrile MS: m/z = 516.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.76 (d, J = 1.6 Hz, 1H), 8.40 (dd, J = 4.8, 1.2 Hz, 1H), 8.11 (dd, J = 8.0, 1.2 Hz, 1H), 8.05 (dd, J = 4.8, 1.6 Hz, 1H), 7.91 (dd, J = 8.0, 2.4 Hz, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.50 (d, J = 8.4 Hz, 2H), 7.39 - 7.27 (m, 3H), 7.07 (dd, J = 8.0, 2.0 Hz, 1H), 6.67 (br s, 2H), 6.34 (dd, J = 8.0, 5.2 Hz, 1H), 3.90 - 3.79 (m, 2H), 3.64 (s, 2H), 3.51 - 3.36 (m, 2H), 2.67 - 2.43 (m, 4H). [00628] Example 103: N-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2-cyanonicotinamide MS: m/z = 523.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.01 (s, 1H), 8.96 (dd, J = 4.8, 1.2 Hz, 1H), 8.31 (dd, J = 8.0, 1.6 Hz, 1H), 8.25 (d, J = 8.4 Hz, 1H), 8.02 - 7.95 (m, 4H), 7.77 (dd, J = 8.0, 5.2 Hz, 1H), 7.51 (d, J = 8.8 Hz, 2H), 7.48 - 7.43 (m, 4H), 7.41 - 7.36 (m, 1H), 7.18 (dd, J = 7.6, 1.6 Hz, 1H), 6.91 (br s, 2H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 5.07 (s, 2H). [00629] Example 104: N-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-3-cyanoisonicotinamide MS: m/z = 523.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 9.22 - 9.03 (m, 3H), 8.96 (d, J = 5.6 Hz, 1H), 8.12 (d, J = 8.4 Hz, 1H), 7.93 - 7.88 (m, 2H), 7.80 (d, J = 8.4 Hz, 1H), 7.76 (d, J = 8.8 Hz, 1H), 7.74 - 7.70 (m, 1H), 7.61 (d, J = 8.0 Hz, 2H), 7.40 - 7.30 (m, 7H), 6.47 (dd, J = 7.2, 6.4 Hz, 1H), 5.19 (s, 2H). [00630] Example 105: N-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-4-cyanonicotinamide MS: m/z = 523.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 9.23 (s, 1H), 9.06 (d, J = 6.0 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 7.97 (d, J = 8.0 Hz, 2H), 7.87 (d, J = 8.0 Hz, 1H), 7.80 - 7.64 (m, 4H), 7.52 - 7.37 (m, 7H), 7.25 - 7.22 (m, 2H), 6.59 - 6.52 (m, 1H), 5.19 (s, 2H). [00631] Example 106: N-(4-(2-(2-Aminopyridin-3-yl)-6-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-6-cyanonicotinamide MS: m/z = 523.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.52 (t, J = 6.0 Hz, 1H), 9.20 (d, J = 1.6 Hz, 1H), 8.61 (d, J = 2.0 Hz, 1H), 8.51 - 8.44 (m, 2H), 8.20 (d, J = 8.0 Hz, 1H), 8.01 (dd, J = 4.8, 1.6 Hz, 1H), 7.78 (d, J = 7.6 Hz, 2H), 7.55 - 7.49 (m, 4H), 7.46 - 7.39 (m, 3H), 7.27 (dd, J = 7.6, 1.6 Hz, 1H), 6.99 (br s, 2H), 6.43 (dd, J = 7.6, 4.8 Hz, 1H), 4.62 (d, J = 6.0 Hz, 2H). [00632] Example 107: N-(1-(4-(2-(2-Aminopyridin-3-yl)-6-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-2-cyanoisonicotinamide MS: m/z = 606.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.90 (d, J = 4.8 Hz, 1H), 8.74 (d, J = 7.6 Hz, 1H), 8.64 (d, J = 2.0 Hz, 1H), 8.46 (d, J = 2.0 Hz, 1H), 8.37 (s, 1H), 8.07 (dd, J = 5.2, 1.6 Hz, 1H), 8.01 (dd, J = 4.8, 1.6 Hz, 1H), 7.78 (d, J = 7.2 Hz, 2H), 7.55 – 7.50 (m, 2H), 7.48 (m, J = 8.4 Hz, 2H), 7.44 - 7.39 (m, 3H), 7.20 (dd, J = 7.6, 1.6 Hz, 1H), 7.07 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.84 - 3.76 (m, 1H), 3.58 (s, 2H), 2.87 (br d, J = 11.6 Hz, 2H), 2.16 - 2.07 (m, 2H), 1.88 - 1.81 (m, 2H), 1.67 - 1.58 (m, 2H). [00633] Example 108 N-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)-6-cyanopicolinamide MS: m/z = 447.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.60 (t, J = 6.4 Hz, 1H), 8.35 - 8.32 (m, 1H), 8.31 - 8.28 (m, 1H), 8.28 - 8.22 (m, 2H), 8.19 (dd, J = 8.0, 1.6 Hz, 1H), 7.99 (dd, J = 4.8, 2.0 Hz, 1H), 7.47 (d, J = 8.4 Hz, 2H), 7.40 - 7.36 (m, 3H), 7.23 (dd, J = 7.6, 2.0 Hz, 1H), 6.96 (br s, 2H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 4.58 (d, J = 6.4 Hz, 2H). [00634] Example 109 4-(4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazine-1-carbonyl)picolinonitrile MS: m/z = 516.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.84 (d, J = 5.2 Hz, 1H), 8.32 (dd, J = 4.8, 1.6 Hz, 1H), 8.20 (dd, J = 8.0, 1.2 Hz, 1H), 8.11 (s, 1H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.75 (dd, J = 4.8, 1.6 Hz, 1H), 7.46 (d, J = 8.0 Hz, 2H), 7.41 - 7.37 (m, 3H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.00 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.69 - 3.64 (m, 2H), 3.60 (s, 2H), 3.31 - 3.27 (m, 2H), 2.60 - 2.54 (m, 2H), 2.42 - 2.37 (m, 2H). [00635] Example 110 2-(4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazine-1-carbonyl)nicotinonitrile MS: m/z = 516.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.86 (dd, J = 4.8, 1.6 Hz, 1H), 8.47 (dd, J = 8.0, 1.6 Hz, 1H), 8.32 (dd, J = 4.8, 1.2 Hz, 1H), 8.20 (dd, J = 8.0, 1.6 Hz, 1H), 7.98 (dd, J = 4.8, 2.0 Hz, 1H), 7.70 (dd, J = 8.0, 4.8 Hz, 1H), 7.47 (d, J = 8.4 Hz, 2H), 7.42 - 7.34 (m, 3H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.00 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.75 – 3.70 (m, 2H), 3.62 (s, 2H), 3.29 - 3.26 (m, 2H), 2.54 - 2.52 (m, 2H), 2.43 - 2.39 (m, 2H). [00636] Example 111: 5-(4-(4-(2-(2-Aminopyridin-3-yl)-6-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carbonyl)picolinonitrile MS: m/z = 592.1[M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d ₆ ) δ 8.78 (s, 1H), 8.64 (d, J = 1.6 Hz, 1H), 8.29 (d, J = 2.0 Hz, 1H), 8.08 (d, J = 4.8 Hz, 1H), 7.93 (dd, J = 8.0, 2.0 Hz, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.65 (d, J = 7.2 Hz, 1H), 7.55 - 7.49 (m, 4H), 7.45 - 7.36 (m, 3H), 7.12 (d, J = 7.6 Hz, 1H), 6.78 (br s, 2H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 3.91 - 3.79 (m, 2H), 3.65 (s, 2H), 3.52 - 3.38 (m, 2H), 2.69 - 2.57 (m, 2H), 2.56 - 2.45 (m, 2H). [00637] Example 112: 5-((4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)amino)pyridazine-3-carbonitrile Example 112 was prepared in a manner similar to Example 47. MS: m/z = 496.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.83 (d, J = 2.8 Hz, 1H), 8.29 - 8.19 (m, 2H), 8.04 - 7.96 (m, 4H), 7.55 - 7.45 (m, 6H), 7.43 - 7.37 (m, 1H), 7.32 (d, J = 2.8 Hz, 1H), 7.18 (dd, J = 7.6, 1.6 Hz, 1H), 6.97 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 4.56 (d, J = 6.0 Hz, 2H). [00638] Example 113 to 118 were prepared in a manner similar to Example 32. [00639] Example 113: N-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)-6-cyanopyrimidine-4-carboxamide MS: m/z = 448.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.89 (t, J = 6.4 Hz, 1H), 9.56 (d, J = 1.2 Hz, 1H), 8.58 (d, J = 1.2 Hz, 1H), 8.29 (dd, J = 4.8, 1.6 Hz, 1H), 8.19 (dd, J = 8.0, 1.2 Hz, 1H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.47 (d, J = 8.4 Hz, 2H), 7.40 - 7.36 (m, 3H), 7.23 (dd, J = 7.6, 2.0 Hz, 1H), 6.94 (br s, 2H), 6.40 (dd, J = 8.0, 4.8 Hz, 1H), 4.59 (d, J = 6.4 Hz, 2H). [00640] Example 114: 6-(4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazine-1-carbonyl)pyrimidine-4-carbonitrile MS: m/z = 517.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.45 (s, 1H), 8.36 (s, 1H), 8.33 (dd, J = 4.8, 1.6 Hz, 1H), 8.20 (dd, J = 8.0, 1.6 Hz, 1H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.47 (d, J = 8.0 Hz, 2H), 7.41 - 7.37 (m, 3H), 7.16 (dd, J = 8.0, 2.0 Hz, 1H), 6.99 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.73 - 3.65 (m, 2H), 3.62 (s, 2H), 3.44 - 3.39 (m, 2H), 2.53 - 2.51 (m, 2H), 2.42 - 2.38 (m, 2H). [00641] Example 115: N-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-6-cyanopyrimidine-4-carboxamide MS: m/z = 523.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ 9.89 (t, J = 6.0 Hz, 1H), 9.57 (d, J = 1.2 Hz, 1H), 8.59 (d, J = 1.2 Hz, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.03 - 7.96 (m, 4H), 7.51 - 7.44 (m, 6H), 7.41 - 7.37 (m, 1H), 7.21 (dd, J = 7.6, 2.0 Hz, 1H), 6.92 (br s, 2H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 4.63 (d, J = 6.0 Hz, 2H). [00642] Example 116: 6-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carbonyl)pyrimidine-4-car bonitrile Example 116 was prepared in a manner similar to Example 32. MS: m/z = 593.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 9.35 (d, J = 1.6 Hz, 1H), 8.15 (d, J = 8.4 Hz, 1H), 8.03 - 7.98 (m, 4H), 7.82 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.45 - 7.38 (m, 5H), 7.16 (dd, J = 7.6, 1.2 Hz, 1H), 7.13 - 7.02 (m, 2H), 6.38 (dd, J = 7.6, 5.2 Hz, 1H), 3.91 - 3.86 (m, 2H), 3.72 - 3.62 (m, 4H), 2.68 - 2.58 (m, 4H). [00643] Example 117: N-(1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-6-cyanopyrimidine-4-ca rboxamide MS: m/z = 607.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.53 (d, J = 1.6 Hz, 1H), 9.06 (d, J = 8.0 Hz, 1H), 8.54 (d, J = 1.2 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.05 - 7.97 (m, 4H), 7.50 - 7.44 (m, 6H), 7.42 - 7.37 (m, 1H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (br s, 2H), 6.38 (dd, J = 8.0, 5.2 Hz, 1H), 3.88 - 3.80 (m, 1H), 3.59 (s, 2H), 2.87 (d, J = 11.6 Hz, 2H), 2.15 - 2.08 (m, 2H), 1.80 - 1.71 (m, 4H). [00644] Example 118: N-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-3-cyanopicolinamide MS: m/z = 523.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.52 (s, 1H), 8.92 (dd, J = 4.8, 1.6 Hz, 1H), 8.60 (dd, J = 8.0, 1.6 Hz, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.02 - 7.96 (m, 4H), 7.80 (dd, J = 7.6, 4.8 Hz, 1H), 7.50 - 7.44 (m, 6H), 7.41 - 7.36 (m, 1H), 7.18 (dd, J = 7.6, 1.6 Hz, 1H), 6.91 (br s, 2H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 5.07 (s, 2H). [00645] Example 119: N-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)-2-cyanopyrimidine-5-carboxamide Example 119 was prepared in a manner similar to Example 23. MS: m/z = 448.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.66 (t, J = 5.6 Hz, 1H), 9.39 (s, 2H), 8.30 (dd, J = 4.8, 1.2 Hz, 1H), 8.20 (dd, J = 8.0, 1.6 Hz, 1H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.51 (d, J = 8.8 Hz, 2H), 7.44 - 7.36 (m, 3H), 7.24 (dd, J = 7.6, 1.6 Hz, 1H), 6.92 (br s, 2H), 6.41 (dd, J = 8.0, 5.2 Hz, 1H), 4.63 (d, J = 5.6 Hz, 2H). [00646] Example 120: N-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2-cyanopyrimidine-5-carboxamide Example 120 was prepared in a manner similar to Example 23. MS: m/z = 524.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.67 (t, J = 5.6 Hz, 1H), 9.40 (s, 2H), 8.27 (d, J = 8.4 Hz, 1H), 8.05 – 8.02 (m, 1H), 8.01 – 7.96 (m, 3H), 7.56 - 7.52 (m, 2H), 7.51 - 7.48 (m, 2H), 7.45 - 7.43 (m, 2H), 7.42 - 7.37 (m, 1H), 7.23 (dd, J = 7.6, 2.0 Hz, 1H), 6.91 (br s, 2H), 6.42 (dd, J = 7.6, 4.8 Hz, 1H), 4.67 (d, J = 5.6 Hz, 2H). [00647] Example 121: N-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)-6-cyanonicotinamide Example 121 was prepared in a manner similar to Example 23. MS: m/z = 447.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.54 (t, J = 6.0 Hz, 1H), 9.19 (d, J = 1.6 Hz, 1H), 8.47 (dd, J = 8.0, 2.4 Hz, 1H), 8.30 (dd, J = 4.8, 1.6 Hz, 1H), 8.20 (d, J = 8.0 Hz, 2H), 7.99 (dd, J = 4.8, 2.0 Hz, 1H), 7.50 (d, J = 8.4 Hz, 2H), 7.43 - 7.36 (m, 3H), 7.24 (dd, J = 7.6, 1.6 Hz, 1H), 6.94 (br s, 2H), 6.41 (dd, J = 7.8, 4.8 Hz, 1H), 4.61 (d, J = 6.0 Hz, 2H). [00648] Example 122: N-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)-2-cyanoisonicotinamide Example 122 was prepared in a manner similar to Example 23 MS: m/z = 447.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.57 (t, J = 6.0 Hz, 1H), 8.92 (d, J = 5.2 Hz, 1H), 8.43 (s, 1H), 8.30 (d, J = 4.8 Hz, 1H), 8.19 (d, J = 8.0 Hz, 1H), 8.14 (d, J = 4.8 Hz, 1H), 8.95 (d, J = 4.4 Hz, 1H), 7.49 (d, J = 8.0 Hz, 1H), 7.44 - 7.35 (m, 3H), 7.24 (d, J = 7.6 Hz, 1H), 6.94 (br s, 2H), 6.41 (dd, J = 7.8, 4.8 Hz, 1H), 4.61 (d, J = 6.0 Hz, 2H). [00649] Example 123: N-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)-5-cyanonicotinamide Example 123 was prepared in a manner similar to Example 23. MS: m/z = 447.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.47 (t, J = 6.0 Hz, 1H), 9.29 (d, J = 2.0 Hz, 1H), 9.18 (d, J = 2.0 Hz, 1H), 8.74 (t, J = 2.0 Hz, 1H), 8.31 (dd, J = 4.8, 1.2 Hz, 1H), 8.20 (dd, J = 8.0, 1.2 Hz, 1H), 7.99 (dd, J = 4.8, 2.0 Hz, 1H), 7.49 (d, J = 8.4 Hz, 1H), 7.42 - 7.36 (m, 3H), 7.24 (dd, J = 8.0, 2.0 Hz, 1H), 6.94 (br s, 2H), 6.41 (dd, J = 8.0, 4.8 Hz, 1H), 4.61 (d, J = 6.0 Hz, 2H). [00650] Example 124: N-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)-5-cyanopicolinamide Example 124 was prepared in a manner similar to Example 23. MS: m/z = 447.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.69 (t, J = 6.4 Hz, 1H), 9.15 (d, J = 2.0 Hz, 1H), 8.52 (dd, J = 8.0, 2.0 Hz, 1H), 8.29 (dd, J = 4.8, 1.2 Hz, 1H), 8.20 -8.12 (m, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.46 (d, J = 8.4 Hz, 2H), 7.44 - 7.38 (m, 3H), 7.22 (dd, J = 7.6, 1.6 Hz, 1H), 6.96 (br s, 2H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 4.56 (d, J = 6.4 Hz, 2H). [00651] Example 125: N-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-5-cyanonicotinamide Example 125 was prepared in a manner similar to Example 23. MS: m/z = 523.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.46 (t, J = 5.6 Hz, 1H), 9.29 (d, J = 2.0 Hz, 1H), 9.18 (d, J = 2.4 Hz, 1H), 8.74 (t, J = 2.0 Hz, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.03 - 7.96 (m, 4H), 7.54 - 7.44 (m, 6H), 7.41 - 7.36 (m, 1H), 7.22 (dd, J = 7.6, 1.6 Hz, 1H), 6.92 (br s, 2H), 6.42 (dd, J = 7.6, 4.8 Hz, 1H), 4.64 (d, J = 5.6 Hz, 2H). [00652] Example 126: N-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-5-cyanopicolinamide Example 126 was prepared in a manner similar to Example 23. MS: m/z = 523.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ9.70 (t, J = 6.4 Hz, 1H), 9.15 (d, J = 1.2 Hz, 1H), 8.54 (dd, J = 8.4, 2.0 Hz, 1H), 8.28 - 8.16 (m, 2H), 8.03 - 7.96 (m, 4H), 7.49 - 7.37 (m, 7H), 7.20 (dd, J = 7.6, 1.6 Hz, 1H), 6.93 (br s, 2H), 6.41 (dd, J =7.6, 4.8 Hz, 1H), 4.62 (d, J = 6.4 Hz, 2H). [00653] Example 127: 4-((4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)amino)picolinonitrile To a solution of Intermediate 1 (150 mg, 474 µmol) and 4-fluoropyridine-2-carbonitrile (58 mg, 474 µmol) in DMSO (2 mL) was added DIEA (306 mg, 2.4 mmol). The mixture was stirred at 100 C for 16 hr. Then the mixture was purified by prep-HPLC (column: Waters xbridge 150 x 25 mm 10 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 18% - 48%, 8 min), 4-((4-(2-(2- aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)amin o)picolinonitrile (Example 127, 48.6 mg, yield: 24%) was obtained as a yellow solid. MS: m/z = 419.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.31 (dd, J = 4.8, 1.2 Hz, 1H), 8.20 (dd, J = 7.6, 1.2 Hz, 1H), 8.14 (d, J = 5.6 Hz, 1H), 7.99 (dd, J = 4.8, 2.0 Hz, 1H), 7.76 (t, J = 6.0 Hz, 1H), 7.48 (d, J = 8.4 Hz, 1H), 7.43 - 7.36 (m, 3H), 7.17 (dd, J = 7.6, 2.0 Hz, 1H), 7.12 (d, J = 2.0 Hz, 1H), 6.98 (br s, 2H), 6.79 (d, J = 3.6 Hz, 1H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 4.48 (d, J = 6.0 Hz, 2H). [00654] Example 128: 5-((4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)amino)picolinonitrile Example 128 was prepared in a manner similar to Example 127. MS: m/z = 419.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.31 (d, J = 3.6 Hz, 1H), 8.20 (d, J = 8.0 Hz, 1H), 8.12 (d, J = 2.8 Hz, 1H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.67 - 7.60 (m, 2H), 7.49 (d, J = 8.0 Hz, 1H), 7.43 - 7.36 (m, 3H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 - 6.95 (m, 3H), 6.37 (dd, J = 8.0, 4.8 Hz, 1H), 4.49 (d, J = 6.0 Hz, 2H). [00655] Example 129: 4-((4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)amino)picolinonitrile Example 129 was prepared in a manner similar to Example 127. MS: m/z = 495.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.14 (d, J = 5.6 Hz, 1H), 8.03 - 7.97 (m, 4H), 7.77 (t, J = 6.0 Hz, 1H), 7.53 - 7.44 (m, 6H), 7.42 - 7.37 (m, 1H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.12 (d, J = 2.0 Hz, 1H), 6.99 (br s, 2H), 6.85 - 6.79 (m, 1H), 6.37 (dd, J = 8.0, 5.2 Hz, 1H), 4.51 (d, J = 6.0 Hz, 2H). [00656] Example 130: 6-((4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)amino)picolinonitrile A mixture of Intermediate 1 (200 mg, 632 µmol), 6-fluoropyridine-2-carbonitrile (92.6 mg, 759 µmol), DIEA (163 mg, 1.26 mmol) in DMSO (1 mL) was stirred under microwave at 120 °C for 1 hr. The reaction mixture was filtered, the filter liquor was purified by prep-HPLC (column: Waters xbridge 150 x 25 mm 10 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 30% - 60%, 9 min), 6-((4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)amino)picolinonitrile (Example 130, 74.5 mg, yield: 28%) was obtained as a brown lyophilized powder. MS: m/z = 419.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.31 (dd, J = 4.8, 1.6 Hz, 1H), 8.22 - 8.16 (m, 1H), 7.98 (dd, J = 4.8, 2.0 Hz, 1H), 7.79 - 7.53(m, 1H), 7.56 (dd, J = 8.4, 7.2 Hz, 1H), 7.46 (d, J = 8.4 Hz, 2H), 7.35 - 7.41 (m, 3H), 7.20 (dd, J = 7.6, 2.0 Hz, 1H), 7.11 - 7.08 (m, 1H), 6.97 (br s, 2H), 6.86 (d, J = 8.4 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 4.55 (d, J = 6.0 Hz, 2H). [00657] Example 131: 5-((4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)amino)nicotinonitrile Example 131 was prepared in a manner similar to Example 130. MS: m/z = 419.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.36 - 8.30 (m, 2H), 8.19 (d, J = 8.0 Hz, 1H), 8.13 (s, 1H), 8.00 - 7.97 (m, 1H), 7.50 (d, J = 8.4 Hz,2H), 7.43 - 7.36 (m, 3H), 7.30 (s, 1H), 7.20 - 7.12 (m, 2H), 7.00 (br s, 2H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 4.44 (d, J = 6.0 Hz, 2H). [00658] Example 132: 2-((4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)amino)isonicotinonitrile Example 132 was prepared in a manner similar to Example 130. MS: m/z = 419.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.30 (d, J = 6.0 Hz,1H), 8.22 - 8.16 (m, 2H), 8.01 - 7.95 (m, 1H), 7.74 – 7.71 (m, 1H), 7.45 (d, J = 8.4 Hz,2H), 7.40 - 7.35 (m, 3H), 7.20 (d, J = 7.6 Hz,1H), 6.95 (br s, 2H), 6.90 (s, 1H), 6.83 (d, J = 5.2 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 4.59 (d, J = 6.0 Hz, 2H). [00659] Example 133: 6-((4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)amino)pyrazine-2-carbonitrile To a solution of Intermediate 1 (200 mg, 632 µmol) and 6-chloropyrazine-2-carbonitrile (88.2 mg, 632 µmol) in NMP (2 mL) was added DIEA (245 mg, 1.9 mmol). The mixture was stirred under microwave at 130 °C for 0.5 hr. The reaction mixture was filtered to give filter liquor. The filter liquor was purified by prep-HPLC (column: Waters Xbridge BEH C18100 x 30 mm x 10 µm; mobile phase: [water (ammonia hydroxide v/v) - ACN]; B%: 22% - 52%, 10 min), 6-((4- (2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzy l)amino)pyrazine-2-carbonitrile (Example 133, 15.6 mg, yield: 5.9%) was obtained as a yellow lyophilized powder. MS: m/z = 420.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.40 - 8.27 (m, 3H), 8.24 - 8.16 (m, 2H), 8.00 – 7.98 (m, 1H), 7.49 (d, J = 8.0 Hz, 2H), 7.43 - 7.37 (m, 3H), 7.25 - 7.17 (m, 1H), 6.97 (br s, 2H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 4.57 (d, J = 6.0 Hz, 2H). [00660] Example 134: 2-((4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)amino)pyrimidine-4-carbonitrile Example 134 was prepared in a manner similar to Example 133. MS: m/z = 420.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.59 (d, J = 4.8 Hz, 1H), 8.51 - 8.47 (m, 1H), 8.32 - 8.29 (m, 1H), 8.20 (dd, J = 8.0, 1.6 Hz, 1H), 7.98 (dd, J = 4.8, 2.0 Hz, 1H), 7.46 - 7.42 (m, 2H), 7.40 - 7.35 (m, 3H), 7.20 (dd, J = 7.6, 1.6 Hz, 1H), 7.15 (d, J = 4.8 Hz, 1H), 6.98 (br s, 2H), 6.38 (dd, J = 7.6, 5.2 Hz, 1H), 4.62- 4.53 (m, 2H). [00661] Example 135: 6-((4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)amino)pyrimidine-4-carbonitrile Example 135 was prepared in a manner similar to Example 133. MS: m/z = 420.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.70 - 8.60 (m, 1H), 8.54 (s, 1H), 8.30 (dd, J = 4.8, 1.2 Hz, 1H), 8.19 (dd, J = 8.0, 1.2 Hz, 1H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.45 (d, J = 8.0 Hz, 2H), 7.42 -7.36 (m, 3H), 7.25 - 7.18 (m, 1H), 7.08 (s, 1H), 6.93 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 4.66 (d, J = 4.8 Hz, 2H). [00662] Example 136: 6-((4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)amino)pyrimidine-4-carbonitrile Example 136 was prepared in a manner similar to Example 133. MS: m/z = 496.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.69 - 8.62 (m, 1H), 8.55 (s, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.03 - 7.96 (m, 4H), 7.49 - 7.43 (m, 6H), 7.42 - 7.37 (m, 1H), 7.23 - 7.18 (m, 1H), 7.09 (s, 1H), 6.95 (br s, 2H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 4.70 (d, J = 5.6 Hz, 2H). [00663] Example 137: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-6-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carbonyl)picolinonitrile Example 137 was prepared in a manner similar to Example 23. MS: m/z = 592.3 [M + H]+.1H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.84 (d, J = 4.8 Hz, 1H), 8.63 (d, J = 2.0 Hz, 1H), 8.46 (d, J = 2.0 Hz, 1H), 8.11 (s, 1H), 8.00 (dd, J = 4.8, 1.6 Hz, 1H), 7.81 - 7.72 (m, 3H), 7.55 - 7.47 (m, 4H), 7.45 - 7.40 (m, 3H), 7.19 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.72 - 3.64 (m, 2H), 3.62 (s, 2H), 3.31 – 3.27 (m, 2H), 2.54 – 2.51 (m, 2H), 2.43 – 2.37 (m, 2H). [00664] Example 138: 6-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carbonyl)picolinonitrile Example 138 was prepared in a manner similar to Example 32. MS: m/z = 592.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.22 – 8.17 (m, 1H), 8.13 (d, J = 7.6 Hz, 1H), 8.06 - 7.95 (m, 4H), 7.90 (d, J = 7.6 Hz, 1H), 7.54 - 7.42 (m, 6H), 7.42 - 7.35 (m, 1H), 7.15 (dd, J = 7.6, 2.0 Hz, 1H), 7.02 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.73 – 3.68 (m, 2H), 3.64 (s, 2H), 3.44 - 3.35 (m, 2H), 2.54 - 2.51 (m, 2H), 2.46 - 2.39 (m, 2H). [00665] Example 139 to 155 were prepared in a manner similar to Example 32. [00666] Example 139: 5-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carbonyl)nicotinonitrile MS: m/z = 592.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.10 (d, J = 2.0 Hz, 1H), 8.89 (d, J = 2.0 Hz, 1H), 8.43 – 8.40 (m, 1H), 8.27 (d, J = 8.0 Hz, 1H), 8.06 - 7.94 (m, 4H), 7.53 - 7.43 (m, 6H), 7.42 - 7.37 (m, 1H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.72 - 3.65 (m, 2H), 3.63 (s, 2H), 3.41 - 3.35 (m, 2H), 2.55 - 2.51 (m, 2H), 2.46 - 2.40 (m, 2H). [00667] Example 140: 2-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carbonyl)isonicotinonitri le MS: m/z = 592.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.76 (d, J = 4.8 Hz, 1H), 8.15 (d, J = 8.4 Hz, 1H), 8.02 - 7.99 (m, 3H), 7.95 (s, 1H), 7.82 (d, J = 8.4 Hz, 1H), 7.59 - 7.52 (m, 3H), 7.48 - 7.44 (m, 3H), 7.43 - 7.41 (m, 2H), 7.41 - 7.33 (m, 2H), 7.18 (dd, J = 7.6, 1.2Hz, 1H), 6.40 (dd, J = 8.0, 5.2 Hz, 1H), 3.96 - 3.87 (m, 2H), 3.73 - 3.69 (m, 4H), 2.72 - 2.68 (m, 2H), 2.62 - 2.58 (m, 2H). [00668] Example 141: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carbonyl)pyrimidine-2-car bonitrile MS: m/z = 593.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d)) δ 9.00 (d, J = 5.2 Hz, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.07 (br s, 1H), 8.01 (d, J = 7.2 Hz, 2H), 7.86 (d, J = 5.2 Hz, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.54 - 7.49 (m, 2H), 7.47 - 7.41 (m, 4H), 7.40 - 7.34 (m, 1H), 7.11 (d, J = 8.0 Hz, 1H), 6.70 (br s, 2H), 6.43 - 6.34 (m, 1H), 3.90 - 3.83 (m, 2H), 3.70 - 3.64 (m, 4H), 2.69 - 2.57 (m, 4H). [00669] Example 142: 6-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carbonyl)nicotinonitrile MS: m/z = 592.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.85 (s, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.08 (dd, J = 8.4, 2.0 Hz, 1H), 8.06 - 7.98 (m, 3H), 7.81 (d, J = 8.4 Hz, 2H), 7.52 (d, J = 8.4 Hz, 2H), 7.47 - 7.35 (m, 5H), 7.12 (dd, J = 7.6, 1.6 Hz, 1H), 6.82 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.88 (t, J = 4.4 Hz, 1H), 3.67 (s, 2H), 3.63 (t, J = 4.8 Hz, 2H), 2.66 (t, J = 4.4 Hz, 2H), 2.56 (t, J = 4.8 Hz, 2H). [00670] Example 143: 3-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carbonyl)picolinonitrile MS: m/z = 592.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.82 (d, J = 4.8 Hz, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.09 (dd, J = 8.0, 1.2 Hz, 1H), 8.05 - 7.95 (m, 4H), 7.83 (dd, J = 8.0, 4.8 Hz, 1H), 7.53 - 7.35 (m, 7H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.02 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.79 - 3.69 (m, 2H), 3.64 (s, 2H), 3.32 - 3.28 (m, 2H), 2.56 - 2.52 (m, 2H), 2.47 - 2.40 (m, 2H). [00671] Example 144: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carbonyl)nicotinonitrile MS: m/z = 592.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.14 (s, 1H), 8.94 (d, J = 4.8 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.04 - 8.00 (m, 2H), 8.00 - 7.96 (m, 2H), 7.65 (d, J = 5.2 Hz, 1H), 7.52 - 7.48 (m, 2H), 7.47 - 7.43 (m, 4H), 7.42 - 7.37 (m, 1H), 7.15 (dd, J = 7.6, 2.0 Hz, 1H), 7.01 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.76 - 3.69 (m, 2H), 3.64 (s, 2H), 3.28 - 3.25 (m, 2H), 2.54 - 2.52 (m, 2H), 2.45 - 2.41 (m, 2H). [00672] Example 145: 3-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carbonyl)isonicotinonitri le MS: m/z = 592.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.90 (d, J = 5.2 Hz, 1H), 8.86 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.06 - 7.94 (m, 5H), 7.54 - 7.36 (m, 7H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.78 - 3.68 (m, 2H), 3.64 (s, 2H), 3.38 - 3.35 (m, 2H), 2.56 - 2.52 (m, 2H), 2.47 - 2.40 (m, 2H). [00673] Example 146: 2-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carbonyl)nicotinonitrile MS: m/z = 592.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.86 (d, J = 4.8 Hz, 1H), 8.47 (dd, J = 8.0, 1.2 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.08 - 7.93 (m, 4H), 7.70 (dd, J = 8.0, 4.8 Hz, 1H), 7.53 - 7.42 (m, 6H), 7.42 - 7.36 (m, 1H), 7.14 (dd, J = 7.6, 1.6 Hz, 1H), 7.02 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.77 - 3.70 (m, 2H), 3.64 (s, 2H), 3.31 - 3.26 (m, 2H), 2.56 - 2.52 (m, 2H), 2.46 - 2.39 (m, 2H). [00674] Example 147: N-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)-4-cyanopicolinamide MS: m/z = 447.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.64 (t, J = 6.4 Hz, 1H), 8.93 (d, J = 5.2 Hz, 1H), 8.38 (s, 1H), 8.29 (dd, J = 4.8, 1.6 Hz, 1H), 8.19 (dd, J = 8.0, 1.2 Hz, 1H), 8.11 (dd, J = 4.8, 1.6 Hz, 1H), 7.98 (dd, J = 4.8, 2.0 Hz, 1H), 7.46 (d, J = 8.4 Hz, 2H), 7.39 - 7.36 (m, 3H), 7.22 (dd, J = 7.6, 2.0 Hz, 1H), 6.96 (br s, 2H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 4.59 (d, J = 6.4 Hz, 2H). [00675] Example 148: N-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)-2-cyanopyrimidine-4-carboxamide MS: m/z = 448.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d)) δ 9.13 (d, J = 5.2 Hz, 1H), 8.41 (dd, J = 4.8, 1.2 Hz, 1H), 8.37 (d, J = 5.2 Hz, 1H), 8.28 - 8.22 (m, 1H), 8.12 (dd, J = 8.0, 1.6 Hz, 1H), 8.02 (dd, J = 5.2, 1.6 Hz, 1H), 7.56 (d, J = 8.4 Hz, 2H), 7.41 (d, J = 8.4 Hz, 2H), 7.36 - 7.27 (m, 3H), 7.21 (dd, J = 7.6, 1.6 Hz, 1H), 6.45 (dd, J = 8.0, 5.2 Hz, 1H), 4.80 (d, J = 6.4 Hz, 2H). [00676] Example 149: 2-(4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazine-1-carbonyl)isonicotinonitrile MS: m/z = 516.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.76 (d, J = 4.8 Hz, 1H), 8.40 (dd, J = 4.8, 1.2 Hz, 1H), 8.10 (dd, J = 8.0, 1.2 Hz, 1H), 8.05 (dd, J = 4.8, 1.6 Hz, 1H), 7.94 (s, 1H), 7.57 (dd, J = 5.2, 1.6 Hz, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.36 - 7.30 (m, 3H), 7.07 (dd, J = 8.0, 1.6 Hz, 1H), 6.62 (br s, 2H), 6.33 (dd, J = 7.6, 4.8 Hz, 1H), 3.88 - 3.84 (m, 2H), 3.67 - 3.67 (m, 4H), 2.63 (t, J = 4.8 Hz, 2H), 2.55 - 2.49 (m, 2H). [00677] Example 150: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-4-cyanopicolinamide MS: m/z = 606.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.75 (d, J = 5.2 Hz, 1H), 8.41 (s, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.06 (dd, J = 4.8, 1.6 Hz, 1H), 8.01 (d, J = 7.6 Hz, 2H), 7.99 - 7.93 (m, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.70 - 7.60 (m, 3H), 7.55 - 7.41 (m, 5H), 7.40 - 7.35 (m, 1H), 7.09 (dd, J = 7.6, 1.6 Hz, 1H), 6.67 (br s, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 4.19 - 4.09 (m, 1H), 3.95 - 3.69 (m, 2H), 3.30 - 3.04 (m, 2H), 2.65 - 2.46 (m, 2H), 2.22 - 2.03 (m, 4H). [00678] Example 151: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-2-cyanopyrimidine-4-ca rboxamide MS: m/z = 607.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d)) δ 9.08 (d, J = 5.2 Hz, 1H), 8.32 (d, J = 5.2 Hz, 1H), 8.13 (d, J = 8.4 Hz, 1H), 8.11 - 8.04 (m, 1H), 8.02 (d, J = 7.6 Hz, 1H), 7.80 (d, J = 8.4 Hz, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.46 - 7.40 (m, 4H), 7.39 - 7.35 (m, 1H), 7.10 (d, J = 7.6 Hz, 1H), 6.61 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 4.12 - 3.96 (m, 1H), 3.65 (s, 2H), 2.95 (d, J = 11.6 Hz, 2H), 2.34 - 2.25 (m, 2H), 2.11 - 2.01 (m, 2H), 1.82 - 1.73 (m, 2H). [00679] Example 152: 4-(4-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazine-1-carbonyl)pyrimidine-2-carbonitrile MS: m/z = 517.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.15 (d, J = 5.2 Hz, 1H), 8.33 (dd, J = 4.8, 1.2 Hz, 1H), 8.20 (dd, J = 8.0, 1.2 Hz, 1H), 8.01 - 7.96 (m, 2H), 7.49 - 7.45 (m, 2H), 7.41 - 7.36 (m, 3H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.00 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.71 - 3.66 (m, 2H), 3.62 (s, 2H), 3.41 - 3.38 (m, 2H), 2.59 - 2.55 (m, 2H), 2.43 - 2.39 (m, 2H). [00680] Example 153: 3-(4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazine-1-carbonyl)picolinonitrile MS: m/z = 516.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.82 (dd, J = 4.8, 1.6 Hz, 1H), 8.31 (dd, J = 4.8, 1.6 Hz, 1H), 8.20 (dd, J = 8.0, 1.2 Hz, 1H), 8.09 (dd, J = 8.0, 1.6 Hz, 1H), 7.98 (dd, J = 4.8, 2.0 Hz, 1H), 7.83 (dd, J = 8.0, 4.8 Hz, 1H), 7.47 (d, J = 8.4 Hz, 2H), 7.41 - 7.36 (m, 3H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 6.99 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.78 – 3.71 (m, 2H), 3.61 (s, 2H), 3.32 – 3.28 (m, 2H), 2.56 - 2.51 (m, 2H), 2.45 – 2.45 (m, 2H). [00681] Example 154: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazine-1-carbonyl)nicotinonitrile MS: m/z = 516.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.14 (s, 1H), 8.93 (d, J = 4.8 Hz, 1H), 8.31 (dd, J = 4.8, 3.6 Hz, 1H), 8.20 (dd, J = 8.0, 1.2 Hz, 1H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.65 (d, J = 4.8 Hz, 1H), 7.47 (d, J = 8.4 Hz, 2H), 7.41 - 7.37 (m, 3H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 6.99 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.73 – 3.68 (m, 2H), 3.61 (s, 2H), 3.27 - 3.25 (m, 2H), 2.54 - 2.52 (m, 2H), 2.42 – 2.39 (m, 2H). [00682] Example 155: 3-(4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazine-1-carbonyl)isonicotinonitrile MS: m/z = 516.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.90 (d, J = 4.8 Hz, 1H), 8.86 (s, 1H), 8.31 (dd, J = 4.8, 1.2 Hz, 1H), 8.20 (dd, J = 8.0, 1.6 Hz, 1H), 8.01 - 7.96 (m, 2H), 7.47 (d, J = 8.0 Hz, 2H), 7.47 -7.35 (m, 3H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 6.99 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.76 - 3.70 (m, 2H), 3.61 (s, 2H), 3.33 - 3.29 (m, 2H), 2.55 - 2.51 (m, 2H), 2.45 - 2.39 (m, 2H). [00683] Example 156: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)(methyl)amino)pyrimidin e-2-carbonitrile To a solution of Intermediate 36 (130 mg, 266 µmol) in DMF (2 mL) was added 4- chloropyrimidine-2-carbonitrile (44 mg, 319 µmol), NaI (3.98 mg, 27 µmol) and K ₂ CO ₃ (110 mg, 797 µmol). The mixture was stirred at 80 °C for 2 hr. The reaction mixture was poured into H ₂ O (10 mL), extracted with EtOAc (15 mL). The organic phase was dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (Eluent of 0~63% EtOAc in petroleum ether), 4-((1- (4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridi n-3-yl)benzyl)piperidin-4- yl)(methyl)amino)pyrimidine-2-carbonitrile (Example 156, 59.4 mg, yield: 37%) was obtained as a yellow solid. MS: m/z = 593.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.18 - 8.16 (m, 2H), 8.02 - 8.00 (m, 2H), 7.97 (dd, J = 5.2, 2.0 Hz, 1H), 7.93 (d, J = 8.8 Hz, 1H), 7.56 (d, J = 8.4 Hz, 2H) , 7.48 - 7.30 (m, 6H), 6.89 - 6.76 (m, 1H), 6.47 (dd, J = 7.6, 5.2 Hz, 1H), 3.75 (s, 2H), 3.35 - 3.31 (m, 1H), 3.14 - 3.11 (m, 2H), 2.98 (s, 3H), 2.39 - 2.33 (m, 2H), 1.98 - 1.87 (m, 2H), 1.72 - 1.69 (m, 2H). [00684] Example 157: 5-((1-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3 - yl)benzyl)piperidin-4-yl)amino)picolinonitrile Intermediate 157 was prepared in a manner similar to Intermediate 84. MS: m/z = 502.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.34 (dd, J = 4.8, 1.2 Hz, 1H), 8.21 (dd, J = 8.0, 1.2 Hz, 1H), 8.06 (d, J = 2.8 Hz, 1H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.61 (d, J = 8.8 Hz, 1H), 7.46 (d, J = 8.4 Hz, 2H), 7.42 - 7.37 (m, 3H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 - 6.96 (m, 3H), 6.91 (d, J = 7.6 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.58 (s, 2H), 2.90 - 2.75 (m, 3H), 2.21 - 2.12 (m, 2H), 1.96 - 1.87 (m, 2H), 1.50 - 1.40 (m, 2H). [00685] Example 158: 5-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyridazine-3-carb onitrile Example 158 was prepared in a manner similar to Example 47. MS: m/z = 579.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.71 (br s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.06 - 7.95 (m, 4H), 7.67 - 7.57 (m, 1H), 7.53 - 7.43 (m, 6H), 7.41 - 7.37 (m, 1H), 7.37 - 7.29 (m, 1H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.60 (s, 2H), 3.51 - 3.37 (m, 1H), 2.83 (d, J = 11.6 Hz, 2H), 2.22 - 2.12 (m, 2H), 1.95 - 1.85 (m, 2H), 1.52 - 1.40 (m, 2H). [00686] Example 159: 5-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)pyridazine-3-carbonitri le Example 159 was prepared in a manner similar to Example 47. MS: m/z = 565.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.15 (d, J = 3.2 Hz, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.06 - 8.02 (m, 2H), 8.01 -7.97 (m, 2H), 7.65 (d, J = 3.2 Hz, 1H), 7.54 - 7.50 (m, 2H), 7.49 - 7.43 (m, 4H), 7.42 - 7.36 (m, 1H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.65 (s, 2H), 3.61 - 3.53 (m, 4H), 2.56 - 2.50 (m, 4H). [00687] Example 160 to 165 were prepared in a manner similar to Example 23. [00688] Example 160: N-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-6-cyanonicotinamide MS: m/z = 523.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.56 (t, J = 5.6 Hz, 1H), 9.20 (d, J = 1.6 Hz, 1H), 8.48 (dd, J = 2.4, 8.0 Hz, 1H), 8.26 (d, J = 8.0 Hz, 1H), 8.20 (d, J = 8.0 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.54 - 7.50 (m, 2H), 7.49 - 7.47 (m, 2H), 7.47 - 7.44 (m, 2H), 7.42 - 7.37 (m, 1H), 7.22 (dd, J = 1.6, 7.6 Hz, 1H), 6.92 (br s, 2H), 6.42 (dd, J = 7.6, 4.8 Hz, 1H), 4.65 (d, J = 5.6 Hz, 2H). [00689] Example 161: N-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2-cyanoisonicotinamide MS: m/z = 523.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.59 (t, J = 5.6 Hz, 1H), 8.93 (d, J = 4.8 Hz, 1H), 8.45 (s, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.15 (dd, J = 5.2, 1.6 Hz, 1H), 8.09 - 7.95 (m, 4H), 7.57 - 7.43 (m, 6H), 7.42 - 7.36 (m, 1H), 7.22 (dd, J = 7.6, 2.0 Hz, 1H), 6.92 (br s, 2H), 6.42 (dd, J = 7.6, 4.8 Hz, 1H), 4.65 (d, J = 5.6 Hz, 2H). [00690] Example 162: N-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-6-cyanopicolinamide MS: m/z = 523.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.62 (t, J = 6.4 Hz, 1H), 8.36 -8.32 (m, 1H), 8.28 - 8.23 (m, 3H), 8.04 - 7.95 (m, 4H), 7.52 - 7.43 (m, 6H), 7.41 - 7.35 (m, 1H), 7.21 (dd, J = 7.6, 1.6 Hz, 1H), 6.93 (br s, 2H), 6.42 (dd, J = 7.6, 4.8 Hz, 1H), 4.62 (d, J = 6.4 Hz, 2H). [00691] Example 163: 3-(4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carbonyl)pyrazine-2-carbo nitrile MS: m/z = 593.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.96 (dd, J = 11.2, 2.4 Hz, 2H), 8.27 (d, J = 8.4 Hz, 1H), 8.06-7.95 (m, 4H), 7.54-7.43 (m, 6H), 7.42-7.37 (m, 1H), 7.18-7.11 (m, 1H), 7.02 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.79 – 3.73 (m, 2H), 3.65 (s, 2H), 3.45 - 3.39 (m, 2H), 2.58 – 2.52 (m, 2H), 2.45 - 2.42 (m, 2H). [00692] Example 164: 3-(4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazine-1-carbonyl)pyrazine-2-carbonitrile MS: m/z = 517.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.90 - 8.82 (m, 2H), 8.34 (d, J = 4.8 Hz, 1H), 8.20 (dd, J = 8.0, 1.2 Hz, 1H), 7.97 (dd, J = 5.2, 1.6 Hz, 1H), 7.56 (d, J = 8.4 Hz, 2H), 7.47 - 7.37 (m, 3H), 7.33 (dd, J = 7.6, 1.6 Hz, 1H), 6.47 (dd, J = 7.6, 5.2 Hz, 1H), 3.93 - 3.85 (m, 2H), 3.72 (s, 2H), 3.51 - 3.44 (m, 2H), 2.69 (t, J = 4.8 Hz, 2H), 2.62 - 2.54 (m, 2H). [00693] Example 165: N-(1-(4-(2-(2-aminopyridin-3-yl)-6-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-6-cyanonicotinamide MS: m/z = 606.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.11 (d, J =1.6 Hz, 1H), 8.72 (d, J =7.6 Hz, 1H), 8.64 (d, J = 2.0 Hz, 1H), 8.47 (d, J = 2.0 Hz, 1H), 8.41 - 8.38 (m, 1H), 8.17 (d, J = 8.0 Hz, 1H),8.00 (dd, J = 4.8, 1.6 Hz, 1H), 7.78 (d, J = 7.2 Hz, 2H), 7.54 - 7.47 (m, 4H), 7.43 - 7.40 (m, 3H), 7.2 (dd, J = 8, 1.6 Hz, 1H), 7.07 (br s, 2H), 6.39 (dd, J = 8, 4.8 Hz, 1H), 3.85 - 3.78 (m, 1H), 3.58 (s, 2H), 2.87 (d, J = 11.2 Hz, 2H), 2.1 (t, J = 11.2 Hz, 2H), 1.85 (d, J = 10.0 Hz, 2H), 1.65 - 1.57 (m, 2H). [00694] Example 166: 5-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carbonyl)picolinonitrile Example 166 was prepared in a manner similar to Example 32. MS: m/z = 592.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.76 (s, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.08 - 7.98 (m, 3H), 7.91 (dd, J = 7.6, 2.0 Hz, 1H), 7.83 - 7.75 (m, 2H), 7.51 - 7.36 (m, 7H), 7.11 (d, J = 7.6 Hz, 1H), 6.94 - 6.64 (m, 2H), 6.40-6.33 (m, 1H), 3.93 - 3.79 (m, 2H), 3.66 (s, 2H), 3.48 - 3.39 (m, 2H), 2.67 - 2.58 (m, 2H), 2.55 - 2.46 (m, 2H). [00695] Example 167: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-6-cyanonicotinamide Example 167 was prepared in a manner similar to Example 32. MS: m/z = 606.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide -d ₆ ) δ 9.11 (s, 1H), 8.71 (d, J = 7.6 Hz, 1H), 8.40 (dd, J = 8.0, 2.0 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.17 (d, J = 8.0 Hz, 1H), 8.08 - 7.96 (m, 4H), 7.51 - 7.37 (m, 7H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.88 - 3.76 (m, 1H), 3.59 (s, 2H), 2.92 - 2.83 (m, 2H), 2.18 - 2.06 (m, 2H), 1.85 (d, J = 10.8 Hz, 2H), 1.67 - 1.56 (m, 2H). [00696] Example 168: N-(4-(2-(2-Aminopyridin-3-yl)-6-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-6-cyanopicolinamide Example 168 was prepared in a manner similar to Example 32. MS: m/z = 523.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide -d ₆ ) δ 9.61 (t, J = 6.4 Hz, 1H), 8.60 (s, 1H), 8.46 (s, 1H), 8.36 - 8.23 (m, 3H), 8.04 - 7.98 (m, 1H), 7.77 (d, J = 7.6 Hz, 2H), 7.55 - 7.40 (m, 7H), 7.29 - 7.23 (m, 1H), 7.01 (s, 2H), 6.45 - 6.41 (m, 1H), 4.59 (d, J = 6.4 Hz, 2H). [00697] Example 169: N-(4-(2-(2-Aminopyridin-3-yl)-6-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2-cyanoisonicotinamide Example 169 was prepared in a manner similar to Example 32. MS: m/z = 523.10 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide -d ₆ ) δ 9.58 (t, J = 5.6 Hz, 1H), 8.93 (d, J = 5.2 Hz, 1H), 8.61 (s, 1H), 8.48 - 8.43 (m, 2H), 8.15 (d, J = 5.2 Hz, 1H), 8.04 - 7.97 (m, 1H), 7.78 (d, J = 7.2 Hz, 2H), 7.55 - 7.50 (m, 4H), 7.47 - 7.40 (m, 3H), 7.28 (dd, J = 7.6, 2.0 Hz, 1H), 6.99 (br s, 2H), 6.43 (dd, J = 7.6, 4.8 Hz, 1H), 4.62 (d, J = 5.6 Hz, 2H). [00698] Example 170: N-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-4-cyanopicolinamide Example 170 was prepared in a manner similar to Example 32. MS: m/z = 523.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.65 (t, J = 6.4 Hz, 1H), 8.93 (d, J = 4.8 Hz, 1H), 8.39 (s, 1H), 8.26 (d, J = 8.0 Hz, 1H), 8.11 (dd, J = 5.2, 1.6 Hz, 1H), 8.04 - 7.96 (m, 4H), 7.50 - 7.43 (m, 6H), 7.41 - 7.37 (m, 1H), 7.21 (dd, J = 7.6, 2.0 Hz, 1H), 6.93 (br s, 2H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 4.63 (d, J = 6.4 Hz, 2H). [00699] Example 171: N-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2-cyanopyrimidine-4-carboxamide Example 171 was prepared in a manner similar to Example 32. MS: m/z = 524.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ )) δ 9.88 (t, J = 6.4 Hz, 1H), 9.25 (d, J = 5.2 Hz, 1H), 8.32 (d, J = 5.2 Hz, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.03 - 7.96 (m, 4H), 7.52 - 7.44 (m, 6H), 7.41 - 7.36 (m, 1H), 7.21 (dd, J = 7.6, 2.0 Hz, 1H), 6.91 (br s, 2H), 6.42 (dd, J = 7.6, 4.8 Hz, 1H), 4.62 (d, J = 6.4 Hz, 2H). [00700] Example 172: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carbonyl)picolinonitrile Example 172 was prepared in a manner similar to Example 32. MS: m/z = 592.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.84 (d, J = 4.8 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.12 (s, 1H), 8.06 - 7.96 (m, 4H), 7.78 - 7.73 (m, 1H), 7.52 - 7.43 (m, 6H), 7.43 - 7.35 (m, 1H), 7.18 - 7.13 (m, 1H), 7.02 (br s, 2H), 6.43 - 6.36 (m, 1H), 3.71 - 3.60 (m, 4H), 3.32 - 3.27 (m, 2H), 2.44 - 2.38 (m, 4H). [00701] Example 173: N-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)-2-cyano-5-fluorobenzo[d]thiazole-7-carboxamide Step 1: N ⁷ -(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin- 3-yl)benzyl)-5- fluorobenzo[d]thiazole-2,7-dicarboxamide A mixture of Intermediate 1 (300 mg, 948 µmol), Intermediate 26 (227.8 mg, 948 µmol), HATU (540.9 mg, 1.42 mmol), DIEA (613 mg, 4.74 mmol) in DMF (2 mL) was stirred at 25 °C for 16 hr. This reaction was filtered and concentrated to give the residue. The residue was purified by prep-HPLC (column: Welch Xtimate C18150 x 25 mm x 5 µm; mobile phase: [water (NH ₃ H ₂ O) - ACN]; B%: 15% - 45%, 8 min), N ⁷ -(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-5-fluorobenzo[d]thiazole-2,7-dicarbox amide (39.5 mg, yield: 12%) was obtained as a light-yellow soild. MS: m/z = 539.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.65 (t, J = 5.6 Hz, 1H), 8.47 (s, 1H), 8.32 - 8.26 (m, 2H), 8.21 - 8.15 (m, 2H), 8.09 (s, 1H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.51 (d, J = 8.0 Hz, 2H), 7.44 - 7.36 (m, 3H), 7.24 (dd, J = 7.6, 1.6 Hz, 1H), 6.95 (br s, 2H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 4.67 (d, J = 5.6 Hz, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 114.4. Step 2: N-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl) benzyl)-2-cyano-5- fluorobenzo[d]thiazole-7-carboxamide To a solution of N ⁷ -(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin- 3-yl)benzyl)-5- fluorobenzo[d]thiazole-2,7-dicarboxamide (20 mg, 37.1 µmol) in pyridine (2 mL), then POCl ₃ (142 mg, 928 µmol) was added dropwise over 5 min, the mixture was stirred at 20 °C for 2 hr. The reaction mixture was filtered to give filter liquor. The residue was purified by prep-HPLC (column: Welch Xtimate C18150 x 25 mm x 5 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 31% - 61%, 2 min), N-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl) benzyl)- 2-cyano-5-fluorobenzo[d]thiazole-7-carboxamide (Example 173, 9.2 mg, yield: 47%) was obtained as a white lyophilized powder. MS: m/z = 521.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.83 (t, J = 5.2 Hz, 1H), 8.51 - 8.41 (m, 2H), 8.30 (d, J = 4.8 Hz, 1H), 8.19 (d, J = 8.0 Hz, 1H), 8.02 - 7.96 (m, 1H), 7.51 (d, J = 8.0 Hz, 2H), 7.43 - 7.35 (m, 3H), 7.24 (d, J = 7.6 Hz, 1H), 6.93 (br s, 2H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 4.68 (d, J = 5.2 Hz, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ - 112.9. [00702] Example 174 to 185 were prepared in a manner similar to Example 173. [00703] Example 174: N-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)-2-cyano-6-fluorobenzo[d]thiazole-4-carboxamide MS: m/z = 521.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.32 (dd, J = 4.8, 1.6 Hz, 1H), 8.21 - 8.13 (m, 3H), 7.97 (dd, J = 5.2, 2.0 Hz, 1H), 7.63 (d, J = 8.4 Hz, 2H), 7.44 - 7.40 (m, 3H), 7.36 - 7.33 (m, 1H), 6.48 (dd, J = 8.0, 5.2 Hz, 1H), 4.58 (s, 2H). ¹⁹ F NMR (400 MHz, Methanol-d ₄ ) δ - 111.1. [00704] Example 175: 7-(4-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazine-1-carbonyl)-5-fluorobenzo[d]thiazole-2- carbonitrile MS: m/z = 590.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.34 (dd, J = 4.8, 1.2 Hz, 1H), 8.20 (dd, J = 8.0, 5.2 Hz, 1H), 8.14 - 8.09 (m, 1H), 7.97 (dd, J = 4.8, 1.6 Hz, 1H), 7.72 (dd, J = 8.8, 2.4 Hz, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.45 -7.41 (m, 1H), 7.40 -7.38 (m, 2H), 7.32 (dd, J = 7.6, 2.0 Hz, 1H), 6.46 (dd, J = 7.6, 4.8 Hz, 1H), 3.81 - 3.70 (m, 4H), 3.68 (s, 2H), 2.60 – 2.52 (m, 4H). ¹⁹ F NMR (400 MHz, Methanol-d ₄ ) δ - 113.8. [00705] Example 176: N-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2-cyano-5-fluorobenzo[d]thiazole-7-ca rboxamide MS: m/z = 597.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.21 - 8.15 (m, 3H), 8.03 - 8.00 (m, 2H), 7.97 (dd, J = 4.8, 1.6 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.59 (d, J = 8.4 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.43 - 7.37 (m, 3H), 7.36 - 7.32 (m, 2H), 6.48 (dd, J = 7.6, 5.2 Hz, 1H), 4.77 (s, 2H). ¹⁹ F NMR (400 MHz, Methanol-d ₄ ) δ - 114.4. [00706] Example 177: N-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2-cyano-6-fluorobenzo[d]thiazole-4-ca rboxamide MS: m/z = 597.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 9.60 - 9.55 (m, 1H), 8.46 - 8.42 (m, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.07 - 7.94 (m, 6H), 7.59 - 7.57 (m, 2H), 7.50 - 7.43 (m, 4H), 7.41 - 7.36 (m, 1H), 7.24 - 7.21 (m, 1H), 6.93 (br s, 2H), 6.46 - 6.40 (m, 1H), 4.77 (d, J = 5.6 Hz, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ - 109.8. [00707] Example 178: N-(4-(5-(3-Acetamidophenyl)-2-(2-aminopyridin-3-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2-cyano-5-fluorobenzo[d]t hiazole-7-carboxamide MS: m/z = 654.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.23 - 8.16 (m, 4H), 7.98 (dd, J = 5.2, 1.6 Hz, 1H), 7.91 (d, J = 8.4 Hz, 1H), 7.76 - 7.74 (m, 1H), 7.62 - 7.57 (m, 3H), 7.48 (d, J = 8.4 Hz, 2H), 7.38 - 7.33 (m, 2H), 6.48 (dd, J = 7.6, 4.8 Hz, 1H), 4.77 (s, 2H), 2.11 (s, 3H). [00708] Example 179: N-(4-(5-(3-acetamidophenyl)-2-(2-aminopyridin-3-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2-cyano-6-fluorobenzo[d]t hiazole-4-carboxamide MS: m/z = 654.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.21 - 8,13 (m, 4H), 7.98 - 7.90 (m, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.77 - 7.74 (m, 1H),7.67 - 7.61 (m, 3H), 7.48 (d, J = 8.4 Hz, 2H), 7.39 - 7.32 (m, 2H), 6.51 (dd, J = 7.6, 4.8 Hz, 1H), 4.79 (s, 2H), 2.12 (s, 3H). ¹⁹ F NMR (400 MHz, Methanol-d ₄ ) δ - 111.1. [00709] Example 180: 7-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carbonyl)-5-fluorobenzo[d ]thiazole-2-carbonitrile MS: m/z = 666.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.34 (dd, J = 8.8, 2.4 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.04 - 7.96 (m, 4H), 7.85 (dd, J = 9.2, 2.0 Hz, 1H), 7.53 - 7.49 (m, 2H), 7.49 - 7.43 (m, 4H), 7.42 - 7.36 (m, 1H), 7.16 (dd, J = 7.6, 1.8 Hz, 1H), 7.01 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.75 - 3.59 (m, 6H), 3.44 - 3.40 (m, 4H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ - 112.4. [00710] Example 181: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carbonyl)-6-fluorobenzo[d ]thiazole-2-carbonitrile MS: m/z = 666.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.19 (d, J = 8.4 Hz, 1H), 8.06 (dd, J = 8.0, 2.4 Hz, 1H), 8.04 - 8.00 (m, 2H), 7.97 - 7.91 (m, 2H), 7.58 - 7.52 (m, 3H), 7.47 - 7.33 (m, 5H), 7.32 (dd, J = 7.6, 2.0 Hz, 1H), 6.46 (dd, J = 7.6, 4.8 Hz, 1H), 4.60 (s, 2H), 3.99 - 3.84 (m, 2H), 3.70 (s, 2H), 2.73 - 2.65 (m, 2H), 2.53 - 2.43 (m, 2H). ¹⁹ F NMR (400 MHz, Methanol-d ₄ ) δ - 111.0. [00711] Example 182: N-(1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-2-cyano-5-fluorobenzo[ d]thiazole-7-carboxamide MS: m/z = 680.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.01 (d, J = 6.8 Hz, 1H), 8.41 (d, J = 7.2 Hz, 1H), 8.27 (d, J = 8.0 Hz, 1H), 8.07 - 7.90 (m, 6H), 7.54 - 7.43 (m, 5H), 7.39 (d, J = 7.2 Hz, 1H), 7.17 (d, J = 6.4 Hz, 1H), 7.00 (br s, 2H), 6.44 - 6.34 (m, 1H), 4.06 - 3.94 (m, 2H), 3.64 - 3.62 (m, 1H), 2.96 - 2.77 (m, 4H), 2.03 - 1.92 (m, 2H), 1.79 - 1.60 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 109.8. [00712] Example 183: N-(1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-2-cyano-6-fluorobenzo[ d]thiazole-4-carboxamide MS: m/z = 680.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide- d ₆ ) δ 8.97 (d, J = 7.6 Hz, 1H), 8.46 (dd, J = 9.6, 1.6 Hz, 1H), 8.39 - 8.33 (m, 1H), 8.25 (d, J = 8.4 Hz, 1H), 8.04 - 7.95 (m, 4H), 7.52 - 7.48 (m, 2H), 7.48 - 7.43 (m, 4H), 7.41 - 7.36 (m, 1H), 7.18 - 7.12 (m, 1H), 7.03 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.94 - 3.82 (m, 1H), 3.61 (s, 2H), 2.96 - 2.85 (m, 2H), 2.19 - 2.08 (m, 2H), 1.93 - 1.83 (m, 2H), 1.74 - 1.61 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ - 113.04. [00713] Example 184: 5-(4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carbonyl)benzo[d]thiazole -2-carbonitrile MS: m/z = 648.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Chlorform-d) δ 8.26 (s, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.07 - 8.03 (m, 2H), 8.00 (d, J = 7.2 Hz, 2H), 7.81 (d, J = 8.4 Hz, 1H), 7.72 (dd, J = 8.4, 1.2 Hz, 1H), 7.51 (d, J = 8.0 Hz, 2H), 7.46 - 7.40 (m, 4H), 7.38 (d, J = 7.2 Hz, 1H), 7.13 - 7.09 (m, 1H), 6.83 (br s, 2H), 6.36 (dd, J = 7.6, 5.2 Hz, 1H), 4.00 - 3.82 (m, 2H), 3.67 (s, 2H), 3.60 - 3.43 (m, 2H), 2.69 - 2.47 (m, 4H). [00714] Example 185: N-(1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-2-cyanobenzo[d]thiazol e-5-carboxamide

MS: m/z = 662.5 [M + H] ⁺ . ¹ H NMR (400 MHz, Chlorform-d) δ 8.55 (s, 1H), 8.14 (d, J= 8.4 Hz, 1H), 8.10 - 8.05 (m, 3H), 8.02 (d, J= 7.2 Hz, 2H), 7.81 (d, J= 8.4 Hz, 1H), 7.57 - 7.51 (m, 2H), 7.47 - 7.35 (m, 5H), 7.10 (dd, J= 7.6, 1.6 Hz, 1H), 6.61 (br s, 2H), 6.37 (dd, J= 7.6, 4.8 Hz, 1H), 6.28 - 6.13 (m, 1H), 4.19 - 4.08 (m, 1H), 3.71 (s, 2H), 3.10 - 2.95 (m, 2H), 2.42 - 2.31 (m, 2H), 2.17 - 2.11 (m, 2H), 1.83 - 1.74 (m, 2H).

[00715] Example 186: 6-((4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)amino)picolinonitrile

To a solution of Intermediate 4 (100 mg, 255 μmol) and 6-fluoropyridine-2-carbonitrile (34.2 mg, 280 μmol) in NMP (2 mL) was added DIEA (164 mg, 1.27 mmol). The mixture was stirred under microwave at 135 °C for 1 hr. The reaction was filtered and concentrated under reduced pressure to give a residue. The crude product was purified by prep-HPLC (column: Phenomenex C18 150*25 mm*10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 47% - 77%, 8 min), 6-((4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyr idin-3- yl)benzyl)amino)picolinonitrile (Example 186, 53 mg, yield: 42%) was obtained as a lightyellow solid. MS: m/z = 495.1 [M + H] ⁺ . ^X H NMR (400 MHz, Dimethylsulfoxi de-d ₆ ) δ 8.27 (d, J= 8 Hz, 1H), 8.04 - 7.98 (m, 4H), 7.79 (t, J= 6.0 Hz, 1H), 7.58 (dd, J= 8.8, 7.2 Hz, 1H), 7.52 - 7.45 (m, 6H), 7.41 - 7.38 (m, 1H), 7.2 (dd, J= 7.6, 1.6 Hz, 1H), 7.12 (d, J= 6.4 Hz, 1H), 6.99 (br s, 2H), 6.88 (d, J= 8.4 Hz, 1H), 6.40 (dd, J= 7.6, 4.8 Hz, 1H), 4.6 (d, J =6.0 Hz, 2H).

[00716] Example 187: 5-((4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)amino)picolinonitrile

To a solution of Intermediate 4 (150 mg, 382 μmol) and 5-fluoropyridine-2-carbonitrile (51.3 mg, 420 μmol) in DMSO (3 mL) was added DIEA (247 mg, 1.91 mmol). The mixture was stirred at 100 °C for 12 hr. The reaction was filtered and concentrated under reduced pressure to give a residue. The crude product was purified by prep-HPLC (column: Waters xbridge 150*25 mm 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 36% - 66%, 8 min), 5-((4-(2-(2- aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)be nzyl)amino)picolinonitrile (Example 187, 22 mg, yield: 11.6%) was obtained as a light-yellow solid. MS: m/z = 495.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.26 (d, J= 8.4 Hz, 1H), 8.14 (d, J= 2.4 Hz, 1H), 8.02 - 7.97 (m, 4H), 7.67 - 7.61 (m, 2H), 7.54 - 7.39 (m, 7H), 7.16 (dd, J= 7.6, 2 Hz, 1H), 7.02 - 7.01 (m, 1H), 6.8 (br s, 2H), 6.37 (dd, J= 7.6, 4.8 Hz, 1H), 4.51 (d, J= 6.0 Hz, 2H). [00717] Example 188: 5-((4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)amino)nicotinonitrile

To a solution of Intermediate 4 (150 mg, 382 μmol) and 5-fluoropyridine-3-carbonitrile (56.0 mg, 459 μmol) in DMSO (3 mL) was added DIEA (247 mg, 1.91 mmol). The mixture was stirred at 100 °C for 12 hr. The reaction was filtered and concentrated under reduced pressure to give a residue. The crude product was purified by prep-HPLC (column: Phenomenex C18 150*25 mm* 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 41% - 71%, 8 min), 5-((4- (2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3 -yl)benzyl)amino)nicotinonitrile (Example 188, 7.0 mg, yield: 3.7%) was obtained as a yellow solid. MS: m/z = 495.5 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfbxide-d ₆ ) δ 8.31 (d, J= 2.8 Hz, 1H), 8.26 (d, J= 8.4 Hz, 1H), 8.14 (d, J= 2.0 Hz, 1H), 8.03 - 7.97 (m, 4H), 7.54 (d, J= 8.4 Hz, 2H), 7.49 - 7.37 (m, 5H), 7.32 - 7.24 (m, 1H), 7.19 - 7.14 (m, 2H), 7.01 (br s, 2H), 6.36 (dd, J= 7.6, 4.8 Hz, 1H), 4.47 (d, J =6.0 Hz, 1H). [00718] Example 189: 2-((4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)amino)isonicotinonitrile Example 189 was prepared in a manner similar to Example 186. MS: m/z = 495.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.26 (d, J = 8.4 Hz, 1H), 8.19 (d, J = 5.2 Hz, 1H), 8.03 - 7.97 (m, 4H), 7.75 - 7.73 (m, 1H), 7.50 - 7.42 (m, 6H), 7.41 - 7.39 (m, 1H), 7.19 (dd, J = 7.6, 1.6 Hz, 1H), 6.97 (br s, 2H), 6.91 (s, 1H), 6.84 (dd, J = 5.2, 1.2 Hz, 1H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 4.63 (d, J =5.6 Hz, 2H). [00719] Example 190: 6-((4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)amino)pyrazine-2-carbonitrile Example 190 was prepared in a manner similar to Example 186. MS: m/z = 496.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.37 (t, J =6.0 Hz, 1H), 8.29 - 8.22 (m, 3H), 8.03 - 7.97 (m, 4H), 7.53 - 7.51 (m, 2H), 7.49 - 7.44 (m, 4H), 7.41 - 7.37 (m, 1H), 7.20 (dd, J = 7.6, 1.6 Hz, 1H), 6.96 (br s, 2H), 6.4 (dd, J = 7.6, 4.8 Hz, 1H), 4.60 (d, J =6.0 Hz, 2H). [00720] Example 191: 2-((4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)amino)pyrimidine-4-carbonitrile Example 191 was prepared in a manner similar to Example 186. MS: m/z = 496.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.60 (d, J =4.4 Hz, 1H), 8.51 - 8.48 (m, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.03 - 7.97 (m, 4H), 7.48 - 7.44 (m, 6H), 7.41 - 7.37 (m, 1H), 7.19 - 7.17 (m, 1H), 7.15 (d, J = 4.8 Hz, 1H), 6.97 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 4.66 – 4.58 (br s, 2H). [00721] Example 192: 4-((2S,6S)-4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,6-dimethylpiperazin-1-y l)pyrimidine-2-carbonitrile Intermediate 28 (100 mg, 204 µmol), 4-chloropyrimidine-2-carbonitrile (28.5 mg, 204 µmol) and DIEA (106 mg, 817 µmol) were taken up into a microwave tube in NMP (2 mL). The sealed tube was heated at 160 °C for 1 hr under microwave. The reaction mixture was quenched by addition 5 mL H ₂ O (5 mL) at 0°C, and then diluted with CH ₂ Cl ₂ (10 mL) and extracted with CH ₂ Cl ₂ 30 mL (15 mL x 2). The combined organic layers were washed with 15 mL aqueous NaCl, dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a residue. After purified by prep-HPLC (column: Welch Xtimate C18150 x 25 mm 5 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 60% - 90%, 20 min), 4-((2S,6S)-4-(4-(2-(2-aminopyridin-3- yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)-2,6-dimet hylpiperazin-1-yl)pyrimidine-2- carbonitrile (Example 192, 10.5 mg, yield: 8.3%) was obtained as a brown lyophilized powder. MS: m/z = 593.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.33 - 8.26 (m, 2H), 8.05 - 7.98 (m, 4H), 7.55 - 7.52 (m, 2H), 7.51 - 7.36 (m, 6H), 7.18 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 4.24 - 4.18 (m, 2H), 3.94 (d, J = 13.6 Hz, 1H), 3.80 (d, J = 13.6 Hz, 1H), 3.11 (dd, J = 12.0, 4.0 Hz, 2H), 2.68 (dd, J = 12.0, 3.6 Hz, 2H), 1.27 (d, J = 6.4 Hz, 6H). [00722] Example 193: 2-((2S,6S)-4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,6-dimethylpiperazin-1-y l)pyrimidine-4-carbonitrile Example 193 was prepared in a manner similar to Example 192. MS: m/z = 593.5 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.72 (d, J = 4.4 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.05 - 7.97 (m, 4H), 7.56 - 7.52 (m, 2H), 7.49 - 7.37 (m, 5H), 7.25 (d, J = 4.8 Hz, 1H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.05 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 4.33 - 4.26 (m, 2H), 3.87 (d, J = 13.6 Hz, 1H), 3.69 (d, J = 13.6 Hz, 1H), 2.95 (dd, J = 11.6, 3.6 Hz, 2H), 2.56 (dd, J = 12.0, 4.8 Hz, 2H), 1.26 (d, J = 6.4 Hz, 6H). [00723] Example 194: 6-((2S,6S)-4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,6-dimethylpiperazin-1-y l)pyrimidine-4-carbonitrile Example 194 was prepared in a manner similar to Example 192. MS: m/z = 593.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.64 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.05 - 7.97 (m, 4H), 7.56 - 7.52 (m, 2H), 7.49 - 7.44 (m, 5H), 7.42 - 7.37(m, 1H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 4.29 - 4.22(m, 2H), 3.95 (d, J = 14.0 Hz, 1H), 3.82 (d, J = 13.6 Hz, 1H), 3.14 (dd, J = 12.0, 4.0 Hz, 2H), 2.69 (dd, J = 12.0, 3.2 Hz, 2H), 1.27 (d, J = 6.4 Hz, 6H). [00724] Example 195: 4-((2R,6R)-4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,6-dimethylpiperazin-1-y l)pyrimidine-2-carbonitrile Example 195 was prepared in a manner similar to Example 192. MS: m/z = 593.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.25 - 8.13 (m, 2H), 8.03 (d, J = 7.2 Hz, 2H), 7.98 (dd, J = 5.2, 1.6 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 8.4 Hz, 2H), 7.46 - 7.40 (m, 4H), 7.37 (d, J = 7.2 Hz, 1H), 7.32 (dd, J = 7.6, 1.6 Hz, 1H), 6.91 (d, J = 6.4 Hz, 1H), 6.47 (dd, J = 7.6, 5.2 Hz, 1H), 4.32 - 4.19 (m, 2H), 3.94 (d, J = 13.6 Hz, 1H), 3.81 (m, J = 13.6 Hz, 1H), 3.20 - 3.12 (m, 2H), 2.78 - 2.70 m, 2H), 1.36 (d, J = 6.4 Hz, 6H). [00725] Example 196: 2-((2R,6R)-4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,6-dimethylpiperazin-1-y l)pyrimidine-4-carbonitrile Example 196 was prepared in a manner similar to Example 192. MS: m/z = 593.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.72 (d, J = 4.8 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.05 - 7.97 (m, 4H), 7.54 (d, J = 8.4 Hz, 2H), 7.49 - 7.44 (m, 4H), 7.42 - 7.38 (m, 1H), 7.25 (d, J = 4.8 Hz, 1H), 7.17 (dd, J = 7.6,1.6 Hz, 1H), 7.05 (br s, 2H), 6.45 - 6.32 (m, 1H), 4.35 - 4.20 (m, 2H), 3.87 (d, J = 14.0 Hz, 1H), 3.69 (d, J = 14.0 Hz, 1H), 3.01 - 2.88 (m, 2H), 2.58 - 2.57 (m, 1H), 2.55 - 2.54 (m, 1H), 1.26 (d, J = 6.4 Hz, 6H). [00726] Example 197: 6-((2R,6R)-4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,6-dimethylpiperazin-1-y l)pyrimidine-4-carbonitrile Example 197 was prepared in a manner similar to Example 192. MS: m/z = 593.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.58 (s, 1H), 8.19 (d, J = 8.4 Hz, 1H), 8.03 (d, J = 7.2 Hz, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.47 - 7.40 (m, 5H), 7.33 (dd, J = 8.0, 1.6 Hz, 1H), 7.23 (s, 1H), 6.48 (dd, J = 7.6, 5.2 Hz, 1H), 4.34 - 4.24 (m, 2H), 3.96 (d, J = 13.6 Hz, 1H), 3.84 (d, J = 13.6 Hz, 1H), 3.24 - 3.16 (m, 2H), 2.80 - 2.72 (m, 2H), 1.36 (d, J = 6.4 Hz, 6H). [00727] Example 198: 4-(7-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-4,7-diazaspiro[2.5]octan-4-yl)pyrimid ine-2-carbonitrile To a solution of Intermediate 30 (50 mg, 103 µmol) and 2-chloropyrimidine-4-carbonitrile (14.3 mg, 103 µmol) in NMP (1 mL) was added DIEA (66.3 mg, 513 µmol). The mixture was stirred at 130 °C for 0.5 hr under microwave. The reaction mixture was filtered. The residue was purified by prep-HPLC (column: Waters xbridge 150 x 25 mm 10 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 47% - 77%, 10 min), 4-(7-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-4,7-diazaspiro[2.5]octan- 4-yl)pyrimidine-2-carbonitrile (Example 198, 15 mg, yield: 24%) was obtained as an off-white lyophilized powder. MS: m/z = 591.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.35 (d, J = 6.0 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.07 - 7.93 (m, 4H), 7.52 - 7.34 (m, 7H), 7.23 (d, J = 6.4 Hz, 1H), 7.12 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (s, 2H), 6.29 (dd, J = 7.6, 4.8 Hz, 1H), 3.59 (s, 2H), 2.51 - 2.50 (m, 6H), 1.25 - 0.75 (m, 4H). [00728] Example 199: 2-(7-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-4,7-diazaspiro[2.5]octan-4-yl)pyrimid ine-4-carbonitrile Example 199 was prepared in a manner similar to Example 198. MS: m/z = 591.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.70 (d, J = 4.8 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.08 - 7.93 (m, 4H), 7.51 - 7.38 (m, 7H), 7.26 (d, J = 4.8 Hz, 1H), 7.11 (dd, J = 7.6, 1.6 Hz, 1H), 7.05 (s, 2H), 6.34 - 6.27 (dd, J = 8.0, 4.8 Hz, 1H), 4.05-3.97 (m, 2H), 3.56 (s, 2H), 3.34 - 3.33 (m, 2H), 2.33 (s, 2H), 0.98 - 0.95 (m, 2H),, 0.80 - 0.75 (m, 2H), [00729] Example 200: 6-(7-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-4,7-diazaspiro[2.5]octan-4-yl)pyrimid ine-4-carbonitrile Example 200 was prepared in a manner similar to Example 198. MS: m/z = 591.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.66 (d, J = 1.2 Hz, 1H), 8.10 - 7.86 (m, 4H), 7.54 (s, 1H), 7.49 - 7.39 (m, 7H), 7.12 (dd, J = 7.2, 1.6 Hz, 1H), 7.07 - 6.96 (m, 2H), 6.29 (dd, J = 7.6, 4.8 Hz, 1H), 3.59 (br s, 2H), 2.48 - 2.44 (m, 6H), 1.25 – 0.75 (m, 4H). [00730] Example 201: 4-((3-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-3-azabicyclo[3.2.1]octan-8-yl)amino)p yrimidine-2-carbonitrile Intermediate 33 (100 mg, 199 µmol), 4-chloropyrimidine-2-carbonitrile (27.8 mg, 199 µmol) and DIEA (129 mg, 997 µmol) were taken up into a microwave tube in NMP (2 mL). The sealed tube was heated at 160 °C for 1 hr under microwave. After purified by prep-HPLC (column: Welch Xtimate 150 x 25 mm x 5 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B %: 60 % - 90 %, 20 min), 4-((3-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b] pyridin-3- yl)benzyl)-3-azabicyclo[3.2.1]octan-8-yl)amino)pyrimidine-2- carbonitrile (Example 201, 12 mg, yield: 9.3 %) was obtained as a brown solid. MS: m/z = 605.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.14 (d, J = 6.4 Hz, 1H), 8.06 - 7.98 (m, 5H), 7.51 - 7.44 (m, 6H), 7.42 - 7.37 (m, 1H), 7.15 (dd, J = 7.6, 1.2 Hz, 1H), 7.06 (br s, 2H), 6.98 (d, J = 5.2 Hz, 1H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.87 - 3.82 (m, 1H), 3.62 (s, 2H), 2.54 - 2.52 (m, 4H), 2.28 - 2.22 (m, 2H), 1.81 - 1.73 (m, 4H). [00731] Example 202: 6-((3-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-3-azabicyclo[3.2.1]octan-8-yl)amino)p yrimidine-4-carbonitrile Example 202 was prepared in a manner similar to Example 201. MS: m/z = 605.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.57 - 8.46 (m, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.08 (d, J = 5.6 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.50 - 7.43 (m, 6H), 7.41 - 7.37 (m, 1H), 7.22 (s, 1H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.05 (s, 2H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 3.94 - 3.88 (m, 1H), 3.61 (s, 2H), 2.53 - 2.51 (m, 4H), 2.27 - 2.22 (m, 2H), 1.79 - 1.69 (m, 4H). [00732] Example 203: 4-(3-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)pyr imidine-2-carbonitrile A solution of Intermediate 31 (80 mg, 164 µmol), 4-chloropyrimidine-2-carbonitrile (25.2 mg, 180 µmol) and DIEA (106 mg, 820 µmol) were taken up into a microwave tube in NMP (2 mL). The sealed tube was heated at 130 °C for 1 hr under microwave. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Waters xbridge 150*25 mm 10 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 55% - 85%, 10 min), 4-(3-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-3,8-diazabicyclo[3.2.1]oc tan-8-yl)pyrimidine-2-carbonitrile (Example 203, 10.5 mg, yield: 11%) was obtained as a light-yellow solid. MS: m/z = 591.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, H), 8.24 (d, J = 6.4 Hz, H), 8.04 – 7.97 (m, 4H), 7.50 - 7.44 (m, 6H), 7.42 - 7.38 (m, 1H), 7.11 (dd, J = 7.6, 1.6 Hz, 1H), 7.05 (br s, 2H), 7.02 (d, J = 6.4 Hz, 1H), 6.31 (dd, J = 7.6, 4.8 Hz, 1H), 4.84 - 4.76 (m, 1H), 4.57 - 4.51 (m,1H), 3.59 (s, 2H), 2.75 - 2.68 (m, 2H), 2.31 – 2.26 (m, 2H), 2.06 - 1.82 (m, 4H). [00733] Example 204: 2-(3-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)pyr imidine-4-carbonitrile Example 204 was prepared in a manner similar to Example 203. MS: m/z = 591.5 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.64 (d, J = 4.8 Hz, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.05 – 7.97 (m, 4H), 7.50 - 7.43 (m, 6H), 7.41 – 7.37 (m, 1H), 7.15 – 7.11 (m, 2H), 7.05 (br s, 2H), 6.33 (dd, J = 7.6, 4.8 Hz, 1H), 4.72 - 4.64 (m, 2H), 3.58 (s, 2H), 2.72 (d, J = 9.2 Hz, 2H), 2.30 (d, J = 10.4 Hz, 2H), 2.04 - 1.96 (m, 2H), 1.90 – 1.85 (m, 2H). [00734] Example 205: 6-(3-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)pyr imidine-4-carbonitrile Example 205 was prepared in a manner similar to Example 203. MS: m/z = 591.5 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.54 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.05 – 7.97 (m, 4H), 7.50 - 7.43 (m, 7H), 7.41 – 7.37 (m, 1H), 7.13 (dd, J = 7.6, 1.6 Hz, 1H), 7.05 (br s, 2H), 6.30 (dd, J = 7.6, 4.4 Hz, 1H), 4.90 - 4.84 (m, 1H), 4.59 - 4.53 (m,1H), 3.59 (s, 2H), 2.72 (d, J = 11.2 Hz, 2H), 2.30 (d, J = 10.4 Hz, 2H), 2.05 – 2.00 (m, 2H), 1.90 – 1.85 (m, 2H). [00735] Example 206: (S)-4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)-2-methylpiperazin-1-yl)pyrimidine-2-c arbonitrile Example 206 was prepared in a manner similar to Example 203. MS: m/z = 579.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.31 - 8.25 (m, 2H), 8.07 - 7.97 (m, 4H), 7.55 -7.53 (m, 2H), 7.50 - 7.45 (m, 4H), 7.42 - 7.37 (m, 1H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.10 - 7.01 (m, 3H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 4.56 (br s, 1H), 4.22 (br s, 1H), 3.71 (d, J = 14.0 Hz, 1H), 3.60 - 3.52 (d, J = 14.0 Hz, 1H), 3.23 – 3.16 (m, 1H), 2.98 (br d, J = 11.2 Hz, 1H), 2.76 (d, J = 14.0 Hz 1H), 2.21 (dd, J = 11.2, 3.2 Hz, 1H), 2.16 - 2.02 (m, 1H), 1.24 (d, J = 6.8 Hz, 3H). [00736] Example 207: (S)-2-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)-2-methylpiperazin-1-yl)pyrimidine-4-c arbonitrile Example 207 was prepared in a manner similar to Example 203. MS: m/z = 579.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.65 (d, J = 4.4 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.08 - 7.96 (m, 4H), 7.56 - 7.53 (m, 2H), 7.49 - 7.44 (m, 4H), 7.42 - 7.37 (m, 1H), 7.20 - 7.12 (m, 2H), 7.05 (s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 4.76 (br s, 1H), 4.39 (d, J = 12.0 Hz, 1H), 3.70 (d, J = 13.6 Hz, 1H), 3.54 (d, J = 14.0 Hz, 1H), 3.20 (dt, J = 13.2, 3.2 Hz, 1H), 2.96 (d, J = 11.2 Hz, 1H), 2.74 (d, J = 11.2 Hz, 1H), 2.20 (dd, J = 11.2, 4.0 Hz, 1H), 2.14 - 2.09 (m, 1H), 1.23 (d, J = 6.4 Hz, 3H). [00737] Example 208: (S)-6-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)-2-methylpiperazin-1-yl)pyrimidine-4-c arbonitrile Example 208 was prepared in a manner similar to Example 203. MS: m/z = 579.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.58 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.08 - 7.95 (m, 4H), 7.56 - 7.44 (m, 7H), 7.41-7.37 (m, 1H), 7.16 (dd, J = 8.0, 2.0 Hz, 1H), 7.04 (s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 4.63 - 4.29 (m, 2H), , 3.70 (d, J = 13.2 Hz, 1H), 3.55 (d, J = 13.2 Hz, 1H), 3.22 - 3.19 (m, 1H), 2.97 (d, J = 11.2 Hz, 1H), 2.73 (d, J = 11.2 Hz, 1H), 2.20 (dd, J = 11.2, 3.2 Hz, 1H), 2.13 - 2.07 (m, 1H), 1.24 (d, J = 6.8 Hz, 3H). [00738] Example 209: 4-((4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)amino)-1,3,5-triazine-2-carbonitrile Step 1: N-[[4-[2-(2-amino-3-pyridyl)-5-phenyl-imidazo[4,5-b]pyridin- 3-yl]phenyl]methyl]-4- chloro-1,3,5-triazin-2-amine To a solution of Intermediate 4 (140 mg, 357 µmol) in THF (4 mL) and H ₂ O (1 mL) was added K ₂ CO ₃ (148 mg, 1.07 mmol) and stirred at 0 °C for 15 min. Then 2,4-dichloro-1,3,5-triazine (70 mg, 464 µmol) in THF (1 mL) was added into the mixture and stirred at 0 °C for 1.5 hr. The reaction was filtered to give the filter liquor and concentrated under reduced pressure to give a residue. The residue was purified by prep-TLC (MeOH : CH ₂ Cl ₂ = 1 : 10) to give N-[[4-[2-(2- amino-3-pyridyl)-5-phenyl-imidazo[4,5-b]pyridin-3-yl]phenyl] methyl]-4-chloro-1,3,5-triazin-2- amine (6.8 mg, yield: 3.4%) as a light-yellow solid. MS: m/z = 506.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.28 - 9.19 (m, 1H), 8.51 - 8.44 (m, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.49 - 7.43 (m, 5H), 7.44 - 7.36 (m, 2H), 7.21 (d, J = 7.2 Hz, 1H), 6.95 (d, J = 7.2 Hz, 1H), 6.44 - 6.37 (m, 1H), 4.71 - 4.59 (m, 2H). Step 2: 4-((4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyr idin-3-yl)benzyl)amino)- 1,3,5-triazine-2-carbonitrile To a solution of N-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din-3- yl)benzyl)-4-chloro-1,3,5-triazin-2-amine (110 mg, 217 µmol) and DABCO (4.88 mg, 43.5 µmol) in DMSO (1 mL) was added KCN (28.3 mg, 435 µmol) and stirred at 0 °C for 15 min. Then the mixture was stirred at 60 °C for 16 hr. The mixture was quenched with 15 mL H ₂ O and extracted with CH ₂ Cl ₂ (15 mL x 3), the combined organic phase was dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated to give a residue. The residue was purified by prep-HPLC (column: Waters xbridge 150 x 25 mm 10 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 37% - 67%, 9 min), 4-((4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyr idin-3- yl)benzyl)amino)-1,3,5-triazine-2-carbonitrile (Example 209, 7.9 mg, yield: 7.3%) was obtained as a yellow solid. MS: m/z = 497.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.44 (t, J = 6.4 Hz, 1H), 8.71 (d, J = 22.0 Hz, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.04 - 7.96 (m, 4H), 7.50 - 7.44 (m, 6H), 7.42 - 7.37 (m, 1H), 7.22 - 7.19 (m, 1H), 6.93 (d, J = 9.2 Hz, 2H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 4.72 - 4.64 (m, 1H). [00739] Example 210: 4-((4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)amino)-6-hydroxy-1,3,5-triazine-2-carb onitrile Step 1: N-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din-3-yl)benzyl)-4,6- dichloro-1,3,5-triazin-2-amine Following the general procedure of Example 209 step 1, the reaction of Intermediate 4 (200 mg, 404 µmol) with 2,4,6-trichloro-1,3,5-triazine (103 mg, 561 µmol) was carried out. After flash silica gel chromatography (Eluent of 50~75% EtOAc in petroleum ether), N-(4-(2-(2- aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)be nzyl)-4,6-dichloro-1,3,5-triazin- 2-amine (120 mg, yield: 42%) was obtained as a yellow solid. MS: m/z = 540.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.66 (t, J = 6.4 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.05 - 7.96 (m, 4H), 7.51 - 7.47 (m, 4H), 7.47 - 7.43 (m, 2H), 7.42 - 7.38 (m, 1H), 7.21 (dd, J = 7.6, 2.0 Hz, 1H), 6.95 (br s, 2H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 4.65 (d, J = 6.4 Hz, 2H). Step 2: 4-((4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyr idin-3-yl)benzyl)amino)- 6-hydroxy-1,3,5-triazine-2-carbonitrile To a solution of N-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din-3- yl)benzyl)-4,6-dichloro-1,3,5-triazin-2-amine (130 mg, 241 µmol) in DMSO (3 mL) was added DABCO (5.4 mg, 48.1 µmol) and KCN (50 mg, 768 µmol), the mixture was stirred at 60 °C for 16 hr. The reaction mixture was diluted with H ₂ O (5 mL) and extracted with CH ₂ Cl ₂ (10 mL x 3). The combined organic layers were washed with 10 mL brine, dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. After purified by prep-HPLC (column: Welch Xtimate C18150 x 25 mm 5 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 22% - 52%, 12 min), 4-((4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyr idin-3- yl)benzyl)amino)-6-hydroxy-1,3,5-triazine-2-carbonitrile (Example 210, 5.2 mg, yield: 4.2%) was obtained as a light-yellow lyophilized powder. MS: m/z = 513.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 12.16 (br s, 1H), 8.39 (br s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.50 - 7.44 (m, 6H), 7.42 - 7.38 (m, 1H), 7.22 (d, J = 7.6 Hz, 1H), 6.94 (br s, 2H), 6.42 (dd, J = 7.6, 4.8 Hz, 1H), 4.67 - 4.58 (m, 2H). [00740] Example 211: 4-(8-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)pyr imidine-2-carbonitrile Example 211 was prepared in a manner similar to Example 203. MS: m/z = 591.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 5.6 Hz, 1H), 8.26 (d, J = 3.6 Hz, 1H), 8.05 – 7.97 (m, 4H), 7.59 (d, J = 8.4 Hz, 2H), 7.50 - 7.43 (m, 4H), 7.41 – 7.37 (m, 1H), 7.18 (dd, J = 7.6, 2.0 Hz, 1H), 7.03 – 7.00 (m, 3H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 4.28 - 4.20 (m, 1H), 3.75 – 3.68 (m, 3H), 3.40 – 3.37 (m, 2H), 3.24 – 3.06 (m, 2H), 2.05 – 2.00 (m, 2H), 1.57 – 1.50 (m, 2H). [00741] Example 212: 2-(8-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)pyr imidine-4-carbonitrile Example 212 was prepared in a manner similar to Example 203. MS: m/z = 591.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.63 (d, J = 4.4 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.05 – 7.97 (m, 4H), 7.59 (d, J = 8.4 Hz, 2H), 7.50 - 7.45 (m, 4H), 7.42 – 7.37 (m, 1H), 7.18 (dd, J = 6.0, 1.6 Hz, 1H), 7.16 (d, J = 4.4 Hz, 1H), 7.01 (br s, 2H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 4.25 - 4.12 (m, 2H), 3.68 (s, 2H), 3.37 – 3.35 (m, 2H), 3.18 – 3.16 (m, 2H), 2.03 – 1.98 (m, 2H), 1.56 - 1.48 (m, 2H). [00742] Example 213: 6-(8-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)pyr imidine-4-carbonitrile Example 213 was prepared in a manner similar to Example 203. MS: m/z = 591.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.56 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.05 – 7.97 (m, 4H), 7.58 (d, J = 8.4 Hz, 2H), 7.50 - 7.45 (m, 4H), 7.42 – 7.37 (m, 1H), 7.17 (dd, J = 8.0, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 4.45 -4.30 (m, 1H), 3.78 – 3.68 (m, 3H), 3.45 – 3.37 (m, 2H), 3.26 – 3.18 (m, 1H), 3.14 – 3.03 (m, 1H), 2.05 – 2.00 (m, 2H), 1.57 – 1.46 (m, 2H). [00743] Example 214: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-1,4-diazepan-1-yl)pyrimidine-2-carbon itrile Example 214 was prepared in a manner similar to Example 203. MS: m/z = 579.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) 8.24 - 8.10 (m, 2H), 8.07 - 8.01 (m, 2H), 7.99 – 7.99 (m, 1H), 7.95 – 7.91 (m, 1H), 7.52 (d, J = 8.0 Hz, 2H), 7.46 - 7.40 (m, 4H), 7.40 - 7.29 (m, 2H), 6.89 - 6.80 (m, 1H), 6.52 - 6.41 (m, 1H), 4.02 - 3.91 (m, 2H), 3.77 (s, 2H), 3.68 - 3.59 (m, 2H), 2.88 - 2.82 (m, 2H), 2.75 – 2.68 (m, 2H), 2.04 - 1.95 (m, 2H). [00744] Example 215: 6-(4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-1,4-diazepan-1-yl)pyrimidine-4-carbon itrile Example 215 was prepared in a manner similar to Example 203. MS: m/z = 579.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.56 (d, J = 5.6 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.08 - 7.96 (m, 4H), 7.49 - 7.37 (m, 8H), 7.13 (d, J = 7.6 Hz, 1H), 7.05 (br s, 2H), 6.41 - 6.29 (m, 1H), 3.93 - 3.83 (m, 2H), 3.73 (d, J = 8.0 Hz, 2H), 3.68 - 3.59 (m, 2H), 2.77 - 2.72 (m, 2H), 2.63 - 2.58 (m, 2H), 1.93 - 1.82 (m, 2H). [00745] Example 216: 4-((1R,4R)-5-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,5-diazabicyclo[2.2.1]he ptan-2-yl)pyrimidine-2- carbonitrile Example 216 was prepared in a manner similar to Example 203. MS: m/z = 577.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 - 8.18 (m, 2H), 8.03 - 7.97 (m, 4H) 7.52 - 7.37 (m, 8H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 6.99 (br s, 2H), 6.41 - 6.37 (m, 1H), 4.89 - 4.68 (m, 1H), 3.84 (s, 2H), 3.70 - 3.67 (m, 2H), 3.56 - 3.53 (m, 1H), 3.42 - 3.41 (m, 1H), 2.94 (t, J = 8.0 Hz, 1H), 2.07 - 1.97 (m, 1H), 1.86 - 1.78 (m, 1H). [00746] Example 217: 2-((1R,4R)-5-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,5-diazabicyclo[2.2.1]he ptan-2-yl)pyrimidine-4- carbonitrile Example 217 was prepared in a manner similar to Example 203. MS: m/z = 577.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.63 - 8.59 (m, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.05 - 7.95 (m, 4H), 7.51 - 7.37 (m, 7H), 7.16 (dd, J = 8.0, 1.6 Hz, 1H), 7.12 (d, J = 4.4 Hz, 1H), 6.99 (br s, 2H), 6.39 (dd, J = 7.6, 5.2 Hz, 1H), 4.81 - 4.73 (m, 1H), 3.87 (s, 2H), 3.69 - 3.62 (m, 2H), 3.45 - 3.40 (m, 2H), 2.96 - 2.94 (m, 1H), 1.99 - 1.97 (m, 1H), 1.84 - 1.82 (m, 1H). [00747] Example 218: 6-((1R,4R)-5-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,5-diazabicyclo[2.2.1]he ptan-2-yl)pyrimidine-4- carbonitrile Example 218 was prepared in a manner similar to Example 203. MS: m/z = 577.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.52 (d, J = 12.4 Hz, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.04 - 8.00 (m, 3H), 7.99 - 7.97 (m, 1H), 7.51 - 7.41 (m, 7H), 7.17 - 7.15 (m, 2H), 6.99 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 4.94 - 4.71 (m, 1H), 3.84 - 3.82 (m, 2H), 3.72 - 3.67 (m, 2H), 3.60 - 3.58 (m, 1H), 3.43 - 3.42 (m, 1H), 2.95 - 2.90 (m, 1H), 2.04 - 1.97 (m, 1H), 1.8 - 1.78 (m, 1H). [00748] Example 219: 4-(5-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)pyr imidine-2-carbonitrile Example 219 was prepared in a manner similar to Example 203. MS: m/z = 591.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.28 - 8.18 (m, 2H), 8.04 - 7.97 (m, 4H), 7.53 (d, J = 8.4 Hz, 2H), 7.49 - 7.43 (m, 4H), 7.42 - 7.37 (m, 1H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (s, 2H), 6.76 (d, J = 6.4 Hz, 1H), 6.42 - 6.35 (m, 1H), 4.76 - 4.73 (m, 0.6H), 4.24 - 4.21 (m, 0.4H), 3.89 - 3.80 (m, 3H), 3.49 – 3.52 (m, 1H), 3.02-3.07 (m, 1H), 2.94 - 2.88 (m, 2H), 2.20 - 2.03 (m, 1H), 1.89 - 1.80 (m, 2H), 1.71 - 1.63 (m, 1H). [00749] Example 220: 2-(5-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)pyr imidine-4-carbonitrile Example 220 was prepared in a manner similar to Example 203. MS: m/z = 591.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.68 - 8.54 (m, 1H), 8.27 (d, J = 8.0 Hz, 1H), 8.06 - 7.95 (m, 4H), 7.53 (d, J = 8.4 Hz, 2H), 7.49 - 7.43 (m, 4H), 7.42 - 7.37 (m, 1H), 7.16 (dd, J = 7.6, 2.0 Hz, 1H), 7.11 (d, J= 4.8 Hz, 1H), 7.02 (s, 2H), 6.39 (dd, J= 7.6, 4.8 Hz, 1H), 4.73 - 4.55 (m, 1H), 3.92 - 3.80 (m, 3H), 3.49 - 3.44 (m, 1H), 3.03 -3.05 (m, 1H), 2.96 - 2.85 (m, 2H), 2.16 - 2.06 (m, 1H), 1.89 - 1.79 (m, 2H), 1.71 - 1.61 (m, 1H).

[00750] Example 221: 6-(5-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)pyr imidine-4-carbonitrile

Example 221 was prepared in a manner similar to Example 203. MS: m/z = 591.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.60 - 8.48 (m, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.05 - 7.97 (m, 4H), 7.52 (d, J= 8.4 Hz, 2H), 7.49 - 7.43 (m, 4H), 7.42 - 7.37 (m, 1H), 7.24 - 7.10 (m, 2H), 7.01 (s, 2H), 6.40 - 6.36 (m, 1H), 4.25 - 4.85 (m, 1H), 3.90 - 3.78 (m, 3H), 3.56 - 3.49 (m, 1H), 3.05-3.07 (m, 1H), 2.94 - 2.86 (m, 2H), 2.17 - 2.08 (m, 1H), 1.90 - 1.79 (m, 2H), 1.71 - 1.63 (m, 1H).

[00751] Example 222: 4-((l-((4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)phenyl)methyl-d2)piperidin-4-yl)amino)pyrimid ine-2-carbonitrile

To a solution of Intermediate 40 (50.0 mg, 105 μmol) inNMP (1 mL) were added 4- chloropyrimidine-2-carbonitrile (16.1 mg, 115 μmol) and DLEA (67.6 mg, 523 μmol, 91.2 μL) under N ₂ atmosphere. The mixture was stirred at 130 °C for 30 min under microwave. Water (5 mL) was added to the mixture and the mixture was extracted with EtOAc (3 x 5 mL). The combined organic layers were washed with brine (10 mL), dried over Na ₂ SO ₄ , filtered, and concentrated. The residue was purified by prep-HPLC (column: Phenomenex C18 80*40mm*3μm; mobile phase: [water (NH ₄ OH + NH ₄ HCO ₃ ) - ACN]; B%: 51% - 81%, 8 min) to give 4-((l-((4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b ]pyridin-3- yl)phenyl)methyl-d2)piperidin-4-yl)amino)pyrimidine-2-carbon itrile (Example 222, 20.3 mg, yield: 33%) was obtained as an off-white solid. MS: m/z = 581.3 [M + H] ⁺ . ¹ H NMR (400MHz, Methanol-d ₄ ) δ 8.24 (d, J= 8.4 Hz, 1H), 8.10 (d, J= 6.0 Hz, 1H), 8.04 - 7.95 (m, 4H), 7.77 (d, J = 8.4 Hz, 2H), 7.67 (d, J= 8.0 Hz, 2H), 7.50 - 7.38 (m, 4H), 6.67 (s, 1H), 6.59 (dd, J= 7.6, 5.6 Hz, 1H), 4.25 - 4.19 (m, 1H), 3.62 - 3.58 (m, 2H), 3.38 - 3.33 (m, 1H), 3.29 - 3.19 (m, 1H), 2.29

- 2.26 (m, 2H), 1.86 - 1.80 (m, 2H).

[00752] Example 223: 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3 -yl)benzyl)piperidin-4-yl)(methyl)amino)- 1,3, 5-triazine-2-carbonitrile

Step 1 : N-(l-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperidin-4-yl)-4-chloro-N-methyl-l,3,5-triazin-2- amine

To a solution of Intermediate 36 (110 mg, 225 μmol) in THF (15 mL) was added DIEA (87.1 mg, 674 μmol). The mixture was stirred at 0 °C for 10 min. Then 2,4-dichloro-l,3,5-triazine (37.1 mg, 247 μmol) in THF (2 mL) was added to the mixture. The mixture was stirred at 0 °C for 1 hr. The reaction mixture was concentrated, and purified by silica gel flash chromatography (Eluent of 0-100% EtOAc in petroleum ether) to give N-(l-(4-(2-(2-aminopyridin-3-yl)-5- phenyl-3H-imidazo[4,5 -b]pyridin-3 -yl)benzyl)piperidin-4-yl)-4-chloro-N-methyl- 1 ,3 , 5-triazin- 2-amine.(40 mg, yield: 30%) as a light-yellow solid. MS: m/z = 603.2 [M + H] ⁺ .

Step 2: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b] pyridin-3- yl)benzyl)piperidin-4-yl)(methyl)amino)-l,3,5-triazine-2-car bonitrile

To a solution of N-(l-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperidin-4-yl)-4-chloro-7V-methyl-l,3,5-triazin-2 -amine (40 mg, 66.3 μmol) in DMSO (1 mL) were added KCN (13.0 mg, 199 μmol) and DABCO (1.5 mg, 13.3 μmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was poured into water (5 mL). The resulting mixture was extracted with CH ₂ CI ₂ (5 mL x 2). The combined organic layers were washed with brine (5 ml) and dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by prep-HPLC (column: Waters xbridge 150*25 mm 10 um ; mobile phase : [water (NH4HCO3) - ACN] ; gradient : 53% - 83% B over 14 min) to give 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b] pyridin-3- yl)benzyl)piperidin-4-yl)(methyl)amino)-l,3,5-triazine-2-car bonitrile (Example 223, 14.0 mg, yield: 36%) as a yellow solid. MS: m/z = 594.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Acetonitrile-d ₆ ) 6 8.58 (d, J= 6.8 Hz, 1H), 8.20 (d, J= 8.4 Hz, 1H), 8.11 - 7.99 (m, 3H), 7.93 (d, J= 8.4 Hz, 1H), 7.57 - 7.52 (m, 2H), 7.51 - 7.40 (m, 5H), 7.18 (dd, J= 7.6, 1.2 Hz, 1H), 6.60 (br s, 2H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 4.63 - 4.53 (m, 1H), 3.66 (d, J = 4.4 Hz, 2H), 3.11 - 3.07(m, 3H), 3.07 - 3.01 (m, 2H), 2.23 - 2.19 (m, 2H), 1.95 -1.88 (m, 2H), 1.72 - 1.69 (m, 2H). [00753] Example 224: (S)-4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl)piperidin-3-yl)amino)-1,3,5-triazine-2 -carbonitrile Example 224 was prepared in a manner similar to Example 223.MS: m/z = 580.3 [M + H] ⁺ .1H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.66 (dd, J = 8.4, 2.8 Hz, 1H), 8.64 (d, J = 16.0 Hz, 1H), 8.27 (d, J = 8.0 Hz, 1H), 8.04 - 7.99 (m, 3H), 7.97 - 7.96 (m, 1H), 7.52 - 7.48 (m, 2H), 7.46 - 7.43 (m, 4H), 7.40 - 7.36 (m, 1H), 7.15 - 7.12 (m, 1H), 7.03 (d, J = 8.4 Hz, 2H), 6.33 - 6.27 (m, 1H), 4.02 - 3.93 (m, 1H), 3.62 (d, J = 8.0 Hz, 2H), 2.91 - 2.84 (m, 1H), 2.74 - 2.69 (m, 1H), 2.03 - 1.98 (m, 2H), 1.87 - 1.82 (m, 1H), 1.76 - 1.71 (m, 1H), 1.57 - 1.50 (m, 1H), 1.36 - 1.32 (m, 1H). [00754] Example 225: (R)-4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)-2-methylpiperazin-1-yl)pyrimidine-2-c arbonitrile A mixture of Intermediate 164 (100 mg, 210 µmol), 4-chloropyrimidine-2-carbonitrile (29.3 mg, 210 µmol) and DIEA (136 mg, 1.05 mmol) in NMP (2 mL) was taken up into a microwave tube. The sealed tube was heated at 130 °C for 1 hr under microwave. The reaction mixture was quenched with H ₂ O (5 mL) at 0°C, and then diluted with CH ₂ Cl ₂ (10 mL) and extracted with CH ₂ Cl ₂ (15 mL x 2). The combined organic layers were washed with brine (15 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-HPLC (column: Welch Xtimate C18150 x 25 mm x 5 µm; mobile phase: [water (HCl) - ACN]; B%: 13% - 43%, 10 min), (R)-4-(4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 -b]pyridin- 3-yl)benzyl)-2-methylpiperazin-1-yl)pyrimidine-2-carbonitril e (Example 225, 14.5 mg HCl salt, yield: 12%) was obtained as a yellow solid. MS: m/z = 579.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.36 - 8.31 (m, 2H), 8.05 - 8.01 (m, 4H), 7.92 (d, J = 8.4 Hz, 2H), 7.87 (dd, J = 7.6, 1.2 Hz, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.47 - 7.41 (m, 3H), 7.09 (d, J = 6.4 Hz, 1H), 6.87 (dd, J = 7.6, 6.4 Hz, 1H), 3.72 (d, J = 11.6 Hz, 1H), 3.63 - 3.55 (m, 2H), 3.49 - 3.36 (m, 2H), 3.35 – 3.31 (m, 2H), 2.86 - 2.66 (m, 2H), 1.46 (d, J = 6.8 Hz, 3H). [00755] Example 226: (R)-2-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)-2-methylpiperazin-1-yl)pyrimidine-4-c arbonitrile Example 226 was prepared in a manner similar to Example 225. MS: m/z = 579.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4) δ 8.65 (d, J = 4.8 Hz, 1H), 8.33 (d, J = 8.4 Hz, 1H), 8.06 - 8.01 (m, 4H), 7.92 (d, J = 8.0 Hz, 2H), 7.87 (d, J = 7.2 Hz, 1H), 7.76 (d, J = 8.0 Hz, 2H), 7.47 - 7.40 (m, 3H), 7.10 (d, J = 4.8 Hz, 1H), 6.86 (t, J = .2 Hz, 1H), 3.71 (d, J = 10.4 Hz, 1H), 3.55 (t, J = 12.4 Hz, 2H), 3.49 - 3.32 (m, 4H), 3.30 - 3.19 (m, 2H), 1.43 (d, J = 7.2 Hz, 3H). [00756] Example 227: (R)-6-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)-2-methylpiperazin-1-yl)pyrimidine-4-c arbonitrile Example 227 was prepared in a manner similar to Example 225. MS: m/z = 579.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.65 (s, 1H), 8.33 (d, J = 8.4 Hz, 1H), 8.05 - 8.02 (m, 4H), 7.93 (d, J = 8.4 Hz, 2H), 7.88 (dd, J = 7.6, 1.2 Hz, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.47 - 7.42 (m, 4H), 6.87 (dd, J = 7.6, 6.4 Hz, 1H), 3.76 - 3.69 (m, 1H), 3.63 - 3.55 (m, 2H), 3.51 - 3.32 (m, 4H), 3.30 - 3.22 (m, 2H), 1.46 (d, J = 7.2 Hz, 3H). [00757] Example 228: 2-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-1,4-diazepan-1-yl)pyrimidine-4-carbon itrile Example 228 was prepared in a manner similar to Example 225. MS: m/z = 579.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.74 - 8.56 (m, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.50 - 7.43 (m, 7H), 7.15 - 7.11 (m, 2H), 7.04 (br s, 2H), 6.37 - 6.32 (m, 1H), 3.87 - 3.77 (m, 4H), 3.74 (s, 2H), 2.81 - 2.70 (m, 4H), 1.90 - 1.84 (m, 2H). [00758] Example 229: N-(3-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-3-azabicyclo[3.2.1]octan-8-yl)-2-cyan opyrimidine-4-carboxamide Example 229 was prepared in a manner similar to Example 32. MS: m/z = 633.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 9.17 (d, J = 4.8 Hz, 1H), 8.72 - 8.60 (m, 1H), 8.34 - 8.25 (m, 2H), 8.04 - 8.01 (m, 3H), 7.92 (d, J = 7.6 Hz, 2H), 7.85 (d, J = 7.2 Hz, 1H), 7.73 (d, J = 7.6 Hz, 2H), 7.48 - 7.40 (m, 3H), 6.90 - 6.87 (m, 1H), 4.52 (s, 2H), 4.21 - 4.16 (m, 1H), 3.55 - 3.43 (m, 4H), 2.81 - 2.73 (m, 2H), 2.23 - 2.14 (m, 2H), 2.05 - 2.00 (m, 2H). [00759] Example 230: N-(3-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-3-azabicyclo[3.2.1]octan-8-yl)-6-cyan opyrimidine-4-carboxamide Example 230 was prepared in a manner similar to Example 32. MS: m/z = 633.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 9.16 (s, 1H), 8.33 (d, J = 8.8 Hz, 1H), 8.17 (d, J = 1.2 Hz, 1H), 8.08 - 8.03 (m, 2H), 7.97 - 7.94 (m, 2H), 7.91 - 7.87 (m, 2H), 7.85 (dd, J = 7.6, 1.6 Hz, 1H), 7.74 (d, J = 8.4 Hz, 2H), 7.44 - 7.40 (m, 3H), 6.88 - 6.81 (m, 1H), 4.51 (s, 2H), 3.85 (t, J = 4.4 Hz, 1H), 3.52 - 3.47 (m, 2H), 3.38 - 3.34 (m, 2H), 2.87 - 2.82 (m, 2H), 2.15 - 2.09 (m, 2H), 2.06 - 1.98 (m, 2H). [00760] Example 231: 2-((3-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-3-azabicyclo[3.2.1]octan-8-yl)amino)p yrimidine-4-carbonitrile Example 231 was prepared in a manner similar to Example 225. MS: m/z = 605.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.61 (d, J = 4.8 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.05 - 7.97 (m, 4H), 7.95 - 7.71 (m, 1H), 7.52 - 7.44 (m, 6H), 7.42 - 7.36 (m, 1H), 7.17 - 7.04 (m, 4H), 6.40 - 6.34 (m, 1H), 3.62 - 3.58 (m, 2H), 2.75 - 2.56 (m, 4H), 2.46 - 2.40 (m, 1H), 2.29 - 2.24 (m, 2H), 1.86 - 1.63 (m, 4H). [00761] Example 232: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)(methyl-d3)amino)pyrimi dine-2-carbonitrile Example 232 was prepared in a manner similar to Example 225. MS: m/z = 596.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol- d ₄ ) δ 8.19 (d, J = 8.4 Hz, 1H), 8.16 (d, J = 6.4 Hz, 1H), 8.03 (d, J = 7.2 Hz, 2H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.58 - 7.54 (m, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.45 - 7.36 (m, 3H), 7.33 (dd, J = 7.6, 1.6 Hz, 1H), 6.93 - 6.71 (m, 1H), 6.48 (dd, J = 7.6, 5.2 Hz, 1H), 3.71 (s, 2H), 3.40 - 3.35 (m, 1H), 3.10 (d, J = 12.0 Hz, 2H), 2.35 - 2.24 (m, 2H), 2.00 - 1.90 (m, 2H), 1.78 - 1.67 (m, 2H). [00762] Example 233: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)(methyl-d3)amino)-1,3,5 -triazine-2-carbonitrile Example 233 was prepared in a manner similar to Example 223. MS: m/z = 597.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.58 (d, J = 6.8 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 7.2 Hz, 2H), 8.01 - 7.97 (m, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.58 - 7.53 (m, 2H), 7.49 - 7.41 (m, 4H), 7.38 - 7.32 (m, 2H), 6.54 - 6.43 (m, 1H), 3.68 (d, J = 7.6 Hz, 2H), 3.52 - 3.40 (m, 1H), 3.11 - 3.06 (m, 2H), 2.28 - 2.19 (m, 2H), 2.00 - 1.97 (m, 2H), 1.75 - 1.69 (m, 2H). [00763] Example 234: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-2-cyano-N-(methyl-d3)p yrimidine-4-carboxamide Example 234 was prepared in a manner similar to Example 32. MS: m/z = 624.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.23 - 9.03 (m, 1H), 8.28 (d, J = 7.6 Hz, 1H), 8.06 - 7.97 (m, 5H), 7.54 - 7.39 (m, 7H), 7.19 - 7.13 (m, 1H), 7.06 - 6.96 (m, 2H), 6.43 - 6.34 (m, 1H), 3.66 - 3.39 (m, 2H), 3.14 - 2.96 (m, 1H), 2.94 - 2.74 (m, 1H), 2.21 - 2.12 (m, 1H), 1.93 - 1.85 (m, 2H), 1.73 - 1.60 (m, 2H), 1.30 - 1.19 (m, 2H). [00764] Example 235: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine-2-carbonitri le Example 235 was prepared in a manner similar to Example 225. MS: m/z = 574.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ )) δ 8.27 (d, J = 6.4 Hz, 1H), 7.98 (d, J = 8.8 Hz, 1H), 7.93 (dd, J = 4.8, 2.0 Hz, 1H), 7.46 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 7.12 (d, J = 6.4 Hz, 1H), 7.04 (br s, 2H), 6.98 (dd, J = 8.0, 2.0 Hz, 1H), 6.90 (d, J = 9.2 Hz, 1H), 6.30 (dd, J = 7.6, 4.8 Hz, 1H), 3.72 - 3.64 (m, 8H), 3.62 (s, 2H), 3.42 - 3.38 (m, 4H), 2.49 - 2.45 (m, 4H). [00765] Example 236: 2-(4-(4-(2-(2-Aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine-4-carbonitri le Example 236 was prepared in a manner similar to Example 225. MS: m/z = 574.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ )) δ 8.65 (d, J = 4.8 Hz, 1H), 7.99 (d, J = 8.8 Hz, 1H), 7.93 (dd, J = 4.8, 1.6 Hz, 1H), 7.47 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 7.16 (d, J = 4.8 Hz, 1H), 7.03 (br s, 2H), 6.99 (dd, J = 8.0, 2.0 Hz, 1H), 6.90 (d, J = 9.2 Hz, 1H), 6.31 (dd, J = 8.0, 5.2 Hz, 1H), 3.82 - 3.76 (m, 4H), 3.71 - 3.66 (m, 4H), 3.62 (s, 2H), 3.42 - 3.38 (m, 4H), 2.49 - 2.44 (m, 4H). [00766] Example 237: 6-(4-(4-(2-(2-Aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine-4-carbonitri le Example 237 was prepared in a manner similar to Example 225. MS: m/z = 574.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.57 (s, 1H), 7.98 (d, J = 8.8 Hz, 1H), 7.93 (dd, J = 4.8, 1.6 Hz, 1H), 7.57 (s, 1H), 7.46 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 7.03 (br s, 2H), 6.98 (dd, J = 7.6, 1.6 Hz, 1H), 6.90 (d, J = 8.8 Hz, 1H), 6.28 (dd, J = 7.6, 4.8 Hz, 1H), 3.81 - 3.65 (m, 8H), 3.61 (s, 2H), 3.42 - 3.38 (m, 4H), 2.49 - 2.44 (m, 4H). [00767] Example 238: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(6-oxo-1,6-dihydropyridin -2- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyri midine-2-carbonitrile Example 238 was prepared in a manner similar to Example 225. MS: m/z = 582.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ )) δ 10.80 (br s, 1H), 8.34 (d, J = 8.0 Hz, 1H), 8.27 (d, J = 6.4 Hz, 1H), 8.21 - 8.11 (m, 1H), 8.01 (dd, J = 4.8, 1.6 Hz, 1H), 7.67 - 7.45 (m, 6H), 7.17 - 7.15 (m, 1H), 7.12 (d, J = 6.4 Hz, 1H), 7.03 (br s, 2H), 6.52 - 6.42 (m, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.79 - 3.67 (m, 4H), 3.66 (s, 2H), 2.60 - 2.52 (m, 4H). [00768] Example 239: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-morpholino-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile

A mixture of Intermediate 48 (100 mg, 206 μmol), 4-chloropyrimidine-2-carbonitrile (28.8 mg, 206 μmol) and DIEA (133 mg, 1.03 mmol) in NMP (2 mL) was taken up into a microwave tube.

The sealed tube was heated at 130 °C for 30 min under microwave. The reaction mixture was filtered.. After purified by prep-HPLC (column: Waters xbridge 150 * 25 mm 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient:28% - 58% B over 18 min), 4-((l-(4-(2-(2- aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5-b]pyridin-3-y l)benzyl)piperi din-4- yl)amino)pyrimidine-2-carbonitrile (Example 239, 39.3 mg, yield: 32%) was obtained as a lightyellow powder. MS: m/z = 588.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.08 (d, J= 6.0 Hz, 1H), 8.04 (d, J= 6.4 Hz, 1H), 7.98 (d, J= 8.8 Hz, 1H), 7.93 (dd, J= 4.4, 1.2 Hz, 1H), 7.42 (d, J= 8.0 Hz, 2H), 7.31 (d, J= 8.4 Hz, 2H), 7.03 (br s, 2H), 7.00 - 6.97 (m, 1H), 6.89 (d, J= 9.2 Hz, 1H), 6.67 (d, J= 6.0 Hz, 1H), 6.30 (dd, J= 7.6, 5.2 Hz, 1H), 3.86 - 3.75 (m, 1H), 3.70 - 3.65 (m, 4H), 3.56 (s, 2H), 3.45 - 3.35 (m, 4H), 2.84 - 2.75 (m, 2H), 2.20 - 2.15 (m, 2H), 1.90 - 1.82 (m, 2H), 1.54 - 1.45 (m, 2H).

[00769] Example 240: 2-((l-(4-(2-(2-Aminopyridin-3-yl)-5-morpholino-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-4-carb onitrile

Example 240 was prepared in a manner similar to Example 225. MS: m/z = 588.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.60 - 8.46 (m, 1H), 7.97 (d, J= 9.2 Hz, 1H), 7.93 (dd, J= 4.8, 1.6 Hz, 1H), 7.85 (d, J= 7.6 Hz, 1H), 7.41 (d, J= 8.4 Hz, 2H), 7.30 (d, J= 8.4 Hz, 2H), 7.06 (d, J= 4.8 Hz, 1H), 7.03 (br s, 2H), 6.99 (dd, J= 8.0, 2.0 Hz, 1H), 6.88 (d, J= 9.2 Hz, 1H), 6.30 (dd, J= 8.0, 5.2 Hz, 1H), 3.68 - 3.65 (m, 4H), 3.54 (s, 2H), 3.41 - 3.38 (m, 5H), 2.85 - 2.75 (m, 2H), 2.10 - 2.00 (m, 2H), 1.88 - 1.78 (m, 2H), 1.59 - 1.48 (m, 2H).

[00770] Example 241: 6-((l-(4-(2-(2-Aminopyridin-3-yl)-5-morpholino-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-4-carb onitrile Example 241 was prepared in a manner similar to Example 225. MS: m/z = 588.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.49 (s, 1H), 8.07 (d, J = 6.8 Hz, 1H), 7.97 (d, J = 8.8 Hz, 1H), 7.95 - 7.89 (m, 1H), 7.42 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 7.04 (br s, 2H), 7.00 - 6.96 (m, 1H), 6.95 - 6.85 (m, 2H), 6.30 (dd, J = 7.6, 4.8 Hz, 1H), 3.90 - 3.75 (m, 1H), 3.70 - 3.60 (m, 4H), 3.55 (s, 2H), 3.43 - 3.35 (m, 4H), 2.85 - 2.75 (m, 2H), 2.15 - 2.04 (m, 2H), 1.90 - 1.75 (m, 2H), 1.55 - 1.43 (m, 2H). [00771] Example 242: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 2-carbonitrile Example 242 was prepared in a manner similar to Example 225. MS: m/z = 583.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 7.6 Hz, 2H), 8.08 (dd, J = 8.4, 6.0 Hz, 2H), 8.01 - 7.95 (m, 2H), 7.54 - 7.45 (m, 4H), 7.30 (t, J = 8.8 Hz, 2H), 7.16 - 7.10 (m, 2H), 7.03 (s, 2H), 6.39 - 6.32 (m, 1H), 3.78 - 3.65 (m, 4H), 3.65 (s, 2H), 2.52 - 2.51 (m, 4H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -113.56. [00772] Example 243: 2-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 4-carbonitrile Example 243 was prepared in a manner similar to Example 225. MS: m/z = 583.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.65 (d, J = 4.8 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.11 - 8.06 (m, 2H), 8.01 - 7.97 (m, 2H), 7.53 - 7.45 (m, 4H), 7.33 - 7.28 (m, 2H), 7.17 - 7.13 (m, 2H), 7.03 (s, 2H), 6.37 (dd, J= 8.0, 4.8 Hz, 1H), 3.82 - 3.77 (m, 4H), 3.64 (s, 2H), 2.51 - 2.51 (m, 4H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -113.56.

[00773] Example 244: N-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)-2-cyanothiazole-4-carboxamide

Step 1 : N-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl) benzyl)-2-bromothiazole- 4-carboxamide

To a solution of 3-(3-(4-(aminomethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)p yridin-2-amine (138 mg, 437 μmol) and 2-bromothiazole-4-carboxylic acid (100 mg, 480 μmol) in DMF (2 mL) were added EDCI (125 mg, 655 μmol), HOBt (88 mg, 655 μmol), and DIEA (282 mg, 2.2 mmol). The mixture was stirred at 25 °C for 3 hr. The mixture was quenched with water (20 mL) and extracted with EtOAc (25 mL x 3). The combined organic layers were dried over Na ₂ SO ₄ , filtered, concentrated and purified by silica gel flash chromatography (eluent of 0~ 3% MeOH in CH ₂ CI ₂ ), N-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl) benzyl)-2- bromothiazole-4-carboxamide (53 mg, yield: 43%) was obtained as a yellow solid. MS: m/z = 506.1, 508.0 [M + H] ⁺ . ¹ HNMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.20 (t, J= 6.4 Hz, 1H), 8.35 - 8.28 (m, 2H), 8.19 (dd, J= 8.0, 1.2 Hz, 1H), 7.99 (dd, J= 4.8, 1.6 Hz, 1H), 7.47 - 7.41 (m, 2H), 7.41 - 7.35 (m, 3H), 7.23 (dd, J= 7.6, 1.6 Hz, 1H), 6.97 (br s, 2H), 6.41 (dd, J= 7.6, 4.8 Hz, 1H), 4.51 (d, J= 6.4 Hz, 2H).

Step 2: N-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl) benzyl)-2-cyanothiazole- 4-carboxamide

To a solution of 7V-[[4-[2-(2-amino-3-pyridyl)imidazo[4,5-b]pyridin-3-yl]phen yl]methyl]-2- bromo-thiazole-4-carboxamide (100 mg, 198 μmol) in pyridine (3.5 mL) was added CuCN (37.1 mg, 415 μmol) at 25 °C. The mixture was stirred at 145 °C for 6 hr. The mixture was filtered and concentrated under reduced pressure. The residue was purified by prep-HPLC (column: Waters xbridge 150*25 mm 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 15% - 45% B over 10 min) to give N-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)-2-cyanothiazole-4-carboxamide (Example 244, 15 mg, yield: 17%) was obtained as a light-yellow solid. MS: m/z = 453.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.49 (d, J= 0.8 Hz, 1H), 8.30 (dt, J= 4.8, 1.2 Hz, 1H), 8.19 (br s, 1H), 8.10 (d, J= 8.0 Hz, 1H), 8.00 (d, J= 4.8 Hz, 1H), 7.50 (d, J= 8.0 Hz, 2H), 7.38 - 7.32 (m, 3H), 7.20 (d, J= 7.6 Hz, 1H), 6.52 (br s, 2H), 6.38 (dd, J= 7.6, 4.8 Hz, 1H), 4.64 (d, J= 6.4 Hz, 2H).

[00774] Example 245: N-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2-cyanothiazole-5-carboxamide

Step 1 : N-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din-3-yl)benzyl)-2- bromothiazole-5-carboxamide

To a solution of Intermediate 4 (300 mg, 764 μmol) in dimethylformamide (2 mL) were added HATU (436 mg, 1.15 mmol), DIEA (395 mg, 3 mmol) and 2-bromothiazole-5-carboxylic acid (175 mg, 841 μmol). The mixture was stirred at 25 °C for 16 hr. The reaction mixture was quenched with H ₂ O (10 mL) at 25 °C, and then extracted with EtOAc (10 mL x 4). The combined organic layers were washed with brine (10 mL x 2), dried over Na ₂ SO ₄ , filtered, concentrated and purified by prep-HPLC (neutral condition: column: Waters xbridge 150*25mm 10 μm; mobile phase: [water (NH4HCO3) - ACN]; B%: 40% - 70%, 9 min) to give N-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din-3-yl)benzyl)-2- bromothiazole-5-carboxamide (142 mg, yield: 32%) as a light-yellow lyophilized powder. MS: m/z = 582.2, 584.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.44 (t, J= 6.0 Hz, 1H), 8.33 - 8.24 (m, 2H), 8.05 - 7.97 (m, 4H), 7.50 - 7.44 (m, 6H), 7.41 - 7.37 (m, 1H), 7.22 (dd, J= 7.6, 1.6 Hz, 1H), 6.93 (br s, 2H), 6.42 (dd, J= 7.6, 5.2 Hz, 1H), 4.58 (d, J= 6.0 Hz, 2H). Step 2 : 7V-(4-(2-(2- Aminopyridin-3 -yl)-5-phenyl-3H-imidazo[4, 5-b]pyridin-3 -yl)benzyl)-2- cyanothiazole-5-carboxamide

To a solution of N-[[4-[2-(2-amino-3-pyridyl)-5-phenyl-imidazo[4,5-b]pyridin- 3- yl]phenyl]methyl]-2-bromo-thiazole-5-carboxamide (100 mg, 172 μmol) in pyridine (4 mL) was added CuCN (32.3 mg, 361 μmol) at 25 °C. The mixture was stirred at 145 °C for 6 hr. Filtered and concentrated under reduced pressure. The residue was purified by prep-HPLC(column: Waters xbridge 150*25 mm 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 35% - 65% B over 10 min) to give N-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din- 3-yl)benzyl)-2-cyanothiazole-5-carboxamide (Example 245, 5 mg, yield: 5.5%) as a light-yellow solid. MS: m/z = 529.2 [M + H] ⁺ . ¹ H NM1 R (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.42 (s, 1H), 8.17 (d, J = 8.4 Hz, 1H), 8.05 – 7.88 (m, 5H), 7.54 (d, J = 8.0 Hz, 2H), 7.47 – 7.36 (m, 5H), 7.18 (d, J = 7.6 Hz, 1H), 6.52 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 4.65 (d, J = 6.0 Hz, 2H). [00775] Example 246: N-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2-cyanothiazole-4-carboxamide Example 246 was prepared in a manner similar to Example 244. MS: m/z = 529.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.28 (s, 1H), 8.03 - 7.93 (m, 2H), 7.82 - 7.76 (m, 3H), 7.66 (d, J = 8.4 Hz, 1H), 7.33 – 7.16 (m, 7H), 6.97 (dd, J = 7.6, 1.6 Hz, 1H), 6.29 (br s, 2H), 6.18 (dd, J = 7.6, 4.8 Hz, 1H), 4.45 (d, J = 6.4 Hz, 1H). [00776] Example 247: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carbonyl)thiazole-2-carbo nitrile Example 247 was prepared in a manner similar to Example 244. MS: m/z = 598.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.02 (s, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.83 – 7.80 (m, 3H), 7.69 (d, J = 8.8 Hz, 1H), 7.34 – 7.20 (m, 7H), 6.94 (dd, J = 7.6, 1.6 Hz, 1H), 6.38 (br s, 2H), 6.17 (dd, J = 7.6, 4.8 Hz, 1H), 3.53 (s, 2H), 3.47 – 3.43 (m, 4H), 2.37 – 2.33 (m, 2H), 2.30 – 2.25 (m, 2H). [00777] Example 248: 4-((7-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-7-azaspiro[3.5]nonan-2-yl)amino)-1,3, 5-triazine-2-carbonitrile Example 248 was prepared in a manner similar to Example 223. MS: m/z = 620.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.72 - 8.46 (m, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.08 - 8.05 (m, 1H), 8.02 (d, J = 8.0 Hz, 2H), 7.81 (d, J = 8.4 Hz, 1H), 7.67 - 7.51 (m, 2H), 7.48 - 7.41 (m, 4H), 7.39 - 7.35 (m, 1H), 7.08 (d, J = 7.6 Hz, 1H), 6.60 (br s, 2H), 6.38 - 6.33 (m, 1H), 5.99 - 5.91 (m, 1H), 4.50 - 4.41 (m, 1H), 3.77 - 3.54 (m, 2H), 2.55 - 2.39 (m, 4H), 1.65 - 1.53 (m, 8H). [00778] Example 249: 4-(7-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1,3,5- triazine-2-carbonitrile Example 249 was prepared in a manner similar to Example 223. MS: m/z = 606.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.68 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.03 - 7.98 (m, 4H), 7.48 - 7.44 (m, 6H), 7.42 - 7.38 (m, 1H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.87 (s, 4H), 3.58 (s, 2H), 2.42 - 2.34 (m, 4H), 1.82 - 1.48 (m, 4H). [00779] Example 250: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-1,4-diazepan-1-yl)-1,3,5-triazine-2-c arbonitrile Example 250 was prepared in a manner similar to Example 223.MS: m/z = 580.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.56 (d, J = 10.4 Hz, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.07 - 8.05 (m, 1H), 8.03 - 8.00 (m, 3H), 7.81 (d, J = 8.4 Hz, 1H), 7.51 - 7.48 (m, 2H), 7.44 - 7.40 (m, 4H), 7.13 - 7.09 (m, 1H), 6.75 (br s, 2H), 6.39 - 6.35 (m, 1H), 3.95 - 3.91 (m, 2H), 3.90 - 3.87 (m, 2H), 3.77 (s, 2H), 2.87 - 2.83 (m, 2H), 2.74 - 2.70 (m, 2H), 2.02 - 2.00 (m, 2H). [00780] Example 251: 4-(7-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2,7-diazaspiro[4.4]nonan-2-yl)-1,3,5- triazine-2-carbonitrile Example 251 was prepared in a manner similar to Example 223. MS: m/z = 606.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Acetonitrile-d ₃ ) δ 8.51 (d, J = 8.4 Hz, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.04 - 7.95 (m, 3H), 7.87 (d, J = 8.4 Hz, 1H), 7.51 - 7.37 (m, 7H), 7.13 - 7.11 (m, 1H), 6.60 (br s, 2H), 6.31 (dd, J = 7.6, 4.8 Hz, 1H), 3.73 - 3.67 (m, 2H), 3.64 - 3.55 (m, 2H), 3.54 - 3.42 (m, 2H), 2.76 - 2.69 (m, 1H), 2.67 - 2.61 (m, 1H), 2.59 - 2.55 (m, 1H), 2.51 - 2.47 (m, 1H), 2.08 - 1.97 (m, 2H), 1.89 - 1.82 (m, 2H). [00781] Example 252: 4-(2-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2,8-diazaspiro[4.5]decan-8-yl)-1,3,5- triazine-2-carbonitrile Example 252 was prepared in a manner similar to Example 223. MS: m/z = 620.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Acetonitrile-d ₃ ) δ 8.52 (s, 1H), 8.17 (d, J = 8.4 Hz, 1H), 8.07 - 7.94 (m, 3H), 7.90 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.47 - 7.37 (m, 5H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 6.57 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.92 - 3.75 (m, 4H), 3.73 (s, 2H), 2.70 (t, J = 6.4 Hz, 2H), 2.52 (s, 2H), 1.72 - 1.69 (m, 2H), 1.67 - 1.62 (m, 4H). [00782] Example 253: 4-(2-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2,7-diazaspiro[4.5]decan-7-yl)-1,3,5- triazine-2-carbonitrile Example 253 was prepared in a manner similar to Example 223. MS: m/z = 620.5 [M + H] ⁺ . ¹ H NMR (400 MHz, Acetonitrile-d ₃ ) δ 8.60 - 8.37 (m, 1H), 8.17 (dd, J = 8.4, 1.2 Hz, 1H), 8.06 - 7.96 (m, 3H), 7.89 (d, J = 8.4 Hz, 1H), 7.53 - 7.37 (m, 7H), 7.21 - 7.08 (m, 1H), 6.61 (br s, 2H), 6.33 (dd, J = 7.6, 4.8 Hz, 1H), 3.95 - 3.82 (m, 2H), 3.80 - 3.73 (m, 1H), 3.69 - 3.62 (m, 2H), 3.61 - 3.51 (m, 1H), 2.89 - 2.83 (m, 1H), 2.58 (d, J = 9.2 Hz, 1H), 2.52 - 2.48 (m, 1H), 1.97 - 1.95 (m, 1H), 1.73 - 1.63 (m, 4H), 1.61 - 1.53 (m, 2H). [00783] Example 254: 4-(9-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2,9-diazaspiro[5.5]undecan-2-yl)-1,3, 5-triazine-2-carbonitrile

Step 1 : 3-(3-(4-((2-(4-Chloro-l,3,5-triazin-2-yl)-2,9-diazaspiro[5.5 ]undecan-9- yl)methyl)phenyl)-5-phenyl-3 H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine To a mixture of Intermediate 162 (100 mg, 189 μmol) in THF (2 mL) and H ₂ O (0.5 mL) was added K ₂ CO ₃ (78.3 mg, 566 μmol) at 0°C. The mixture was stirred at 0°C for 15 minutes and 2,4-dichloro-l,3,5-triazine (28.3 mg, 189 μmol) was added. The mixture was stirred at 0 °C for 15 minutes, and then was quenched with H ₂ O (20 mL), extracted with EtOAc (20 mL x 3). The combined organic phases were washed with brine (20 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. The mixture was purified by silica gel flash chromatography (eluent 0-8% MeOH in CH ₂ CI ₂ ) and prep-TLC (10% MeOH in CH ₂ CI ₂ ) to give 3-(3-(4-((2-(4-chloro- l,3,5-triazin-2-yl)-2,9-diazaspiro[5.5]undecan-9-yl)methyl)p henyl)-5-phenyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (17.4 mg, yield: 29%) as a yellow solid. MS: m/z = 665.3 [M+Na] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.25 (d, J= 2.0 Hz, 1H), 8.06 (d, J= 8.0 Hz, 1H), 8.00 - 7.93 (m, 3H), 7.73 (d, J= 8.4 Hz, 1H), 7.50 - 7.44 (m, 2H), 7.38 - 7.29 (m, 5H), 7.06 - 6.98 (m, 1H), 6.54 (br s, 2H), 6.33 - 6.25 (m, 1H), 3.77 - 3.59 (m, 6H), 2.63 - 2.38 (m, 4H), 1.61- 1.48 (m, 8H).

Step 2: 4-(9-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3Zf-imidazo[4,5-b] pyridin-3-yl)benzyl)-2,9- diazaspiro[5.5 ]undecan-2-yl)- 1 ,3 , 5-triazine-2-carbonitrile

To a solution of 3-[3-[4-[[2-(4-chloro-l,3,5-triazin-2-yl)-2,9-diazaspiro[5.5 ]undecan-9- yl]methyl]phenyl]-5-phenyl-imidazo[4,5-b]pyridin-2-yl]pyridi n-2-amine (150 mg, 233 μmol) in DMSO (dry) (5 mL) were added KCN (330 mg, 5.07 mmol) and DABCO (5.23 mg, 46.6 μmol) at 20 °C. The mixture was stirred at 20 °C for 12 hr. Water (10 mL) was added to the mixture. The aqueous layer was extracted with EtOAc (20 mL x 2). The combined organic layers were washed with H ₂ O (15 mL x 2), brine (15 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. The residue was purified by prep-TLC (CH ₂ CI ₂ : MeOH = 10 : 1) to give 4-(9-(4- (2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3 -yl)benzyl)-2,9- diazaspiro[5.5]undecan-2-yl)-l,3,5-triazine-2-carbonitrile (Example 254, 38.1 mg, yield: 26%) as a yellow solid. MS: m/z = 634.3 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.67 (d, J= 3.2 Hz, 1H), 8.27 (d, J= 8.4 Hz, 1H), 8.03 - 7.97 (m, 4H), 7.47 - 7.37 (m, TH), 7.18 - 7.13 (m, 1H), 7.04 (d, J= 6.4 Hz, 2H), 6.36 (dd, J= 7.6, 4.8 Hz, 1H), 3.80 - 3.78 (m, 1H), 3.73 (s, 2H), 3.67 - 3.65 (m, 1H), 3.59 (d, J = 8.8 Hz, 2H), 2.46 - 2.44 (m, 2H), 2.38 - 2.30 (m, 2H), 1.61 - 1.51 (m, 4H), 1.48 - 1.38 (m, 4H). [00784] Example 255: (R)-4-(7-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)-2,7-diazaspiro[4.4]nonan-2-yl)-1,3,5- triazine-2-carbonitrile Example 255 was prepared in a manner similar to Example 254. MS: m/z = 606.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.54 (d, J = 4.0 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 8.05 - 7.99 (m, 2H), 7.98 - 7.91 (m, 2H), 7.58 - 7.51 (m, 2H), 7.49 - 7.32 (m, 5H), 7.33 - 7.28 (m, 1H), 6.44 (dd, J = 7.2, 4.8 Hz, 1H), 3.77 (d, J = 2.8 Hz, 2H), 3.69 - 3.52 (m, 4H), 2.86 - 2.58 (m, 4H), 2.10 - 1.99 (m, 2H), 1.96 - 1.87 (m, 2H). [00785] Example 256: 4-((2R,6R)-4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,6-dimethylpiperazin-1-y l)-1,3,5-triazine-2-carbonitrile Example 256 was prepared in a manner similar to Example 223. MS: m/z = 594.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.76 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.08 - 7.95 (m, 4H), 7.57 - 7.36 (m, 7H), 7.18 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 4.40 - 4.33 (m, 2H), 4.00 - 3.79 (m, 2H), 3.18 - 3.09 (m, 2H), 2.77 - 2.68 (m, 2H), 1.35 (d, J = 6.4 Hz, 6H). [00786] Example 257: 4-(5-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-1, 3,5-triazine-2-carbonitrile Example 257 was prepared in a manner similar to Example 223. MS: m/z = 592.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Acetonitrile-d ₃ ) δ 8.52 - 8.39 (m, 1H), 8.17 (d, J= 8.4 Hz, 1H), 8.04 - 7.97 (m, 3H), 7.89 (d, J= 8.4 Hz, 1H), 7.54 (d, J= 8.4 Hz, 2H), 7.50 - 7.35 (m, 5H), 7.15 (d, J= 6.0 Hz, 1H), 6.57 (br s, 2H), 6.38 (dd, J= 7.6, 4.8 Hz, 1H), 4.76 - 4.62 (m, 1H), 3.95 - 3.81 (m, 3H), 3.58 - 3.46 (m, 1H), 3.08 - 3.04 (m, 1H), 3.06 (s, 1H), 1.78 - 1.66 (m, 2H), 1.30 - 1.24 (m, 2H). [00787] Example 258: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4, 5- b]pyridin-3 -yl)benzyl)piperazin- 1 -yl)pyrimidine-2-carbonitrile

To a solution of Intermediate 53 (147 mg, 485 μmol, TFA salt) and Intermediate 50 (200 mg, 485 μmol, HC1 salt) in DMF (5 mL) were added Nal (36.3 mg, 242 μmol) and K ₂ CO ₃ (335 mg, 2.43 mmol). The mixture was stirred at 50 °C for 2 hr. The reaction mixture was diluted with H ₂ O (20 mL) and extracted with EtOAc (30 mL* 3). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0 ~ 7% MeOH in CH ₂ CI ₂ ) to give 4-(4-(4-(2-(2-aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4, 5-b]pyri din-3- yl)benzyl)piperazm-l-yl)pyrimidine-2-carbonitrile (Example 258, 46.2 mg, yield: 17%) as yellow solid. MS: m/z = 529.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.20 (d, J = 6.4 Hz, 1H), 8.01 - 7.96 (m, 2H), 7.54 (d, J = 8.0 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 7.30 - 7.25 (m, 2H), 6.97 (d, J = 6.4 Hz, 1H), 6.47 (dd, J = 7.6, 5.2 Hz, 1H), 3.85 - 3.75 (m, 4H), 3.65 (s, 2H), 2.64 - 2.59 (m, 4H), 2.23 - 2.15 (m, 1H), 1.00 - 0.93 (m, 4H).

[00788] Example 259: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(2-oxo-l,2-dihydropyridin -3- yl)-3H-imidazo[4,5 -b]py ridin-3 -yl)benzyl)piperazin- 1 -yl)pyrimidine-2-carbonitrile

Example 259 was prepared in a manner similar to Example 225. MS: m/z = 582.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.51 (d, J= 8.4 Hz, 1H), 8.35 (dd, J= 7.2, 2.0 Hz, 1H), 8.20 - 8.13 (m, 2H), 7.98 (dd, J= 4.8, 1.6 Hz, 1H), 7.56 (d, J= 8.4 Hz, 2H), 7.52 - 7.48 (m, 1H), 7.45 (d, J= 8.4 Hz, 2H), 7.32 (dd, J= 7.6, 1.6 Hz, 1H), 6.95 (d, J= 6.4 Hz, 1H), 6.54 - 6.49 (m, 1H), 6.47 (dd, J= 8.0, 5.2 Hz, 1H), 3.83 - 3.73 (m, 4H), 3.68 (s, 2H), 2.62 - 2.57 (m, 4H).

[00789] Example 260: 4-(4-(4-(2-(2-aminopyridin-3-yl)-5-(l-methyl-2-oxo-l,2- dihy dropyridin-3 -yl)-3H-imidazo[4, 5-b]pyridin-3 -yl)benzyl)piperazin- 1 -yl)py rimidine-2- carbonitrile

To a solution of Intermediate 57 (150 mg, 339 μmol) and Intermediate 53 (103 mg, 339 μmol, TFA) in DMF (2 mL) were added K ₂ CO ₃ (234 mg, 1.69 mmol) and Nal (10.2 mg, 67.7 μmol). The mixture was stirred at 80 °C for 16 hr. The reaction mixture was quenched with H ₂ O (5 mL) at 25°C, and then diluted with CH ₂ CI ₂ (10 mL) and extracted with H ₂ O (15 mL x 2). The combined organic layers were washed with brine (15 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-HPLC (column: Waters xbridge 150 * 25 mm * 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 30% - 50% B over 14 min), 4-(4-(4-(2-(2-aminopyridin-3 -yl)-5-( 1 -methyl-2-oxo- 1 ,2-dihy dropyridin-3 -yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-l-yl)pyrimidine- 2-carbonitrile (Example 260, 10.6 mg, yield: 5.3%) was obtained as a yellow solid. MS: m/z = 596.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.46 (d, J= 8.4 Hz, 1H), 8.27 - 8.22 (m, 1H), 8.20 - 8.14 (m, 2H), 8.00 - 7.96 (m, 1H), 7.74 (dd, J= 6.8, 2.4 Hz, 1H), 7.56 (d, J= 8.4 Hz, 2H), 7.45 (d, J= 8.4 Hz, 2H), 7.32 (dd, J= 8.0, 2.0 Hz, 1H), 7.01 - 6.92 (m, 1H), 6.52 - 6.42 (m, 2H), 3.83 - 3.74 (m, 4H), 3.70 - 3.67 (m, 5H), 2.62 - 2.57 (m, 4H).

[00790] Example 261: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(l-methyl-2-oxo-l,2- dihydropyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)pi peridin-4-yl)amino)pyrimidine-2- carbonitrile

To a solution of Intermediate 57 (160 mg, 361 μmol) and Intermediate 51 (88.1 mg, 278 μmol) in DMF (5 mL) were added Nal (10.8 mg, 72.3 μmol) and K ₂ CO ₃ (299 mg, 2.17 mmol). The mixture was stirred at 50 °C for 2 hr. The reaction mixture was diluted with H ₂ O (50 mL) and extracted with EtOAc (50 mL x 2). The combined organic layers were washed with brine (50 mL x 2), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0~10% MeOH in CH ₂ Cl ₂ ) and then purified by prep-HPLC (column: Waters Xbridge 150 x 25mm x 5um; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 22% - 52% B over 10 min), 4-((1-(4-(2-(2-aminopyridin-3-yl)-5-(1-methyl-2- oxo-1,2-dihydropyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)b enzyl)piperidin-4- yl)amino)pyrimidine-2-carbonitrile (Example 261, 54.5 mg, yield: 24%) was obtained as a light- yellow lyophilized powder. MS: m/z = 610.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide- d ₆ ) δ 8.64 (d, J = 8.4 Hz, 1H), 8.21 - 8.17 (m, 2H), 8.09 - 8.05 (m, 2H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.85 (dd, J = 6.8, 2.0 Hz, 1H), 7.50 - 7.48 (m, 4H), 7.13 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.40 - 6.35 (m, 2H), 3.88 - 3.76 (m, 1H), 3.59 (s, 2H), 3.55 (s, 3H), 2.85 - 2.80 (m, 2H), 2.19 - 2.10 (m, 2H), 1.98 - 1.83 (m, 2H), 1.55 - 1.43 (m, 2H) [00791] Example 262: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-cyclobutyl-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile Example 262 is prepared in a manner similar to Example 261. MS: m/z = 557.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.25 - 8.02 (m, 3H), 7.97 (dd, J = 4.8, 2.0 Hz, 1H), 7.45 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4 Hz, 1H), 7.09 (dd, J = 7.6, 1.6 Hz, 1H), 6.97 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 3.86 - 3.76 (m, 1H), 3.74 - 3.64 (m, 1H), 3.58 (s, 2H), 2.87 - 2.75 (m, 2H), 2.28 - 2.09 (m, 6H), 1.99 - 1.74 (m, 4H), 1.56 - 1.42 (m, 2H). [00792] Example 263: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(cyclohex-1-en-1-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 263 was prepared in a manner similar to Example 225. MS: m/z = 583.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6) δ 8.22 - 8.01 (m, 3H), 7.97 (dd, J = 4.8, 2.0 Hz, 1H), 7.52 (d, J = 8.4 Hz, 1H), 7.48 - 7.41 (m, 2H), 7.40 - 7.33 (m, 2H), 7.97 (dd, J = 8.0, 2.0 Hz, 1H), 7.06 - 6.95 (m, 3H), 6.76 - 6.53 (m, 2H), 6.34 (dd, J = 8.0, 5.2 Hz, 1H), 3.91 - 3.69 (m, 1H), 3.61 (s, 2H), 2.83 - 2.77 (m, 2H), 2.46 - 2.42 (m, 2H), 2.22 - 2.09 (m, 4H), 1.89 - 1.87 (m, 2H), 1.72 - 1.64 (m, 2H), 1.62 - 1.54 (m, 2H), 1.53 - 1.38 (m, 2H). [00793] Example 264: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-cyclohexyl-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile Example 264 was prepared in a manner similar to Example 225. MS: m/z = 585.4. [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.03 (d, J = 8.0 Hz, 1H), 8.01 - 7.96 (m, 1H), 7.94 (dd, J = 5.2, 2.0 Hz, 1H), 7.50 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 7.33 - 7.22 (m, 2H), 6.68 - 6.57(m, 1H), 6.44 (dd, J = 7.6, 4.8 Hz, 1H), 4.06 - 3.85 (m, 1H), 3.64 (s, 2H), 2.95 (d, J = 11.6 Hz, 2H), 2.81 - 2.73 (m, 1H), 2.31 - 2.19 (m, 2H), 2.03 - 1.96 (m, 2H), 1.93 - 1.87 (m, 2H), 1.86 - 1.79 (m, 2H), 1.77 - 1.68 (m, 1H), 1.66 - 1.51 (m, 4H), 1.46 - 1.35 (m, 2H), 1.33 - 1.24 (m, 1H). [00794] Example 265: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(3-cyanophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile A mixture of Intermediate 61 (60 mg, 200 µmol), 4-chloropyrimidine-2-carbonitrile (18.4 mg, 132 µmol) and DIEA (47 mg, 360 µmol) in NMP (2 mL) was taken up into a microwave tube. The sealed tube was stirred at 130 °C for 0.5 hr under microwave. The reaction mixture was poured into H ₂ O (10 mL), extracted with CH ₂ Cl ₂ (15 mL x 3). The organic phase was dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by prep-HPLC (column: Phenomenex C18150*25mm*10 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 40% - 70% B over 14 min) to give 4-((1-(4-(2-(2-Aminopyridin- 3-yl)-5-(3-cyanophenyl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl )piperidin-4- yl)amino)pyrimidine-2-carbonitrile (Example 265, 5.9 mg, yield: 8%) as an off-white lyophilized powder. MS: m/z = 604.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.43 - 8.29 (m, 2H), 8.23 (d, J= 8.4 Hz, 1H), 8.04 - 7.93 (m, 3H), 7.74 - 7.68 (m, 1H), 7.63 - 7.54 (m, 3H), 7.46 (d, J= 8.4 Hz, 2H), 7.33 (dd, J= 7.6, 1.6 Hz, 1H), 6.67 - 6.51 (m, 1H), 6.47 (dd, J= 7.6, 4.8 Hz, 1H), 4.09 - 3.86 (m, 1H), 3.66 (s, 2H), 3.01 - 2.92 (m, 2H), 2.32 - 2.23 (m, 2H), 2.03 - 1.98 (m, 2H), 1.66 - 1.55 (m, 2H).

[00795] Example 266: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(6-oxo-l,6-dihydropyridi n-3- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile

Example 266 was prepared in a manner similar to Example 225. MS: m/z = 596.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 11.92 - 11.76 (m, 1H), 8.20 (d, J= 8.4 Hz, 1H), 8.13 (dd, J= 9.2, 2.4 Hz, 1H), 8.10 - 8.03 (m, 3H), 7.99 (dd, J= 4.8, 1.6 Hz, 1H), 7.83 (d, J= 8.4 Hz, 1H), 7.49 - 7.46 (m, 2H), 7.44 - 7.40 (m, 2H), 7.11 (d, J= 6.0 Hz, 1H), 7.04 (br s, 2H), 6.70 - 6.66 (m, 1H), 6.43 (d, J= 9.6 Hz, 1H), 6.36 (dd, J= 7.6, 4.4 Hz, 1H), 3.86 - 3.78 (m, 1H), 3.58 (s, 2H), 2.85 - 2.81 (m, 2H), 2.20 - 2.12 (m, 2H), 1.94 - 1.86 (m, 2H), 1.54 - 1.45 (m, 2H).

[00796] Example 267: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(6-oxo-l,6-dihydropyridi n-2- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile

To a solution of Intermediate 63 (80 mg, 162 μmo) and 4-chloropyrimidine-2-carbonitrile (23 mg, 162 μmol) in ACN (3 mL) were added Nal (2.4 mg, 16 μmol) and K ₂ CO ₃ (67 mg, 487 μmol). The mixture was stirred at 80 °C for 2hr. The reaction mixture was quenched with H ₂ O (10 mL) at 25 °C, and extracted with EtOAc (15 mL x 2). The combined organic layers were washed with brine (20 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by prep-HPLC (column: Waters xbridge 150*25 mm 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 22% - 52%, 18 min) to give 4-((l-(4-(2-(2- aminopyridin-3-yl)-5-(6-oxo-1,6-dihydropyridin-2-yl)-3H-imid azo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile (Example 267, 15.5 mg, yield: 16%) as a yellow solid. MS: m/z = 596.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.77 (br s, 1H), 8.33 (d, J = 8.4 Hz, 1H), 8.21 - 8.13 (m, 1H), 8.10 - 8.00 (m, 3H), 7.67 - 7.42 (m, 6H), 7.16 d, J = 6.8 Hz, 1H), 7.03 (br s, 2H), 6.67 (d, J = 5.6 Hz, 1H), 6.50 - 6.42 (m, 1H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.88 - 3.76 (m, 1H), 3.60 (s, 2H), 2.86 - 2.80 (m, 2H), 2.22 - 2.12 (m, 2H), 1.93 - 1.85 (m, 2H), 1.56 - 1.45 (m, 2H). [00797] Example 268: 4-(2-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2,7-diazaspiro[3.5]nonan-7-yl)-1,3,5- triazine-2-carbonitrile Example 268 was prepared in a manner similar to Example 93. MS: m/z = 606.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Acetonitrile-d ₃ ) δ 8.52 (s, 1H), 8.17 (d, J = 8.4 Hz, 1H), 8.02 - 7.99 (m, 3H), 7.89 (d, J = 8.4 Hz, 1H), 7.48 - 7.39 (m, 7H), 7.17 - 7.12 (m, 1H), 6.55 (br s, 2H), 6.40 - 6.33 (m, 1H), 3.81 - 3.73 (m, 6H), 3.11 (s, 4H), 1.82 - 1.78 (m, 4H). [00798] Example 269: (S)-4-(7-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)-2,7-diazaspiro[4.4]nonan-2-yl)-1,3,5- triazine-2-carbonitrile Example 269 was prepared in a manner similar to Example 223. MS: m/z = 606.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.54 (d, J = 4.8 Hz, 1H), 8.13 (d, J = 8.4 Hz, 1H), 8.05 (dd, J = 4.8, 1.6 Hz, 1H), 8.01 (d, J = 8.0 Hz, 2H), 7.80 (d, J = 8.4 Hz, 1H), 7.51 - 7.37 (m, 7H), 7.11 - 7.03 (m, 1H), 6.63 (br s, 2H), 6.34 (dd, J = 7.6, 5.2 Hz, 1H), 3.74 - 3.56 (m, 6H), 2.79 - 2.72 (m, 2H), 2.62 - 2.57 (m, 2H), 2.10 - 2.04 (m, 2H), 2.01 - 1.91 (m, 2H). [00799] Example 270: 4-(3-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-1, 3,5-triazine-2-carbonitrile Example 270 was prepared in a manner similar to Example 223. MS: m/z = 592.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.52 (s, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.08 (dd, J = 4.8, 1.6 Hz, 1H), 8.04 - 8.01 (m, 2H), 7.81 (d, J = 8.4 Hz, 1H), 7.50 - 7.38 (m, 7H), 7.09 (dd, J = 7.6, 1.6 Hz, 1H), 6.63 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 4.83 - 4.79 (m, 2H), 3.62 (s, 2H), 2.86 - 2.80 (m, 2H), 2.42 - 2.36 (m, 2H), 2.13-2.10 (m, 2H), 1.99 - 1.95 (m, 2H). [00800] Example 271: 4-(8-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-1, 3,5-triazine-2-carbonitrile Example 271 was prepared in a manner similar to Example 223. MS: m/z = 592.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.55 (s, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.08 (d, J = 3.6 Hz, 1H), 8.04 - 8.01 (m, 2H), 7.81 (d, J = 8.4 Hz, 1H), 7.57 (d, J = 8.0 Hz, 2H) 7.47 - 7.38 (m, 5H), 7.13 (dd, J = 8.0, 1.2 Hz, 1H), 6.70 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 4.42 - 4.33 (m, 2H), 3.69 (s, 2H), 3.40 - 3.36 (m, 2H), 3.27 (d, J = 12.8 Hz, 2H), 2.12 - 2.06 (m, 2H), 1.32 - 1.30 (m, 2H). [00801] Example 272: 4-((1R,4R)-5-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,5-diazabicyclo[2.2.1]he ptan-2-yl)-1,3,5-triazine-2- carbonitrile Example 272 was prepared in a manner similar to Example 223. MS: m/z = 578.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.54 (d, J = 18.4 Hz, 1H), 8.13 (d, J = 8.4 Hz, 1H), 8.08 - 8.05 (m, 1H), 8.01 (d, J = 7.2 Hz, 2H), 7.80 (d, J = 8.4 Hz, 1H), 7.52 - 7.35 (m, 7H), 7.09 (dd, J = 8.0, 1.6 Hz, 1H), 6.62 (s, 2H), 6.38- 6.34 (m, 1H), 4.98 - 4.95 (m, 1H), 3.87 (s, 2H), 3.85 - 3.81 (m, 1H), 3.75 - 3.70 (m, 1H), 3.47 - 3.42 (m, 1H), 3.06 (d, J = 10.0 Hz, 1H), 2.72 (dd, J = 13.2, 10.8 Hz, 1H), 2.12 (d, J = 10.0 Hz, 1H), 1.87 (d, J = 10.0 Hz, 1H). [00802] Example 273: (R)-4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)-2-methylpiperazin-1-yl)-1,3,5-triazin e-2-carbonitrile Example 273 was prepared in a manner similar to Example 223. MS: m/z = 580.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Acetonitrile-d ₃ ) δ 8.56 (d, J = 4.8 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 8.05 - 8.02 (m, 3H), 7.90 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.49 - 7.39 (m, 5H), 7.16 (dd, J = 8.0, 1.6 Hz, 1H), 6.60 (br s, 1H), 6.39 (dd, J = 8.0, 4.8 Hz, 1H), 4.95 - 4.74 (m, 1H), 4.60 - 4.40 (m, 1H), 3.72 - 3.54 (m, 2H), 3.36 - 3.23 (m, 1H), 3.02 - 2.91 (m, 1H), 2.84 - 2.73 (m, 1H), 2.29 - 2.24 (m, 1H), 2.18 - 2.16 (m, 1H), 1.35 - 1.32 (m, 3H). [00803] Example 274: (S)-4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)-2-methylpiperazin-1-yl)-1,3,5-triazin e-2-carbonitrile Example 274 was prepared in a manner similar to Example 223. MS: m/z = 580.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Acetonitrile-d ₃ ) δ 8.57 (d, J = 4.4 Hz, 1H), 8.19 (d, J = 8.4 Hz, 1H), 8.07 - 8.01 (m, 3H), 7.91 (d, J = 8.0 Hz, 1H), 7.58 (d, J = 8.0 Hz, 2H), 7.50 - 7.40 (m, 5H), 7.19 - 7.14 (m, 1H), 6.62 (br s, 2H), 6.40 (dd, J = 7.6, 5.2 Hz, 1H), 4.99 - 4.74 (m, 1H), 4.63 - 4.39 (m, 1H), 3.73 - 3.55 (m, 2H), 3.36 - 3.27 (m, 1H), 3.03 - 2.95 (m, 1H), 2.84 - 2.75 (m, 1H), 2.29 - 2.23 (m, 1H), 2.13 - 2.09 (m, 1H), 1.35 - 1.32 (m, 3H). [00804] Example 275: 4-((2S,6S)-4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,6-dimethylpiperazin-1-y l)-1,3,5-triazine-2-carbonitrile Example 275 was prepared in a manner similar to Example 223. MS: m/z = 594.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Acetonitrile-d ₃ ) δ 8.59 (s, 1H), 8.17 (d, J = 8.4 Hz, 1H), 8.05 - 7.96 (m, 3H), 7.90 (d, J = 8.4 Hz, 1H), 7.60 - 7.53 (m, 2H), 7.49 - 7.39 (m, 5H), 7.19 - 7.11 (m, 1H), 6.62 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 4.41 (br s, 2H), 3.96 - 3.78 (m, 2H), 3.22 - 3.11 (m, 2H), 2.74 (dd, J = 12.4, 3.6 Hz, 2H), 1.40 (d, J = 6.4 Hz, 6H). [00805] Example 276: 4-(7-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-4,7-diazaspiro[2.5]octan-4-yl)-1,3,5- triazine-2-carbonitrile Example 276 was prepared in a manner similar to Example 223. MS: m/z = 592.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Acetonitrile-d ₃ ) δ 8.60 (d, J = 4.0 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 8.05 - 8.00 (m, 3H), 7.91 (d, J = 8.4 Hz, 1H), 7.54 - 7.41 (m, 7H), 7.14 (dd, J = 7.6, 1.6 Hz, 1H), 6.58 (br s, 2H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 4.11 - 3.98 (m, 2H), 3.61 (s, 2H), 2.66 - 2.57 (m, 2H), 2.47 - 2.41 (m, 2H), 1.00 - 0.95 (m, 2H), 0.90 - 0.85 (m, 2H). [00806] Example 277: 4-((2R,6S)-4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,6-dimethylpiperazin-1-y l)-1,3,5-triazine-2-carbonitrile Example 277 was prepared in a manner similar to Example 254. MS: m/z = 594.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.60 (s, 1H), 8.16 (d, J = 8.4 Hz, 1H), 8.08 - 8.02 (m, 3H), 7.84 (d, J = 8.4 Hz, 1H), 7.59 (d, J = 8.4 Hz, 2H), 7.47 - 7.39 (m, 5H), 7.18 - 7.16 (m, 1H), 6.88 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 4.78 - 4.70 (m, 2H), 3.67 (s, 2H), 2.84 (d, J = 11.6 Hz, 2H), 2.38 - 2.32 (m, 2H), 1.41 (d, J = 6.8 Hz, 6H). [00807] Example 278: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)azepan-4-yl)amino)-1,3,5-triazine-2-ca rbonitrile Example 278 was prepared in a manner similar to Example 268. MS: m/z = 594.4 [M + H]+. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.92 - 8.89 (m, 1H), 8.71 - 8.54 (m, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.54 - 7.49 (m, 2H), 7.48 - 7.43 (m, 4H), 7.40 - 7.36 (m, 1H), 7.15 (d, J = 7.6 Hz, 1H), 7.05 (br s, 2H), 6.38 - 6.34 (m, 1H), 4.14 - 3.99 (m, 1H), 3.76 - 3.65 (m, 2H), 2.67 - 2.63 (m, 2H), 1.98 - 1.50 (m, 8H). [00808] Example 279: 4-((4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-1,4-oxazepan-6-yl)amino)-1,3,5-triazi ne-2-carbonitrile Example 279 was prepared in a manner similar to Example 93. MS: m/z = 596.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.91 - 8.84 (m, 1H), 8.65 - 8.58 (m, 1H), 8.29 - 8.24 (m, 1H), 8.04 - 7.96 (m, 4H), 7.59 - 7.54 (m, 2H), 7.48 - 7.40 (m, 5H), 7.12 - 7.03 (m, 3H), 6.34 - 6.24 (m, 1H), 4.39 - 4.14 (m, 2H), 3.96 - 3.91 (m, 1H), 3.85 - 3.79 (m, 2H), 3.71 - 3.68 (m, 2H), 3.00 - 2.88 (m, 2H), 2.82 - 2.74 (m, 2H). [00809] Example 280: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-methyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile Example 280 was prepared in a manner similar to Example 225. MS: m/z = 517.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6) δ 8.13 - 8.03 (m, 3H), 7.99 (dd, J = 4.8, 2.0 Hz, 1H) 7.45 (d, J = 8.0 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.0 Hz, 1H), 7.09 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.68 (d, J = 6.0 Hz, 1H), 6.34 (dd, J = 8.0, 5.2 Hz, 1H), 3.89 - 3.74 (m, 1H), 3.57 (s, 2H), 2.85 - 2.79 (m, 2H), 2.52 (s, 3H), 2.19 - 2.10 (m, 2H), 1.94 - 1.85 (m, 2H), 1.57 - 1.43 (m, 2H). [00810] Example 281: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(2-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 2-carbonitrile Example 281 was prepared in a manner similar to Example 225. MS: m/z = 583.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.31 - 8.26 (m, 2H), 8.00 (dd, J = 4.8, 1.2 Hz, 1H), 7.85 - 7.76 (m, 2H), 7.52 - 7.42 (m, 5H), 7.37 - 7.27 (m, 2H), 7.18 - 7.14 (m, 1H), 7.11 (d, J = 6.4 Hz, 1H), 7.00 (br s, 2H), 6.37 (dd, J = 7.2, 4.8 Hz, 1H), 3.80 - 3.63 (m, 4H), 3.62 (s, 2H), 2.49 - 2.46 (m, 4H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -117.17. [00811] Example 282: 2-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(2-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 4-carbonitrile Example 282 was prepared in a manner similar to Example 225. MS: m/z = 583.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.64 (d, J = 4.8 Hz, 1H), 8.30 (d, J = 8.4 Hz, 1H), 8.00 (dd, J = 4.8, 2.0 Hz, 1H), 7.84 - 7.76 (m, 2H), 7.51 - 7.43 (m, 5H), 7.38 - 7.30 (m, 2H), 7.20 - 7.13 (m, 2H), 6.99 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.80 - 3.73 (m, 4H), 3.62 (s, 2H), 2.54 - 2.52 (m, 4H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -117.18. [00812] Example 283: 2-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(3-oxo-1,4-diazepan-1-yl) -3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 4-carbonitrile Example 283 was prepared in a manner similar to Example 225. MS: m/z = 601.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ )) δ 8.64 (d, J = 4.8 Hz, 1H), 8.00 - 7.89 (m, 2H), 7.47 - 7.42 (m, 3H), 7.34 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 4.4 Hz, 1H), 7.03 - 6.95 (m, 3H), 6.80 (d, J = 8.8 Hz, 1H), 6.32 (dd, J = 7.6, 4.8 Hz, 1H), 4.18 (s, 2H), 3.86 - 3.73 (m, 6H), 3.61 (s, 2H), 3.20 - 3.15 (m, 2H), 2.48 - 2.46 (m, 4H), 1.68 - 1.61 (m, 2H). [00813] Example 284: 6-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(3-oxo-1,4-diazepan-1-yl) -3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 4-carbonitrile Example 284 was prepared in a manner similar to Example 225. MS: m/z = 601.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.56 (d, J = 0.8 Hz, 1H), 7.95 (d, J = 9.2 Hz, 1H), 7.93 (dd, J = 4.8, 2.0 Hz, 1H), 7.57 (s, 1H), 7.46 - 7.42 (m, 3H), 7.35 (d, J = 8.0 Hz, 2H), 7.02 - 6.96 (m, 3H), 6.80 (d, J = 8.8 Hz, 1H), 6.30 (dd, J = 7.6, 4.8 Hz, 1H), 4.18 (s, 2H), 3.83 - 3.80 (m, 2H), 3.77 - 3.67 (m, 4H), 3.61 (s, 2H), 3.20 - 3.16 (m, 2H), 2.48 - 2.45 (m, 4H), 1.67 - 1.62 (m, 2H). [00814] Example 285: 4-(8-(4-(2-(2-Aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-1, 3,5-triazine-2-carbonitrile To a solution of Intermediate 56 (300 mg, 656 µmol) and Intermediate 71 (200 mg, 606 µmol, TFA salt) in CH ₃ CN (10 mL) were added NaI (19.7 mg, 132 µmol) and K ₂ CO ₃ (544 mg, 3.94 mmol). The mixture was stirred at 50 °C for 5 hr. The reaction mixture was diluted with H ₂ O (10 mL) and extracted with CH ₂ Cl ₂ (10 mL x 2). The combined organic layers were washed with brine (10 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0~5% MeOH in CH ₂ Cl ₂ ), and then the crude product was triturated with CH ₃ CN (5mL) at 25 °C for 30 min. After purified again by prep-TLC (100% EtOAc), 4-(8-(4-(2-(2-aminopyridin-3-yl)-5-morpholino-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-3,8-diazabicyclo[3.2.1]oc tan-3-yl)-1,3,5-triazine-2- carbonitrile (Example 285, 21.7 mg, yield: 5.2%) was obtained as a light-yellow solid. MS: m/z = 601.5 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.71 (s, 1H), 8.02 - 7.94 (m, 2H), 7.53 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 7.04 - 6.98 (m, 3H), 6.90 (d, J = 8.8 Hz, 1H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 4.29 (d, J = 12.0 Hz, 1H), 4.18 (d, J = 12.0 Hz, 1H), 3.71 - 3.66 (m, 4H), 3.64 (s, 2H), 3.44 - 3.35 (m, 6H), 3.19 (d, J = 12.8 Hz, 2H), 2.03 - 1.96 (m, 2H), 1.54 - 1.43 (m, 2H). [00815] Example 286: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-isopropyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile Example 286 was prepared in a manner similar to Example 261. MS: m/z = 545.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.29 - 8.01 (m, 3H), 7.97 (dd, J = 4.8, 1.6 Hz, 1H), 7.44 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4 Hz, 1H), 7.00 (dd, J = 7.6, 1.6 Hz, 1H), 6.94 (br s, 2H), 6.67 (d, J = 6.4 Hz, 1H), 6.35 (dd, J = 8.0, 5.2 Hz, 1H), 3.92 - 3.69 (m, 1H), 3.57 (s, 2H), 3.13 - 2.99 (m, 1H), 2.81 - 2.75 (m, 2H), 2.20 - 2.14 (m, 2H), 1.92 - 1.80 (m, 2H), 1.55 - 1.43 (m, 2H), 1.23 (d, J = 6.8 Hz, 6H). [00816] Example 287: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-methoxy-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile Example 287 was prepared in a manner similar to Example 261. MS: m/z = 533.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.13 - 8.03 (m, 3H), 7.95 (dd, J = 4.8, 1.2 Hz, 1H), 7.46 - 7.43 (m, 2H), 7.38 - 7.34 (m, 2H), 7.04 (dd, J = 7.6, 1.6 Hz, 1H), 6.96 (br s, 2H), 6.81 (d, J = 8.8 Hz, 1H), 6.67 (d, J = 6.0 Hz, 1H), 6.34 (dd, J = 7.6, 4.8 Hz, 1H), 3.81 - 3.75 (m, 4H), 3.57 (s, 2H), 2.82 - 2.79 (m, 2H), 2.16 - 2.11 (m, 2H), 1.90 - 1.87 (m, 2H), 1.53 - 1.43 (m, 2H). [00817] Example 288: 2-(2-Aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin-1-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyri dine-5-carboxamide Example 288 was prepared in a manner similar to Example 261. MS: m/z = 546.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.32 (d, J = 8.4 Hz, 1H), 8.10 - 8.00 (m, 4H), 7.63 - 7.57 (m, 2H), 7.45 (br s, 4H), 7.22 - 7.17 (m, 1H), 6.95 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.42 - 6.37 (m, 1H), 3.89 - 3.74 (m, 1H), 3.57 (s, 2H), 2.86 - 2.80 (m, 2H), 2.22 - 2.13 (m, 2H), 1.91 - 1.81 (m, 2H), 1.52 - 1.43 (m, 2H). [00818] Example 289: 2-(2-Aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin-1-yl)methyl)phenyl)-N,N-dimethyl-3H-imida zo[4,5-b]pyridine-5- carboxamide Example 289 was prepared in a manner similar to Example 261. MS: m/z = 574.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.28 (d, J = 8.0 Hz, 1H), 8.12 - 8.03(m, 2H), 8.00 (dd, J = 4.8, 1.6 Hz, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.45 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.18 (dd, J = 7.6, 1.6 Hz, 1H), 6.98 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.39 (dd, J = 8.0, 5.2Hz, 1H), 3.88 - 3.74 (m, 1H), 3.57 (s, 2H), 2.98 (s, 3H), 2.95 (s, 3H), 2.85 - 2.76 (m, 2H), 2.19 - 2.05 (m, 2H), 1.95 - 1.81 (m, 2H), 1.56 - 1.39 (m, 2H). [00819] Example 290: 6-(4-(4-(2-(2-Aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine-4-carbonitri le Example 290 was prepared in a manner similar to Example 261. MS: m/z = 529.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.57 (d, J = 1.2 Hz, 1H), 8.04 (d, J = 8.0 Hz, 1H), 7.96 (dd, J = 4.8, 2.0 Hz, 1H), 7.57 (d, J = 0.8 Hz, 1H), 7.46 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.4 Hz, 1H), 7.06 (dd, J = 7.6, 1.6 Hz, 1H), 6.97 (br s, 2H), 6.32 (dd, J = 7.6, 4.8 Hz, 1H), 3.84 - 3.66 (m, 4H), 3.62 (s, 2H), 2.49 - 2.45 (m, 4H), 2.21 - 2.13 (m, 1H), 0.96 - 0.89 (m, 2H), 0.85 - 0.79 (m, 2H). [00820] Example 291: 6-((1-(4-(2-(2-Aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4 ,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-4-carb onitrile Example 291 was prepared in a manner similar to Example 261. MS: m/z = 543.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.50 (s, 1H), 8.08 (d, J = 7.2 Hz, 1H), 8.03 (d, J = 8.0 Hz, 1H), 7.96 (dd, J = 4.8, 1.6 Hz, 1H), 7.43 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 8.4 Hz, 1H), 7.07 (dd, J = 7.6, 1.8 Hz, 1H), 7.01 - 6.87 (m, 3H), 6.34 (dd, J = 7.6, 4.8 Hz, 1H), 3.95 - 3.79 (m, 1H), 3.56 (s, 2H), 2.81 (d, J = 11.2 Hz, 2H), 2.20 - 2.08 (m, 3H), 1.90 (m, 2H), 1.59 - 1.42 (m, 2H), 0.97 - 0.89 (m, 2H), 0.86 - 0.78 (m, 2H). [00821] Example 292: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)piperazin-1-yl)-1,3,5-triazine-2-carbo nitrile Example 292 was prepared in a manner similar to Example 285. MS: m/z = 575.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.72 (s, 1H), 7.98 (d, J = 8.8 Hz, 1H), 7.95 - 7.91 (m, 1H), 7.46 (d, J = 7.6 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 7.03 - 6.97 (m, 3H), 6.90 (d, J = 9.2 Hz, 1H), 6.32 (dd, J = 7.2, 4.4 Hz, 1H), 3.87 - 3.79 (m, 4H), 3.72 - 3.59 (m, 8H), 3.42 - 3.38 (m, 4H), 3.34 - 3.33 (m, 2H). [00822] Example 293: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(2-cyanophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 2-carbonitrile Example 293 was prepared in a manner similar to Example 225. MS: m/z = 590.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ )) δ 8.38 (d, J = 8.0 Hz, 1H), 8.26 (d, J = 6.4 Hz, 1H), 8.01 (dd, J = 4.8, 2.0 Hz, 1H), 7.95 (d, J = 8.0 Hz, 1H), 7.92 - 7.77 (m, 3H), 7.67 - 7.57 (m, 1H), 7.49 - 7.43 (m, 4H), 7.19 (dd, J = 7.6, 2.0 Hz, 1H), 7.10 (d, J = 6.8 Hz, 1H), 7.00 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.68 - 3.67 (m, 4H), 3.61 (s, 2H), 2.49 - 2.45 (m, 4H). [00823] Example 294: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(4-cyanophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 2-carbonitrile Example 294 was prepared in a manner similar to Example 225. MS: m/z = 590.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ )) δ 8.25 (dd, J = 8.4, 2.0 Hz, 3H), 8.18 (d, J = 6.8 Hz, 1H), 8.06 (d, J = 8.4 Hz, 1H), 8.00 (dd, J = 5.2, 2.0 Hz, 1H), 7.80 (d, J = 8.8 Hz, 2H), 7.58 (d, J = 8.8 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.34 (dd, J = 7.6, 2.0 Hz, 1H), 6.95 (d, J = 6.4 Hz, 1H), 6.48 (dd, J = 7.6, 5.2 Hz, 1H), 3.83 - 3.74 (m, 4H), 3.70 (s, 2H), 2.63 - 2.57 (m, 4H). [00824] Example 295: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(3-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 2-carbonitrile Example 295 was prepared in a manner similar to Example 225. MS: m/z = 583.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.23 - 8.16 (m, 2H), 8.01 - 7.95 (m, 2H), 7.87 (d, J = 8.4 Hz, 1H), 7.81 - 7.76 (m, 1H), 7.59 (d, J = 8.4 Hz, 2H), 7.49 - 7.44 (m, 3H), 7.34 (dd, J = 7.6, 4.6 Hz, 1H), 7.13 - 7.09 (m, 1H), 6.95 (d, J = 6.4 Hz, 1H), 6.48 (dd, J = 7.6, 5.2 Hz, 1H), 3.78 - 3.76 (m, 4H), 3.70 (s, 2H), 2.61 (t, J = 4.8 Hz, 4H). ¹⁹ F NMR (400 MHz, Methanol-d ₄ ) δ -115.26. [00825] Example 296: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(3-chlorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 2-carbonitrile Example 296 was prepared in a manner similar to Example 225. MS: m/z = 599.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.23 - 8.16 (m, 2H), 8.05 (s, 1H) 8.00 - 7.95 (m, 3H), 7.59 (d, J = 8.4 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.46 - 7.36 (m, 2H), 7.34 (dd, J = 7.6, 1.6 Hz, 1H), 6.94 (d, J = 6.4 Hz, 1H), 6.48 (dd, J = 7.6, 4.8 Hz, 1H), 3.73 - 3.80 (m, 4H), 3.70 (s, 2H), 2.63 - 2.59 (m, 4H). [00826] Example 297: 2-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(3-chlorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 4-carbonitrile Example 297 was prepared in a manner similar to Example 225. MS: m/z = 599.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.65 (d, J = 4.8 Hz, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.07 - 8.00 (m, 4H), 7.54 – 7.45 (m, 6H), 7.19 - 7.14 (m, 2H), 7.05 (br s, 2H), 6.38 (dd, J = 7.2, 5.2 Hz, 1H), 3.79 - 3.77 (m, 4H), 3.65 (s, 2H), 2.47 – 2.35 (m, 4H). [00827] Example 298: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4 ,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile Example 298 was prepared in a manner similar to Example 225. MS: m/z = 543.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.10 - 8.01 (m, 3H), 7.96 (dd, J =4.8, 1.6 Hz, 1H), 7.43 (d, J = 8.0 Hz, 2H), 7.33 (d, = 8.0 Hz, 2H), 7.24 (d, J = 8.0 Hz, 1H), 7.06 (dd, J = 7.6, 1.6 Hz, 1H), 6.98 (br s, 2H), 6.67 (d, J = 6.4 Hz, 1H), 6.34 (dd, J = 7.6, 4.8 Hz, 1H), 3.88 - 3.75 (m, 1H), 3.57 (s, 2H), 2.85 - 2.78 (m, 2H), 2.20 - 2.11 (m, 3H), 1.93 - 1.89 (m, 2H), 1.56 - 1.45 (m, 2H), 0.96 - 0.90 (m, 2H), 0.85 - 0.80 (m, 2H). [00828] Example 299: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(tetrahydro-2H-pyran-4-y l)- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile Example 299 was prepared in a manner similar to Example 261. MS: m/z = 587.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.16 - 8.01 (m, 3H), 7.97 (dd, J = 4.8, 1.6 Hz, 1H), 7.47 - 7.42 (m, 2H), 7.39 - 7.30 (m, 3H), 7.09 (dd, J = 8.0, 1.6 Hz, 1H), 6.94 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.35 (dd, J = 7.6, 4.8, Hz, 1H), 3.96 - 3.88 (m, 2H), 3.87 - 3.75 (m, 1H), 3.57 (s, 2H), 3.47 - 3.39 (m, 2H), 3.04 - 2.94 (m, 1H), 2.86 - 2.77 (m, 2H), 2.21 - 2.08 (m, 2H), 1.95 - 1.83 (m, 2H), 1.79 - 1.71 (m, 4H), 1.55 - 1.43 (m, 2H). [00829] Example 300: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)azetidin-3-yl)amino)-1,3,5-triazine-2- carbonitrile Example 300 was prepared in a manner similar to Example 93. MS: m/z = 552.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.40 (d, J = 6.4 Hz, 1H), 8.76 - 8.63 (m, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.05 - 7.96 (m, 4H), 7.49 - 7.37 (m, 7H), 7.16 (dd, J = 7.6, 2.0 Hz, 1H), 7.00 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 4.51 - 4.36 (m, 1H), 3.70 (s, 2H), 3.61 (t, J = 7.2 Hz, 2H), 3.15 - 3.05 (m, 2H). [00830] Example 301: 4-(6-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2,6-diazaspiro[3.4]octan-2-yl)-1,3,5- triazine-2-carbonitrile Example 301 was prepared in a manner similar to Example 93. MS: m/z = 592.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.67 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.06 - 7.96 (m, 4H), 7.52 - 7.43 (m, 6H), 7.41 - 7.36 (m, 1H), 7.17 (dd, J = 8.0, 2.0 Hz, 1H), 7.02 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 4.12 (s, 4H), 3.69 (s, 2H), 2.78 (s, 2H), 2.62 - 2.58 (m, 2H), 2.16 - 2.10 (m, 2H). [00831] Example 302: 4-(7-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2,7-diazaspiro[4.4]nonan-2-yl)pyrimid ine-2-carbonitrile Example 302 was prepared in a manner similar to Example 267. MS: m/z = 605.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.19 (d, J = 8.4 Hz, 1H), 8.14 - 8.10 (m, 1H), 8.02 (d, J = 7.2 Hz, 2H), 7.97 - 7.91 (m, 2H), 7.56 (d, J = 8.4 Hz, 2H), 7.47 - 7.37 (m, 5H), 7.34 - 7.28 (m, 1H), 6.64 (d, J = 6.4 Hz, 1H), 6.46 - 6.39 (m, 1H), 3.76 (s, 2H), 3.67 - 3.54 (m, 2H), 3.47 - 3.41 (m, 2H), 2.88 - 2.81 (m, 1H), 2.77 - 2.66 (m, 2H), 2.65 - 2.55 (m, 1H), 2.15 - 2.03 (m, 2H), 1.98 - 1.90 (m, 2H). [00832] Example 303: 4-(6-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2,6-diazaspiro[3.3]heptan-2-yl)-1,3,5 -triazine-2-carbonitrile Example 303 was prepared in a manner similar to Example 93. MS: m/z = 578.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.67 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.07 - 7.97 (m, 4H), 7.49 - 7.39 (m, 7H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.00 (br s, 2H), 6.44 - 6.38 (m, 1H), 4.28 (s, 4H), 3.64 (s, 2H), 3.40 (s, 4H). [00833] Example 304: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(2-chlorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)-1,3,5-tria zine-2-carbonitrile Example 304 was prepared in a manner similar to Example 261. MS: m/z = 600.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.71 (s, 1H), 8.29 (d, J = 8.0 Hz, 1H), 8.02 - 7.98 (m, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.58 - 7.53 (m, 2H), 7.47 - 7.43 (m, 6H), 7.16 (dd, J = 7.6, 1.2 Hz, 1H), 6.95 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.85 - 3.77 (m, 4H), 3.60 (s, 2H), 2.60 - 2.54 (m, 4H). [00834] Example 305: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-chlorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 305 was prepared in a manner similar to Example 261. MS: m/z = 613.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.29 (d, J = 8.4 Hz, 1H), 8.11 - 7.98 (m, 3H), 7.63 (d, J = 8.0 Hz, 1H), 7.59 - 7.52 (m, 2H), 7.46 - 7.40 (m, 6H), 7.16 (d, J = 7.2 Hz, 1H), 6.97 (br s, 2H), 6.66 (d, J = 6.0 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.86 - 3.72 (m, 1H), 3.54 (s, 2H), 2.79 (m, 2H), 2.19 - 2.06 (m, 2H), 1.86 (m, 2H), 1.54 - 1.39 (m, 2H). [00835] Example 306: 2-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-chlorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-4-carbonitrile Example 306 was prepared in a manner similar to Example 261. MS: m/z = 613.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.61 (d, J = 4.8 Hz, 1H), 8.29 (d, J = 8 Hz, 1H), 8.00 (d, J = 4.8 Hz, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.57 7.37 (m, 9H), 7.21 (d, J = 7.6 Hz, 1H), 7.09 (d, J = 4.4 Hz, 1H), 6.96 (br s, 2H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 4.42 - 4.33 (m, 2H), 3.82 (s, 2H), 3.37 - 3.35 (m, 2H), 3.17 - 3.09 (m, 2H), 2.78 - 2.70 (m, 1H), 1.93 - 1.86 (m, 2H). [00836] Example 307: 6-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-chlorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-4-carbonitrile Example 307 was prepared in a manner similar to Example 261. MS: m/z = 613.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.49 (s, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.06 (d, J = 6.8 Hz, 1H), 8.00 (dd, J = 5.2, 2.0 Hz, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.58 - 7.53 (m, 2H), 7.45 - 7.42 (m, 6H), 7.16 (dd, J = 7.6, 2.0 Hz, 1H), 6.97 (br s, 2H), 6.92 (s, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.93 - 3.75 (m, 1H), 3.54 (s, 2H) 2.85 - 2.75 (m, 2H), 2.16 - 2.07 (m, 2H), 1.93 - 1.84 (m, 2H), 1.52 - 1.43 (m, 2H). [00837] Example 308: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-chlorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 308 was prepared in a manner similar to Example 261. MS: m/z = 613.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.28 (d, J = 8.4 Hz, 1H), 8.11 - 7.98 (m, 6H), 7.54 - 7.44 (m, 6H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (br s, 2H), 6.68 (d, J = 6.0 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.88 - 3.75 (m, 1H), 3.59 (s, 2H), 2.87 - 2.79 (d, J = 11.2 Hz, 2H), 2.16 (m, 2H), 1.90 (d, J = 11.2 Hz, 2H), 1.56 - 1.43 (m, 2H). [00838] Example 309: 2-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(3-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 4-carbonitrile Example 309 was prepared in a manner similar to Example 261. MS: m/z = 583.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.65 (d, J = 4.4 Hz, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.05 (d, J = 8.4 Hz, 1H), 8.02 - 7.99 (m, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.83 (d, J = 10.0 Hz, 1H), 7.54 - 7.46 (m, 5H), 7.27 - 7.21 (m, 1H), 7.19 - 7.14 (m, 2H), 7.04 (br s, 2H), 6.38 (dd, J = 8.0, 5.2 Hz, 1H), 3.83 - 3.75 (m, 4H), 3.65 (s, 2H), 3.38 - 3.33 (m, 4H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -112.91. [00839] Example 310: 6-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(3-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 4-carbonitrile Example 310 was prepared in a manner similar to Example 261. MS: m/z = 583.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.57 (s, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.05 (d, J = 8.4 Hz, 1H), 8.00 (dd, J = 4.8, 1.6 Hz, 1H), 7.91 (d, J = 7.6 Hz, 1H), 7.83 (d, J = 10.4 Hz, 1H), 7.58 - 7.56 (m, 1H), 7.54 - 7.47 (m, 5H), 7.27 - 7.21 (m, 1H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.83 - 3.69 (m, 4H), 3.65 (s, 2H), 3.38 - 3.34 (m, 2H), 3.30 - 3.26 (m, 2H). ¹⁹ F NMR (377 MHz, Dimethylsulfoxide-d ₆ ) δ -112.89. [00840] Example 311: 6-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(3-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-4-carbonitrile Example 311 was prepared in a manner similar to Example 261. MS: m/z = 597.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.51 - 8.42 (m, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.10 - 8.04 (m, 2H), 8.00 (dd, J = 4.8, 2.0 Hz, 1H), 7.91 (d, J = 10.8 Hz, 1H), 7.84 - 7.81 (m, 1H), 7.52 - 7.45 (m, 5H), 7.25 - 7.16 (m, 2H), 7.04 (br s, 2H), 6.93 (s, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.92 - 3.81 (m, 1H), 3.59 (s, 2H), 2.86 - 2.81 (m, 2H), 2.16 - 2.10 (m, 2H), 1.94 - 1.86 (m, 2H), 1.55 - 1.46 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -112.913. [00841] Example 312: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(2-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)-1,3,5-tria zine-2-carbonitrile Example 312 was prepared in a manner similar to Example 285. MS: m/z = 584.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.72 (s, 1H), 8.30 (d, J = 8.4 Hz, 1H), 8.00 (dd, J = 4.8, 2.0 Hz, 1H), 7.83 - 7.77 (m, 2H), 7.51 - 7.44 (m, 5H), 7.36 - 7.29 (m, 2H), 7.17 (dd, J = 7.6, 2.0 Hz, 1H), 6.98 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.87 - 3.79 (m, 4H), 3.63 (s, 2H), 2.54 - 2.51 (m, 4H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ. -117.168. [00842] Example 313: 2-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-4-carbonitrile Example 313 was prepared in a manner similar to Example 261. MS: m/z = 597.4 [M + H] ⁺ .1H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.61 (d, J = 4.4 Hz, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.00 (dd, J = 4.8, 1.6 Hz, 1H), 7.83 - 7.77 (m, 2H), 7.52 - 7.39 (m, 6H), 7.35 - 7.29 (m, 2H), 7.20 (dd, J = 7.6, 0.8 Hz, 1H), 7.10 (d, J = 4.8 Hz, 1H), 6.98 (br s, 2H), 6.40 (dd, J = 7.6, 5.2 Hz, 1H), 4.41 - 4.37 (m, 1H), 3.83 (s, 2H), 3.14 (t, J = 11.2 Hz 2H), 2.81 - 2.70 (m, 2H), 1.93 - 1.87 (m, 2H), 1.30 - 1.23 (m, 2H). ¹⁹ F NMR (377 MHz, Dimethylsulfoxide-d ₆ ) δ -117.15. [00843] Example 314: 6-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(2-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 4-carbonitrile Example 314 was prepared in a manner similar to Example 261. MS: m/z = 583.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.56 (s, 1H), 8.30 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 4.4 Hz, 1H), 7.83 - 7.78 (m, 2H), 7.56 (s, 1H), 7.50 - 7.45 (m, 5H), 7.36 - 7.28 (m, 2H), 7.16 (d, J = 7.6 Hz, 1H), 7.00 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.78 - 3.70 (m, 4H), 3.62 (s, 2H), 2.48 - 2.46 (m, 4H). ¹⁹ F NMR (377 MHz, Dimethylsulfoxide-d ₆ ) δ -117.16. [00844] Example 315: 6-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-4-carbonitrile Example 315 was prepared in a manner similar to Example 261. MS: m/z = 597.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.52 - 8.42 (m, 1H), 8.29 (d, J = 12.0 Hz, 1H), 8.07 (d, J = 7.6 Hz, 1H), 8.00 (dd, J = 4.8, 2.0 Hz, 1H), 7.83 - 7.78 (m, 2H), 7.48 - 7.43 (m, 5H), 7.35 - 7.29 (m, 2H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 6.99 (br s, 2H), 6.92 (s, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.93 - 3.80 (m, 1H), 3.56 (s, 2H), 2.83 - 2.78 (m, 2H), 2.15 - 2.08 (m, 2H), 1.93 - 1.83 (m, 2H), 1.54 - 1.44 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -117.177. [00845] Example 316: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 316 was prepared in a manner similar to Example 261. MS: m/z = 597.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.30 (d, J = 8.0 Hz, 1H), 8.13 - 7.96 (m, 3H), 7.84 - 7.75 (m, 2H), 7.50 - 7.42 (m, 5H), 7.36 - 7.28 (m, 2H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.00 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.38 (dd, J = 8.0, 4.8 Hz, 1H), 3.87 - 3.74 (m, 1H), 3.57 (s, 2H), 2.85 - 2.76 (m, 2H), 2.14 (m, 2H), 1.88 (d, J = 10.0 Hz, 2H), 1.54 - 1.41 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -117.176. [00846] Example 317: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(3-oxo-1,4-diazepan-1-yl) -3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 2-carbonitrile

To a solution of Intermediate 91 (150 mg, 335 μmol) and Intermediate 53 (117 mg, 368 μmol) in DMF (5 mL) were added Nal (10.0 mg, 66.9 μmol) and K ₂ CO ₃ (139 mg, 1.00 mmol) in one portion at 20 °C. The mixture was stirred at 20 °C for 12 hr and 80 °C for 2 hr. Water (10 mL) was added at 20 °C and extracted with EtOAc (20 mL x 3). The combined organic layers were washed with water (20 mL x 2), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by prep-HPLC (column: Phenomenex C18 75 x 30 mm x 3 μm; mobile phase: [water (NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN]; gradient: 28% - 58% B over 7 min) to give 4-(4-(4-(2-(2-aminopyridin-3-yl)-5-(3-oxo-l,4-diazepan-l-yl) -3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazin-l-yl)pyrimidine-2-carbonitri le (Example 317, 40.8 mg, yield: 20%) as a yellow solid. MS: m/z = 601.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 5 8.27 (d, J= 6.4 Hz, 1H), 7.97 - 7.92 (m, 2H), 7.47 - 7.42 (m, 3H), 7.35 (d, J= 8.0 Hz, 2H), 7.12 (d, J= 6.4 Hz, 1H), 7.02 - 6.79 (m, 3H), 6.80 (d, J= 8.8 Hz, 1H), 6.32 (dd, J= 7.6, 5.2 Hz 1H), 4.18 (s, 2H), 3.82 - 3.68 (m, 6H), 3.62 (s, 2H), 3.25 - 3.05 (m, 2H), 2.49 - 2.42 (m, 4H), 1.65 - 1.62 (m, 2H).

[00847] Example 318: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(3-oxo-l,4-diazepan-l-yl )- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile

Example 318 was prepared in a manner similar to Example 317. MS : m/z = 615.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.09 - 7.95 (m, 2H), 7.94 - 7.92 (m, 2H), 7.46 - 7.43 (m, 1H), 7.41 (d, J= 8.0 Hz, 2H), 7.33 (d, J= 8.4 Hz, 2H), 7.02 - 6.99 (m, 3H), 6.80 (d, J= 9.2 Hz, 1H), 6.65 (d, J= 8.0 Hz, 1H), 6.34 - 6.30 (m, 1H), 4.17 (s, 2H), 3.83 - 3.75 (m, 3H), 3.56 (s, 2H), 3.19 - 3.15 (m, 2H), 2.82 - 2.78 (m, 2H), 2.16 - 2.09 (m, 2H), 1.89 - 1.86 (m, 2H), 1.68 - 1.62 (m, 2H), 1.49 - 1.45 (m, 2H). [00848] Example 319: 2-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(4-cyanophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 4-carbonitrile Example 319 was prepared in a manner similar to Example 261. MS: m/z = 590.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ )) δ 8.65 (d, J = 4.8 Hz, 1H), 8.34 (d, J = 8.4 Hz, 1H), 8.24 (d, J = 8.4 Hz, 2H), 8.13 (d, J = 8.4 Hz, 1H), 8.01 (dd, J = 4.8, 2.0 Hz, 1H), 7.94 (d, J = 8.4 Hz, 2H), 7.54 - 7.46 (m, 4H), 7.19 - 7.14 (m, 2H), 7.03 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.84 - 3.78(m, 4H), 3.64 (s, 2H), 3.30 - 3.29 (m, 4H). [00849] Example 320: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-cyanophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 320 was prepared in a manner similar to Example 261. MS: m/z = 604.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ )) δ 8.27 - 8.22 (m,, 3H), 8.05 (d, J = 8.4 Hz, 1H), 8.03 - 7.97 (m, 2H), 7.79 (d, J = 8.8 Hz, 2H), 7.56 (d, J = 8.4 Hz, 2H), 7.46 (d, J = 8.4 Hz, 2H), 7.34 (dd, J = 7.6, 1.6 Hz 1H), 6.65 - 6.57 (m, 1H), 6.48 (dd, J = 7.6, 5.2 Hz, 1H), 4.02 - 3.92 (m, 1H), 3.68 (s, 2H), 3.03 - 2.95 (m, 2H), 2.33 - 2.25 (m, 2H), 2.03 - 2.00 (m, 1H), 1.69 - 1.54 (m, 3H). [00850] Example 321: 2-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-cyanophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-4-carbonitrile Example 321 was prepared in a manner similar to Example 261. MS: m/z = 604.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.44 (br s, 1H), 8.19 - 8.11 (m, 3H), 8.09 (dd, J = 4.8, 1.6 Hz, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.72 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.11 (dd, J = 7.6, 1.6 Hz, 1H), 6.83 (d, J = 4.8 Hz, 1H), 6.65 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 5.34 (d, J = 8.0 Hz, 1H), 3.98 - 3.84 (m, 1H), 3.65 (s, 2H), 2.94 - 2.88 (m, 2H), 2.36 - 2.23 (m, 2H), 2.14 - 2.05 (m, 2H), 1.68 - 1.62 (m, 2H). [00851] Example 322: 2-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(2-cyanophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 4-carbonitrile To a solution of Intermediate 93 (200 mg, 458 µmol) and Intermediate 86 (95.3 mg, 503 µmol) in DMF (3 mL) were added NaI (13.7 mg, 91.5 µmol), K ₂ CO ₃ (189 mg, 1.37 mmol). The mixture was stirred at 80 °C for 12 hr. The reaction mixture was filtered and purified by prep- HPLC (column: Waters xbridge 150 * 25mm * 10 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 50% - 70% B over 14 min) to give 2-(4-(4-(2-(2-aminopyridin-3-yl)-5-(2- cyanophenyl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin- 1-yl)pyrimidine-4-carbonitrile (Example 322, 81 mg, yield: 30%) as a light-yellow solid. MS: m/z = 590.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.62 (d, J = 4.4 Hz, 1H), 8.38 (d, J = 8.0 Hz, 1H), 8.02 - 8.00 (m, 1H), 7.63 (d, J = 7.6 Hz, 1H), 7.87 - 7.80 (m, 3H), 7.61 - 7.58 (m, 1H), 7.51 - 7.44 (m, 4H), 7.19 - 7.10 (m, 2H), 6.99 (br s, 2H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 3.76 -3.74 (m, 4H), 3.46 (s, 2H), 2.50 - 2.46 (m, 4H). [00852] Example 323: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(5-oxo-1,4-diazepan-1-yl )- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile Example 323 was prepared in a manner similar to Example 323. MS: m/z = 615.5 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.92 - 7.81 (m, 4 H), 7.59 - 7.55 (m, 1H), 7.51 - 7.22 (m, 4H), 7.14 - 6.94 (m, 3H), 6.87 (d, J = 7.6 Hz, 1H), 6.67 - 6.66 (m, 1H), 6.32 - 6.31 (m, 1H), 3.92 - 3.62 (m, 5H), 3.56 (s, 2H), 3.21 - 3.09 (m, 2H), 2.81 - 2.78 (m, 2H), 2.38 - 2.49 (m, 2H), 2.13 - 2.11 (m, 2H), 1.92 -1.81 (m, 2H), 1.56 - 1.41 (m, 2H). [00853] Example 324: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(2-chlorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 2-carbonitrile Example 324 was prepared in a manner similar to Example 225. MS: m/z = 599.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.30 - 8.25 (m, 2H), 8.00 (dd, J = 4.8, 2.0 Hz, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.58 - 7.53 (m, 2H), 7.47 - 7.42 (m, 6H), 7.15 (dd, J = 7.6, 2.0 Hz, 1H), 7.09 (d, J = 6.4 Hz, H), 6.96 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.72 - 3.58 (m, 6H), 2.49 - 2.46 (m, 4H). [00854] Example 325: 2-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(2-chlorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 4-carbonitrile Example 325 was prepared in a manner similar to Example 225. MS: m/z = 599.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ )) δ 8.63 (d, J = 4.8 Hz, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.03 - 7.99 (m, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.59 - 7.53 (m, 2H), 7.48 - 7.42 (m, 6H), 7.18 - 7.13 (m, 2H), 6.97 (br s, 2H), 6.38 (dd, J = 8.0, 4.8 Hz, 1H), 3.83 - 3.73 (m, 4H), 3.59 (s, 2H), 2.49 - 2.44 (m, 4H). [00855] Example 326: 6-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(2-chlorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 4-carbonitrile Example 326 was prepared in a manner similar to Example 225. MS: m/z = 599.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.55 (s, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.00 (dd, J = 4.8, 1.6 Hz, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.59 - 7.53 (m, 3H), 7.48 - 7.41 (m, 6H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 6.97 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.85 - 3.62 (m, 4H), 3.59 (s, 2H), 2.48 - 2.44 (m, 4H). [00856] Example 327: 5-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carbonyl)thiazole-2-carbo nitrile Example 327 was prepared in a manner similar to Example 245. MS: m/z = 598.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Acetonitrile-d ₃ ) δ 8.23 - 8.18 (m, 2H) 8.06 - 8.04 (m, 3H), 7.92 (d, J = 8.0 Hz, 1H), 7.57 - 7.43 (m, 7H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 6.60 (b rs, 2H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 3.75 - 3.67 (m, 6H), 2.59 - 2.52 (m, 4H). [00857] Example 328: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)-1,3,5-triazine-2-carbo nitrile Example 328 was prepared in a manner similar to Example 223. MS: m/z = 566.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) 8.56 (s, 1H), 8.15 (d, J = 8.0 Hz, 1H), 8.05 - 8.01 (m, 3H), 7.82 (d, J = 8.0 Hz, 1H), 7.53 - 7.51 (m, 2H), 7.45-7.43 (m, 4H), 7.41 - 7.39 (m, 1H), 7.13 (d, J = 4.0 Hz, 1H), 6.91 (br s, 2H), 6.40-6.36 (m, 1H), 3.97 - 3.92 (m, 4H), 3.67 (s, 2H), 2.61 - 2.57 (m, 4H). [00858] Example 329: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(cyclohex-1-en-1-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 2-carbonitrile Example 329 was prepared in a manner similar to Example 225. MS: m/z = 569.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6) δ 8.27 (d, J = 6.4 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H), 8.02 - 7.94 (m, 1H), 7.53 (d, J = 8.4 Hz, 1H), 7.48 (d, J = 8.0 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 7.15 - 7.07 (m, 2H), 7.03 (br s, 2H), 6.68 - 6.60 (m, 1H), 6.34 (dd, J = 7.6, 4.8 Hz, 1H), 3.77- 3.57 (m, 6H), 3.31 (s, 2H), 2.45 - 2.39 (m, 4H), 2.20 - 2.18 (m, 2H), 1.72 - 1.56 (m, 4H). [00859] Example 330: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(3,6-dihydro-2H-pyran-4-y l)- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidi ne-2-carbonitrile Example 330 was prepared in a manner similar to Example 225. MS: m/z = 571.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 6.0 Hz, 1H), 8.16 (d, J = 8.4 Hz, 1H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.48 (d, J = 8.4 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H), 7.14 - 7.08 (m, 2H), 7.02 (br s, 2H), 6.69 - 6.68 (m, 1H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 4.28 - 4.22 (m, 2H), 3.80 (t, J = 5.6 Hz, 2H), 3.75 - 3.58 (m, 6H), 3.32 - 3.31 (m, 6H). [00860] Example 331: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(3-cyanophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 2-carbonitrile Example 331 was prepared in a manner similar to Example 225. MS: m/z = 590.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.48 - 8.43 (m, 1H), 8.38 (d, J = 8.4 Hz, 1H), 8.33 (d, J = 8.4 Hz, 1H), 8.27 (d, J = 6.4 Hz, 1H), 8.12 (d, J = 8.4 Hz, 1H), 8.01 (dd, J = 4.8, 2.0 Hz, 1H), 7.87 (d, J =7.6 Hz, 1H), 7.69 (dd, J = 7.6, 7.6 Hz, 1H), 7.54 - 7.47 (m, 4H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.11 (d, J = 6.8 Hz, 1H), 7.05 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.70 - 3.69 (m, 4H), 3.65 (s, 2H), 2.49 - 2.47 (m, 4H). [00861] Example 332: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(6-oxo-1,6-dihydropyridin -3- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyri midine-2-carbonitrile Example 332 was prepared in a manner similar to Example 225. MS: m/z = 582.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 12.01 - 11.61 (m, 1H), 8.27 (d, J = 6.0 Hz, 1H), 8.20 (d, J = 8.0 Hz, 1H), 8.13 (dd, J = 9.6, 2.8 Hz, 1H), 8.08 - 8.03 (m, 1H), 7.98 (dd, J = 4.4, 1.2 Hz, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.53 - 7.41 (m, 4H), 7.15 - 7.09 (m, 2H), 7.04 (br s, 2H), 6.43 (d, J = 9.6 Hz, 1H), 6.35 (dd, J = 8.0, 5.2 Hz, 1H), 3.78 - 3.66 (m, 4H), 3.64 (s, 2H), 2.52 - 2.51 (m, 4H). [00862] Example 333: 2-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(6-oxo-1,6-dihydropyridin -2- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyri midine-4-carbonitrile Example 333 was prepared in a manner similar to Example 225. MS: m/z = 582.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.81 (br s, 1H), 8.65 (d, J = 4.8 Hz, 1H), 8.33 (d, J = 8.4 Hz, 1H), 8.18 - 8.16 (m, 1H), 8.01 (dd, J = 4.4, 1.2 Hz, 1H), 7.64 - 7.46 (m, 6H), 7.18 - 7.14 (m, 2H), 7.03 (br s, 2H), 6.50 - 6.43 (m, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.82 - 3.76 (m, 4H), 3.65 (s, 2H), 2.65 - 2.55 (m, 4H). [00863] Example 334: 6-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(6-oxo-1,6-dihydropyridin -2- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyri midine-4-carbonitrile Example 334 was prepared in a manner similar to Example 225. MS: m/z = 582.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.90 (br s, 1H), 8.56 (s, 1H), 8.33 (d, J = 8.0 Hz, 1H), 8.20 - 8.14 (m, 1H), 8.00 (dd, J = 4.8, 2.0 Hz, 1H), 7.64 - 7.46 (m, 7H), 7.15 (dd, J = 7.6, 2.0 Hz, 1H), 7.03 (br s, 2H), 6.47 (d, J = 8.4 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.82 - 3.76 (m, 4H), 3.65 (s, 2H), 2.53 - 2.52 (m, 4H). [00864] Example 335: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-cyanophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 335 was prepared in a manner similar to Example 267. MS: m/z = 604.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.28 (d, J = 8.4 Hz, 1H), 8.08 - 7.95 (m, 2H), 7.91 - 7.78 (m, 3H), 7.75 - 7.71 (m, 1H), 7.57 - 7.50 (m, 5H), 7.39 - 7.29 (m, 1H), 6.66 - 6.54 (m, 1H), 6.53 - 6.42 (m, 1H), 4.07 - 3.89 (m, 1H), 3.73 (s, 2H), 3.07 - 2.95 (m, 2H), 2.43 - 2.29 (m, 2H), 2.02 - 1.94 (m, 2H), 1.67 - 1.56 (m, 2H). [00865] Example 336: N-(1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-2-cyano-N-methylpyrimi dine-4-carboxamide Example 336 was prepared in a manner similar to Example 32. MS: m/z = 621.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.15 (dd, J = 5.2, 3.2 Hz, 1H), 8.30 - 8.24 (m, 1H), 8.05 - 7.96 (m, 5H), 7.51 - 7.40 (m, 7H), 7.17 - 7.10 (m, 1H), 7.03 (d, J = 4.8 Hz, 2H), 6.42 - 6.31 (m, 1H), 3.61 - 3.51 (m, 2H), 2.95 - 2.77 (m, 5H), 2.19 - 2.11 (m, 1H), 1.91 - 1.84 (m, 2H), 1.70 - 1.63 (m, 2H), 1.36 - 1.07 (m, 2H). [00866] Example 337: (R)-4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl)piperidin-3-yl)amino)-1,3,5-triazine-2 -carbonitrile Example 337 was prepared in a manner similar to Example 93. MS: m/z = 580.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.87 (br s, 1H), 8.63 (d, J = 16.8 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.25 - 7.97 (m, 4H), 7.52 - 7.38 (m, 7H), 7.13 (d, J = 7.6 Hz, 1H), 7.04 (d, J = 7.6 Hz, 2H), 6.33 - 6.27 (m, 1H), 4.08 - 3.88 (m, 1H), 3.62 (d, J = 8.0 Hz, 2H), 2.93 - 2.86 (m, 1H), 2.75 - 2.69 (m, 1H), 2.05 - 1.95 (m, 3H), 1.88 - 1.82 (m, 1H), 1.76 - 1.69 (m, 1H), 1.59 - 1.49 (m, 1H). [00867] Example 338: 4-((1S,4S)-5-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,5-diazabicyclo[2.2.1]he ptan-2-yl)-1,3,5-triazine-2- carbonitrile Example 338 was prepared in a manner similar to Example 223. MS: m/z = 578.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.54 (d, J = 18.4 Hz, 1H), 8.13 (d, J = 8.0 Hz, 1H), 8.06 (d, J = 4.4 Hz, 1H), 8.01 (d, J = 7.2 Hz, 2H), 7.80 (d, J = 8.4 Hz, 1H), 7.51 - 7.38 (m, 7H), 7.10 (dd, J = 7.6, 1.6 Hz, 1H), 6.65 (br s, 2H), 6.39 - 6.35 (m, 1H), 4.97 - 4.95 (m, 1H), 3.87 (s, 2H), 3.85 - 3.82 (m, 1H), 3.74 - 3.72 (m, 1H), 3.49 - 3.43 (m, 1H), 3.08 - 3.04 (m, 1H), 2.76 - 2.68 (m, 1H), 2.21 - 2.14 (m, 1H), 1.89 -1.85 (m, 1H). [00868] Example 339: 4-((3aR,6aS)-5-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)hexahydropyrrolo[3,4-c]pyr rol-2(1H)-yl)pyrimidine-2- carbonitrile Example 339 was prepared in a manner similar to Example 225. MS: m/z = 591.2 [M+H]+.1H NMR (400 MHz, Dimethylsulfoxide-d6) δ 8.38 - 8.16 (m, 2H), 8.09 - 7.90 (m, 4H), 7.53 - 7.33 (m, 7H), 7.15 (d, J =7.6 Hz, 1H), 7.02 (br s, 2H), 6.78 (d, J =5.6 Hz, 1H), 6.37 - 6.35 (m, 1H), 3.82 - 3.60 (m, 4H), 2.98 - 2.96 (m, 2H), 2.65 -2.53 (m, 6H). [00869] Example 340: 4-((3aR,6aS)-5-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)hexahydropyrrolo[3,4-c]pyr rol-2(1H)-yl)-1,3,5-triazine-2- carbonitrile

Example 340 was prepared in a manner similar to Example 223. MS: m/z = 592.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.54 (s, 1H), 8.19 (d, J= 8.8 Hz, 1H), 8.03 (d, J= 7.6 Hz, 2H), 7.98 (d, J= 4.8 Hz, 1H), 7.94 (d, J= 8.0 Hz, 1H), 7.50 (d, J= 8.0 Hz, 2H) , 7.46 - 7.35 (m, 5H), 7.32 (d, J= 7.6 Hz, 1H), 6.48 (dd, J= 7.6, 5.2 Hz, 1H), 3.91 - 3.81 (m, 2H), 3.75 - 3. ), 3.08 - 3.02 (m, 2H), 2.80 - 2.72 (m, 2H), 2.67 - 2.58 (m, 2H).

[00870] Example 341: 4-((3aR,6aR)-5-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)hexahydropyrrolo[3,4-c]pyr rol-2(1H)-yl)pyrimidine-2- carbonitrile

To a mixture of Intermediate 103 (87.9 mg, TFA salt, 267 μmol) and Intermediate 14 (100 mg, 243 μmol) in DMF (1 mL) was added DIEA (126 mg, 169 μL). The mixture was stirred at 80 °C for 12 hr. The mixture was queneched with H ₂ O (50 mL) and extracted with EtOAc (30 mL x 2). The combined organic layers were washed with brine (20 mL), dried over Na ₂ SO ₄ , filtered and concentrated. The mixture was purified by prep-HPLC (column: Phenomenex C18 80*40mm*3um; mobile phase: [water (NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN]; gradient: 62% - 92% B over 7 min) to give 4-((3aR,6aR)-5-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imida zo[4,5- b]pyridin-3-yl)benzyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl )pyrimidine-2-carbonitrile (Example 341, 25.4 mg, yield: 18%) as a yellow solid. MS: m/z = 591.4 [M+H] ⁺ . ¹ HNMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.32 - 8.15 (m, 2H), 8.05 - 7.97 (m, 4H), 7.53 - 7.43 (m, 6H), 7.42 - 7.37 (m, 1H), 7.17 (dd, J= 7.6, 1.6 Hz, 1H), 7.02 (br s, 2H), 6.74 (d, J= 6.4 Hz, 1H), 6.43 - 6.34 (m, 1H), 4.04 - 3.91 (m, 2H), 3.86 - 3.78 (m, 1H), 3.65 - 3.57 (m, 1H), 3.16 - 3.06 (m, 2H), 2.96 - 2.86 (m, 2H), 2.73 - 2.62 (m, 2H), 2.44 - 2.26 (m, 2H).

[00871] Example 342: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(4-chlorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-l-yl)pyrimidine- 2-carbonitrile Example 342 was prepared in a manner similar to Example 225. MS: m/z = 599.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.30 - 8.26 (m, 2H), 8.08 - 7.99 (m, 4H), 7.55 - 7.50 (m, 4H), 7.49 - 7.45 (m, 2H), 7.17 - 7.10 (m, 2H), 7.03 (br s, 2H), 6.36 (dd, J = 8.0, 4.8 Hz, 1H), 3.81 - 3.66 (m, 4H), 3.65 (s, 2H), 2.49 - 2.46 (m, 4H). [00872] Example 343: 2-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(4-chlorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 4-carbonitrile Example 343 was prepared in a manner similar to Example 225. MS: m/z = 599.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ )) δ 8.65 (d, J = 4.8 Hz, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.08 - 7.99 (m, 4H), 7.55 - 7.50 (m, 4H), 7.49 - 7.44 (m, 2H), 7.18 - 7.12 (m, 2H), 7.03 (br s, 2H), 6.37 (dd, J = 8.0, 4.8 Hz, 1H), 3.82 - 3.77 (m, 4H), 3.64 (s, 2H), 2.61 - 2.54 (m, 4H). [00873] Example 344: 6-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(4-chlorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 4-carbonitrile Example 344 was prepared in a manner similar to Example 225. MS: m/z = 599.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.57 (s, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.09 - 7.99 (m, 4H), 7.58 - 7.45 (m, 7H), 7.14 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (br s, 2H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 3.87 - 3.66 (m, 4H), 3.64 (s, 2H), 2.49 - 2.44 (m, 4H). [00874] Example 345: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(4-methyl-5-oxo-1,4- diazepan-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperazi n-1-yl)pyrimidine-2-carbonitrile Example 345 was prepared in a manner similar to Example 341. MS: m/z = 615.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 6.4 Hz, 1H), 7.99 - 7.91 (m, 2H), 7.46 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 7.12 (d, J = 6.4 Hz, 1H), 7.05 - 6.98 (m, 3H), 6.90 (d, J = 8.8 Hz, 1H), 6.31 (dd, J = 7.6, 4.4 Hz, 1H), 3.78 - 3.65 (m, 9H), 3.62 (s, 2H), 3.52 - 3.40 (m, 2H), 2.82 (s, 3H), 2.62 - 2.57 (m, 5H). [00875] Example 346: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-methyl-5-oxo-1,4- diazepan-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidi n-4-yl)amino)pyrimidine-2- carbonitrile Example 346 was prepared in a manner similar to Example 341. MS: m/z = 629.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.12 - 8.03 (m, 2H), 7.98 - 7.92 (m, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 7.05 - 6.98 (m, 3H), 6.89 (d, J = 8.8 Hz, 1H), 6.67 (d, J = 6.0 Hz, 1H), 6.32 (dd, J = 7.6, 4.8 Hz, 1H), 3.81 - 3.66 (m, 5H), 3.57 (s, 2H), 3.48 - 3.44 (m, 2H), 2.81 - 2.79 (m, 5H), 2.63 - 2.57 (m, 2H), 2.20 - 2.09 (m, 2H), 1.94 - 1.83 (m, 2H), 1.53 - 1.44 (m, 2H). [00876] Example 347: 2-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(3-oxo-1,4-diazepan-1-yl )- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-4-carbonitrile To a solution of Intermediate 87 (105 mg, 516 µmol) and Intermediate 91 (210 mg, 469 µmol) in NMP (0.5 mL) were added K ₂ CO ₃ (194 mg, 1.41 mmol) and NaI (14.1 mg, 93.8 µmol). The mixture was stirred at 80 °C for 1 hr. The crude product was concentrated. The filtrate was purified by prep-HPLC column: Phenomenex C1875 x 30 mm x 3 μm; mobile phase: [water (NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN]; gradient: 35%-75%, B over 7 min) to give 2-((1-(4-(2-(2- Aminopyridin-3-yl)-5-(3-oxo-1,4-diazepan-1-yl)-3H-imidazo[4, 5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-4-carbonitrile (Example 347, 21.9 mg, yield: 7.6 %) as a light-yellow solid. MS: m/z = 615.5 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.54 (br s, 1H), 8.02 - 7.89 (m, 2H), 7.84 (d, J = 7.2 Hz, 1H), 7.50 - 7.27 (m, 5H), 7.12 - 6.92 (m, 4H), 6.80 (d, J = 8.8 Hz, 1H), 6.32 (dd, J = 7.2, 5.2 Hz 1H), 4.17 (s, 2H), 3.82 - 3.81 (m, 2H), 3.76 - 3.63 (m, 1H), 3.55 (s, 2H), 3.18 - 3.17 (m, 2H), 2.91 - 2.77 (m, 2H), 2.00 - 2.16 (m, 2H), 1.87 - 1.79 (m, 2H), 1.65 - 1.64 (m, 2H), 1.61 - 1.43 (m, 2H). [00877] Example 348: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(1-methyl-6-oxo-1,6- dihydropyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)pi perazin-1-yl)pyrimidine-2- carbonitrile Example 348 was prepared in a manner similar to Example 341. MS: m/z = 596.1 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.48 (d, J = 2.8 Hz, 1H), 8.30 - 8.20 (m, 2H), 8.08 (dd, J = 9.6, 2.8 Hz, 1H), 7.99 (dd, J = 4.8, 2.0 Hz, 1H), 7.84 (d, J = 8.8 Hz, 1H), 7.53 - 7.47 (m, 2H), 7.46 - 7.38 (m, 2H), 7.16 - 7.09 (m, 2H), 7.03 (br s, 2H), 6.49 (d, J = 9.6 Hz, 1H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 3.82 - 3.65 (m, 4H), 3.64 (s, 2H), 3.52 (s, 3H), 3.35 - 3.33 (m, 4H). [00878] Example 349: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(1-methyl-2-oxo-1,2- dihydropyridin-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)pi perazin-1-yl)pyrimidine-2- carbonitrile Example 349 was prepared in a manner similar to Example 341. MS: m/z = 596.2 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.33 - 8.24 (m, 2H), 8.05 (d, J = 8.4 Hz, 1H), 8.01 (dd, J = 4.8, 2.0 Hz, 1H), 7.76 (d, J = 7.2 Hz, 1H), 7.55 - 7.49 (m, 2H), 7.48 - 7.43 (m, 2H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.11 (d, J = 6.8 Hz, 1H), 7.08 - 6.98 (m, 3H), 6.86 (dd, J = 7.2, 2.0 Hz, 1H), 6.37 (dd, J = 7.6, 4.4 Hz, 1H), 3.93 – 3.66 (m, 4H), 3.64 (s, 2H), 3.44 (s, 3H), 3.35 - 3.32 (m, 4H). [00879] Example 350: 2-(4-(4-(2-(2-Aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine-4-carbonitri le Example 350 was prepared in a manner similar to Example 261. MS: m/z = 529.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.64 (d, J = 4.8 Hz, 1H), 8.04 (d, J = 8.0 Hz, 1H), 7.96 (dd, J = 4.4, 1.6 Hz, 1H), 7.47 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 7.24 (d, J = 8.4 Hz, 1H), 7.16 (d, J = 4.4 Hz, 1H), 7.06 (dd, J = 7.6, 2.0 Hz, 1H), 6.97 (br s, 2H), 6.34 (dd, J = 8.0, 4.8 Hz, 1H), 3.82 - 3.74 (m, 4H), 3.62 (s, 2H), 2.49 - 2.45 (m, 4H), 2.21 - 2.12 (m, 1H), 0.97 - 0.90 (m, 2H), 0.86 - 0.80 (m, 2H). [00880] Example 351: 2-((1-(4-(2-(2-Aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4 ,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-4-carb onitrile Example 351 was prepared in a manner similar to Example 261. MS: m/z = 543.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.62 (d, J = 4.8 Hz, 1H), 8.03 (d, J = 8.0 Hz, 1H), 7.99 - 7.94 (m, 1H), 7.49 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.4 Hz, 1H), 7.13 - 7.07 (m, 2H), 6.95 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 4.48 - 4.32 (m, 2H), 3.84 (s, 2H), 3.18 - 3.10 (m, 2H), 2.80 - 2.69 (m, 1H), 2.32 - 2.22 (m, 1H), 2.22 - 2.11 (m, 1H), 1.95 - 1.87 (m, 2H), 1.33 - 1.23 (m, 2H), 0.95 - 0.89 (m, 2H), 0.84 - 0.79 (m, 2H). [00881] Example 352: 2-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-4-carbonitrile Example 352 was prepared in a manner similar to Example 261. MS: m/z = 597.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.62 (d, J = 4.4 Hz, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.11 - 8.04 (m, 2H), 8.02 - 7.94 (m, 2H), 7.54 (d, J = 8.0 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.34 - 7.26 (m, 2H), 7.19 (dd, J = 7.6, 2.0 Hz, 1H), 7.10 (d, J = 4.8 Hz, 1H), 7.02 (br s, 2H), 6.40 (dd, J = 8.0, 5.2 Hz, 1H), 4.44 - 4.38 (m, 2H), 3.86 (s, 2H), 3.20 - 3.09 (m, 2H), 2.81 - 2.71 (m, 1H), 2.45 - 2.19 (m, 1H), 1.95 - 1.89 (m, 2H), 1.34 - 1.21 (m, 2H). ¹⁹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -113.573. [00882] Example 353: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(3-chlorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 353 was prepared in a manner similar to Example 225. MS: m/z = 613.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.22 (d, J = 8.4 Hz, 1H), 8.07 - 8.03 (m, 1H), 8.03 - 7.93 (m, 4H), 7.58 (d, J = 8.0 Hz, 2H), 7.48 - 7.32 (m, 5H), 6.63 - 6.56 (m, 1H), 6.48 (dd, J = 7.6, 5.2 Hz, 1H), 4.03 - 3.89 (m, 1H), 3.68 (s, 2H), 3.04 - 2.93 (m, 2H), 2.35 - 2.25 (m, 2H), 2.05 - 1.99 (m, 2H), 1.67 - 1.58 (m, 2H). [00883] Example 354: 2-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(1-methyl-6-oxo-1,6- dihydropyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)pi perazin-1-yl)pyrimidine-4- carbonitrile Example 354 was prepared in a manner similar to Example 341. MS: m/z = 596.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.65 (d, J = 4.8 Hz, 1H), 8.47 (d, J = 2.8 Hz, 1H), 8.23 (d, J = 8.4 Hz, 1H), 8.09 (dd, J = 9.6, 2.8 Hz, 1H), 7.99 (dd, J = 5.2, 2.0 Hz, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.55 - 7.48 (m, 2H), 7.45 - 7.38 (m, 2H), 7.18 - 7.10 (m, 2H), 7.02 (br s, 2H), 6.49 (d, J = 9.6 Hz, 1H), 6.36 (dd, J = 7.6, 5.2 Hz, 1H), 3.82 - 3.76 (m, 4H), 3.64 (s, 2H), 3.52 (s, 3H), 3.35 - 3.32 (m, 4 H). [00884] Example 355: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(1-methyl-6-oxo-1,6- dihydropyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)pi peridin-4-yl)amino)pyrimidine-2- carbonitrile Example 355 was prepared in a manner similar to Example 341. MS: m/z = 610.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.47 (d, J = 2.4 Hz, 1H), 8.23 (d, J = 8.8 Hz, 1H), 8.14 - 8.00 (m, 3H), 7.99 (dd, J = 4.8, 2.0 Hz, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.50 - 7.45 (m, 2H), 7.44 - 7.35 (m, 2H), 7.12 (dd, J = 8.0, 2.0 Hz, 1H), 7.02 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.48 (d, J = 9.6 Hz, 1H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.91 - 3.74 (m, 1H), 3.59 (s, 2H), 3.52 (s, 3H), 2.89 - 2.78 (m, 2H), 2.21 - 2.07 (m, 2H), 1.95 - 1.79 (m, 2H), 1.58 - 1.40 (m, 2H). [00885] Example 356: 2-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(1-methyl-6-oxo-1,6- dihydropyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)pi peridin-4-yl)amino)pyrimidine-4- carbonitrile Example 356 was prepared in a manner similar to Example 341. MS: m/z = 610.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.64 - 8.51 (m, 1H), 8.46 (d, J = 2.0 Hz, 1H), 8.22 (d, J = 8.4 Hz, 1H), 8.08 (dd, J = 9.6, 2.0 Hz, 1H), 7.99 (d, J = 3.6 Hz, 1H), 7.90 - 7.77 (m, 2H), 7.50 - 7.44 (m, 2H), 7.43 - 7.36 (m, 2H), 7.12 (d, J = 7.6 Hz, 1H), 7.07 (d, J = 4.4 Hz, 1H), 7.03 (br s, 2H), 6.48 (d, J = 9.2 Hz, 1H), 6.35 (dd, J = 7.6, 5.2 Hz, 1H), 3.80 - 3.64 (m, 1H), 3.57 (s, 2H), 3.51 (s, 3H), 2.90 - 2.74 (m, 2H), 2.20 - 2.00 (m, 2H), 1.91 - 1.76 (m, 2H), 1.62 - 1.42 (m, 2H). [00886] Example 357: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(3-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 357 was prepared in a manner similar to Example 225. MS: m/z = 597.5 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.23 (d, J = 8.4 Hz, 1H), 8.06 - 7.96 (m, 3H), 7.89 (d, J = 8.4 Hz, 1H), 7.82 - 7.78 (m, 1H), 7.59 (d, J = 8.4 Hz, 2H), 7.50 - 7.44 (m, 3H), 7.37 - 7.35 (m, 1H), 7.16 - 7.09 (m, 1H), 6.66 - 6.59 (m, 1H), 6.51 (dd, J = 7.6, 5.2 Hz, 1H), 3.91 - 3.89 (m, 1H), 3.70 (s, 2H), 3.04 - 2.97 (m, 2H), 2.36 - 2.28 (m, 2H), 2.06 - 2.01 (m, 2H), 1.68 - 1.59 (m, 2H); ¹⁹ F NMR (400 MHz, Methanol-d ₄ ) δ -115.29. [00887] Example 358: 2-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(3-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-4-carbonitrile Example 358 was prepared in a manner similar to Example 261. MS: m/z = 597.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.62 (d, J = 4.8 Hz, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.05 (d, J = 8.4 Hz, 1H), 8.01 - 8.01 (m, 1H), 7.90 (d, J = 7.6 Hz, 1H), 7.82 (d, J = 10.8 Hz, 1H), 7.57 - 7.48 (m, 4H), 7.44 (d, J = 8.4 Hz, 2H), 7.23 - 7.19 (m, 2H), 7.10 (d, J = 4.4 Hz, 1H), 7.02 (br s, 2H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 4.48 - 4.41 (m, 2H), 3.87 (s, 2H), 3.17 - 3.11 (m, 2H), 2.77 - 2.74 (m, 1H), 1.94 - 1.89 (m, 2H), 1.31 - 1.24 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -112.913. [00888] Example 359: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(1-methyl-2-oxo-1,2- dihydropyridin-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)pi peridin-4-yl)amino)pyrimidine-2- carbonitrile Example 359 was prepared in a manner similar to Example 341. MS: m/z = 610.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.28 (d, J = 8.4 Hz, 1H), 8.12 - 7.93 (m, 4H), 7.75 (d, J = 7.2 Hz, 1H), 7.53 - 7.39 (m, 4H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.08 - 6.98 (m, 3H), 6.85 (dd, J = 7.2, 2.0 Hz, 1H), 6.67 (d, J = 6.0 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.87 - 3.73 (m, 1H), 3.59 (s, 2H), 3.43 (s, 3H), 2.89 - 2.79 (m, 2H), 2.22 - 2.08 (m, 2H), 1.95 - 1.81 (m, 2H), 1.59 - 1.39 (m, 2H). [00889] Example 360: 2-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(1-methyl-2-oxo-1,2- dihydropyridin-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)pi peridin-4-yl)amino)pyrimidine-4- carbonitrile Example 360 was prepared in a manner similar to Example 341. MS: m/z = 610.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.61 - 8.49 (m, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.09 - 7.97 (m, 2H), 7.89 - 7.82 (m, 1H), 7.75 (d, J = 7.2 Hz, 1H), 7.52 - 7.40 (m, 4H), 7.18 (dd, J = 7.6, 1.2 Hz, 1H), 7.09 - 6.99 (m, 4H), 6.86 (dd, J = 7.2, 2.0 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.78 - 3.64 (m, 1H), 3.58 (s, 2H), 3.43 (s, 3H), 2.88 - 2.80 (m, 2H), 2.16 - 2.03 (m, 2H), 1.89 - 1.80 (m, 2H), 1.62 - 1.48 (m, 2H). [00890] Example 361: 4-(7-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2,7-diazaspiro[3.5]nonan-2-yl)pyrimid ine-2-carbonitrile Example 361 was prepared in a manner similar to Example 267. MS: m/z = 605.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.29 - 8.20 (m, 2H), 8.04 - 7.97 (m, 4H), 7.50 - 7.44 (m, 6H), 7.42 - 7.37 (m, 1H), 7.17 (d, J = 7.6 Hz, 1H), 7.03 (br s, 2H), 6.63 (d, J = 6 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.80 (s, 4H), 3.56 (s, 2H), 3.31 - 3.27 (m, 2H), 2.37 - 2.35 (m, 2H), 1.82 - 1.76 (m, 4H). [00891] Example 362: 4-((7-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-7-azaspiro[3.5]nonan-2-yl)amino)pyrim idine-2-carbonitrile Example 362 was prepared in a manner similar to Example 267. MS: m/z = 619.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.50 - 8.32 (m, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.05 - 7.96 (m, 4H), 7.50 - 7.43 (m, 7H), 7.42 - 7.36 (m, 1H), 7.16 (dd, J = 8.0, 2.0 Hz, 1H), 7.04 (br s, 2H), 6.65 (d, J = 6.0 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 4.48 - 4.17 (m, 1H), 3.54 (s, 2H), 3.31 - 3.29 (m, 2H), 2.35 - 2.31 (m, 2H), 2.30 - 2.23 (m, 4H), 1.67 - 1.64 (m, 2H), 1.58 - 1.54 (m, 2H). [00892] Example 363: 4-(8-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2,8-diazaspiro[4.5]decan-2-yl)-1,3,5- triazine-2-carbonitrile Example 363 was prepared in a manner similar to Example 223. MS: m/z = 620.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.55 (d, J = 11.2 Hz, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.06 (d, J = 5.2 Hz, 1H), 8.01 (d, J = 7.6 Hz, 2H), 7.81 (d, J = 8.0 Hz, 1H), 7.65 - 7.60 (m, 1H), 7.51 - 7.39 (m, 6H), 7.10 (d, J = 8.0 Hz, 1H), 6.69 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.93 - 3.76 (m, 2H), 3.71 - 3.66 (m, 2H), 3.52 (s, 2H), 2.88 - 2.49 (m, 4H), 2.05 - 1.92 (m, 6H). [00893] Example 364: 4-(9-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-3,9-diazaspiro[5.5]undecan-3-yl)pyrim idine-2-carbonitrile Example 364 was prepared in a manner similar to Example 225. MS: m/z = 633.5 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.21 (d, J = 6.8 Hz, 1H), 8.05 - 7.96 (m, 4H), 7.48 - 7.38 (m, 7H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.08 (d, J = 6.8 Hz, 1H), 7.03 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.68 - 3.61 (m, 2H), 3.59 (s, 2H), 3.31 - 3.27 (m, 2H), 2.44 - 2.38 (m, 4H), 1.56 - 1.45 (m, 8H). [00894] Example 365: 4-(9-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-3,9-diazaspiro[5.5]undecan-3-yl)-1,3, 5-triazine-2-carbonitrile Example 365 was prepared in a manner similar to Example 223. MS: m/z = 634.3 [M +H] ⁺ .1H NMR (400 MHz,Chlorofrm-d) δ 8.53 (s, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.09 - 8.05 (m, 1H), 8.02 (d, J = 7.6 Hz, 2H), 7.81 (d, J = 8.4 Hz, 1H), 7.61 - 7.51 (m, 2H), 7.47 - 7.41 (m, 4H), 7.40 - 7.36 (m, 1H), 7.09 (d, J = 6.4 Hz, 1H), 6.60 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.87 - 3.81 (m, 4H), 3.79 - 3.64 (m, 2H), 2.77 - 2.51 (m, 4H), 1.61 - 1.60 (m, 8H). [00895] Example 366: 4-(6-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2,6-diazaspiro[3.3]heptan-2-yl)pyrimi dine-2-carbonitrile Example 366 was prepared in a manner similar to Example 341. MS: m/z = 577.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.32 - 8.14 (m, 2H), 8.08 - 7.94 (m, 4H), 7.50 - 737 (m, 7H), 7.15 (d, J = 7.6 Hz, 1H), 7.01 (br s, 2H), 6.62 (d, J = 5.6 Hz, 1H), 6.46 - 6.32 (m, 1H), 4.20 (s, 4H), 3.64 (s, 2H), 3.38 (s, 4H). [00896] Example 367: 4-((3aS,6aS)-5-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)hexahydropyrrolo[3,4-c]pyr rol-2(1H)-yl)pyrimidine-2- carbonitrile

To a solution of Intermediate 102 (81.0 mg HC1 salt, 155 μmol) in NMP (0.8 mL) were added 4- chloropyrimidine-2-carbonitrile (21.6 mg, 155 μmol) and DIEA (59.9 mg, 81 μL). The mixture was stirred at 5 °C for 10 min. The residue was purified by pre-HPLC column: Welch Xtimate C18 150 x 25 mm x 5 μm; mobile phase: [water (NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN]; gradient: 60% - 90% B over 7 min to give 4-((3aS,6aS)-5-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)hexahydropyrrolo[3,4-c]pyr rol-2(1H)-yl)pyrimidine-2- carbonitrile (Example 367, 11.0 mg, yield: 12%) as a white solid. MS: m/z = 591.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J= 8.0 Hz, 1H), 8.22 (d, J= 6.4 Hz, 1H), 8.06 - 8.01 (m, 2H), 8.01 - 7.97 (m, 2H), 7.53 - 7.37 (m, TH), 7.17 (dd, J= 7.6, 1.6 Hz, 1H), 7.03 (br s, 2H), 6.74 (d, J= 6.4 Hz, 1H), 6.39 (dd, J= 7.6, 4.8 Hz, 1H), 4.02-3.91 (m, 2H), 3.83 (dd, J= 10.8, 6.8 Hz, 1H), 3.61 (dd, J= 9.2, 6.4 Hz, 1H), 3.13 - 3.07 (m, 2H), 2.95 - 2.88 (m, 2H), 2.72 - 2.62 (m, 2H), 2.44 - 2.29 (m, 2H).

[00897] Example 368: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-l-yl)-l,3,5-tria zine-2-carbonitrile

Example 368 was prepared in a manner similar to Example 261. MS: m/z = 584.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethyl sulfoxide-d ₆ ) δ 8.73 (s, 1H), 8.27 (d, J= 8.4 Hz, 1H), 8.08 (dd, J= 8.8, 6.0 Hz, 2H), 8.01 - 7.97 (m, 2H), 7.53 - 7.50 (m, 2H), 7.48 - 7.45 (m, 2H), 7.33 - 7.28 (m, 2H), 7.15 (d, J= 6.8 Hz, 1H), 7.02 (br s, 2H), 6.39 (dd, J= 8.0, 4.8 Hz, 1H), 3.89 - 3.79 (m, 4H), 3.65 (s, 2H), 3.37 - 3.33 (m, 2H), 3.32 - 3.26 (m, 2H). ¹⁹ F NMR (377 MHz, Dimethylsulfoxide- d ₆ ) δ -113.57. [00898] Example 369: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(4-chlorophenyl)-3H- imidazo[4, 5-b]pyridin-3 -yl)benzyl)piperazin- 1 -yl)- 1 ,3 , 5-triazine-2-carbonitrile

Example 369 was prepared in a manner similar to Example 261. MS: m/z = 600.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.73 (s, 1H), 8.29 (d, J= 8.4 Hz, 1H), 8.06 (d, J= 8.4 Hz, 2H), 8.01 (d, J= 8.0 Hz, 2H), 7.55 - 7.52 (m, 4H), 7.49 - 7.46 (m, 2H), 7.16 (d, J= 7.2 Hz, 1H), 7.03 (br s, 2H), 6.39 (dd, J= 7.6, 4.8 Hz, 1H), 3.89 - 3.80 (m, 4H), 3.65 (s, 2H), 3.37 - 3.34 (m, 2H), 3.31 - 3.26 (m, 2H).

[00899] Example 370: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

To a solution of Intermediate 107 (250 mg, 581 μmol) and Intermediate 51 (180 mg, 567 μmol) in ACN (10 mL) were added K ₂ CO ₃ (482 mg, 3.49 mmol) and Nal (17.4 mg, 116 μmol). The mixture was stirred at 80 °C for 3 hr. The reaction mixture was diluted with H ₂ O (50 mL) and extracted with CH ₂ CI ₂ (50 mL x 2). The combined organic layers were washed with brine (50 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0~8% MeOH in CH ₂ CI ₂ ), 4-((l-(4-(2-(2- aminopyridin-3-yl)-5-(4-fluorophenyl)-3H-imidazo[4,5-b]pyrid in-3-yl)benzyl)piperi din-4- yl)amino)pyrimidine-2-carbonitrile (Example 370, 76.6 mg, yield: 22%) was obtained as a lightyellow solid. MS: m/z = 597.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J= 8.4 Hz, 1H), 8.15 - 8.01 (m, 4H), 8.01 - 7.92 (m, 2H), 7.52 - 7.49 (m, 4H), 7.33 - 7.28 (m, 2H), 7.14 (d, J= 6.8 Hz, 1H), 7.03 (br s, 2H), 6.67 (d, J= 6.4 Hz, 1H), 6.37 (dd, J= 7.6, 4.8 Hz, 1H), 3.95 - 3.73 (m, 1H), 3.59 (s, 2H), 2.87 - 2.80 (m, 2H), 2.20 - 2.18 (m, 2H), 1.95 - 1.86 (m, 2H), 1.57 - 1.41 (m, 2H).

[00900] Example 371: 2-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(4-chlorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-4-carbonitrile

To a solution of 3-(3-(4-(chloromethyl)phenyl)-5-(4-chlorophenyl)-3H-imidazo[ 4,5-b]pyridin-2- yl)pyridin-2-amine (refer to Intermediate 43 for detail procedures, 200 mg HC1 salt, 414 μmol) and Intermediate 87 (131 mg TFA salt, 414 μmol) in DMF (5 mL) were added Nal (32 mg, 207 μmol) and K ₂ CO ₃ (286 mg, 2.07 mmol). The mixture was stirred at 50 °C for 1 hr. The reaction mixture was filtered. After purified by prep-HPLC (column: Waters xbridge 150 x 25 mm 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 59% - 89% B over 14 min), 2-((l-(4- (2-(2-aminopyridin-3-yl)-5-(4-chlorophenyl)-3H-imidazo[4,5-b ]pyridin-3-yl)benzyl)piperi din-4- yl)amino)pyrimidine-4-carbonitrile (Example 371, 48.1 mg, yield: 19%) was obtained as a yellow solid. MS: m/z = 613.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.62 (d, J= 4.8 Hz, 1H), 8.28 (d, J= 9.2 Hz, 1H), 8.08 - 8.03 (m, 2H), 8.02 - 7.98 (m, 2H), 7.56 - 7.50 (m, 4H), 7.43 (d, J= 8.4 Hz, 2H), 7.19 (dd, J= 7.6, 1.6 Hz, 1H), 7.10 (d, J= 4.8 Hz, 1H), 7.01 (br s, 2H), 6.40 (dd, J= 8.0, 4.8Hz, 1H), 4.41 (d, J= 12.8 Hz, 2H), 3.86 (s, 2H), 3.18 - 3.11 (m, 2H), 2.79 - 2.70 (m, 1H), 1.95 - 1.86 (m, 2H), 1.32 - 1.22 (m, 2H).

[00901] Example 372: 2-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(3-chlorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-4-carbonitrile

Example 372 was prepared in a manner similar to Example 261. MS: m/z = 613.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.62 (d, J= 4.4 Hz, 1H), 8.29 (d, J= 8.4 Hz, 1H), 8.07 - 8.04 (m, 2H), 8.03 - 7.99 (m, 2H), 7.55 (d, J= 8.4 Hz, 2H), 7.53 - 7.40 (m, 5H), 7.22 - 7.18 (m, 1H), 7.10 (d, J= 4.8 Hz, 1H), 7.01 (br s, 2H), 6.40 (dd, J= 7.6, 4.8 Hz, 1H), 4.43 - 4.36 (m, 2H), 3.87 (s, 2H), 3.18 - 3.10 (m, 2H), 2.78 - 2.72 (m, 1H), 1.93 - 1.89 (m, 2H), 1.32 - 1.24 (m, 2H).

[00902] Example 373: 6-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(3-chlorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-4-carbonitrile Example 373 was prepared in a manner similar to Example 261. MS: m/z = 613.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.49 (s, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.08 - 7.98 (m, 5H), 7.52 - 7.44 (m, 6H), 7.17 (dd, J = 8.0, 2.0Hz, 1H), 7.04 (s, 2H), 6.92 (s, 1H), 6.38 (dd, J = 8.0, 4.8 Hz, 1H), 4.00 - 3.76 (m, 1H), 3.59 (s, 2H), 2.87 - 2.80 (m, 2H), 2.16 - 2.09 (m, 2H), 1.93 - 1.82 (m, 2H), 1.56 - 1.45 (m, 2H). [00903] Example 374: 6-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(3-chlorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 4-carbonitrile Example 374 was prepared in a manner similar to Example 261. MS: m/z = 599.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.57 (s, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.07 - 8.04 (m, 2H), 8.03 - 7.99 (m, 2H), 7.58 - 7.56 (m, 1H), 7.54 - 7.50 (m, 3H), 7.49 - 7.46 (m, 3H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.05 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.81 - 3.69 (m, 4H), 3.65 (s, 2H), 3.36 - 3.34 (m, 2H), 3.32 - 3.29 (m, 2H). [00904] Example 375: 4-((1S,4S)-5-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,5-diazabicyclo[2.2.1]he ptan-2-yl)pyrimidine-2- carbonitrile Example 375 was prepared in a manner similar to Example 225. MS: m/z = 577.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.26 (d, J = 8.4 Hz, 1H), 8.24 – 8.18 (m, 1H), 8.04 - 7.96 (m, 4H), 7.52 - 7.39 (m, 7H), 7.16 (dd, J = 7.6,1.6 Hz, 1H), 7.00 (br s, 2H), 6.42 - 6.35 (m, 1H), 6.99 - 6.67 (m, 1H),), 4.94 - 4.65 (m, 1H), 3.84 (s, 2H), 3.71 - 3.53 (m, 2H), 3.44 - 3.38 (m, 2H), 3.00 - 2.89 (m, 1H), 2.06 - 1.95 (m, 1H), 1.88 - 1.76 (m, 1H). [00905] Example 376: 6-((1S,4S)-5-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,5-diazabicyclo[2.2.1]he ptan-2-yl)pyrimidine-4- carbonitrile Example 376 was prepared in a manner similar to Example 225. MS: m/z = 577.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.52 (d, J = 12.8 Hz, 1H), 8.26 (d, J = 8.0 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.53 - 7.37 (m, 8H), 7.17 - 7.15 (m, 1H), 7.00 (br s, 2H), 6.39 (dd, J = 8.0, 4.8 Hz, 1H), 5.00 - 4.67 (m, 1H), 3.86 - 3.79 (m, 2H), 3.72 - 3.57 (m, 2H), 3.45 - 3.36 (m, 2H), 2.96 - 2.89 (m, 1H), 2.05 - 1.96 (m, 1H), 1.87 - 1.78 (m, 1H). [00906] Example 377: 2-((1S,4S)-5-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,5-diazabicyclo[2.2.1]he ptan-2-yl)pyrimidine-4- carbonitrile Example 377 was prepared in a manner similar to Example 225. MS: m/z = 577.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.61 (dd, J = 13.2, 4.8 Hz, 1H), 8.26 (d, J = 8.0 Hz, 1H), 8.04 - 7.96 (m, 4H), 7.52 - 7.49 (m, 2H), 7.47 - 7.43 (m, 3H), 7.42 - 7.37 (m, 2H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.13 (d, J = 4.8 Hz, 1H), 7.01 (br s, 2H), 6.39 (dd, J = 7.2, 4.4 Hz, 1H), 4.84 - 4.70 (m, 1H), 3.83 (s, 2H), 3.70 - 3.64 (m, 2H), 3.45 - 3.35 (m, 2H), 2.98 - 2.93 (m, 1H), 2.59 - 2.52 (m, 2H), 2.00 - 1.96 (m, 1H), 1.85 - 1.81 (m, 1H). [00907] Example 378: 4-((2S,6R)-4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,6-dimethylpiperazin-1-y l)pyrimidine-2-carbonitrile Example 378 was prepared in a manner similar to Example 225. MS: m/z = 593.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) 8.21 - 8.18 (m, 2H), 8.06 - 8.04 (m, 2H), 8.00 - 7.98 (m, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.62 (d, J = 8.0 Hz, 2H), 7.48 - 7.41 (m, 4H), 7.39 - 7.37 (m, 1H), 7.35 (dd, J = 7.2, 1.6 Hz, 1H), 6.88 (d, J = 6.4 Hz, 1H), 6.48 (dd, J = 7.6, 4.8 Hz, 1H), 3.67 (s, 2H), 3.30 - 3.27 (m, 2H), 2.89 - 2.87(m, 1H), 2.89 - 2.85 (m, 1H), 2.39 - 2.31 (m, 2H), 1.26 (d, J = 6.0 Hz, 6H). [00908] Example 379: 2-((2S,6R)-4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,6-dimethylpiperazin-1-y l)pyrimidine-4-carbonitrile Example 379 was prepared in a manner similar to Example 225. MS: m/z = 593.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.67 (d, J = 4.8 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.06 - 8.03 (m, 2H), 8.02 - 7.98 (m, 2H), 7.60 (d, J = 8.4 Hz, 2H), 7.49 (d, J = 8.4 Hz, 2H), 7.46 - 7.43 (m, 2H), 7.41 - 7.38 (m, 1H), 7.19 - 7.15 (m, 2H), 7.06 (br s, 2H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 4.60 - 4.59 (m, 2H), 3.65 (s, 2H), 2.78 (d, J = 11.2 Hz, 2H), 2.27 - 2.23 (m, 2H), 1.28 (d, J = 6.4 Hz, 6H). [00909] Example 380: 6-((2S,6R)-4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,6-dimethylpiperazin-1-y l)pyrimidine-4-carbonitrile Example 380 was prepared in a manner similar to Example 225. MS: m/z = 593.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.54 (s, 1H), 8.20 (d, J = 8.4 Hz, 1H), 8.05 (d, J = 7.2 Hz, 2H), 7.99 (dd, J = 5.2, 1.6 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.62 (d, J = 8.4 Hz, 2H), 7.43 - 7.41 (m, 4H), 7.39 -7.37 (m, 1H), 7.34 (dd, J = 7.6, 1.6 Hz, 1H), 7.23 (s, 1H), 6.49 (dd, J = 7.6, 4.8 Hz, 1H), 3.69 (s, 2H), 3.34- 3.30 (m, 2H), 2.86 (d, J = 11.2 Hz, 2H), 2.33 (d, J = 11.2 Hz, 2H), 1.37 (d, J = 6.4 Hz, 6H). [00910] Example 381: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-oxo-1,2-dihydropyridi n-3- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile Example 381 was prepared in a manner similar to Example 225. MS: m/z = 596.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 11.98 (br s, 1H), 8.68 (d, J = 8.4 Hz, 1H), 8.23 (dd, J = 7.2, 2.0 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 8.12 - 7.01 (m, 2H), 8.01 - 7.97 (m, 1H), 7.49 - 7.41 (m, 5H), 7.13 (d, J = 7.6 Hz, 1H), 7.04 (br s, 2H), 6.67 (d, J = 6.0Hz, 1H), 6.39 - 6.34 (m, 2H), 3.90 - 3.75 (m, 1H), 3.59 (s, 2H), 2.86 - 2.80 (m, 2H), 2.20 - 2.10 (m, 2H), 1.94 - 1.84 (m, 2H), 1.56 - 1.45 (m, 2H). [00911] Example 382: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-chlorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)-1,3, 5-triazine-2-carbonitrile Example 382 was prepared in a manner similar to Example 261. MS: m/z = 614.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethyl sulfoxide -d ₆ ) δ 8.97 - 8.90 (m, 1H), 8.68 - 8.61 (m, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.09 - 7.97 (m, 4H), 7.53 (d, J = 8.4 Hz, 2H), 7.50 - 7.43 (m, 4H), 7.15 (d, J = 7.6 Hz, 1H), 7.03 (br s, 2H), 6.36 – 6.35 (m, 1H), 3.84 - 3.69 (m, 1H), 3.57 (s, 2H), 2.89 - 2.81 (m, 2H), 2.15 - 2.02 (m, 2H), 1.86 - 1.80 (m, 2H), 1.64 - 1.50 (m, 2H). [00912] Example 383: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(4-cyanopyridin-3-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 2-carbonitrile Example 383 was prepared in a manner similar to Example 261. MS: m/z = 591.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.20 (s, 1H), 8.84 (d, J = 5.2 Hz, 1H), 8.43 (d, J = 8.4 Hz, 1H), 8.26 (d, J = 6.4 Hz, 1H), 8.04 - 7.96 (m, 3H), 7.51 - 7.45 (m, 4H), 7.21 (d, J = 6.0 Hz, 1H), 7.11 (d, J = 6.4 Hz, 1H), 7.01 (br s, 2H), 6.40 (dd, J = 7.6, 5.2 Hz, 1H), 3.76 - 3.63 (m, 4H), 3.61 (s, 2H), 2.48 - 2.43 (m, 4H). [00913] Example 384: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-cyanopyridin-3-yl)-3H - imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 384 was prepared in a manner similar to Example 261. MS: m/z = 605.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.25 - 9.24 (m, 1H), 8.84 (d, J = 4.8 Hz, 1H), 8.43 (d, J = 8.0 Hz, 1H), 8.09 - 8.02 (m, 3H), 7.97 (d, J = 4.8 Hz, 1H), 7.65 (s, 1H), 7.51 - 7.41 (m, 4H), 7.25 - 7.19 (m, 1H), 7.01 (br s, 2H), 6.67 - 6.66 (m, 1H), 6.44 - 6.38 (m, 1H), 4.06 - 3.69 (m, 1H), 3.55 (s, 2H), 2.82 - 2.80 (m, 2H), 2.15 - 2.08 (m, 2H), 1.92 - 1.81 (m, 2H), 1.52 - 1.42 (m, 2H). [00914] Example 385: 4-((1-((4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin- 3- yl)phenyl)methyl-d2)piperidin-4-yl)amino)pyrimidine-2-carbon itrile Example 385 was prepared in a manner similar to Example 261. MS: m/z = 505.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.33 (d, J = 4.4 Hz, 1H), 8.21 (d, J = 8.0 Hz, 1H), 8.11 - 8.03 (m, 2H), 7.99 (d, J = 4.4 Hz, 1H), 7.47 - 7.43 (m, 2H), 7.41 - 7.37 (m, 3H), 7.16 (d, J = 8.0 Hz, 1H), 7.02 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.87 - 3.74 (m, 1H), 2.85 - 2.78 (m, 2H), 2.20 - 2.09 (m, 2H), 1.93 - 1.83 (m, 2H), 1.53 - 1.43 (m, 2H) [00915] Example 386: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(4-methyl-3-oxo-1,4- diazepan-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperazi n-1-yl)pyrimidine-2-carbonitrile Example 386 was prepared in a manner similar to Example 341. MS: m/z = 615.3 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 6.4 Hz, 1H), 8.00 - 7.90 (m, 2H), 7.44 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 7.11 (d, J = 6.4 Hz, 1H), 7.05 - 6.92 (m, 3H), 6.80 (d, J = 8.8 Hz, 1H), 6.30 (dd, J = 7.6, 4.8 Hz, 1H), 4.27 (s, 2H), 3.83 - 3.77 (m, 2H), 3.75 - 3.65 (m, 6H), 3.62 (s, 2H), 3.48 - 3.43 (m, 2H), 2.76 (s, 3H), 2.46 - 2.44 (m, 2H), 1.74 - 1.67 (m, 2H). [00916] Example 387: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(3-oxomorpholino)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 387 was prepared in a manner similar to Example 261. MS: m/z = 602.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.24 (d, J = 8.4 Hz, 1H), 8.12 - 8.03 (m, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.84 (d, J = 8.8 Hz, 1H), 7.48 - 7.42 (m, 2H), 7.41 - 7.36 (m, 2H), 7.12 (dd, J = 7.6, 1.6 Hz, 1H), 6.95 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 4.25 (s, 2H), 3.98 - 3.92 (m, 2H), 3.86 - 3.83 (m, 2H), 3.57 (s, 2H), 3.18 - 3.13 (m, 1H), 2.82 - 2.79 (m, 2H), 2.16 - 2.11 (m, 2H), 1.92 - 1.84 (m, 2H), 1.55 - 1.47 (m, 2H). [00917] Example 388: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-cyclopentyl-3H-imidazo[4 ,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile Example 388 was prepared in a manner similar to Example 261. MS: m/z = 571.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.13 - 8.03 (m, 3H), 7.97 (dd, J = 4.8, 1.6 Hz, 1H), 7.44 (d, J = 7.2 Hz, 2H), 7.39 - 7.34 (m, 2H), 7.30 (d, J = 8.0 Hz, 1H), 7.09 (dd, J = 4.8, 1.6 Hz, 1H), 6.94 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 3.85 - 3.75 (m, 1H), 3.57 (s, 2H), 3.22 - 3.18 (m, 1H), 2.85 - 2.76 (m, 2H), 2.19 - 2.10 (m, 2H), 2.00 - 1.95 (m, 2H), 1.90 - 1.76 (m, 2H), 1.75 - 1.68 (m, 4H), 1.62 - 1.57 (m, 2H), 1.52 - 1.43 (m, 2H). [00918] Example 389: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(dimethylamino)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 389 was prepared in a manner similar to Example 261. MS: m/z = 546.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.06 - 7.95 (m, 1H), 7.92 (dd, J = 4.8, 1.6 Hz, 1H), 7.86 (d, J = 9.2 Hz, 1H), 7.47 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.21 (dd, J = 7.6, 1.6 Hz, 1H), 6.71 (d, J = 9.2 Hz, 1H), 6.63 - 6.56 (m, 1H), 6.44 (dd, J = 7.6, 4.8 Hz, 1H), 4.09 - 3.79 (m, 1H), 3.63 (s, 2H), 3.07 (s, 6H), 2.96 - 2.93 (m, 2H), 2.30 - 2.20 (m, 2H), 1.98 - 1.04 (m, 2H), 1.55 - 1.64 (m, 2H). [00919] Example 390: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3 - yl)benzyl)piperidin-4-yl)(methyl)amino)pyrimidine-2-carbonit rile Example 390 was prepared in a manner similar to Example 261. MS: m/z = 517.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.33 (d, J = 4.4 Hz, 1H), 8.26 - 8.18 (m, 2H), 7.99 (d, J = 4.0 Hz, 1H), 7.49 - 7.44 (m, 2H), 7.42 - 7.36 (m, 3H), 7.17 (d, J = 7.6 Hz, 1H), 7.08 - 6.84 (m, 3H), 6.38 (dd, J = 7.2, 4.8 Hz, 1H), 4.91 - 4.34 (m, 1H), 3.59 (s, 2H), 2.99 - 2.84 (m, 5H), 2.23 - 2.10 (m, 2H), 1.91 - 1.77 (m, 2H), 1.65 - 1.53 (m, 2H). [00920] Example 391: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)-1,3,5-triazine-2 -carbonitrile Example 391 was prepared in a manner similar to Example 223. MS: m/z = 580.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Acetonitrile-d ₃ ) δ 8.61 - 8.47 (m, 1H), 8.17 (d, J = 8.4 Hz, 1H), 8.06 - 7.98 (m, 3H), 7.90 (d, J = 8.4 Hz, 1H), 7.52 - 7.39 (m, 7H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 6.94 - 6.74 (m, 1H), 6.57 (br s, 2H), 6.42 - 6.33 (m, 1H), 3.96 - 3.78 (m, 1H), 3.62 (s, 2H), 2.96 - 2.84 (m, 2H), 2.25 - 2.18 (m, 2H), 1.66 - 1.57 (m, 2H), 1.34 - 1.21 (m, 2H). [00921] Example 392: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3 - yl)benzyl)-4-methylpiperidin-4-yl)amino)pyrimidine-2-carboni trile Example 392 was prepared in a manner similar to Example 261. MS: m/z = 517.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.33 (dd, J = 4.8, 1.3 Hz, 1H), 8.20 (dd, J = 8.0, 1.6 Hz, 1H), 8.09 (d, J = 6.0 Hz, 1H), 8.00 - 7.97 (m, 1H), 7.61 (br s, 1H), 7.46 - 7.42 (m, 2H), 7.41- 7.34 (m, 3H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.08 - 6.93 (m, 2H), 6.81 (d, J = 6.4 Hz, 1H), 6.36 (dd, J = 8.0, 5.2 Hz, 1H), 3.57 - 3.48 (m, 2H), 3.30 (s, 2H), 2.33 - 2.17 (m, 4H), 1.73 - 1.62 (m, 2H), 1.40 (s, 3H). [00922] Example 393: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(1-methyl-6-oxo-1,6- dihydropyridin-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)pi peridin-4-yl)amino)pyrimidine-2- carbonitrile Example 393 was prepared in a manner similar to Example 261. MS: m/z = 610.5 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.36 (d, J = 8.0 Hz, 1H), 8.12 - 8.03 (m, 2H), 8.01 (dd, J = 4.8, 2.0 Hz, 1H), 7.66 (d, J = 8.4 Hz, 1H), 7.49 - 7.40 (m, 5H), 7.19 (dd, J = 7.6, 1.6 Hz, 1H), 7.00 (br s, 2H), 6.66 (d, J = 6.0 Hz, 1H), 6.47 (dd, J = 9.2, 1.2 Hz, 1H), 6.40 (dd, J = 8.0, 4.8 Hz, 1H), 6.33 (dd, J = 6.8, 1.2 Hz, 1H), 3.84 - 3.73 (m, 1H), 3.55 (s, 2H), 3.30 (s, 3H), 2.84 - 2.76 (m, 2H), 2.18 - 2.09 (m, 2H), 1.89 - 1.85 (m, 2H), 1.54 - 1.42 (m, 2H). [00923] Example 394: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(1-methyl-6-oxo-1,6- dihydropyridin-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)pi perazin-1-yl)pyrimidine-2- carbonitrile Example 394 was prepared in a manner similar to Example 261. MS: m/z = 596.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.37 (d, J = 8.4 Hz, 1H), 8.31 - 8.24 (m, 1H), 8.05 - 7.97 (m, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.51 - 7.42 (m, 5H), 7.21 - 7.17 (m, 1H), 7.11 (d, J = 6.0 Hz, 1H), 7.00 (br s, 2H), 6.48 (d, J = 9.2 Hz, 1H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 6.33 (d, J = 6.8 Hz, 1H), 3.75 - 3.64 (m, 4H), 3.62 (s, 2H), 3.31 (s, 3H), 2.48 - 2.44 (m, 4H). [00924] Example 395: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(3-methoxyphenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 395 was prepared in a manner similar to Example 261. MS: m/z = 609.5 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.26 (d, J = 8.4 Hz, 1H), 8.17 - 8.02 (m, 2H), 8.02 - 7.98 (m, 2H), 7.63 - 7.57 (m, 2H), 7.50 - 7.43 (m, 4H), 7.41 - 7.35 (m, 1H), 7.18 (dd, J = 8.0, 2.0 Hz, 1H), 7.11 - 7.01 (m, 2H), 6.97 (dd, J = 8.0, 2.0 Hz, 1H), 6.68 (d, J = 6.0 Hz, 1H), 6.39 (dd, J = 8.0, 4.8 Hz, 1H), 3.85 - 3.80 (m, 1H), 3.79 (s, 3H), 3.59 (s, 2H), 3.30 - 3.29 (m, 2H), 2.86 - 2.79 (m, 2H), 2.19 - 2.11 (m, 2H), 1.93 - 1.84 (m, 2H). [00925] Example 396: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(tert-butyl)-3H-imidazo[ 4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile Example 396 was prepared in a manner similar to Example 261. MS: m/z = 559.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Acetonitrile-d ₃ ) δ 8.17 - 7.87 (m, 3H), 7.49 - 7.43 (m, 3H), 7.36 (d, J = 8.0 Hz, 2H), 7.09 (d, J = 7.6 Hz, 1H) 6.63 - 6.54 (m, 1H), 6.48 (br s, 2H), 6.36 (dd, J = 8.0, 5.2 Hz, 1H), 6.33 - 6.20 (m, 1H), 4.06 - 3.76 (m, 1H), 3.63 (s, 2H), 2.92 - 2.84 (m, 2H), 2.31 - 2.27 (m, 2H), 2.02 - 1.97 (m, 2H), 1.62 - 1.52 (m, 2H), 1.34 (s, 9H). [00926] Example 397: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-ethyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile Example 397 was prepared in a manner similar to Example 261. MS: m/z = 531.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.12 - 8.01 (m, 3H), 7.97 (dd, J = 4.8, 2.0 Hz, 1H), 7.47 - 7.42 (m, 2H), 7.38 - 7.34 (m, 2H), 7.28 (d, J = 8.4 Hz, 1H), 7.08 (dd, J = 7.6, 1.6 Hz, 1H), 6.97 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.34 (dd, J = 7.2, 4.4 Hz, 1H), 3.89 - 7.73 (m, 1H), 3.57 (s, 2H), 2.84 - 2.76 (m, 4H), 2.18 - 2.12 (m, 2H), 1.95 - 1.81(m, 2H), 1.55 - 1.44 (m, 2H), 1.21 (t, J = 7.6 Hz, 3H). [00927] Example 398: 2-(2-Aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin-1-yl)methyl)phenyl)-N-methyl-3H-imidazo[4 ,5-b]pyridine-5-carboxamide Example 398 was prepared in a manner similar to Example 261. MS: m/z = 560.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.32 (d, J = 8.0 Hz, 1H), 8.14 - 8.13 (m, 1H), 8.12 - 8.02 (m, 3H), 8.00 (d, J = 4.4 Hz, 1H), 7.51 - 7.39 (m, 4H), 7.15 (d, J = 7.6 Hz, 1H), 6.96 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.38 (dd, J = 7.2, 4.8 Hz, 1H), 3.98 - 3.69 (m, 1H), 3.57 (s, 2H), 2.89 - 2.78 (m, 5H), 2.18 - 2.12 (m, 2H), 1.97 - 1.81 (m, 2H), 1.52 - 1.45 (m, 2H). [00928] Example 399: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(3-cyanopyridin-4-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 2-carbonitrile Example 399 was prepared in a manner similar to Example 261. MS: m/z = 591.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.09 (s, 1H), 8.91 (d, J = 5.6 Hz, 1H), 8.45 (d, J = 8.4 Hz, 1H), 8.26 (d, J = 6.4 Hz, 1H), 8.04 - 7.99 (m, 3H), 7.51 - 7.45 (m, 4H), 7.24 - 7.21 (m, 1H), 7.11 (d, J = 6.4 Hz, 1H), 7.01 (br s, 2H), 6.40 (dd, J = 7.6, 5.2 Hz, 1H), 3.70 - 3.60 (m, 6H), 2.48 - 2.45 (m, 4H). [00929] Example 400: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(3-cyanopyridin-4-yl)-3H - imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 400 was prepared in a manner similar to Example 261. MS: m/z = 605.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.08 (s, 1H), 8.91 (d, J = 5.2 Hz, 1H), 8.45 (d, J = 8.4 Hz, 1H), 8.10 - 7.96 (m, 5H), 7.52 - 7.46 (m, 2H), 7.46 - 7.40 (m, 2H), 7.22 (dd, J = 8.0, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 3.91 - 3.69 (m, 1H), 3.56 (s, 2H), 2.87 - 2.75 (m, 2H), 2.20 - 2.05 (m, 2H), 1.93 - 1.79 (m, 2H), 1.55 - 1.41 (m, 2H). [00930] Example 401: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-fluoro-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile Example 401 was prepared in a manner similar to Example 261. MS: m/z = 521.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.41 - 8.35 (m, 1H), 8.12 - 8.01 (m, 2H), 7.98 (dd, J = 4.8, 2.0 Hz, 1H), 7.47 - 7.43 (m, 2H), 7.40 - 7.37 (m, 2H), 7.17 - 7.14 (m, 2H), 6.91 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.84 - 3.76 (m, 1H), 3.56 (s, 2H), 2.81 (d, J = 11.2 Hz, 2H), 2.14 (t, J = 10.8 Hz, 2H), 1.91 - 1.83 (m, 2H), 1.53 - 1.44 (m, 2H), ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -74.090. [00931] Example 402: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-6-fluoro-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile

Example 402 was prepared in a manner similar to Example 261. MS : m/z = 521.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Acetonitrile-d ₃ ) δ 8.26 (s, 1H), 8.21 - 7.95 (m, 2H), 7.90 (dd, J= 8.8, 2.8 Hz, 1H), 7.51 (d, J= 8.8 Hz, 2H), 7.35 (d, J= 8.8 Hz, 2H), 7.16 (d, J= 8.8 Hz, 1H), 6.75 - 6.49 (m, 3H), 6.37 (dd, J= 8.8, 2.8 Hz, 1H), 6.27 (br s, 1H), 4.02 - 3.83 (m, 1H), 3.63 (s, 2H), 2.88 (d, J = 11.2 Hz, 2H), 2.26 - 2.21 (m, 2H), 2.17 - 2.13 (m, 2H), 1.60 - 1.49 (m, 2H). ¹⁹ F NMR (376 MHz, Acetonitrile-d ₆ ) δ -136.38.

[00932] Example 403: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(2-oxooxazolidin-3-yl)-3 H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

Example 403 was prepared in a manner similar to Example 261. MS: m/z = 588.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.25 (d, J= 8.8 Hz, 1H), 8.15 - 8.02 (m, 3H), 7.98 - 7.97 (m, 1H), 7.46 - 7.42 (m, 2H), 7.40 - 7.35 (m, 2H), 7.10 - 7.08 (m, 1H), 6.97 (br s, 2H), 6.67 (d, J= 6.0 Hz, 1H), 6.36 (dd, J= 7.6, 4.8 Hz, 1H), 4.41 (t, J= 8.0 Hz, 2H), 4.07 (t, J= 8.0 Hz, 2H), 3.88 - 3.72 (m, 1H), 3.57 (s, 2H), 2.82 - 2.79 (m, 2H), 2.18 - 2.10 (m, 2H), 1.92 - 1.83 (m, 2H), 1.54 - 1.44 (m, 2H).

[00933] Example 404: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(6-fluoropyridin-3-yl)-3 H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

To a solution of Intermediate 131 (200 mg, 464 μmol) and Intermediate 51 (147 mg, 464 μmol) in DMF (5 mL) were added Nal (34.8 mg, 232 μmol) and K ₂ CO ₃ (321 mg, 2.32 mmol). The mixture was stirred at 50 °C for 1 hr. The reaction mixture was filtered. After purified by prep- HPLC (column: Waters xbridge 150 * 25 mm 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 38% - 68% B over 14 min), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(6-fluoropyridin-3- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile (Example 404, 56 mg, yield: 20%) was obtained as a yellow solid. MS: m/z = 598.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.89 (d, J= 2.4 Hz, 1H), 8.61 - 8.53 (m, 1H), 8.33 (d, J= 8.4 Hz, 1H), 8.14 - 8.03 (m, 3H), 8.01 (dd, J= 4.8, 1.6 Hz, 1H), 7.50 - 7.43 (m, 4H), 7.30 (dd, J= 8.8, 2.8 Hz, 1H), 7.20 - 7.14 (m, 1H), 7.04 (br s, 2H), 6.67 (d, J= 6.0 Hz, 1H), 6.39 (dd, J= 7.6, 5.2 Hz, 1H), 3.85 - 3.77 (m, 1H), 3.59 (s, 2H), 2.83 (d, J= 12.0 Hz, 2H), 2.20 - 2.11 (m, 2H), 1.93 - 1.83 (m, 2H), 1.54 - 1.43 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethyl sulfoxide-d ₆ ) δ - 69.579.

[00934] Example 405: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile

To a solution of Intermediate 51 (165 mg, 810 μmol) and Intermediate 117 (300 mg, 810 μmol) in DMF (3 mL) was added DIEA (314 mg, 2.43 mmol). The mixture was degassed and purged with N ₂ three times and stirred at 25 °C for 16 hr under N ₂ . The reaction mixture was quenched with H ₂ O (10 mL) at 25 °C, and then extracted with CH ₂ CI ₂ (5 mL x 3). The combined organic layers were washed with brine (10 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 1 ~ 8% MeOH in CH ₂ CI ₂ ) to give 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile (Example 405, 226 mg, yield: 52%) as a light yellow solid. MS: m/z = 537.2 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J= 8.0 Hz, 1H), 8.14 - 8.02 (m, 2H), 7.99 (dd, J= 4.8, 1.6 Hz, 1H), 7.52 - 7.36 (m, 5H), 7.16 (dd, J= 7.6, 1.6 Hz, 1H), 6.94 (br s, 2H), 6.67 (d, J= 6.0 Hz, 1H), 6.38 (dd, J= 7.6, 4.8 Hz, 1H), 3.88 - 3.74 (m, 1H), 3.57 (s, 2H), 2.86 - 2.75 (m, 2H), 2.20 - 2.07 (m, 2H), 1.94 - 1.79 (m, 2H), 1.57 - 1.40 (m, 2H).

[00935] Example 406: 2-(2-Aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin-l-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyri dine-5-carbonitrile

To a solution of Intermediate 132 (235 mg, 651 μmol) and Intermediate 51 (207 mg, 651 μmol, TFA) in DMF (5 mL) were added K ₂ CO ₃ (450 mg, 3.26 mmol) and Nal (9.76 mg, 65.1 μmol). The mixture was stirred at 60 °C for 1 hr. After purified by prep-HPLC (column: Waters xbridge 150 * 25 mm * 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 25% - 55% B over 14 min), 2-(2-aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin-4-yl)ami no)piperidin-l- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridine-5-carbonitrile (Example 406, 36.2 mg, yield: 11%) was obtained as a yellow solid. MS: m/z = 528.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.42 (d, J= 8.0 Hz, 1H), 8.13 - 7.97 (m, 4H), 7.50 - 7.41 (m, 4H), 7.22 (d, J= 8.0 Hz, 1H), 6.99 (s, 2H), 6.67 (d, J= 6.0 Hz, 1H), 6.43 - 6.33 (m, 1H), 3.92 - 3.69 (m, 1H), 3.57 (s, 2H), 2.87 - 2.78 (m, 2H), 2.21 - 2.12 (m, 2H), 1.94 - 1.84 (m, 2H), 1.55 - 1.45 (m, 2H).

[00936] Example 407 : 4-(4-(4-(2-(2-Aminopyridin-3 -yl)-5 -(3 -cyanopyridin-2-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-l-yl)pyrimidine- 2-carbonitrile

Example 407 was prepared in a manner similar to Example 261. MS : m/z = 591.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.93 (dd, J= 4.8, 1.6 Hz, 1H), 8.46 - 8.35 (m, 2H), 8.29 - 8.20 (m, 2H), 8.02 (dd, J= 4.8, 2.0 Hz, 1H), 7.64 (dd, J= 8.0, 4.8 Hz, 1H), 7.54 - 7.49 (m, 2H), 7.48 - 7.39 (m, 2H), 7.24 (dd, J= 8.0, 2.0 Hz, 1H), 7.11 (d, J= 6.4 Hz, 1H), 7.01 (br s, 2H), 6.41 (dd, J= 7.6, 4.8 Hz, 1H), 3.71 - 3.66 (m, 2H), 3.61 (s, 2H), 3.31 - 3.29 (m, 2H), 2.53 - 2.51 (m, 2H), 2.48 - 2.44 (m, 2H).

[00937] Example 408: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(3-cyanopyridin-2-yl)-3H - imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

To a solution of Intermediate 134 (140 mg, 320 μmol) and Intermediate 51 (65.0 mg TFA salt, 320 μmol) in DMF (2 mL) were added K ₂ CO ₃ (221 mg, 1.60 mmol) and Nal (14.4 mg, 95.9 μmol). The mixture was stirred at 50 °C for 0.5 hr. The mixture was filtered, and the filtrate was concentrated to give the crude product. After purified by prep-HPLC (column: Waters xbridge 150 * 25 mm * 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 28% - 58% B over 14 min), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(3-cyanopyridin-2-yl)-3H -imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile (Example 408, 24.1 mg, yield: 12%) was obtained as light-yellow solid. MS: m/z = 605.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.93 (dd, J= 4.8, 1.6 Hz, 1H), 8.42 - 8.36 (m, 2H), 8.24 (d, J= 8.4 Hz, 1H), 8.10 - 8.00 (m, 3H), 7.63 (dd, J= 7.6, 4.4 Hz, 1H), 7.50 (d, J= 8.4 Hz, 2H), 7.42 (d, J= 8.4 Hz, 2H), 7.23 (dd, J= 7.6, 1.6 Hz, 1H), 7.02 (br s, 2H), 6.72 - 6.60 (m, 1H), 6.41 (dd, J= 7.6, 5.2 Hz, 1H), 3.95 - 3.68 (m, 1H), 3.56 (s, 2H), 2.86 - 2.79 (m, 2H), 2.17 - 2.09 (m, 2H), 1.92 - 1.83 (m, 2H), 1.52 - 1.41 (m, 2H).

[00938] Example 409: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(2-cyanopyridin-3-yl)-3H - imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

Example 409 was prepared in a manner similar to Example 261. MS: m/z = 605.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.78 (d, J= 4.4 Hz, 1H), 8.43 (d, J= 8.0 Hz, 1H), 8.36 (d, J= 8.0 Hz, 1H), 8.11 - 7.99 (m, 3H), 7.94 (d, J= 8.0 Hz, 1H), 7.84 (dd, J= 8.0, 4.4 Hz, 1H), 7.54 - 7.38 (m, 4H), 7.21 (d, J= 7.2 Hz, 1H), 7.01 (br s, 2H), 6.66 (d, J= 5.6 Hz, 1H), 6.41 (dd, J= 7.2, 4.8 Hz, 1H), 3.88 - 3.71 (m, 1H), 3.56 (s, 2H), 2.86 - 2.73 (m, 2H), 2.22 - 2.05 (m, 2H), 1.93 - 1.76 (m, 2H), 1.55 - 1.40 (m, 2H).

[00939] Example 410: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(trifluoromethyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

Example 410 was prepared in a manner similar to Example 261. MS: m/z = 571.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.44 (d, J= 8.0 Hz, 1H), 8.24 - 7.97 (m, 3H), 7.87 (d, J= 8.0 Hz, 1H), 7.51 - 7.40 (m, 4H), 7.21 (dd, J= 7.6, 1.6 Hz, 1H), 6.91 (s, 2H), 6.67 (d, J= 6.0 Hz, 1H), 6.40 (dd, J= 7.6, 4.8 Hz, 1H), 3.96 - 3.65 (m, J= 5.0 Hz, 1H), 3.57 (s, 2H), 2.88 - 2.76 (m, 2H), 2.23 - 2.09 (m, 2H), 1.89 (m, 2H), 1.57 - 1.42 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxi de-d ₆ ) δ -64.17.

[00940] Example 411: 2-(2-Aminopyridin-3 -yl)-3 -(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin-l-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyri dine-6-carbonitrile

Step 1 : 2-(2-Aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin-4-yl)ami no)piperidin-l- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridine-6-carboxamide

To a solution of Intermediate 137 (270 mg, 713 μmol) and Intermediate 51 (145 mg, 713 μmol) in DMF (5 mL) were added K ₂ CO ₃ (493 mg, 3.56 mmol) and Nal (10.7 mg, 71.3 μmol). The mixture was stirred at 60 °C for 1 hr. The reaction mixture was diluted with H ₂ O (50 mL) and extracted with CH ₂ CI ₂ (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give 2-(2- aminopyridin-3 -yl)-3 -(4-((4-((2-cyanopyrimidin-4-yl)amino)piperidin- 1 -yl)methyl)phenyl)-3H- imidazo[4,5-b]pyridine-6-carboxamide (230 mg, yield: 38%) as a yellow solid. MS: m/z = 546.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.85 (d, J= 2.0 Hz, 1H), 8.65 (d, J= 1.6 Hz, 1H), 8.22 - 8.17 (m, 1H), 8.09 - 8.07 (m, 1H), 8.01 - 7.99 (m, 1H), 7.61 - 7.50 (m, 2H), 7.48 - 7.39 (m, 4H), 7.21 - 7.17 (m, 1H), 6.95 (s, 2H), 6.70 - 6.66 (m, 1H), 6.39 (dd, J= 7.6, 4.8 Hz, 1H), 3.86 - 3.77 (m, 1H), 3.56 (s, 2H), 2.85 - 2.77 (m, 2H), 2.18 - 2.13 (m, 2H), 1.90 - 1.85 (m, 2H), 1.50 - 1.43 (m, 2H).

Step 2 : 2-(2-Aminopyridin-3 -yl)-3 -(4-((4-((2-cy anopyrimidin-4-yl)amino)piperidin- 1 - yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridine-6-carbonitrile To a solution of 2-(2-aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin-4-yl)ami no)piperidin-l- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridine-6-carboxamide (200 mg, 367 μmol) in CH ₂ CI ₂ (2 mL) was added Burgess reagent (174 mg, 733 μmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was quenched with NaHCO ₃ (10 mL) at 0 °C, and then diluted with H ₂ O (20 mL) and extracted with CH ₂ CI ₂ (20 mL x 2). The combined organic layers were washed with brine (40 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-HPLC (column: Phenomenex C ₁₈ 75 * 30 mm * 3 μm; mobile phase: [water (NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN]; gradient: 33% - 63% B over 7 min), 2-(2-aminopyridin-3-yl)-3- (4-((4-((2-cyanopyrimidin-4-yl)amino)piperidin-l-yl)methyl)p henyl)-3H-imidazo[4,5- b]pyridine-6-carbonitrile (Example 411, 6.1 mg, yield: 3.1%) was obtained as a yellow solid. MS: m/z = 528.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Acetonitrile-d ₆ ) δ 8.64 (d, J= 2.0 Hz, 1H), 8.47 (d, J= 2.0 Hz, 1H), 8.06 - 8.04 (m, 1H), 7.52 (d, J= 8.4 Hz, 2H), 7.36 (d, J= 8.0 Hz, 2H), 7.19 - 7.15 (m, 1H), 6.59 - 6.57 (m, 2H), 6.37 (dd, J= 8.0, 4.8 Hz, 1H), 6.29 - 6.22 (m, 1H), 4.01 - 3.76 (m, 1H), 3.61 (s, 2H), 2.93 - 2.78 (m, 2H), 2.26 - 2.19 (m, 2H), 2.00 - 1.96 (m, 2H), 1.60 - 1.46 (m, 2H).

[00941] Example 412: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5,6-dimethyl-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile

Example 412 was prepared in a manner similar to Example 261. MS: m/z = 531.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.12 - 8.03 (m, 2H), 7.97 - 7.94 (m, 2H), 7.45 (d, J= 8.0 Hz, 2H), 7.33 (d, J= 8.4 Hz, 2H), 7.07 - 7.02 (m, 3H), 6.67 (d, J= 5.6 Hz, 1H), 6.33 (dd, J= 7.6, 4.8 Hz, 1H), 3.90 - 3.72 (m, 1H), 3.57 (s, 2H), 2.86 - 2.79 (m, 2H), 2.45 (s, 3H), 2.38 (s, 3H), 2.18 - 2.11 (m, 2H), 1.92 - 1.85 (m, 2H), 1.54 - 1.45 (m, 2H).

[00942] Example 413: 4-((l-(4-(2-(2-aminopyridin-3-yl)-lH-imidazo[4,5-b]pyrazin-l - yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile

Example 413 was prepared in a manner similar to Example 261. MS: m/z = 504.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.58 (d, J= 2.4 Hz, 1H), 8.38 (d, J= 2.4 Hz, 1H), 8.14 - 8.00 (m, 3H), 7.49 - 7.40 (m, 4H), 7.27 (dd, J = 8.0, 1.6 Hz, 1H), 6.96 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.42 (dd, J = 7.6, 4.8 Hz, 1H), 3.91 - 3.66 (m, 1H), 3.56 (s, 2H), 2.85 - 2.70 (m, 2H), 2.20 - 2.05 (m, 2H), 1.94 - 1.81 (m, 2H), 1.54 - 1.42 (m, 2H). [00943] Example 414: Methyl 2-(2-aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin-1-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyri dine-5-carboxylate Example 414 was prepared in a manner similar to Example 261. MS: m/z = 561.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.33 (d, J = 8.4 Hz, 1H), 8.15 - 7.99 (m, 4H), 7.50 - 7.40 (m, 4H), 7.17 (dd, J = 7.62.0 Hz, 1H), 6.98 (s, 2H), 6.68 (d, J = 6.0 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.85 (s, 3H), 3.84 - 3.67 (m, 1H), 3.58 (s, 2H), 2.88 - 2.79 (m, 2H), 2.22 - 2.10 (m, 2H), 1.94 - 1.82 (m, 2H), 1.57 - 1.44 (m, 2H). [00944] Example 415: 2-(2-Aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin-1-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyri dine-5-carboxylic acid To a solution of Example 414 (200 mg, 357 µmol)in THF (2 mL) and H ₂ O (2 mL) was added LiOH·H ₂ O (15 mg, 357 µmol). After purified by prep-HPLC (column: Waters xbridge 150 * 25 mm * 10 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 11% - 41% B over 10 min), 2-(2-aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin-4-yl)ami no)piperidin-1- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridine-5-carboxylic acid (Example 415, 120 mg, yield: 44%) was obtained as a yellow solid. MS: m/z = 547.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.42 (d, J = 8.4 Hz, 1H), 8.31 (d, J = 8.0 Hz, 1H), 8.22 - 8.13 (m, 1H), 8.08 (d, J = 5.2 Hz, 1H), 7.96 - 7.88 (m, 3H), 7.70 (d, J = 7.2 Hz, 2H), 6.98 - 6.81 (m, 2H), 4.58 - 4.49 (m, 2H), 4.48 - 4.25 (m, 1H), 3.77 - 3.63 (m, 2H), 3.60 - 3.35 (m, 2H), 2.37 - 2.27 (m, 2H), 2.18 - 1.99 (m, 2H). [00945] Example 416: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(fluoromethoxy)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 416 was prepared in a manner similar to Example 261. MS: m/z = 551.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.25 (d, J = 8.4 Hz, 1H), 8.15 - 8.00 (m, 2H), 7.97 (dd, J = 4.8, 1.6 Hz, 1H), 7.45 (d, J = 8.0 Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H), 7.10 (dd, J = 7.6, 2.0 Hz, 1H), 6.98 (d, J = 8.8 Hz, 1H), 6.90 (br s, 2H), 6.67 (d, J = 6.4 Hz, 1H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 6.10 - 5.92 (m, 2H), 3.88 - 3.73 (m, 1H), 3.57 (s, 2H), 2.81 (d, J = 11.2 Hz, 2H), 2.18 - 2.10 (m, 2H), 1.93 - 1.83 (m, 2H), 1.59 - 1.38 (m, 2H), ¹⁹ F NMR (400 MHz, Dimethylsulfoxide- d ₆ ) δ-153.916. [00946] Example 417: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(tetrahydrofuran-3-yl)-3 H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 417 was prepared in a manner similar to Example 261. MS: m/z = 573.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.18 - 8.02 (m, 3H), 7.98 (dd, J = 4.8, 2.0 Hz, 1H), 7.45 (d, J = 8.4 Hz, 2H), 7.40 - 7.33 (m, 3H), 7.11 (dd, J = 8.0, 2.0 Hz, 1H), 6.96 (br s, 2H), 6.67 (d, J = 6.4 Hz, 1H), 6.36 (dd, J =7.6, 4.8 Hz, 1H), 4.05 (t, J = 8.0 Hz, 1H), 3.93 - 3.87 (m, 1H), 3.84 - 3.68 (m, 3H), 3.65 - 3.55 (m, 3H), 2.86 - 2.79 (m, 2H), 2.31 - 2.22 (m, 1H), 2.19 - 2.07 (m, 3H), 1.96 - 1.82 (m, 2H), 1.58 - 1.43 (m, 2H). [00947] Example 418: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(5-cyanopyridin-2-yl)-3H - imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 418 was prepared in a manner similar to Example 261. MS: m/z = 605.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.90 (s, 1H), 8.59 (dd, J = 8.4, 1.2 Hz, 1H), 8.44 (d, J = 8.4 Hz, 1H), 8.21 (dd, J= 8.4, 1.2 Hz, 1H), 8.19 - 8.13 (m, 1H), 8.11 - 8.07 (m, 1H), 7.97 (d, J= 8.4 Hz, 1H), 7.61 - 7.54 (m, 2H), 7.42 (d, J= 7.6 Hz, 2H), 7.10 (d, J= 8.0 Hz, 1H), 6.67 (br s, 2H), 6.46 (d, J= 6.4 Hz, 1H), 6.39 - 6.35 (m, 1H), 4.39 - 3.80 (m, 1H), 3.73 (s, 2H), 3.23 - 2.88 (m, 2H), 2.51 - 2.30 (m, 2H), 2.17 - 2.07 (m, 2H), 1.37 - 1.27 (m, 2H).

[00948] Example 419: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(6-cyanopyridin-3-yl)-3H - imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

Example 419 was prepared in a manner similar to Example 261. MS: m/z = 605.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.41 (d, J= 2.0 Hz, 1H), 8.62 (dd, J= 8.0, 2.0 Hz, 1H), 8.38 (d, J= 8.4 Hz, 1H), 8.23 (d, J= 8.4 Hz, 1H), 8.14 (d, J= 8.4 Hz, 1H), 8.12 - 8.04 (m, 2H), 8.02 (dd, J= 4.8, 2.0 Hz, 1H), 7.54 - 7.45 (m, 4H), 7.18 (dd, J= 7.6, 1.6 Hz, 1H), 7.05 (br s, 2H), 6.67 (d, J= 6.4 Hz, 1H), 6.40 (dd, J= 7.6, 4.8 Hz, 1H), 3.90 - 3.73 (m, 1H), 3.59 (s, 2H), 2.88 - 2.78 (m, 2H), 2.23 - 2.09 (m, 2H), 1.94 - 1.82 (m, 2H), 1.56 - 1.44 (m, 2H).

[00949] Example 420: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(oxetan-3-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

To a solution of Intermediate 145 (60.5 mg, 134 μmol) in DMF (1 mL) were added DIEA (69.2 mg, 536 μmol) and Intermediate 51 (29.9 mg, 147 μmol). The mixture was stirred at 25 °C for 12 hr under N ₂ . After purified by prep-HPLC(column: Welch Xtimate C18 150 * 25 mm * 5 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 37% - 67% B over 7 min), 4-((l-(4-(2- (2-aminopyridin-3 -yl)-5 -(oxetan-3 -yl)-3H-imidazo[4, 5-b]pyridin-3 -yl)benzyl)piperidin-4- yl)amino)pyrimidine-2-carbonitrile (Example 420, 1.9 mg, yield: 2.5% for 2 steps) was obtained as yellow solid. MS: m/z = 559.1 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethyl sulfoxide-d ₆ ) δ 8.18 (d, J= 6.8 Hz, 1H), 8.10 - 8.00 (m, 2H), 8.00 - 7.95 (m, 1H), 7.50 - 7.30 (m, 5H), 7.10 (dd, J= 6.4, 1.6 Hz, 1H), 6.97 (br s, 2H), 6.68 (d, J= 4.8 Hz, 1H), 6.40 - 6.30 (m, 1H), 4.88 (dd, J= 6.8, 4.4 Hz, 2H), 4.78 - 4.70 (m, 2H), 4.55 - 4.40 (m, 1H), 3.85 - 3.75 (m, 1H), 3.65 - 3.50 (m, 2H), 2.90 - 2.75 (m, 2H), 2.25 - 2.05 (m, 2H), 1.95 - 1.80 (m, 2H), 1.55 - 1.45 (m, 2H). [00950] Example 421: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-methoxyphenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 421 was prepared in a manner similar to Example 341. MS: m/z = 609.2 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.22 (d, J = 8.0 Hz, 1H), 8.08 (d, J = 6.0 Hz, 2H), 8.03 - 7.90 (m, 3H), 7.91 (d, J = 8.8 Hz, 1H), 7.50 - 7.40 (m, 4H), 7.18 - 7.00 (m, 5H), 6.68 (d, J = 6.0 Hz, 1H), 6.40 - 6.30 (m, 1H), 4.00 - 3.70 (m, 4H), 3.59 (s, 2H), 2.83 (d, J = 10.8 Hz, 2H), 2.30 - 2.10 (m, 2H), 2.00 - 1.80 (m, 2H), 1.60 - 1.40 (m, 2H). [00951] Example 422: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-methoxyphenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 422 was prepared in a manner similar to Example 261. MS: m/z = 609.1 [M +H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.14 (d, J = 8.4 Hz, 1H), 8.03 - 8.01 (m, 1H), 7.99 - 7.95 (m, 1H), 7.90 (d, J = 8.8 Hz, 1H), 7.64 (dd, J = 7.2 Hz, 1.2 Hz, 1H), 7.55 (d, J = 7.2 Hz, 2H), 7.47 (d, J = 8.0 Hz, 2H), 7.38 - 7.32 (m, 2H), 7.11 (d, J = 8.4 Hz, 1H), 7.00 (t, J = 7.2 Hz, 1H), 6.61 - 6.58 (m, 1H), 6.48 (dd, J = 7.2, 5.2 Hz, 1H), 4.06 - 3.94 (m, 1H), 3.86 (s, 3H), 3.83 - 3.73 (m, 2H), 3.09 - 3.02 (m, 2H), 2.54 - 2.31 (m, 2H), 2.10 - 2.01 (m, 2H), 1.66 - 1.58 (m, 2H). [00952] Example 423: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(trifluoromethoxy)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile ( Example 423 was prepared in a manner similar to Example 261. MS: m/z = 587.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.41 (d, J = 8.4 Hz, 1H), 8.12-7.98 (m, 3H), 7.45 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.4 Hz, 1H), 7.18 (dd, J = 7.6, 1.6 Hz, 1H), 6.85 (s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.88-3.74 (m, 1H), 3.56 (s, 2H), 2.83-2.74 (m, 2H), 2.18-2.09 (m, 2H), 1.94-1.82 (m, 2H), 1.56-1.44 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -55.510. [00953] Example 424: 4-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(2-cyanopyridin-3-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)pyrimidine- 2-carbonitrile ( Example 424 was prepared in a manner similar to Example 261. MS: m/z = 591.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.79 (dd, J = 4.8, 1.2 Hz, 1H), 8.43 (d, J = 8.0 Hz, 1H), 8.37 (dd, J = 8.0, 1.2 Hz, 1H), 8.26 (d, J = 6.4 Hz, 1H), 8.02 (dd, J = 4.8, 1.6 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.85 (dd, J = 8.0, 4.8 Hz, 1H), 7.51 - 7.46 (m, 4H), 7.21 (dd, J = 7.6, 1.6 Hz, 1H), 7.11 (d, J = 6.8 Hz, 1H), 7.01 (br s, 2H), 6.40 (dd, J = 7.6, 4.4 Hz, 1H), 3.74 - 3.64 (m, 4H), 3.61 (s, 2H), 2.49 - 2.43 (m, 4H). [00954] Example 425: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-isopropoxy-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile Example 425 was prepared in a manner similar to Example 341. MS: m/z = 561.1 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.20 - 8.02 (m, 3H), 7.95 (dd, J = 4.8, 1.6 Hz, 1H), 7.47 - 7.41 (m, 2H), 7.38 - 7.31 (m, 2H), 7.06 (dd, J = 7.6, 1.6 Hz, 1H), 6.97 (br s, 2H), 6.73 (d, J = 8.4 Hz, 1H), 6.67 (d, J = 6.0 Hz, 1H), 6.34 (dd, J = 7.6, 4.8 Hz, 1H), 5.08 - 4.98 (m, 1H), 3.93 - 3.72 (m, 1H), 3.57 (s, 2H), 2.85 - 2.74 (m, 2H), 2.22 - 2.07 (m, 2H), 1.96 - 1.78 (m, 2H), 1.56 - 1.41 (m, 2H), 1.24 (d, J = 6.4 Hz, 6H). [00955] Example 426: 4-((4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)amino)pyrimidine-2-carb onitrile Example 426 was prepared in a manner similar to Example 225. MS: m/z = 580.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.34 (s, 1H), 8.32 - 8.22 (m, 2H), 8.06 - 7.95 (m, 4H), 7.52 - 7.42 (m, 6H), 7.45 - 7.36 (m, 1H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (br s, 2H), 7.01 - 6.97 (m, 1H), 6.38 (dd, J = 8.0, 4.8 Hz, 1H), 3.61 (s, 2H), 3.32 - 3.31 (m, 2H), 2.98 - 2.66 (m, 6H). [00956] Example 427: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(methoxy-d3)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 427 was prepared in a manner similar to Example 261. MS: m/z = 536.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.13 - 8.04 (m, 3H), 7.95 (dd, J = 4.8, 1.6 Hz, 1H), 7.46 - 7.42 (m, 2H), 7.39 - 7.35 (m, 2H), 7.04 (dd, J = 7.6, 1.6 Hz, 1H), 6.96 (s, 2H), 6.81 (d, J = 8.4 Hz, 1H), 6.67 (d, J = 6.0 Hz, 1H), 6.34 (dd, J = 7.6, 4.8 Hz, 1H), 3.81 - 3.79 (m, 1H), 3.57 (s, 2H), 2.84 - 2.71 (m, 2H), 2.18 - 2.09 (m, 2H), 1.92 - 1.84 (m, 2H), 1.52 - 1.43 (m, 2H). [00957] Example 428: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(6-cyanopyridin-2-yl)-3H - imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 428 was prepared in a manner similar to Example 341. MS: m/z = 605.1 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.48 - 8.40 (m, 2H), 8.38 - 8.33 (m, 1H), 8.26 - 797 (m, 5H), 7.56 - 7.43 (m, 4H), 7.18 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.39 (dd, J = 8.0, 5.2 Hz, 1H), 3.91 - 3.73 (m, 1H), 3.50 (s, 2H), 2.88 - 2.79 (m, 2H), 2.20 - 2.10 (m, 2H), 1.94 - 1.81 (m, 2H), 1.56 - 1.39 (m, 2H). [00958] Example 429: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-cyanopyridin-4-yl)-3H - imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 429 was prepared in a manner similar to Example 261. MS: m/z = 605.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.82 (d, J = 5.2 Hz, 1H), 8.62 (s, 1H), 8.39 (d, J = 8.0 Hz, 1H), 8.32 (dd, J = 4.8, 1.6 Hz, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.11 - 8.04 (m, 2H), 8.02 (dd, J = 4.8, 1.6 Hz, 1H), 7.52 - 7.45 (m, 4H), 7.18 (dd, J = 7.6, 1.6 Hz, 1H), 7.06 (s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.87 - 3.74 (m, 1H), 3.60 (s, 2H), 2.89 - 2.80 (m, 2H), 2.20 - 2.11 (m, 2H), 1.95 - 1.82 (m, 2H), 1.58 - 1.43 (m, 2H). [00959] Example 430: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(5-cyanopyridin-3-yl)-3H - imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 430 was prepared in a manner similar to Example 261. MS: m/z = 605.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.48 (d, J = 2.0 Hz, 1H), 9.03 (s, 1H), 8.86 (s, 1H), 8.38 (d, J = 8.4 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 8.13 - 7.99 (m, 3H), 7.54 - 7.45 (m, 4H), 7.18 (d, J = 6.8 Hz, 1H), 7.06 (s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 3.82 - 3.81 (m, 1H), 3.60 (s, 2H), 2.89 - 2.76 (m, 2H), 2.21 - 2.09 (m, 2H), 1.94 - 1.81 (m, 2H), 1.61 - 1.43(m, 2H). [00960] Example 431: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(pyridin-3-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 431 was prepared in a manner similar to Example 341. MS: m/z = 580.3 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.23 (d, J = 1.6 Hz, 1H), 8.70 - 8.50 (m, 1H), 8.40 - 8.25 (m, 2H), 8.20 - 7.90 (m, 4H), 7.60-7.40 (m, 5H), 7.30 - 7.10 (m, 1H), 7.10-6.90 (m, 1H), 6.67 (d, J = 6.4 Hz, 1H), 6.38 (dd, J = 7.2, 4.8 Hz, 1H), 3.81 - 3.80 (m, 1H), 3.59 (s, 2H), 2.83 - 2.81 (m, 2H), 2.25 - 2.05 (m, 2H), 1.95-1.70 (m, 2H), 1.60-1.40 (m, 2H). [00961] Example 432: 4-(1-(4-(2-(2-Aminopyridin-3-yl)-5-(pyridin-3-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)pyrimidine- 2-carbonitrile Example 432 was prepared in a manner similar to Example 341. MS: m/z = 566.3 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.23 (br s, 1H), 8.59 (d, J = 2.8 Hz, 1H), 8.40 - 8.20 (m, 3H), 8.10 - 7.90 (m, 2H), 7.60-7.40 (m, 5H), 7.25 - 7.00 (m, 4H), 6.50-6.30 (m, 1H), 4.00- 3.50 (m, 8H), 3.30-3.10 (m, 2H). [00962] Example 433: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(pyridin-4-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 433 was prepared in a manner similar to Example 341. MS: m/z = 580.4 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.68 - 8.64 (m, 2H), 8.35 (d, J = 8.4 Hz, 1H), 8.16 (d, J = 8.8 Hz, 1H), 8.11 - 8.05 (m, 2H), 8.03 - 7.99 (m, 3H), 7.52 - 7.45 (m, 4H), 7.18 (dd, J = 7.6, 2.0 Hz, 1H), 7.04 (br s, 2H), 6.68 (d, J = 6.4 Hz, 1H), 6.39 (dd, J = 8.0, 4.8 Hz, 1H), 3.90 - 3.73 (m, 1H), 3.60 (s, 2H), 2.84 - 2.82 (m, 2H), 2.22 - 2.09 (m, 2H), 1.95 - 1.81 (m, 2H), 1.57 - 1.43 (m, 2H). [00963] Example 434: 4-((7-(4-(2-(2-Aminopyridin-3-yl)-5-morpholino-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl)-7-azaspiro[3.5]nonan-2-yl)amino)-1,3, 5-triazine-2-carbonitrile

Example 434 was prepared in a manner similar to Example 261. MS: m/z = 629.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.27 - 9.08 (m, 1H), 8.74 - 8.56 (m, 1H), 8.08 - 7.81 (m, 2H), 7.40 (d, J= 7.6 Hz, 2H), 7.36 - 7.25 (m, 2H), 7.04 (s, 2H), 7.01 - 6.95 (m, 1H), 6.92 - 6.86 (m, 1H), 6.29 (dd, J= 7.6, 4.8 Hz, 1H), 4.39 - 4.21 (m, 1H), 3.75 - 3.65 (m, 4H), 3.50 (s, 2H), 3.45 - 3.35 (m, 4H), 2.37 - 2.14 (m, 6H), 1.81 - 1.72 (m, 2H), 1.64 - 1.57 (m,2H), 1.56 - 1.49 (m, 2H).

[00964] Example 435: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(methylthio)-3H-imidazo[ 4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile

Example 435 was prepared in a manner similar to Example 261. MS: m/z = 571.0 [M + Na] ⁺ .

¹ H NMR (400MHz, DMSO-d ₆ ) δ 8.11 - 8.04 (m, 3H), 7.97 (dd, J= 4.8, 2.0 Hz, 1H), 7.45 (d, J= 8.4 Hz, 2H), 7.38 (d, J= 8.4 Hz, 2H), 7.27 (d, J= 8.4 Hz, 1H), 7.11 (dd, J= 7.6, 1.6 Hz, 1H), 7.0 (br s, 2H), 6.67 (d, J= 6.0 Hz, 1H), 6.36 (dd, J= 8.0, 5.2 Hz, 1H), 3.91 - 3.70 (m, 1H), 3.57 (s, 2H), 2.86 - 2.75 (m, 2H), 2.46 (s, 3H), 2.19 - 2.07 (m, 2H), 1.94 - 1.81 (m, 2H), 1.54 - 1.40 (m, 2H).

[00965] Example 436: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(methylsulfonyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

To a solution of Example 435 (50 mg, 91.1 μmol) in THF (2 mL) and MeOH (0.5 mL) was added oxone (280 mg, 456 μmol). The mixture was stirred at 25 °C for 16 hr. After purified by prep-HPLC (column: Waters xbridge 150 * 25 mm 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 18% - 48% B over 14 min), 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5- (methylsulfonyl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperi din-4-yl)amino)pyrimidine-2- carbonitrile (Example 436, 9.1 mg, yield: 16%) was obtained as light yellow solid. MS: m/z = 581.3 [M + H] ⁺ . ¹ HNMR (400MHz, Chloroform-d) δ 8.27 (d, J= 8.4 Hz, 1H), 8.18 - 8.08 (m, 3H), 7.51 (d, J= 8.0 Hz, 2H), 7.34 (d, J= 8.0 Hz, 2H), 7.09 (dd, J= 8.0, 1.6 Hz, 1H), 6.67 (hr s, 2H), 6.44 (d, J= 6.0 Hz, 1H), 6.36 (dd, J= 7.6, 4.8 Hz, 1H), 3.65 (s, 2H), 3.19 (s, 3H), 2.99 - 2.89 (m, 2H), 2.33 - 2.25 (m, 2H), 2.10 - 2.04 (m, 2H), 1.76 - 1.66 (m, 3H).

[00966] Example 437: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(4-methoxypyridin-2-yl)- 3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

Step 1 : (2-(2-Aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)oxy )methyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)boronic acid

A mixture of Intermediate 129 (200 mg, 392 μmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(l,3,2- dioxaborolane) (199 mg, 784 μmol), KOAc (115 mg, 1.18 mmol) and Pd(dppf)C12 (28.7 mg, 39.2 μmol) in 1,4-dioxane (2 mL) was degassed and purged with N2 three times. The mixture was stirred at 80 °C for 2 hr under N2 atmosphere. (2-(2-Aminopyridin-3-yl)-3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-3H-imidazo[4,5-b]pyrid in-5-yl)boronic acid was obtained as a black liquid, which was used in the next step directly without work-up and purification. MS: m/z = 476.1 [M + H] ⁺ .

Step 2: 3-(3-(4-(((tert-Butyldimethylsilyl)oxy)methyl)phenyl)-5-(4-m ethoxypyridin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

A mixture of (2-(2-aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)oxy )methyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)boronic acid (460 mg, 968 μmol), 2-bromo-4-methoxypyridine (182 mg, 968 μmol), Pd(dppf)Cl ₂ (70.8 mg, 96.8 μmol) and CS ₂ CO ₃ (946 mg, 2.90 mmol) in 1,4- dioxane (5 mL) and H ₂ O (1 mL) was degassed and purged with N2 three times. The mixture was stirred at 80 °C for 16 hr under N2 atmosphere. The reaction mixture was quenched with H ₂ O (10 mL), diluted with EtOAc (10 mL) and extracted with EtOAc (15 mL x 2). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 10% ~ 40% EtOAc in petroleum ether), 3-(3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-5-(4-methoxypyridin-2- yl)-3H-imidazo[4,5-b]pyri din-2- yl)pyridin-2-amine (250 mg, yield: 56% for two steps) was obtained as a black solid. MS: m/z = 539.2 [M + H] ⁺ . ¹ HNMR (400 MHz, Chloroform-d) δ 8.54 - 8.46 (m, 2H), 8.17 (d, J= 8.4 Hz, 1H), 8.06 (dd, J= 4.8, 1.6 Hz, 1H), 7.88 (d, J= 2.4 Hz, 1H), 7.52 - 7.48 (m, 2H), 7.43 - 7.38 (m, 2H), 7.14 (dd, J= 7.6, 1.2 Hz, 1H), 6.80 (dd, J= 5.6, 2.4 Hz, 1H), 6.71 (br s, 2H), 6.38 (dd, J= 7.6, 4.8 Hz, 1H), 4.86 (s, 2H), 3.87 (s, 3H), 0.98 (s, 9H), 0.15 (s, 6H).

Step 3 : (4-(2-(2-Aminopyridin-3-yl)-5-(4-methoxypyridin-2-yl)-3H-imi dazo[4,5-b]pyridin-3- yl)phenyl)methanol

To a solution of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-(4-m ethoxypyridin-2- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (250 mg, 464 μmol) in THF (3 mL) was added TBAF (364 mg, 1.39 mmol, 1 M in THF). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was quenched with H ₂ O (5 mL) at 25 °C, diluted with CH ₂ CI ₂ (10 mL) and extracted with CH ₂ CI ₂ (15 mL x 3). The combined organic layers were washed with brine (50 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The mixture was triturated with EtOAc : petroleum ether = 1 : 10 at 25 °C for 10 min. (4-(2-(2-Aminopyridin-3- yl)-5-(4-methoxypyridin-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl) phenyl)methanol (160 mg, yield: 81%) was obtained as a black solid. MS: m/z = 425.5 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.52 (d, J= 5.6 Hz, 1H), 8.44 (d, J= 8.4 Hz, 1H), 8.29 (d, J= 8.4 Hz, 1H), 8.01 (dd, J= 4.8, 2.0 Hz, 1H), 7.70 (d, J= 2.4 Hz, 1H), 7.54 - 7.45 (m, 4H), 7.25 (dd, J= 7.6, 2.0 Hz, 1H), 7.03 (dd, J= 5.6, 2.4 Hz, 1H), 6.97 (br s, 2H), 6.43 (dd, J= 7.6, 4.8 Hz, 1H), 5.36 (t, J= 5.6 Hz, 1H), 4.61 (d, J= 5.6 Hz, 2H), 3.85 (s, 3H).

Step 4: 3-(3-(4-(Chloromethyl)phenyl)-5-(4-methoxypyridin-2-yl)-3H-i midazo[4,5-b]pyridin-2- yl)pyridin-2-amine

To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(4-methoxypyridin-2-yl)-3H-imi dazo[4,5- b]pyridin-3-yl)phenyl)methanol (160 mg, 377 μmol) in CH ₂ CI ₂ (5 mL) was added SOCl ₂ (135 mg, 1.13 mmol). The mixture was stirred at 25 °C for 0.4 hr. The reaction was concentrated under reduced pressure to give 3-(3-(4-(chloromethyl)phenyl)-5-(4-methoxypyridin-2-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (180 mg, HC1 salt) as a yellow solid. MS: m/z = 443.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.62 (d, J= 6.8 Hz, 1H), 8.58 - 8.55 (m, 1H), 8.52 - 8.48 (m, 1H), 8.24 (d, J= 2.4 Hz, 1H), 8.07 - 8.04 (m, 1H), 7.85 (d, J= 6.4 Hz, 1H), 7.73 (d, J= 8.0 Hz, 2H), 7.63 (d, J= 8.4 Hz, 2H), 7.55 (dd, J= 7.2, 2.4 Hz, 1H), 6.91 - 6.84 (m, 1H), 4.80 (s, 2H), 4.26 (s, 3H).

Step 5: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(4-methoxypyridin-2-yl)- 3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile

To a solution of 3-(3-(4-(chloromethyl)phenyl)-5-(4-methoxypyridin-2-yl)-3H-i midazo[4,5- b]pyridin-2-yl)pyridin-2-amine (180 mg, 376 μmol, HC1 salt) and Intermediate 55 (119 mg, 376 μmol, TFA salt) in DMF (4 mL) were added K ₂ CO ₃ (259 mg, 1.88 mmol) and Nal (5.63 mg, 37.6 μmol). The mixture was stirred at 50 °C for 1 hr. The reaction mixture was quenched with H ₂ O (5 mL) at 25 °C, diluted with CH ₂ CI ₂ (10 mL) and extracted with CH ₂ CI ₂ (15 mL x 2). The combined organic layers were washed with brine (50 mL x3), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 1% ~ 7% MeOH in CH ₂ CI ₂ ), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(4-methoxypyridin-2-yl)- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile (Example 437, 93.9 mg, yield: 40% for two steps) was obtained as a yellow solid. MS: m/z = 610.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.51 (d, J= 5.6 Hz, 1H), 8.45 (d, J= 8.4 Hz, 1H), 8.30 (d, J= 8.4 Hz, 1H), 8.14 - 7.98 (m, 3H), 7.74 - 7.71 (m, 1H), 7.54 - 7.45 (m, 4H), 7.22 (d, J= 7.2 Hz, 1H), 7.06 - 7.00 (m, 3H), 6.68 (d, J= 5.6 Hz, 1H), 6.41 (dd, J= 7.6, 4.8 Hz, 1H), 3.83 (s, 3H), 3.82 - 3.75 (m, 1H), 3.61 (s, 2H), 2.87 - 2.80 (m, 2H), 2.20 - 2.11 (m, 2H), 1.95 - 1.85 (m, 2H), 1.57 - 1.46 (m, 2H).

[00967] Example 438: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(l-methyl-1H-l,2,3-triaz ol-4- yl)-3H-imidazo[4, 5 -b]py ridin-3 -yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile

To a solution of 4 -bromo- 1 -methyl -1H- 1,2, 3 -tri azole (400 mg, 2.5 mmol) and 4-(4, 4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)pyridine-2-carbonitrile (272 mg, 1.18 mmol) in 1,4-dioxane (4 mL) were added Pd(dppf)Cl ₂ (101 mg, 123 μmol) and KOAc (1.05 g, 3.22 mmol) at 25 °C. The mixture was degassed, purged with N2 three times, and stirred at 100 °C for 12 hr. Then 4- ((l-(4-(2-(2-aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5-b]py ridin-3-yl)benzyl)piperi din-4- yl)amino)pyrimidine-2-carbonitrile (200 mg, 372 mmol), Cs ₂ CO ₃ (360 mg, 1.1 mmol) and Pd(dppf)Cl ₂ (30 mg, 37 μmol) at 25 °C were added to the above mixture. The mixture was degassed and purged with N2 three times and stirred at 100 °C for 12 hr. The mixture was quenched with H ₂ O (50 mL) and extracted with EtOAc (50 mL x 3). The combined organic layers were washed with brine (50 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0 ~ 7% MeOH in CH ₂ CI ₂ ), 4-((l-(4-(2-(2- aminopyridin-3-yl)-5-(l-methyl-1H-l,2,3-triazol-4-yl)-3H-imi dazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile (Example 438, 18.7 mg, yield: 8% for two steps) was obtained as an off white solid. MS: m/z = 584.2 [M + 1] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.15 (s, 1H), 8.09 (d, J= 8.4 Hz, 1H), 7.98 (d, J= 8.4 Hz, 1H), 7.93 - 7.83 (m, 2H), 7.42 (d, J= 8.4 Hz, 2H), 7.31 (d, J= 8.4 Hz, 2H), 7.16 (dd, J= 7.6, 1.6 Hz, 1H), 6.50 (d, J = 4.4 Hz, 1H), 6.35 (dd, J= 7.6, 5.2 Hz, 1H), 4.01 (s, 3H), 3.93 - 3.79 (m, 1H), 3.57 (s, 2H), 2.92 - 2.81 (m, 2H), 2.25 - 2.13 (m, 2H), 1.93 - 1.89 (m, 2H), 1.58 - 1.45 (m, 2H).

[00968] Example 439: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluoro-3-methoxypheny l)- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile

To a solution of Example 405 (200 mg, 372 μmol) and (4-fluoro-3-methoxy-phenyl)boronic acid (69.6 mg, 410 μmol) in 1,4-dioxane (10 mL) and H ₂ O (2 mL) were added Cs ₂ CO ₃ (364 mg, 1.12 mmol) and Pd(PPh ₃ ) ₄ (43.1 mg, 37.2 μmol) at 25 °C. The mixture was degassed and purged with N2 three times and stirred at 100 °C for 2 hr. The reaction mixture was quenched with water (20 mL) and extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (20 mL), dried over Na ₂ SO ₄ , filtered and concentrated. After purified by prep-HPLC (column: C18 150 x 30 mm; mobile phase: [water (NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN]; gradient:5% - 84% B over 7 min), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(4-fluoro-3- methoxyphenyl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidi n-4-yl)amino)pyrimidine-2- carbonitrile (Example 439, 130 mg, yield: 56%) was obtained as a light yellow solid. MS: m/z = 627.: 3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J= 8.4 Hz, 1 H), 8.14 - 7.96 (m, 4 H), 7.81 (dd, J= 8.4, 1.6 Hz, 1 H), 7.68 - 7.59 (m, 1 H), 7.52 - 7.42 (m, 4 H), 7.29 (dd, J= 11.2, 8.8 Hz, 1 H), 7.18 (dd, J= 7.6, 1.6 Hz, 1 H), 7.06 (s, 2 H), 6.68 (d, J = 6.0 Hz, 1 H), 6.39 (dd, J= 7.6, 4.8 Hz, 1 H), 3.89 (s, 3 H), 3.86 - 3.74 (m, 1 H), 3.59 (s, 2 H), 2.88 - 2.77 (m, 2 H), 2.21 - 2.09 (m, 2 H), 1.96 - 1.81 (m, 2 H), 1.58 - 1.40 (m, 2 H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -135.378. [00969] Example 440: N-(3-(2-(2-Aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin-1-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyri din-5-yl)phenyl)acetamide Example 440 was prepared in a manner similar to Example 261. MS: m/z = 636.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.05 (s, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.15 (s, 1H), 8.13 - 8.01 (m, 2H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.69 - 7.63 (m, 2H), 7.50 - 7.43 (m, 4H), 7.38 (t, J = 8.0 Hz, 1H), 7.14 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.95 - 3.68 (m, 1H), 3.59 (s, 2H), 2.88 - 2.79 (m, 2H), 2.19 - 2.11 (m, 2H), 2.03 (s, 3H), 1.95 - 1.75 (m, 2H), 1.56 - 1.43 (m, 2H). [00970] Example 441: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)(methyl-d3) amino)pyrimidine-2-carbonitrile Step 1: tert-Butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-(4-fluorophenyl)-3H-imidazo [4,5-b]pyridin- 3-yl)benzyl)piperidin-4-yl)(methyl-d3)carbamate To a solution of Intermediate 107 (100 mg, 232 µmol) in DMF (3 mL) were added tert-butyl (methyl-d3)(piperidin-4-yl)carbamate (refer to Intermediate 41 for detail procedures, 60 mg, 279 µmol), NaI (35 mg, 233 µmol) and K ₂ CO ₃ (129 mg, 930 µmol) at 25 °C. The mixture was stirred at 50 °C for 1 hr. The reaction mixture was poured into H ₂ O (50 mL). The mixture was extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (40 mL), dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated to dryness. After purified by silica gel flash chromatography (MeOH in CH ₂ Cl ₂ = 0% to 3%), tert-butyl (1-(4-(2-(2- aminopyridin-3-yl)-5-(4-fluorophenyl)-3H-imidazo[4,5-b]pyrid in-3-yl)benzyl)piperidin-4- yl)(methyl-d3)carbamate (130 mg, yield: 71%) was obtained as a yellow solid. MS: m/z = 611.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.12 - 8.05 (m, 2H), 8.01 - 7.96 (m, 2H), 7.50 - 7.41 (m, 4H), 7.34 - 7.27 (m, 2H), 7.15 (dd, J = 8.0, 2.0 Hz, 1H), 7.02 (s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.88 - 3.67 (m, 1H), 3.57 (s, 2H), 2.96 - 2.86 (m, 2H), 2.08 - 1.97 (m, 2H), 1.74 - 1.63 (m, 2H), 1.56 - 1.47 (m, 2H), 1.40 (s, 9H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -113.59 (s, 1F). Step 2: 3-(5-(4-Fluorophenyl)-3-(4-((4-((methyl-d3)amino)piperidin-1 -yl)methyl)phenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine To a solution of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-(4-fluorophenyl)-3H-imidazo [4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)(methyl-d3)carbamate (130 mg, 213 µmol) in CH ₂ Cl ₂ (5 mL) was added TFA (121 mg, 1.1 mmol) at 25 °C. The reaction mixture was stirred at 25 °C for 1 hr. The reaction mixture was concentrated under reduced pressure. 3-(5-(4-Fluorophenyl)-3- (4-((4-((methyl-d3)amino)piperidin-1-yl)methyl)phenyl)-3H-im idazo[4,5-b]pyridin-2- yl)pyridin-2-amine (100 mg) was used into the next step without further purification. MS: m/z = 511.2 [M + H] ⁺ . Step 3: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H-imid azo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)(methyl-d3)amino)pyrimidine-2-carbo nitrile To a solution of 3-(5-(4-fluorophenyl)-3-(4-((4-((methyl-d3)amino)piperidin-1 - yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-am ine (100 mg, 196 µmol) and 4- chloropyrimidine-2-carbonitrile (33 mg, 235 µmol) in NMP (3 mL) was added DIEA (76 mg, 588 µmol) at 25 °C. The mixture was stirred at 130 °C for 1 hr. The reaction mixture was poured into H ₂ O (50 mL) and extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (40 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0~5% MeOH in CH ₂ Cl ₂ ), 4-((1-(4-(2-(2- aminopyridin-3-yl)-5-(4-fluorophenyl)-3H-imidazo[4,5-b]pyrid in-3-yl)benzyl)piperidin-4- yl)(methyl-d3)amino)pyrimidine-2-carbonitrile (Example 441, 21.6 mg, yield: 17% for two steps) was obtained as a yellow solid. MS: m/z = 614.7 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.24 (d, J = 6.4 Hz, 1H), 8.10 - 8.06 (m, 2H), 8.01 - 7.97 (m, 2H), 7.52 - 7.43 (m, 5H), 7.30 (t, J = 8.8 Hz, 2H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.62 (s, 2H), 3.29 - 3.28 (m, 1H), 2.99 - 2.91 (m, 2H), 2.21 - 2.14 (m, 2H), 1.89 - 1.79 (m, 2H), 1.63 - 1.56 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -113.48. [00971] Example 442: 4-((1-((4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methyl-d2)piperidin-4-yl)( methyl-d3)amino)pyrimidine-2- carbonitrile Step 1: tert-Butyl (1-((4-(2-(2-aminopyridin-3-yl)-5-(4-fluorophenyl)-3H-imidaz o[4,5- b]pyridin-3-yl)phenyl)methyl-d2)piperidin-4-yl)(methyl-d3)ca rbamate To a solution of Intermediate 195 (100 mg, 232 µmol) in DMF (3 mL) were added tert-butyl (methyl-d3)(piperidin-4-yl)carbamate (refer to Intermediate 41 for detail procedures, 60 mg, 279 µmol), NaI (35 mg, 232 µmol) and K ₂ CO ₃ (128 mg, 926 µmol) at 25 °C, the mixture was stirred at 50 °C for 1 hr. The reaction mixture was poured into H ₂ O (50 mL), extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (40 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0~3% MeOH in CH ₂ Cl ₂ ), tert-butyl (1-((4-(2-(2-aminopyridin-3-yl)-5-(4- fluorophenyl)-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)methyl-d2 )piperidin-4-yl)(methyl- d3)carbamate (130 mg, yield: 70%) was obtained as a yellow solid. MS: m/z = 613.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.11 - 8.04 (m, 2H), 8.01 - 7.94 (m, 2H), 7.51 - 7.40 (m, 4H), 7.30 (t, J = 8.8 Hz, 2H), 7.14 (dd, J = 7.6, 2.0 Hz, 1H), 7.03 (s, 2H), 6.37 (dd, J = 8.0, 4.8 Hz, 1H), 3.81 - 3.79 (m, 1H), 2.95 - 2.85 (m, 2H), 2.07 - 1.99 (m, 2H), 1.76 - 1.62 (m, 2H), 1.56 - 1.47 (m, 2H), 1.39 (s, 9H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -113.59. Step 2: 3-(5-(4-Fluorophenyl)-3-(4-((4-((methyl-d3)amino)piperidin-1 -yl)methyl-d2)phenyl)- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine To a solution of tert-butyl (1-((4-(2-(2-aminopyridin-3-yl)-5-(4-fluorophenyl)-3H-imidaz o[4,5- b]pyridin-3-yl)phenyl)methyl-d2)piperidin-4-yl)(methyl-d3)ca rbamate (130 mg, 212 µmol) in CH ₂ Cl ₂ (5 mL) was added TFA (121 mg, 1.1 mmol) at 25 °C. The reaction mixture was stirred at 25 °C for 1 hr. The reaction mixture was concentrate under reduced pressure. The crude product 3-(5-(4-fluorophenyl)-3-(4-((4-((methyl-d3)amino)piperidin-1 -yl)methyl-d2)phenyl)- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (105 mg) was used into the next step without further purification. MS: m/z = 513.1 [M + H] ⁺ . Step 3: 4-((1-((4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H-imi dazo[4,5-b]pyridin-3- yl)phenyl)methyl-d2)piperidin-4-yl)(methyl-d3)amino)pyrimidi ne-2-carbonitrile To a solution of 3-(5-(4-fluorophenyl)-3-(4-((4-((methyl-d3)amino)piperidin-1 -yl)methyl- d2)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (100 mg, 195 µmol) and 4- chloropyrimidine-2-carbonitrile (33 mg, 235 µmol) in NMP (3 mL) was added DIEA (76 mg, 588 µmol) at 25 °C. The mixture was stirred at 130 °C for 1 hr. The reaction mixture was poured into H ₂ O (50 mL), extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (40 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0~5% MeOH in CH ₂ Cl ₂ ), 4-((1-((4-(2-(2- aminopyridin-3-yl)-5-(4-fluorophenyl)-3H-imidazo[4,5-b]pyrid in-3-yl)phenyl)methyl- d2)piperidin-4-yl)(methyl-d3)amino)pyrimidine-2-carbonitrile (Example 442, 20.5 mg, yield: 17% for two steps) was obtained as a yellow solid. MS: m/z = 616.5 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.24 (d, J = 6.4 Hz, 1H), 8.08 (dd, J = 8.8, 5.6 Hz, 2H), 8.01 - 7.97 (m, 2H), 7.55 - 7.42 (m, 5H), 7.30 (t, J = 8.8 Hz, 2H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.07 - 6.92 (m, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.29 - 3.28 (m, 1H), 2.99 - 2.92 (m, 2H), 2.22 - 2.13 (m, 2H), 1.88 - 1.79 (m, 2H), 1.65 - 1.55 (m, 2H). ¹⁹ F NMR (400 MHz,Dimethylsulfoxide-d ₆ ) δ -113.58. [00972] Example 443: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)azetidin-3-yl)amino)pyrimi dine-2-carbonitrile Example 443 was prepared in a manner similar to Example 261. MS: m/z = 569.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.64 (d, J = 6.8 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.15 (d, J = 6.0 Hz, 1H), 8.11 - 8.05 (m, 2H), 8.02 - 7.97 (m, 2H), 7.49 - 7.42 (m, 4H), 7.30 (t, J = 8.8 Hz, 2H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.73 (d, J = 6.0 Hz, 1H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 4.56 - 4.38 (m, 1H), 3.71 (s, 2H), 3.68 - 3.61 (m, 2H), 3.04 (t, J = 6.4 Hz, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -113.566. [00973] Example 444: 4-((7-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-7-azaspiro[3.5]nonan-2-yl )amino)pyrimidine-2-carbonitrile Example 444 was prepared in a manner similar to Example 261. MS: m/z = 637.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.44 - 8.31 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.14 - 8.02 (m, 3H), 8.01 - 7.93 (m, 2H), 7.50 - 7.39 (m, 4H), 7.29 (t, J = 8.8 Hz, 2H), 7.19 - 7.11 (m, 1H), 7.04 (br s, 2H), 6.64 (d, J = 6.0 Hz, 1H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 4.47 - 4.19 (m, 1H), 3.53 (s, 2H), 2.41 - 2.33 (m, 2H), 2.32 - 2.19 (m, 4H), 1.75 - 1.61 (m, 4H), 1.60 - 1.51 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -113.573. [00974] Example 445: 4-((2-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2-azaspiro[3.3]heptan-6-y l)amino)pyrimidine-2-carbonitrile Example 445 was prepared in a manner similar to Example 261. MS: m/z = 609.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.43 - 8.29 (m, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.08 (dd, J = 8.8, 5.6 Hz, 3H), 8.00 (dd, J = 4.8, 1.6 Hz, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.51 - 7.36 (m, 4H), 7.30 (t, J = 8.4 Hz, 2H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.00 (br s, 2H), 6.63 (d, J = 6.0 Hz, 1H), 6.40 (dd, J = 7.6, 4.4 Hz, 1H), 4.35 - 4.14 (m, 1H), 3.60 (s, 2H), 3.30 - 3.25 (m, 2H), 3.20 - 3.05 (m, 2H), 2.58 - 2.52 (m, 2H), 2.20 - 1.94 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide- d ₆ ) δ -113.587. [00975] Example 446: 4-((2-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2-azaspiro[3.5]nonan-7-yl )amino)pyrimidine-2-carbonitrile Example 446 was prepared in a manner similar to Example 261. MS: m/z = 637.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.12 - 8.03 (m, 3H), 8.02 - 7.92 (m, 3H), 7.51 - 7.38 (m, 4H), 7.30 (t, J = 8.8 Hz, 2H), 7.19 - 7.12 (m, 1H), 6.99 (br s, 2H), 6.65 (d, J = 6.0 Hz 1H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.85 - 3.74 (m, 1H), 3.67 (s, 2H), 3.06 - 2.89 (m, 4H), 1.95 - 1.87 (m, 2H), 1.84 - 1.74 (m, 2H), 1.60 - 1.50 (m, 2H), 1.27 - 1.22 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -113.580. [00976] Example 447: 4-(6-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,6-diazaspiro[3.3]heptan -2-yl)pyrimidine-2-carbonitrile Example 447 was prepared in a manner similar to Example 261. MS: m/z = 595.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.26 (d, J = 8.4 Hz, 1H), 8.22 (d, J = 6.0 Hz, 1H), 8.07 (dd, J = 8.4, 5.6 Hz, 2H), 8.01 - 7.94 (m, 2H), 7.43 (s, 4H), 7.29 (t, J = 8.8 Hz, 2H), 7.17 - 7.10 (m, 1H), 7.05 - 6.92 (m, 2H), 6.70 - 6.52 (m, 1H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 4.26 - 4.15 (m, 4H), 3.63 (s, 2H), 3.42 - 3.35 (s, 4H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ - 113.581. [00977] Example 448: 4-(8-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-3,8-diazabicyclo[3.2.1]oc tan-3-yl)pyrimidine-2-carbonitrile Example 448 was prepared in a manner similar to Example 261. MS: m/z = 609.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.33 - 8.20 (m, 2H), 8.08 (dd, J = 8.8, 5.6 Hz, 2H), 8.00 (dd, J= 4.8, 1.6 Hz, 1H), 7.97 (d, J= 8.4 Hz, 1H), 7.58 (d, J= 8.4 Hz, 2H), 7.46 (d, J= 8.0 Hz, 2H), 7.30 (t, J= 8.8 Hz, 2H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.08 - 6.95 (m, 3H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 4.44 - 4.11 (m, 1H), 3.84 - 3.57 (m, 3H), 3.33 (s, 2H), 3.26 - 3.03 (m, 2H), 2.06 - 1.97 (m, 2H), 1.65 - 1.42 (m, 2H). 19F NMR (400 MHz, Dimethylsulfoxide-d6) δ - 113.573.

[00978] Example 449: 4-((3aR,6aS)-5-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl )- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)hexahydropyrrolo[3,4-c] pyrrol-2(1H)-yl)pyrimidine-2- carbonitrile

Example 449 was prepared in a manner similar to Example 261. MS: m/z = 609.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.34 - 8.16 (m, 2H), 8.07 (dd, J= 8.8, 5.6 Hz, 2H), 8.02 - 7.94 (m, 2H), 7.54 - 7.35 (m, 4H), 7.29 (t, J= 8.8 Hz, 2H), 7.14 (dd, J= 7.6, 1.6 Hz, 1H), 7.01 (s, 2H), 6.79 (d, J= 6.0 Hz, 1H), 6.37 (dd, J= 7.6, 4.8 Hz, 1H), 3.87 - 3.73 (m, 1H), 3.68 (s, 2H), 3.53 - 3.42 (m, 1H), 3.04 - 2.90 (m, 2H), 2.71 - 2.52 (m, 6H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -113.558.

[00979] Example 450: 4-((3aS,6aS)-5-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl )- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)hexahydropyrrolo[3,4-c] pyrrol-2(1H)-yl)pyrimidine-2- carbonitrile Step 1: tert-Butyl (3aS,6aS)-5-(4-(2-(2-aminopyridin-3-yl)-5-(4-fluorophenyl)-3 H-imidazo[4,5- b]pyridin-3-yl)benzyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-c arboxylate

To a solution of Intermediate 107 (200 mg, 465 μmol), tert-butyl (3aS,6aS)- hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (109 mg, 512 μmol) in DMF (2 mL) were added K2CO3 (129 mg, 931 μmol) and Nal (6.97 mg, 46.5 μmol). The mixture was stirred at 80 °C for 2 hr. The reaction mixture was poured into H ₂ O (15 mL), extracted with EtOAc (15 mL x 3). The organic phase was dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 52% EtOAc in petroleum ether), tert-butyl (3aS,6aS)-5-(4-(2-(2-aminopyridin-3-yl)-5-(4- fluorophenyl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)hexahydro pyrrolo[3,4-c]pyrrole-2(1H)- carboxylate (190 mg, yield: 67%) was obtained as a yellow oil. MS: m/z = 606.1 [M + H] ⁺ . Step 2 : 3 -(5-(4-Fluorophenyl)-3 -(4-(((3 aR,6aR)-hexahy dropyrrolo[3,4-c]pyrrol-2( 1H)- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-am ine

To a solution of (3aS,6aS)-5-(4-(2-(2-aminopyridin-3-yl)-5-(4-fluorophenyl)-3 H-imidazo[4,5- b]pyridin-3-yl)benzyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-c arboxylate (190 mg, 314 μmol) in 1,4-dioxane (2 mL) was added HC1 in 1,4-dioxane (4 M, 2 mL). The mixture was stirred at 25 °C for 2 hr. The reaction mixture was concentrated directly. 3-(5-(4-fluorophenyl)-3-(4- (((3aR,6aR)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)methyl)ph enyl)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (160 mg, HC1 salt, yield: 94%) was obtained as a yellow solid. ¹ HNMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 12.29 (s, 1H), 10.05 (s, 1H), 9.78 (s, 1H), 8.37 (d, J= 8.4 Hz, 2H), 8.17 - 8.02 (m, 4H), 7.93 - 7.79 (m, 3H), 7.66 (d, J= 8.4 Hz, 2H), 7.32 (t, J= 8.8 Hz, 2H), 6.91 (dd, J= 7.2, 6.4 Hz, 1H), 4.70 - 4.49 (m, 2H), 3.50 - 3.41 (m, 2H), 3.40 - 3.28 (m, 4H), 3.18 - 3.08 (m, 1H), 3.05 - 2.91 (m, 2H), 2.90 - 2.75 (m, 1H), 2.45 - 2.32 (m, 2H). Step 3 : 4-((3aS,6aS)-5-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl )-3H-imidazo[4,5- b]pyridin-3 -yl)benzyl)hexahy dropyrrolo[3 ,4-c]pyrrol-2( 1H)-yl)pyrimidine-2-carbonitrile To a solution of 3-(5-(4-fluorophenyl)-3-(4-(((3aR,6aR)-hexahydropyrrolo[3,4- c]pyrrol-2(1H)- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-am ine (113 mg, 223.50 μmol, HC1 salt), 4-chloropyrimidine-2-carbonitrile (37.4 mg, 268 μmol) in DMF (2 mL) were added K ₂ CO ₃ (92.7 mg, 671 μmol) and Nal (3.35 mg, 22.4 μmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was poured into H ₂ O (15 mL), extracted with EtOAc (15 mL x 3). The organic phase was dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-HPLC (column: Phenomenex C18 150 x 25 mm x 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 50% - 80% B over 11 min), 4-((3aS,6aS)-5-(4-(2-(2- aminopyridin-3-yl)-5-(4-fluorophenyl)-3H-imidazo[4,5-b]pyri din-3- yl)benzyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyrimidine- 2-carbonitrile (Example 450, 10 mg, yield: 7%) was obtained as a light yellow lyophilized powder. MS: m/z = 609.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.31 - 8.20 (m, 2H), 6.91 (dd, J = 8.8, 5.6 Hz, 2H), 8.04 - 7.92 (m, 2H), 7.51 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H) , 7.30 (t, J = 8.8 Hz, 2H), 7.16 (dd, J = 8.0, 1.6 Hz, 1H) , 7.01 (br s, 2H), 6.75 (d, J = 6.4 Hz, 1H), 7.16 (dd, J = 8.0, 5.2 Hz, 1H), 4.04 - 3.90 (m, 2H), 3.88 - 3.78 (m, 1H), 3.67 - 3.56 (m, 1H), 3.15 - 3.07 (m, 2H), 2.97 - 2.87 (m, 2H), 2.71 - 2.64 (m, 2H), 2.41 - 2.31 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -113.580. [00980] Example 451: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl-4-d)amino)p yrimidine-2-carbonitrile Example 451 was prepared in a manner similar to Example 261. MS: m/z = 598.7 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.11 - 8.03 (m, 4H), 8.01 - 7.96 (m, 2H), 7.47 (q, J = 8.4 Hz, 4H), 7.29 (t, J = 8.8 Hz, 2H), 7.15 (dd, J = 7.6, 2.0 Hz, 1H), 7.03 (s, 2H), 6.67 (br d, J = 6.0 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.59 (s, 2H), 2.85 - 2.80 (m, 2H), 2.16 (t, J = 10.4 Hz, 2H), 1.90 - 1.86 (m, 2H), 1.52 - 1.46 (m, 2H). ¹⁹ F NMR (400MHz, Dimethylsulfoxide-d ₆ ) δ - 113.6. [00981] Example 452: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5,6-dimethyl-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl)piperidin-4-yl-4-d)amino)pyrimidine-2- carbonitrile Example 452 was prepared in a manner similar to Example 261. MS: m/z = 532.7 [M + H] ⁺ . ¹ H NMR (400MHz, Methanol-d ₄ ) δ 8.00 (d, J = 5.6 Hz, 1H), 7.94 (dd, J = 5.2, 1.6 Hz, 1H), 7.89 (s, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.23 (dd, J = 7.6, 1.6 Hz, 1H), 6.59 (d, J = 5.6 Hz, 1H), 6.43 (dd, J = 7.6, 5.2 Hz, 1H), 3.65 (s, 2H), 2.95 (d, J = 11.6 Hz, 2H), 2.53 (s, 3H), 2.44 (s, 3H), 2.27 (t, J = 11.2 Hz, 2H), 1.99 (d, J = 12.8 Hz, 2H), 1.64 - 1.56 (m, 2H). [00982] Example 453: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(cyclopent-l-en-l-yl)-3H - imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

Step 1 : (4-(2-(2-Aminopyridin-3-yl)-5-(cyclopent-l-en-l-yl)-3H-imida zo[4,5-b]pyridin-3- yl)phenyl)methanol

A mixture of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-(cyc lopent-l-en-l-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (refer to Intermediate 118 for detail procedures, 275 mg, 553 μmol) in TBAF (2.5M in THF, 4 mL) was degassed and purged with N2 three times. The mixture was stirred at 25 °C for 0.5 hr under N2 atmosphere. The reaction mixture was poured into H ₂ O (15 mL), extracted with EtOAc (15mL x 3). The organic phase was dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure, (4-(2-(2-aminopyridin-3- yl)-5-(cyclopent-l-en-l-yl)-3H-imidazo[4,5-b]pyridin-3-yl)ph enyl)methanol (220 mg, crude) was obtained as a gray solid. MS: m/z = 384.1 [M + H] ⁺ .

Step 2 : 3 -(3 -(4-(Chloromethyl)phenyl)-5-(cyclopent- 1 -en- 1 -yl)-3H-imidazo[4, 5-b]pyridin-2- yl)pyridin-2-amine

To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(cyclopent-l-en-l-yl)-3H-imida zo[4,5-b]pyridin- 3-yl)phenyl)methanol (220 mg, 574 μmol) in CH ₂ Cl ₂ (4 mL) was added SOCl ₂ (68 mg, 574 μmol). The mixture was stirred at 45 °C for 0.3 hr. The mixture was concentrated under reduced pressure, 3 -(3 -(4-(chloromethyl)phenyl)-5 -(cyclopent- 1 -en- 1 -yl)-3H-imidazo[4, 5- b]pyridin-2-yl)pyridin-2-amine (251 mg, crude) was obtained as a yellow solid. MS: m/z = 402.0 [M + H] ⁺ .

Step 3: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(cyclopent-l-en-l-yl)-3H -imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile

To a solution of 3-(3-(4-(chloromethyl)phenyl)-5-(cyclopent-l-en-l-yl)-3H-imi dazo[4,5- b]pyridin-2-yl)pyridin-2-amine (251 mg, 625 μmol) and Intermediate 51 (218 mg, 687 μmol) in DMF (2 mL) were added K ₂ CO ₃ (432 mg, 3.1 mmol) and Nal (28.1 mg, 187 μmol). The mixture was stirred at 50 °C for 1 hr. The reaction mixture was poured into H ₂ O (15 mL), extracted with EtOAc (15 mL x 3). The organic phase was dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 15% MeOH in CH ₂ Cl ₂ ), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(cyclopent-l-en-l-yl)-3H - imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile (Example 453, 107.8 mg, yield: 30%) was obtained as an off white solid. MS: m/z = 569.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.26 - 8.03 (m, 3H), 7.98 (dd, J = 4.8, 2.0 Hz, 1H), 7.57 (d, J = 8.4 Hz, 1H), 7.48 - 7.42 (m, 2H), 7.40 - 7.33 (m, 2H), 7.11 (dd, J = 8.0, 2.0 Hz, 1H), 7.03 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.53 (t, J = 1.6 Hz, 1H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.89 - 3.71 (m, 1H), 3.57 (s, 2H), 3.35 - 3.34 (m, 2H), 2.86 - 2.76 (m, 2H), 2.71 - 2.65 (m, 2H), 2.20 - 2.10 (m, 2H), 1.99 - 1.83 (m, 4H), 1.54 - 1.44 (m, 2H). [00983] Example 454: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-vinyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile Example 454 was prepared in a manner similar to Example 261. MS: m/z = 529.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.16 (d, J = 8.4 Hz, 1H), 8.07 (dd, J = 13.6, 6.0 Hz, 2H), 7.98 (dd, J = 4.4, 1.2 Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.50 - 7.43 (m, 2H), 7.42 - 7.34 (m, 2H), 7.12 (dd, J = 8.0, 1.6 Hz, 1H), 7.02 (br s, 2H), 6.85 (dd, J = 17.6, 10.4 Hz, 1H), 6.67 (br d, J = 5.6 Hz, 1H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 6.11 (d, J = 16.8 Hz, 1H), 5.40 (d, J = 12.0 Hz, 1H), 3.89 - 3.74 (m, 1H), 3.58 (s, 2H), 2.82 (d, J = 10.4 Hz, 2H), 2.23 – 2.09 (m, 2H), 1.95 - 1.82 (m, 2H), 1.57 - 1.42 (m, 2H). [00984] Example 455: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5,6-dimethyl-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl)piperidin-4-yl)(methyl-d ₃ )amino)pyrimidine-2-carbonitrile Example 455 was prepared in a manner similar to Example 441. MS: m/z = 548.3 [M + H] ⁺ .1H NMR (400 MHz, Methanol-d ₄ ) δ 8.16 (d, J = 6.4 Hz, 1H), 7.95 (dd, J = 5.2, 1.6 Hz, 1H), 7.92 - 7.89 (m, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 7.26 (dd, J = 7.6, 1.6 Hz, 1H), 6.91 - 6.76 (m, 1H), 6.45 (dd, J = 7.6, 5.2 Hz, 1H), 4.91 - 4.89 (m, 1H), 3.67 (s, 2H), 3.07 (d, J = 11.2 Hz, 2H), 2.54 (s, 3H), 2.46 (s, 3H), 2.31 - 2.23 (m, 2H), 2.00 - 1.89 (m, 2H), 1.74 - 1.65 (m, 2H). [00985] Example 456: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(5-fluoropyridin-2-yl)-3 H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile To a solution of Intermediate 189 (200 mg, 484 µmol) in DMF (5 mL) were added Intermediate 51 (113 mg, 557 µmol), NaI (35 mg, 232 µmol) and K ₂ CO ₃ (256 mg, 1.86 mmol) at 25 °C, the mixture was stirred at 50 °C for 3 hr. The reaction mixture was poured into H ₂ O (50 mL). The mixture was extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (40 mL), dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated to dryness. After purified by silica gel flash chromatography (Eluent of 0~7% MeOH in CH ₂ Cl ₂ ), 4-((1-(4-(2-(2- aminopyridin-3-yl)-5-(5-fluoropyridin-2-yl)-3H-imidazo[4,5-b ]pyridin-3-yl)benzyl)piperidin-4- yl)amino)pyrimidine-2-carbonitrile (Example 456, 40.2 mg, yield: 14%) was obtained as an off white solid. MS: m/z = 598.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.68 (d, J = 2.8 Hz, 1H), 8.41 (d, J = 8.4 Hz, 1H), 8.33 (d, J = 8.4 Hz, 1H), 8.24 (dd, J = 8.8, 4.8 Hz, 1H), 8.15 - 8.04 (m, 2H), 8.03 - 7.98 (m, 1H), 7.87 - 7.79 (m, 1H), 7.53 - 7.43 (m, 4H), 7.18 (dd, J = 8.0, 2.0 Hz, 1H), 7.03 (br s, 2H), 6.69 (d, J = 6.4 Hz, 1H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.91 - 3.74 (m, 1H), 3.61 (s, 2H), 2.89 - 2.78 (m, 2H), 2.24 - 2.13 (m, 2H), 1.97 - 1.84 (m, 2H), 1.60 - 1.44 (m, 2H). [00986] Example 457: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(methylamino)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 457 was prepared in a manner similar to Example 261. MS: m/z = 532.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.25 - 7.94 (m, 2H), 7.90 (dd, J = 4.8, 1.6 Hz, 1H), 7.80 (d, J = 8.4 Hz, 1H), 7.42 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 7.05 (br s, 2H), 6.93 (dd, J = 8.0, 2.0 Hz, 1H), 6.84 - 6.52 (m, 2H), 6.48 (d, J = 8.8 Hz, 1H), 6.28 (dd, J = 8.0, 5.2 Hz, 1H), 3.93 - 3.65 (m, 1H), 3.56 (s, 2H), 2.85 - 2.75 (m, 2H), 2.71 (d, J = 4.4 Hz, 3H), 2.20 - 2.10 (m, 2H), 1.93 - 1.80 (m, 2H), 1.54 - 1.41 (m, 2H). [00987] Example 458: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(bis(methyl-d ₃ )amino)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Step 1: Methyl 4-((6-(bis(methyl-d ₃ )amino)-3-nitropyridin-2-yl)amino)benzoate To a mixture of methyl 4-((6-chloro-3-nitropyridin-2-yl)amino)benzoate (refer to Intermediate 13 for detail procedures, 10.8 g, 35.2 mmol), bis(methyl-d ₃ )amine (2.0 g, 39.1 mmol) in ACN (120 mL) was added DIEA (15.1 g, 117mmol). The mixture was degassed and purged with N ₂ three times and stirred at 80 °C for 2 hr under N ₂ atmosphere. The reaction mixture was filtered, methyl 4-((6-(bis(methyl-d ₃ )amino)-3-nitropyridin-2-yl)amino)benzoate (8.0 g, yield: 51%) was obtained as a yellow solid. MS: m/z = 323.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 11.02 (s, 1H), 8.30 (d, J = 9.6 Hz, 1H), 8.05 - 8.02 (m, 2H), 7.81 - 7.78 (m, 2H), 6.13 (d, J = 9.6 Hz, 1H), 3.91 (s, 3H). Step 2: Methyl 4-(2-(2-aminopyridin-3-yl)-5-(bis(methyl-d ₃ )amino)-3H-imidazo[4,5-b]pyridin- 3-yl)benzoate A mixture of methyl 4-((6-(bis(methyl-d ₃ )amino)-3-nitropyridin-2-yl)amino)benzoate (6.4 g, 19.8 mmol), 2-aminonicotinaldehyde (2.67 g, 21.8 mmol) and Na ₂ S ₂ O ₄ (13.8 g, 79.4mmol) in DMSO (150 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 100 °C for 16 hr under N ₂ atmosphere. The reaction mixture was diluted with H ₂ O (200 mL) and extracted with EtOAc (200 mL x 3). The combined organic layers were washed with brine (200 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 29% EtOAc in petroleum ether), methyl 4-(2-(2- aminopyridin-3-yl)-5-(bis(methyl-d ₃ )amino)-3H-imidazo[4,5-b]pyridin-3-yl)benzoate (5.0 g, yield: 59%) was obtained as a yellow solid. MS: m/z = 395.3 [M + H] ⁺ , ¹ H NMR (400 MHz, Chloroform-d) δ 8.14 (d, J= 8.8 Hz, 2H), 8.00 (dd, J= 5.2, 2.0 Hz, 1H), 7.84 (d, J= 8.8 Hz, 1H), 7.48 (d, J= 8.4 Hz, 2H), 7.00 - 6.96 (m, 1H), 6.56 (d, J= 8.8 Hz, 3H), 6.35 (dd, J= 7.6, 5.2 Hz, 1H), 3.95 (s, 3H).

Step 3 : (4-(2-(2-Aminopyridin-3-yl)-5-(bis(methyl-d3)amino)-3H-imida zo[4,5-b]pyridin-3- yl)phenyl)methanol

To a mixture of methyl 4-(2-(2-aminopyridin-3-yl)-5-(bis(methyl-d ₃ )amino)-3.H-imidazo[4,5- b]pyridin-3-yl)benzoate (5.0 g, 12.7 mmol) in THF (150 mL) was added LiAlH ₄ (2.5 M in THF, 7.61 mL). The mixture was degassed and purged with N2 three times and stirred at 0 °C for 2 hr under N ₂ atmosphere. The reaction mixture was quenched with Na ₂ SO ₄ ·10H ₂ O (1.5 g) at 0 °C and filtered. The filtrate was concentrated under reduced pressure, (4-(2-(2-aminopyridin-3-yl)- 5-(bis(methyl-d ₃ )amino)-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (4.6g, yield: 91%) was obtained as a yellow solid. MS: m/z = 367.2 [M + H] ⁺ .

Step 4: 2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-N,N-bis(m ethyl-d3)-3H- imidazo[4, 5-b]pyridin-5 -amine

To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(bis(methyl-d ₃ )amino)-3H-imidazo[4,5- b]pyridin-3-yl)phenyl)methanol (600 mg, 715 μmol) in CH ₂ CI ₂ (50 mL) was added SOCI ₂ (8.96 g, 75.3 mmol). The mixture was stirred at 40 °C for 1 hr. The mixture was concentrated under reduced pressure, 2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-N,N-bis(m ethyl-d ₃ )-3H- imidazo[4,5-b]pyridin-5-amine (5.0 mg, yield: 97%) was obtained as a yellow solid. MS: m/z = 385.0 [M + H] ⁺ .

Step 5: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(bis(methyl-d ₃ )amino)-3H-imidazo[4,5-b]pyridin- 3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile

To a solution of 2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-N,N-bis(m ethyl-d ₃ )-3H- imidazo[4,5-b]pyridin-5-amine (300 mg, 779 μmol) and Intermediate 51 (158 mg, 779 μmol) in DMF (5 mL) were added Nal (58.4 mg, 390 μmol) and K ₂ CO ₃ (539 mg, 3.90 mmol). The mixture was stirred at 50 °C for 1 hr. The reaction mixture was diluted with H ₂ O (20 mL) and extracted with EtOAc (50 mL x 2). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 6% MeOH in CH ₂ CI ₂ ), 4-((l-(4-(2-(2- aminopyridin-3-yl)-5-(bis(methyl-d3)amino)-3H-imidazo[4,5-b] pyridin-3-yl)benzyl)piperidin-4- yl)amino)pyrimidine-2-carbonitrile (Example 458, 89 mg, yield: 20%) was obtained as a yellow solid. MS: m/z = 552.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.15 (dd, J= 17.6, 6.0 Hz, 2H), 7.94 - 7.89 (m, 2H), 7.43 (d, J= 8.0 Hz, 2H), 7.31 (d, J= 8.4 Hz, 2H), 7.06 (s, 2H), 6.97 (dd, J = 7.6, 1.6 Hz, 1H), 6.71 - 6.64 (m, 2H), 6.30 (dd, J = 7.6, 4.8 Hz, 1H), 3.86 - 3.73 (m, 1H), 3.57 (s, 2H), 2.81 (d, J = 10.4 Hz, 2H), 2.17 - 2.10 (m, 2H), 1.91 - 1.84 (m, 2H), 1.52 - 1.43 (m, 2H). [00988] Example 459: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-((methyl-d ₃ )amino)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 459 was prepared in a manner similar to Example 458. MS: m/z = 535.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.15 - 7.97 (m, 2H), 7.93 - 7.85 (m, 1H), 7.80 (d, J = 8.8 Hz, 1H), 7.42 (d, J = 7.2 Hz, 2H), 7.30 (d, J = 7.6 Hz, 2H), 7.05 (br s, 2H), 6.93 (d, J = 7.2 Hz, 1H), 6.72 - 6.60 (m, 2H), 6.47 (d, J = 8.4 Hz, 1H), 6.32 - 6.24 (m, 1H), 3.85 - 3.75 (m, 1H), 3.56 (s, 2H), 2.85 - 2.75 (m, 2H), 2.20 - 2.10 (m, 2H), 1.94 - 1.81 (m, 2H), 1.52 - 1.40 (m, 2H). [00989] Example 460: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(azetidin-1-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Step 1: 4-((6-(Azetidin-1-yl)-3-nitropyridin-2-yl)amino)benzyl acetate To a solution of 4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl acetate (refer to Intermediate 178 for detail procedures, 5 g, 15.5 mmol) in MeCN (100 mL) were added DIEA (5.02 g, 38.9 mmol) and azetidine (2.18 g, 23.3 mmol, HCl salt). The mixture was stirred at 90 °C for 16 hr. The reaction was concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 50% ~ 100% EtOAc in petroleum ether), 4-((6-(azetidin-1-yl)-3- nitropyridin-2-yl)amino)benzyl acetate (5.0 g, yield: 92%) was obtained as a yellow solid. MS: m/z = 342.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.94 (s, 1H), 8.16 (d, J = 9.2 Hz, 1H), 7.80 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 5.97 (d, J = 9.2 Hz, 1H), 5.04 (s, 2H), 4.17 (t, J = 7.2 Hz, 4H), 2.41 - 2.33 (m, 2H), 2.06 (s, 3H). Step 2: 4-(2-(2-Aminopyridin-3-yl)-5-(azetidin-1-yl)-3H-imidazo[4,5- b]pyridin-3-yl)benzyl acetate To a solution of 4-((6-(azetidin-1-yl)-3-nitropyridin-2-yl)amino)benzyl acetate (500 mg, 1.46 mmol) in DMSO (20 mL) were added Na ₂ S ₂ O ₄ (1.17 g, 5.84 mmol, 87% purity) and 2- aminonicotinaldehyde (214 mg, 1.75 mmol). The mixture was stirred at 100 °C for 4 hr. The reaction mixture was quenched with H ₂ O (25 mL) at 25 °C, then diluted with CH ₂ Cl ₂ (50 mL) and washed with H ₂ O (50 mL x 3) and brine (100 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 30% ~ 60% EtOAc in petroleum ether), 4-(2-(2-aminopyridin-3-yl)-5-(azetidin-1-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl acetate (280 mg, yield: 46%) was obtained as a green solid. MS: m/z = 415.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 7.96 - 7.88 (m, 2H), 7.48 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.01 (dd, J = 7.6, 1.6 Hz, 1H), 6.90 (br s, 2H), 6.41 - 6.31 (m, 2H), 5.15 (s, 2H), 3.91 (t, J = 7.2 Hz, 4H), 2.33 - 2.23 (m, 2H), 2.10 (s, 3H). Step 3: (4-(2-(2-Aminopyridin-3-yl)-5-(azetidin-1-yl)-3H-imidazo[4,5 -b]pyridin-3- yl)phenyl)methanol To a solution of 4-(2-(2-aminopyridin-3-yl)-5-(azetidin-1-yl)-3H-imidazo[4,5- b]pyridin-3- yl)benzyl acetate (280 mg, 676 µmol) in THF (4 mL),MeOH (4 mL) and H ₂ O (1 mL) was added K ₂ CO ₃ (280 mg, 2.03 mmol). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was quenched with H ₂ O (5 mL) at 25 °C, and extracted with CH ₂ Cl ₂ (20 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give (4-(2-(2-aminopyridin-3-yl)-5-(azetidin-1-yl)-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (240 mg, yield: 95%) as a yellow solid. MS: m/z = 373.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 7.96 - 7.87 (m, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 7.00 - 6.97 (m, 3H), 6.37 (d, J = 8.8 Hz, 1H), 6.33 (dd, J = 7.6, 4.8 Hz, 1H), 5.34 (t, J = 6.0 Hz, 1H), 4.57 (d, J = 6.0 Hz, 2H), 3.90 (t, J = 7.2 Hz, 4H), 2.32 - 2.22 (m, 2H). Step 4: 4-(2-(2-Aminopyridin-3-yl)-5-(azetidin-1-yl)-3H-imidazo[4,5- b]pyridin-3-yl)benzyl methanesulfonate To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(azetidin-l-yl)-3H-imidazo[4,5 -b]pyridin-3- yl)phenyl)methanol (140 mg, 376 μmol) in CH ₂ CI ₂ (15 mL) were added TEA (114 mg, 1.13 mmol) and MsCl (140 mg, 1.22 mmol) at 0 °C. The mixture was stirred at 0 °C for 1 hr. Additional MsCl (100 mg, 873 μmol) was added at 0 °C. The mixture was stirred at 0 °C for 15 minutes. The reaction mixture was quenched with saturated NaHCO ₃ aqueous (20 mL) at 0 °C and was then diluted with CH ₂ CI ₂ (10 mL) and extracted with CH ₂ CI ₂ (15 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. 4-(2-(2-Aminopyridin-3-yl)-5-(azetidin-l-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl methanesulfonate (170 mg) was obtained as a yellow solid. MS: m/z = 451.0 [M + H] ⁺ .

Step 5: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(azetidin-l-yl)-3H-imida zo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile

To a solution of 4-(2-(2-aminopyridin-3-yl)-5-(azetidin-l-yl)-3H-imidazo[4,5- b]pyridin-3- yl)benzyl methanesulfonate (170 mg, 377 μmol) and Intermediate 51 (120 mg, 377 μmol, TFA) in DMF (2 mL) were added K ₂ CO ₃ (209 mg, 1.51 mmol) and Nal (11.3 mg, 75.5 μmol). The mixture was stirred at 50 °C for 1 hr. The mixture was filtered through Celite and concentrated under reduced pressure. After purified by prep-HPLC(column: Waters xbridge 150 x 25 mm x 10 μm; mobile phase: [water (NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN];gradient: 30% - 60% B over 11 min), 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(azetidin-l-yl)-3H-imida zo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile (Example 460, 17.7 mg, yield: 8.4% for two steps) was obtained as a yellow solid. MS: m/z = 558.5 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.08 - 8.05 (d, J= 6.8 Hz, 2H), 7.94 - 7.89 (m, 2H), 7.42 (d, J= 8.4 Hz, 2H), 7.30 (d, J= 8.4 Hz, 2H), 7.01 (br s, 2H), 6.94 (d, J= 6.8 Hz, 1H), 6.67 (d, J= 6.4 Hz, 1H), 6.37 (d, J= 8.4 Hz, 1H), 6.29 (dd, J= 7.6, 4.8 Hz, 1H), 3.91 (t, J= 7.6 Hz, 4H), 3.84 - 3.75 (m, 1H), 3.56 (s, 2H), 2.85 - 2.77 (m, 2H), 2.32 - 2.24 (m, 2H), 2.19 - 2.09 (m, 2H), 1.94 - 1.82 (m, 2H), 1.53 - 1.43 (m, 2H).

[00990] Example 461: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(isoxazol-4-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile A mixture of Example 405 (50 mg, 93.1 μmol), isoxazol-4-ylboronic acid (26.3 mg, 233 μmol), cata CXium A PdG ₃ (67.8 mg, 93.1 μmol), K ₃ PO ₄ (59.3 mg, 279 μmol) and PCy ₃ (13.1 mg, 46.6 μmol) in DMF (2 mL) was degassed and purged with N2 three times, and then was stirred at 80 °C for 3 hr under N2 atmosphere. The reaction mixture was filtered and concentrated. After purified by prep-HPLC (column: Waters xbridge 150 x 25 mm 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 40% - 70% B over 11 min), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5- (isoxazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperid in-4-yl)amino)pyrimidine-2- carbonitrile (Example 461, 19.0 mg, yield: 35%) was obtained as a light-yellow lyophilized powder. MS: m/z = 570.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.14 - 8.09 (m, 2H), 8.01 - 7.94 (m, 2H), 7.61 - 7.38 (m, 6H), 7.32 - 7.14 (m, 1H), 7.12 - 7.06 (m, 1H), 7.01 (d, J= 6.4 Hz, 2H), 6.68 (d, J= 5.6 Hz, 1H), 6.39 - 6.34 (m, 1H), 4.06 - 3.77 (m, 3H), 3.09 - 2.98 (m, 2H), 2.61 - 2.55 (m, 2H), 2.02 - 1.94 (m, 2H), 1.63 - 1.54 (m, 2H).

[00991] Example 462: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(oxazol-5-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

Example 462 was prepared in a manner similar to Example 461. MS: m/z = 570.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.29 (s, 1H), 8.24 (d, J= 8.4 Hz, 1H), 8.03 - 7.97 (m, 2H), 7.86 (d, J= 8.4 Hz, 1H), 7.60 (s, 1H), 7.55 (d, J= 8.4 Hz, 2H), 7.43 (d, J= 8.4 Hz, 2H), 7.31 (dd, J= 7.6, 1.6 Hz, 1H), 6.60 (d, J= 5.6 Hz, 1H), 6.47 (dd, J= 7.6, 5.2 Hz, 1H), 4.06 - 3.87 (m, 1H), 3.67 (s, 2H), 2.98 (d, J= 14.0 Hz, 2H), 2.33 - 2.25 (m, 2H), 2.02 (d, J= 11.2 Hz, 2H), 1.67 - 1.57 (m, 2H).

[00992] Example 463: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(5-methylisoxazol-4-yl)- 3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

Example 463 was prepared in a manner similar to Example 461. MS: m/z = 584.3 [M + H] ⁺ . ¹ H

NMR (400 MHz, Methanol-d ₄ ) δ 8.29 (d, J= 8.8 Hz, 1H), 8.11 - 7.87 (m, 2H), 7.59 (d, J= 8.4 Hz, 2H), 7.50 (d, J = 8.4 Hz, 1H), 7.42 (d, J = 8.4 Hz, 2H), 7.36 (dd, J = 8.0, 2.0 Hz, 1H), 6.68 - 6.52 (m, 1H), 6.46 (dd, J = 8.0, 5.2 Hz, 1H), 4.95 - 4.89 (m, 1H), 4.05 - 3.80 (m, 1H), 3.69 (s, 2H), 3.05 - 2.86 (m, 2H), 2.30 (s, 3H), 2.30 - 2.23 (m, 2H), 2.06 - 1.97 (m, 2H), 1.68 - 1.56 (m, 2H). [00993] Example 464: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(3-methylisoxazol-4-yl)- 3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Step 1: 3-(3-(4-(((tert-Butyldimethylsilyl)oxy)methyl)phenyl)-5-(3-m ethylisoxazol-4-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine To a solution of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-chlo ro-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (refer to Intermediate 117 for detail procedures, 500 mg, 1.07 mmol) and (3-methylisoxazol-4-yl)boronic acid (150 mg, 1.18 mmol) in 1,4-dioxane (10 mL) and H ₂ O (2 mL) were added Pd(dppf)Cl ₂ (78.5 mg, 107 umol) and Cs ₂ CO ₃ (1.05 g, 3.22 mmol). The mixture was degassed and purged with N ₂ three times, and stirred at 100 °C for 16 hr under N ₂ atmosphere. The reaction mixture was diluted with H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (100 mL x 2). The combined organic layers were washed with brine (100 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 20% ~ 50% EtOAc in petroleum ether), 3-(3-(4- (((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-(3-methyliso xazol-4-yl)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (180 mg, yield: 30%) was obtained as a brown solid. MS: m/z = 513.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.47 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.02 - 7.98 (m, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.50 - 7.44 (m, 4H), 7.21 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (s, 2H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 4.81 (s, 2H), 2.38 (s, 3H), 0.91 (s, 9H), 0.09 (s, 6H). Step 2 : (4-(2-(2- Aminopyridin-3 -yl)-5-(3 -methylisoxazol-4-yl)-3H-imidazo[4, 5-b]pyridin-3 - yl)phenyl)methanol

To a solution of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-(3-m ethylisoxazol-4- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (180 mg, 351 μmol) in THF (5 mL) was added TBAF (1 M, 0.7 mL). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was diluted with H ₂ O (20 mL) and extracted with CH ₂ CI ₂ (20 mL x 2). The combined organic layers were washed with brine (20 mL x 2), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. (4-(2-(2-Aminopyridin-3-yl)-5-(3-methylisoxazol-4-yl)-3H-imi dazo[4,5-b]pyridin-3-yl)phenyl)m ethanol (110 mg, yield: 79%) was obtained as a yellow solid. MS: m/z = 398.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.45 (s, 1H), 8.25 (d, J= 8.4 Hz, 1H), 8.00 (dd, J= 4.8, 2.0 Hz, 1H), 7.76 (d, J= 8.4 Hz, 1H), 7.48 - 7.41 (m, 4H), 7.21 (dd, J = 7.6, 2.0 Hz, 1H), 6.98 (s, 2H), 6.44 - 6.39 (m, 1H), 5.34 (t, J= 5.6 Hz, 1H), 4.58 (d, J= 5.2 Hz, 2H), 2.39 (s, 3H).

Step 3 : 3-(3-(4-(Chloromethyl)phenyl)-5-(3-methylisoxazol-4-yl)-3H-i midazo[4,5-b]pyridin-2- yl)pyridin-2-amine

To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(3-methylisoxazol-4-yl)-3H-imi dazo[4,5- b]pyridin-3-yl)phenyl)methanol (110 mg, 276 μmol) in CH ₂ CI ₂ (2 mL) was added SOCl ₂ (98.5 mg, 828 μmol). The mixture was stirred at 40 °C for 0.5 hr. The reaction was concentrated under reduced pressure to give 3-(3-(4-(chloromethyl)phenyl)-5-(3-methylisoxazol-4-yl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (130 mg, crude) as a yellow solid and used directly in the next step without purification. MS: m/z = 417.0 [M + H] ⁺ .

Step 4: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(3-methylisoxazol-4-yl)- 3H-imidazo[4,5-b]pyridin- 3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile

To a solution of 3-(3-(4-(chloromethyl)phenyl)-5-(3-methylisoxazol-4-yl)-3H-i midazo[4,5- b]pyridin-2-yl)pyridin-2-amine (130 mg, 312 μmol) and Intermediate 51 (98.9 mg, 312 μmol, TFA salt) in DMF (2 mL) were added K ₂ CO ₃ (216 mg, 1.56 mmol) and Nal (4.67 mg, 31.2 μmol). The mixture was stirred at 60 °C for 1 hr. After purified by prep-HPLC (column: Waters xbridge 150 x 25 mm x 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 35% - 65% B over 10 min), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(3-methylisoxazol-4-yl)- 3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile (Example 464, 40.7 mg, yield: 22% for two steps) was obtained as a yellow solid. MS: m/z = 584.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.47 (s, 1H), 8.26 (d, J= 8.4 Hz, 1H), 8.10 - 7.98 (m, 3H), 7.77 (d, J= 8.4 Hz, 1H), 7.48 - 7.41 (m, 4H), 7.22 (dd, J= 7.6, 1.6 Hz, 1H), 7.08 (s, 2H), 6.66 (d, J = 6.0 Hz, 1H), 6.43 - 6.37 (m, 1H), 3.91 - 3.72 (m, 1H), 3.57 (s, 2H), 2.82 - 2.76 (m, 2H), 2.34 (s, 3H), 2.14 - 2.08 (m, 2H), 1.90 - 1.83 (m, 2H), 1.51 - 1.42 (m, 2H). [00994] Example 465: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(3-methyl-1H-pyrazol-5-y l)- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile Example 465 was prepared in a manner similar to Example 464. MS: m/z = 583.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 12.64 (s, 1H), 8.21 - 7.92 (m, 5H), 7.52 - 739 (m, 4H), 7.14 - 7.09 (m, 1H), 6.99 (s, 2H), 6.67 (d, J = 5.6 Hz, 1H), 6.48 - 6.23 (m, 2H), 3.88 - 3.75 (m, 1H), 3.58 (s, 2H), 2.89 - 2.80 (m, 2H), 2.24 (s, 3H), 2.17 - 2.09 (m, 2H), 1.94 - 1.84 (m, 2H), 1.54 - 1.45 (m, 2H). [00995] Example 466: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(1-ethyl-1H-pyrazol-4-yl )- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile Example 466 was prepared in a manner similar to Example 464. MS: m/z = 597.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ 8.20 - 8.13 (m, 2H), 8.02 - 8.11(m, 2H), 7.98 (dd, J = 4.8, 2.0 Hz, 1H), 7.93 (s, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.50 - 7.44 (m, 2H), 7.43 - 7.38 (m, 2H), 7.10 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.68 (d, J = 6.0 Hz, 1H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 4.15 (q, J = 7.2 Hz, 2H), 3.91 - 3.72 (m, 1H), 3.59 (s, 2H), 2.90 - 2.79 (m, 2H), 2.22 - 2.11 (m, 2H), 1.94 - 1.83 (m, 2H), 1.55 - 1.45 (m, 2H), 1.37 (t, J = 7.6 Hz, 3H). [00996] Example 467: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(1-methyl-1H-pyrazol-5-y l)- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile Example 467 was prepared in a manner similar to Example 464. MS: m/z = 583.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.29 (d, J = 8.4 Hz, 1H), 8.13 - 7.98 (m, 3H), 7.81 (d, J = 8.4 Hz, 1H), 7.51 - 7.40 (m, 5H), 7.23 (dd, J = 7.2, 1.6 Hz, 1H), 7.08 (s, 2H), 6.84 (d, J = 2.0 Hz, 1H), 6.67 (d, J = 6.0 Hz, 1H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 3.98 (s, 3H), 3.88 - 3.74 (m, 1H), 3.63 - 3.57 (m, 2H), 2.86 - 2.74 (m, 2H), 2.21 - 2.07 (m, 2H), 1.92 - 1.85 (m, 2H), 1.55 - 1.44 (m, 2H). [00997] Example 468: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(3-(2-oxopyrrolidin-1- yl)phenyl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4- yl)amino)pyrimidine-2- carbonitrile

Step 1: 1-(3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyr rolidin-2-one A mixture of 1-(3-bromophenyl)pyrrolidin-2-one (300 mg, 1.25 mmol), 4,4,4',4',5,5,5',5'- octamethyl-2,2'-bi(1,3,2-dioxaborolane) (349 mg, 1.37 mmol), Pd(dppf)Cl ₂ (91.4 mg, 125 µmol) and AcOK (368 mg, 3.75 mmol) in 1,4-dioxane (5 mL) and H ₂ O (1 mL) was degassed and purged with N ₂ three times, and was stirred at 80 °C for 16 hr under N ₂ atmosphere. The mixture was used for the next step directly without work-up and purification. 1-(3-(4,4,5,5- Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrrolidin-2-one (358 mg, crude) was obtained as a black oil. MS: m/z = 288.0 [M + H] ⁺ . Step 2: 1-(3-(2-(2-Aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsily l)oxy)methyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)phenyl)pyrrolidin-2-one A mixture of 1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyr rolidin-2-one (358 mg, 1.25 mmol), 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-chlo ro-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (refer to Intermediate 117 for detail procedures, 581 mg, 1.25 mmol), Pd(dppf)Cl ₂ (91.2 mg, 125 µmol) and Cs ₂ CO ₃ (1.22 g, 3.74 mmol) in 1,4- dioxane (5 mL) and H ₂ O (1 mL) was degassed and purged with N ₂ three times, and then was stirred at 80 °C for 16 hr under N ₂ atmosphere. The reaction mixture was quenched with H ₂ O (10 mL) and extracted with CH ₂ Cl ₂ (15 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 1% ~ 80% EtOAc in petroleum ether), 1- (3-(2-(2-aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl) oxy)methyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)phenyl)pyrrolidin-2-one (500 mg, yield: 60%) was obtained as a brown solid. MS: m/z = 591.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.20 - 8.15 (m, 2H), 7.90 (dd, J= 4.8, 1.6 Hz, 1H), 7.85 (d, J= 8.4 Hz, 1H), 7.67 (d, J= 8.0 Hz, 1H), 7.60 - 7.57 (m, 1H), 7.38 - 7.30 (m, 5H), 7.09 (dd, J= 7.6, 1.6 Hz, 1H), 6.90 (br s, 2H), 6.28 (dd, J= 7.6, 4.8 Hz, 1H), 4.71 (s, 2H), 3.80 - 3.76 (m, 2H), 2.03 - 1.92 (m, 4H), 0.84 - 0.80 (m, 9H), 0.00 (s, 6H).

Step 3; l-(3-(2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H -imidazo[4,5-b]pyridin- 5-yl)phenyl)pyrrolidin-2-one

To a solution of l-(3-(2-(2-aminopyridin-3-yl)-3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-3H-imidazo[4,5-b]pyrid in-5-yl)phenyl)pyrrolidin-2-one (600 mg, 1.02 mmol) in THF (5 mL) was added TBAF (2.03 mmol, 1 M). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was quenched with H ₂ O (10 mL) at 25 °C, and extracted with CH ₂ CI ₂ (20 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 1% ~ 100% EtOAc in petroleum ether), l-(3-(2-(2- aminopyridin-3 -yl)-3 -(4-(hydroxymethyl)phenyl)-3H-imidazo[4, 5-b]pyri din-5 - yl)phenyl)pyrrolidin-2-one (200 mg, yield: 40%) was obtained as a yellow solid. MS: m/z = 477.1 [M + H] ⁺ .

Step 4; l-(3-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5- yl)phenyl)pyrrolidin-2-one

To a solution of l-(3-(2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H -imidazo[4,5- b]pyridin-5-yl)phenyl)pyrrolidin-2-one (230 mg, 483 μmol) in CH ₂ CI ₂ (5 mL) was added SOCl ₂ (115 mg, 965 μmol) at 0 °C. The mixture was stirred at 40 °C for 0.5 hr. The reaction mixture was quenched with H ₂ O (1 mL) at 25 °C and concentrated under reduced pressure to give a residue. And the reaction mixture was diluted with aqueous Na ₂ CO ₃ (10 mL) and extracted with CH ₂ CI ₂ (15 mL x 2). The combined organic layers were washed with brine (15 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure, l-(3-(2-(2-aminopyridin-3-yl)-3-(4- (chloromethyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)phenyl)p yrrolidin-2-one (180 mg) was obtained as a yellow solid. MS: m/z = 495.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide- d ₆ ) δ 8.32 - 8.26 (m, 2H), 8.02 (dd, J= 4.8, 1.6 Hz, 1H), 7.97 (d, J= 8.4 Hz, 1H), 7.79 (d, J= 8.0 Hz, 1H), 7.71 (dd, J= 8.0, 1.2 Hz, 1H), 7.64 - 7.59 (m, 2H), 7.56 - 7.52 (m, 2H), 7.49 - 7.43 (m, 1H), 7.32 (d, J= 7.6 Hz, 1H), 7.08 (br s, 2H), 6.52 - 6.47 (m, 1H), 4.87 (s, 2H), 3.89 (t, J= 7.2 Hz, 2H), 2.55 - 2.52 (m, 2H), 2.11 - 2.07 (m, 2H).

Step 5: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(3-(2-oxopyrrolidin-l-yl )phenyl)-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile To a solution of l-(3-(2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)phenyl)pyrrolidin-2-one (180 mg, 364 μmol) and Intermediate 51 (115 mg, 364 μmol) in DMF (5 mL) were added K ₂ CO ₃ (151 mg, 1.09 mmol) and Nal (10.9 mg, 72.7 μmol). The mixture was stirred at 50 °C for 16 hr. The mixture was filtered through Celite, and the filtrate was concentrated. After purified by prep-HPLC(column: Waters xbridge 150 x 25 mm x 10 μm; mobile phase: [water (NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN]; gradient: 37% - 67% B over 11 min), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(3-(2-oxopyrrolidin-l-yl )phenyl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl )amino)pyrimidine-2-carbonitrile (Example 468, 41.8 mg, yield: 17% for two steps) was obtained as a light-yellow lyophilized powder. MS: m/z = 662.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.30 - 8.26 (m, 2H), 8.09 - 8.05 (m, 2H), 8.00 (dd, J= 4.8, 1.6 Hz, 1H), 7.97 (d, J= 8.4 Hz, 1H), 7.79 (d, J= 8.0 Hz, 1H), 7.69 (dd, J = 8.0, 1.2 Hz, 1H), 7.49 - 7.42 (m, 5H), 7.18 (dd, J= 7.6, 2.0 Hz, 1H), 7.04 (br s, 2H), 6.68 (br d, J= 6.0 Hz, 1H), 6.39 (dd, J= 8.0, 5.2 Hz, 1H), 3.87 - 3.75 (m, 3H), 3.59 (s, 2H), 2.86 - 2.78 (m, 2H), 2.49 - 2.47 (m, 2H), 2.21 - 2.12 (m, 2H), 2.10 - 2.04 (m, 2H), 1.95 - 1.86 (m, 2H), 1.59 - 1.48 (m, 2H).

[00998] Example 469: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluoro-2-methoxypheny l)- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile

A mixture of Example 405 (200 mg, 372 μmol), (4-fluoro-2-methoxyphenyl)boronic acid (63.3 mg, 372 μmol), CS ₂ CO ₃ (364 mg, 1.12 mmol), Pd(dppf)Cl ₂ (54.5 mg, 74.5 μmol) in 1,4-dioxane (2.5 mL) and H ₂ O (0.5 mL) were degassed and purged with N2 three times, and then was stirred at 80 °C for 16 hr under N ₂ atmosphere. The reaction mixture was filtered and concentrated under reduced pressure. After purified by prep-HPLC (column: Waters xbridge 150 x 25 mm 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 44% - 64% B over 11 min), 4-((l- (4-(2-(2-aminopyridin-3-yl)-5-(4-fluoro-2-methoxyphenyl)-3H- imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile (Example 469, 37.4 mg, yield: 15%) was obtained as a light yellow lyophilized powder. MS: m/z = 627.5 [M + H] ⁺ . ¹ H NMR (400MHz, Methanol^) δ 8.13 (d, J= 8.4 Hz, 1H), 8.05 - 7.95 (m, 2H), 7.88 (d, J= 8.4 Hz, 1H), 7.71- 7.67 (m, 1H), 7.52 (d, J= 8.4 Hz, 2H), 7.43 (d, J= 8.4 Hz, 2H), 7.32 (dd, J= 8.0, 2.0 Hz, 1H), 6.90 (dd, J= 11.2, 2.4 Hz, 1H), 6.73 (td, J= 16.0, 2.4 Hz, 1H), 6.60 - 6.58 (m, 1H), 6.47 (dd, J = 7.6, 4.8 Hz, 1H), 3.99 - 3.91 (m, 1H), 3.88 (s, 3H), 3.65 (s, 2H), 2.97 - 2.91 (m, 2H), 2.34 - 2.20 (m, 2H), 2.07 - 1.93 (m, 2H), 1.68 - 1.55 (m, 2H). ¹⁹ F NMR (400MHz, Methanol-d ₄ ) δ -112.4. [00999] Example 470: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-(trifluoromethyl)phen yl)- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile Example 470 was prepared in a manner similar to Example 469. MS: m/z = 647.3 [M + H] ⁺ . ¹ H NMR (400MHz, Dimethylsulfoxide-d ₆ ) δ 8.30 (d, J = 8.4 Hz, 1H), 8.11 - 7.97 (m, 3H), 7.84 (d, J = 7.6 Hz, 1H), 7.77 - 7.72 (m, 1H), 7.67 - 7.62 (m, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.51 (d, J = 8.4 Hz, 1H), 7.39 (q, J = 8.4 Hz, 4H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.02 (br s, 2H), 6.66 (br d, J = 6.0 Hz, 1H), 6.38 (dd, J = 7.6, 4.4 Hz, 1H), 3.86 - 3.72 (m, 1H), 3.53 (s, 2H), 2.78 (br d, J = 10.4 Hz, 2H), 2.16 - 2.07 (m, 2H), 1.90 - 1.80 (m, 2H), 1.48 - 1.44 (m, 2H). ¹⁹ F NMR (400MHz, Dimethylsulfoxide-d ₆ ) δ -55.4. [001000] Example 471: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-(trifluoromethyl)phen yl)- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile Example 471 was prepared in a manner similar to Example 469. MS: m/z = 647.3 [M + H] ⁺ . ¹ H NMR (400MHz, Dimethylsulfoxide-d ₆ ) δ 8.36 - 8.21 (m, 3H), 8.12 - 7.96 (m, 4H), 7.84 - 7.80 (m, 2H), 7.47 (br s, 4H), 7.16 - 7.14 (m, 1H), 7.03 (s, 2H), 6.67 (br s, 1H), 6.38 (br s, 1H), 3.88 - 3.74 (m, 1H), 3.59 (br s, 2H), 2.82 - 2.81 (m, 2H), 2.15 - 2.14 (m, 2H), 1.89 - 1.87 (m, 2H), 1.51 - 1.41 (m, 2H). ¹⁹ F NMR (400MHz, Dimethylsulfoxide-d ₆ ) δ -61.0. [001001] Example 472: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-methyl-2H-1,2,3-triaz ol-4- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile

A mixture of Example 405 (150 mg, 279 μmol), (2-methyl-2H ,2,3-triazol-4-yl)boronic acid (43 mg, 335 μmol), cataCXiumAPdG ₃ (118 mg, 540 μmol), K ₃ PO ₄ (119 mg, 559 μmol) and PCy ₃ (7.8 mg, 28 μmol) in DMF (3 mL) was degassed and purged with N2 three times. The mixture was stirred at 90 °C for 16 hr under N2 atmosphere. The reaction mixture was poured into H ₂ O (15 mL), extracted with EtOAc (15 mL x 3). The organic phase was dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by prep- HPLC(column: Waters xbridge 150 x 25 mm 5 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 34% - 64% B over 11 min), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(2-methyl-2H-l,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin -4-yl)amino)pyrimidine-2- carbonitrile (Example 472, 20.5 mg, yield: 12%) was obtained as an off white lyophilized powder. MS: m/z = 584.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.29 (d, J= 8.0 Hz, 1H), 8.13 - 8.08 (m, 1H), 8.08 - 8.03 (m, 2H), 8.00 (dd, J= 4.8, 1.6 Hz, 1H), 7.95 (d, J= 8.0 Hz, 1H), 7.54 - 7.38 (m, 4H), 7.15 (dd, J= 7.6, 2.0 Hz, 1H), 6.99 (br s, 2H), 6.68 (d, J= 6.0 Hz, 1H), 6.38 (dd, J =7.6, 4.8 Hz, 1H), 4.22 (s, 3H), 3.90 - 3.73 (m, 1H), 3.60 (br s, 2H), 2.90 - 2.80 (m, 2H), 2.20 - 2.12 (m, 2H), 1.93 - 1.87 (m, 2H), 1.56 - 1.46 (m, 2H).

[001002] Example 473: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(3,5-dimethylisoxazol-4- yl)- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile

Example 473 was prepared in a manner similar to Example 472. MS: m/z = 598.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ 8.28 (d, J= 8.4 Hz, 1H), 8.23 - 7.94 (m, 3H), 7.55 (d, J= 8.4 Hz, 1H), 7.50 - 7.37 (m, 4H), 7.22 (dd, J= 8.0, 2.0 Hz, 1H), 7.09 (s, 2H), 6.67 (d, J= 6.0 Hz, 1H), 6.40 (dd, J= 7.6, 4.8 Hz, 1H), 3.89 - 3.69 (m, 1H), 3.57 (s, 2H), 2.79 (d, J= 10.8 Hz, 2H), 2.52 (s, 3H), 2.31 (s, 3H), 2.17 - 2.06 (m, 2H), 1.92 - 1.80 (m, 2H), 1.54 - 1.41 (m, 2H). [001003] Example 474: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(1-(difluoromethyl)-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin -4-yl)amino)pyrimidine-2- carbonitrile Example 474 was prepared in a manner similar to Example 472. MS: m/z = 619.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ 8.71 (s, 1H), 8.29 (s, 1H), 8.24 (d, J = 8.4 Hz, 1H), 8.13 - 7.96 (m, 3H), 7.91 - 7.59 (m, 2H), 7.51 - 7.40 (m, 4H), 7.13 (dd, J = 7.6, 1.6 Hz, 1H), 7.00 (s, 2H), 6.68 (d, J = 6.4 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.92 - 3.72 (m, 1H), 3.59 (s, 2H), 2.91 - 2.76 (m, 2H), 2.22 - 2.06 (m, 2H), 1.97 - 1.83 (m, 2H), 1.56 - 1.43 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -94.48. [001004] Example 475: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2,4-difluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 475 was prepared in a manner similar to Example 472. MS: m/z = 615.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.21 (d, J = 8.4 Hz, 1H), 8.09 - 7.88 (m, 3H), 7.84 (dd, J = 8.4, 2.0 Hz, 1H), 7.58 - 7.51 (m, 2H), 7.48 - 7.42 (m, 2H), 7.33 (dd, J = 7.8, 1.6 Hz, 1H), 7.12 - 6.97 (m, 2H), 6.65 - 6.44 (m, 1H), 6.48 (dd, J = 7.6, 4.8 Hz, 1H), 4.15 - 3.78 (m, 1H), 3.67 (s, 2H), 3.01 - 2.91 (m, 2H), 2.33 - 2.21 (m, 2H), 2.05 - 1.96 (m, 2H), 1.66 - 1.55 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -111.59, -114.05. [001005] Example 476: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(6-methoxypyridin-2-yl)- 3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 476 was prepared in a manner similar to Example 472. MS: m/z = 610.5 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.56 (d, J= 8.4 Hz, 1H), 8.22 (d, J= 8.8 Hz, 1H), 8.07 - 7.94 (m, 2H), 7.88 (d, J= 7.6 Hz, 1H), 7.72 - 7.65 (m, 1H), 7.60 - 7.53 (m, 2H), 7.50 - 7.45 (m, 2H), 7.34 (dd, J= 7.6, 2.0 Hz, 1H), 6.76 (d, J= 8.0 Hz, 1H), 6.65 - 6.54 (m, 1H), 6.49 (dd, J= 7.6, 5.2 Hz, 1H), 4.05 (s, 3H), 4.02 - 3.89 (m, 1H), 3.68 (s, 2H), 3.02 - 2.94 (m, 2H), 2.33 - 2.24 (m, 2H), 2.04 - 2.00 (m, 2H), 1.67 - 1.57 (m, 2H).

[001006] Example 477: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(2-methylpyridin-4-yl)-3 H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

A mixture of Example 405 (200 mg, 372 μmol), (2-methylpyridin-4-yl)boronic acid (56 mg, 410 μmol), K ₃ PO ₄ (158 mg, 745 μmol), PCy ₃ (10.4 mg, 37 μmol) and cataCXiumAPdG ₃ (136 mg, 186 μmol) in DMF (3 mL) were degassed and purged with N2 three times, and then was stirred at 120 °C for 2 hr under N2 atmosphere. The reaction mixture was diluted with H ₂ O (10 mL) and extracted with EtOAc (10 mL x 2). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by prep-HPLC (column: Phenomenex C18 150 x 25mm x 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 32% - 62% B over 11 min), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5- (2-methylpyridin-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl) piperidin-4-yl)amino)pyrimidine- 2-carbonitrile (Example 477, 46.3 mg, yield: 21%) was obtained as a yellow powder. MS: m/z = 594.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.45 (d, J= 5.2 Hz, 1H), 8.31 - 8.24 (m, 1H), 8.09 (d, J= 8.4 Hz, 1H), 8.05 - 7.98 (m, 2H), 7.95 (s, 1H), 7.90 - 7.86 (m, 1H), 7.60 - 7.54 (m, 2H), 7.49 - 7.38 (m, 2H), 7.34 (dd, J= 7.6, 2.0 Hz, 1H), 6.66 - 6.54 (m, 1H), 6.48 (dd, J= 7.6, 4.8 Hz, 1H), 4.09 - 3.85 (m, 1H), 3.70 - 3.65 (m, 2H), 3.02 - 2.95 (m, 2H), 2.58 (s, 3H), 2.33 - 2.24 (m, 2H), 2.05 - 1.97 (m, 2H), 1.67 - 1.58 (m, 2H).

[001007] Example 478: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(5-methylpyridin-3-yl)-3 H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 478 was prepared in a manner similar to Example 472. MS: m/z = 594.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.98 (d, J = 2.0 Hz, 1H), 8.41 - 8.33 (m, 1H), 8.29 - 8.21 (m, 2H), 8.07 - 7.93 (m, 3H), 7.56 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 8.4 Hz, 2H), 7.32 (dd, J = 7.6, 1.6 Hz, 1H), 6.68 - 6.53 (m, 1H), 6.47 (dd, J = 7.6, 5.2 Hz, 1H), 4.13 - 3.79 (m, 1H), 3.67 (s, 2H), 3.01 - 2.92 (m, 2H), 2.42 (s, 3H), 2.27 (t, J = 12.0 Hz, 2H), 2.06 - 1.98 (m, 2H), 1.67 - 1.55 (m, 2H). [001008] Example 479: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(1-isopropyl-1H-pyrazol- 4- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile Example 479 was prepared in a manner similar to Example 472. MS: m/z = 611.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.15 - 8.10 (m, 1H), 8.04 (d, J = 8.4 Hz, 1H), 8.01 - 7.96 (m, 1H), 7.96 - 7.91 (m, 2H), 7.64 (d, J = 8.4 Hz, 1H), 7.47 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.20 (dd, J = 7.6, 1.6 Hz, 1H), 6.58 (d, J = 5.6 Hz, 1H), 6.41 (dd, J = 7.6, 5.2 Hz, 1H), 4.55 - 4.45 (m, 1H), 4.00 - 3.85 (m, 1H), 3.59 (s, 2H), 2.91 (d, J = 11.6 Hz, 2H), 2.25 - 2.16 (m, 2H), 1.98 (d, J = 10.4 Hz, 2H), 1.61 - 1.52 (m, 2H), 1.47 (d, J = 6.4 Hz, 6H). [001009] Example 480: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(isothiazol-4-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 480 was prepared in a manner similar to Example 472. MS: m/z = 586.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ 9.46 (s, 1H), 9.11 (s, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.09 - 8.04 (m, 2H), 8.02 - 7.92 (m, 2H), 7.52 - 7.38 (m, 4H), 7.22 - 7.11 (m, 1H), 7.08 - 6.96 (m, 2H), 6.67 (d, J = 6.4 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.92 - 3.73 (m, 1H), 3.59 (s, 2H), 2.88 - 2.79 (m, 2H), 2.16 (t, J = 10.4 Hz, 2H), 1.93 - 1.87 (m, 2H), 1.58 - 1.43 (m, 2H). [001010] Example 481: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(5-cyano-1-methyl-1H- pyrrol-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin- 4-yl)amino)pyrimidine-2- carbonitrile Example 481 was prepared in a manner similar to Example 472. MS: m/z = 607.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.08 (d, J = 8.4 Hz, 1H), 8.04 - 7.99 (m, 1H), 7.97 (dd, J = 4.8, 1.2 Hz, 1H), 7.66 (d, J = 8.4 Hz, 1H), 7.60 - 7.56 (m, 1H), 7.54 (d, J = 8.0 Hz, 2H), 7.42 (d, J = 8.4 Hz, 2H), 7.34 - 7.25 (m, 2H), 6.60 (d, J = 6.4 Hz, 1H), 6.46 (dd, J = 7.6, 5.2 Hz, 1H), 4.05 - 3.90 (m, 1H), 3.81 (s, 3H), 3.63 (s, 2H), 3.01 - 2.92 (m, 2H), 2.35 - 2.26 (m, 2H), 2.06 - 2.00 (m, 2H), 1.67 - 1.59 (m, 2H). [001011] Example 482: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(thiazol-4-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 482 was prepared in a manner similar to Example 469. MS: m/z = 608.2 [M + Na] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 9.05 (s, 1H), 8.25 - 8.20 (m, 2H), 8.09 - 8.05 (m, 1H), 8.03 - 7.94 (m, 2H), 7.57 - 7.53 (m, 2H), 7.47 - 7.43 (m, 2H), 7.34 - 7.28 (m, 1H), 6.60 (d, J = 5.6 Hz, 1H), 6.50 - 6.44 (m, 1H), 4.06 - 3.88 (m, 1H), 3.66 (s, 2H), 2.97 (d, J = 11.2 Hz, 2H), 2.28 (t, J = 11.2 Hz, 2H), 2.05 - 1.99 (m, 2H), 1.67 - 1.58 (m, 2H). [001012] Example 483: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(isothiazol-5-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 483 was prepared in a manner similar to Example 469. MS: m/z = 586.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.49 (d, J= 2.0 Hz, 1H), 8.23 (d, J= 8.4 Hz, 1H), 8.11 - 7.90 (m, 3H), 7.84 (d, J= 2.0 Hz, 1H), 7.57 (d, J= 8.4 Hz, 2H), 7.44 (d, J= 8.4 Hz, 2H), 7.33 (dd, J = 7.6, 1.6 Hz, 1H), 6.66 - 6.54 (m, 1H), 6.48 (dd, J= 7.6, 5.2 Hz, 1H), 4.09 - 3.86 (m, 1H), 3.68 (s, 2H), 2.98 (d, J= 11.2 Hz, 2H), 2.35 - 2.24 (m, 2H), 2.02 (d, J= 9.6 Hz, 2H), 1.68 - 1.55 (m, 2H).

[001013] Example 484: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(l,5-dimethyl-1H-pyrazol -4- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile

A mixture of Example 405 (250 mg, 430 μmol), (l,5-dimethyl-1H-pyrazol-4-yl)boronic acid (72 mg, 516 μmol), CS ₂ CO ₃ (14 mg, 43 μmol), XphosPdG ₄ (370 mg, 430 μmol) in 1,4-dioxane (2 mL) was degassed and purged with N2 three times, and then was stirred at 90 °C for 16 hr under N2 atmosphere. The reaction mixture was diluted with H ₂ O (20 mL) and extracted with EtOAc (20 mL x 2). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by prep-HPLC (column: Waters Xbridge BEH C18 150 x 25 mm x 5 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 27% -57% B over 10 min), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(l,5-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin -4-yl)amino)pyrimidine-2- carbonitrile (Example 484, 17 mg, yield: 6%) was obtained as a yellow solid. MS: m/z = 597.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.15 - 8.08 (m, 1H), 8.05 - 7.95 (m, 2H), 7.89 (s, 1H), 7.68 - 7.62 (m, 1H), 7.57 - 7.50 (m, 2H), 7.46 - 7.40 (m, 2H), 7.34 (dd, J= 7.6, 1.6 Hz, 1H), 6.64 - 6.55 (m, 1H), 6.47 (dd, J= 7.6, 5.2 Hz, 1H), 4.04 - 3.89 (m, 1H), 3.79 (s, 3H), 3.67 (s, 2H), 2.95 (d, J= 11.6 Hz, 2H), 2.52 (s, 3H), 2.26 (t, J= 11.2 Hz, 2H), 2.06 - 1.96 (m, 2H), 1.67 - 1.51 (m, 2H).

[001014] Example 485: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-bromo-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile Example 485 was prepared in a manner similar to Example 341. MS: m/z = 581.2, 583.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.17 (d, J = 8.4 Hz, 1H), 8.12 - 8.02 (m, 2H), 7.99 (dd, J = 4.8, 2.0 Hz, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.48 - 7.45 (m, 2H), 7.41 - 7.38 (m, 2H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 6.93 (br s, 2H), 6.68 (d, J = 6.0 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.86 - 3.76 (m, 1H), 3.57 (s, 2H), 2.85 - 2.78 (m, 2H), 2.15 (t, J = 11.6 Hz, 2H), 1.93 - 1.84 (m, 2H), 1.54 - 1.44 (m, 2H). [001015] Example 486: 4-((1-((4-(2-(2-Aminopyridin-3-yl)-5-bromo-3H-imidazo[4,5- b]pyridin-3-yl)phenyl)methyl-d ₂ )piperidin-4-yl)amino)pyrimidine-2-carbonitrile Example 486 was prepared in a manner similar to Example 261. MS: m/z = 583.2, 585.2 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.17 (d, J = 8.4 Hz, 1H), 8.12 - 8.02 (m, 2H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.48 - 7.44 (m, 2H), 7.41 - 7.37 (m, 2H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 6.92 (br s, 2H), 6.67 (d, J = 6.4 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.87 - 3.76 (m, 1H), 2.85 - 2.78 (m, 2H), 2.19 - 2.11 (m, 2H), 1.93 - 1.84 (m, 2H), 1.54 - 1.44 (m, 2H). [001016] Example 487: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)-1,3, 5-triazine-2-carbonitrile Example 487 was prepared in a manner similar to Example 261. MS: m/z = 598.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.92 (dd, J = 7.6, 5.2 Hz, 1H), 8.65 (d, J = 29.2 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.08 (dd, J = 8.4, 5.6 Hz, 2H), 8.02 - 7.95 (m, 2H), 7.51 - 7.42 (m, 4H), 7.30 (t, J = 8.8 Hz, 2H), 7.17 - 7.13 (m, 1H), 7.03 (s, 2H), 6.41 - 6.34 (m, 1H), 3.86 - 3.69 (m, 1H), 3.58 (d, J = 4.0 Hz, 2H), 2.91 - 2.79 (m, 2H), 2.18 - 2.03 (m, 2H), 1.88 - 1.78 (m, 2H), 1.66 - 1.50 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -113.58. [001017] Example 488: 4-((1-((4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methyl-d2)piperidin-4-yl)( methyl)amino)pyrimidine-2- carbonitrile Example 488 was prepared in a manner similar to Example 261. MS: m/z = 613.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.21 - 8.14 (m, 2H), 8.10 - 8.04 (m, 2H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.59 - 7.53 (m, 2H), 7.49 - 7.44 (m, 2H), 7.32 (dd, J = 7.6, 1.6 Hz, 1H), 7.16 (t, J = 8.8 Hz, 2H), 6.88 - 6.78 (m, 1H), 6.48 (dd, J = 8.0, 5.2 Hz, 1H), 3.11 - 3.05 (m, 2H), 2.99 (s, 3H), 2.37 - 2.23 (m, 2H), 2.07 - 2.00 (m, 1H), 2.00 - 1.88 (m, 2H), 1.76 - 1.66 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -115.70. [001018] Example 489: 4-((1-((4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methyl-d2)piperidin-4-yl)a mino)pyrimidine-2-carbonitrile Example 489 was prepared in a manner similar to Example 261. MS: m/z = 599.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.11 - 8.04 (m, 4H), 8.01 - 7.95 (m, 2H), 7.50 - 7.43 (m, 4H), 7.29 (t, J = 8.8 Hz, 2H), 7.14 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (s, 2H), 6.68 (d, J = 6.0 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.89 - 3.73 (m, 1H), 2.88 - 2.78 (m, 2H), 2.21 - 2.07 (m, 2H), 1.93 - 1.84 (m, 2H), 1.57 - 1.43 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -113.56. [001019] Example 490: 4-(7-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,7-diazaspiro[3.5]nonan- 2-yl)pyrimidine-2-carbonitrile

Example 490 was prepared in a manner similar to Example 261. MS: m/z = 623.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.28 (d, J= 8.4 Hz, 1H), 8.22 (d, J= 6.0 Hz, 1H), 8.10 - 8.06 (m, 2H), 8.02 - 7.97 (m, 2H), 7.50 - 7.43 (m, 4H), 7.33 - 7.28 (m, 2H), 7.16 (dd, J= 7.6, 2.0 Hz, 1H), 7.03 (s, 2H), 6.64 (d, J= 6.0 Hz, 1H), 6.39 (dd, J= 7.6, 4.8Hz, 1H), 3.81 (s, 4H), 3.57 (s, 2H), 2.42 - 2.31 (m, 4H), 1.81 - 1.77 (m, 4H).

[001020] Example 491: 4-(2-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,7-diazaspiro[3.5]nonan- 7-yl)pyrimidine-2-carbonitrile

Example 491 was prepared in a manner similar to Example 261. MS: m/z = 623.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J= 8.4 Hz, 1H), 8.22 (d, J= 6.4 Hz, 1H), 8.09 - 8.05 (m, 2H), 8.01 - 7.96 (m, 2H), 7.45 - 7.42 (m, 4H), 7.32 - 7.27 (m, 2H), 7.16 (dd, J= 8, 2 Hz, 1H), 7.12 (d, J= 6.4 Hz, 1H), 6.99 (s, 2H), 6.39 (dd, J= 7.2, 6.4 Hz, 1H), 3.70 (s, 2H), 3.60 (s, 4H), 3.07 (s, 4H), 1.77 - 1.72 (m, 4H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d6) δ - 113.588.

[001021] Example 492: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(methylsulfinyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

To a solution of Example 435 (110 mg, 200 μmol) in THF (2 mL) and MeOH (0.5 mL) was added oxone (370 mg, 601 μmol). The mixture was stirred at 25 °C for 2 hr. The reaction mixture was concentrated under reduced pressure. After purified by prep-HPLC (column: Waters xbridge 150 * 25 mm 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 20% - 40% B over 11 min), 4-((1-(4-(2-(2-aminopyridin-3-yl)-5-(methylsulfinyl)-3H-imid azo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile (Example 492, 4.7 mg, yield: 4%) was obtained as light yellow solid. MS: m/z = 565.2 [M + H] ⁺ . ¹ H NMR (400MHz, Methanol-d ₄ ) δ 8.42 (d, J = 8.0 Hz, 1H), 8.06 - 7.96 (m, 3H), 7.54 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 8.0 Hz, 2H), 7.32 (dd, J = 7.6, 1.2 Hz, 1H), 6.63 - 6.59 (m, 1H), 6.47 (dd, J = 7.6, 5.2 Hz, 1H), 4.02 - 3.91 (m, 1H), 3.66 (s, 2H), 2.98 - 2.91 (m, 2H), 2.86 (s, 3H), 2.32 - 2.22 (m, 2H), 2.07 - 1.96 (m, 2H), 1.61 - 1.57 (m, 2H). [001022] Example 493: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5,7-dimethyl-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile Example 493 was prepared in a manner similar to Example 261. MS: m/z = 531.7 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.07 (dd, J = 12.4, 6.0 Hz, 2H), 7.96 (dd, J = 4.8, 1.6 Hz, 1H), 7.44 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 7.09 - 7.06 (m, 2H), 7.02 (s, 2H), 6.67 (br d, J = 6.0 Hz, 1H), 6.34 (dd, J = 7.6, 4.8 Hz, 1H), 3.86 - 3.76 (m, 1H), 3.56 (s, 2H), 2.85 - 2.80 (m, 2H), 2.61 (s, 3H), 2.47 (s, 3H), 2.18 - 2.11 (m, 2H), 1.92 - 1.84 (m, 1H), 1.53 - 1.44 (m, 2H). [001023] Example 494: 4-((1-(4-(8-(2-aminopyridin-3-yl)-6-hydroxy-9H-purin-9- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile Step 1: (4-((6-Chloro-5-nitropyrimidin-4-yl)amino)phenyl)methanol A mixture of 4,6-dichloro-5-nitropyrimidine (10 g, 51.6 mmol), (4-aminophenyl)methanol (5.08 g, 41.2 mmol) in THF (300 mL) was added TEA (4.69 g, 46.4 mmol) at 0°C. The mixture was degassed and purged with N ₂ three times, and then was stirred at 0 °C for 0.5 hr under N ₂ atmosphere. And then it was stirred at 25°C for 3 hr The reaction mixture was diluted with water (400 mL) and extracted with EtOAc (300 mL x 3). The combined organic layers were washed with brine (400 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 37% EtOAc in petroleum ether), (4-((6-chloro-5-nitropyrimidin-4-yl)amino)phenyl)methanol (8.6 g, yield: 59%) was obtained as an orange solid. MS: m/z = 280.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.07 (s, 1H), 8.49 (s, 1H), 7.43 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 4.49 (s, 3H). Step 2: 4-((6-Chloro-5-nitropyrimidin-4-yl)amino)benzyl acetate A mixture of (4-((6-chloro-5-nitropyrimidin-4-yl)amino)phenyl)methanol (8 g, 28.5 mmol), DMAP (348 mg, 2.85 mmol) and TEA (8.65 g, 85.5 mmol) in CH ₂ Cl ₂ (200 mL) was added Ac ₂ O (2.91 g, 28.5 mmol). The mixture was degassed and purged with N ₂ three times, and then was stirred at 0 °C for 2 hr under N ₂ atmosphere. The reaction mixture was diluted with water (200 mL) and extracted with EtOAc (200 mL x 3). The combined organic layers were washed with brine (200 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 100% EtOAc in petroleum ether), 4-((6-chloro-5-nitropyrimidin-4-yl)amino)benzyl acetate (1.0 g, yield: 9%) was obtained as a yellow solid. MS: m/z = 304.8 [M + H] ⁺ , ¹ H NMR (400 MHz, Chloroform-d) δ 11.28 (s, 1H), 10.91 (s, 1H), 8.10 - 7.90 (m, 1H), 7.45 (d, J = 8.0 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 5.13 (s, 2H), 2.05 (s, 3H). Step 3: 4-(8-(2-Aminopyridin-3-yl)-6-hydroxy-9H-purin-9-yl)benzyl acetate A mixture of 4-((6-chloro-5-nitropyrimidin-4-yl)amino)benzyl acetate (343 mg, 3.10 mmol), 2- aminonicotinaldehyde (416 mg, 3.41 mmol) and Na ₂ S ₂ O ₄ (2.16 g, 12.4 mmol) in DMSO (100 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 100 °C for 16 hr under N ₂ atmosphere. The reaction mixture was diluted with H ₂ O (100 mL) and extracted with EtOAc (100 mL x 3). The combined organic layers were washed with brine (200 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 80% EtOAc in petroleum ether), 4-(8-(2-aminopyridin-3-yl)-6- hydroxy-9H-purin-9-yl)benzyl acetate (200 mg, yield: 12%) was obtained as a yellow solid. MS: m/z = 376.9 [M + H] ⁺ , ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 12.67 - 12.14 (m, 1H), 8.02 (s, 1H), 7.95 (dd, J = 4.8, 1.6 Hz, 1H), 7.45 (d, J = 8.8 Hz, 2H), 7.40 (d, J = 8.0 Hz, 2H), 7.14 (dd, J = 7.6, 1.6 Hz, 1H), 6.79 (s, 2H), 6.39 (dd, J =7.6, 4.8 Hz, 1H), 5.14 (s, 2H), 2.10 (s, 3H). Step 4: 8-(2-Aminopyridin-3-yl)-9-(4-(hydroxymethyl)phenyl)-9H-purin -6-ol To a mixture of 4-(8-(2-aminopyridin-3-yl)-6-hydroxy-9H-purin-9-yl)benzyl acetate (150 mg, 399 μmol) in MeOH (10 mL), THF (10 mL) and H ₂ O (5 mL) was added K ₂ CO ₃ (55.1 mg, 399 μmol). The mixture was stirred at 25 °C for 0.5 hr. The mixture was filtered and concentrated under reduced pressure to give 8-(2-aminopyri din-3 -yl)-9-(4-(hydroxymethyl)phenyl)-9H-purin- 6-oI (100 mg, yield: 75%) as a yellow solid. MS: m/z = 335.0 [M + H] ⁺ .

Step 5: 8-(2 -Aminopyri din-3 -yl)-9-(4-(chloromethyl)phenyl)-9H-purin-6-ol

To a solution of 8-(2-aminopyridin-3-yl)-9-(4-(hydroxymethyl)phenyl)-9H-purin -6-ol (100 mg, 299 μmol) in CH ₂ CI ₂ (10 mL) was added SOCI ₂ (214 mg, 1.79 mmol). The mixture was stirred at 25 °C for 1 hr. The mixture was concentrated under reduced pressure to give 8-(2- aminopyridin-3-yl)-9-(4-(chloromethyl)phenyl)-9H-purin-6-ol (100 mg, yield: 95%) as a yellow solid. MS: m/z = 353.1 [M + H] ⁺ .

Step 6: 4-((l-(4-(8-(2-Aminopyridin-3-yl)-6-hydroxy-9H-purin-9-yl)be nzyl)piperidin-4- yl)amino)pyrimidine-2-carbonitrile

To a solution of 8-(2-aminopyridin-3-yl)-9-(4-(chloromethyl)phenyl)-9H-purin- 6-ol (100 mg, 283 μmol) and Intermediate 51 (57.6 mg, 283 μmol) in DMF (5 mL) were added Nal (21.2 mg, 142 μmol) and K ₂ CO ₃ (196 mg, 1.42 mmol). The mixture was stirred at 50 °C for 1 hr. The reaction mixture was filtered and concentrated. After purified by prep-HPLC (column: Waters xbridge 150 x 25 mm 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 12% - 42% B over 10 min), 4-((l-(4-(8-(2-aminopyri din-3 -yl)-6-hydroxy-9H-purin-9-yl)benzyl)piperi di n-4- yl)amino)pyrimidine-2-carbonitrile (Example 494, 15.3 mg, yield: 9%) was obtained as a yellow solid. MS: m/z = 520.1 [M + H] ⁺ . ¹ HNMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 12.56 - 12.18 (m, 1H), 8.12 - 8.02 (m, 3H), 7.94 (dd, J= 4.8, 1.6 Hz, 1H), 7.43 (d, J= 8.4 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 7.06 (dd, J= 8.0, 2.0 Hz, 1H), 6.89 (s, 2H), 6.67 (d, J= 6.0 Hz, 1H), 6.34 (dd, J= 8.0, 4.8 Hz, 1H), 3.86 - 3.75 (m, 1H), 3.55 (s, 2H), 2.79 (d, J= 11.6 Hz, 2H), 2.17 - 2.09 (m, 2H), 1.91 - 1.82 (m, 2H), 1.53 - 1.43 (m, 2H).

[001024] Example 495: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(pyridin-2-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

Example 495 was prepared in a manner similar to Example 261. MS: m/z = 580.3 [M + H] ⁺ . ¹ H

NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.67 (d, J= 4.8 Hz, 1H), 8.47 (d, J= 8.4 Hz, 1H), 8.31 (d, J = 8.4 Hz, 1H), 8.19 (d, J = 8.0 Hz, 1H), 8.14 - 8.03 (m, 2H), 8.03 - 7.97 (m, 1H), 7.93 - 7.86 (m, 1H), 7.53 - 7.44 (m, 4H), 7.40 (dd, J = 6.4, 4.8 Hz, 1H), 7.18 (d, J = 6.8 Hz, 1H), 7.01 (s, 2H), 6.68 (d, J = 5.2 Hz, 1H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.91 - 3.73 (m, 1H), 3.60 (s, 2H), 2.88 - 2.78 (m, 2H), 2.24 - 2.07 (m, 2H), 1.97 - 1.82 (m, 2H), 1.59 - 1.42 (m, 2H). [001025] Example 496: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-hydroxy-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile Step 1: (4-((6-Methoxy-3-nitropyridin-2-yl)amino)phenyl)methanol To a solution of 2-chloro-6-methoxy-3-nitropyridine (20 g, 106 mmol) and (4- aminophenyl)methanol (13.1 g, 106 mmol) in 1,4-dioxane (220 mL) was added DIEA (41.1 g, 318 mmol). The mixture was stirred at 110 °C for 16 hr. The reaction mixture was diluted with H ₂ O (500 mL) and extracted with CH ₂ Cl ₂ (500 mL x 3). The combined organic layers were washed with brine (400 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. (4-((6-Methoxy-3-nitropyridin-2-yl)amino)phenyl)methanol (29 g, yield: 97%) was obtained as a yellow solid MS: m/z = 276.0 [M + H] ⁺ . Step 2: 4-((6-Methoxy-3-nitropyridin-2-yl)amino)benzyl acetate To a solution of (4-((6-methoxy-3-nitropyridin-2-yl)amino)phenyl)methanol (29 g, 105 mmol) and TEA (32.0 g, 316 mmol) in CH ₂ Cl ₂ (160 mL) were added Ac ₂ O (10.8 g, 105 mmol) and DMAP (1.29 g, 10.5 mmol). The mixture was stirred at 0 °C for 0.5 hr. The reaction mixture was diluted with H ₂ O (500 mL) and extracted with CH ₂ Cl ₂ (500 mL x 3). The combined organic layers were washed with brine (200 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 43% EtOAc in petroleum ether), 4-((6-methoxy-3-nitropyridin-2-yl)amino)benzyl acetate (30 g, yield: 87%) was obtained as a yellow solid. MS: m/z = 318.0 [M + H] ⁺ . ¹ H NMR (400MHz, Chloroform-d) δ 10.66 (s, 1H), 8.42 (d, J = 9.2 Hz, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 6.25 (d, J = 8.8 Hz, 1H), 5.11 (s, 2H), 3.97 (s, 3H), 2.12 (s, 3H). Step 3: 4-(2-(2-Aminopyridin-3-yl)-5-methoxy-3H-imidazo[4,5-b]pyridi n-3-yl)benzyl acetate A mixture of 4-((6-methoxy-3-nitropyridin-2-yl)amino)benzyl acetate (15 g, 47.3 mmol), 2- aminonicotinaldehyde (6.93 g, 56.7 mmol), Na ₂ S ₂ O ₄ (32.9 g, 189 mmol) in DMSO (100 mL) was degassed and purged with N2 three times, and then was stirred at 100 °C for 16 hr under N2 atmosphere. The reaction mixture was diluted with H ₂ O (1500 mL) and extracted with EtOAc (500 mL x 3). The combined organic layers were washed with brine (300 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. The product was triturated with CH ₂ CI ₂ : EtOAc = 2:1 (60 mL) and filtered. 4-(2-(2-Aminopyridin-3-yl)-5-methoxy-3H- imidazo[4,5-b]pyridin-3-yl)benzyl acetate (10 g, yield: 50%) was obtained as a brown solid. MS: m/z = 390.1 [M + H] ⁺ . ¹ H NMR (400MHz, Chloroform-d) δ 9.42 - 8.88 (m, 2H), 8.02 (d, J = 8.8 Hz, 1H), 7.74 (d, J= 5.6 Hz, 1H), 7.56 (d, J= 8.0 Hz, 2H), 7.41 - 7.33 (m, 3H), 6.83 (d, J = 8.8 Hz, 1H), 6.55 - 6.48 (m, 1H), 5.25 (s, 2H), 3.86 (s, 3H), 2.19 (s, 3H).

Step 4 : 2-(2-Aminopyridin-3 -yl)-3 -(4-(bromomethyl)phenyl)-3H-imidazo[4, 5-b]pyridin-5-ol To a solution of 4-(2-(2-aminopyridin-3-yl)-5-methoxy-3H-imidazo[4,5-b]pyridi n-3-yl)benzyl acetate (500 mg, 1.28 mmol) in CH ₂ CI ₂ (20 mL) was added BBr ₃ (3.22 g, 12.8 mmol). The mixture was stirred at 80 °C for 12 hr. The mixture was concentrated under reduced pressure to give 2-(2-aminopyridin-3-yl)-3-(4-(bromomethyl)phenyl)-3H-imidazo [4,5-b]pyridin-5-ol (480 mg, crude) as a brown solid. MS: m/z = 395.9, 397.9 [M + H] ⁺ .

Step 5: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-hydroxy-3H-imidazo[4,5-b ]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile

To a solution of 2-(2-aminopyridin-3-yl)-3-(4-(bromomethyl)phenyl)-3H-imidazo [4,5-b]pyridin- 5-ol (200 mg, 505 μmol) and Intermediate 51 (103 mg, 323 μmol, TFA) in DMF (2 mL) were added K ₂ CO ₃ (349 mg, 2.52 mmol) and Nal (22.7 mg, 151 μmol). The mixture was stirred at 50 °C for 0.5 hr. The reaction mixture was filtered and concentrated. After purified by prep- HPLC(column: Waters xbridge 150 x 25 mm 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 40% - 70% B over 11 min), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-hydroxy-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile (Example 496, 23.1 mg delivered, yield: 8.4%) was obtained as a light yellow lyophilized powder. MS: m/z = 519.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 11.02 - 10.64 (m, 1H), 8.10 - 8.01 (m, 3H), 7.92 (dd, J= 4.8, 1.6 Hz, 1H), 7.46 - 7.42 (m, 2H), 7.37 - 7.34 (m, 2H), 7.05 - 6.99 (m, 3H), 6.69 - 6.61 (m, 2H), 6.31 (dd, J= 7.6, 4.8 Hz, 1H), 3.88 - 3.77 (m, 1H), 3.56 (s, 2H), 2.83 - 2.78 (m, 2H), 2.17 - 2.10 (m, 2H), 1.92 - 1.84 (m, 2H), 1.54 - 1.44 (m, 2H).

[001026] Example 497: 4-((l-(4-(5-Amino-2-(2-aminopyridin-3-yl)-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile

Step 1: Methyl 4-((6-((tert-butoxycarbonyl)amino)-3-nitropyridin-2-yl)amino )benzoate A mixture of methyl 4-((6-chloro-3-nitropyridin-2-yl)amino)benzoate (refer to Intermediate 13 for detail procedures, 5 g, 16 mmol), tert-butyl carbamate (1.9 g, 16 mmol), Cs ₂ CO ₃ (10.6 g, 32.5 mmol), XPhos (775 mg, 1.63 mmol) and Pd(OAc)2 (365 mg, 1.63 mmol) in 1,4-dioxane (60 mL) was degassed and purged with N ₂ three times, and then was stirred at 100 °C for 16 hr under N ₂ atmosphere. The reaction mixture was diluted with H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (100 mL x 3). The combined organic layers were washed with brine (50 mL x 3), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. Methyl 4-((6-((tert- butoxycarbonyl)amino)-3-nitropyridin-2-yl)amino)benzoate (6 g, yield: 77%) was obtained as a brown solid. MS: m/z = 333.0 [M + H - t-Bu] ⁺ . Step 2: Methyl 4-(2-(2-aminopyridin-3-yl)-5-((tert-butoxycarbonyl)amino)-3H -imidazo[4,5- b]pyridin-3-yl)benzoate To a solution of methyl 4-((6-((tert-butoxycarbonyl)amino)-3-nitropyridin-2-yl)amino )benzoate (2.55 g, 6.57 mmol) in DMSO (20 mL) were added Na ₂ S ₂ O ₄ (5.38 g, 26.3 mmol, 85% purity) and 2-aminonicotinaldehyde (882 mg, 7.22 mmol). The mixture was stirred at 80 °C for 16 hr. The reaction mixture was quenched with H ₂ O (25 mL) at 25 °C. The mixture was diluted with CH ₂ Cl ₂ (50 mL), washed with H ₂ O (50 mL x 3) and brine (100 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 30% ~ 50% EtOAc in petroleum ether), methyl 4-(2-(2-aminopyridin-3-yl)-5-((tert- butoxycarbonyl)amino)-3H-imidazo[4,5-b]pyridin-3-yl)benzoate (260 mg, yield: 33%) was obtained as a yellow solid. MS: m/z = 461.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.71 (s, 1H), 8.15 (d, J = 8.8 Hz, 1H), 8.06 (d, J = 8.4 Hz, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.88 - 7.76 (m, 1H), 7.58 (d, J = 8.4 Hz, 2H), 7.14 (dd, J = 7.6, 1.2 Hz, 1H), 6.83 (s, 2H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 3.89 (s, 3H), 1.45 (s, 9H). Step 3: tert-Butyl (2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imid azo[4,5-b]pyridin-5-yl)carbamate

To a solution of methyl 4-(2-(2-aminopyridin-3-yl)-5-((tert-butoxycarbonyl)amino)-3H - imidazo[4,5-b]pyridin-3-yl)benzoate (250 mg, 543 μmol) in THF (5 mL) was added LiAlH ₄ (41.2 mg, 1.1 mmol) at 0°C. After addition, the resulting mixture was stirred at 25°C for 1 hr. Then the reaction mixture was filtered. The filtrate was concentrated to give tert-butyl (2-(2- aminopyridin-3 -yl)-3 -(4-(hydroxymethyl)phenyl)-3H-imidazo[4, 5-b]pyri din-5 -yl)carbamate (230 mg, yield: 66%) as a yellow solid . MS: m/z = 433.1 [M + 1] ⁺ .

Step 4: tert-Butyl (2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imida zo[4,5- b]pyridin-5-yl)carbamate

To a solution of tert-butyl (2-(2-aminopy ri din-3 -yl)-3 -(4-(hy droxy methy l)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)carbamate (230 mg, 532 μmol) in CH ₂ CI ₂ (5 mL) was added SOCI ₂ (189 mg, 1.6 mmol) at 0 °C. The mixture was stirred at 40 °C for 0.5 hr. The reaction mixture was quenched with H ₂ O (1 mL) at 25 °C and concentrated under reduced pressure. tert-Butyl (2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3T/-imid azo[4,5-b]pyridin-5-yl)carbamate (260 mg, HC1 salt) was obtained as a yellow solid. MS: m/z = 451.0 [M + H] ⁺ .

Step 5: tert-Butyl (2-(2-aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin-4-yl)am ino)piperidin-l- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)carbamate

To a solution of tert-butyl (2-(2-aminopy ri din-3 -yl)-3 -(4-(chl oromethy l)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)carbamate (260 mg, 533 μmol, HC1 salt) and Intermediate 51 (169 mg, 533 μmol, TFA) in DMF (5 mL) were added K ₂ CO ₃ (369 mg, 2.67 mmol) and Nal (40 mg, 267ol). The mixture was stirred at 50 °C for 1 hr. The reaction mixture was quenched with H ₂ O (25 mL) at 25 °C, and then diluted with CH ₂ CI ₂ (50 mL). The organic layer was washed with H ₂ O (50 mL x 3) and brine (100 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. Tert-butyl (2-(2-aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin-l-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyri din-5-yl)carbamate (300 mg, yield: 67%) was obtained as a yellow solid. MS: m/z = 618.1 [M + H] ⁺ .

Step 6: 4-((l-(4-(5-Amino-2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile

A mixture of tert-butyl (2-(2-aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin-l-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyri din-5-yl)carbamate (260 mg, 421 μmol, HC1 salt) in 4 M HC1 in 1,4-dioxane (3 mL) was stirred at 25 °C for 2 hr. The reaction was concentrated under reduced pressure to give product as a yellow solid. The product was diluted with aqueous NaHCO ₃ (10 mL) and extracted with CH ₂ CI ₂ (10 mL x 3). The combined organic layers were washed with brine (20 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by prep-HPLC (column: Waters xbridge 150 x 25 mm 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 16% - 46% B over 11 min), 4-((l- (4-(5-amino-2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin -3-yl)benzyl)piperidin-4- yl)amino)pyrimidine-2-carbonitrile (Example 497, 21.9 mg, yield: 10%) was obtained as a yellow powder. MS: m/z = 518.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.06 - 7.95 (m, 1H), 7.90 (dd, J= 4.8, 1.2 Hz, 1H), 7.82 (d, J= 8.4 Hz, 1H), 7.53 - 7.45 (m, 2H), 7.33 (d, J= 8.0 Hz, 2H), 7.19 (dd, J= 7.6, 1.2 Hz, 1H), 6.67 - 6.50 (m, 2H), 6.42 (dd, J= 7.6, 4.8 Hz, 1H), 4.08 - 3.75 (m, 1H), 3.64 (s, 2H), 2.97 - 2.86 (m, 2H), 2.25 (t, J= 11.2 Hz, 2H), 2.05 - 1.95 (m, 2H), 1.67 - 1.55 (m, 2H).

[001027] Example 498: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(2-chloro-4-fluorophenyl )- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile

A mixture of Example 405 (300 mg, 559 μmol), (2-chloro-4-fluorophenyl)boronic acid (107 mg, 615 μmol), K ₂ CO ₃ (232 mg, 1.68 mmol) and Pd(PPh3)4 (65 mg, 56 μmol) in THF (2.5 mL) and H ₂ O (0.5 mL) was degassed and purged with N2 three times, and then was stirred at 80 °C for 2 hr under N2 atmosphere. The reaction mixture was diluted with H ₂ O (10 mL) and extracted with EtOAc (10 mL x 2). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by prep-HPLC (column: Phenomenex C18 150 x 25 mm x 10 μm; mobile phase: [water (NH4HCO3) - ACN]; gradient: 48% - 78% B over 11 min), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(2-chloro-4- fluorophenyl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin -4-yl)amino)pyrimidine-2- carbonitrile (Example 498, 129.5 mg, yield: 37%) was obtained as a yellow powder. MS: m/z = 631.3 [M + H] ⁺ . ¹ HNMR (400 MHz, Dimethysulfoxide-d ₆ ) δ 8.29 (d, J= 8.0 Hz, 1H), 8.13 - 7.94 (m, 3H), 7.66 - 7.53 (m, 3H), 7.46 - 7.38 (m, 4H), 7.36 - 7.30 (m, 1H), 7.15 (dd, J= 7.6, 1.6 Hz, 1H), 6.98 (s, 2H), 6.66 (d, J= 6.0 Hz, 1H), 6.38 (dd, J= 8.0, 5.2 Hz, 1H), 3.91 - 3.63 (m, 1H), 3.55 (s, 2H), 2.85 - 2.75 (m, 2H), 2.17 - 2.06 (m, 2H), 1.92 - 1.79 (m, 2H), 1.54 - 1.41 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -111.64. [001028] Example 499: 4-((1-(4-(2-(2-aminopyridin-3-yl)-5-(4-fluorophenyl)-6-methy l- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile Step 1: (4-((6-Chloro-5-methyl-3-nitropyridin-2-yl)amino)phenyl)meth anol To a solution of 2,6-dichloro-3-methyl-5-nitropyridine (2 g, 9.7 mmol) and (4- aminophenyl)methanol (1.2 g, 9.7 mmol) in 1,4-dioxane (25 mL) was added DIEA (2.5 g, 19.3 mmol) at 25 °C. The mixture was stirred at 70 °C for 12 hr. The reaction mixture was poured into H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (50 mL x 2). The combined organic layers were washed with brine (40 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0~60% EtOAc in petroleum ether), (4-((6- chloro-5-methyl-3-nitropyridin-2-yl)amino)phenyl)methanol (2.3 g, yield: 81%) was obtained as a yellow solid. MS: m/z = 293.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.96 (s, 1H), 8.55 (d, J = 0.6 Hz, 1H), 7.54 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 5.16 (t, J = 6.4 Hz, 1H), 4.49 (d, J = 6.0 Hz, 2H), 2.29 (s, 3H). Step 2: 4-((6-Chloro-5-methyl-3-nitropyridin-2-yl)amino)benzyl acetate To a solution of (4-((6-chloro-5-methyl-3-nitropyridin-2-yl)amino)phenyl)meth anol (2.3 g, 7.8 mmol) and acetic anhydride (1.2 g, 11.8 mmol) in CH2Cl2(25 mL) were added TEA (2.4 g, 23.5 mmol) and DMAP (96 g, 783 µmol) at 0 °C. The mixture was stirred at 0 °C for 2 hr. The reaction mixture was poured into H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (50 mL x 2). The combined organic layers were washed with brine (40 mL), dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated. After purified by silica gel flash chromatography (Eluent of 0 ~ 40% EtOAc in petroleum ether), 4-((6-chloro-5-methyl-3-nitropyridin-2-yl)amino)benzyl acetate (2.5 g, yield: 94%) was obtained as a yellow solid. MS: m/z = 335.8 [M + H] ⁺ .9.98 (s, 1H), 8.57 (s, 1H), 7.61 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 5.06 (s, 2H), 2.30 (s, 3H), 2.07 (s, 3H). Step 3: 4-((6-(4-Fluorophenyl)-5-methyl-3-nitropyridin-2-yl)amino)be nzyl acetate To a solution of 4-((6-chloro-5-methyl-3-nitropyridin-2-yl)amino)benzyl acetate (2.2 g, 6.6 mmol) in 1,4-dioxane (30 mL) and H ₂ O (10 mL) were added Cs ₂ CO ₃ (6.4 g, 20 mmol), (4- fluorophenyl)boronic acid (1 g, 7.2 mmol) and Pd(dppf)Cl ₂ (240 mg, 328 µmol) at 25 °C. The reaction mixture was degassed and purged with N ₂ three times, and then was stirred at 85 °C for 12 hr under N ₂ . The reaction mixture was poured into H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (50 mL x 2). The combined organic layers were washed with brine (40 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Eluent of 0 ~ 60% EtOAc in petroleum ether), 4-((6-(4-fluorophenyl)-5-methyl-3-nitropyridin- 2-yl)amino)benzyl acetate (1.8 g, yield: 67%) was obtained as a yellow solid. MS: m/z = 396.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.95 (s, 1H), 8.52 (s, 1H), 7.74 - 7.68 (m, 4H), 7.37 - 7.30 (m, 4H), 5.02 (s, 2H), 2.33 (s, 3H), 2.05 (s, 3H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -111.84. Step 4: 4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-6-methyl-3H-im idazo[4,5-b]pyridin-3- yl)benzyl acetate To a solution of 4-((6-(4-fluorophenyl)-5-methyl-3-nitropyridin-2-yl)amino)be nzyl acetate (1.8 mg, 4.6 mmol) in DMSO (50 mL) were added 2-aminonicotinaldehyde (667 mg, 5.5 mmol) and Na ₂ S ₂ O ₄ (3.2 g, 18.2 mmol) at 25 °C. The mixture was stirred at 100 °C for 12hr. The reaction mixture was poured into H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (50 mL x 2). The combined organic layers were washed with brine (400 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified silica gel by flash chromatography (Eluent of 0 ~ 3% MeOH in CH ₂ Cl2), 4-(2-(2-aminopyridin-3-yl)-5-(4-fluorophenyl)-6-methyl-3H-im idazo[4,5-b]pyridin-3- yl)benzyl acetate (1.4 g, yield: 52%) was obtained as a yellow solid. MS: m/z = 468.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.14 (s, 1H), 7.99 (dd, J = 4.8, 2.0 Hz, 1H), 7.56 - 7.51 (m, 2H), 7.50 - 7.43 (m, 4H), 7.27 (t, J = 8.8 Hz, 2H), 7.18 (dd, J = 7.6, 1.6 Hz, 1H), 6.92 (s, 2H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 5.13 (s, 2H), 2.43 (s, 3H), 2.08 (s, 3H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -114.38. Step 5: (4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-6-methyl-3H-i midazo[4,5-b]pyridin-3- yl)phenyl)methanol To a solution of 4-(2-(2-aminopyridin-3-yl)-5-(4-fluorophenyl)-6-methyl-3H-im idazo[4,5- b]pyridin-3-yl)benzyl acetate (1.3 g, 2.8 mmol) in H ₂ O (1 mL), MeOH (3 mL) and THF (3 mL) was added K ₂ CO ₃ (769 mg, 5.6 µmol) at 25 °C. The mixture was stirred at 25 °C for 1 hr. The reaction mixture was poured into H ₂ O (50 mL) and extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (40 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. (4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-6-methyl-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (860 mg, yield: 57%) was obtained as a yellow solid. MS: m/z = 426.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.13 (s, 1H), 7.99 (dd, J = 4.8, 2.0 Hz, 1H), 7.53 (dd, J = 8.4, 5.6 Hz, 2H), 7.45 - 7.36 (m, 4H), 7.26 (t, J = 9.2 Hz, 2H), 7.18 (dd, J = 7.6, 1.6 Hz, 1H), 7.00 (s, 2H), 6.40 (dd, J = 7.85, 4.8 Hz, 1H), 5.31 (t, J = 6.0 Hz, 1H), 4.55 (d, J = 6.0 Hz, 2H), 2.43 (s, 3H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -114.42. Step 6: 3-(3-(4-(Chloromethyl)phenyl)-5-(4-fluorophenyl)-6-methyl-3H -imidazo[4,5-b]pyridin- 2-yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-5-(4-fluorophenyl)-6-methyl-3H-i midazo[4,5- b]pyridin-3-yl)phenyl)methanol (200 mg, 470 µmol) in CH2Cl ₂ (5 mL) was added SOCl2 (280 mg, 2.4 mmol) at 25 °C. The mixture was stirred at 40 °C for 0.5 hr. The reaction mixture was concentrated under reduced pressure to give 3-(3-(4-(chloromethyl)phenyl)-5-(4-fluorophenyl)- 6-methyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (200 mg, crude) as a yellow solid, which was used in the next step without further purification. MS: m/z = 444.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.15 (s, 1H), 8.00 (dd, J = 4.8, 1.6 Hz, 1H), 7.60 - 7.51 (m, 4H), 7.45 (d, J = 8.0 Hz, 2H), 7.27 (t, J = 8.8 Hz, 2H), 7.22 - 7.17 (m, 1H), 6.97 (br s, 2H), 6.43 (dd, J = 7.2, 4.8 Hz, 1H), 4.82 (s, 2H), 2.44 (s, 3H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -114.34. Step 7: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-6-methy l-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile To a solution of 3-(3-(4-(chloromethyl)phenyl)-5-(4-fluorophenyl)-6-methyl-3H -imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (200 mg, 451 µmol) in DMF (3 mL) were added Intermediate 51 (110 mg, 541 µmol), NaI (34 mg, 225 µmol) and K ₂ CO ₃ (249 mg, 1.8 mmol) at 25 °C. The mixture was stirred at 40 °C for 1 hr. The reaction mixture was poured into H ₂ O (50 mL) and extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (40 mL), dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated to dryness. After purified by silica gel flash chromatography (Eluent of 0~5% MeOH in CH ₂ Cl ₂ ), 4-((1-(4-(2-(2- aminopyridin-3-yl)-5-(4-fluorophenyl)-6-methyl-3H-imidazo[4, 5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile (Example 499, 126.3 mg, yield: 45% for two steps) was obtained as a yellow solid. MS: m/z = 611.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.15 (s, 1H), 8.09 (d, J = 6.0 Hz, 1H), 8.04 (d, J = 7.2 Hz, 1H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.58 - 7.51 (m, 2H), 7.46 - 7.36 (m, 4H), 7.31 - 7.25 (m, 2H), 7.11 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.37 (dd, J = 7.6, 4.4 Hz, 1H), 3.87 - 3.73 (m, 1H), 3.55 (s, 2H), 2.85 - 2.75 (m, 2H), 2.44 (s, 3H), 2.20 - 2.06 (m, 2H), 1.94 - 1.80 (m, 2H), 1.55 - 1.41 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -114.39. [001029] Example 500: 2-(2-Aminopyridin-3-yl)-1-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin-1-yl)methyl)phenyl)-1H-benzo[d]imidazole- 6-carbonitrile Step 1: 3-((4-(Hydroxymethyl)phenyl)amino)-4-nitrobenzonitrile To a solution of 3-fluoro-4-nitrobenzonitrile (6.74 g, 40.6 mmol) and (4-aminophenyl)methanol (5 g, 40.6 mmol) in DMSO (50 mL) was added DIEA (26 g, 203 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was diluted with H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (100 mL x 3). The combined organic layers were washed with brine (120 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. 3-((4- (Hydroxymethyl)phenyl)amino)-4-nitrobenzonitrile (10.5 g, crude) was obtained as a yellow solid. ¹ H NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ 9.47 (s, 1H), 8.23 (d, J = 8.8 Hz, 1H), 7.42 - 7.37 (m, 3H), 7.33 - 7.28 (m, 2H), 7.20 (dd, J = 8.8, 2.0 Hz, 1H), 5.23 (t, J = 5.6 Hz, 1H), 4.52 (d, J = 6.0 Hz, 2H). Step 2: 4-((5-Cyano-2-nitrophenyl)amino)benzyl acetate To a solution of 3-((4-(hydroxymethyl)phenyl)amino)-4-nitrobenzonitrile (5 g, 18.6 mmol) and TEA (5.64 g, 56 mmol) in CH ₂ Cl ₂ (50 mL) were added Ac ₂ O (2.84 g, 28 mmol) and DMAP (227 mg, 1.86 mmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was diluted with H ₂ O (300 mL) and extracted with CH ₂ Cl ₂ (200 mL x 3). The combined organic layers were washed with brine (300 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 10% EtOAc in petroleum ether), 4-((5-cyano-2-nitrophenyl)amino)benzyl acetate (5.5 g, yield: 95%) was obtained as a red solid. ¹ H NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ 9.45 (s, 1H), 8.23 (d, J = 8.8 Hz, 1H), 7.51 (d, J = 1.6 Hz, 1H), 7.45 - 7.41 (m, 2H), 7.37 - 7.32 (m, 2H), 7.25 (dd, J = 8.8, 1.6 Hz, 1H), 5.08 (s, 2H), 2.08 (s, 3H). Step 3: 4-(2-(2-Aminopyridin-3-yl)-6-cyano-1H-benzo[d]imidazol-1-yl) benzyl acetate A mixture of 4-((5-cyano-2-nitrophenyl)amino)benzyl acetate (3 g, 9.65 mmol) , 2- aminonicotinaldehyde (1.29 g, 10.6 mmol), Na ₂ S ₂ O ₄ (7.9 g, 39 mmol) in DMSO (30 mL) was degassed and purged with N ₂ three times, and then was stirred at 100 °C for 16 hr under N ₂ atmosphere. The reaction mixture was diluted with H ₂ O (100 mL) and extracted with CH ₂ CI ₂ (200 mL x 3). The combined organic layers were washed with brine (300 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 10 ~ 50% EtOAc in petroleum ether and 50% CH ₂ CI ₂ in MeOH), 4- (2-(2-aminopyridin-3-yl)-6-cyano-1H-benzo[d]imidazol-l-yl)be nzyl acetate (600 mg, yield: 16%) was obtained as a yellow solid. MS: m/z = 384.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ 8.03 - 7.94 (m, 2H), 7.76 - 7.68 (m, 2H), 7.59 - 7.46 (m, 4H), 7.21 (dd, J = 7.6, 1.6 Hz, 1H), 6.91 (s, 2H), 6.42 (dd, J= 7.6, 4.8 Hz, 1H), 5.17 (s, 2H), 2.11 (s, 3H). Step 4: 2-(2- Aminopyridin-3 -yl)- 1 -(4-(hy droxymethyl)phenyl)- 1H-benzo[d]imidazole-6- carbonitrile

To a solution of 4-(2-(2-aminopyridin-3-yl)-6-cyano-1H-benzo[d]imidazol-l-yl) benzyl acetate (570 mg, 1.49 mmol) in THF (2 mL) was added K ₂ CO ₃ (616 mg, 4.46 mmol) in MeOH (2 mL) and H ₂ O (2 mL). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was diluted with H ₂ O (20 mL) and extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. 2-(2- Aminopyridin-3 -yl)- 1 -(4-(hy droxymethyl)phenyl)- 1H-benzo[d]imidazole-6- carbonitrile (500 mg, crude) was obtained as a yellow solid. MS: m/z = 342.0 [M + H] ⁺ . Step 5 : 2-(2- Aminopyridin-3 -yl)- 1 -(4-(chloromethyl)phenyl)- 1H-benzo[d]imidazole-6- carbonitrile

To a solution of 2 -(2-aminopyridin-3-yl)-l-(4-(hydroxymethyl)phenyl)-1H-benzo[ d] imidazole- 6-carbonitrile (500 mg, 1.46 mmol) in CH ₂ CI ₂ (2 mL) was added SOCl ₂ (348 mg, 2.93 mmol). The mixture was stirred at 50 °C for 1 hr and then concentrated under reduced pressure. 2-(2- Aminopyridin-3 -yl)- 1 -(4-(chloromethyl)phenyl)- 1H-benzo[d]imidazole-6-carbomtrile (530 mg, crude) was obtained as a yellow solid. MS: m/z = 360.0 [M + H] ⁺ .

Step 6 : 2-(2- Aminopyridin-3 -yl)- 1 -(4-((4-((2-cy anopyrimidin-4-yl)amino)piperidin- 1 - yl)methyl)phenyl)-1H-benzo[d]imidazole-6-carbomtrile

To a solution of 2-(2-aminopyridin-3-yl)-l-(4-(chloromethyl)phenyl)-1H-benzo[ d]imidazole-6- carbonitrile (300 mg, 757 μmol) and Intermediate 51 (240 mg, 757 μmol) in DMF (3 mL) were added Nal (56.7 mg, 379 μmol) and K ₂ CO ₃ (418 mg, 3.03 mmol). The mixture was stirred at 25 °C for 16 hr. The reaction mixture was diluted with H ₂ O (15 mL) and extracted with EtOAc (20 mL x 2). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by prep-HPLC (column: Phenomenex C18150 x 25 mm x 10 um; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 35% - 65% B over 11 min), 2-(2-aminopyridin-3-yl)-1-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin-1-yl)methyl)phenyl)-1H-benzo[d]imidazole- 6-carbonitrile (Example 500, 157.7 mg, yield: 40%) was obtained as a yellow powder. MS: m/z = 527.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ 8.30 - 7.90 (m, 4H), 7.78 - 7.65 (m, 2H), 7.54 - 739 (m, 4H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (s, 2H), 6.84 - 6.63 (m, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.89 - 3.74 (m, 1H), 3.59 (s, 2H), 2.83 (d, J = 11.2 Hz, 2H), 2.15 (t, J = 10.8 Hz, 2H), 1.95 - 1.80 (m, 2H), 1.56 – 1.43 (m, 2H). [001030] Example 501: 2-(2-Aminopyridin-3-yl)-1-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin-1-yl)methyl)phenyl)-1H-benzo[d]imidazole- 5-carbonitrile Step 1: 4-((4-(Hydroxymethyl)phenyl)amino)-3-nitrobenzonitrile To a solution of 4-chloro-3-nitrobenzonitrile (5 g, 27 mmol) and (4-aminophenyl)methanol (4.05 g, 33 mmol) in DMSO (50 mL) was added DIEA (8.85 g, 68 mmol). The mixture was stirred at 100 °C for 1 hr. The mixture was added H ₂ O (500 mL), and stirred at 5 °C for 10 min. After filtration, 4-((4-(hydroxymethyl)phenyl)amino)-3-nitrobenzonitrile (7.7 g) was obtained as a yellow solid. ¹ H NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ 9.89 (s, 1H), 8.58 (d, J = 2.0 Hz, 1H), 7.75 (dd, J = 8.8, 2.0 Hz, 1H), 7.42 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 7.04 (d, J = 9.2 Hz, 1H), 5.27 (t, J = 5.6 Hz, 1H), 4.53 (d, J = 5.6 Hz, 2H). Step 2: 4-((4-Cyano-2-nitrophenyl)amino)benzyl acetate To a solution of 4-((4-(hydroxymethyl)phenyl)amino)-3-nitrobenzonitrile (7.7 g, 28.6 mmol) and TEA (8.68 g, 86 mmol) in CH ₂ Cl ₂ (70 mL) were added Ac ₂ O (5.84 g, 57 mmol) and DMAP (349 mg, 2.9 mmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was diluted with H ₂ O (300 mL) and extracted with CH ₂ Cl ₂ (200 mL x 3). The combined organic layers were washed with brine (130 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 10 ~ 50% EtOAc in petroleum ether), 4-((4-cyano-2-nitrophenyl)amino)benzyl acetate (7.4 g, yield: 83%) was obtained as a yellow solid. ¹ H NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ 9.89 (s, 1H), 8.59 (d, J = 2.0 Hz, 1H), 7.77 (dd, J = 8.8, 2.0 Hz, 1H), 7.47 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.11 (d, J = 8.8 Hz, 1H), 5.10 (s, 2H), 2.08 (s, 3H). Step 3: 4-(2-(2-Aminopyridin-3-yl)-5-cyano-1H-benzo[d]imidazol-1-yl) benzyl acetate A mixture of 4-((4-cyano-2-nitrophenyl)amino)benzyl acetate (7.4 g, 24 mmol), 2- aminonicotinaldehyde (3.19 g, 26 mmol), Na ₂ S ₂ O ₄ (16.6 g, 95 mmol) in DMSO (200 mL) was degassed and purged with N ₂ three times, and then was stirred at 100 °C for 16 hr under N ₂ atmosphere. The reaction mixture was diluted with H ₂ O (300 mL) and extracted with CH ₂ Cl ₂ (200 mL x 3). The combined organic layers were washed with brine (150 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 50% EtOAc in petroleum ether), 4-(2-(2-aminopyridin-3-yl)-5- cyano-1H-benzo[d]imidazol-1-yl)benzyl acetate (3.6 g, yield: 33%) was obtained as a yellow solid. MS: m/z = 384.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ 8.37 (s, 1H), 8.00 (dd, J = 4.8, 1.6 Hz, 1H), 7.71 - 7.66 (m, 1H), 7.60 - 7.53 (m, 2H), 7.50 - 7.45 (m, 2H), 7.36 - 7.33 (m, 1H), 7.22 (dd, J = 7.6, 2.0 Hz, 1H), 6.88 (br s, 2H), 6.42 (dd, J = 7.6, 4.8 Hz, 1H), 5.17 (s, 2H), 2.11 (s, 3H). Step 4: 2-(2-Aminopyridin-3-yl)-1-(4-(hydroxymethyl)phenyl)-1H-benzo [d]imidazole-5- carbonitrile To a solution of 4-(2-(2-aminopyridin-3-yl)-5-cyano-1H-benzo[d]imidazol-1-yl) benzyl acetate (700 mg, 1.83 mmol) in THF (2 mL) were added K ₂ CO ₃ (757 mg, 5.48 mmol), MeOH (2 mL) and H ₂ O (2 mL). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was diluted with H ₂ O (20 mL) and extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. 2-(2-Aminopyridin-3-yl)-1-(4-(hydroxymethyl)phenyl)-1H-benzo [d]imidazole-5- carbonitrile (500 mg, crude) was obtained as a yellow solid. MS: m/z = 342.0 [M + H] ⁺ . Step 5: 2-(2-Aminopyridin-3-yl)-1-(4-(chloromethyl)phenyl)-1H-benzo[ d]imidazole-5- carbonitrile To a solution of 2-(2-aminopyridin-3-yl)-1-(4-(hydroxymethyl)phenyl)-1H-benzo [d]imidazole- 5-carbonitrile (500 mg, 1.46 mmol) in CH ₂ Cl ₂ (2 mL) was added SOCl ₂ (348 mg, 2.93 mmol). The mixture was stirred at 50 °C for 1 hr. The mixture was concentrated under reducedpressure to give 2-(2-aminopyridin-3-yl)-1-(4-(chloromethyl)phenyl)-1H-benzo[ d]imidazole-5- carbonitrile (500 mg, crude) as a yellow solid. MS: m/z = 359.9 [M + H] ⁺ . Step 6 : 2-(2-Aminopyridin-3 -yl)- 1 -(4-((4-((2-cy anopyrimidin-4-yl)amino)piperidin- 1 - yl)methyl)phenyl)-1H-benzo[d]imidazole-5-carbonitrile

To a solution of 2-(2-aminopyridin-3-yl)-l-(4-(chloromethyl)phenyl)-1H-benzo[ d]imidazole-5- carbonitrile (200 mg, 556 μmol) and Intermediate 51 (212 mg, 667 μmol) in DMF (3 mL) were added Nal (83.3 mg, 556 μmol) and K ₂ CO ₃ (230 mg, 1.67 mmol). The mixture was stirred at 50 °C for 1 hr. The reaction mixture was diluted with H ₂ O (15 mL) and extracted with EtOAc (20 mL x 2). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by prep-HPLC (column: Phenomenex C18 150 x 25 mm x 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 35% - 55% B over 11 min), 2-(2-aminopyridin-3-yl)-l-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin- 1 -yl)methyl)phenyl)- 1H-benzo[d]imidazole-5 -carbonitrile (Example 501, 30.4 mg, yield: 10%) was obtained as an off white solid. MS: m/z = 527.1 [M + H] ⁺ . ¹ HNMR (400 MHz, Methanol^) δ 8.22 (d, J= 1.2 Hz, 1H), 8.08 - 7.95 (m, 2H), 7.67 - 7.58 (m, 3H), 7.45 - 7.38 (m, 3H), 7.30 (dd, J= 7.6, 1.6 Hz, 1H), 6.62 (d, J= 5.2 Hz, 1H), 6.46 (dd, J= 7.6, 5.2 Hz, 1H), 4.04 - 3.88 (m, 1H), 3.68 (s, 2H), 2.96 (d, J= 11.6 Hz, 2H), 2.28 (t, J= 10.8 Hz, 2H), 2.07 - 1.99 (m, 2H), 1.68 - 1.57 (m, 2H).

[001031] Example 502: 4-((l-((4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin- 3- yl)phenyl)methyl-d ₂ )piperidin-4-yl)(methyl-d ₃ )amino)pyrimidine-2-carbonitrile

Step 1 : (4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)ph enyl)methan-d ₂ -ol To a mixture of methyl 4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)ben zoate (300 mg, 869 μmol) in THF (5 mL) was added LiAlD4 (42.9 mg, 1.13 mmol). The mixture was purged with N2 three times and stirred at 25 °C for 1 hr under N ₂ atmosphere. The reaction mixture was filtered and concentrated under reduced pressure. (4-(2-(2-Aminopyri din-3 -yl)-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methan-d ₂ -ol (270 mg, yield: 97.3%) was obtained as a pink solid. MS: m/z = 319.9 [M + H] ⁺ .

Step 2 : 3 -(3 -(4-(Chloromethyl-d ₂ )phenyl)-3H-imidazo[4, 5-b]pyridin-2-yl)pyridin-2-amine To a solution of (4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)ph enyl)methan-d ₂ - ol (270 mg, 845 μmol) in CH ₂ CI ₂ (5 mL) was added SOCI ₂ (101 mg, 845 μmol). The mixture was stirred at 40 °C for 1 hr. The reaction mixture was quenched with H ₂ O (0.5 mL) at 0 °C, filtered and concentrated under reduced pressure. 3-(3-(4-(Chloromethyl-d ₂ )phenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (300 mg, HC1 salt, yield: 94.8%) was obtained as a pink solid. MS: m/z = 338.0 [M + H] ⁺ .

Step 3: Tert-butyl (l-((4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)phenyl)methyl-d ₂ )piperidin-4-yl)(methyl-d ₃ )carbamate

To a solution of 3-(3-(4-(chloromethyl-d ₂ )phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2- amine (300 mg, 802 μmol, HC1 salt), tert-butyl (methyl-d ₃ )(piperidin-4-yl)carbamate (174 mg, 802 μmol) in DMF (5 mL) were added Nal (24.0 mg, 160 μmol) and K ₂ CO ₃ (332 mg, 2.40 mmol). The mixture was stirred at 50 °C for 1 hr. The mixture was diluted with H ₂ O (20 mL) and extracted with CH ₂ CI ₂ (30 mL x 3). The combined organic layers were washed with brine (30 mL x 4), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 3 ~ 8% CH ₂ CI ₂ in MeOH), tert-butyl (1- ((4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)p henyl)methyl-d ₂ )piperidin-4- yl)(methyl-d ₃ )carbamate (340 mg, yield: 67.1%) was obtained as a purple solid. MS: m/z = 519.2 [M + H] ⁺ . ¹ HNMR (400MHz, Chloroform^ 5 8.46 - 8.36 (m, 1H), 8.13 - 8.04 (m, 2H), 7.65 - 7.48 (m, 2H), 7.38 - 7.30 (m, 3H), 7.10 - 7.04 (m, 1H), 6.65 - 6.56 (m, 2H), 6.38 - 6.33 (m, 1H), 3.09 - 2.99 (m, 1H), 2.34 - 2.08 (m, 2H), 1.94 - 1.71 (m, 2H), 1.71 - 1.62 (m, 4H), 1.48 (s, 9H).

Step 4 : 3 -(3 -(4-((4-((Methyl-d3)amino)piperidin- 1 -yl)methyl-d2)pheny l)-3H-imidazo[4, 5- b]pyridin-2-yl)pyridin-2-amine

To a solution of tert-butyl (l-((4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)phenyl)methyl-d ₂ )piperidin-4-yl)(methyl-d ₃ )carbamate (340 mg, 656 μmol) in MeOH (1 mL) was added HC1 in dioxane (4 M, 163.88 μL). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was filtered and concentrated under reduced pressure. 3-(3-(4-((4-((Methyl- d3)amino)piperidin-l-yl)rnethyl-d ₂ )phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (280 mg, yield: 93.8%) was obtained as a pink solid. MS: m/z = 419.3 [M + H] ⁺ . ¹ HNMR (400MHz, Methanol-d ₄ ) δ 8.46 (dd, J= 4.8, 1.2 Hz, 1H), 8.34 (dd, J= 8.0, 1.2 Hz, 1H), 8.02 (dd, J= 6.0, 1.2 Hz, 1H), 7.90 - 7.85(m, 3H), 7.66 (d, J= 8.4 Hz, 2H), 7.54 (dd, J= 8.0, 4.8 Hz, 1H), 6.87 (dd, J= 7.6, 6.4 Hz, 1H), 3.74 - 3.70 (m, 2H), 3.51 - 3.43 (m, 1H), 3.28 - 3.21 (m, 2H), 2.41 - 2.34 (m, 2H), 2.16 - 2.03 (m, 2H). Step 5: 4-((l-((4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin- 3-yl)phenyl)methyl- d2)piperidin-4-yl)(methyl-d3)amino)pyrimidine-2-carbonitrile

To a solution of 3-(3-(4-((4-((methyl-d ₃ )amino)piperidin-l-yl)methyl-d ₂ )phenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (150 mg, 358.38 μmol), 4-chloropyrimidine-2- carbonitrile (50.0 mg, 358 μmol) in NMP (3 mL) was added DIEA (139 mg, 1.08 mmol). The mixture was stirred at 130 °C for 0.5 hr. After purified by prep-HPLC (column: Welch Xtimate C ₁ 8 150 x 25 mm x 5 μm; mobile phase: [water (HC1) - ACN]; gradient: 0% - 25% B over 8 min), the cbrude product was neutralized with sarurated NaHCO ₃ and extracted with CH ₂ CI ₂ (10 mL x 3). The combined organic layers were washed with brine (10 mL x 2), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. 4-((l-((4-(2-(2-Aminopyridin-3-yl)-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methyl-d ₂ )piperidin-4-yl)(methyl-d ₃ )amino)pyrimidine-2- carbonitrile (Example 502, 37.3 mg, yield: 18.2%) was obtained as a yellow solid. MS: m/z = 522.3 [M + H] ⁺ . ¹ HNMR (400MHz, Methanol-d ₄ ) δ 8.34 (dd, J= 4.8, 1.2 Hz, 1H), 8.20 (dd, J= 8.0, 1.2 Hz, 1H), 8.16 (d, J= 6.4 Hz, 1H), 7.98 (dd, J= 5.2, 2.0 Hz, 1H), 7.55 (d, J= 8.4 Hz, 2H), 7.45 - 7.39 (m, 3H), 7.32 (dd, J= 7.6, 2.0 Hz, 1H), 6.90 - 6.76 (m, 1H), 6.46 (dd, J= 7.6, 5.2 Hz, 1H), 3.30 - 3.27 (m, 1H), 3.06 (br d, J= 12.0 Hz, 2H), 2.31 - 2.23 (m, 2H), 1.99 - 1.90 (m, 2H), 1.71 - 1.67 (m, 2H).

[001032] Example 503: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3 - yl)benzyl)piperidin-4-yl-4-d)amino)pyrimidine-2-carbonitrile

Example 503 was prepared in a manner similar to Example 261. MS: m/z = 504.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.33 (d, J= 4.8 Hz, 1H), 8.21 (d, J= 8.0 Hz, 1H), 8.12 - 8.03 (m, 2H), 7.99 (dd, J= 4.4, 1.2 Hz, 1H), 7.47 - 7.43 (m, 2H), 7.41 - 7.36 (m, 3H), 7.16 (dd, J= 7.6, 1.6 Hz, 1H), 7.01 (s, 2H), 6.67 (d, J= 6.0 Hz, 1H), 6.37 (dd, J= 7.6, 4.8 Hz, 1H), 3.56 (s, 2H), 2.85 - 2.77 (m, 2H), 2.19 - 2.09 (m, 2H), 1.92 - 1.82 (m, 2H), 1.53 - 1.43 (m, 2H).

[001033] Example 504: 4-((l-((4-(2-(2-Aminopyridin-3-yl)-5,6-dimethyl-3H-imidazo[4 ,5- b]pyridin-3-yl)phenyl)methyl-d ₂ )piperidin-4-yl)amino)pyrimidine-2-carbonitrile

Step 1 : (4-(2-(2-Aminopyridin-3-yl)-5,6-dimethyl-3H-imidazo[4,5-b]py ridin-3- yl)phenyl)methan-d2-ol

To a mixture of methyl 4-(2-(2-aminopyridin-3-yl)-5,6-dimethyl-3H-imidazo[4,5-b]pyr idin-3- yl)benzoate (refer to Intermediate 138 for detail procedures, 290 mg, 777 μmol) in THF (20 mL) was added Li AID4 (2.5 M in THF, 80 μL). The mixture was degassed and purged with N ₂ three times and stirred at 0 °C for 2 hr under N2 atmosphere. The reaction mixture was quenched with Na ₂ SO ₄ ·10H ₂ O (1.0 g) at 0 °C, filtered, and concentrated. (4-(2-(2-Aminopyridin-3-yl)-5,6- dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)methan-d2-ol (260 mg, yield: 96%) was obtained as a yellow solid. MS: m/z = 347.9 [M + H] ⁺ .

Step 2: 3-(3-(4-(Chloromethyl-d2)phenyl)-5,6-dimethyl-3H-imidazo[4,5 -b]pyridin-2-yl)pyridin- 2-amine

To a solution of (4-(2-(2-aminopyridin-3-yl)-5,6-dimethyl-3H-imidazo[4,5-b]py ridin-3- yl)phenyl)methan-d2-ol (260 mg, 748 μmol) in CH ₂ CI ₂ (15 mL) was added SOCl ₂ (534 mg, 4.49 mmol). The mixture was stirred at 40 °C for 1 hr. The mixture was concentrated to give 3-(3- (4-(chloromethyl-d2)phenyl)-5,6-dimethyl-3H-imidazo[4,5-b]py ridin-2-yl)pyridin-2-amine (270 mg, yield: 99%) as a yellow solid. MS: m/z = 366.0 [M + H] ⁺ .

Step 3 : 4-((l-((4-(2-(2-Aminopyridin-3-yl)-5,6-dimethyl-3H-imidazo[4 ,5-b]pyridin-3- yl)phenyl)methyl-d ₂ )piperidin-4-yl)amino)pyrimidine-2-carbonitrile

To a solution of 3-(3-(4-(chloromethyl-d2)phenyl)-5,6-dimethyl-3H-imidazo[4,5 -b]pyridin-2- yl)pyridin-2-amine (250 mg, 683 μmol) and Intermediate 51 (139 mg, 683 μmol) in DMF (5 mL) were added Nal (51.2 mg, 342 μmol) and K ₂ CO ₃ (472 mg, 342 μmol). The mixture was stirred at 50 °C for 1 hr. The reaction mixture was filtered. After purified by prep-HPLC (column: Waters xbridge 150 x 25 mm 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 32% - 62% B over 10 min), 4-((l-((4-(2-(2-aminopyridin-3-yl)-5,6-dimethyl-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methyl-d ₂ )piperidin-4-yl)amino)pyrimidine-2-carbonitrile (Example 504, 66 mg, yield: 18%) was obtained as a yellow solid. MS: m/z = 533.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.11 - 8.05 (m, 2H), 7.97 - 7.94 (m, 2H), 7.45 (d, J = 8.0 Hz, 2H), 7.34 (d, J= 8.0 Hz, 2H), 7.07 - 7.03 (m, 3H), 6.67 (d, J = 6.0 Hz, IH), 6.33 (dd, J = 7.6, 4.8, 1H), 3.81 - 3.77 (m, 1H), 2.84 - 2.80 (m, 2H), 2.45 (s, 3H), 2.39 (s, 3H), 2.16 - 2.11 (m, 2H), 1.91 - 1.86 (m, 2H), 1.52 - 1.45 (m, 2H).

[001034] Example 505: 4-((l-(4-(8-(2-Aminopyridin-3-yl)-9H-purin-9- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile

Step 1 : Methyl 4-((6-chloro-5-nitropyrimidin-4-yl)amino)benzoate

To a mixture of 4,6-dichloro-5-nitropyrimidine (3.0 g, 15.5 mmol) and methyl 4-aminobenzoate (1.87 g, 12.4 mmol) in THF (20 mL) was added TEA (1.41 g, 13.9 mmol). The mixture was degassed and purged with N ₂ three times and stirred at 0 °C for 4 hr under N2 atmosphere. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (50 mL x 3). The combined organic layers were washed with brine (100 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 8% EtOAc in petroleum ether), methyl 4-((6-chloro-5-nitropyrimidin-4- yl)amino)benzoate (3.0 g, yield: 61%) was obtained as a yellow solid. MS: m/z = 308.9 [M + H] ⁺ , ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.32 (s, 1H), 8.63 (s, 1H), 7.97 (d, J= 8.8 Hz, 2H), 7.74 (d, J= 8.8 Hz, 2H), 3.85 (s, 3H)

Step 2: Methyl 4-((5-aminopyrimidin-4-yl)amino)benzoate

To a solution of methyl 4-((6-chloro-5-nitropyrimidin-4-yl)amino)benzoate (1.5 g, 4.86 mmol) in MeOH (20 mL) was added Pd/C (517 mg, 486 μmol, 10% purity). The mixture was degassed and purged with H ₂ three times and stirred at 25 °C for 16 hr under H ₂ . The reaction mixture was filtered and concentrated to give methyl 4-((5-aminopyrimidin-4-yl)amino)benzoate (1 g, yield: 78%) as a brown solid. MS: m/z = 244.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.31 (s, 1H), 8.45 (s, 1H), 7.99 (br.s, 4H), 7.82 (s, 1H), 6.77 - 5.98 (m, 2H), 3.85 (s, 3H).

Step 3: Methyl 4-(8-(2-aminopyri din-3 -yl)-9H-purin-9-yl)benzoate A mixture of methyl 4-((5-aminopyrimidin-4-yl)amino)benzoate (1.0 g, 4.09 mmol), 2- aminonicotinaldehyde (550 mg, 4.50 mmol) and Cu(Oac) ₂ (149 mg, 819 mmol) in CH ₃ COOH (100 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 60 °C for 16 hr under N ₂ atmosphere. The reaction mixture was neutralized with NH ₃ ·H ₂ O (adjusted pH to 7 ~ 8). The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (200 mL x 3). The combined organic layers were washed with brine (200 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0 ~ 8% MeOH in CH ₂ Cl ₂ ), methyl 4-(8-(2-aminopyridin-3-yl)-9H- purin-9-yl)benzoate(300 mg, yield: 17%) was obtained as a yellow solid. MS: m/z = 347.0 [M + H] ⁺ , ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.29 (s, 1H), 8.94 (s, 1H), 8.10 - 9.08 (m, 2H), 8.04 (dd, J = 4.8, 2.0 Hz, 1H), 7.63 - 7.61 (m, 2H), 7.35 (d, J = 6.4 Hz, 1H), 6.79 (s, 2H), 6.50 (dd, J = 7.6, 5.2 Hz, 1H), 3.89 (s, 3H) Step 4: (4-(8-(2-Aminopyridin-3-yl)-9H-purin-9-yl)phenyl)methanol To a mixture of methyl 4-(8-(2-aminopyridin-3-yl)-9H-purin-9-yl)benzoate (300 mg, 866 µmol) in THF (20 mL) was added LiAlH ₄ (2.5 M in THF, 693 μL). The mixture was degassed and purged with N ₂ three times and stirred at 0 °C for 2 hr under N ₂ atmosphere. The reaction mixture was quenched with Na ₂ SO ₄ ·10H ₂ O (1.0 g) at 0 °C, filtered, and concentrated. (4-(8-(2- Aminopyridin-3-yl)-9H-purin-9-yl)phenyl)methanol (202 mg, yield: 73%) was obtained as a yellow solid. MS: m/z = 319.0 [M + H] ⁺ . Step 5: 3-(9-(4-(Chloromethyl)phenyl)-9H-purin-8-yl)pyridin-2-amine To a solution of (4-(8-(2-aminopyridin-3-yl)-9H-purin-9-yl)phenyl)methanol (202 mg, 635 µmol) in CH ₂ Cl ₂ (20 mL) was added SOCl ₂ (453 mg, 3.81 mmol). The mixture was stirred at 40 °C for 1 hr. The mixture was concentrated to give 3-(9-(4-(chloromethyl)phenyl)-9H-purin-8- yl)pyridin-2-amine (103 mg, yield: 48%) as a yellow solid. MS: m/z = 337.0 [M + H] ⁺ . Step 6: 4-((1-(4-(8-(2-Aminopyridin-3-yl)-9H-purin-9-yl)benzyl)piper idin-4- yl)amino)pyrimidine-2-carbonitrile To a solution of 3-(9-(4-(chloromethyl)phenyl)-9H-purin-8-yl)pyridin-2-amine (103 mg, 306 µmol) and Intermediate 51 (62 mg, 306 µmol) in DMF (5 mL) were added NaI (22.3 mg, 153 µmol) and K ₂ CO ₃ (127 mg, 918 µmol). The mixture was stirred at 50 ºC for 1 hr. The reaction mixture was filtered. After purified by prep-HPLC (column: Waters xbridge 150 x 25 mm 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 20% - 50% B over 11 min), 4-((1-(4- (8-(2-Aminopyridin-3-yl)-9H-purin-9-yl)benzyl)piperidin-4-yl )amino)pyrimidine-2-carbonitrile (Example 505, 5 mg, yield: 3%) was obtained as a yellow solid. MS: m/z = 504.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.26 (s, 1H), 8.91 (s, 1H), 8.10 - 8.01 (m, 3H), 7.43 - 7.41 (m, 4H), 7.25 (dd, J = 8.0, 1.6 Hz, 1H), 6.87 (s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 3.84 - 3.78 (m, 1H), 3.56 (s, 2H), 2.83 - 2.77 (m, 2H), 2.17 - 2.09 (m, 2H), 1.91 - 1.82 (m, 2H), 1.52 - 1.43 (m, 2H) [001035] Example 506 and 507: (S)-4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(tetrahydrofuran- 3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)am ino)pyrimidine-2-carbonitrile & (R)-4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(tetrahydrofuran-3-y l)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile Example 417 (56 mg, 97.8 µmol) was submitted to SFC (column: DAICEL CHIRALPAK IG (250 ,mm x 30 mm, 10 um); mobile phase: [CO ₂ -i-PrOH (0.1% NH ₃ ·H ₂ O)]; B%: 50%, isocratic elution mode). (S)-4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(tetrahydrofuran-3-y l)-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile (Example 506, stereochemistry arbitrarily assigned, 12.9 mg, yield: 23%) was obtained as an off-white solid. MS: m/z = 573.3 [M + H] ⁺ . ¹ H NMR (400MHz, Dimethylsulfoxide-d ₆ ) δ 8.16 - 8.03 (M, 3H), 7.97 (dd, J = 4.8, 1.6 Hz, 1H), 7.46 - 7.42 (m, 2H), 7.38 - 7.33 (m, 3H), 7.10 (d, J = 7.6 Hz, 1H), 6.96 (s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 4.04 (t, J = 8.0 Hz, 1H), 3.93 - 3.86 (m, 1H), 3.84 - 3.68 (m, 3H), 3.66 - 3.56 (m, 3H), 2.86 - 2.77 (m, 2H), 2.31 - 2.21 (m, 1H), 2.17 - 2.05 (m, 3H), 1.94 - 1.83 (m, 2H), 1.54 - 1.42 (m, 2H). (R)-4-((1-(4-(2-(2- aminopyridin-3-yl)-5-(tetrahydrofuran-3-yl)-3H-imidazo[4,5-b ]pyridin-3-yl)benzyl)piperidin-4- yl)amino)pyrimidine-2-carbonitrile (Example 507, stereochemistry arbitrarily assigned, 15.9 mg, yield: 28%) was obtained as an off-white solid. MS: m/z = 573.2 [M + H] ⁺ . ¹ H NMR (400MHz, Dimethylsulfoxide-d ₆ ) δ 8.16 - 8.04 (m, 3H), 7.97 (dd, J = 4.8, 1.6 Hz, 1H), 7.47 - 7.42 (m, 2H), 7.39 - 7.32 (m, 3H), 7.10 (dd, J = 7.6, 1.2 Hz, 1H), 6.96 (s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 4.04 (t, J = 8.0 Hz, 1H), 3.92 - 3.86 (m, 1H), 3.84 - 3.67 (m, 3H), 3.66 - 3.56 (m, 3H), 2.85 - 2.77 (m, 2H), 2.31 - 2.21 (m, 1H), 2.20 - 2.03 (m, 3H), 1.93 - 1.82 (m, 2H), 1.54 - 1.43 (m, 2H). [001036] Example 508: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(hydroxymethyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

Step 1: Methyl 2-(2-aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)oxy) methyl)phenyl)-3H- imidazo[4,5-b]pyridine-5-carboxylate To a solution of methyl 2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imida zo[4,5- b]pyridine-5-carboxylate (refer to Intermediate 140 for detail procedures, 900 mg, 2.40 mmol) in CH ₂ Cl ₂ (10 mL) were added imidazole (245 mg, 3.60 mmol) and TBSCl (470 mg, 3.12 mmol) at 0 °C. This mixture was stirred at 25 °C for 1 hr. The mixture was quenched with H ₂ O (30 mL) and extracted with CH ₂ Cl ₂ (30 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated. Methyl 2-(2-aminopyridin-3-yl)-3- (4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-3H-imidazo[ 4,5-b]pyridine-5-carboxylate (1.10 g, yield: 93.7%) was obtained as a yellow solid. MS: m/z = 490.4 [M + H] ⁺ . Step 2: (2-(2-Aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)oxy )methyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)methanol To a solution of methyl 2-(2-aminopyridin-3-yl)-3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-3H-imidazo[4,5-b]pyrid ine-5-carboxylate (300 mg, 613 µmol) in THF (5 mL) was added LiAlH ₄ (34.9 mg, 919 µmol) at 0 ºC. The mixture was degassed and purged with N ₂ three times and stirred at 25 °C for 0.5 hr. The mixture was diluted with THF (20 mL). Na ₂ SO ₄ 10 H ₂ O was added in portions until no bubbles were formed. The resulting mixture was stirred at 25 °C for 20 min and filtered. The filter cake was washed with THF (20mL x 2). The combined filtrate was concentrated to give (2-(2- aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)oxy)methy l)phenyl)-3H-imidazo[4,5- b]pyridin-5-yl)methanol (244 mg, yield: 86.3%) as a yellow oil. MS: m/z = 462.4 [M + H] ⁺ . Step 3: (2-(2-Aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)oxy )methyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)methyl acetate To a solution of (2-(2-aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)oxy )methyl)phenyl)- 3H-imidazo[4,5-b]pyridin-5-yl)methanol (244 mg, 529 µmol) in CH ₂ Cl ₂ (10 mL) were added TEA (160 mg, 1.59 mmol), DMAP (6.46 mg, 52.9 μmol) and Ac ₂ O (80.9 mg, 793 μmol) at 25 °C. This mixture was stirred at 25 °C for 0.5 hr. The mixture was quenched with H ₂ O (50 mL) and extracted with EtOAc (30 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated. (2-(2-Aminopyridin-3-yl)-3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-3H-imidazo[4,5-b]pyrid in-5-yl)methyl acetate (240 mg, yield: 90.2%) was obtained as a yellow oil. MS: m/z = 504.4 [M + H] ⁺ .

Step 4: (2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imid azo[4,5-b]pyridin-5- yl)methyl acetate

To a solution of (2-(2-aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)oxy )methyl)phenyl)- 3H-imidazo[4,5-b]pyridin-5-yl)methyl acetate (240 mg, 476 μmol) in THF (10 mL) was added TBAF (IM in THF) (1 M, 714.76 μL) at 25 °C. This mixture was stirred at 25 °C for 1 hr. The mixture was quenched with H ₂ O (50 mL) and extracted with EtOAc (30 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated. (2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imid azo[4,5- b]pyridin-5-yl)methyl acetate (180 mg, yield: 97.0%) was obtained as a yellow oil. MS: m/z = 390.2 [M + H] ⁺ .

Step 5 : (2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imida zo[4,5-b]pyridin-5- yl)methyl acetate

To a solution of (2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imid azo[4,5- b]pyridin-5-yl)methyl acetate (180 mg, 462 μmol) in CH ₂ CI ₂ (10 mL) was added SOCI ₂ (82.5 mg, 693 μmol) at 25 °C. This mixture was stirred at 25 °C for 1 hr. The reaction mixture was concentrated to give (2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imida zo[4,5- b]pyridin-5-yl)methyl acetate (180 mg, yield: 95.5%) as a yellow oil. MS: m/z = 408.2 [M + H] ⁺ .

Step 6: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(hydroxymethyl)-3H-imida zo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile

To a solution of (2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imida zo[4,5- b]pyridin-5-yl)methyl acetate (230 mg, 564 μmol) and Intermediate (126 mg, 620 μmol) in DMF (3 mL) were added K ₂ CO ₃ (117 mg, 846 μmol) and Nal (8.45 mg, 56.4 μmol) at 25 °C. This mixture was stirred at 80 °C for 1 hr. The mixture was quenched with H ₂ O (30 mL) and extracted with EtOAc (30 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated. After purified by prep-HPLC (column: Phenomenex C18 75 x 30 mm x 3 μm; mobile phase: [water (NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN]; gradient: 31% - 61% B over 7 min), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(hydroxymethyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile (Example 508, 94.5 mg, yield: 31.5%) was obtained as a yellow solid. MS: m/z = 533.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.19 (d, J= 8.0 Hz, 1 H), 8.14 - 8.02 (m, 2 H), 7.97 (dd, J= 4.8, 2.0 Hz, 1 H), 7.50 (d, J= 8.4 Hz, 1 H), 7.45 (d, J= 8.0 Hz, 2 H), 7.36 (d, J= 8.4 Hz, 2 H), 7.10 (dd, J= 7.6, 1.6 Hz, 1 H), 7.02 (s, 2 H) 6.68 (d, J= 6.0 Hz, 1 H), 6.35 (dd, J= 7.6, 4.8 Hz, 1 H), 5.46 (t, J= 6.0 Hz, 1 H), 4.58 (d, J= 6.0 Hz, 2 H) 3.87 - 3.75 (m, 1 H) 3.57 (s, 2 H) 2.87 - 2.77 (m, 2 H) 2.21 - 2.09 (m, 2 H) 1.95 - 1.81 (m, 2 H) 1.56 - 1.42 (m, 2 H). [001037] Example 509: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(fluoromethyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

To a solution of Example 508 (70.0 mg, 131 μmol) in CH ₂ CI ₂ (3 mL) was added DAST (42.4 mg, 263 μmol) at 0 °C. The mixture was stirred at 0 °C for 1 hr. The mixture was quenched with saturated NaHCO ₃ (30 mL) and extracted with CH ₂ CI ₂ (30 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated. After purified by prep-HPLC (column: Phenomenex C18 75 x 30 mm x 3 μm; mobile phase: [water (NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN]; gradient: 40% - 70% B over 7 min), 4-((l-(4-(2-(2- aminopyridin-3-yl)-5-(fluoromethyl)-3H-imidazo[4,5-b]pyridin -3-yl)benzyl)piperi din-4- yl)amino)pyrimidine-2-carbonitrile (Example 509, 8.20 mg, yield: 11.7%) was obtained as a light yellow solid. MS: m/z = 535.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.27 (d, J= 8.0 Hz, 1 H), 8.18 - 8.02 (m, 2 H), 7.99 (d, J= 3.6 Hz, 1 H), 7.54 (d, J= 8.4 Hz, 1 H), 7.46 (d, J= 8.0 Hz, 2 H), 7.39 (d, J= 8.0 Hz, 2 H), 7.15 (d, J= 7.6 Hz, 1 H), 6.99 (s, 2 H), 6.68 (d, J= 6.0 Hz, 1 H), 6.36 (dd, J= 8.0, 5.2 Hz, 1 H), 5.50 (d, J= 47.2 Hz, 2 H), 3.89 - 3.75 (m, 1 H), 3.57 (s, 2 H), 2.88 - 2.76 (m, 2 H), 2.24 - 2.07 (m, 2 H), 1.96 - 1.80 (m, 2 H), 1.59 - 1.39 (m, 2 H).

[001038] Example 510: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(pyrrolidin-l-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 510 was prepared in a manner similar to Example 261. MS: m/z = 572.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.11 - 8.04 (m, 2H), 7.92 - 7.88 (m, 2H), 7.42 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 7.08 (s, 2H), 6.94 (dd, J = 7.6, 1.6 Hz, 1H), 6.67 (d, J = 6.0 Hz, 1H), 6.50 (d, J = 8.8 Hz, 1H), 6.29 (dd, J = 8.0, 5.2 Hz, 1H), 3.81 (br.s, 1H), 3.56 (s, 2H), 3.34 - 3.30 (m, 3H), 2.83 - 2.78 (m, 2H), 2.17 - 2.08 (m, 2H), 1.95 - 1.80 (m, 7H), 1.53 - 1.42 (m, 2H). [001039] Example 511: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-methoxypyridin-4-yl)- 3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile To a solution of Intermediate 199 (540 mg, 1.22 mmol) in DMF (5 mL) were added Intermediate 51 (273 mg, 1.34 mmol), DIEA (4.88 mmol, 849 μL). The mixture was stirred at 80 °C for 8 hr. After purified by prep-HPLC (column: Phenomenex C1875 x 30 mm x 3 μm; mobile phase: [water (NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN]; gradient: 46% - 76% B over 7 min), 4- ((1-(4-(2-(2-aminopyridin-3-yl)-5-(2-methoxypyridin-4-yl)-3H -imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile (Example 511, 169 mg, yield: 22.6%) was obtained as a light yellow solid. MS: m/z = 610.1 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.31 (d, J = 8.4 Hz, 1H), 8.24 (d, J = 5.2 Hz, 1H), 8.16 - 8.04 (m, 3H), 8.01 (dd, J = 4.8, 1.6 Hz, 1H), 7.62 (dd, J = 5.6, 1.2 Hz, 1H), 7.52 - 7.47 (m, 2H), 7.46 - 7.43 (m, 2H), 7.41 (s, 1H), 7.18 (dd, J = 8.0, 1.6 Hz, 1H), 7.05 (s, 2H), 6.69 (d, J = 5.6 Hz, 1H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.87 (s, 3H), 3.84 - 3.72 (m, 1H), 3.60 (s, 2H), 3.22 - 3.11 (m, 2H), 2.83 - 2.68 (m, 2H), 2.16 - 2.09 (m, 2H), 1.94 - 1.85 (m, 2H). [001040] Example 512: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(5-methoxypyridin-3-yl)- 3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 512 was prepared in a manner similar to Example 341. MS: m/z = 610.3 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.86 (d, J = 1.6 Hz, 1H), 8.32 - 8.30 (m, 2H), 8.14 - 8.03 (m, 3H), 8.01 (dd, J = 4.8, 2.0 Hz, 1H), 7.92 (dd, J = 2.8, 2.0 Hz, 1H), 7.52 - 7.44 (m, 4H), 7.19 (dd, J = 8.0, 2.0 Hz, 1H), 7.06 (s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 3.88 (s, 3H), 3.86 - 3.75 (m, 1H), 3.59 (s, 2H), 2.89 - 2.77 (m, 2H), 2.21 - 2.09 (m, 2H), 1.57 - 1.42 (m, 2H). [001041] Example 513: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-ethynyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile Step 1: 3-(3-(4-(((tert-Butyldimethylsilyl)oxy)methyl)phenyl)-5-ethy nyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine A solution of Intermediate 129 (1 g, 1.96 mmol), Pd(PPh3)4 (113 mg, 98 µmol) and tributyl(ethynyl)stannane (1.23 g, 3.92 mmol) in 1,4-dioxane (10 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 100 °C for 16 hr under N ₂ atmosphere. The reaction was concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 30 ~ 50% EtOAc in petroleum ether), 3-(3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-5-ethynyl-3H-imidazo[4 ,5-b]pyridin-2-yl)pyridin-2- amine (900 mg, yield: 60%) was obtained as a black solid. MS: m/z = 456.7 [M + H] ⁺ . Step 2: (4-(2-(2-Aminopyridin-3-yl)-5-ethynyl-3H-imidazo[4,5-b]pyrid in-3-yl)phenyl)methanol To a solution of 3-(3-(4-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-5-ethy nyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (160 mg, 351 μmol) in THF (4 mL) was added TBAF (92 mg, 351 μmol, 1 M). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was quenched with H ₂ O (10 mL) at 25 °C, and extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. (4-(2-(2-Aminopyridin-3-yl)-5-ethynyl-3H-imidazo[4,5-b]pyrid in-3-yl)phenyl)methanol (130 mg, yield: 63%) was obtained as a brown solid. MS: m/z = 341.9 [M + H] ⁺ .

Step 3 : 3-(3-(4-(Chloromethyl)phenyl)-5-ethynyl-3H-imidazo[4,5-b]pyr idin-2-yl)pyridin-2- amine

To a solution of (4-(2-(2-aminopyridin-3-yl)-5-ethynyl-3H-imidazo[4,5-b]pyrid in-3- yl)phenyl)methanol (130 mg, 381 μmol) in CH ₂ CI ₂ (5 mL) was added SOCI ₂ (90.7 mg, 762 μmol) at 0 °C. The mixture was stirred at 40 °C for 0.5 hr. The reaction mixture was quenched with H ₂ O (1 mL) at 25 °C, and concentrated under reduced pressure to give 3-(3-(4- (chloromethyl)phenyl)-5-ethynyl-3H-imidazo[4,5-b]pyridin-2-y l)pyridin-2-amine (130 mg, yield: 52%) as a brown solid. MS: m/z = 360.0.

Step 4: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-ethynyl-3H-imidazo[4,5-b ]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile

To a solution of 3-(3-(4-(chloromethyl)phenyl)-5-ethynyl-3H-imidazo[4,5-b]pyr idin-2- yl)pyridin-2-amine (130 mg, 328 μmol) and Intermediate 51 (104 mg, 328 μmol) in DMF (5 mL) were added K ₂ CO ₃ (226.7 mg, 1.64 mmol) and Nal (24.6 mg, 164 μmol). The mixture was stirred at 25 °C for 16 hr. The mixture was filtered, and concentrated. After purified by silica gel flash chromatography (Eluent of 0% ~ 6% MeOH in CH ₂ CI ₂ ) and purified by prep-TLC (CH ₂ CI ₂ : MeOH = 10:1), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-ethynyl-3H-imidazo[4,5-b ]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbo nitrile (Example 513, 42.5 mg, yield: 24%) was obtained as a yellow solid. MS: m/z = 527.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.18 - 8.09 (m, 1H), 8.08 - 7.94 (m, 2H), 7.61 - 7.51 (m, 3H), 7.39 (d, J= 8.4 Hz, 2H), 7.30 (dd, J= 7.6, 1.6 Hz, 1H), 6.60 (d, J= 6.0 Hz, 1H), 6.45 (dd, J= 7.6, 5.2 Hz, 1H), 4.12 - 3.82 (m, 1H), 3.75 - 3.59 (m, 3H), 3.01 - 2.91 (m, 2H), 2.28 (t, J= 10.8 Hz, 2H), 2.04 - 1.98 (m, 2H), 1.66 - 1.59 (m, 2H).

[001042] Example 514: N-(3-(2-(2-Aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin-l-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyri din-5-yl)phenyl)-N- methylacetamide

Example 514 was prepared in a manner similar to Example 464. MS: m/z = 650.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.28 (d, J = 8.4 Hz, 1 H), 8.15 – 7.90 (m, 6 H), 7.58 - 7.42 (m, 5 H), 7.36 (d, J = 7.2 Hz, 1 H), 7.16 (dd, J = 7.6, 1.6 Hz, 1 H), 7.07 (s, 2 H), 6.68 (d, J = 6.0 Hz, 1 H), 6.38 (dd, J = 7.6, 4.8 Hz, 1 H), 3.88 - 3.74 (m, 1 H), 3.59 (s, 2 H), 3.19 (s, 3 H), 2.89 - 2.75 (m, 2 H), 2.21 - 2.07 (m, 2 H), 1.96 - 1.71 (m, 5 H), 1.57 - 1.41 (m, 2 H). [001043] Example 515: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(3-methoxypyridin-4-yl)- 3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 515 was prepared in a manner similar to Example 341. MS: m/z = 610.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.53 (s, 1H), 8.32 - 8.25 (m, 2H), 8.14 - 7.95 (m, 4H), 7.64 (d, J = 4.8 Hz, 1H), 7.51 - 7.41 (m, 4H), 7.11 (d, J = 7.6 Hz, 1H), 7.02 (s, 2H), 6.67 (d, J = 6.4 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.98 (s, 3H), 3.87 - 3.71 (m, 1H), 3.57 (s, 2H), 2.87 - 2.76 (m, 2H), 2.20 - 2.09 (m, 2H), 1.94 - 1.81 (m, 2H), 1.55 - 1.41 (m, 2H). [001044] Example 516: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(6-methoxypyridin-3-yl)- 3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

To a solution of Intermediate 203 (240 mg, 542 μmol) in DMF (1 mL) were added DIEA (280 mg, 2.17 mmol) and Intermediate 51 (143 mg, 704 μmol). The mixture was stirred at 25 °C for 2 hr. After purified by prep-HPLC (column: Phenomenex C18 80 x 30mm x 5 μm; mobile phase: [water (NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN]; gradient: 50% - 80% B over 7 min), 4-((l-(4-(2- (2-aminopyridin-3 -yl)-5 -(6-methoxypyridin-3 -yl)-3H-imidazo[4, 5-b]pyri din-3 - yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile (Example 516, 126 mg, yield: 38.3%) was obtained as a yellow solid. MS: m/z = 610.2 [M+H| ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.85 (d, J= 2.4 Hz, 1H), 8.40 - 8.20 (m, 2H), 8.15 - 7.90 (m, 4H), 7.60 - 7.40 (m, 4H), 7.15 (dd, J= 7.6, 1.6 Hz, 1H), 7.05 (s, 2H), 6.92 (d, J= 9.2 Hz, 1H), 6.67 (d, J= 6.0 Hz, 1H), 6.37 (dd, J= 7.6, 4.8 Hz 1H), 3.89 (s, 3H), 3.90 - 3.70 (m, 1H), 3.59 (s, 2H), 2.83 - 2.80 (m, 2H), 2.30 - 2.10 (m, 2H), 1.89 - 1.82 (m, 2H), 1.60 - 1.40 (m, 2H).

[001045] Example 517: 4-((l-(4-(5-(3-Aminophenyl)-2-(2-aminopyridin-3-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

Example 517 was prepared in a manner similar to Example 469. MS: m/z = 594.3 [M+H| ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.16 (d, J= 8.0 Hz, 1H), 8.05 - 7.92 (m, 2H), 7.87 (d, J= 8.4 Hz, 1H), 7.56 - 7.52 (m, 2H), 7.47 - 7.43 (m, 2H), 7.41 (t, J= 1.6 Hz, 1H), 7.37 - 7.33 (m, 1H),

7.31 (dd, J= 7.6, 1.6 Hz, 1H), 7.17 (t, J= 8.0 Hz, 1H), 6.75 (dd, J= 7.6, 1.2 Hz, 1H), 6.64 - 6.55 (m, 1H), 6.47 (dd, J= 7.6, 4.8 Hz, 1H), 4.10 - 3.81 (m, 1H), 3.66 (s, 2H), 3.01 - 2.93 (m, 2H),

2.32 - 2.23 (m, 2H), 2.04 - 1.98 (m, 2H), 1.66 - 1.58 (m, 2H).

[001046] Example 518 and 519: N-(3-(2-(2-Aminopyridin-3-yl)-3-(4-((4-((2- cyanopyrimidin-4-yl)amino)piperidin-l-yl)methyl)phenyl)-3H-i midazo[4,5-b]pyridin-5- yl)phenyl)isobutyramide & N-(3 -(3 -(4-((4-((2-cyanopyrimidin-4-yl)amino)piperidin- 1 - yl)methyl)phenyl)-2-(2-isobutyramidopyridin-3-yl)-3H-imidazo [4,5-b]pyri din-5- yl)phenyl)isobutyramide

To a solution of Example 517 (220 mg, 371 μmol) and TEA (103 μL, 741 μmol) in THF (5 mL) was added 2-methylpropanoyl chloride (43.4 mg, 408 μmol) dropwise. The mixture was degassed and purged with N ₂ three times and stirred at 0 °C for 0.5 hr under N ₂ . The reaction mixture was filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (MeOH in CH ₂ CI ₂ = 1 to 10%) and prep-HPLC (column: Welch Xtimate C18 150 x 25mm x 5 μm; mobile phase: [water (HC1) - ACN]; gradient: 12% - 42% B over 8 min), N-(3 -(2-(2-aminopyridin-3 -yl)-3 -(4-((4-((2-cyanopyrimidin-4-yl)amino)piperidin- 1 - yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)phenyl)isobu tyramide (Example 518, 19.8 mg, yield: 7.6%) was obtained as a light yellow solid. MS: m/z = 664.3 [M+H] ⁺ . ¹ HNMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.93 (br s, IH), 8.28 (d, J= 8.4 Hz, IH), 8.21 - 8.16 (m, IH), 8.12 - 8.03 (m, 2H), 8.00 (dd, J= 4.8, 1.6 Hz, IH), 7.87 (d, J= 8.4 Hz, IH), 7.71 - 7.64 (m, 2H), 7.50 - 7.43 (m, 4H), 7.37 (t, J= 8.0 Hz, IH), 7.15 (dd, J= 7.6, 1.6 Hz, IH), 6.99 (br s, 2H), 6.68 (d, J= 5.6 Hz, IH), 6.38 (dd, J= 7.6, 4.8 Hz, IH), 3.88 - 3.73 (m, IH), 3.59 (s, 2H), 2.88 - 2.80 (m, 2H), 2.63 - 2.55 (m, IH), 2.21 - 2.12 (m, 2H), 1.93 - 1.85 (m, 2H), 1.54 - 1.46 (m, 2H), 1.08 (d, J= 6.8 Hz, 6H). N-(3-(3-(4-((4-((2-cyanopyrimidin-4-yl)amino)piperidin-l- yl)methyl)phenyl)-2-(2-isobutyramidopyridin-3-yl)-3H-imidazo [4,5-b]pyri din-5- yl)phenyl)isobutyramide (Example 519, 51 mg, yield: 17.5%) was obtained as a light yellow solid. MS: m/z = 734.3 [M+H] ⁺ . ¹ HNMR (400 MHz, Dimethylsulfoxide-d ₆ ) 10.55 (br s, IH), 9.94 (br s, IH), 8.44 (dd, J= 4.8, 1.6 Hz, IH), 8.23 - 8.19 (m, IH), 8.14 (d, J= 8.4 Hz, IH), 8.09 - 8.05 (m, 2H), 7.82 (d, J= 8.0 Hz, IH), 7.75 - 7.68 (m, 4H), 7.46 - 7.39 (m, 4H), 7.12 (dd, J= 7.6, 4.8 Hz, IH), 6.67 (d, J= 6.0 Hz, IH), 3.87 - 3.75 (m, IH), 3.56 (s, 2H), 2.86 - 2.79 (m, 2H), 2.65 - 2.58 (m, 2H), 2.18 - 2.10 (m, 2H), 1.94 - 1.85 (m, 2H), 1.52 - 1.45 (m, 2H), 1.10 (d, J= 6.8 Hz, 6H), 0.90 (d, J= 6.8 Hz, 6H).

[001047] Example 520: Methyl (3-(2-(2-aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin- 4-yl)amino)piperidin-l-yl)methyl)phenyl)-3H-imidazo[4,5-b]py ridin-5-yl)phenyl)carbamate Example 520 was prepared in a manner similar to Example 469. MS: m/z = 652.2 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.74 (br s, 1H), 8.27 (d, J = 8.0 Hz, 1H), 8.13 - 8.02 (m, 3H), 8.00 (dd, J = 4.4, 1.6 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.66 - 7.61 (m, 1H), 7.51 - 7.43 (m, 5H), 7.39 - 7.34 (m, 1H), 7.16 (dd, J = 8.0, 2.0 Hz, 1H), 7.00 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.87 - 3.75 (m, 1H), 3.67 (s, 3H), 3.59 (s, 2H), 2.87 - 2.80 (m, 2H), 2.20 - 2.11 (m, 2H), 1.93 - 1.85 (m, 2H), 1.54 - 1.45 (m, 2H). [001048] Example 521: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(3-(dimethylamino)phenyl )- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile Example 521 was prepared in a manner similar to Example 469. MS: m/z = 622.3 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.23 (d, J = 8.4 Hz, 1H), 8.09 (d, J = 6.0 Hz, 1H), 8.05 (d, J = 7.2 Hz, 1H), 8.00 (dd, J = 4.8, 1.6 Hz, 1H), 7.96 (d, J = 8.4 Hz, 1H), 7.49 - 7.44 (m, 4H), 7.42 - 7.40 (m, 1H), 7.34 - 7.31 (m, 1H), 7.27 - 7.23 (m, 1H), 7.19 (dd, J = 7.6, 1.6 Hz, 1H), 7.06 (br s, 2H), 6.76 (dd, J = 8.0, 2.0 Hz, 1H), 6.68 (d, J = 6.0 Hz, 1H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.88 - 3.74 (m, 1H), 3.59 (s, 2H), 2.92 (s, 6H), 2.85 - 2.79 (m, 2H), 2.19 - 2.10 (m, 2H), 1.94 - 1.86 (m, 2H), 1.53 - 1.44 (m, 2H). [001049] Example 522: N-(1-(3-(2-(2-Aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin -4- yl)amino)piperidin-1-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyri din-5-yl)phenyl)piperidin-4-yl)- N-methylacetamide

Step 1 : N-(l-(3-(2-(2-Aminopyridin-3-yl)-3-(4-(((tert-butyldimethyls ilyl)oxy)methyl)phenyl)- 3H-imidazo[4,5-b]pyridin-5-yl)phenyl)piperidin-4-yl)-N-methy lacetamide

To a solution of Intermediate 129 (500 mg, 833 μmol) in 1,4-dioxane (25 mL) and H2O (5 mL) were added Intermediate 204 (328 mg, 916 μmol), CS ₂ CO ₃ (813.75 mg, 2.50 mmol) and Pd(dppf)CI ₂ (60.9 mg, 83.3 μmol) at 20 °C. The reaction mixture was stirred at 100 °C for 2 hr. Water (30 mL) was added. The mixture was extracted with EtOAc (30 mL x 3). The combined organic layers were washed with brine (30 mL x 2), dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (MeOH in CH ₂ CI ₂ = 0 - 20 %), N-(l-(3-(2-(2-aminopyridin-3-yl)-3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-3H-imidazo[4,5-b]pyrid in-5-yl)phenyl)piperidin-4-yl)- N-methylacetamide (370 mg, 67.1% yield) was obtained as a purple solid. MS: m/z = 662.4 [M + H] ⁺ .

Step 2 : N-( 1 -(3 -(2-(2- Aminopyridin-3 -yl)-3 -(4-(hy droxymethyl)phenyl)-3H-imidazo[4, 5- b]pyridin-5-yl)phenyl)piperidin-4-yl)-N-methylacetamide To a solution of -(l-(3-(2-(2-aminopyridin-3-yl)-3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-3H-imidazo[4,5-b]pyrid in-5-yl)phenyl)piperidin-4-yl)- N-methylacetamide (360 mg, 544 μmol) in THF (12 mL) was added TBAF (1 M in THF, 816 μL). The reaction mixture was stirred at 20 °C for 1 hr. Water (20 mL) was added. The mixture was extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (20 mL x 2), dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. N-(l-(3-(2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl) -3H-imidazo[4,5-b]pyri din-5- yl)phenyl)piperidin-4-yl)- N-methylacetamide (298 mg, 544 μmol, crude) was obtained as a purple solid, which was used directly into the next step. MS: m/z = 548.3 [M + H] ⁺ .

Step 3 : N-(l-(3-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)- 3H-imidazo[4,5- b]pyridin-5-yl)phenyl)piperidin-4-yl)- N-methylacetamide

To a solution of N-(l-(3-(2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl) -3H- imidazo[4,5-b]pyridin-5-yl)phenyl)piperidin-4-yl)- N-methylacetamide (150 mg, 274 μmol) in CH ₂ CI ₂ (6 mL) was added SOCI ₂ (97.8 mg, 822 μmol). The reaction mixture was stirred at 20 °C for 2 hr. The reaction mixture was concentrated to give N-(l-(3-(2-(2-aminopyridin-3-yl)-3- (4-(chloromethyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)pheny l)piperidin-4-yl)- N- methylacetamide (155 mg, 274 μmol, crude) as a gray solid, which was used directly into the next step. MS: m/z = 566.1 [M + H] ⁺ .

Step 4 : N-( 1 -(3 -(2-(2- Aminopyridin-3 -yl)-3 -(4-((4-((2-cyanopyrimidin-4-yl)amino)piperidin- 1 - yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)phenyl)piper idin-4-yl)- N-methylacetamide To a solution of N-(l-(3-(2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)- 3H-imidazo[4,5- b]pyridin-5-yl)phenyl)piperidin-4-yl)- N-methylacetamide (155 mg, 274 μmol) and Intermediate 51 (61.2 mg, 301 μmol) in DMF (5 mL) were added K ₂ CO ₃ (114 mg, 822 μmol) and Nal (8.21 mg, 54.8 μmol) at 20 °C. The reaction mixture was stirred at 80 °C for 2 hr. Water (20 mL) was added. The resulting mixture was extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (20 mL x 2), dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. The residue was re-crystallized from MeCN (5 mL). N- (1 -(3 -(2-(2- Aminopyridin-3 -yl)-3 -(4-((4-((2-cyanopyrimidin-4-yl)amino)piperidin- 1 - yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)phenyl)piper idin-4-yl)- N-methylacetamide (Example 522, 73.0 mg, yield: 36.4% for 3 steps) was obtained as a gray solid. MS: m/z = 733.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.24 (d, J= 8.4 Hz, 1H), 8.10 - 7.95 (m, 4H), 7.64 (s, 1H), 7.50 - 7.42 (m, 5H), 7.28 (t, J= 8.0 Hz, 1H), 7.18 (d, J= 8.4 Hz, 1H), 7.06 (s, 2H), 6.99 (d, J= 8.0 Hz, 1H), 6.67 (s, 1H), 6.39 (s, 1H), 4.43 (s, 1H), 3.87 - 3.78 (m, 3H), 3.58 (s, 2H), 2.89 (s, 1H), 2.85 - 2.78 (m, 5H), 2.76 - 2.73 (m, 1H), 2.65 (s, 1H), 2.15 (s, 2H), 2.06 (s, 1H), 1.98 (s, 2H), 1.88 - 1.81 (m, 2H), 1.79 - 1.73 (m, 1H), 1.72 - 1.64 (m, 1H), 1.57 - 1.46 (m, 3H).

[001050] Example 523: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluoro-2-methylphenyl )- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile Example 523 was prepared in a manner similar to Example 469. MS: m/z = 611.4 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.11 - 8.02 (m, 2H), 8.00 (dd, J = 4.8, 2.0 Hz, 1H), 7.52 (d, J = 8.4 Hz, 1H), 7.47 - 7.37 (m, 5H), 7.20 - 7.07 (m, 3H), 7.02 (s, 2H), 6.66 (d, J = 6.4 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.85 - 3.74 (m, 1H), 3.55 (s, 2H), 2.79 (d, J = 10.4 Hz, 2H), 2.32 (s, 3H), 2.18 - 2.08 (m, 2H), 1.92 - 1.79 (m, 2H), 1.53 - 1.41 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -114.725. [001051] Example 524: 2-(2-(2-aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin-1-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyri din-5-yl)-5-fluorobenzamide Step 1: 2-(2-(2-Aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)o xy)methyl)phenyl)-3H- imidazo[4,5-b]pyridin-5-yl)-5-fluorobenzamide To a mixture of 3-(3-(4-(((tert-butyldimthylsilyl)oxy)methyl)phenyl)-5-chlor o-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (refer to Intermediate 117 for detail procedures, 300 mg, 644 µmol) and (2-cyano-4-fluorophenyl)boronic acid (117 mg, 708 µmol) in 1,4-dioxane (5 mL) and H ₂ O (1 mL) were added Cs ₂ CO ₃ (629.2 mg, 1.9 mmol, 3 eq) and Pd(dppf)Cl ₂ (47.1 mg, 64.4 µmol). The mixture was stirred at 100 ºC for 2 hr under N ₂ . The mixture was diluted with H ₂ O (50 mL) and extracted with EtOAc (100 mL x 2). The combined organic layers were washed with brine (100 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography ((ethyl acetate in EtOH=3/1) in petroleum ether = 0 to 40%), 2- (2-(2-aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)oxy )methyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)-5-fluorobenza mide (300 mg, 81.6% yield) was obtained as a brown solid. MS: m/z = 569.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.23 (d, J= 8.4 Hz, 1H), 8.00 (dd, J= 4.8, 1.6 Hz, 1H), 7.92 - 7.84 (m, 1H), 7.65 (dd, J= 8.4, 5.6 Hz, 1H), 7.58 (d, J= 8.4 Hz, 1H) 7.52 - 7.47 (m, 2H), 7.47 - 7.43 (m, 3H), 7.38 - 7.26 (m, 2H), 7.14 (dd, J= 7.6, 1.6 Hz, 1H), 7.02 - 6.98 (m, 2H), 6.38 (dd, J= 8.0, 5.2 Hz, 1H), 4.78 (s, 2H), 0.91 (s, 9H), 0.10 (s, 6H).

Step 2: 2-(2-(2-Aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5-b]pyridin-5- yl)-5-fluorobenzamide

To a mixture of 2-(2-(2-aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)o xy)methyl)phenyl)- 3H-imidazo[4,5-b]pyridin-5-yl)-5-fluorobenzamide (290 mg, 510 μmol) in THF (1 mL) was added TBAF (1 M in THF, 765 μL), the mixture was stirred at 20 °C for 1 hr. H ₂ O (50 mL) was added and extracted with EtOAc (30 mL x 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated, 2-(2-(2-aminopyridin-3- yl)-3-(4-(hydroxymethyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-y l)-5-fluorobenzamide (20 mg, yield: 94.9%) was obtained as a yellow solid. MS: m/z = 455.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.22 (d, J= 8.4 Hz, 1H), 8.00 (dd, J= 4.8, 1.8 Hz, 1H), 7.89 (s, 1H), 7.65 (dd, J= 8.4, 5.6 Hz, 1H), 7.58 (d, J= 8.0 Hz, 1H), 7.49 - 7.44 (m, 3H), 7.42 - 7.38 (m, 2H), 7.37 - 7.31 (m, 1H), 7.30 - 7.24 (m, 1H), 7.17 (dd, J= 7.6, 2.0 Hz, 1H), 7.09 - 6.88 (m, 1H), 6.42 (dd, J= 7.6, 5.2 Hz, 1H), 4.56 (d, J= 6.0 Hz, 1H).

Step 3 : 2-(2-(2-Aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imi dazo[4,5-b]pyridin-5- yl)-5-fluorobenzamide

To a mixture of 2-(2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-im idazo[4,5- b]pyridin-5-yl)-5-fluorobenzamide (200 mg, 440 μmol) in CH ₂ CI ₂ (2 mL) was added SOCI ₂ (157.1 mg, 1.32 mmol), the mixture was stirred at 20 °C for 1 hr. The mixture was concentrated, 2-(2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imi dazo[4,5- b]pyridin-5-yl)-5-fluorobenzamide (208 mg, yield: 99.9%) was obtained as a yellow solid. MS: m/z = 473.1 [M + H] ⁺ .

Step 4 : 2-(2-(2-Aminopyridin-3 -yl)-3 -(4-((4-((2-cyanopyrimidin-4-yl)amino)piperidin- 1 - yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)-5-fluoroben zamide

To a mixture of 2-(2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imi dazo[4,5- b]pyridin-5-yl)-5-fluorobenzamide (200 mg, 423 μmol) and Intermediate 51 (94.6 mg, 465 μmol) in DMF (4 mL) was added DIEA (164 mg, 1.27 mmol). The mixture was stirred at 80 °C for 2 hr. H ₂ O (50 mL) was added and extracted with EtOAc (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by prep-HPLC (column: C18150 × 30 mm; mobile phase: [water (NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN]; gradient: 46% - 76% B over 7 min), 2-(2-(2-aminopyridin-3- yl)-3-(4-((4-((2-cyanopyrimidin-4-yl)amino)piperidin-1-yl)me thyl)phenyl)-3H-imidazo[4,5- b]pyridin-5-yl)-5-fluorobenzamide (Example 524, 100 mg, yield: 37%) was obtained as a yellow solid. MS: m/z = 640.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.23 (d, J = 8.0 Hz, 1H), 8.16 - 7.96 (m, 3H), 7.89 (s, 1H), 7.67 (dd, J = 8.4, 5.6 Hz, 1H), 7.59 (d, J =8.4 Hz, 1H), 7.50 - 7.39 (m, 5H), 7.38 - 7.32 (m, 1H), 7.30 - 7.26 (m, 1H), 7.28 (dd, J=9.1, 2.0 Hz, 1 H) 7.11 (dd, J = 7.6, 2.0 Hz, 1H), 7.02 (br s, 2H), 6.67 (d, J = 6.4 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.88 - 3.74 (m, 1H), 3.54 (s, 2H), 2.85 - 2.75 (m, 2H), 2.21 - 2.06 (m, 2H), 1.94 - 1.79 (m, 2H), 1.57 - 1.41 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -114.071. [001052] Example 525: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-cyano-4-fluorophenyl) - 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile To a mixture of Example 524 (60 mg, 93.8 µmol) in CH ₂ Cl ₂ (1 mL) were added POCl ₃ (86.3 mg, 563 µmol) and Py (59.4 mg, 750 µmol). The mixture was stirred at 25 ºC for 1 hr. Water (20 mL) was added. The pH was adjusted to 10 with saturated NaHCO ₃ (10 mL). The mixture was extracted with CH ₂ Cl ₂ (30 mL x 2). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by prep-HPLC (column: Xtimate C18150 x 40 mm x 10 μm; mobile phase: [water (FA) - ACN]; gradient: 15% - 45% B over 7 min), 4-((1-(4-(2-(2-aminopyridin-3-yl)-5-(2-cyano-4-fluorophenyl) -3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile (Example 525, 13.7 mg, yield: 23.5%) was obtained as a yellow solid. MS: m/z = 622.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.38 (d, J = 8.4 Hz, 1H), 8.11 - 8.00 (m, 3H), 7.98 - 7.89 (m, 2 H) 7.83 (d, J = 8.4 Hz, 1H), 7.73 - 7.67 (m, 1H), 7.51 - 7.39 (m, 4H), 7.19 (dd, J = 7.6, 1.6 Hz, 1H), 7.00 (br s, 2H), 6.66 (d, J = 6.0 Hz, 1H), 6.40 (dd, J = 8.0, 4.8 Hz, 1H), 3.87 - 3.72 (m, 1H), 3.55 (s, 2H), 2.86 - 2.73 (m, 2H), 2.19 - 2.05 (m, 2H), 1.94 - 1.79 (m, 2H), 1.57 - 1.40 (m, 2H). ¹⁹ F NMR (376.5 MHz, Dimethylsulfoxide-d ₆ ) δ -112.011. [001053] Example 526: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluoro-2- (trifluoromethyl)phenyl)-3H-imidazo[4,5-b]pyridin-3-yl)benzy l)piperidin-4- yl)amino)pyrimidine-2-carbonitrile Example 526 was prepared in a manner similar to Example 341. MS: m/z = 665.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.30 (d, J = 8.0 Hz, 1H), 8.20 - 7.93 (m, 3H), 7.74 (dd, J = 8.2, 2.0 Hz, 1H), 7.66 - 7.60 (m, 2H), 7.52 (d, J = 8.0 Hz, 1H), 7.45 - 7.33 (m, 4H), 7.17 (dd, J = 7.6, 2.0 Hz, 1H), 7.03 (s, 2H), 6.66 (d, J = 6.0 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.84 - 3.73 (m, 1H), 3.53 (s, 2H), 2.86 - 2.74 (m, 2H), 2.19 - 2.08 (m, 2H), 1.92 - 1.78 (m, 2H), 1.57 - 1.37 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ [001054] Example 527: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(o-tolyl)-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile Example 527 was prepared in a manner similar to Example 469. MS: m/z = 593.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide -d ₆ ) δ 8.26 (d, J = 8.4 Hz, 1H), 8.12 - 7.95 (m, 3H), 7.53 (d, J = 8.4 Hz, 1H), 7.47 - 7.37 (m, 5H), 7.31 - 7.25 (m, 3H), 7.17 (d, J = 6.4 Hz, 1H), 7.02 (s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.83 - 3.73 (m, 1H), 3.55 (s, 2H), 2.79 (d, J = 10.8 Hz, 2H), 2.31 (s, 3H), 2.18 - 2.05 (m, 2H), 1.93 - 1.79 (m, 2H), 1.54 - 1.39 (m, 2H). [001055] Example 528: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(m-tolyl)-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile Example 528 was prepared in a manner similar to Example 469. MS: m/z = 593.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.25 (dd, J = 8.0, 3.2 Hz, 1H), 8.13 - 7.92 (m, 4H), 7.86 - 7.78 (m, 2H), 7.53 - 7.41 (m, 4H), 7.38 - 7.30 (m, 1H), 7.23 - 7.12 (m, 2H), 7.03 (s, 2H), 6.68 (s, 1H), 6.42 - 6.33 (m, 1H), 3.89 - 3.74 (m, 1H), 3.60 (s, 2H), 2.89 - 2.77 (m, 2H), 2.36 (s, 3H), 2.21 - 2.08 (m, 2H), 1.96 - 1.83 (m, 2H), 1.59 - 1.43 (m, 2H). [001056] Example 529: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(p-tolyl)-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile Example 529 was prepared in a manner similar to Example 341. MS: m/z = 593.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.24 (d, J = 8.4 Hz, 1H), 8.11 - 8.05 (m, 2H), 8.00 (dd, J = 4.8, 1.8 Hz, 1H), 7.94 - 7.92 (m, J = 8.4 Hz, 3H), 7.52 - 7.42 (m, 4H), 7.27 (d, J = 8.0 Hz, 2H), 7.15 (dd, J = 7.6, 2.0 Hz, 1H), 7.04 (br s, 2H), 6.68 (d, J = 6.0 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.88 - 3.76 (m, 1H), 3.60 (s, 2H), 2.97 - 2.77 (m, 2H), 2.34 (s, 3H), 2.23 - 2.07 (m, 2H), 1.98 - 1.77 (m, 2H), 1.55 - 1.42 (m, 2H). [001057] Example 530: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(3-(trifluoromethyl)phen yl)- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile Example 530 was prepared in a manner similar to Example 341. MS: m/z = 647.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.38 - 8.30 (m, 3H), 8.14 (d, J = 8.4 Hz, 1H), 8.10 - 8.04 (m, 2H), 8.01 (dd, J = 4.8, 2.0 Hz, 1H), 7.77 - 7.68 (m, 2H), 7.52 - 7.44 (m, 4H), 7.19 (dd, J = 7.6, 1.6 Hz, 1H), 7.07 (s, 2H), 6.68 (br d, J = 6.4 Hz, 1H), 6.39 (dd, J = 8.0, 4.8 Hz, 1H), 3.81 (br s, 1H), 3.60 (s, 2H), 2.83 - 2.81 (m, 2H), 2.20 - 2.09 (m, 2H), 1.94 - 1.80 (m, 2H), 1.54 - 1.45 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -61.256. [001058] Example 531: Isopropyl 2-(2-aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin-1-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyri dine-5-carboxylate

Step 1: Isopropyl 2-(2-aminopyridin-3-yl)-3-(4-(((tert-butyldimethylsilyl)oxy) methyl)phenyl)- 3H-imidazo[4,5-b]pyridine-5-carboxylate

To a solution of methyl 2-(2-aminopyridin-3-yl)-3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-3H-imidazo[4,5-b]pyrid ine-5-carboxylate (refer to Example 508 for detail procedures, 280 mg, 572 μmol) in z-PrOH (10 mL) was added z-PrOLi (45.3 mg, 686 μmol). The reaction mixture was stirred at 65 °C for 0.5 hr. After cooling to 25 °C, water (20 mL) was added. The mixture was extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (20 mL x 2), dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (MeOH in CH ₂ CI ₂ = 0 - 20%), isopropyl 2-(2-aminopyridin-3-yl)-3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-3H-imidazo[4,5-b]pyrid ine-5-carboxylate (160 mg, yield: 54.1%) was obtained as a yellow solid. MS: m/z = 518.3 [M + H] ⁺ .

Step 2: Isopropyl 2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H-imida zo[4,5- b]pyridine-5-carboxylate

To a solution of isopropyl 2-(2-aminopyridin-3-yl)-3-(4-(((tert- butyldimethylsilyl)oxy)methyl)phenyl)-3H-imidazo[4,5-b]pyrid ine-5-carboxylate (150 mg, 290 μmol) in THF (5 mL) was added TBAF (1 M in THF, 435 μL). The reaction mixture was stirred at 20 °C for 1 hr. Water (20 mL) was added. The mixture was extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (20 mL x 2), dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. Isopropyl 2-(2-aminopyridin-3-yl)- 3-(4-(hydroxymethyl)phenyl)-3H-imidazo[4,5-b]pyridine-5-carb oxylate (117 mg, crude) was obtained as a brown solid, which was used directly into the next step. MS: m/z = 404.2 [M + H] ⁺ . Step 3: Isopropyl 2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imidaz o[4,5- b]pyridine-5-carboxylate

To a solution of isopropyl 2-(2-aminopyridin-3-yl)-3-(4-(hydroxymethyl)phenyl)-3H- imidazo[4,5-b]pyridine-5-carboxylate (107 mg, 265 μmol) in CH ₂ CI ₂ (3 mL) was added SOCI ₂ (94.6 mg, 795 μmol). The reaction mixture was stirred at 20 °C for 2 hr. The reaction mixture was concentrated to give isopropyl 2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H- imidazo[4,5-b]pyridine-5-carboxylate (112 mg, 265 μmol, crude) as a yellow solid, which was used directly into the next step. MS: m/z = 422.1 [M + H] ⁺ .

Step 4: Isopropyl 2-(2-aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin-4-yl)ami no)piperidin-l- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridine-5-carboxylate

To a solution of isopropyl 2-(2-aminopyridin-3-yl)-3-(4-(chloromethyl)phenyl)-3H-imidaz o[4,5- b]pyridine-5-carboxylate (112 mg, 265 μmol) and Intermediate 51 (59.2 mg, 291 μmol) in DMF (3 mL) were added Nal (7.94 mg, 53.0 μmol) and K ₂ CO ₃ (110 mg, 795 μmol) at 20 °C. The reaction mixture was stirred at 20 °C for 12 hr. The reaction mixture was diluted with H ₂ O (20 ml) and extracted with EtOAc (20 ml). The organic layer was separated, dried over anhydrous Na ₂ SO ₄ and concentrated. After purified by prep-HPLC (column: C18 150 x 30 mm; mobile phase: [water (NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN]; gradient: 50%-80% B over 7 min), isopropyl 2- (2-aminopyridin-3 -yl)-3 -(4-((4-((2-cyanopyrimidin-4-yl)amino)piperidin- 1 -yl)methyl)phenyl)- 3H-imidazo[4,5-b]pyridine-5-carboxylate (Example 531, 28.4 mg, yield: 18.2% for 3 steps) was obtained as a yellow solid. MS: m/z = 589.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.32 (d, J= 8.4 Hz, 1H), 8.11 - 8.03 (m, 3H), 8.01 (dd, J= 4.4, 1.6 Hz, 1H), 7.50 - 7.40 (m, 4H), 7.18 (dd, J= 7.6, 1.6 Hz, 1H), 7.00 (s, 2H), 6.67 (d, J= 6.0 Hz, 1H), 6.38 (dd, J= 8.0, 5.2 Hz, 1H), 5.17 - 5.08 (m, 1H), 3.82 (br.s, 1H), 3.58 (s, 2H), 2.87 - 2.78 (m, 2H), 2.21 - 2.11 (m, 2H), 1.93 - 1.84 (m, 2H), 1.56 - 1.43 (m, 2H), 1.32 (d, J= 6.4 Hz, 6H). [001059] Example 532: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-1H-benzo[d]imidazol-l- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile

Example 532 was prepared in a manner similar to Example 261. MS: m/z = 502.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.13 - 8.02 (m, 2H), 7.96 (dd, J= 4.8, 1.6 Hz, 1H), 7.80 (d, J= 7.2 Hz, 1H), 7.49 (d, J= 8.4 Hz, 2H), 7.37 (d, J= 8.4 Hz, 2H), 7.35 - 7.27 (m, 2H), 7.20 (d, J= 7.2 Hz, 1H), 7.11 - 7.06 (m, 3H), 6.67 (d, J= 6.0 Hz, 1H), 6.34 (dd, J= 7.6, 4.8 Hz, 1H), 3.81 (s, 1H), 3.59 (s, 2H), 2.87 - 2.77 (m, 2H), 2.19 - 2.10 (m, 2H), 1.94 - 1.83 (m, 2H), 1.57 - 1.43 (m, 2H).

[001060] Example 533 : 4-((l-(4-(2-(2-Aminopyridin-3-yl)-1H-imidazo[4,5-b]pyridin-l - yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile

Example 533 was prepared in a manner similar to Example 261. MS: m/z = 503.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.51 (dd, J= 4.8, 1.2 Hz, 1H), 8.12 - 8.03 (m, 2H), 8.00 (dd, J= 4.8, 1.6 Hz, 1H), 7.65 (d, J= 8.0 Hz, 1H), 7.52 - 7.47 (m, 2H), 7.44 - 7.39 (m, 2H), 7.32 (dd, J= 8.0, 4.8 Hz, 1H), 7.15 (dd, J= 7.6, 1.2 Hz, 1H), 7.05 (s, 2H), 6.67 (d, J= 6.4 Hz, 1H), 6.38 (dd, J= 7.6, 4.8 Hz, 1H), 3.81 (s, 1H), 3.59 (s, 2H), 2.86 - 2.77 (m, 2H), 2.22 - 2.07 (m, 2H), 1.93 - 1.83 (m, 2H), 1.56 - 1.43 (m, 2H).

[001061] Example 534: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(6-methylpyridin-3-yl)-3 H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

To a solution of Example 405 (200 mg, 372 μmol) and (6-methyl-3-pyridyl)boronic acid (56.1 mg, 410 μmol) in 1,4-dioxane (5 mL) and H ₂ O (1 mL) were added Pd(dppf)CI ₂ (27.3 mg, 37.2 μmol) and CS ₂ CO ₃ (364 mg, 1.12 mmol) at 25 °C. The mixture was degassed and purged with N2 three times and stirred at 100 °C for 1 hr. The mixture was quenched with H ₂ O (50 mL) and extracted with EtOAc (50 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered, and concentrated. After purified by silica gel flash chromatography (MeOH in CH ₂ CI ₂ = 0 - 10%), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(6- methylpyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)pip eridin-4-yl)amino)pyrimidine-2- carbonitrile (Example 534, 87.7 mg, yield: 40%) was obtained as a yellow solid. MS: m/z = 594.1 [M + H]+. 1H NMR (400 MHz, Dimethylsulfoxide-d6) 9.10 (d, J = 2.0 Hz, 1 H), 8.34 - 8.22 (m, 2 H), 8.13 - 7.97 (m, 4 H), 7.53 - 7.43 (m, 4 H), 7.34 (d, J = 8.4 Hz, 1 H), 7.16 (dd, J = 7.6, 1.6 Hz, 1 H), 7.04 (s, 2 H), 6.68 (d, J = 6.4 Hz, 1 H), 6.39 (dd, J = 7.6, 4.8 Hz, 1 H), 3.90 - 3.75 (m, 1 H), 3.59 (s, 2 H), 2.90 - 2.76 (m, 2 H), 2.50 (s, 3 H), 2.23 - 2.11 (m, 2 H), 1.96 - 1.84 (m, 2 H), 1.58 - 1.40 (m, 2 H). [001062] Example 535: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(difluoromethoxy)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 535 was prepared in a manner similar to Example 261. MS: m/z = 569.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.33 (d, J = 8.4 Hz, 1H), 8.07 (dd, J = 9.6, 6.0 Hz, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.75 - 7.51 (m, 1H), 7.48 - 7.42 (m, 2H), 7.39 - 7.35 (m, 2H), 7.13 - 7.05 (m, 2H), 6.89 (s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.84 - 3.78 (m, 1H), 3.57 (s, 2H), 2.87 - 2.77 (m, 2H), 2.21 - 2.08 (m, 2H), 1.95 - 1.82 (m, 2H), 1.57 - 1.42 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -86.292. [001063] Example 536: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-methoxypyridin-3-yl)- 3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 536 was prepared in a manner similar to Example 341. MS: m/z = 610.3 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.66 (s, 1H), 8.46 (d, J = 6.4 Hz, 1H), 8.25 (d, J = 8.4 Hz, 1H), 8.10 - 8.03 (m, 2H), 8.02 - 7.96 (dd, J = 4.8, 1.6 Hz, 1H), 7.85 (d, J = 8.4 Hz, 1H), 7.46 - 7.42 (m, 4H), 7.20 (d, J = 6.0 Hz, 1H), 7.17 - 7.13 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (s, 2H), 6.66 (d, J = 6.0 Hz, 1H), 6.41 - 6.35 (m, 1H), 3.92 (s, 3H), 3.85 (br.s, 1H), 3.56 (s, 2H), 2.80 - 2.75 (m, 2H), 2.30 - 2.10 (m, 2H), 1.89 (d, J = 10.4 Hz, 2H), 1.60 - 1.40 (m, 2H). [001064] Example 537 & 538: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-methoxypyridin-3- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile & 4- ((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-hydroxypyridin-3-yl)-3H -imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile

To a solution of Intermediate 212 (350 mg, 790 μmol) and Intermediate 51 (177 mg, 869 μmol) in DMF (12 mL) were added Nal (23.7 mg, 158 μmol) and K ₂ CO ₃ (328 mg, 2.37 mmol) at 20 °C. The reaction mixture was stirred at 80 °C for 2 hr. The mixture was diluted with H ₂ O (30 mL) and extracted with EtOAc (50 mL x 3). The combined organic layers were washed with brine (50 mL x 2), dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by prep-HPLC (column: C18 150 x 30 mm; mobile phase: [water (NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN]; gradient: 50% - 80% B over 7 min), 4-((l-(4-(2-(2- aminopyridin-3-yl)-5-(2-methoxypyridin-3-yl)-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin- 4-yl)amino)pyrimidine-2-carbonitrile (Example 537, 12.7 mg, yield: 2.6% for 4 steps) was obtained as an off-white solid. MS: m/z = 610.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 - 8.21 (m, 2H), 8.12 - 8.03 (m, 3H), 8.00 (d, J= 8.0 Hz, 2H), 7.48

- 7.42 (m, 4H), 7.16 - 7.09 (m, 2H), 7.02 (s, 2H), 6.67 (d, J= 6.0 Hz, 1H), 6.38 (dd, J= 8.0, 5.2 Hz, 1H), 3.96 (s, 3H), 3.87 - 3.73 (m, 1H), 3.57 (s, 2H), 2.87 - 2.76 (m, 2H), 2.20 - 2.09 (m, 2H), 1.93 - 1.80 (m, 2H), 1.57 - 1.41 (m, 2H). 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(2- hydroxypyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)pi peridin-4-yl)amino)pyrimidine-2- carbonitrile (Example 538, 53.8 mg, yield: 11.4% for 4 steps) was obtained as an off-white solid. MS: m/z = 596.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 11.99 (s, 1H), 8.68 (d, J= 8.4 Hz, 1H), 8.25 - 8.17 (m, 2H), 8.14 - 8.03 (m, 2H), 7.99 (d, J= 3.6 Hz, 1H), 7.50

- 7.41 (m, 5H), 7.13 (d, J= 7.6 Hz, 1H), 7.05 (s, 2H), 6.67 (d, J= 6.0 Hz, 1H), 6.40 - 6.33 (m, 2H), 3.93 - 3.73 (m, 1H), 3.59 (s, 2H), 2.87 - 2.78 (m, 2H), 2.22 - 2.09 (m, 2H), 1.94 - 1.83 (m, 2H), 1.58 - 1.42 (m, 2H).

[001065] Example 539: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(l,3-dimethyl-1H-pyrazol -4- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile Example 539 was prepared in a manner similar to Example 261. MS: m/z = 597.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.18 (s, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.10 - 8.04 (m, 2H), 7.99 (dd, J = 4.8, 2.0 Hz, 1H), 7.57 (d, J = 8.4 Hz, 1H), 7.48 - 7.44 (m, 2H), 7.43 - 7.39 (m, 2H), 7.19 (dd, J = 7.6, 1.6 Hz, 1H), 7.10 (s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.83 - 3.75 (m, 4H), 3.57 (s, 2H), 2.83 - 2.77 (m, 2H), 2.27 (s, 3H), 2.20 - 2.03 (m, 2H), 1.92 - 1.84 (m, 2H), 1.53 - 1.43 (m, 2H). [001066] Example 540: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-1H-imidazo[4,5-c]pyridin-1 - yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile Example 540 was prepared in a manner similar to Example 261. MS: m/z = 503.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.09 (s, 1H), 8.38 (d, J = 5.6 Hz, 1 H), 8.13 - 8.02 (m, 2 H), 7.99 (dd, J = 4.8, 2.0 Hz, 1 H), 7.49 (d, J = 8.4 Hz, 2 H), 7.41 (d, J = 8.0 Hz, 2 H), 7.26 (d, J = 5.2 Hz, 1 H), 7.16 (dd, J = 7.6, 1.6 Hz, 1 H), 6.96 (s, 2 H), 6.67 (d, J = 6.0 Hz, 1 H), 6.38 (dd, J = 7.6, 4.8 Hz, 1 H), 3.90 - 3.74 (m, 1 H), 3.58 (s, 2 H), 2.87 - 2.77 (m, 2 H), 2.23 - 2.07 (m, 2 H), 1.95 - 1.81 (m, 2 H), 1.57 - 1.41 (m, 2 H). [001067] Example 541: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluorophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)(methyl)ami no)pyrimidine-2-carbonitrile Example 541 was prepared in a manner similar to Example 261. MS: m/z = 611.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.24 (d, J = 6.0 Hz, 1H), 8.10 - 8.05 (m, 2H), 8.01 - 7.96 (m, 2H), 7.52 - 7.43 (m, 4H), 7.30 (t, J = 8.8 Hz, 2H), 7.15 (dd, J = 8.0, 1.6 Hz, 1H), 7.02 (s, 3H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.62 (s, 2H), 2.94 (s, 6H), 2.22 - 2.13 (m, 2H), 1.89 - 1.80 (m, 2H), 1.65 - 1.56 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -113.59. [001068] Example 542: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(6-(difluoromethoxy)pyri din- 3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)am ino)pyrimidine-2-carbonitrile

A mixture of (6-(difluoromethoxy)pyridin-3-yl)boronic acid (101 mg, 536 μmol), Example 405 (240 mg, 447 μmol), CS ₂ CO ₃ (437 mg, 1.3 mmol), Pd(dppf)CI ₂ (32.7 mg, 45 μmol) in H ₂ O (1 mL) and 1,4-dioxane (5 mL) was degassed and purged with N2 three times. The mixture was stirred at 100 °C for 1 hr under N2 atmosphere. The reaction mixture was diluted with H ₂ O (30 mL) and extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-HPLC (column: Phenomenex C18 150 x 25 mm x 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 47% - 77% B over 11 min), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5- (6-(difluoromethoxy)pyridin-3 -yl)-3H-imidazo[4, 5-b]pyridin-3 -yl)benzyl)piperidin-4- yl)amino)pyrimidine-2-carbonitrile (Example 542, 68.7 mg, yield: 24%) was obtained as an off white solid. MS: m/z = 646.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethysulfoxide-d ₆ ) 6 8.92 (d, J = 2.4 Hz, 1H), 8.50 (dd, J= 8.8, 2.4 Hz, 1H), 8.31 (d, J= 8.4 Hz, 1H), 8.15 - 7.96 (m, 4H), 7.95 - 7.77 (m, 1H), 7.52 - 7.43 (m, 4H), 7.22 - 7.13 (m, 2H), 7.04 (br s, 2H), 6.67 (d, J= 6.0 Hz, 1H), 6.39 (dd, J= 7.6, 4.8 Hz, 1H), 3.81 (dd, J= 6.8, 2.4 Hz, 1H), 3.59 (s, 2H), 2.83 (d, J= 10.8 Hz, 2H), 2.16 (t, J= 10.8 Hz, 2H), 1.89 (d, J= 10.4 Hz, 2H), 1.57 - 1.43 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ -87.27.

[001069] Example 543: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(2-(difluoromethoxy)pyri din- 4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)am ino)pyrimidine-2-carbonitrile

Example 543 was prepared in a manner similar to Example 469. MS: m/z = 646.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ 8.42 - 8.31 (m, 2H), 8.21 (d, J= 8.4 Hz, 1H), 8.13 - 7.99 (m, 3H), 7.96 - 7.87 (m, 1.3H), 7.73 (s, 0.5H), 7.66 (s, 1H), 7.55 (s, 0.3H), 7.53 - 7.42 (m, 4H), 7.19 (dd, J= 7.6, 1.6 Hz, 1H), 7.11 - 6.97 (m, 2H), 6.67 (d, J= 6.0 Hz, 1H), 6.39 (dd, J= 7.6, 4.8 Hz, 1H), 3.91 - 3.74 (m, 1H), 3.60 (s, 2H), 2.83 (d, J= 11.2 Hz, 2H), 2.23 - 2.11 (m, 2H), 1.95 - 1.80 (m, 2H), 1.59 - 1.42 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethysulfoxide-d ₆ ) 6 - 87.12.

[001070] Example 544: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluoro-2-hydroxypheny l)-

3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino )pyrimidine-2-carbonitrile

To a solution of Example 485 (200 mg, 344 μmol) and (4-fluoro-2-hydroxy-phenyl)boronic acid (59.0 mg, 378 μmol) in 1,4-dioxane (10 mL) and H ₂ O (2 mL) were added CS ₂ CO ₃ (336 mg, 1.03 mmol) and Pd(dppf)CI ₂ (25.2 mg, 34.4 μmol) at 25 °C. The mixture was degassed and purged with N2 three times and stirred at 100 °C for 2 hr. The reaction mixture was quenched with water (20 mL) and extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (20 mL), dried over Na ₂ SO ₄ , filtered and concentrated. The crude was purified by silica gel flash chromatography (MeOH in CH ₂ CI ₂ = 0 - 20%) to give 4-((l-(4-(2-(2- aminopyridin-3-yl)-5-(4-fluoro-2-hydroxyphenyl)-3H-imidazo[4 ,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile (Example 544, 35.2 mg, yield: 17%) as a yellow solid. MS: m/z = 613.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 13.19 (s, 1 H), 8.40 (d, J= 8.4 Hz, 1 H), 8.20 - 8.05 (m, 4 H), 8.02 (dd, J= 4.8, 1.6 Hz, 1 H), 7.58 - 7.43 (m, 4 H), 7.24 (d, J= 6.8 Hz, 1 H), 7.08 (s, 2 H), 6.77 (td, J= 8.4, 2.8 Hz, 1 H), 6.71 - 6.62 (m, 2 H), 6.47 - 6.34 (m, 1 H), 3.92 - 3.69 (m, 1 H), 3.61 (s, 2 H), 2.93 - 2.72 (m, 2 H), 2.27 - 2.09 (m, 2 H), 1.97 - 1.83 (m, 2 H), 1.57 - 1.47 (m, 2 H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -109.982.

[001071] Example 545: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluoro-3-hydroxypheny l)- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile

[001072] Example 545 was prepared in a manner similar to Example 544. MS: m/z =

613.2 [M + H] ⁺ . ¹ HNMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 10.00 (s, 1 H), 8.24 (d, J= 8.4 Hz, 1 H), 8.15 - 8.03 (m, 2 H), 8.01 - 7.96 (m, 1 H), 7.88 (d, J = 8.4 Hz, 1 H), 7.63 (dd, J = 9.2, 2.0 Hz, 1 H), 7.52 - 7.40 (m, 5 H), 7.26 - 7.17 (m, 1 H), 7.15 - 7.11 (m, 1 H), 7.01 (s, 2 H), 6.72 - 6.64 (m, 1 H), 6.42 - 6.30 (m, 1 H), 3.95 - 3.69 (m, 1 H), 3.60 (s, 2 H), 2.95 - 2.78 (m, 2 H), 2.23 - 2.07 (m, 2 H), 1.98 - 1.81 (m, 2 H), 1.62 - 1.53 (m, 2 H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxi de-d ₆ ) δ -136.277.

[001073] Example 546: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(l-methyl-1H-imidazol-5- yl)- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile

Example 546 was prepared in a manner similar to Example 469. MS: m/z = 583.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ 8.21 (d, J= 8.4 Hz, 1H), 8.16 - 7.92 (m, 3H), 7.76 (d, J= 8.4 Hz, 1H), 7.67 (s, 1H), 7.55 (s, 1H), 7.49 - 7.39 (m, 4H), 7.21 (dd, J= 7.6, 1.6 Hz, 1H), 7.09 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.39 (dd, J= 7.6, 4.8 Hz, 1H), 3.89 - 3.77 (m, 1H), 3.75 (s, 3H), 3.58 (s, 2H), 2.86 - 2.74 (m, 2H), 2.13 (t, J= 10.8 Hz, 2H), 1.89 (d, J= 10.8 Hz, 2H), 1.56 - 1.41 (m, 2H).

[001074] Example 547: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(5-methylpyridin-2-yl)-3 H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

A mixture of Example 405 (100 mg, 186 μmol), (5-methylpyridin-2-yl)boronic acid (76.5 mg, 559 μmol), cataCXium A Pd G3 (15.8 mg, 18.6 μmol), CuBr (20 mg, 140 μmol) and CS ₂ CO ₃ (182 mg, 559 μmol) in 1,4-dioxane (3 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 90 °C for 3 hr under N2 atmosphere. The reaction mixture was poured into H ₂ O (15 mL) and extracted with EtOAc (15 mL x 3). The combined organic phases were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-HPLC (column: Waters Xhridge 150 x 25 mm x 5 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 34% - 64% B over 11 min), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5- (5-methylpyridin-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl) piperidin-4-yl)amino)pyrimidine- 2-carbonitrile (Example 547, 15.5 mg, yield: 14%) was obtained as a yellow solid. MS: m/z = 594.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.46 - 8.43 (m, 1H), 8.38 (d, J= 6.0 Hz, 1H), 8.22 (d, J = 8.0 Hz, 1H), 8.17 (d, J = 8.0 Hz, 1H), 8.03 - 7.93 (m, 2H), 7.70 - 7.63 (m, 1H), 7.57 - 7.52 (m, 2H), 7.49 - 7.42 (m, 2H), 7.32 (dd, J = 7.6, 1.6 Hz, 1H), 6.63 - 6.54 (m, 1H), 6.46 (dd, J = 7.6, 5.2 Hz, 1H), 4.13 - 3.79 (m, 1H), 3.66 (s, 2H), 3.00 - 2.92 (m, 2H), 2.38 (s, 3H), 2.32 - 2.22 (m, 2H), 2.02 - 1.97 (m, 2H), 1.68 - 1.55 (m, 2H). [001075] Example 548: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-cyanopyridin-2-yl)-3H - imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 548 was prepared in a manner similar to Example 261. MS: m/z = 605.5 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.81 (d, J = 4.8 Hz, 1H), 8.57 - 8.50 (m, 2H), 8.21 (d, J = 8.0 Hz, 1H), 8.18 - 8.11 (m, 1H), 8.09 (d, J = 4.8 Hz, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 4.8 Hz, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.16 (d, J = 7.6 Hz, 1H), 6.69 (br s, 2H), 6.43 (d, J = 6.0 Hz, 1H), 6.38 (dd, J = 8.0, 4.8 Hz, 1H), 4.22 - 3.79 (m, 1H), 3.69 (s, 2H), 2.99 - 2.91 (m, 2H), 2.35 - 2.27 (m, 2H), 2.12 - 2.06 (m, 2H), 1.38 - 1.28 (m, 2H). [001076] Example 549: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-6-bromo-5-(4-fluorophenyl) - 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile Example 549 was prepared in a manner similar to Example 261. MS: m/z = 675.0, 677.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.64 (s, 1H), 8.20 - 7.93 (m, 3H), 7.66 - 7.55 (m, 2H), 7.45 - 7.37 (m, 4H), 7.29 - 7.27 (m, 2H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 6.96 (br s, 2H), 6.66 (d, J = 6.0 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.85 - 3.71 (m, 1H), 3.54 (s, 2H), 2.83 - 2.72 (m, 2H), 2.18 - 2.08 (m, 2H), 1.92 - 1.77 (m, 2H), 1.53 - 1.38 (m, 2H). [001077] Example 550: 2-(2-Aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin-1-yl)methyl)phenyl)-5-methyl-3H-imidazo[4 ,5-b]pyridine-6-carbonitrile

Example 550 was prepared in a manner similar to Example 261. MS: m/z = 542.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.72 (s, 1H), 8.13 - 8.03 (m, 2H), 8.00 (dd, J= 4.4, 1.6 Hz, 1H), 7.51 - 7.43 (m, 2H), 7.42 - 7.36 (m, 2H), 7.16 (dd, J= 7.6, 1.6 Hz, 1H), 6.93 (br s, 2H), 6.67 (d, J= 6.0 Hz, 1H), 6.38 (dd, J= 7.6, 4.8 Hz, 1H), 3.87 - 3.75 (m, 1H), 3.57 (s, 2H), 2.85 - 2.77 (m, 2H), 2.70 (s, 3H), 2.22 - 2.10 (m, 2H), 1.92 - 1.83 (m, 2H), 1.56 - 1.43 (m, 2H). [001078] Example 551: 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(3-fluoropyridin-4-yl)-3 H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

A mixture of Example 405 (100 mg, 186 μmol), (3-fluoropyridin-4-yl)boronic acid (26.2 mg, 186 μmol), Na ₂ CO ₃ (59.2 mg, 559 μmol), Pd(dppf)CI ₂ (13.6 mg, 18.6 μmol) in H ₂ O (0.5 mL) and 1,4-dioxane (2 mL) was degassed and purged with N2 three times. The mixture was stirred at 100 °C for 16 hr under N2 atmosphere. The reaction mixture was poured into H ₂ O (15 mL) and extracted with EtOAc (15 mL x 3). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-HPLC (column: Phenomenex C18 150 x 25 mm x 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 38% - 68% B over 11 min), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(3-fluoropyridin-4- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile (Example 551, 19.2 mg, yield: 16%) was obtained as a pink lyophilized powder. MS: m/z = 598.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.69 (d, J= 2.8 Hz, 1H), 8.51 (d, J= 4.8 Hz, 1H), 8.36 (d, J= 8.0 Hz, 1H), 8.14 - 7.97 (m, 3H), 7.97 - 7.91 (m, 1H), 7.85 (dd, J= 6.8, 5.2 Hz 1H), 7.48 - 7.43 (m, 4H), 7.18 (dd, J= 7.6, 1.6 Hz 1H), 6.99 (s, 2H), 6.66 (d, J= 6.4 Hz, 1H), 6.38 (dd, J= 7.6, 4.8 Hz 1H), 3.90 - 3.71 (m, 1H), 3.57 (s, 2H), 2.87 - 2.74 (m, 2H), 2.21 - 2.05 (m, 2H), 1.94 - 1.81 (m, 2H), 1.58 - 1.37 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -131.931.

[001079] Example 552: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(5-methoxypyridin-2-yl)- 3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

To a solution of Intermediate 242 (150 mg, 339 μmol, HC1 salt) and Intermediate 51 (103 mg, 325 μmol, TFA salt) in DMF (5 mL) were added K ₂ CO ₃ (140 mg, 1.02 mmol) and Nal (10.2 mg, 67.7 μmol). The mixture was stirred at 50 °C for 0.5 hr. The reaction mixture was poured into H ₂ O (50 mL) and extracted with CH ₂ CI ₂ (15 mL x 3). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 6% MeOH in CH ₂ CI ₂ ), 4-((l-(4-(2-(2- aminopyridin-3-yl)-5-(5-methoxypyridin-2-yl)-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin- 4-yl)amino)pyrimidine-2-carbonitrile (Example 552, 50.2 mg, yield: 24%) was obtained as a light-yellow solid. MS: m/z = 610.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.39 - 8.33 (m, 2H), 8.26 (d, J= 8.4 Hz, 1H), 8.13 (d, J= 8.8 Hz, 1H), 8.09 - 8.03 (m, 2H), 8.00 (dd, J= 4.8, 1.6 Hz, 1H), 7.51 - 7.44 (m, 5H), 7.15 (dd, J= 7.6, 1.6 Hz, 1H), 7.02 (s, 2H), 6.68 (d, J= 6.0 Hz, 1H), 6.38 (dd, J= 7.6, 4.8 Hz, 1H), 3.87 (s, 3H), 3.85 - 3.77 (m, 1H), 3.60 (s, 2H), 2.88 - 2.79 (m, 2H), 2.22 - 2.12 (m, 2H), 1.96 - 1.84 (m, 2H), 1.56 - 1.45 (m, 2H). [001080] Example 553: 2-(2-Aminopyridin-3-yl)-l-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin- 1 -yl)methyl)phenyl)- 1H-imidazo[4,5-c]pyridine-6-carbonitrile

Example 553 was prepared in a manner similar to Example 261. MS: m/z = 528.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.22 (d, J= 0.8 Hz, 1H), 8.12 - 8.04 (m, 3H), 8.03 - 8.02 (m, 1H), 7.51 - 7.48 (m, 2H), 7.45 - 7.43 (m, 2H), 7.22 (dd, J= 7.6, 1.6 Hz, 1H), 6.88 (s, 2H), 6.67 (d, J= 6.0 Hz, 1H), 6.41 (dd, J= 7.6, 4.8 Hz, 1H), 3.88 - 3.73 (m, 1H), 3.58 (s, 2H), 2.82 (d, J= 11.6 Hz, 2H), 2.18 - 2.12 (m, 2H), 1.89 (d, J= 10.4 Hz, 2H), 1.54 - 1.47 (m, 2H). [001081] Example 554: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(4-methyloxazol-5-yl)-3H - imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 554 was prepared in a manner similar to Example 469. MS: m/z = 584.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.38 (s, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.11 - 8.01 (m, 3H), 7.71 (d, J = 8.4 Hz, 1H), 7.50 - 7.47 (m, 2H), 7.46 - 7.43 (m, 2H), 7.27 - 7.24 (m, 1H), 7.10 (s, 2H), 6.68 (d, J = 6.0 Hz, 1H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 3.90 - 3.73 (m, 1H), 3.59 (s, 2H), 2.80 (d, J = 10.8 Hz, 2H), 2.35 (s, 3H), 2.17 - 2.10 (m, 2H), 1.93 - 1.85 (m, 2H), 1.54 - 1.46 (m, 2H). [001082] Example 555: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(1-cyclopropyl-1H-pyrazo l-4- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile A mixture of example 405 (300 mg, 559 µmol),(1-cyclopropyl-1H-pyrazol-4-yl)boronic acid (93.4 mg, 615 µmol), Cs ₂ CO ₃ (546 mg, 1.68 mmol), Pd(dppf)Cl ₂ (40.9 mg, 55.9 µmol) in H ₂ O (0.2 mL) and 1,4-dioxane (1 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 100 °C for 16 hr under N ₂ atmosphere. The reaction mixture was poured into H ₂ O (50 mL) and extracted with EtOAc (50 mL x 3). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by prep- HPLC (column: Waters xbridge BEH C18 150 x 25 mm x 5 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 31% - 61% B over 10 min), 4-((1-(4-(2-(2-aminopyridin-3-yl)-5- (1-cyclopropyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-y l)benzyl)piperidin-4- yl)amino)pyrimidine-2-carbonitrile (Example 555, 77.6 mg, yield: 22%) was obtained as a light- yellow lyophilized powder. MS: m/z = 609.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.25 (s, 1H), 8.15 (d, J = 8.4 Hz, 1H), 8.11 - 8.03 (m, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.89 (s, 1H), 7.68 (d, J = 8.4 Hz, 1H), 7.49 - 7.45 (m, 2H), 7.42 - 7.38 (m, 2H), 7.10 (d, J = 6.4 Hz, 1H), 7.00 (s, 2H), 6.68 (d, J = 6.0 Hz, 1H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.88 - 3.71 (m, 2H), 3.59 (s, 2H), 2.83 (d, J = 11.2 Hz, 2H), 2.20 - 2.11 (m, 2H), 1.94 - 1.85 (m, 2H), 1.55 - 1.45 (m, 2H), 1.09 - 1.04 (m, 2H), 1.00 - 0.93 (m, 2H). [001083] Example 556: 2-(2-Aminopyridin-3-yl)-1-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin-1-yl)methyl)phenyl)-1H-imidazo[4,5-b]pyra zine-5,6-dicarbonitrile Example 556 was prepared in a manner similar to Example 261. MS: m/z = 554.2 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.13 (dd, J = 4.4,1.6 Hz, 1H), 8.09 - 8.05 (m, 2H), 7.56 - 7.51 (m, 2H), 7.48 - 7.44 (m, 2H), 7.29 (dd, J = 8.0, 1.6 Hz, 1H), 7.20 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.46 (dd, J = 8.0, 4.8 Hz, 1H), 3.87 - 3.76 (m, 1H), 3.59 (s, 2H), 2.86 - 2.76 (m, 2H), 2.21 - 2.10 (m, 2H), 1.94 - 1.83 (m, 2H), 1.57 - 1.41 (m, 2H). [001084] Example 557: 2-(2-Aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin-1-yl)methyl)phenyl)-5-(4-fluorophenyl)-3H -imidazo[4,5-b]pyridine-6- carbonitrile Example 557 was prepared in a manner similar to Example 261. MS: m/z = 622.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.90 (s, 1H), 8.13 - 7.99 (m, 3H), 7.83 (dd, J = 8.4, 5.2 Hz, 2H), 7.48 - 7.42 (m, 4H), 7.38 - 7.36 (m, 2H), 7.19 (dd, J = 7.6, 1.2 Hz, 1H), 6.94 (br s, 2H), 6.69 (d, J = 6.0 Hz, 1H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 3.90 - 3.70 (m, 1H), 3.56 (s, 2H), 2.84 - 2.76 (m, 2H), 2.19 - 2.06 (m, 2H), 1.92 - 1.77 (m, 2H), 1.56 - 1.41 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -111.61. [001085] Example 558: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-fluoropyridin-3-yl)-3 H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 558 was prepared in a manner similar to Example 469. MS: m/z = 598.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.42 - 8.24 (m, 3H), 8.16 - 7.94 (m, 3H), 7.88 (dd, J = 8.0, 4.4 Hz, 1H), 7.53 - 7.40 (m, 5H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 6.99 (s, 2H), 6.73 - 6.61 (m, 1H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.90 - 3.75 (m, 1H), 3.58 (s, 2H), 2.89 - 2.77 (m, 2H), 2.22 - 2.09 (m, 2H), 1.97 - 1.79 (m, 2H), 1.56 - 1.34 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide- d ₆ ) δ -70.367. [001086] Example 559: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(1-methyl-1H-1,2,4-triaz ol-3- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile Example 559 was prepared in a manner similar to Example 261. MS: m/z = 584.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.52 (s, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.13 - 8.03 (m, 3H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.51 - 7.41 (m, 4H), 7.19 - 7.11 (m, 1H), 6.97 (s, 2H), 6.68 (d, J = 5.2 Hz, 1H), 6.40 - 6.32 (m, 1H), 3.92 (s, 3H), 3.88 - 3.75 (m, 1H), 3.59 (s, 2H), 2.91 - 2.80 (m, 2H), 2.22 - 2.12 (m, 2H), 1.93 - 1.83 (m, 2H), 1.55 - 1.46 (m, 2H). [001087] Example 560: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(5-ethoxypyridin-2-yl)-3 H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 560 was prepared in a manner similar to Example 261. MS: m/z = 624.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.39 - 8.32 (m, 2H), 8.26 (d, J = 8.4 Hz, 1H), 8.15 - 8.03 (m, 3H), 8.00 (dd, J = 5.2, 2.0 Hz, 1H), 7.52 - 7.43 (m, 5H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.02 (br s, 2H), 6.68 (d, J = 6.0 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 4.15 (q, J = 6.8 Hz, 2H), 3.90 - 3.75 (m, 1H), 3.60 (s, 2H), 2.90 - 2.80 (m, 2H), 2.22 - 2.12 (m, 2H), 1.97 - 1.83 (m, 2H), 1.57 - 1.45 (m, 2H), 1.36 (t, J = 7.2 Hz, 3H). [001088] Example 561: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-fluoropyridin-4-yl)-3 H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 561 was prepared in a manner similar to Example 469. MS: m/z = 598.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.44 - 8.28 (m, 2H), 8.26 - 8.16 (m, 1H), 8.12 - 7.93 (m, 4H), 7.75 (s, 1H), 7.52 - 7.45 (m, 4H) 7.24 - 7.13 (m, 1H), 7.04 (br s, 2H), 6.72 - 6.60 (m, 1H), 6.45 - 6.33 (m, 1H), 3.88 - 3.75 (m, 1H), 3.60 (s, 2H), 2.89 - 2.77 (m, 2H), 2.26 - 2.08 (m, 2H), 1.96 - 1.81 (m, 2H), 1.59 - 1.43 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ 68.690. [001089] Example 562: 4-((1-(4-(2-(3-Aminopyrazin-2-yl)-5-(2-methyl-2H-1,2,3-triaz ol-4- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile Example 562 was prepared in a manner similar to Example 261. MS: m/z = 585.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.35 (d, J = 8.0 Hz, 1H), 8.13 - 7.93 (m, 5H), 7.76 (br s, 2H), 7.48 (d, J = 2.4 Hz, 1H), 7.44 - 7.40 (m, 2H), 7.38 - 7.33 (m, 2H), 6.68 (d, J = 5.2 Hz, 1H), 4.21 (s, 3H), 3.90 - 3.76 (m, 1H), 3.60 (s, 2H), 2.93 - 2.82 (m, 2H), 2.25 - 2.12 (m, 2H), 1.98 - 1.84 (m, 2H), 1.59 - 1.43 (m, 2H). [001090] Example 563: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(3-methoxypyridin-2-yl)- 3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 563 was prepared in a manner similar to Example 261. MS: m/z = 610.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.26 - 8.20 (m, 2H), 8.12 - 8.02 (m, 2H), 7.99 (dd, J = 4.8, 2.0 Hz, 1H), 7.69 (d, J = 8.0 Hz, 1H), 7.60 - 7.56 (m, 1H), 7.45 - 7.39 (m, 5H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.00 (br s, 2H), 6.66 (d, J = 6.0 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.88 - 3.78 (m, 1H), 3.76 (s, 3H), 3.55 (s, 2H), 2.84 - 2.75 (m, 2H), 2.17 - 2.07 (m, 2H), 1.89 - 1.80 (m, 2H), 1.51 - 1.40 (m, 2H). [001091] Example 564: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(1-methyl-1H-1,2,3-triaz ol-5- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile Example 564 was prepared in a manner similar to Example 261. MS: m/z = 584.2 [M + H] ⁺ . ¹ HNMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.40 - 8.31 (m, 2H), 8.14 - 7.97 (m, 3H), 7.89 (d, J = 8.4 Hz, 1H), 7.55 - 7.40 (m, 4H), 7.24 (dd, J = 7.6, 1.6 Hz, 1H), 7.09 (s, 2H), 6.67 (d, J = 5.6 Hz, 1H), 6.41 (dd, J = 8.0, 4.8 Hz, 1H), 4.16 (s, 3H), 3.89 - 3.72 (m, 1H), 3.58 (s, 2H), 2.85 - 2.73 (m, 2H), 2.20 - 2.08 (m, 2H), 1.97 - 1.81 (m, 2H), 1.57 - 1.41 (m, 2H). [001092] Example 565: 2-(2-Aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin-1-yl)methyl)phenyl)-6-methyl-3H-imidazo[4 ,5-b]pyridine-5-carbonitrile Example 565 was prepared in a manner similar to Example 261. MS: m/z = 542.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.19 (s, 1H), 8.12 - 8.05 (m, 1H), 8.02 (dd, J = 5.2, 2.0 Hz, 1H), 7.70 (d, J = 8.0 Hz, 2H), 7.55 (d, J = 8.0 Hz, 2H), 7.36 (dd, J = 7.6, 1.6 Hz, 1H), 6.66 (d, J = 6.0 Hz, 1H), 6.48 (dd, J = 8.0, 5.2 Hz, 1H), 4.32 - 4.15 (m, 3H), 3.50 - 3.38 (m, 2H), 3.17 - 3.00 (m, 2H), 2.70 (s, 3H), 2.27 - 2.20 (m, 2H), 1.87 - 1.77 (m, 2H). [001093] Example 566: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(5-methyl-1,3,4-oxadiazo l-2- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile Example 566 was prepared in a manner similar to Example 261. MS: m/z = 585.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) δ 8.35 - 8.27 (m, 1H), 8.27 - 8.20 (m, 2H), 8.19 - 8.10 (m 1H), 8.06 (dd, J = 4.8, 1.6 Hz, 1H), 7.54 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 8.0 Hz, 2H), 7.08 (dd, J = 7.6, 1.2 Hz, 1H), 6.95 - 6.83 (m, 2H), 6.50 - 6.43 (m, 1H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 5.47 - 5.24 (m, 1H), 3.74 (s, 2H), 3.11 - 2.94 (m, 2H), 2.63 (s, 3H), 2.35 - 2.28 (m, 2H), 2.09 (d, J = 10.4 Hz, 2H), 1.75 - 1.62 (m, 2H). [001094] Example 567: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(1-methyl-1H-1,2,4-triaz ol-5- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile Example 567 was prepared in a manner similar to Example 261. MS: m/z = 584.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.37 (d, J = 8.4 Hz, 1H), 8.16 (d, J = 8.4 Hz, 1H), 8.11 - 7.98 (m, 4H), 7.51 - 7.40 (m, 4H), 7.26 (dd, J = 7.6, 1.6 Hz, 1H), 7.09 (s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.42 (dd, J = 7.6, 4.8 Hz, 1H), 4.08 (s, 3H), 3.88 - 3.72 (m, 1H), 3.58 (s, 2H), 2.85 - 2.73 (m, 2H), 2.19 - 2.09 (m, 2H), 1.93 - 1.82 (m, 2H), 1.53 - 1.42 (m, 2H). [001095] Example 568: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-methyl-2H-1,2,3-triaz ol-2- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile Example 568 was prepared in a manner similar to Example 261. MS: m/z = 584.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.40 (d, J = 8.4 Hz, 1H), 8.12 - 7.96 (m, 4H), 7.90 (s, 1H), 7.52 - 7.43 (m, 4H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 6.95 (s, 2H), 6.68 (d, J = 5.6 Hz, 1H), 6.41 - 6.35 (m, 1H), 3.94 - 3.68 (m, 1H), 3.59 (s, 2H), 2.87 - 2.79 (m, 2H), 2.36 (s, 3H), 2.22 - 2.13 (m, 2H), 1.93 - 1.85 (m, 2H), 1.59 - 1.48 (m, 2H). [001096] Example 569: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-methyl-4H-1,2,4-triaz ol-3- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile Example 569 was prepared in a manner similar to Example 261. MS: m/z = 584.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.53 (s, 1H), 8.36 (d, J = 8.4 Hz, 1H), 8.17 (d, J = 8.4 Hz, 1H), 8.12 - 7.99 (m, 3H), 7.49 - 7.45 (m, 4H), 7.25 (dd, J = 8.0 Hz, 2.0 Hz, 1H), 7.08 (s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.41(dd, J = 7.6 Hz, 4.8 Hz, 1H), 3.85 - 3.81 (m, 1H), 3.80 (s, 3H), 3.58 (s, 2H), 2.83 - 2.75 (m, 2H), 2.20 - 2.08 (m, 2H), 1.95 - 1.83 (m, 2H), 1.54 - 1.43 (m, 2H). [001097] Example 570: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(3-fluoropyridin-2-yl)-3 H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 570 was prepared in a manner similar to Example 341. MS: m/z = 620.1 [M + Na] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.53 (d, J = 4.8 Hz, 1H), 8.34 (d, J = 8.0 Hz, 1H), 8.11 - 7.98 (m, 4H), 7.86 - 7.76 (m, 1H), 7.59 - 7.50 (m, 1H), 7.48 - 7.39 (m, 4H), 7.18 (d, J = 7.6, 1H), 6.98 (br s, 2H), 6.72 - 6.64 (m, 1H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.86 - 3.77 (m, 1H), 3.56 (s, 2H), 2.87 - 2.75 (m, 2H), 2.21 - 2.09 (m, 2H), 1.94 - 1.79 (m, 2H), 1.56 - 1.41 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -121.825. [001098] Example 571: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(6-methylpyridin-2-yl)-3 H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 571 was prepared in a manner similar to Example 341. MS: m/z = 616.1 [M + Na] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.48 (d, J = 8.4 Hz, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.23 - 7.86 (m, 4H), 7.77 (t, J = 8.0 Hz, 1H), 7.53 - 7.41 (m, 4H), 7.26 (d, J = 7.6 Hz, 1H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.39 (dd, J = 7.6, 4.4 Hz, 1H), 3.90 - 3.75 (m, 1H), 3.60 (s, 2H), 2.92 - 2.78 (m, 2H), 2.57 (s, 3H), 2.24 - 2.11 (m, 2H), 1.95 - 1.76 (m, 2H), 1.60 - 1.40 (m, 2H). [001099] Example 572: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(1-(difluoromethyl)-1H- 1,2,4-triazol-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)pip eridin-4-yl)amino)pyrimidine-2- carbonitrile Example 572 was prepared in a manner similar to Example 261. MS: m/z = 620.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.18 (s, 1H), 8.34 (d, J = 8.4 Hz, 1H), 8.19 (d, J = 8.4 Hz, 1H), 8.11 - 7.84 (m, 4H), 7.51 - 7.41 (m, 4H), 7.19 - 7.12 (m, 1H), 6.99 (s, 2H), 6.68 (d, J = 6.0 Hz, 1H), 6.40 - 6.35 (m, 1H), 3.88 - 3.77 (m, 1H), 3.59 (s, 2H), 2.89 - 2.81 (m, 2H), 2.23 - 2.13 (m, 2H), 1.95 - 1.84 (m, 2H), 1.54 - 1.43 (m, 2H).19F NMR (400 MHz, [001100] Example 573: 4-((1-(4-(2-(4-Aminopyrimidin-5-yl)-5-(5-fluoropyridin-2-yl) -3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 573 was prepared in a manner similar to Example 261. MS: m/z = 599.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.66 (d, J = 2.0 Hz, 1H), 8.53 - 8.29 (m, 3H), 8.25 - 8.19 (m, 1H), 8.17 - 7.99 (m, 2H), 7.94 (s, 1H), 7.85 - 7.66 (m, 3H), 7.52 (s, 4H), 6.87 - 6.62 (m, 1H), 3.98 - 3.67 (m, 1H), 3.60 (s, 2H), 2.89 - 2.78 (m, 2H), 2.26 - 2.12 (m, 2H), 1.95 - 1.85 (m, 2H), 1.57 - 1.43 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -127.659. [001101] Example 574: 4-((1-(4-(2-(3-Aminopyrazin-2-yl)-5-(5-fluoropyridin-2-yl)-3 H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 574 was prepared in a manner similar to Example 261. MS: m/z = 599.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ 8.67 (d, J = 2.4 Hz, 1H), 8.48 - 8.33 (m, 2H), 8.20 (dd, J = 8.8, 4.8 Hz, 1H), 8.13 - 8.04 (m, 2H), 8.02 (d, J = 2.0 Hz, 1H), 7.90 - 7.73 (m, 3H), 7.49 (d, J = 2.4 Hz, 1H), 7.47 - 7.37 (m, 4H), 6.68 (d, J = 6.0 Hz, 1H), 3.95 - 3.75 (m, 1H), 3.61 (s, 2H), 2.94 - 2.81 (m, 2H), 2.24 - 2.14 (m, 2H), 1.97 - 1.86 (m, 2H), 1.55 - 1.47 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -127.539. [001102] Example 575: 4-((1-(4-(5-(5-Fluoropyridin-2-yl)-2-(pyridin-3-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 575 was prepared in a manner similar to Example 261. MS: m/z = 583.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ 8.81 - 8.53 (m, 3H), 8.47 - 8.33 (m, 2H), 8.25 (dd, J = 8.8, 4.8 Hz, 1H), 8.20 - 7.98 (m, 2H), 7.94 - 7.80 (m, 2H), 7.57 - 7.48 (m, 4H), 7.45 (dd, J = 8.0, 4.8 Hz, 1H), 6.85 - 6.65 (m, 1H), 3.92 - 3.74 (m, 1H), 3.62 (s, 2H), 2.90 -2.82 (m, 2H), 2.23 - 2.12 (m, 2H), 1.97 - 1.84 (m, 2H), 1.58 - 1.45 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide- d ₆ ) δ -127.614. [001103] Example 576: 4-((1-(4-(2-(2-Aminophenyl)-5-(5-fluoropyridin-2-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 576 was prepared in a manner similar to Example 261. MS: m/z = 597.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ 8.66 (d, J = 2.8 Hz, 1H), 8.42 - 8.35 (m, 1H), 8.30 - 8.19 (m, 2H), 8.14 - 8.04 (m, 2H), 7.90 - 7.77 (m, 1H), 7.50 - 7.38 (m, 4H), 7.12 - 7.01 (m, 1H), 6.81 (d, J= 8.0 Hz, 2H), 6.68 (d, J= 6.0 Hz, 1H), 6.32 - 6.28 (m, 2H), 3.94 - 3.72 (m, 1H), 3.59 (s, 2H), 2.83 (d, J= 10.8 Hz, 2H), 2.27 - 2.05 (m, 2H), 1.96 - 1.81 (m, 2H), 1.60 - 1.40 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ -127.98.

[001104] Example 577: 4-((l-(4-(5-(5-Fluoropyridin-2-yl)-2-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile

Example 577 was prepared in a manner similar to Example 261. MS: m/z = 582.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.52 (d, J= 2.8 Hz, 1H), 8.47 (d, J= 8.4 Hz, 1H), 8.34 (dd, J= 8.8, 4.4 Hz, 1H), 8.23 (d, J= 8.4 Hz, 1H), 8.06 - 7.95 (m, 1H), 7.63 - 7.55 (m, 5H), 7.48 - 7.44 (m, 3H), 7.40 (d, J= 7.6 Hz, 2H), 6.60 (d, J= 4.8 Hz, 1H), 4.08 - 3.85 (m, 1H), 3.69 (s, 2H),3.02 - 2.98 (m, 2H), 2.34 - 2.27 (m, 2H), 2.04 - 1.99 (m, 2H), 1.67 - 1.58 (m, 2H).

[001105] Example 578: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(5-(methoxy-d ₃ )pyridin-2-yl)- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile

To a solution of Intermediate 232 (150 mg, 446 μmol) and Intermediate 51 (82 mg, 404 μmol) in DMF (3 mL) were added K ₂ CO ₃ (186 mg, 1.3 mmol) and Nal (2.5 mg, 17 μmol). The mixture was stirred at 50 °C for 1 hr. The reaction mixture was quenched with H ₂ O (10 mL) at 25 °C and extracted with CH ₂ CI ₂ (15 mL x 2). The combined organic layers were washed with brine (50 mL x3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 5% MeOH in CH ₂ CI ₂ )., 4-((l-(4-(2-(2- aminopyridin-3-yl)-5-(5-(methoxy-d ₃ )pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile (Example 578, 22.5 mg, yield: 11% for three steps) was obtained as a yellow solid. MS: m/z = 613.2 [M + H] ⁺ . D% : 3D = 99.3%. ¹ H NMR (400 MHz, Dimethylsulfbxide-d ₆ ) δ 8.39 - 8.34 (m, 2H), 8.27 (d, J= 8.4 Hz, 1H), 8.14 (d, J= 8.8 Hz, 1H), 8.07 - 8.02 (m, 2H), 8.00 (dd, J= 4.8, 1.6 Hz, 1H), 7.51 - 7.44 (m, 5H), 7.16 (dd, J= 7.6, 1.6 Hz, 1H), 7.02 (s, 2H), 6.68 (d, J= 6.0 Hz, 1H), 6.38 (dd, J= 7.6, 4.8 Hz, 1H), 3.92 - 3.72 (m, 1H), 3.60 (s, 2H), 2.87 - 2.80 (m, 2H), 2.21 - 2.12 (m, 2H), 1.95 - 1.85 (m, 2H), 1.55 - 1.45 (m, 2H).

[001106] Example 579: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(5-(difluoromethoxy)pyri din- 2-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)am ino)pyrimidine-2-carbonitrile

To a solution of Intermediate 233 (115 mg, 240 μmol, HC1 salt) and Intermediate 51 (76.2 mg, 240 μmol, TFA) in DMF (2 mL) were added K ₂ CO ₃ (166 mg, 1.20 mmol) and Nal (10.8 mg, 72 μmol). The mixture was stirred at 25 °C for 16 hr. The reaction mixture was poured into H ₂ O (15 mL) and extracted with EtOAc (15 mL x 3). The organic phase was dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 6% MeOH in CH ₂ CI ₂ ), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(5- (difluoromethoxy)pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl )benzyl)piperidin-4- yl)amino)pyrimidine-2-carbonitrile (Example 579, 54.5 mg, yield: 35% for three steps) was obtained as an off white solid. MS: m/z = 646.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.57 (d, J= 2.8 Hz, 1H), 8.41 (d, J= 8.4 Hz, 1H), 8.41 (d, J= 8.4 Hz, 1H), 8.23 (d, J= 8.8 Hz, 1H), 8.12 - 8.03 (m, 2H), 8.03 - 7.98 (m, 1H), 7.77 (dd, J =8.8, 2.8 Hz, 1H), 7.57 - 7.52 (m, 0.5H), 7.51 - 7.46 (m, 3H), 7.39 - 7.31 (m, 0.5H), 7.19 - 7.12 (m, 1H), 7.09 (s, 2H), 6.78 - 6.60 (m, 1H), 6.39 (dd, J =7.6, 4.8 Hz, 1H), 3.93 - 3.74 (m, 1H), 3.60 (br s, 2H), 2.88 - 2.79 (m, 2H), 2.23 - 2.10 (m, 2H), 1.99 - 1.83 (m, 2H), 1.58 - 1.43 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ -82.472.

[001107] Example 580: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(5-(fluoromethoxy)pyridi n-2- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile Example 580 was prepared in a manner similar to Example 261. MS: m/z = 628.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.51 (d, J = 2.8 Hz, 1H), 8.39 (d, J = 8.4 Hz, 1H), 8.30 (d, J = 8.4 Hz, 1H), 8.19 (d, J = 8.8 Hz, 1H), 8.25 - 8.01 (m, 2H), 8.00 (dd, J = 4.8, 2.0 Hz, 1H), 7.68 (dd, J = 8.8, 3.2 Hz, 1H), 7.51 - 7.45 (m, 4H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (s, 2H), 6.68 (d, J = 6.0 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 5.96 (d, J = 53.6 Hz, 2H), 3.87 - 3.76 (m, 1H), 3.60 (s, 2H), 2.90 - 2.80 (m, 2H), 2.24 - 2.10 (m, 2H), 1.95 - 1.85 (m, 2H), 1.57 - 1.44 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -151.294. [001108] Example 581: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(5-methoxypyrimidin-2-yl )- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile Example 581 was prepared in a manner similar to Example 261. MS: m/z = 611.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.66 (s, 2H), 8.42 - 8.38 (m, 1H), 8.33 - 8.28 (m, 1H), 8.14 (d, J = 7.2 Hz, 1H), 8.08 (d, J = 6.0 Hz, 1H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.51 - 7.41 (m, 4H), 7.13 (dd, J = 7.6, 1.6 Hz, 1H), 7.00 (br s, 2H), 6.70 (d, J = 6.0 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.96 (s, 3H), 3.88 - 3.73 (m, 1H), 3.59 (s, 2H), 2.86 - 2.79(m, 2H), 2.22 - 2.12 (m, 2H), 1.94 - 1.85 (m, 2H), 1.57 - 1.46 (m, 2H). [001109] Example 582: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(5-methylpyrazin-2-yl)-3 H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 582 was prepared in a manner similar to Example 261. MS: m/z = 595.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.21 (s, 1H), 8.62 (s, 1H), 8.35 - 8.33 (m, 2H), 8.10 - 8.01 (m, 3H), 7.51 - 7.47 (m, 4H), 7.20 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (s, 2H), 6.67 (d, J = 6.4 Hz, 1H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 3.88 - 3.77 (m, 1H), 3.60 (s, 2H), 2.86-2.81 (m, 2H), 2.54 (s, 3H), 2.20 - 2.13 (m, 2H), 1.93-1.86 (m, 2H), 1.55 - 1.47 (m, 2H). [001110] Example 583: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(5-methoxypyrazin-2-yl)- 3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 583 was prepared in a manner similar to Example 261. MS: m/z = 611.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.91 (d, J = 1.2 Hz, 1H), 8.40 (d, J = 1.2 Hz, 1H), 8.32 (d, J = 8.4 Hz, 1H), 8.25 (d, J = 8.4 Hz, 1H), 8.10 - 8.00 (m, 3H), 7.48 (dd, J = 14.0, 8.4 Hz, 4H), 7.20 (dd, J = 7.2, 1.6 Hz, 1H), 7.03 (s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 3.95 (s, 3H), 3.83 - 3.81 (m, 1H), 3.60 (s, 2H), 2.86 - 2.81 (m, 2H), 2.22 - 2.14 (m, 2H), 1.94 - 1.86 (m, 2H), 1.55 - 1.47 (m, 2H) [001111] Example 584: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(6-ethoxypyridin-3-yl)-3 H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 584 was prepared in a manner similar to Example 469. MS: m/z = 624.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.83 (d, J = 2.0 Hz, 1H), 8.34 - 8.22 (m, 2H), 8.13 - 7.94 (m, 4H), 7.51 - 7.42 (m, 4H), 7.15 (d, J = 7.2 Hz, 1H), 7.04 (s, 2H), 6.88 (d, J = 8.8 Hz, 1H), 6.73 - 6.63 (m, 1H), 6.38 (dd, J = 8.0, 5.2 Hz, 1H), 4.34 (m, J = 7.2 Hz, 2H), 3.87 - 3.76 (m, 1H), 3.59 (s, 2H), 2.92 - 2.74 (m, 2H), 2.22 - 2.09 (m, 2H), 1.93 - 1.78 (m, 2H), 1.56 - 1.44 (m, 2H), 1.33 (t, J = 7.2 Hz, 3H). [001112] Example 585: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(5-cyclopropoxypyridin-2 - yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile

To a solution of Intermediate 339 (166 mg, 354 μmol, HC1 salt) and Intermediate 51 (108 mg, 531 μmol) inDMF (1 mL) were added K ₂ CO ₃ (147 mg, 1.06 mmol) andNal (5.31 mg, 35.4 μmol). The mixture was stirred at 80 °C for 8 hr. The mixture was diluted with H2O (10 mL) and extracted with ethyl acetate (10 mL x 2). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by prep-HPLC (column: C18 150 x 30mm; mobile phase: [water (NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN]; gradient: 54% - 84% B over 7 min), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(5-cyclopropoxypyridin-2 -yl)-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile (Example 585, 45.5 mg, yield: 20% for three steps) was obtained as a light yellow solid. MS: m/z = 658.2 [M + Na] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.45 (d, J= 3.2 Hz, 1H), 8.36 (d, J= 8.4 Hz, 1H), 8.27 (d, J= 8.4 Hz, 1H), 8.14 (d, J= 8.8 Hz, 1H), 8.13 - 8.02 (m, 2H), 8.00 (dd, J= 4.8, 2.0 Hz, 1H), 7.60 (dd, J= 8.4, 2.8 Hz, 1H), 7.51 - 7.44 (m, 4H), 7.16 (dd, J= 8.0, 2.0 Hz, 1H), 7.02 (br s, 2H), 6.67 (d, J= 6.0 Hz, 1H), 6.38 (dd, J= 7.6, 4.8 Hz, 1H), 4.01 - 3.96 (m, 1H), 3.89 - 3.73 (m, 1H), 3.60 (s, 2H), 2.92 - 2.79 (m, 2H), 2.21 - 2.12 (m, 2H), 1.95 - 1.82 (m, 2H), 1.56 - 1.44 (m, 2H), 0.85 - 0.80 (m, 2H), 0.73 - 0.69 (m, 2H).

[001113] Example 586: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(5-isopropoxypyridin-2-y l)- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile

To a solution of Intermediate 340 (199 mg, 424 μmol) and Intermediate 51 (112 mg, 551 μmol) in DMF (1 mL) were added Nal (6.35 mg, 42.4 μmol) and K ₂ CO ₃ (176 mg, 1.27 mmol). The mixture was stirred at 25 °C for 12 hr. The mixture was diluted with and extracted with EtOAc

(5 mL x 2). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by prep-HPLC (column: C18 150 x 30 mm; mobile phase: [water (NH ₃ H ₂ O+NH ₄ HCO ₃ ) - ACN]; gradient:59% - 89% B over 7 min), 4-((l-(4-(2-(2-aminopyridin- 3-yl)-5-(5-isopropoxypyridin-2-yl)-3H-imidazo[4,5-b]pyridin- 3-yl)benzyl)piperi din-4- yl)amino)pyrimidine-2-carbonitrile (Example 586, 79.5 mg, yield: 29.4% for three steps) was obtained as a light yellow solid. MS: m/z = 638.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.39 - 8.30 (m, 2H), 8.25 (d, J= 8.4 Hz, 1H), 8.14 - 8.01 (m, 3H), 8.00 (dd, J= 4.8, 1.6 Hz, 1H), 7.51 -7.43 (m, 5H), 7.15 (dd, J= 7.6, 1.2 Hz, 1H), 7.03 (br s, 2H), 6.68 (br d, J= 6.4 Hz, 1H), 6.37 (dd, J= 7.6, 4.8 Hz, 1H), 4.77 - 4.68 (m, 1H), 3.82 - 3.81 (m, 1H), 3.60 (s, 2H), 2.84 - 2.82 (m, 2H), 2.19 - 2.13 (m, 2H), 1.95 -1.83 (m, 2H), 1.55 - 1.42 (m, 2H), 1.30 (d, J = 6.0 Hz, 6H).

[001114] Example 587: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(6-cyclopropylpyridin-3- yl)- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile

To a solution of Intermediate 341 (190 mg, 420 μmol, HC1 salt) and Intermediate 51 (102 mg, 503 μmol) in DMF (3 mL) were added K ₂ CO ₃ (174 mg, 1.26 mmol) and Nal (6.29 mg, 42.0 μmol). The mixture was stirred at 25 °C for 12 hr. The mixture was diluted with H ₂ O (10 mL) and extracted with ethyl acetate (10 mL x 2). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by prep-HPLC (column: C18 150 x 30 mm; mobile phase: [water (NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN]; gradient: 45% - 75% B over 7 min), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(6-cyclopropylpyridin-3- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile (Example 587, 93.4 mg, yield: 36% for three steps) was obtained as a light yellow solid. MS: m/z = 620.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.05 (d, J= 2.4 Hz, 1H), 8.28 (d, J= 8.4 Hz, 1H),

8.21 (dd, J= 8.4, 2.4 Hz, 1H), 8.07 (dd, J= 12.8, 6.0 Hz, 2H), 8.02 - 7.97 (m, 2H), 7.50 - 7.42 (m, 4H), 7.37 (d, J= 8.4 Hz, 1H), 7.16 (dd, J= 7.6, 1.6 Hz, 1H), 7.04 (br s, 2H), 6.67 (d, J= 6.4 Hz, 1H), 6.38 (dd, J= 7.6, 4.8 Hz, 1H), 3.95 - 3.71 (m, 1H), 3.59 (s, 2H), 2.90 - 2.75 (m, 2H),

2.21 - 2.09 (m, 3H), 1.99 - 1.82 (m, 2H), 1.59 - 1.45 (m, 2H), 0.99 - 0.93 (m, 4H).

[001115] Example 588: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(3-methyl-4H-l,2,4-triaz ol-4- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile Example 588 was prepared in a manner similar to Example 261. MS: m/z = 584.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.43 (d, J = 8.4 Hz, 1H), 8.19 - 7.91 (m, 4H), 7.83 (d, J = 8.4 Hz, 1H), 7.52 - 7.41 (m, 4H), 7.25 (dd, J =7.6, 1.6 Hz, 1H), 7.04 (s, 2H), 6.74 - 6.60 (m, 1H), 6.41 (dd, J =7.6, 4.8 Hz, 1H), 3.91 - 3.69 (m, 1H), 3.58 (br s, 2H), 2.83 - 2.75 (m, 2H), 2.56 (s, 3H), 2.19 - 2.07 (m, 2H), 1.96 - 1.80 (m, 2H), 1.54 - 1.42 (m, 2H). [001116] Example 589: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(3-methyl-1H-1,2,4-triaz ol-1- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile Example 589 was prepared in a manner similar to Example 261. MS: m/z = 584.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.97 (s, 1H), 8.41 (d, J = 8.4 Hz, 1H), 8.10 - 8.05 (m, 2H), 8.02 - 7.99 (m, 1H), 7.85 - 7.84 (m, 1H), 7.48 - 7.42 (m, 4H), 7.17 (dd, J = 7.6, 1.2 Hz, 1H), 6.93 (s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 3.86 - 3.78 (m, 1H), 3.58 (s, 2H), 2.85 - 2.80 (m, 2H), 2.38 (s, 3H), 2.18 - 2.12 (m, 2H), 1.93 - 1.86 (m, 2H), 1.54 - 1.47 (m, 2H). [001117] Example 590: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(1H-1,2,4-triazol-1-yl)- 3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 590 was prepared in a manner similar to Example 261. MS: m/z = 570.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.12 (s, 1H), 8.45 (d, J = 8.4 Hz, 1H), 8.29 (s, 1H), 8.10 - 8.04 (m, 2H), 8.02 - 8.00 (m, 1H), 7.89 (d, J = 8.8 Hz, 1H), 7.46 - 7.44 (m, 4H), 7.20 - 7.16 (m, 1H), 6.93 (s, 2H), 6.67 (d, J = 5.6 Hz, 1H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 3.88 - 3.76 (m, 1H), 3.58 (s, 2H), 2.85 - 2.81 (m, 2H), 2.18 - 2.12 (m, 2H), 1.89 - 1.87 (m, 2H), 1.54 - 1.47 (m, 2H). [001118] Example 591: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(1H-1,2,3-triazol-1-yl)- 3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 591 was prepared in a manner similar to Example 261. MS: m/z = 570.1 [M+H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.59 (s, 1H), 8.41 (d, J = 8.8 Hz, 1H), 8.24 (d, J = 8.4 Hz, 1H), 8.05 - 7.96 (m, 2H), 7.86 (s, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.46 (d, J = 8.4 Hz, 2H), 7.33 (dd, J = 8.0, 2.0 Hz, 1H), 6.64 - 6.57 (m, 1H), 6.48 (dd, J = 7.6, 5.2 Hz, 1H), 4.06 - 3.89 (m, 1H), 3.70 (s, 2H), 3.04 - 2.94 (m, 2H), 2.37 - 2.26 (m, 2H), 2.07 - 1.98 (m, 2H), 1.66 - 1.59 (m, 2H). [001119] Example 592: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2H-1,2,3-triazol-2-yl)- 3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 592 was prepared in a manner similar to Example 261. MS: m/z = 570.2 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.44 (d, J = 8.4 Hz, 1H), 8.13 (s, 2H), 8.11 - 8.02 (m, 3H), 8.00 (dd, J = 4.8, 1.6 Hz, 1H), 7.50 - 7.42 (m, 4H), 7.19 - 7.15 (m, 1H), 6.95 (br s, 2H), 6.68 (d, J = 5.6 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.88 - 3.76 (m, 1H), 3.59 (s, 2H), 2.86 - 2.79 (m, 2H), 2.21 - 2.12 (m, 2H), 1.93 - 1.84 (m, 2H), 1.54 - 1.45 (m, 2H). [001120] Example 593: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-methyl-1H-1,2,3-triaz ol-1- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile Example 593 was prepared in a manner similar to Example 261. MS: m/z = 584.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.55 - 8.41 (m, 1H), 8.39 - 8.29 (m, 1H), 8.17 - 7.96 (m, 4H), 7.54 - 7.42 (m, 4H), 7.26 - 7.12 (m, 1H), 6.92 (br s, 2H), 6.75 - 6.60 (m, 1H), 6.48 - 6.34 (m, 1H), 3.91 - 3.74 (m, 1H), 3.58 (s, 2H), 2.89 - 2.77 (m, 2H), 2.32 (s, 3H), 2.23 - 2.10 (m, 2H), 1.97 - 1.81 (m, 2H), 1.60 - 1.44 (m, 2H). [001121] Example 594: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(oxazol-4-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 594 was prepared in a manner similar to Example 261. MS: m/z = 570.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.49 (s, 1H), 8.45 (s, 1H), 8.27 (d, J = 8.0 Hz, 1H), 8.14 - 8.03 (m, 2H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.49 - 7.39 (m, 4H), 7.13 (dd, J = 7.6, 1.2 Hz, 1H), 6.98 (br s, 2H), 6.68 (d, J = 6.4 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.95 - 3.71 (m, 1H), 3.58 (s, 2H), 2.86 - 2.80 (m, 2H), 2.20 - 2.12 (m, 2H), 1.97 - 1.84 (m, 2H), 1.57 - 1.45 (m, 2H). [001122] Example 595: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-fluoropyridin-3-yl)-3 H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 595 was prepared in a manner similar to Example 261. MS: m/z = 620.2 [M + Na] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.98 (d, J = 10.8 Hz, 1H), 8.61 (dd, J = 7.2, 5.6 Hz, 1H), 8.34 (d, J = 8.4 Hz, 1H), 8.12 - 7.97 (m, 3H), 7.83 (d, J = 6.8 Hz, 1H), 7.50 - 7.42 (m, 5H), 7.18 (d, J = 6.4 Hz, 1H), 7.01 (br s, 2H), 6.66 (d, J = 6.0 Hz, 1H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.82 - 3.76 (m, 1H), 3.57 (s, 2H), 2.86 - 2.75 (m, 2H), 2.21 - 2.08 (m, 2H), 1.99 - 1.80 (m, 2H), 1.54 - 1.44 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -108.465. [001123] Example 596: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-methylpyridin-2-yl)-3 H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 596 was prepared in a manner similar to Example 261. MS: m/z = 616.2 [M + Na] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.53 (d, J = 4.8 Hz, 1H), 8.46 (d, J = 8.4 Hz, 1H), 8.30 (d, J = 8.4 Hz, 1H), 8.07 (dd, J = 14.0, 6.0 Hz, 2H), 8.02 - 7.97 (m, 2H), 7.53 - 7.45 (m, 4H), 7.23 (d, J = 4.0 Hz, 1H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (br s, 2H), 6.68 (d, J = 6.0 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.82 (s, 1H), 3.61 (s, 2H), 2.89 - 2.80 (m, 2H), 2.34 (s, 3H), 2.22 - 2.11 (m, 2H), 1.94 - 1.85 (m, 2H), 1.58 - 1.44 (m, 2H). [001124] Example 597: 4-((1-(4-(2-(2-aminopyridin-3-yl)-5-(6-(methoxy-d3)pyridin-3 -yl- 2-d)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)ami no)pyrimidine-2-carbonitrile Example 597 was prepared in a manner similar to Example 261.MS: m/z = 613.3 [M + H] ⁺ . D%: 3D% = 57.4%, 4D% = 38.2%. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.85 (s, 1H), 8.30 (dd, J = 8.8, 2.8 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.11 - 7.95 (m, 4H), 7.50 - 7.41 (m, 4H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (br s, 2H), 6.96 - 6.87 (m, 1H), 6.67 (d, J = 6.0 Hz, 1H), 6.38 (dd, J = 7.6, 4.4 Hz, 1H), 3.90 - 3.75 (m, 1H), 3.59 (s, 2H), 2.89 - 2.79 (m, 2H), 2.21 - 2.10 (m, 2H), 1.95 - 1.83 (m, 2H), 1.57 - 1.44 (m, 2H). [001125] Example 598: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(6-(methoxy-d ₃ )pyridin-3-yl)- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile Example 598 was prepared in a manner similar to Example 261. MS: m/z = 613.3 [M + H] ⁺ . D%: 3D% = 98.9%. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.85 (d, J = 2.0 Hz, 1H), 8.35 - 8.23 (m, 2H), 8.13 - 7.95 (m, 4H), 7.52 - 7.40 (m, 4H), 7.17 - 7.11 (m, 1H), 7.04 (s, 2H), 6.91 (d, J= 8.4 Hz, 1H), 6.67 (d, J= 6.0 Hz, 1H), 6.38 (dd, J= 7.6, 4.8 Hz, 1H), 3.98 - 3.70 (m, 1H), 3.59 (s, 2H), 2.87 - 2.78 (m, 2H), 2.21 - 2.09 (m, 2H), 1.94 - 1.84 (m, 2H), 1.56 - 1.46 (m, 2H). [001126] Example 599: 2-(2-Aminopyridin-3-yl)-3-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin-l-yl)methyl)phenyl)-5-hydroxy-3H-imidazo[ 4,5-b]pyridine-6-carbonitrile

Example 599 was prepared in a manner similar to Example 261. MS: m/z = 544.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.57 (s, 1H), 8.18 - 8.04 (m, 2H), 7.98 - 7.92 (m, 1H), 7.52 - 7.33 (m, 5H), 7.09 (d, J= 6.4 Hz, 1H), 6.91 (s, 2H), 6.69 (d, J= 6.4 Hz, 1H), 6.34 (dd, J= 7.6, 4.8 Hz, 1H), 3.88 - 3.78 (m, 1H), 3.65 - 3.59 (m, 2H), 2.86 - 2.80 (m, 2H), 2.27 - 2.15 (m, 2H), 1.94 - 1.85 (m, 2H), 1.56 - 1.47 (m, 2H).

[001127] Example 600: 4-((l-(4-(2-(2-Amino-4-fluoropyridin-3-yl)-5-(5-fluoropyridi n-2- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile

To a solution of Intermediate 270 (20 mg, 41.2 μmol, HC1 salt) and Intermediate 51 (13.1 mg, 41.2 μmol, TFA) in DMF (1 mL) were added K ₂ CO ₃ (28.5 mg, 206 μmol) and Nal (618 μg, 4.12 μmol). The mixture was stirred at 50 °C for 1 hr. The reaction mixture was quenched with H ₂ O (5 mL) at 25 °C and extracted with CH ₂ CI ₂ (15 mL x 2). The combined organic layers were washed with brine (50 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-TLC (SiCI ₂ , CH ₂ CI ₂ : MeOH = 10 : 1), 4-((l-(4-(2-(2-amino-4- fluoropyridin-3-yl)-5-(5-fluoropyridin-2-yl)-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4- yl)amino)pyrimidine-2-carbonitrile (Example 600, 7.9 mg, yield: 29% for three steps) was obtained as a yellow solid. MS: m/z = 616.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.56

- 8.48 (m, 2H), 8.37 (dd, J= 8.8, 4.4 Hz, 1H), 8.28 (d, J= 8.4 Hz, 1H), 8.08 - 7.98 (m, 1H), 7.66

- 7.61 (m, 1H), 7.55 - 7.47 (m, 4H), 7.35 - 7.30 (m, 1H), 6.61 (d, J= 5.6 Hz, 1H), 6.38 (dd, J= 8.8, 6.0 Hz, 1H), 4.05 - 3.93 (m, 1H), 3.73 (s, 2H), 3.06 - 2.98 (m, 2H), 2.43 - 2.31 (m, 2H), 2.10 - 2.03 (m, 2H), 1.68 - 1.60 (m, 2H). ¹⁹ F NMR (400 MHz, Methanol-d ₄ ) δ -102.89, -129.57. [001128] Example 601: 4-((l-(4-(5-(5-Fluoropyridin-2-yl)-2-(pyrimidin-5-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

Example 601 was prepared in a manner similar to Example 261. MS: m/z = 584.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.24 (s, 1H), 8.89 (s, 2H), 8.69 (d, J= 2.8 Hz, 1H), 8.47 - 8.43 (m, 2H), 8.28 - 8.24 (m, 1H), 8.11 - 8.04 (m, 2H), 7.87 - 7.82 (m, 1H), 7.60 - 7.57 (m, 2H), 7.56 - 7.54 (m, 2H), 6.68 (d, J= 5.2 Hz, 1H), 3.89 - 3.78 (m, 1H), 3.63 (s, 2H), 2.85 (d, J= 11.2 Hz, 2H), 2.22 - 2.16 (m, 2H), 1.95 - 1.87 (m, 2H), 1.55 - 1.47 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ = -127.404.

[001129] Example 602: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-6-(5-fluoropyridin-2-yl)-1 H- benzo[d]imidazol-l-yl)benzyl)piperidin-4-yl)amino)pyrimidine -2-carbonitrile

To a solution of Intermediate 272 (300 mg, 698 μmol, HC1 salt) and Intermediate 51 (221 mg, 698 μmol, TFA) in DMF (5 mL) were added K ₂ CO ₃ (289 mg, 2.09 mmol) and Nal (20.9 mg, 140 μmol). The mixture was stirred at 50 °C for 1 hr. The reaction mixture was quenched with H ₂ O (50 mL) at 25 °C and extracted with CH ₂ CI ₂ (50 mL x 3). The combined organic layers were washed with brine (50 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-HPLC (column: Phenomenex C18 150 x 25 mm x 10 μm; mobile phase: [water (NH ₃ H ₂ O) - ACN]; gradient: 38% - 68%, over 11 min), 4-((l-(4-(2- (2-aminopyridin-3-yl)-6-(5-fluoropyridin-2-yl)-1H-benzo[d]im idazol-l-yl)benzyl)piperidin-4- yl)amino)pyrimidine-2-carbonitrile (Example 602, 55.0 mg, yield: 13% for two steps) was obtained as a light yellow lyophilized powder. MS: m/z = 597.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.60 (d, J= 2.8 Hz, 1H), 8.08 (dd, J= 8.8, 4.4 Hz, 3H), 8.04 - 8.01 (m, 1H), 7.98 (dd, J = 4.8, 1.8 Hz, 1H), 7.90 - 7.88 (m, 2H), 7.81 - 7.76 (m, 1H), 7.54 - 7.52 (m, 2H), 7.44 (d, J = 8.4 Hz, 2H), 7.11 - 7.08 (m, 3H), 6.70 - 6.65 (m, 1H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 3.87 - 3.77 (m, 1H), 3.61 (s, 2H), 2.84 - 2.83 (m, 2H), 2.20 - 2.14 (m, 2H), 1.93 - 1.87 (m, 2H), 1.55 - 1.48 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ )) δ =-130.25. [001130] Example 603: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(5-fluoropyrimidin-2-yl) -3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile Example 603 was prepared in a manner similar to Example 261. MS: m/z = 599.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ 9.00 (s, 3H), 8.43 (d, J = 8.4 Hz, 1H), 8.34 (d, J = 8.4 Hz, 1H), 8.15 - 8.02 (m, 2H), 8.02 - 7.97 (m, 1H), 7.52 - 7.40 (m, 4H), 7.20 - 7.10 (m, 1H), 7.00 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.89 - 3.74 (m, 1H), 3.59 (s, 2H), 2.92 - 2.77 (m, 2H), 2.23 - 2.10 (m, 2H), 1.95 - 1.80 (m, 2H), 1.61 - 1.42 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ -139.07. [001131] Example 604: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(5-methylpyrimidin-2-yl) - 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile Example 604 was prepared in a manner similar to Example 261. MS: m/z = 595.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ 8.84 - 8.66 (m, 2H), 8.46 (d, J = 8.4 Hz, 1H), 8.32 (d, J = 8.4 Hz, 1H), 8.19 - 8.02 (m, 2H), 8.01 - 7.96 (m, 1H), 7.61 - 7.28 (m, 4H), 7.22 - 7.08 (m, 1H), 7.00 (s, 2H), 6.77 - 6.57 (m, 1H), 6.44 - 6.30 (m, 1H), 3.89 - 3.70 (m, 1H), 3.60 (br s, 2H), 2.98 - 2.69 (m, 2H), 2.32 (s, 3H), 2.25 - 2.09 (m, 2H), 1.95 - 1.75 (m, 2H), 1.55 - 1.43 (m, 2H). [001132] Example 605: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(5-fluoropyrazin-2-yl)-3 H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

Example 605 was prepared in a manner similar to Example 261. MS: m/z = 599.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.04 - 8.91 (m, 1H), 8.85 - 8.73 (m, 1H), 8.39 (d, J= 8.4 Hz, 1H), 8.32 (d, J= 8.4 Hz, 1H), 8.15 - 7.97 (m, 3H), 7.53 - 7.47 (m, 4H), 7.16 (dd, J= 7.6, 1.6 Hz, 1H), 7.02 (br s, 2H), 6.67 (d, J= 6.0 Hz, 1H), 6.40 (dd, J= 7.6, 4.8 Hz, 1H), 3.95 - 3.70 (m, 1H), 3.60 (s, 2H), 2.87 - 2.80 (m, 2H), 2.21 - 2.12 (m, 2H), 1.95 - 1.84 (m, 2H), 1.57 - 1.44 (m, 2H). ¹⁹ FNMR(400 MHZ, Dimethysulfoxide-d ₆ ) δ -82.705.

[001133] Example 606: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(6-(fluoromethoxy)pyridi n-3- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile

To a solution of Intermediate 277 (250 mg, 542 μmol, HC1 salt) and Intermediate 51 (172 mg, 542 μmol, TFA) in DMF (3 mL) were added K ₂ CO ₃ (300 mg, 1.17 mmol) and Nal (40.7 mg, 271 μmol). The mixture was stirred at 25 °C for 16 hr. The reaction mixture was quenched with H ₂ O (5 mL) at 25 °C and extracted with EtOAc (10 mL x 3). The combined organic layers were washed with brine (50 mL x3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-HPLC (column: Phenomenex C18 150 x 25 mm x 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 35% - 65% B over 11 min), 4-((l-(4-(2-(2- aminopyridin-3-yl)-5-(6-(fluoromethoxy)pyridin-3-yl)-3H-imid azo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile (Example 606, 145.3 mg, yield: 43% for three steps) was obtained as a yellow powder. MS: m/z = 628.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfbxide-d ₆ ) δ 8.97 - 8.84 (m, 1H), 8.43 (d, J= 8.8 Hz, 1H), 8.30 (d, J= 8.4 Hz, 1H), 8.20 - 7.89 (m, 4H), 7.57 - 7.36 (m, 4H), 7.22 - 6.98 (m, 4H), 6.83 - 6.60 (m, 1H), 6.45 - 6.32 (m, 1H), 6.24 - 6.02 (m, 2H), 4.01 - 3.67 (m, 1H), 3.65 - 3.59 (s, 2H), 2.90 - 2.77 (m, 2H), 2.23 - 2.09 (m, 2H), 1.96 - 1.80 (m, 2H), 1.57 - 1.40 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -154.35.

[001134] Example 607: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(l-(fluoromethyl)-6-oxo- l,6- dihydropyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)pi peridin-4-yl)amino)pyrimidine-2- carbonitrile

Example 607 was prepared in a manner similar to Example 261. MS: m/z = 628.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.60 (d, J= 2.4 Hz, 1H), 8.27 (d, J= 8.4 Hz, 1H), 8.17 (dd, J= 9.6, 2.4 Hz, 1H), 8.12 - 7.96 (m, 3H), 7.86 (d, J= 8.4 Hz, 1H), 7.50 - 7.41 (m, 4H), 7.16 - 7.11 (m, 1H), 7.02 (s, 2H), 6.68 (d, J= 6.4 Hz, 1H), 6.60 (d, J= 9.6 Hz, 1H), 6.37 (dd, J= 7.6, 4.8 Hz, 1H), 6.03 (d, J= 50.8 Hz, 1H), 3.92 - 3.66 (m, 1H), 3.59 (s, 2H), 2.89 - 2.78 (m, 2H), 2.21 - 2.10 (m, 2H), 1.95 - 1.82 (m, 2H), 1.56 - 1.44 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -172.673.

[001135] Example 608: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(2-(methyl-d ₃ )-2H-l,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin -4-yl)amino)pyrimidine-2- carbonitrile

To a solution of Intermediate 281 (420 mg, 920 μmol, HC1 salt) and Intermediate 51 (292 mg, 920 μmol, TFA) in DMF (5 mL) were added K ₂ CO ₃ (636 mg, 4.6 mmol) and Nal (13.8 mg, 92 μmol). The mixture was stirred at 50 °C for 1 hr. The reaction mixture was quenched with H ₂ O (50 mL) at 25 °C and extracted with CH ₂ CI ₂ (50 mL x 2). The combined organic layers were washed with brine (50 mL x3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 1% ~ 6% MeOH in CH ₂ CI ₂ ), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(2-(methyl-d ₃ )-2H-1,2,3-triazol-4-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile (Example 608, 301.2 mg, yield: 53% for two steps) was obtained as a green solid. MS: m/z = 587.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 88.27 (d, J= 8.4 Hz, 1H), 8.09 - 7.91 (m, 5H), 7.48 - 7.40 (m, 4H), 7.16 - 7.08 (m, 1H), 6.93 (s, 2H), 6.67 (d, J= 6.0 Hz, 1H), 6.37 (dd, J= 7.6, 4.8 Hz, 1H), 3.85 - 3.77 (m, 1H), 3.58 (s, 2H), 2.86 - 2.80 (m, 2H), 2.19 - 2.12 (m, 2H), 1.93 - 1.84 (m, 2H), 1.53 - 1.46 (m, 2H).

[001136] Example 609: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(2-ethyl-2H-l,2,3-triazo l-4- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile

Example 609 was prepared in a manner similar to Example 261. MS: m/z = 620.2 [M + Na] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.28 (d, J= 8.0 Hz, 1H), 8.13 - 8.04 (m, 3H), 8.02 - 7.92 (m, 2H), 7.51 - 7.40 (m, 4H), 7.14 (d, J= 6.4 Hz, 1H), 6.98 (s, 2H), 6.68 (d, J= 5.6 Hz, 1H), 6.37 (dd, J= 7.6, 4.8 Hz, 1H), 4.57 - 4.46 (m, 2H), 3.89 - 3.77 (m, 1H), 3.64 - 3.55 (m, 2H), 2.89 - 2.77 (m, 2H), 2.22 - 2.09 (m, 2H), 1.95 - 1.84 (m, 2H), 1.55 - 1.44 (m, 5H).

[001137] Example 610: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(2-isopropyl-2H-l,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin -4-yl)amino)pyrimidine-2- carbonitrile

To a solution of Intermediate 289 (146 mg, 328 μmol) and Intermediate 51 (73.4 mg, 361 μmol) in DMF (5 mL) were added K ₂ CO ₃ (136 mg, 984 μmol) and Nal (9.84 mg, 65.6 μmol) at 20 °C. The reaction mixture was stirred at 20 °C for 12 hr. The mixture was diluted with H ₂ O (10 mL) and extracted with EtOAc (10 mL x 2). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by prep-HPLC (column: C18 150 x 30 mm; mobile phase: [water(NH ₃ H ₂ O+NH ₄ HCO ₃ )-ACN];gradient:51%- 81% B over 7 min), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(2-isopropyl-2H-l,2,3-tr iazol-4-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile (Example 610, 53.3 mg, yield: 26.6% for three steps) was obtained as an off-white solid. MS: m/z = 612.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.15 - 8.03 (m, 3H), 7.99 (dd, J = 4.8, 1.6Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.50 - 7.41 (m, 4H), 7.14 (dd, J = 7.6, 1.6, Hz, 1H), 7.00 (s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.37 (dd, J = 8.0, 4.8 Hz, 1H), 4.93 - 4.82 (m, 1H), 3.82 - 3.81 (m, 1H), 3.59 (s, 2H), 2.87 - 2.78 (m, 2H), 2.23 - 2.09 (m, 2H), 1.96 - 1.78 (m, 2H), 1.58 - 1.43 (m, 8H). [001138] Example 611: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(1-isopropyl-1H-1,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin -4-yl)amino)pyrimidine-2- carbonitrile Example 611 was prepared in a manner similar to Example 261. MS: m/z = 612.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.42 (s, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.12 - 8.04 (m, 3H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.49 - 7.41 (m, 4H), 7.11 (dd, J = 7.6, 1.6 Hz, 1H), 6.97 (br s, 2H), 6.68 (d, J = 6.0 Hz, 1H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 4.93 - 4.82 (m, 1H), 3.87 - 3.76 (m, 1H), 3.59 (s, 2H), 2.89 - 2.79 (m, 2H), 2.22 - 2.11 (m, 2H), 1.94 - 1.79 (m, 2H), 1.54 - 1.47 (m, 8H). [001139] Example 612: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-methyl-5-(methyl-d ₃ )-2H- 1,2,3-triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)pip eridin-4-yl)amino)pyrimidine-2- carbonitrile Example 612 was prepared in a manner similar to Example 261. MS: m/z = 601.3 [M + H] ⁺ . D%: 3D% = 100%, ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.25 (d, J = 8.0 Hz, 1H), 8.12 - 8.03 (m, 2H), 8.02 - 8.00 (m, 1H), 7.91 (d, J = 8.4 Hz, 1H), 7.51 - 7.40 (m, 4H), 7.25 (dd, J = 8.0, 1.2 Hz, 1H), 7.09 (br s, 2H), 6.67 (d, J = 6.4 Hz, 1H), 6.41 (dd, J = 7.6, 4.8, Hz, 1H), 4.12 (s, 3H), 3.85 - 3.75 (m, 1H), 3.58 (s, 2H), 3.21 - 3.09 (m, 2H), 2.83 - 2.76 (m, 2H), 2.17 - 2.08 (m, 2H), 1.93 - 1.83 (m, 2H).

[001140] Example 613: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(2H-l,2,3-triazol-4-yl)- 3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

Step 1 : 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(2-(tetrahydro-2H-pyran- 2-yl)-2H-l,2,3-triazol-4- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile A mixture of Example 405 (250 mg, 466 μmol), 2-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)-2H-l,2,3-triazole (143 mg, 512 μmol), Pd(dppf)Cl ₂ (34.1 mg, 46.5 μmol), and CS ₂ CO ₃ (455 mg, 1.40 mmol) in H ₂ O (0.5 mL) and 1,4-dioxane (2 mL) was degassed and purged with N2 three times. The mixture was stirred at 100 °C for 16 hr under N ₂ atmosphere. The reaction mixture was poured into H ₂ O (15 mL) and extracted with EtOAc (15 mL x 3). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(2-(tetrahydro-2H- pyran-2-yl)-2H-1,2,3-triazol-4-yl)-3H-imidazo[4,5-b]pyridin- 3-yl)benzyl)piperidin-4- yl)amino)pyrimidine-2-carbonitrile (285 mg) was obtained as a brown solid. MS: m/z = 654.4 [M + H| ⁺

Step 2: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(2H-l,2,3-triazol-4-yl)- 3H-imidazo[4,5-b]pyridin- 3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile

To a solution of 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(2-(tetrahydro-2H-pyran- 2-yl)-2H-l,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin -4-yl)amino)pyrimidine-2- carbonitrile (285 mg, 436 μmol) in CH ₂ CI ₂ (4 mL) was added TFA (2 mL). The mixture was stirred at 25 °C for 2 hr. The pH of reaction mixture was adjusted to 8 with aq. Sat. NaHCO ₃ . The mixture was extracted with CH ₂ CI ₂ (20 mL x 3). The combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-HPLC( column: Phenomenex C18 150 x 25 mm x 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 18% - 48% B over 11 min), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(2H-l,2,3-triazol-4- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile (Example 613, 12.2 mg, yield: 5% for two steps) was obtained as an off white solid. MS: m/z = 570.3 [M + H] ⁺ . 1H NMR (400 MHz, Methanol-d ₄ ) δ 8.30 - 8.13 (m, 2H), 8.11 - 8.05 (m, 1H), 8.04 - 7.95 (m, 2H), 7.54 (d, J =8.4 Hz, 2H), 7.44 (d, J =8.4 Hz, 2H), 7.30 (dd, J = 7.6, 1.6 Hz, 1H), 6.66 - 6.53 (m, 1H), 6.46 (dd, J =8.0, 5.2 Hz, 1H), 4.07 - 3.84 (m, 1H), 3.67 (br s, 2H), 3.07 - 2.88 (m, 2H), 2.38 - 2.17 (m, 2H), 2.10 - 1.90 (m, 2H), 1.69 - 1.57 (m, 2H). [001141] Example 614: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2,5-dimethyl-2H-1,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin -4-yl)amino)pyrimidine-2- carbonitrile Example 614 was prepared in a manner similar to Example 261. MS: m/z = 598.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.25 (d, J = 8.4 Hz, 1H), 8.10 - 8.00 (m, 3H), 7.91 (d, J = 8.4 Hz, 1H), 7.49 - 7.43 (m, 4H), 7.25 (dd, J = 8.0, 2.0 Hz, 1H), 7.09 (s, 2H), 6.67 (d, J = 5.6 Hz, 1H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 4.12 (s, 3H), 3.87 - 3.73 (m, 1H), 3.58 (s, 2H), 2.84 - 2.75 (m, 2H), 2.34 (s, 3H), 2.18 - 2.06 (m, 2H), 1.93 - 1.82 (m, 2H), 1.56 - 1.42 (m, 2H). [001142] Example 615: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-cyclopropyl-2H-1,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin -4-yl)amino)pyrimidine-2- carbonitrile Example 615 was prepared in a manner similar to Example 261. MS: m/z = 610.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.27 (d, J = 8.4 Hz, 1H), 8.13 - 8.02 (m, 3H), 7.99 (dd, J = 4.8, 1.6, Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.49 - 7.41 (m, 4H), 7.16 - 7.12 (m, 1H), 6.98 (s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 4.23 - 4.15 (m, 1H), 3.81 - 3.79 (m, 1H), 3.58 (s, 2H), 2.87 - 2.79 (m, 2H), 2.20 - 2.10 (m, 2H), 1.94 - 1.83 (m, 2H), 1.56 - 1.43 (m, 2H), 1.27 - 1.23 (m, 2H), 1.15 - 1.09 (m, 2H). [001143] Example 616: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-methyl-2H-1,2,3-triaz ol-4- yl-5-d)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl) amino)pyrimidine-2-carbonitrile Example 616 was prepared in a manner similar to Example 261. MS: m/z = 585.2 [M + H] ⁺ . D%: 1D% = 96.2%. ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.17 (d, J = 8.0 Hz, 1H), 8.04 - 7.95 (m, 3H), 7.53 (d, J = 8.0 Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H), 7.31 - 7.23 (m, 1H), 6.60 (d, J = 5.2 Hz, 1H), 6.45 (dd, J = 7.6, 5.2 Hz, 1H), 4.21 (s, 3H), 4.04 - 3.89 (m, 1H), 3.67 (s, 2H), 3.02 - 2.92 (m, 2H), 2.38 - 2.22 (m, 2H), 2.04 - 1.97 (m, 2H), 1.68 - 1.56 (m, 2H). [001144] Example 617: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(1-(difluoromethyl)-6-ox o- 1,6-dihydropyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzy l)piperidin-4- yl)amino)pyrimidine-2-carbonitrile Example 617 was prepared in a manner similar to Example 469. MS: m/z = 646.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.38 - 8.35 (m, 1H), 8.30 - 8.22 (m, 2H), 8.17 - 7.97 (m, 4H), 7.97 - 7.72 (m, 1H), 7.53 - 7.40 (m, 4H), 7.18 - 7.14 (m, 1H), 7.06 (s, 2H), 6.75 - 6.62 (m, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.96 - 3.75 (m, 1H), 3.59 (s, 2H), 2.90 - 2.75 (m, 2H), 2.22 - 2.05 (m, 2H), 1.97 - 1.77 (m, 2H), 1.58 - 1.40 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -103.343. [001145] Example 618: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-(fluoromethyl)-2H-1,2 ,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin -4-yl)amino)pyrimidine-2- carbonitrile To a solution of Intermediate 304 (1.6 g, 3.39 mmol, HCl salt) and Intermediate 51 (1.08 g, 3.39 mmol, TFA) in DMF (30 mL) were added K ₂ CO ₃ (1.41 g, 10.2 mmol) and NaI (35.2 mg, 235 μmol). The mixture was degassed, purged with N ₂ three times, and stirred at 50 °C for 1 hr under N ₂ . The reaction mixture was diluted with CH ₂ CI ₂ (50 mL), washed with brine (30 mL x 4), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 5% ~ 8% MeOH in CH ₂ CI ₂ ), 4-((l-(4-(2-(2- aminopyridin-3-yl)-5-(2-(fluoromethyl)-2H-l,2,3-triazol-4-yl )-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile (Example 618, 1.01 g, yield 47% for three steps) was obtained as a yellow solid. MS: m/z = 602.3 [M+H| ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.38 - 8.31 (m, 2H), 8.11 - 7.98 (m, 4H), 7.50 - 7.43 (m, 4H), 7.19 - 7.13 (m, 1H), 6.97 (br s, 2H), 6.68 (d, J= 6.0 Hz, 1H), 6.48 (d, J= 51.6 Hz, 2H), 6.38 (dd, J= 7.6, 4.8 Hz, 1H), 3.88 - 3.75 (m, 1H), 3.59 (s, 2H), 2.86 - 2.81 (m, 2H), 2.20 - 2.12 (m, 2H), 1.94 - 1.85 (m, 2H), 1.55 - 1.45 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -166.260. [001146] Example 619: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(l-(fluoromethyl)-1H-l,2 ,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin -4-yl)amino)pyrimidine-2- carbonitrile

Inter

Example 619 was prepared in a manner similar to Example 261. MS: m/z = 602.2 [M+H| ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.79 (s, 1H), 8.32 (d, J= 8.4 Hz, 1H), 8.15 - 8.03 (m, 3H), 7.99 (dd, J= 4.8, 1.6 Hz, 1H), 7.52 - 7.41 (m, 4H), 7.14 (dd, J= 7.6, 1.6 Hz, 1H), 6.97 (br s, 2H), 6.68 (d, J= 6.0 Hz, 1H), 6.48(d, J= 50.4 Hz, 2H), 6.37 (dd, J= 7.6, 4.4 Hz, 1H), 3.84 - 3.80 (m, 1H), 3.58 (s, 2H), 2.86 - 2.81 (m, 2H), 2.21 - 2.10 (m, 2H), 1.92 - 1.87 (m, 2H), 1.59 - 1.43 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8 -166.65.

[001147] Intermediate 620: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(2-(difluoromethyl)-2H- l,2,3-triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)pip eridin-4-yl)amino)pyrimidine-2- carbonitrile Example 620 was prepared in a manner similar to Example 261. MS: m/z = 620.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.99 (s, 1H), 8.33 (d, J= 8.0 Hz, 1H), 8.30 - 7.90 (m, 5H), 7.52 - 7.40 (m, 4H), 7.14 (d, J= 6.8 Hz, 1H), 6.98 (br s, 2H), 6.68 (d, J= 6.0 Hz, 1H), 6.37 (dd, J= 7.2, 4.8 Hz, 1H), 3.91 - 3.72 (m, 1H), 3.58 (s, 2H), 2.91 - 2.74 (m, 2H), 2.24 - 2.09 (m, 2H), 1.96 - 1.78 (m, 2H), 1.57 - 1.42 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ - 96.38.

[001148] Example 621: 4-((l-(4-(2-(3-Aminopyrazin-2-yl)-5-(2-(methyl-d ₃ )-2H-l,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin -4-yl)amino)pyrimidine-2- carbonitrile

To a solution of Intermediate 308 (220 mg, 481 μmol, HC1 salt) and Intermediate 51 (153 mg, 481 μmol, TFA) in DMF (3 mL) were added K ₂ CO ₃ (332 mg, 2.41 mmol) and Nal (7.21 mg, 48.1 μmol). The mixture was stirred at 50 °C for 1 hr. The reaction mixture was quenched with H ₂ O (5 mL) at 25 °C and extracted with CH ₂ CI ₂ (15 mL x 2). The combined organic layers were washed with brine (50 mL x3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-HPLC (column: Waters Xbridge BEH C18 150 x 25 mm x 5 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 32%-62% B over 10 min), 4-((l-(4-(2- (3-aminopyrazin-2-yl)-5-(2-(methyl-d ₃ )-2H-l,2,3-triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile (Example 621, 57.8 mg, yield: 20% for two steps) was obtained as a yellow lyophilized powder. MS: m/z = 588.1 [M + H] ⁺ . D%: 3D% = 99.1%. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.35 (d, J= 8.4 Hz, 1H), 8.24 - 7.86 (m, 5H), 7.77 (br s, 2H), 7.51 - 7.30 (m, 5H), 6.68 (d, J= 5.6 Hz, 1H), 3.91 - 3.77 (m, 1H), 3.59 (s, 2H), 2.91 - 2.81 (m, 2H), 2.24 - 2.11 (m, 2H), 2.00 - 1.79 (m, 2H), 1.59 - 1.41 (m, 2H). [001149] Example 622: 4-((l-(4-(2-(3-Aminoisoxazol-4-yl)-5-(5-fluoropyridin-2-yl)- 3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

Example 622 was prepared in a manner similar to Example 261. MS: m/z = 588.4 [M+H| ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.66 (d, J= 2.8 Hz, 1H), 8.41 - 8.36 (m, 1H), 8.33 - 8.29 (m, 1H), 8.15 (dd, J= 9.2, 4.8 Hz, 1H), 8.12 - 8.06 (m, 2H), 7.80 - 7.78 (m, 1H), 7.65 - 7.59 (m, 4H), 7.52 (s, 1H), 6.71 - 6.64 (m, 3H), 3.91 - 3.77 (m, 1H), 3.69 (s, 2H), 2.96 - 2.88 (m, 2H), 2.28 - 2.18 (m, 2H), 1.97 - 1.88 (m, 2H), 1.59 - 1.50 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -127.739.

[001150] Example 623: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(6-(fluoromethoxy- d ₂ )pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)pi peridin-4-yl)amino)pyrimidine-2- carbonitrile

To a solution of Intermediate 313 (300 mg, 601 μmol, HC1 salt) and Intermediate 51 (191 mg, 601 μmol, TFA) in DMF (6 mL) were added K ₂ CO ₃ (249 mg, 1.80 mmol) and Nal (18.0 mg, 120 μmol). The mixture was stirred at 50 °C for 1 hr. The reaction mixture was quenched with H ₂ O (10 mL) at 25 °C and extracted with CH ₂ CI ₂ (10 mL x 3). The combined organic layers were washed with brine (20 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 5% ~ 8% MeOH in CH ₂ CI ₂ ) and triturated with EtOAc (10 mL) at 25 °C for 5 min., 4-((l-(4-(2-(2-aminopyridin- 3-yl)-5-(6-(fluoromethoxy-d ₂ )pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)pi peridin-4- yl)amino)pyrimidine-2-carbonitrile (Intermediate 623, 86.5 mg, yield: 23% for two steps) was obtained as an off-white solid. MS: m/z = 630.2 [M + H] ⁺ . D%: 2D% = 98.2%. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.90 (d, J= 2.4 Hz, 1H), 8.42 (dd, J= 8.4, 2.4 Hz, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.09 - 7.99 (m, 4H), 7.50 - 7.43 (m, 4H), 7.18 - 7.13 (m, 1H), 7.09 (d, J= 8.8 Hz, 1H), 7.01 (br s, 2H), 6.67 (br d, J= 5.2 Hz, 1H), 6.39 (dd, J= 7.6, 4.8 Hz, 1H), 3.84 - 3.79 (m, 1H), 3.59 (br s, 2H), 2.85 - 2.79 (m, 2H), 2.19 - 2.11 (m, 2H), 1.93 - 1.83 (m, 2H), 1.55 - 1.46 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -155.547. [001151] Example 624: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(1-(fluoromethyl-d ₂ )-6-oxo- 1,6-dihydropyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzy l)piperidin-4- yl)amino)pyrimidine-2-carbonitrile Example 624 was prepared in a manner similar to Example 261. MS: m/z = 630.2 [M + H] ⁺ . D%: 2D% = 98.4%. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.60 (d, J = 2.8 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.18 (dd, J = 9.6, 2.4 Hz, 1H), 8.14 - 8.02 (m, 2H), 8.01 - 7.96 (m, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.51 - 7.40 (m, 4H), 7.16 - 7.10 (m, 1H), 7.02 (br s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 6.61 (d, J = 9.6 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.85 - 3.74 (m, 1H), 3.59 (s, 2H), 2.91 - 2.75 (m, 2H), 2.18 - 2.09 (m, 2H), 1.95 - 1.84 (m, 2H), 1.55 - 1.44 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -173.761. [001152] Example 625: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(1-ethyl-1H-1,2,3-triazo l-4- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile Example 625 was prepared in a manner similar to Example 261. MS: m/z = 598.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.41 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.12 - 8.04 (m, 3H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.50 - 7.40 (m, 4H), 7.11 (dd, J = 8.0, 2.0 Hz, 1H), 6.97 (s, 2H), 6.68 (d, J = 6.0 Hz, 1H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 4.42 (q, J = 7.2 Hz, 2H), 3.89 - 3.77 (m, 1H), 3.59 (s, 2H), 2.93 - 2.79 (m, 2H), 2.25 - 2.09 (m, 2H), 1.97 - 1.84 (m, 2H), 1.54 - 1.42 (m, 5H). [001153] Example 626: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-(cyanomethyl)-2H-1,2, 3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin -4-yl)amino)pyrimidine-2- carbonitrile

To a solution of Intermediate 318 (90 mg, 204 μmol) and Intermediate 51 (53.8 mg, 265 μmol) in DMF (1 mL) were added Nal (3.05 mg, 20.4 μmol) and K ₂ CO ₃ (84.5 mg, 611 μmol). The mixture was stirred at 25 °C for 12 hr under N2. The reaction mixture was quenched with H ₂ O (10 mL) at 25 °C and extracted with CH ₂ CI ₂ (10 mL x 3). The combined organic layers were washed with brine (20 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-HPLC (column: Phenomenex C18 80 x 30mm x 5μm; mobile phase: [water (NH ₃ H ₂ O+NH ₄ HCO ₃ ) - ACN]; gradient:45% - 75% B over 7 min), 4-((l-(4-(2-(2- aminopyridin-3-yl)-5-(2-(cyanomethyl)-2H-l,2,3-triazol-4-yl) -3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile (Example 626, 21.6 mg, yield: 17% for three steps) was obtained as an off-white solid. MS: m/z = 609.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.32 (d, J= 8.4 Hz, 1H), 8.28 (s, 1H), 8.09 (d, J= 5.6 Hz, 2H), 8.02 - 7.95 (m, 2H), 7.51 - 7.39 (m, 4H), 7.15 (dd, J= 7.6, 1.2 Hz, 1H), 6.97 (s, 2H), 6.68 (d, J= 6.0 Hz, 1H), 6.38 (dd, J= 8.0, 5.2 Hz, 1H), 5.99 (s, 2H), 3.95 - 3.75 (m, 1H), 3.59 (br s, 2H), 2.97 - 2.69 (m, 2H), 2.28 - 2.03 (m, 2H), 2.01 - 1.82 (m, 2H), 1.59 - 1.39 (m, 2H).

[001154] Example 627: 4-((l-(4-(2-(3-Aminopyrazin-2-yl)-5-(2-(fluoromethyl)-2H-1,2 ,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin -4-yl)amino)pyrimidine-2- carbonitrile

Example 627 was prepared in a manner similar to Example 261. MS: m/z = 603.2 [M+H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.41 (d, J= 8.4 Hz, 1H), 8.33 (s, 1H), 8.12 - 7.99 (m, 4H), 7.77 (br s, 2H), 7.49 (d, J= 2.4 Hz, 1H), 7.46 - 7.41 (m, 2H), 7.40 - 7.36 (m, 2H), 6.68 (d, J = 6.8 Hz, 1H), 6.48 (d, J= 51.6 Hz, 2H), 3.87 - 3.79 (m, 1H), 3.59 (s, 2H), 2.88 - 2.83 (m, 2H), 2.21 - 2.14 (m, 2H), 1.96 - 1.88 (m, 2H), 1.57 - 1.47 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -166.381. [001155] Example 628: 4-((l-(4-(2-(3-Aminopyrazin-2-yl)-5-(l-(fluoromethyl)-1H-l,2 ,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin -4-yl)amino)pyrimidine-2- carbonitrile

Example 628 was prepared in a manner similar to Example 261. MS: m/z = 603.3 [M+H| ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.58 (s, 1H), 8.30 (d, J= 8.4 Hz, 1H), 8.19 (d, J= 8.4 Hz, 1H), 8.04 - 7.98 (m, 1H), 7.94 (d, J= 2.0 Hz, 1H), 7.52 - 7.48 (m, 3H), 7.38 - 7.34(m, 2H), 6.64 - 6.58 (m, 1H), 6.38 (d, J= 50.8 Hz, 2H), 4.05 - 3.92 (m, 1H), 3.69 (s, 2H), 3.04 - 3.00 (m, 2H), 2.35 - 2.26 (m, 2H), 2.07 - 2.01 (m, 2H), 1.70 - 1.60 (m, 2H). ¹⁹ F NMR (400 MHz, Methanol^) 5 -169.788.

[001156] Example 629: 4-((l-(4-(2-(3-Aminopyrazin-2-yl)-5-(2-ethyl-2H-1,2,3-triazo l-4- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile

To a mixture of Intermediate 323 (190 mg, 440 μmol) and Intermediate 51 (98.4 mg, 484 μmol) in DMF (3 mL) were added Nal (6.59 mg, 44.0 μmol) and K ₂ CO ₃ (182 mg, 1.32 mmol). The mixture was stirred at 20 °C for 2 hr. The reaction mixture was quenched with H ₂ O (50 mL) and extracted with EtOAc (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by prep-HPLC (column: C18 150 x 30 mm; mobile phase: [water(NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN]; gradient: 48% - 78% B over 7 min), 4-((l-(4-(2-(3-aminopyrazin-2-yl)-5-(2-ethyl-2H-l,2,3-triazo l-4-yl)- 3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)py rimidine-2-carbonitrile (Example 629, 107 mg, yield: 40% for two steps) was obtained as a yellow solid. MS: m/z = 621.1 [M + Na] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.33 (d, J= 8.4 Hz, 1H), 8.12 - 7.93 (m, 5H), 7.78 (br s, 2H), 7.47 (d, J= 2.4 Hz, 1H), 7.45 - 7.33 (m, 4H), 6.68 (d, J= 6.0 Hz, 1H), 4.50 (q, J= 7.2 Hz, 2H), 3.89 - 3.75 (m, 1H), 3.59 (s, 2H), 2.96 - 2.80 (m, 2H), 2.24 - 2.10 (m, 2H), 1.98 - 1.82 (m, 2H), 1.57 - 1.41 (m, 5H).

[001157] Example 630: 4-((l-(4-(2-(3-Aminopyrazin-2-yl)-5-(2-isopropyl-2H-l,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin -4-yl)amino)pyrimidine-2- carbonitrile

To a solution of Intermediate 324 (187 mg, 419 μmol) and Intermediate 51 (93.8 mg, 461 μmol) in DMF (8 mL) were added K ₂ CO ₃ (174 mg, 1.26 mmol) and Nal (12.6 mg, 84 μmol) at 20 °C. The reaction mixture was stirred at 20 °C for 12 hr. The mixture was diluted with H ₂ O (20 mL) and extracted with EtOAc (20 mL x 2). The combined organic layers were washed with brine (20 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by prep-HPLC (column: Xtimaie C18 150 x 40 mm x 10 μm; mobile phase: [water(FA)-ACN];gradient:25%- 55% B over 7 min), the fractions were concentrated to remove most of MeCN. The product was diluted with CH ₂ CI ₂ (30 mL) and washed with sat. NaHCO ₃ (30 mL x 2). The organic layer was dried over anhydrous Na ₂ SO ₄ , filtered and concentrated to give 4-((l-(4-(2-(3-aminopyrazin-2- yl)-5-(2-isopropyl-2H-l,2,3-triazol-4-yl)-3H-imidazo[4,5-b]p yridin-3-yl)benzyl)piperidin-4- yl)amino)pyrimidine-2-carbonitrile (Example 630, 61.0 mg, yield: 23.6% for 3 steps) as a yellow solid. MS: m/z = 613.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.37 - 8.32 (m, 1H), 8.12 - 7.96 (m, 5H), 7.78 (s, 2H), 7.48 - 7.34 (m, 5H), 6.70 - 6.64 (m, 1H), 4.91 -

4.84 (m, 1H), 3.88 - 3.76 (m, 1H), 3.59 (s, 2H), 2.91 - 2.80 (m, 2H), 2.20 - 2.11 (m, 2H), 1.96 -

1.85 (m, 2H), 1.56 - 1.48 (m, 8H).

[001158] Example 631 : 4-((l-(4-(2-(3-Aminopyrazin-2-yl)-5-(2-cyclopropyl-2H-l,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin -4-yl)amino)pyrimidine-2- carbonitrile

751 To a solution of Intermediate 325 (130 mg, 642 μmol, HC1 salt) and Intermediate 51 (130 mg, 642 μmol) in DMF (3 mL) were added Nal (8.02 mg, 53.5 μmol) and K ₂ CO ₃ (222 mg, 1.60 mmol). The mixture was stirred at 25 °C for 1 hr. The mixture was diluted with water (10 mL) and extracted with ethyl acetate (10 mL x 2). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by prep-HPLC (column: Cl 8 150 x 30 mm; mobile phase: [water (NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN]; gradient: 55% - 85% B over 7 min), 4-((l-(4-(2-(3-aminopyrazin-2-yl)-5-(2-cyclopropyl-2H-1,2,3- triazol-4-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile (Example 631, 60.8 mg, yield: 19% for three steps) was obtained as a light yellow solid. MS: m/z = 611.1 [M + H] ⁺ . ¹ HNMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.35 (d, J= 8.0 Hz, 1H), 8.13 - 8.03 (m, 2H), 8.03 - 8.00 (m, 2H), 7.97 (d, J= 8.0 Hz, 1H), 7.78 (br s, 2H), 7.48 (d, J= 2.0 Hz, 1H), 7.43 (d, J= 8.4 Hz, 2H), 7.36 (d, J= 8.4 Hz, 2H), 6.69 (d, J= 6.0 Hz, 1H), 4.27 - 4.14 (m, 1H), 3.94 - 3.74 (m, 1H), 3.60 (s, 2H), 2.88 - 2.82 (m, 2H), 2.24 - 2.12 (m, 2H), 1.97 - 1.83 (m, 2H), 1.58 - 1.43 (m, 2H), 1.27 - 1.23 (m, 2H), 1.16 - 1.10 (m, 2H).

[001159] Example 632 & 633: 4-((l-(4-(2-(3-Aminopyrazin-2-yl)-5-(2-(cyanomethyl)-2H- l,2,3-triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)pip eridin-4-yl)amino)pyrimidine-2- carbonitrile & 2-(4-(2-(3 -aminopyrazin-2-yl)-3 -(4-((4-((2-cyanopyrimidin-4-yl)amino)piperidin- l-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)-2H-1,2,3- triazol-2-yl)acetamide

To a solution of a mixture of Intermediate 326 and Intermediate 327 (104 mg, 236 μmol, HC1 salt) and Intermediate 51 (57.5 mg, 283 μmol) in DMF (2 mL) were added Nal (3.53 mg, 23.6 μmol) and K ₂ CO ₃ (97.7 mg, 707 μmol). The mixture was stirred at 50 °C for 1 hr. The mixture was diluted with water (10 mL) and extracted with EtOAc (10 mL x 2). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by prep- HPLC (column: C18 150 x 30 mm; mobile phase: [water (NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN]; gradient: 47% - 77% B over 7 min)), 4-((l-(4-(2-(3-aminopyrazin-2-yl)-5-(2-(cyanomethyl)-2H- l,2,3-triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)pip eridin-4-yl)amino)pyrimidine-2- carbonitrile (Example 632, 10.6 mg, yield: 7.7% for three steps) was obtained as a light yellow solid. MS: m/z = 610.3 [M + H] ⁺ . ¹ HNMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.39 (d, J= 8.4 Hz, 1H), 8.25 (s, 1H), 8.15 - 8.03 (m, 2H), 8.03 - 7.97 (m, 2H), 7.78 (br s, 2H), 7.48 (d, J= 2.4 Hz, 1H), 7.46 - 7.41 (m, 2H), 7.39 - 7.32 (m, 2H), 6.68 (d, J = 6.0 Hz, 1H), 5.99 (s, 2H), 3.89 - 3.71 (m, 1H), 3.59 (s, 2H), 2.92 - 2.80 (m, 2H), 2.26 - 2.10 (m, 2H), 1.97 - 1.83 (m, 2H), 1.62 - 1.44 (m, 2H). 2-(4-(2-(3-Aminopyrazin-2-yl)-3-(4-((4-((2-cyanopyrimidin-4- yl)amino)piperidin-1-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyri din-5-yl)-2H-1,2,3-triazol-2- yl)acetamide (Example 633, 27.8 mg, yield: 20% for three steps) was also obtained as a light yellow solid. MS: m/z = 628.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.35 (d, J = 8.4 Hz, 1H), 8.18 - 8.02 (m, 3H), 8.01 (d, J = 2.4 Hz, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.77 (br s, 2H), 7.67 (s, 1H), 7.48 (d, J = 2.4 Hz, 1H), 7.45 - 7.41 (m, 2H), 7.40 - 7.34 (m, 3H), 6.68 (d, J = 6.4 Hz, 1H), 5.16 (s, 2H), 3.97 - 3.69 (m, 1H), 3.59 (s, 2H), 2.88 - 2.83 (m, 2H), 2.23 -2.11 (m, 2H), 1.94 - 1.82 (m, 2H), 1.58 - 1.45 (m, 2H) [001160] Example 634: 4-((1-(4-(2-(3-Aminopyrazin-2-yl)-5-(2-methyl-2H-1,2,3-triaz ol-4- yl-5-d)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl) amino)pyrimidine-2-carbonitrile Example 634 was prepared in a manner similar to Example 261. MS: m/z = 586.3 [M + H] ⁺ . 1D% = 98.4%. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.35 (d, J = 8.4 Hz, 1H), 8.13 - 8.05 (m, 2H), 8.02 - 7.95 (m, 2H), 7.78 (br s, 2H), 7.48 (d, J = 2.0 Hz, 1H), 7.45 - 7.41 (m, 2H), 7.38 - 7.34 (m, 2H), 6.68 (d, J = 6.4 Hz, 1H), 4.21 (s, 3H), 3.89 - 3.77 (m, 1H), 3.59 (s, 2H), 2.89 - 2.82 (m, 2H), 2.21 - 2.12 (m, 2H), 1.96 - 1.87 (m, 2H), 1.55 - 1.45 (m, 2H). [001161] Example 635: 4-((1-(4-(2-(3-Aminopyrazin-2-yl)-5-(2,5-dimethyl-2H-1,2,3- triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin -4-yl)amino)pyrimidine-2- carbonitrile Example 635 was prepared in a manner similar to Example 261. MS: m/z = 599.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.30 (br d, J = 6.8 Hz, 1H), 8.15 - 7.98 (m, 3H), 7.98 - 7.77 (m, 3H), 7.52 (s, 1H), 7.46 - 7.28 (m, 4H), 6.67 (br s, 1H), 4.11 (s, 3H), 3.87 - 3.71 (m, 1H), 3.58 (hr s, 2H), 2.89 - 2.73 (m, 2H), 2.27 (s, 3H), 2.17 - 2.04 (m, 2H), 1.93 - 1.80 (m, 2H), 1.51 - 1.48 (m, 2H).

[001162] Example 636: 4-((l-(4-(2-(3-Aminopyrazin-2-yl)-5-(6-methoxypyridin-3-yl)- 3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

To a solution of Intermediate 331 (197 mg, 410 μmol, HC1 salt) and Intermediate 51 (130 mg, 410 μmol, TFA) in DMF (3 mL) were added K ₂ CO ₃ (283 mg, 2.05 mmol) and Nal (12.3 mg, 82.0 μmol). The mixture was stirred at 50 °C for 1 hr. The reaction mixture was quenched with H ₂ O (5 mL) at 25 °C and extracted with CH ₂ CI ₂ (15 mL x 2). The combined organic layers were washed with brine (50 mL x3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-HPLC (column: Daisogel SP ODS RPS 150 x 25 mm x 5 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 38% - 68% B over 11 min), 4-((l-(4-(2-(3- aminopyrazin-2-yl)-5-(6-methoxypyridin-3-yl)-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin- 4-yl)amino)pyrimidine-2-carbonitrile (Example 636, 159 mg, yield: 62% for three steps) was obtained as a yellow lyophilized powder. MS : m/z = 611.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.84 (d, J= 2.4 Hz, 1H), 8.36 - 8.27 (m, 2H), 8.11 - 7.98 (m, 4H), 7.82 (br s, 2H), 7.49 (d, J= 2.4 Hz, 1H), 7.45 - 7.36 (m, 4H), 6.91 (d, J= 8.8 Hz, 1H), 6.68 (d, J= 6.0 Hz, 1H), 3.89 (s, 3H), 3.87 - 3.77 (m, 1H), 3.60 (s, 2H), 2.91 - 2.80 (m, 2H), 2.22 - 2.12 (m, 2H), 1.97 - 1.83 (m, 2H), 1.60 - 1.44 (m, 2H).

[001163] Example 637: 4-((l-(4-(2-(3-Aminopyrazin-2-yl)-5-(6-(methoxy-d ₃ )pyridin-3- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile

To a solution of Intermediate 332 (389 mg, 805 μmol, HC1 salt) and Intermediate 51 (255 mg, 805 μmol, TFA) in DMF (5 mL) were added K ₂ CO ₃ (556 mg, 4.02 mmol) and Nal (24.1 mg, 161 μmol). The mixture was stirred at 50 °C for 1 hr. The reaction mixture was quenched with H ₂ O (20 mL) at 25 °C and extracted with CH ₂ CI ₂ (50 mL x 2). The combined organic layers were washed with brine (50 mL x3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-HPLC (column: Daisogel SP ODS RPS 150 x 25 mm x 5 μm; mobile phase: [water (NH4HCO3) - ACN]; gradient: 50% - 80% B over 11 min), 4-((l-(4-(2-(3- aminopyrazin-2-yl)-5-(6-(methoxy-d ₃ )pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile (Example 637, 113 mg, yield: 23% for three steps) was obtained as a light yellow lyophilized powder. MS: m/z = 614.3 [M + H] ⁺ . D%: 3D% = 100.0%. ¹ HNMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.84 (d, J= 2.4 Hz, 1H), 8.35 - 8.26 (m, 2H), 8.10 - 7.99 (m, 4H), 7.82 (br s, 2H), 7.49 (d, J= 2.4 Hz, 1H), 7.44 - 7.36 (m, 4H), 6.90 (d, J= 8.8 Hz, 1H), 6.67 (d, J= 6.0 Hz, 1H), 3.88 - 3.75 (m, 1H), 3.59 (s, 2H), 2.88 - 2.79 (m, 2H), 2.24 - 2.13 (m, 2H), 1.97 - 1.86 (m, 2H), 1.57 - 1.47 (m, 2H).

[001164] Example 638: 4-((l-(4-(2-(3-Aminopyrazin-2-yl)-5-(5-(methoxy-d ₃ )pyridin-2- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile

To a solution of Intermediate 334 (360 mg, 745 μmol, HC1 salt) and Intermediate 51 (236 mg, 745 μmol, TFA) in DMF (5 mL) were added K ₂ CO ₃ (515 mg, 3.72 mmol) and Nal (22.3 mg, 149 μmol). The mixture was stirred at 50 °C for 1 hr. The reaction mixture was quenched with H ₂ O (5 mL) at 25 °C and extracted with CH ₂ CI ₂ (15 mL x 2). The combined organic layers were washed with brine (50 mL x3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-HPLC (column: Daisogel SP ODS RPS 150 x 25 mm x 5 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 38% - 68% B over 11 min), 4-((l-(4-(2-(3- aminopyrazin-2-yl)-5-(5-(methoxy -d ₃ )pyri din-2 -yl)-3H-imidazo[4,5-b]pyri din-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile (Example 638, 219 mg, yield: 48% for three steps) was obtained as a yellow lyophilized powder. MS: m/z = 614.3 [M + H] ⁺ . D%: 3D% = 97.6%. ¹ HNMR (400 MHz, Dimethylsulfoxide^) 88.43 - 8.31 (m, 3H), 8.14 - 8.05 (m, 3H), 8.01 (d, J= 2.0 Hz, 1H), 7.81 (br s, 2H), 7.51 - 7.47 (m, 2H), 7.46 - 7.42 (m, 2H), 7.41 - 7.37 (m, 2H), 6.68 (d, J= 6.0 Hz, 1H), 3.95 - 3.77 (m, 1H), 3.61 (s, 2H), 2.91 - 2.84 (m, 2H), 2.22 - 2.12 (m, 2H), 1.96 - 1.86 (m, 2H), 1.57 - 1.49 (m, 2H). [001165] Example 639: 4-((l-(4-(2-(3-Aminopyrazin-2-yl)-5-(6-(fluoromethoxy)pyridi n-3- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile

To a solution of Intermediate 335 (420 mg, 843 μmol, HC1 salt), Intermediate 335 (294 mg, 927 μmol, TFA salt) in DMF (2 mL) were added K ₂ CO ₃ (582 mg, 4.21 mmol) and Nal (37.9 mg, 253 μmol). The mixture was stirred at 25 °C for 16 hr. The reaction mixture was quenched with H ₂ O (20 mL) and extracted with EtOAc (30 mL x 3). The combined organic layers were washed with brine (30 mL x 3), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 5% MeOH in CH ₂ CI ₂ ), 4-((l-(4-(2-(3-aminopyrazin-2-yl)-5-(6-(fluoromethoxy)pyridi n-3-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile (Example 639, 269 mg, yield: 51% for three steps) was obtained as a yellow solid. MS: m/z = 629.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.90 (d, J= 2.0 Hz, 1H), 8.41 (dd, J =8.4, 2.4 Hz, 1H), 8.37 (d, J= 8.4 Hz, 1H), 8.15 - 8.03 (m, 3H), 8.02 (d, J= 2.0 Hz, 1H), 7.82 (br s, 2H), 7.49 (d, J= 2.4 Hz, 1H), 7.46 - 7.41 (m, 2H), 7.41 - 7.36 (m, 2H), 7.09 (d, J= 8.8 Hz, 1H), 6.68 (br d, J= 6.4 Hz, 1H), 6.12 (d, J= 52.8 Hz, 2H), 3.91 - 3.76 (m, 1H), 3.60 (s, 2H), 2.89 - 2.82 (m, 2H), 2.22 - 2.11 (m, 2H), 1.96 - 1.84 (m, 2H), 1.57 - 1.45 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ -154.386.

[001166] Example 640: 4-((l-(4-(2-(3-Aminopyrazin-2-yl)-5-(6-(fluoromethoxy- ak)pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperi din-4-yl)amino)pyrimidine-2- carbonitrile

To a solution of Intermediate 336 (207 mg, 414 μmol, HC1 salt) and Intermediate 51 (131 mg, 414 μmol, TFA) in DMF (5 mL) were added K ₂ CO ₃ (172 mg, 1.24 mmol) and Nal (6.2 mg, 41.4 μmol). The mixture was stirred at 50 °C for 1 hr. The reaction mixture was quenched with H ₂ O (30 mL) at 25 °C and extracted with CH ₂ CI ₂ (20 mL x 2). The combined organic layers were washed with brine (50 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 1% ~ 5% MeOH in CH ₂ CI ₂ ) and triturated with EtOAc (10 mL) at 25 °C for 5 min., 4-((l-(4-(2-(3-aminopyrazin-2- yl)-5-(6-(fluoromethoxy-d ₂ )pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)pi peridin-4- yl)amino)pyrimidine-2-carbonitrile (Example 640, 104 mg, yield: 39% for two steps) was obtained as a yellow solid. MS: m/z = 631.2 [M + H] ⁺ . D%: 2D% = 96.6%. ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.94 - 8.86 (m, 1H), 8.44 - 8.34 (m, 2H), 8.10 - 8.01 (m, 4H), 7.80 (br s, 2H), 7.51 - 7.47 (m, 1H), 7.46 - 7.41 (m, 2H), 7.40 - 7.36 (m, 2H), 7.09 (d, J= 8.4 Hz, 1H), 6.68 (d, J= 5.2 Hz, 1H), 3.89 - 3.77 (m, 1H), 3.60 (s, 2H), 2.88 - 2.82 (m, 2H), 2.22 - 2.14 (m, 2H), 1.95 - 1.87 (m, 2H), 1.56 - 1.47 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -155.59. [001167] Example 641: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(6-cyclopropoxypyridin-3 - yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile

To a mixture of Intermediate 337 (191 mg, 407 μmol) and Intermediate 51 (91.1 mg, 448 μmol) in DMF (4 mL) were added Nal (12.2 mg, 81.5 μmol) and K ₂ CO ₃ (169 mg, 1.22 mmol). The mixture was stirred at 80 °C for 12 hr. The mixture was diluted with H ₂ O (50 mL) and extracted with EtOAc (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by silica gel flash chromatography (Methanol in CH ₂ CI ₂ = 0 - 10 %) and prep-HPLC (column: C18 150 x 30 mm; mobile phase: [water (NH ₃ H ₂ O + NH ₄ HCO ₃ ) - ACN]; gradient: 48% - 78% B over 7 min), 4- ((l-(4-(2-(2-aminopyridin-3-yl)-5-(6-cyclopropoxypyridin-3-y l)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile (Example 641, 50.7 mg, yield 20% for 3 steps) was obtained as a white solid. MS: m/z = 658.2 [M + Na] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.87 (d, J= 2.0 Hz, 1H), 8. 34 - 8. 24 (m, 2H), 8.12 - 8.04 (m, 2H), 8.01 - 7.95 (m, 2H), 7.52 - 7.43 (m, 4H), 7.16 (d, J= 7.2 Hz, 1H), 7.04 (br s, 2H), 6.95 (d, J= 8.8 Hz, 1H), 6.67 (d, J= 6.4 Hz, 1H), 6.38 (dd, J= 7.6, 4.8 Hz, 1H), 4.28 - 4.19 (m, 1H), 3.90 - 3.75 (m, 1H), 3.59 (s, 2H), 2.90 - 2.78 (m, 2H), 2.21 - 2.11 (m, 2H), 1.94 - 1.80 (m, 2H), 1.55 - 1.40 (m, 2H), 0.82 - 0.73 (m, 2H), 0.70 - 0.61 (m, 2H).

[001168] Example 642: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(6-isopropoxypyridin-3-y l)-

3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino )pyrimidine-2-carbonitrile

Example 642 was prepared in a manner similar to Example 261. MS: m/z = 660.2 [M + Na] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.84 (d, J= 2.0 Hz, 1H), 8.32 - 8.23 (m, 2H), 8.12 - 8.03 (m, 2H), 8.01 - 7.92 (m, 2H), 7.52 - 7.41 (m, 4H), 7.15 (dd, J =7.6, 1.6 Hz, 1H), 7.03 (br s, 2H), 6.82 (d, J= 8.8 Hz, 1H), 6.67 (d, J =6.0 Hz, 1H), 6.38 (dd, J =8.0, 4.8 Hz, 1H), 5.32 - 5.21 (m, 1H), 3.88 - 3.74 (m, 1H), 3.59 (s, 2H), 2.91 - 2.76 (m, 2H), 2.21 - 2.09 (m, 2H), 1.96 - 1.81 (m, 2H), 1.55 - 1.43 (m, 2H), 1.33 - 1.29 (m, 6H).

[001169] Example 643: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(6-isopropylpyridin-3-yl )-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

To a solution of Intermediate 342 (186 mg, 409 μmol) and Intermediate 51 (99.7 mg, 491 μmol) in DMF (6 mL) were added K ₂ CO ₃ (170 mg, 1.23 mmol) and Nal (12.3 mg, 81.8 μmol) at 20 °C. The reaction mixture was stirred at 20 °C for 12 hr and 80 °C for 2 hr. The mixture was diluted with H ₂ O (20 mL) and extracted with EtOAc (20 mL x 2). The combined organic layers were washed with brine (20 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by prep-HPLC (column: C18 150 x 30 mm; mobile phase: [water(NH ₃ H ₂ O+NH ₄ HCO ₃ )-ACN];gradient:56%-86% B over 7 min), 4-((l-(4-(2-(2- aminopyridin-3-yl)-5-(6-isopropylpyridin-3-yl)-3H-imidazo[4, 5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile (Example 643, 64.2 mg, 99.0 μmol, 24% yield for 3 steps) was obtained as a yellow solid. MS: m/z = 622.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.13 - 9.11 (m, 1H), 8.32 - 8.25 (m, 2H), 8.13 - 7.99 (m, 4H), 7.51 - 7.44 (m, 4H), 7.36 (d, J= 8.0 Hz, 1H), 7.17 (dd, J= 8.0, 2.0 Hz, 1H), 7.03 (s, 2H), 6.67 (d, J= 6.0 Hz, 1H), 6.39 (dd, J= 7.6, 4.8 Hz, 1H), 3.82 (br s, 1H), 3.59 (s, 2H), 3.10 - 3.00 (m, 1H), 2.88 - 2.79 (m, 2H), 2.22 - 2.11 (m, 2H), 1.94 - 1.84 (m, 2H), 1.55 - 1.44 (m, 2H), 1.24 (d, J= 7.2 Hz, 6H).

[001170] Example 644: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(5-cyclopropylpyridin-2- yl)- 3H-imidazo[4,5-Z>]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile

To a solution of Intermediate 343 (238 mg, 525 μmol) in DMF (3 mL) were added Intermediate 51 (128 mg, 631 μmol), K ₂ CO ₃ (218 mg, 1.58 mmol), Nal (7.88 mg, 52.5 μmol). The mixture was stirred at 25 °C for 12 hr under N ₂ . The mixture was diluted with H ₂ O (20 mL) and extracted with EtOAc (10 mL x 2). The combined organic layers were washed with brine (15 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purified by prep-HPLC (column: Welch Xtimate C18 150 x 30mm x 5 μm; mobile phase: [water( NH ₄ HCO ₃ ) - ACN];gradient: 57% - 87% B over 7 min), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(5- cyclopropylpyridin-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzy l)piperidin-4- yl)amino)pyrimidine-2-carbonitrile (Example 644, 99.6 mg, yield: 30.6% for three steps) was obtained as a light yellow solid. MS: m/z = 620.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.49 (d, J= 2.0 Hz, 1H), 8.42 (d, J= 8.4 Hz, 1H), 8.28 (d, J= 8.4 Hz, 1H), 8.13 - 8.03 (m, 3H), 8.00 (dd, J= 4.8, 2 Hz, 1H), 7.53 - 7.43 (m, 5H), 7.16 (dd, J= 7.6, 2.4 Hz, 1H), 7.02 (br s, 2H), 6.68 (d, J= 6.0 Hz, 1H), 6.38 (dd, J= 7.6, 4.8 Hz, 1H), 3.89 - 3.74 (m, 1H), 3.60 (s, 2H), 2.90 - 2.76 (m, 2H), 2.23 - 2.16 (m, 2H), 2.15 - 1.95 (m, 1H), 1.94 - 1.84 (m, 2H), 1.59 - 1.47 (m, 2H), 1.07 - 1.03 (m, 2H), 0.82 - 0.77 (m, 2H).

[001171] Example 645: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(6-(difluoromethyl)pyrid in-3- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile

To a solution of Intermediate 344 (405 mg, 811 μmol, HC1 salt) and Intermediate 51 (260 mg, 820 μmol, TFA salt) in DMF (4 mL) were added K ₂ CO ₃ (336 mg, 2.43 mmol) and Nal (12.2 mg, 81.1 μmol). The mixture was stirred at 25°C for 16 hr. The reaction mixture was quenched with H ₂ O (20 mL) and extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (20 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 6% MeOH in CH ₂ CI ₂ ), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(6-(difluoromethyl)pyrid in-3-yl)-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carb onitrile (Example 645, 227.8 mg, yield: 45% for three steps) was obtained as a brown solid. MS: m/z =630.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.32 (s, 1H), 8.64 - 8.48 (m, 1H), 8.36 (d, J= 8.4 Hz, 1H), 8.15 (d, J= 8.4 Hz, 1H), 8.11 - 8.03 (m, 2H), 8.03 -7.99 (m, 1H), 7.80 (d, J= 8.0 Hz, 1H), 7.52 - 7.43 (m, 4H), 7.20 - 7.13 (m, 1H), 7.14 - 6.86 (m, 3H), 6.67 (d, J= 5.6 Hz, 1H), 6.39 (dd, J =7.6, 4.8 Hz, 1H), 3.89 - 3.74 (m, 1H), 3.59 (s, 2H), 2.90 - 2.75 (m, 2H), 2.21 - 2.10 (m, 2H), 1.98 - 1.77 (m, 2H), 1.60 - 1.40 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethysulfoxide-d ₆ ) δ - 115.381.

[001172] Example 646: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(6-(trifluoromethyl)pyri din-3- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile

Example 646 was prepared in a manner similar to Example 261. MS: m/z =648.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₆ ) 9.45 (s, 1H), 8.72 - 8.48 (m, 1H), 8.29 (d, J= 8.8 Hz, 1H), 8.10 (d, J= 8.4 Hz, 1H), 8.04 - 7.94 (m, 2H), 7.88 (d, J= 8.0 Hz, 1H), 7.57 (d, J= 8.4 Hz, 2H), 7.47 (d, J= 8.4 Hz, 2H), 7.38 - 7.28 (m, 1H), 6.67 - 6.52 (m, 1H), 6.48 (dd, J= 7.6, 4.8 Hz ,1H), 4.07 - 3.88 (m, 1H), 3.67 (s, 2H), 3.05 - 2.89 (m, 2H), 2.36 - 2.20 (m, 2H), 2.05 - 1.98 (m, 2H), 1.59 - 1.58 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethysulfoxide^) 6 -69.247. [001173] Example 647: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(5-ethylpyridin-2-yl)-3H - imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile

To a solution of Intermediate 346 (237 mg, 496 μmol, HC1 salt) and Intermediate 51 (158 mg, 496 μmol, TFA salt) in DMF (5 mL) were added K ₂ CO ₃ (343 mg, 2.48 mmol) and Nal (14.9 mg, 99.3 μmol). The mixture was stirred at 50 °C for 1 hr. The reaction mixture was quenched with H ₂ O (10 mL) at 25 °C and extracted with CH ₂ CI ₂ (15 mL x 2). The combined organic layers were washed with brine (50 mL x3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-HPLC (column: CD07 - Daisogel SP-100-8-ODS-PK 150 x 25 x 10 μm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 42% - 72% B over 10 min), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(5-ethylpyridin-2-yl)-3H -imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile (Example 647, 100 mg, yield: 33% for two steps) was obtained as a yellow lyophilized powder. MS: m/z = 608.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.53 (d, J= 1.6 Hz, 1H), 8.43 (d, J= 8.4 Hz, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.14 - 8.02 (m, 3H), 8.00 (dd, J= 4.8, 1.6 Hz, 1H), 7.74 (dd, J= 8.0, 1.2 Hz, 1H), 7.53 - 7.43 (m, 4H), 7.19 - 7.13 (m, 1H), 7.02 (br s, 2H), 6.68 (d, J= 6.0 Hz, 1H), 6.38 (dd, J= 7.6, 4.8 Hz, 1H), 3.91 - 3.74 (m, 1H), 3.60 (s, 2H), 2.89 - 2.79 (m, 2H), 2.66 (q, J= 7.6 Hz, 2H), 2.22 - 2.12 (m, 2H), 1.94 - 1.81 (m, 2H), 1.57 - 1.45 (m, 2H), 1.21 (t, J= 7.6 Hz, 3H).

[001174] Example 648: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(5-(fluoromethyl)pyridin -2- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile

To a solution of Intermediate 348 (158 mg, 328 μmol, HC1 salt) and Intermediate 51 (104 mg, 328 μmol, TFA) in DMF (5 mL) were added K ₂ CO ₃ (227 mg, 1.64 mmol) and Nal (9.84 mg, 65.7 μmol). The mixture was stirred at 50 °C for 1 hr. The reaction mixture was quenched with H ₂ O (5 mL) at 25 °C and extracted with CH ₂ CI ₂ (15 mL x 2). The combined organic layers were washed with brine (50 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by silica gel flash chromatography (Eluent of 0% ~ 6% MeOH in CH ₂ CI ₂ ), 4-((l-(4-(2-(2-aminopyridin-3-yl)-5-(5-(fluoromethyl)pyridin -2-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrim idine-2-carbonitrile (Example 648, 116 mg, yield: 52% for three steps) was obtained as a yellow solid. MS: m/z = 612.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.73 (s, 1H), 8.49 (d, J= 8.4 Hz, 1H), 8.32 (d, J= 8.4 Hz, 1H), 8.23 (d, J= 8.4 Hz, 1H), 8.13 - 8.02 (m, 2H), 8.01 (dd, J= 4.8, 2.0 Hz, 1H), 7.99 - 7.94 (m, 1H), 7.52 - 7.46 (m, 4H), 7.17 (dd, J= 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.68 (d, J= 6.0 Hz, 1H), 6.39 (dd, J= 7.6, 4.8 Hz, 1H), 5.53 (d, J= 47.2 Hz, 2H), 3.93 - 3.71 (m, 1H), 3.61 (s, 2H), 2.89 - 2.80 (m, 2H), 2.23 - 2.13 (m, 2H), 1.95 - 1.85 (m, 2H), 1.58 - 1.46 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ -206.809.

[001175] Example 649: 4-((l-(4-(2-(2-Aminopyridin-3-yl)-5-(5-(difluoromethyl)pyrid in-2- yl)-3H-imidazo[4,5-Z>]pyridin-3-yl)benzyl)piperidin-4-yl) amino)pyrimidine-2-carbonitrile

To a solution of Intermediate 349 (270 mg, 541 μmol, HC1 salt) and Intermediate 51 (172 mg, 541 μmol, TFA salt) in DMF (5 mL) were added K ₂ CO ₃ (299 mg, 1.16 mmol) and Nal (41 mg, 270 μmol). The mixture was stirred at 25 °C for 16 hr. The reaction mixture was with H ₂ O (5 mL) at 25 °C and extracted with EtOAc (10 mL x 3). The combined organic layers were washed with brine (10 mL x3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purified by prep-HPLC (column: CD07-Daisogel SP-100-8-ODS-PK 150 x 25 x 10 μm; mobile phase: [water (NH4HCO3) - ACN]; gradient: 38% - 68% B over 10 min), 4-((l-(4-(2-(2- aminopyridin-3-yl)-5-(5-(difluoromethyl)pyridin-2-yl)-3H-imi dazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile (Example 649, 170.4 mg, yield: 48% for two steps) was obtained as a yellow powder. MS: m/z = 630.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 8.87 (s, 1H), 8.51 (d, J= 8.4 Hz, 1H), 8.37 - 8.29 (m, 2H), 8.14 - 8.00 (m, 4H), 7.53 - 7.46 (m, 4H), 7.35 - 7.16 (m, 2H), 7.06 - 7.00 (m, 2H), 6.68 (d, J= 6.0 Hz, 1H), 6.39 (dd, J= 7.6, 4.8 Hz, 1H), 3.90 - 3.72 (m, 1H), 3.60 (s, 2H), 2.88 - 2.80 (m, 2H), 2.22 - 2.12 (m, 2H), 1.97 - 1.86 (m, 2H), 1.58 - 1.47 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide- d ₆ ) δ -111.254. [001176] Example 650: 4-((1-(4-(2-(2-Aminopyridin-3-yl)-5-(5-(trifluoromethyl)pyri din-2- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amin o)pyrimidine-2-carbonitrile Example 650 was prepared in a manner similar to Example 261. MS: m/z = 648.6 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) δ 9.06 (s, 1H), 8.53 (d, J = 8.4 Hz, 1H), 8.41 - 8.26 (m, 3H), 8.21 - 7.97 (m, 3H), 7.57 - 7.42 (m, 4H), 7.18 (d, J = 7.6 Hz, 1H), 7.03 (br s, 2H), 6.68 (d, J = 5.6 Hz, 1H), 6.43 - 6.35 (m, 1H), 3.92 - 3.72 (m, 1H), 3.60 (s, 2H), 2.90 - 2.78 (m, 2H), 2.22 - 2.10 (m, 2H), 1.96 - 1.83 (m, 2H), 1.57 - 1.44 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide- II. Biological Evaluation Example 1: NanoBRET Target Engagement (TE) Assay [001177] NanoBRET is a highly specific and validated cell-based technique for assessing target engagement (Vasta et al., 2018, Cell Chem Biol.25(2):206-214). The NanoBRET Target Engagement (TE) Intracellular Kinase Assays are based on the NanoBRET System (Promega Corporation), an energy transfer technique designed to measure molecular proximity in living cells. The NanoBRET TE Assays measure the apparent affinity of test compounds by competitive displacement of the NanoBRET tracer compound, which is a cell permeable molecule engineered to be reversibly bound to a NanoLuc® luciferase-kinase fusion expressed in cells. For compound screening, when a test compound binds to the selected kinase, the BRET signal is attenuated. For kinase inhibitors in particular, intracellular target selectivity is fundamental to pharmacological mechanism and allows the proteins of interest to be in the correct cellular confirmation. Although non-cell-based techniques have been developed to measure kinase binding or enzymatic inhibition with accuracy and precision, such approaches can fail to accurately predict engagement of the full-length target protein in the more complex and biologically relevant cellular context (Knight and Shokat, 2005, Chem. Biol.12, 621–637; Smyth and Collins, 2009, J. Chem. Biol.2, 131–151). The NanoBRET assay procedure was used to interrogate the compounds against the full length AKT E17K per manufacturers suggestions. Briefly, HEK-293 cells (ATCC Cat # CRL-1573) were used for transfection purposes using FuGENE HD Transfection Reagent (Promega Cat # E2311). All cells were evaluated for viability prior to transfection and optimization of the transfection was done prior to experimentation. Greater than 95% viability was used for all experiments. Following transfection, cells were washed and resuspended in Opti-MEM. NanoBRET assays were performed in white, 384-well plates (Corning) at a density of 2x10 ⁵ cells/well. All example compounds were prepared as concentrated stock solutions in DMSO (Sigma-Aldrich). Compounds are dissolved in DMSO to make 10 mM stock solution. Example compounds were transferred as 40uL of 10 mM stock solution to a 384 pp-plate (LABCYTE, PP-0200) and diluted in 3-fold. 10-point dilution via transferring 12 μL compound into 24 μL DMSO by Apricot liquid handler. A Labcyte ECHO 550 compound dispenser was used to facilitate compound transfer directly to cells. Cells were equilibrated for 2 hr with energy transfer probes and example compound prior to BRET measurements. The AKTE17K (Promega Cat # NV2421) as well as specific probe (NanoBRET tracer, Promega Cat # N264B) was prepared at a concentration of 20X in tracer dilution buffer (12.5 mM HEPES, 31.25% PEG-400, pH 7.5). For target engagement analysis, the energy transfer probes were added to the cells at concentrations optimized for the target in question (AKT E17K). Following compound incubation, NanoBRET NanoGlo Substrate (Promega Cat # N157D) and Extracellular Nanoluc Inhibitor (Promega Cat # N235C) was added according to the manufacturer’s recommended protocol, and luminescence was measured on Envision Reader (Perkin Elmer) Multimode Luminometer equipped with 450nmBPfilter (donor)and 600nmLPfilter (acceptor), using 0.5 s integration time. Milli-BRET units (mBU) are calculated by multiplying the raw BRET values by 1000. Apparent tracer affinity values (EC50) were determined using the sigmoidal dose- response (variable slope). Competitive displacement data were then plotted and data were fit to determine the EC ₅₀ value for each example compound. Table 4 provides the assay results for select examples. Activity is defined as “+“, for EC ₅₀ between 600-10,000 nanomolar; “++” for EC ₅₀ between 60-600 nanomolar; “+++” for EC ₅₀ between 15-60 nanomolar; and “++++”, for EC ₅₀ less than 15 nanomolar. Table 4

III. Preparation of Pharmaceutical Dosage Forms Example 1: Oral capsule [001178] The active ingredient is a compound of Table 1, or a pharmaceutically acceptable salt or solvate thereof. A capsule for oral administration is prepared by mixing 1-1000 mg of active ingredient with starch or other suitable powder blend. The mixture is incorporated into an oral dosage unit such as a hard gelatin capsule, which is suitable for oral administration. Example 2: Solution for injection [001179] The active ingredient is a compound of Table 1, or a pharmaceutically acceptable salt or solvate thereof, and is formulated as a solution in sesame oil at a concentration of 50 mg- eq/mL. [001180] The examples and embodiments described herein are for illustrative purposes only and various modifications or changes suggested to persons skilled in the art are to be included within the spirit and purview of this application and scope of the appended claims.