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Title:
3-(6-AMINOPYRIDIN-3-YL)BENZAMIDE DERIVATIVES AS RIPK2 INHIBITORS
Document Type and Number:
WIPO Patent Application WO/2022/066917
Kind Code:
A1
Abstract:
Disclosed are compounds of Formula (1) and pharmaceutically acceptable salts thereof, wherein L1, R1, R2, R3, R4, R6, R7, R8, R9 and X5 are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, to pharmaceutical compositions which contain them, and to their use for treating diseases, disorders, and conditions associated with RIPK2.

Inventors:
TON-NU THU (US)
WANG HAIXIA (US)
WANG XIOALUN (US)
Application Number:
PCT/US2021/051764
Publication Date:
March 31, 2022
Filing Date:
September 23, 2021
Export Citation:
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Assignee:
TAKEDA PHARMACEUTICALS CO (JP)
TON NU THU (US)
WANG HAIXIA (US)
WANG XIOALUN (US)
International Classes:
A61P29/00; A61K31/44; A61K31/4427; A61P35/00; C07D213/74; C07D213/82; C07D241/14; C07D241/26; C07D401/04; C07D401/12; C07D401/14; C07D403/04; C07D405/04; C07D405/12; C07D405/14; C07D413/04; C07D413/12; C07D413/14; C07D417/04; C07D498/04
Domestic Patent References:
WO2003093297A22003-11-13
WO2019161495A12019-08-29
WO2018052773A12018-03-22
WO1991011172A11991-08-08
WO1994002518A11994-02-03
WO1998055148A11998-12-10
Foreign References:
US6106864A2000-08-22
Other References:
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Attorney, Agent or Firm:
RUSSO, Matthew J. et al. (US)
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Claims:
WHAT IS CLAIMED IS: 1. A compound of Formula 1, or a pharmaceutically acceptable salt thereof in which: (a) L1 is a bond or -C(O)-; R1 is selected from: (i) halo and cyano; (ii) amino having first and second substituents, wherein the first substituent is selected from hydrogen and C1-4 alkyl, and the second substituent is selected from hydrogen, C1-6 alkyl, C3-8 cycloalkyl, C2-8 heterocyclyl, C2-8 heterocyclyl-C1-3 alkyl, C6-14 aryl, C1-9 heteroaryl and C1-9 heteroaryl-C1-3 alkyl, wherein the second substituent on amino may be hydrogen only when L1 is -C(O)-, and wherein C1-6 alkyl, C3-8 cycloalkyl, C2-8 heterocyclyl and C2-8 heterocyclyl-C1-3 alkyl are each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, oxo, cyano, C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C1-4 alkyl; C6-14 aryl, C1-9 heteroaryl and C1-9 heteroaryl- C1-3 alkyl are each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C1-4 alkyl; and the C1-4 alkyl, C1-4 alkoxy and C3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C1-4 alkoxy; (iii) C1-6 alkyl and C1-6 alkoxy, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C1-4 alkoxy, C3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C1-4 alkyl, wherein the C1-4 alkoxy and C3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C1-4 alkoxy, and wherein R1 is not C1-6 alkoxy when L1 is -C(O)-; (iv) C3-8 cycloalkyl, C2-8 heterocyclyl and C2-8 heterocyclyl-C1-3 alkyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, oxo, cyano, C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C1-4 alkyl, wherein the C1-4 alkyl, C1-4 alkoxy and C3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C1-4 alkoxy; and (v) C6-14 aryl, C1-9 heteroaryl and C1-9 heteroaryl-C1-3 alkyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C1-4 alkyl, wherein the C1-4 alkyl, C1-4 alkoxy and C3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C1-4 alkoxy; R2 is selected from hydrogen and C1-4 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo and hydroxy; and R3 is selected from: (i) C1-6 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano and C1-4 alkoxy; and (ii) C3-8 cycloalkyl, C3-8 cycloalkyl-C1-3 alkyl, and C2-8 heterocyclyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C1-4 alkyl and C1-4 alkoxy, wherein the C1-4 alkyl and C1-4 alkoxy optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo and hydroxy; or R2 and R3, together with the nitrogen atom to which they are both attached, form a C2-8 heterocyclyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C1-4 alkyl and C1-4 alkoxy, wherein the C1-4 alkyl and C1-4 alkoxy optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo and hydroxy; or (b) L1 is a bond; R1 and R2 together form a –(CH2)n-O-CH2CH2- bridge which spans the carbon and nitrogen atoms to which R1 and R2 are attached, wherein n is selected from 0 and 1, and wherein the (CH2)n end of the bridge is attached to the carbon atom to which R1 is attached; and R3 is C1-6 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano and C1-4 alkoxy; X5 is selected from N and C(R5); R4, R5, R6 and R7 are each independently selected from hydrogen, halo and C1-4 alkyl; R8 is C1-4 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo; and R9 is selected from C3-8 cycloalkyl, C2-8 heterocyclyl, C6-14 aryl and C1-9 heteroaryl, each substituted with from 0 to 3 optional substituents independently selected from C1-4 alkyl; wherein each of the heterocyclyl and heteroaryl moieties independently has 1 to 4 ring members which are heteroatoms, each of the heteroatoms independently selected from N, O, and S, provided when R2 and R3 form a heterocyclyl moiety, at least one of the heteroatoms is N. 2. The compound or pharmaceutically acceptable salt according to claim 1, wherein L1 is a bond or -C(O)-; R1 is selected from: (i) halo and cyano; (ii) amino having first and second substituents, wherein the first substituent is selected from hydrogen and C1-4 alkyl, and the second substituent is selected from hydrogen, C1-6 alkyl, C3-8 cycloalkyl, C2-8 heterocyclyl, C2-8 heterocyclyl-C1-3 alkyl, C6-14 aryl, C1-9 heteroaryl and C1-9 heteroaryl-C1-3 alkyl, wherein the second substituent on amino may be hydrogen only when L1 is -C(O)-, and wherein C1-6 alkyl, C3-8 cycloalkyl, C2-8 heterocyclyl and C2-8 heterocyclyl-C1-3 alkyl are each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, oxo, cyano, C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C1-4 alkyl; C6-14 aryl, C1-9 heteroaryl and C1-9 heteroaryl- C1-3 alkyl are each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C1-4 alkyl; and the C1-4 alkyl, C1-4 alkoxy and C3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C1-4 alkoxy; (iii) C1-6 alkyl and C1-6 alkoxy, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C1-4 alkoxy, C3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C1-4 alkyl, wherein the C1-4 alkoxy and C3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C1-4 alkoxy, and wherein R1 is not C1-6 alkoxy when L1 is -C(O)-; (iv) C3-8 cycloalkyl, C2-8 heterocyclyl and C2-8 heterocyclyl-C1-3 alkyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, oxo, cyano, C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C1-4 alkyl, wherein the C1-4 alkyl, C1-4 alkoxy and C3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C1-4 alkoxy; and (v) C6-14 aryl, C1-9 heteroaryl and C1-9 heteroaryl-C1-3 alkyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C1-4 alkyl, wherein the C1-4 alkyl, C1-4 alkoxy and C3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C1-4 alkoxy; R2 is selected from hydrogen and C1-4 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo and hydroxy; and R3 is selected from: (i) C1-6 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano and C1-4 alkoxy; and (ii) C3-8 cycloalkyl, C3-8 cycloalkyl-C1-3 alkyl, and C2-8 heterocyclyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C1-4 alkyl and C1-4 alkoxy, wherein the C1-4 alkyl and C1-4 alkoxy optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo and hydroxy; or R2 and R3, together with the nitrogen atom to which they are both attached, form a C2-8 heterocyclyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C1-4 alkyl and C1-4 alkoxy, wherein the C1-4 alkyl and C1-4 alkoxy optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo and hydroxy. 3. The compound or pharmaceutically acceptable salt according to claim 2, wherein R1 is cyano. 4. The compound or pharmaceutically acceptable salt according to claim 2, wherein R1 is amino having first and second substituents, wherein the first substituent is selected from hydrogen and C1-4 alkyl, and the second substituent is selected from hydrogen, C1-6 alkyl, C3-8 cycloalkyl, C2-8 heterocyclyl, C2-8 heterocyclyl-C1-3 alkyl, C6-14 aryl, C1-9 heteroaryl and C1-9 heteroaryl-C1-3 alkyl, wherein the second substituent on amino may be hydrogen only when L1 is -C(O)-, and wherein C1-6 alkyl, C3-8 cycloalkyl, C2-8 heterocyclyl and C2-8 heterocyclyl-C1-3 alkyl are each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, oxo, cyano, C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C1-4 alkyl; C6-14 aryl, C1-9 heteroaryl and C1-9 heteroaryl- C1-3 alkyl are each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C1-4 alkyl; and the C1-4 alkyl, C1-4 alkoxy and C3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C1-4 alkoxy. 5. The compound or pharmaceutically acceptable salt according to claim 4, wherein each of the heterocyclyl and heteroaryl moieties for R1 independently has 1 to 2 ring members which are heteroatoms, each of the heteroatoms independently selected from N and O. 6. The compound or pharmaceutically acceptable salt according to claim 2, wherein R1 is selected from C1-6 alkyl and C1-6 alkoxy, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C1-4 alkoxy, C3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C1-4 alkyl, wherein the C1-4 alkoxy and C3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C1-4 alkoxy, and wherein R1 is not C1-6 alkoxy when L1 is -C(O)-. 7. The compound or pharmaceutically acceptable salt according to claim 2, wherein R1 is selected from C3-8 cycloalkyl, C2-8 heterocyclyl and C2-8 heterocyclyl-C1-3 alkyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, oxo, cyano, C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C1-4 alkyl, wherein the C1-4 alkyl, C1-4 alkoxy and C3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C1-4 alkoxy.

8. The compound or pharmaceutically acceptable salt according to claim 7, wherein each of the heterocyclyl moieties for R1 independently has 1 to 2 ring members which are heteroatoms, each of the heteroatoms independently selected from N and O. 9. The compound or pharmaceutically acceptable salt according to claim 2, wherein R1 is selected from C6-14 aryl, C1-9 heteroaryl and C1-9 heteroaryl-C1-3 alkyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C1-4 alkyl, wherein the C1-4 alkyl, C1-4 alkoxy and C3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C1-4 alkoxy. 10. The compound or pharmaceutically acceptable salt according to claim 2, wherein R1 is selected from phenyl, C1-5 heteroaryl and C1-5 heteroaryl-C1-3 alkyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C1-4 alkyl, wherein the C1-4 alkyl, C1-4 alkoxy and C3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C1-4 alkoxy. 11. The compound or pharmaceutically acceptable salt according to any one of claims 9 and 10, wherein each of the heteroaryl moieties for R1 independently has 1 to 3 ring members which are heteroatoms, each of the heteroatoms independently selected from N, O and S. 12. The compound or pharmaceutically acceptable salt according to any one of claims 2 to 11, wherein R2 is selected from hydrogen and C1-4 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo and hydroxy. 13. The compound or pharmaceutically acceptable salt according to any one of claims 2 to 11, wherein R2 is selected from hydrogen, methyl and ethyl, and wherein the methyl and ethyl substituents are substituted with hydroxy. 14. The compound or pharmaceutically acceptable salt according to any one of claims 2 to 13, wherein R3 is selected from: (i) C1-6 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano and C1-4 alkoxy; and (ii) C3-8 cycloalkyl, C3-8 cycloalkyl-C1-3 alkyl, and C2-8 heterocyclyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C1-4 alkyl and C1-4 alkoxy, wherein the C1-4 alkyl and C1-4 alkoxy optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo and hydroxy. 15. The compound or pharmaceutically acceptable salt according to claim 14, wherein each of the heterocyclyl moieties for R3 independently has 1 to 2 ring members which are heteroatoms, each of the heteroatoms independently selected from N and O. 16. The compound or pharmaceutically acceptable salt according to any one of claims 2 to 11, wherein R2 and R3, together with the nitrogen atom to which they are both attached, form a C2-8 heterocyclyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C1-4 alkyl and C1-4 alkoxy, wherein the C1-4 alkyl and C1-4 alkoxy optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo and hydroxy. 17. The compound or pharmaceutically acceptable salt according to claim 16, wherein each of the heterocyclyl moieties formed from R2 and R3 has 1 to 2 ring members, each of the heteroatoms independently selected from N and O, provided at least one of the heteroatoms is N. 18. The compound or pharmaceutically acceptable salt according to any one of claims 1 to 17, wherein L1 is a bond. 19. The compound or pharmaceutically acceptable salt according to any one of claims 1 to 17, wherein L1 -C(O)-. 20. The compound or pharmaceutically acceptable salt according to claim 1, wherein L1 is a bond; R1 and R2 together form a –(CH2)n-O-CH2CH2- bridge which spans the carbon and nitrogen atoms to which R1 and R2 are attached, wherein n is selected from 0 and 1, and wherein the (CH2)n-end of the bridge is attached to the carbon atom to which R1 is attached; and R3 is C1-6 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano and C1-4 alkoxy.

21. The compound or pharmaceutically acceptable salt according to claim 20, wherein n is 1. 22. The compound or pharmaceutically acceptable salt according to claim 20, wherein n is 0. 23. The compound or pharmaceutically acceptable salt according to any one of claims 1 to 22, wherein X5 is C(R5). 24. The compound or pharmaceutically acceptable salt according to any one of claims 1 to 22, wherein X5 is N. 25. The compound or pharmaceutically acceptable salt according to any one of claims 1 to 23, wherein R5 is hydrogen. 26. The compound or pharmaceutically acceptable salt according to any one of claims 1 to 25, wherein R4 and R7 are each hydrogen. 27. The compound or pharmaceutically acceptable salt according to any one of claims 1 to 26, wherein R6 is selected from hydrogen and halo. 28. The compound or pharmaceutically acceptable salt according to any one of claims 1 to 27, wherein R8 is C1-3 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo. 29. The compound or pharmaceutically acceptable salt according to any one of claims 1 to 28, wherein R9 is selected from C3-6 cycloalkyl, C2-5 heterocyclyl, phenyl and C1-5 heteroaryl, each substituted with from 0 to 3 optional substituents independently selected from C1-4 alkyl. 30. The compound or pharmaceutically acceptable salt according to claim 29, wherein each of the heterocyclyl and heteroaryl moieties for R9 independently has 1 to 2 ring members which are heteroatoms, each of the heteroatoms independently selected from N, O and S. 31. The compound according to claim 1, which is selected from the following compounds: 5-(5-cyano-6-((cis-3-methoxytetrahydro-2H-pyran-4-yl)amino)pyridin-3-yl)-2- fluoro-4-methyl-N-(1H-pyrazol-3-yl)benzamide; 5-(5-cyano-6-((2-hydroxyethyl)(methyl)amino)pyridin-3-yl)-2-fluoro-4-methyl-N- (1H-pyrazol-3-yl)benzamide; 5-(5-cyano-6-(((3R,4S)-3-methoxytetrahydro-2H-pyran-4-yl)amino)pyridin-3-yl)-2- fluoro-4-methyl-N-(1H-pyrazol-3-yl)benzamide; 5-(5-cyano-6-((tetrahydrofuran-3-yl)amino)pyridin-3-yl)-2-fluoro-4-methyl-N-(1H- pyrazol-3-yl)benzamide; (S)-5-(5-cyano-6-(3-hydroxy-3-methylpyrrolidin-1-yl)pyridin-3-yl)-2-fluoro-4- methyl-N-(1H-pyrazol-3-yl)benzamide; 5-(5-cyano-6-(ethyl(2-hydroxyethyl)amino)pyridin-3-yl)-2-fluoro-4-methyl-N-(1H- pyrazol-3-yl)benzamide; 5-(5-cyano-6-((2-hydroxyethyl)amino)pyridin-3-yl)-2-fluoro-4-methyl-N-(1H- pyrazol-3-yl)benzamide; N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(2-methyl- 2H-1,2,3-triazol-4-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(1-methyl- 1H-1,2,3-triazol-4-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((2-hydroxyethyl)amino)-5-(1-methyl-1H-pyrazol-4- yl)pyridin-3-yl)-4-methylbenzamide; (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(1-methyl-1H- pyrazol-3-yl)pyridin-3-yl)-4-methylbenzamide; (R)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(1-methyl-1H- pyrazol-3-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((1-(hydroxymethyl)cyclopropyl)(methyl)amino)-5-(1- methyl-1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((2-hydroxyethyl)amino)-5-(1H-pyrazol-4-yl)pyridin- 3-yl)-4-methylbenzamide; N-cyclopropyl-5-(5-ethoxy-6-((1-hydroxy-2-methylpropan-2-yl)amino)pyridin-3- yl)-2-fluoro-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(1-methyl- 1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-5-(5-(ethylamino)-6-((1-hydroxy-2-methylpropan-2- yl)amino)pyridin-3-yl)-2-fluoro-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2-yl-1,1-d2)amino)-5-(1- methyl-1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide; 5-(5-(cyclopropylcarbamoyl)-4-fluoro-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl-1,1-d2)amino)-N,N-dimethylnicotinamide; N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- isopropoxypyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2-yl-1,1-d2)amino)-5- isopropoxypyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(1-methyl-1H- pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((1-(hydroxymethyl)cyclopropyl)amino)-5-(1-methyl- 1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((2-(hydroxymethyl)propan-2-yl-1,1,1,3,3,3- d6)amino)-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((2-hydroxyethyl-1,1,2,2-d4)amino)-5-(1-methyl-1H- pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(4H-1,2,4- triazol-4-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(1-methyl- 1H-1,2,3-triazol-4-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(1H- imidazol-1-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(1H- pyrazol-1-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(1- (methyl-d3)-1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((2-(hydroxymethyl)propan-2-yl-1,1,1,3,3,3- d6)amino)-5-(1-(methyl-d3)-1H-pyrazol-4-yl)pyridin-3-yl)-4- methylbenzamide; N-cyclopropyl-2-fluoro-5-(4-(2-hydroxyethyl)-3,4-dihydro-2H-pyrido[3,2- b][1,4]oxazin-7-yl)-4-methylbenzamide; (R)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(1-methyl-1H- pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide; (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(1-methyl-1H- pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-5-(1-ethyl-1,2,3,5-tetrahydropyrido[2,3-e][1,4]oxazepin-7-yl)-2- fluoro-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((1-(hydroxymethyl)cyclopropyl)amino)-5-(1-methyl- 1H-pyrazol-3-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(isoxazol-5- yl)pyridin-3-yl)-4-methylbenzamide; (S)-N-cyclopropyl-5-(5-(1-ethyl-1H-pyrazol-4-yl)-6-((1-hydroxypropan-2- yl)amino)pyridin-3-yl)-2-fluoro-4-methylbenzamide; (R)-N-cyclopropyl-5-(5-(1-ethyl-1H-pyrazol-4-yl)-6-((1-hydroxypropan-2- yl)amino)pyridin-3-yl)-2-fluoro-4-methylbenzamide; N-cyclopropyl-5-(5-(1-ethyl-1H-pyrazol-4-yl)-6-((1- (hydroxymethyl)cyclopropyl)amino)pyridin-3-yl)-2-fluoro-4- methylbenzamide; (S)-N-cyclopropyl-2-fluoro-5-(5-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)-6-((1- hydroxypropan-2-yl)amino)pyridin-3-yl)-4-methylbenzamide; (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(1-(2- methoxyethyl)-1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide; (R)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(2-methyl-2H- 1,2,3-triazol-4-yl)pyridin-3-yl)-4-methylbenzamide; (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(oxazol-5- yl)pyridin-3-yl)-4-methylbenzamide; (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(2- methylthiazol-5-yl)pyridin-3-yl)-4-methylbenzamide; (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(1-methyl-1H- imidazol-2-yl)pyridin-3-yl)-4-methylbenzamide; (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(2-methyl-2H- 1,2,3-triazol-4-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((1-(hydroxymethyl)cyclopropyl)amino)-5-(2-methyl- 2H-1,2,3-triazol-4-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((2-hydroxyethyl)amino)-5-(2-methyl-2H-1,2,3- triazol-4-yl)pyridin-3-yl)-4-methylbenzamide; (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(thiazol-5- yl)pyridin-3-yl)-4-methylbenzamide; (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(isothiazol-4- yl)pyridin-3-yl)-4-methylbenzamide; (R)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)(methyl)amino)-5-(1- methyl-1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide; (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(2- methyloxazol-5-yl)pyridin-3-yl)-4-methylbenzamide; (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(isothiazol-5- yl)pyridin-3-yl)-4-methylbenzamide; (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(3- methylisothiazol-5-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((2-hydroxyethyl)amino)-5-(1-methyl-1H-pyrazol-3- yl)pyridin-3-yl)-4-methylbenzamide; (S)-N-cyclopropyl-5-(5-(1,3-dimethyl-1H-pyrazol-4-yl)-6-((1-hydroxypropan-2- yl)amino)pyridin-3-yl)-2-fluoro-4-methylbenzamide; (S)-N-cyclopropyl-5-(5-(1,5-dimethyl-1H-pyrazol-4-yl)-6-((1-hydroxypropan-2- yl)amino)pyridin-3-yl)-2-fluoro-4-methylbenzamide; (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)(methyl)amino)-5-(1- methyl-1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(oxazol-4- yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(5-(3-(hydroxymethyl)-2-methyl-2H-pyrrol-4-yl)-6-(((S)- 1-hydroxypropan-2-yl)amino)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-5-(5-(1-ethyl-1H-pyrazol-4-yl)-6-((2-hydroxyethyl)amino)pyridin-3- yl)-2-fluoro-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(5-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)-6-((2- hydroxyethyl)amino)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((2-methoxyethyl)amino)-5-(1-methyl-1H-pyrazol-4- yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((2-hydroxyethyl)amino)-5-(2-methyloxazol-5- yl)pyridin-3-yl)-4-methylbenzamide; (S)-N-cyclopropyl-2-fluoro-5-(5-(3-(hydroxymethyl)-1-methyl-1H-pyrazol-4-yl)-6- ((1-hydroxypropan-2-yl)amino)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((2-hydroxyethyl)amino)-5-(3-methylisothiazol-5- yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((2-hydroxyethyl)amino)-5-(isothiazol-5-yl)pyridin-3- yl)-4-methylbenzamide; N-cyclopropyl-2-fluoro-5-(6-((2-hydroxyethyl)amino)-5-(oxazol-5-yl)pyridin-3-yl)- 4-methylbenzamide; 5-(5-cyano-6-((2-hydroxyethyl)(methyl)amino)pyridin-3-yl)-2-fluoro-N-(isoxazol- 3-yl)-4-methylbenzamide; 5-(5-cyano-6-((2-hydroxyethyl)amino)pyridin-3-yl)-2-fluoro-N-(isoxazol-3-yl)-4- methylbenzamide; (S)-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(1-methyl-1H-pyrazol-4- yl)pyridin-3-yl)-N-(isoxazol-3-yl)-4-methylbenzamide; 5-(5-cyano-6-(((3R,4S)-3-methoxytetrahydro-2H-pyran-4-yl)amino)pyridin-3-yl)-2- fluoro-N-(isoxazol-3-yl)-4-methylbenzamide; 5-(5-cyano-6-(((3R,4R)-3-methoxytetrahydro-2H-pyran-4-yl)amino)pyridin-3-yl)-2- fluoro-N-(isoxazol-3-yl)-4-methylbenzamide; (S)-5-(5-cyano-6-(3-hydroxy-3-methylpyrrolidin-1-yl)pyridin-3-yl)-2-fluoro-N- (isoxazol-3-yl)-4-methylbenzamide; (S)-5-(5-cyano-6-(3-hydroxypyrrolidin-1-yl)pyridin-3-yl)-2-fluoro-N-(isoxazol-3- yl)-4-methylbenzamide; (S)-5-(5-cyano-6-(3-hydroxypyrrolidin-1-yl)pyridin-3-yl)-2-fluoro-4-methyl-N-(1H- pyrazol-3-yl)benzamide; (S)-5-(5-cyano-6-((tetrahydrofuran-3-yl)amino)pyridin-3-yl)-2-fluoro-N-(isoxazol- 3-yl)-4-methylbenzamide; 5-(5-cyano-6-(ethyl(2-hydroxyethyl)amino)pyridin-3-yl)-2-fluoro-N-(isoxazol-3- yl)-4-methylbenzamide; 5-(5-cyano-6-((2-hydroxyethyl)(methyl)amino)pyridin-3-yl)-N-cyclopropyl-2- fluoro-4-methylbenzamide; 5-(5-cyano-6-(ethyl(2-hydroxyethyl)amino)pyridin-3-yl)-N-cyclopropyl-2-fluoro-4- methylbenzamide; 5-(5-cyano-6-morpholinopyridin-3-yl)-N-cyclopropyl-2-fluoro-4-methylbenzamide; 5-(5-cyano-6-((2-hydroxyethyl)(3-hydroxypropyl)amino)pyridin-3-yl)-N- cyclopropyl-2-fluoro-4-methylbenzamide; 5-(5-cyano-6-((2-hydroxy-2-methylpropyl)(methyl)amino)pyridin-3-yl)-N- cyclopropyl-2-fluoro-4-methylbenzamide; (S)-5-(5-cyano-6-((2-hydroxypropyl)(methyl)amino)pyridin-3-yl)-N-cyclopropyl-2- fluoro-4-methylbenzamide; (S)-5-(5-cyano-6-((1-hydroxypropan-2-yl)amino)pyridin-3-yl)-N-cyclopropyl-2- fluoro-4-methylbenzamide; 5-(5-cyano-6-(3-fluoro-4-hydroxypyrrolidin-1-yl)pyridin-3-yl)-N-cyclopropyl-2- fluoro-4-methylbenzamide; 5-(5-cyano-6-(3-hydroxy-3-methylpyrrolidin-1-yl)pyridin-3-yl)-N-cyclopropyl-2- fluoro-4-methylbenzamide; 5-(6-(bis(2-hydroxyethyl)amino)-5-cyanopyridin-3-yl)-N-cyclopropyl-2-fluoro-4- methylbenzamide; 5-(5-cyano-6-(3-hydroxypyrrolidin-1-yl)pyridin-3-yl)-N-cyclopropyl-2-fluoro-4- methylbenzamide; 5-(5-cyano-6-((2,3-dihydroxypropyl)(methyl)amino)pyridin-3-yl)-N-cyclopropyl-2- fluoro-4-methylbenzamide; 5-(5-cyano-6-(2-(hydroxymethyl)morpholino)pyridin-3-yl)-N-cyclopropyl-2-fluoro- 4-methylbenzamide; 5-(5-cyano-6-((1,3-dihydroxypropan-2-yl)amino)pyridin-3-yl)-N-cyclopropyl-2- fluoro-4-methylbenzamide; (S)-5-(5-cyano-6-((3-hydroxy-3-methylbutan-2-yl)amino)pyridin-3-yl)-N- cyclopropyl-2-fluoro-4-methylbenzamide; 5-(5-cyano-6-((2-hydroxypropyl)amino)pyridin-3-yl)-N-cyclopropyl-2-fluoro-4- methylbenzamide; 5-(5-cyano-6-(oxetan-3-ylamino)pyridin-3-yl)-N-cyclopropyl-2-fluoro-4- methylbenzamide; 5-(5-cyano-6-((tetrahydrofuran-3-yl)amino)pyridin-3-yl)-N-cyclopropyl-2-fluoro-4- methylbenzamide; 5-(5-cyano-6-((3-hydroxy-2-methoxypropyl)amino)pyridin-3-yl)-N-cyclopropyl-2- fluoro-4-methylbenzamide; 5-(5-cyano-6-((3R,4S)-3,4-dihydroxypyrrolidin-1-yl)pyridin-3-yl)-N-cyclopropyl-2- fluoro-4-methylbenzamide; 5-(5-cyano-6-((2-hydroxy-2-methylpropyl)amino)pyridin-3-yl)-N-cyclopropyl-2- fluoro-4-methylbenzamide; 5-(5-cyano-6-(((3R,4S)-4-hydroxytetrahydrofuran-3-yl)(methyl)amino)pyridin-3- yl)-N-cyclopropyl-2-fluoro-4-methylbenzamide; 5-(5-cyano-6-((2-hydroxyethyl)amino)pyridin-3-yl)-N-cyclopropyl-2-fluoro-4- methylbenzamide; 5-(5-cyano-6-(3-methoxy-3-methylpyrrolidin-1-yl)pyridin-3-yl)-N-cyclopropyl-2- fluoro-4-methylbenzamide; 5-(5-cyano-6-(3-hydroxyazetidin-1-yl)pyridin-3-yl)-N-cyclopropyl-2-fluoro-4- methylbenzamide; 5-(5-cyano-6-((2-methoxyethyl)(methyl)amino)pyridin-3-yl)-N-cyclopropyl-2- fluoro-4-methylbenzamide; (R)-5-(5-cyano-6-((2-hydroxybutyl)amino)pyridin-3-yl)-N-cyclopropyl-2-fluoro-4- methylbenzamide; 2-fluoro-5-(6-((2-hydroxyethyl)amino)-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)- N-(isoxazol-3-yl)-4-methylbenzamide; (S)-2-((1-hydroxypropan-2-yl)amino)-5-(5-(isoxazol-3-ylcarbamoyl)-2- methylphenyl)-N,N-dimethylnicotinamide; (R)-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(1-methyl-1H-pyrazol-4- yl)pyridin-3-yl)-N-(isoxazol-3-yl)-4-methylbenzamide; 2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(1-methyl-1H-pyrazol-4- yl)pyridin-3-yl)-N-(isoxazol-3-yl)-4-methylbenzamide; 2-fluoro-5-(6-((2-hydroxyethyl)amino)-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)- 4-methyl-N-(1H-pyrazol-3-yl)benzamide; (R)-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(1-methyl-1H-pyrazol-4- yl)pyridin-3-yl)-4-methyl-N-(1H-pyrazol-3-yl)benzamide; (S)-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(1-methyl-1H-pyrazol-4- yl)pyridin-3-yl)-4-methyl-N-(1H-pyrazol-3-yl)benzamide; 2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(1-methyl-1H-pyrazol-4- yl)pyridin-3-yl)-4-methyl-N-(1H-pyrazol-3-yl)benzamide; N-cyclopropyl-2-fluoro-5-(5-((1-(hydroxymethyl)cyclopropyl)amino)-6-(2-methyl- 2H-1,2,3-triazol-4-yl)pyrazin-2-yl)-4-methylbenzamide; 5-(6-bromo-5-((2-hydroxyethyl)amino)pyrazin-2-yl)-N-cyclopropyl-2-fluoro-4- methylbenzamide; N-cyclopropyl-2-fluoro-5-(5-((2-hydroxyethyl)amino)-6-(1-methyl-1H-pyrazol-4- yl)pyrazin-2-yl)-4-methylbenzamide; (S)-N-cyclopropyl-2-fluoro-5-(5-((1-hydroxypropan-2-yl)amino)-6-(1-methyl-1H- pyrazol-4-yl)pyrazin-2-yl)-4-methylbenzamide; 6-(5-(cyclopropylcarbamoyl)-4-fluoro-2-methylphenyl)-3-((1-hydroxy-2- methylpropan-2-yl)amino)-N,N-dimethylpyrazine-2-carboxamide; (S)-N-cyclopropyl-2-fluoro-5-(5-((1-hydroxypropan-2-yl)amino)-6-(2-methyl-2H- 1,2,3-triazol-4-yl)pyrazin-2-yl)-4-methylbenzamide; (R)-N-cyclopropyl-2-fluoro-5-(5-((1-hydroxypropan-2-yl)amino)-6-(2-methyl-2H- 1,2,3-triazol-4-yl)pyrazin-2-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(oxazol-2- yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(oxazol-5- yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-methoxypyridin-3- yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((2-hydroxyethyl)amino)-5-methoxypyridin-3-yl)-4- methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxypropan-2-yl)amino)-5-methoxypyridin-3-yl)-4- methylbenzamide; 3-(5-(azetidine-1-carbonyl)-6-((1-hydroxy-2-methylpropan-2-yl)amino)pyridin-3- yl)-N-cyclopropyl-4-methylbenzamide; N-cyclopropyl-3-(5-ethoxy-6-((1-hydroxy-2-methylpropan-2-yl)amino)pyridin-3- yl)-4-methylbenzamide; N-cyclopropyl-3-(5-(cyclopropylmethoxy)-6-((1-hydroxy-2-methylpropan-2- yl)amino)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-isopropoxypyridin- 3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(1-methyl-1H- pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(1H-pyrazol-4- yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(5-methyl-1H- pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-phenylpyridin-3- yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-methylpyridin-3- yl)-4-methylbenzamide; N-cyclopropyl-3-(5-ethyl-6-((1-hydroxy-2-methylpropan-2-yl)amino)pyridin-3-yl)- 4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-propylpyridin-3- yl)-4-methylbenzamide; 3-(5-cyclohexyl-6-((1-hydroxy-2-methylpropan-2-yl)amino)pyridin-3-yl)-N- cyclopropyl-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(piperidin-4- yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (methylamino)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(5-(dimethylamino)-6-((1-hydroxy-2-methylpropan-2- yl)amino)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(pyrrolidin-1- yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(2-((1-hydroxy-2-methylpropan-2-yl)amino)-4'-methyl-[3,3'- bipyridin]-5-yl)-4-methylbenzamide; N-cyclopropyl-3-(2-((1-hydroxy-2-methylpropan-2-yl)amino)-[3,3'-bipyridin]-5-yl)- 4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(thiazol-4- yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(2-((1-hydroxy-2-methylpropan-2-yl)amino)-[3,4'-bipyridin]-5-yl)- 4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(piperidin-1- yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-morpholinopyridin- 3-yl)-4-methylbenzamide; N-cyclopropyl-3-(2'-((1-hydroxy-2-methylpropan-2-yl)amino)-[2,3'-bipyridin]-5'- yl)-4-methylbenzamide; N-cyclopropyl-3-(5-(1-ethyl-1H-pyrazol-4-yl)-6-((1-hydroxy-2-methylpropan-2- yl)amino)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(5-(ethylamino)-6-((1-hydroxy-2-methylpropan-2- yl)amino)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(isothiazol-4- yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(1-ethyl-1,2,3,5-tetrahydropyrido[2,3-e][1,4]oxazepin-7-yl)-4- methylbenzamide; N-cyclopropyl-4-methyl-3-(1-propyl-1,2,3,5-tetrahydropyrido[2,3-e][1,4]oxazepin- 7-yl)benzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl-1,1-d2)amino)-5-(1-methyl- 1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(thiazol-5- yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-4-methyl-3-(1-methyl-1,2,3,5-tetrahydropyrido[2,3-e][1,4]oxazepin- 7-yl)benzamide; N-cyclopropyl-3-(1-(2-methoxyethyl)-1,2,3,5-tetrahydropyrido[2,3-e][1,4]oxazepin- 7-yl)-4-methylbenzamide; N-cyclopropyl-3-(1-(2-hydroxyethyl)-1,2,3,5-tetrahydropyrido[2,3-e][1,4]oxazepin- 7-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(thiazol-2- yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(5-(1-ethyl-1H-imidazol-4-yl)-6-((1-hydroxy-2-methylpropan-2- yl)amino)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(1-methyl-1H- imidazol-2-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(1-methyl-1H- imidazol-4-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(5-(1-ethyl-1H-imidazol-2-yl)-6-((1-hydroxy-2-methylpropan-2- yl)amino)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(1- (trifluoromethyl)-1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(5-(1-cyclopropyl-1H-pyrazol-4-yl)-6-((1-hydroxy-2- methylpropan-2-yl)amino)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(isothiazol-3- yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(5-methyl-1H- imidazol-2-yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(1H-imidazol-2- yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(1H-imidazol-4- yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(isothiazol-5- yl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(5-(1,5-dimethyl-1H-imidazol-2-yl)-6-((1-hydroxy-2- methylpropan-2-yl)amino)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(5-(1,4-dimethyl-1H-imidazol-2-yl)-6-((1-hydroxy-2- methylpropan-2-yl)amino)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (methoxymethyl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-4-methyl-3-(1-(2,2,2-trifluoroethyl)-1,2,3,5-tetrahydropyrido[2,3- e][1,4]oxazepin-7-yl)benzamide; 2-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(5-(isoxazol-3-ylcarbamoyl)-2- methylphenyl)-N,N-dimethylnicotinamide; 5-(4-fluoro-5-(isoxazol-3-ylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N,N-dimethylnicotinamide; (S)-5-(4-fluoro-5-(isoxazol-3-ylcarbamoyl)-2-methylphenyl)-2-((1-hydroxypropan- 2-yl)amino)-N,N-dimethylnicotinamide; 5-(5-(azetidine-1-carbonyl)-6-((1-hydroxy-2-methylpropan-2-yl)amino)pyridin-3- yl)-N-cyclopropyl-2-fluoro-4-methylbenzamide; 2-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(5-(isothiazol-3-ylcarbamoyl)-2- methylphenyl)-N,N-dimethylnicotinamide; 5-(4-fluoro-5-(isothiazol-3-ylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N,N-dimethylnicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)nicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N-methylnicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N-(3,3,3-trifluoropropyl)nicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1- (hydroxymethyl)cyclopropyl)amino)-N-methylnicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-N-ethyl-2-((1-hydroxy-2- methylpropan-2-yl)amino)nicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N-(2-hydroxyethyl)nicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N-(oxetan-3-yl)nicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxypropan-2-yl)amino)- N-methylnicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N-(1-hydroxypropan-2-yl)nicotinamide; N-cyclopropyl-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)nicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N-(tetrahydrofuran-3-yl)nicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N-(1-methylpyrrolidin-3-yl)nicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N-(1-methyl-5-oxopyrrolidin-3-yl)nicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N,N-dimethylnicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N-isopropylnicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N-((1-methylazetidin-3-yl)methyl)nicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N-(2-methoxycyclopropyl)nicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N-(1-methylazetidin-3-yl)nicotinamide; N-(1-cyanopropyl)-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)nicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N-(oxetan-3-ylmethyl)nicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N-(1-methoxy-2-methylpropan-2-yl)nicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N-(tetrahydro-2H-pyran-4-yl)nicotinamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(morpholine-4- carbonyl)pyridin-3-yl)-4-methylbenzamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N-(2-methylcyclopropyl)nicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-N-(1,1-difluoropropan-2-yl)-2-((1- hydroxy-2-methylpropan-2-yl)amino)nicotinamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(2- methylmorpholine-4-carbonyl)pyridin-3-yl)-4-methylbenzamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-N-ethyl-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-methylnicotinamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(4- methylpiperazine-1-carbonyl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(3-hydroxy-3- methylazetidine-1-carbonyl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(2-methylazetidine- 1-carbonyl)pyridin-3-yl)-4-methylbenzamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N-methyl-N-(oxetan-3-yl)nicotinamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(3- hydroxyazetidine-1-carbonyl)pyridin-3-yl)-4-methylbenzamide; N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(2-methylaziridine- 1-carbonyl)pyridin-3-yl)-4-methylbenzamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N-(2-methoxyethyl)-N-methylnicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N-(2-methoxyethyl)-N-methylnicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((2-hydroxyethyl)amino)-N- methylnicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N-(oxazol-2-ylmethyl)nicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1- (hydroxymethyl)cyclopentyl)amino)-N-methylnicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((3- (hydroxymethyl)tetrahydrofuran-3-yl)amino)-N-methylnicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxybutan-2-yl)amino)- N,N-dimethylnicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((3-(hydroxymethyl)oxetan-3- yl)amino)-N-methylnicotinamide; 5-(5-(cyclopropylcarbamoyl)-4-fluoro-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N,N-dimethylnicotinamide; (R)-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxypropan-2- yl)amino)-N,N-dimethylnicotinamide; (S)-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxypropan-2- yl)amino)-N,N-dimethylnicotinamide; 2-((1-hydroxy-2-methylpropan-2-yl)amino)-N-methyl-5-(2-methyl-5- (phenylcarbamoyl)phenyl)nicotinamide; 5-(5-((1H-pyrazol-3-yl)carbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N,N-dimethylnicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1- (hydroxymethyl)cyclobutyl)amino)-N-methylnicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N-(1-(oxazol-2-yl)ethyl)nicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1- (hydroxymethyl)cyclopropyl)amino)-N,N-dimethylnicotinamide; 2-((1-hydroxy-2-methylpropan-2-yl)amino)-N,N-dimethyl-5-(2-methyl-5-(thiazol-4- ylcarbamoyl)phenyl)nicotinamide; N-(2-aminoethyl)-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)nicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-N-(2-(dimethylamino)ethyl)-2-((1- hydroxy-2-methylpropan-2-yl)amino)nicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2-methylpropan-2- yl)amino)-N-(2-(methylamino)ethyl)nicotinamide; 2-((1-cyclopropyl-2-hydroxyethyl)amino)-5-(5-(cyclopropylcarbamoyl)-2- methylphenyl)-N,N-dimethylnicotinamide; 3-(5-acetamido-6-((1-hydroxy-2-methylpropan-2-yl)amino)pyridin-3-yl)-N- cyclopropyl-4-methylbenzamide; (S)-5-(5-(cyclopropylcarbamoyl)-4-fluoro-2-methylphenyl)-2-((1-hydroxypropan-2- yl)amino)-N,N-dimethylnicotinamide; (S)-2-((1-hydroxypropan-2-yl)amino)-N,N-dimethyl-5-(2-methyl-5-((1-methyl-1H- pyrazol-3-yl)carbamoyl)phenyl)nicotinamide; 5-(4-fluoro-2-methyl-5-((1-methyl-1H-pyrazol-3-yl)carbamoyl)phenyl)-2-((1- hydroxy-2-methylpropan-2-yl)amino)-N,N-dimethylnicotinamide; 5-(5-((1H-imidazol-4-yl)carbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N,N-dimethylnicotinamide; 5-(4-fluoro-2-methyl-5-((1-methyl-1H-pyrazol-3-yl)carbamoyl)phenyl)-2-((1- hydroxypropan-2-yl)amino)-N,N-dimethylnicotinamide; 5-(5-(cyclopropylcarbamoyl)-4-fluoro-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-methyl-N-(oxetan-3-yl)nicotinamide; 5-(5-(cyclopropylcarbamoyl)-4-fluoro-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-(2-methoxyethyl)-N-methylnicotinamide; 5-(5-(cyclopropylcarbamoyl)-4-fluoro-2-methylphenyl)-2-((2- hydroxyethyl)(methyl)amino)-N,N-dimethylnicotinamide; 5-(5-(cyclopropylcarbamoyl)-4-fluoro-2-methylphenyl)-2-((1- (hydroxymethyl)cyclopropyl)(methyl)amino)-N,N-dimethylnicotinamide; 5-(5-(cyclopropylcarbamoyl)-2-(fluoromethyl)phenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N,N-dimethylnicotinamide; 2-chloro-N-cyclopropyl-5-(6-((2-hydroxyethyl)amino)-5-(1-methyl-1H-pyrazol-4- yl)pyridin-3-yl)-4-methylbenzamide; and a pharmaceutically acceptable salt of any one of the aforementioned compounds. 32. A pharmaceutical composition comprising: a compound or pharmaceutically acceptable salt as defined in any one of claims 1 to 31; and a pharmaceutically acceptable excipient. 33. A compound or pharmaceutically acceptable salt as defined in any one of claims 1 to 31 for use as a medicament. 34. A compound or pharmaceutically acceptable salt as defined in any one of claims 1 to 31 for use in treating a disease, disorder or condition selected from Type I hypersensitivity reactions, autoimmune diseases, inflammatory disorders, cancer, and non-malignant proliferative disorders. 35. A compound or pharmaceutically acceptable salt as defined in any one of claims 1 to 31 for use in treating a disease, disorder or condition selected from allergic rhinitis, asthma, atopic dermatitis, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, lupus nephritis, psoriasis, immune thrombocytopenic purpura, inflammatory bowel disease, chronic obstructive pulmonary disease, Sjögren’s syndrome, ankylosing spondylitis, Behcet’s disease, graft versus host disease, pemphigus vulgaris, idiopathic plasmacytic lymphadenopathy, atherosclerosis, myocardial infarction, and thrombosis.

36. A method for inhibiting RIPK2 in a subject, the method comprising administering to the subject a compound or pharmaceutically acceptable salt as defined in any one of claims 1 to 31. 37. A method of treating a disease, disorder or condition in a subject, the method comprising administering to the subject a compound or pharmaceutically acceptable salt as defined in any one of claims 1 to 31, wherein the disease, disorder or condition is associated with RIPK2. 38. A method of treating a disease, disorder or condition in a subject, the method comprising administering to the subject a compound or pharmaceutically acceptable salt as defined in any one of claims 1 to 31, wherein the disease, disorder or condition is selected from Type I hypersensitivity reactions, autoimmune diseases, and inflammatory disorders, cancer, and non-malignant proliferative disorders. 39. A method of treating a disease, disorder or condition in a subject, the method comprising administering to the subject a compound or pharmaceutically acceptable salt as defined in any one of claims 1 to 31, wherein the disease, disorder or condition is selected from allergic rhinitis, asthma, atopic dermatitis, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, lupus nephritis, psoriasis, immune thrombocytopenic purpura, inflammatory bowel disease, chronic obstructive pulmonary disease, Sjögren’s syndrome, ankylosing spondylitis, Behcet’s disease, graft versus host disease, pemphigus vulgaris, idiopathic plasmacytic lymphadenopathy, atherosclerosis, myocardial infarction, and thrombosis. 40. A combination comprising a compound or pharmaceutically acceptable salt as defined in any one of claims 1 to 31, and at least one additional pharmacologically active agent.
Description:
3-(6-AMINOPYRIDIN-3-YL)BENZAMIDE DERIVATIVES AS RIPK2 INHIBITORS FIELD OF THE INVENTION [0001] This invention relates to 3-(6-aminopyridin-3-yl)benzamide derivatives which are selective inhibitors of receptor-interacting protein kinase 2 (RIPK2), to pharmaceutical compositions which contain them, and to their use to treat diseases, disorders, and conditions associated with RIPK2, including inflammatory bowel disease (IBD) and cancer. BACKGROUND OF THE INVENTION [0002] Receptor-interacting protein kinase 2 (RIPK2) is a serine/threonine protein kinase which mediates a pro-inflammatory signaling cascade involving nucleotide-binding oligomerization domain-containing protein 1 and 2 (NOD1 and NOD2). The cytosolic pattern recognition receptors (PPRs) NOD1 and NOD2 function in the innate immune system, detecting invasive bacteria via binding to diaminopimelic acid or muramyl dipeptide (MDP) residues present in bacterial peptidoglycan. Following activation, NOD1 and NOD2 associate with RIPK2, which subsequently undergoes autophosphorylation and polyubiquitination via interaction with XIAP and other E3 ligases. The RIPK2-ubiquitin complex activates TAK1 and IKK kinases, which promote upregulation of the mitogen-activated protein kinase and NF-κB signaling pathways. See, e.g., P. Canning, Q. Ruan, T. Schwerd, et al., “Inflammatory signaling by NOD-RIPK2 is inhibited by clinically relevant Type II Kinase Inhibitors,” Chemistry & Biology 22:1174-84 (2015) and M. Hrdinka, L. Schlicher, B. Dai, et al., “Small molecule inhibitors reveal an indispensable scaffolding role of RIPK2 in NOD2 signaling,” The EMBO Journal 37: e99372 (2018) and references cited therein. [0003] Dysregulation of the RIPK2-NOD signaling pathway has been implicated in several inflammatory and autoimmune diseases, including IBD. See R. Caruso, N. Warner, N. Inohara, and G. Nunez, “NOD1 and NOD2: signaling, host defense, and inflammatory disease,” Immunity 41: 898–908 (2014); L. Jostins, S. Ripke, R. Weersma, et al., “Hostmicrobe interactions have shaped the genetic architecture of inflammatory bowel disease,” Nature 491: 119–24 (2012); and D. Philpott, M. Sorbara, M. Robertson, et al., “NOD proteins: regulators of inflammation in health and disease,” Nat. Rev. Immunol.14: 9– 23 (2014). Genetic variants in NOD2 are known risk factors in Crohn’s disease. See J. Hugot, M. Chamaillard, H. Zouali, et al., “Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease,” Nature 411: 599–603 (2001) and Y. Ogura, D. Bonen, N. Inohara, et al., “A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease,” Nature 411: 603–06 (2001). Certain mutations in NOD2 reduce its binding to MDP and may promote excessive inflammatory signaling from other PPRs, including NOD1. See A. Couturier-Maillard, T. Secher, A. Rehman, et al., “NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer,” J. Clin. Invest.123: 700–11 (2013); N. Inohara, Y. Ogura, A. Fontalba, et al., “Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn’s disease,” J. Biol. Chem.278: 5509–12 (2003). Another mutation disrupts NOD2 inhibition, increasing RIPK2 activation. See M. Sorbara, L. Ellison, M. Ramjeet, et al., “The protein ATG16L1 suppresses inflammatory cytokines induced by the intracellular sensors Nod1 and Nod2 in an autophagy-independent manner,” Immunity 39: 858–73 (2013). Excessive RIPK2 activation has also been identified in pediatric patients with Crohn’s disease. See A. Negroni, L. Stronati, M. Pierdomenico, et al., “Activation of NOD2-mediated intestinal pathway in a pediatric population with Crohn’s disease,” Inflamm. Bowel Dis.15: 1145–54 (2009). [0004] In addition to Crohn’s disease, mutations in the RIPK2-NOD signaling pathways have been linked to other disorders, including Blau Syndrome and early-onset sarcoidosis, which are pediatric granulomatous diseases characterized by arthritis, dermatitis, uveitis and cranial neuropathies. Other mutations in the RIPK2-NOD signaling pathways have been linked to allergic airway inflammation, arthritis and multiple sclerosis. See, e.g., F. Caso F, Galozzi P, Costa L, et al., “Autoinflammatory granulomatous diseases: from Blau Syndrome and Early-Onset Sarcoidosis to NOD2-mediated disease and Crohn’s disease,” RMD Open 1: e000097 (2015); J. Jun, F. Cominelli, and D. Abbott, “RIP2 activity in inflammatory disease and implications for novel therapeutics.” J. Leukoc. Biol.94: 927–32 (2013); F. Goh, K. Cook, N. Upton, et al., “Receptor-interacting protein 2 gene silencing attenuates allergic airway inflammation,” J. Immunol.191: 2691–99 (2013); and P. Shaw, M. Barr, R. Lukens, et al., “Signaling via the RIP2 adaptor protein in central nervous system-infiltrating dendritic cells promotes inflammation and autoimmunity, Immunity 34: 75–84 (2011). [0005] RIPK2 is thought to play a role in cancer. A recent study demonstrated that RIPK2 is overexpressed in tissues of gastric cancer and may play a role in its tumorigenicity and proliferation. See Q. Yang, S. Tian, Z. Liu, et al., “Knockdown of RIPK2 Inhibits Proliferation and Migration, and Induces Apoptosis via the NF-κB Signaling Pathway in Gastric Cancer,” Frontiers in Genetics 12:84 (2021). Another study showed RIPK2 is overexpressed in colorectal cancer, and with Fusobacterium nucleatum, may be involved in the regulation of metastases in colorectal cancer. See Y. Chen, Y. Chen, J. Zhang, et al. “Fusobacterium nucleatum promotes metastasis in colorectal cancer by activating autophagy signaling via the upregulation of CARD3 expression,” Theranostics . 10:323-39 (2020).

RIPK2 has also been shown to influence the formation and progression of oral squamous cell cancer, inflammatory breast cancer and bladder cancer. See X. Wang,W. Jiang, N. Duan, et al. “NODI, RIP2 and Caspasel2 are potentially novel biomarkers for oral squamous cell carcinoma development and progression,” Int. J. Clin. Exp. Pathol. 7:1677-86 (2014); A. Zare, A. Petrova, M. Agoumi, et al., “RIPK2: new elements in modulating inflammatory breast cancer pathogenesis,” Cancers (Basel) 10:184 (2018); and H. Zhang and A. Chin, “Role of Rip2 in development of tumor-infiltrating MDSCs and bladder cancer metastasis,” PLOS ONE 9(4): e94793 (2014).

[0006] Inhibitors of RIPK2 are expected to be useful for treating cancer and inflammatory and autoimmune diseases, including IBD.

SUMMARY OF THE INVENTION

[0007] This invention provides 3-(6-aminopyridin-3-yl)benzamide derivatives and pharmaceutically acceptable salts thereof. This invention also provides pharmaceutical compositions that comprise the 3-(6-aminopyridin-3-yl)benzamide derivatives and provides for their use to treat diseases, disorders and conditions associated with RIPK2, including cancer and inflammatory and autoimmune diseases, including IBD and other gastrointestinal diseases, disorders and conditions.

[0008] One aspect of the invention provides compounds of Formula 1 : or a pharmaceutically acceptable salt thereof in which:

(a) L 1 is a bond or -C(O)-;

R 1 is selected from:

(i) halo and cyano; (ii) amino having first and second substituents, wherein the first substituent is selected from hydrogen and C 1-4 alkyl, and the second substituent is selected from hydrogen, C1-6 alkyl, C 3-8 cycloalkyl, C 2-8 heterocyclyl, C 2-8 heterocyclyl-C 1-3 alkyl, C 6-14 aryl, C 1-9 heteroaryl and C 1-9 heteroaryl-C 1-3 alkyl, wherein the second substituent on amino may be hydrogen only when L 1 is -C(O)-, and wherein C1-6 alkyl, C 3-8 cycloalkyl, C2-8 heterocyclyl and C 2-8 heterocyclyl-C 1-3 alkyl are each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, oxo, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl; C 6-14 aryl, C 1-9 heteroaryl and C 1-9 heteroaryl- C 1-3 alkyl are each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl, C 1-4 alkoxy, C3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl; and the C 1-4 alkyl, C 1-4 alkoxy and C3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; (iii) C1-6 alkyl and C1-6 alkoxy, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkoxy, C3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl, wherein the C 1-4 alkoxy and C3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy, and wherein R 1 is not C 1-6 alkoxy when L 1 is -C(O)-; (iv) C 3-8 cycloalkyl, C2-8 heterocyclyl and C2-8 heterocyclyl-C 1-3 alkyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, oxo, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl, wherein the C 1-4 alkyl, C 1-4 alkoxy and C 3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; and (v) C 6-14 aryl, C 1-9 heteroaryl and C 1-9 heteroaryl-C 1-3 alkyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl, wherein the C 1-4 alkyl, C 1-4 alkoxy and C 3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; R 2 is selected from hydrogen and C 1-4 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo and hydroxy; and R 3 is selected from: (i) C 1-6 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; and (ii) C 3-8 cycloalkyl, C 3-8 cycloalkyl-C 1-3 alkyl, and C2-8 heterocyclyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl and C 1-4 alkoxy, wherein the C 1-4 alkyl and C 1-4 alkoxy optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo and hydroxy; or R 2 and R 3 , together with the nitrogen atom to which they are both attached, form a C2-8 heterocyclyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl and C 1-4 alkoxy, wherein the C 1-4 alkyl and C 1-4 alkoxy optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo and hydroxy; or (b) L 1 is a bond; R 1 and R 2 together form a –(CH 2 )n-O-CH 2 CH 2 - bridge which spans the carbon and nitrogen atoms to which R 1 and R 2 are attached, wherein n is selected from 0 and 1, and wherein the (CH 2 )n end of the bridge is attached to the carbon atom to which R 1 is attached; and R 3 is C 1-6 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; X 5 is selected from N and C(R 5 ); R 4 , R 5 , R 6 and R 7 are each independently selected from hydrogen, halo and C 1-4 alkyl; R 8 is C1-4 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo; and R 9 is selected from C3-8 cycloalkyl, C2-8 heterocyclyl, C6-14 aryl and C1-9 heteroaryl, each substituted with from 0 to 3 optional substituents independently selected from C 1-4 alkyl; wherein each of the heterocyclyl and heteroaryl moieties independently has 1 to 4 ring members which are heteroatoms, each of the heteroatoms independently selected from N, O, and S, provided when R 2 and R 3 form a heterocyclyl moiety, at least one of the heteroatoms is N. [0009] Another aspect of the invention provides a compound which is selected from the group of compounds described in the examples and their pharmaceutically acceptable salts. [0010] A further aspect of the invention provides a pharmaceutical composition which includes a compound of Formula 1 or a pharmaceutically acceptable salt thereof, or any one of the compounds or pharmaceutically acceptable salts defined in the preceding paragraph; and a pharmaceutically acceptable excipient. [0011] An additional aspect of the invention provides a compound of Formula 1 or a pharmaceutically acceptable salt thereof, or any one of the compounds described in the examples or a pharmaceutically acceptable salt thereof, for use as a medicament. [0012] Another aspect of the invention provides a compound of Formula 1 or a pharmaceutically acceptable salt thereof, or any one of the compounds described in the examples or a pharmaceutically acceptable salt thereof, for use in treating a disease, disorder or condition associated with RIPK2. [0013] A further aspect of the invention provides a compound of Formula 1 or a pharmaceutically acceptable salt thereof, or any one of the compounds described in the examples or a pharmaceutically acceptable salt thereof, for use in treating a disease, disorder or condition selected from Type I hypersensitivity reactions, autoimmune diseases, inflammatory disorders, cancer, and non-malignant proliferative disorders. [0014] An additional aspect of the invention provides a compound of Formula 1 or a pharmaceutically acceptable salt thereof, or any one of the compounds described in the examples or a pharmaceutically acceptable salt thereof, for use in treating a disease, disorder or condition selected from allergic rhinitis, asthma, atopic dermatitis, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, lupus nephritis, psoriasis, immune thrombocytopenic purpura, inflammatory bowel disease, chronic obstructive pulmonary disease, Sjögren’s syndrome, ankylosing spondylitis, Behcet’s disease, graft versus host disease, pemphigus vulgaris, idiopathic plasmacytic lymphadenopathy, atherosclerosis, myocardial infarction, and thrombosis. [0015] Another aspect of the invention provides a compound of Formula 1 or a pharmaceutically acceptable salt thereof, or any one of the compounds described in the examples or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment of a disease, disorder or condition associated with RIPK2. [0016] A further aspect of the invention provides a method for inhibiting RIPK2 in a subject, the method comprising administering to the subject a compound of Formula 1 or a pharmaceutically acceptable salt thereof, or any one of the compounds described in the examples or a pharmaceutically acceptable salt thereof. [0017] An additional aspect of the invention provides a method for treating a disease, disorder or condition associated with RIPK2, the method comprising administering to the subject an effective amount of a compound of Formula 1 or a pharmaceutically acceptable salt thereof, or any one of the compounds described in the examples or a pharmaceutically acceptable salt thereof. [0018] Another aspect of the invention provides a method for treating a disease, disorder or condition in a subject, the method comprising administering to the subject an effective amount of a compound of Formula 1 or a pharmaceutically acceptable salt thereof, or any one of the compounds described in the examples or a pharmaceutically acceptable salt thereof, wherein the disease, disorder or condition is selected from Type I hypersensitivity reactions, autoimmune diseases, and inflammatory disorders, cancer, and non-malignant proliferative disorders [0019] A further aspect of the invention provides a method for treating a disease, disorder or condition in a subject, the method comprising administering to the subject an effective amount of a compound of Formula 1 or a pharmaceutically acceptable salt thereof, or any one of the compounds described in the examples or a pharmaceutically acceptable salt thereof, wherein the disease, disorder or condition is selected from allergic rhinitis, asthma, atopic dermatitis, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, lupus nephritis, psoriasis, immune thrombocytopenic purpura, inflammatory bowel disease, chronic obstructive pulmonary disease, Sjögren’s syndrome, ankylosing spondylitis, Behcet’s disease, graft versus host disease, pemphigus vulgaris, idiopathic plasmacytic lymphadenopathy, atherosclerosis, myocardial infarction, and thrombosis. [0020] An additional aspect of the invention provides a compound of Formula 1 or a pharmaceutically acceptable salt thereof, or any one of the compounds described in the examples or a pharmaceutically acceptable salt thereof; and at least one additional pharmacologically active agent. DETAILED DESCRIPTION OF THE INVENTION [0021] Unless otherwise indicated, this disclosure uses definitions provided below. [0022] “Substituted,” when used about a chemical substituent or moiety (e.g., a C 1-6 alkyl group), means that one or more hydrogen atoms of the substituent or moiety have been replaced with one or more non-hydrogen atoms or groups, provided valence requirements are met and a chemically stable compound results from the substitution. [0023] “About” or “approximately,” when used about a measurable numerical variable, refers to the indicated value of the variable and to all values of the variable that are within the experimental error of the indicated value or within ±10 percent of the indicated value, whichever is greater. [0024] “Alkyl” refers to straight chain and branched saturated hydrocarbon groups, generally having a specified number of carbon atoms (e.g., C 1-4 alkyl refers to an alkyl group having 1 to 4 (i.e., 1, 2, 3 or 4) carbon atoms, C 1-6 alkyl refers to an alkyl group having 1 to 6 carbon atoms, and so on). Examples of alkyl groups include methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, i-butyl, t-butyl, pent-1-yl, pent-2-yl, pent-3-yl, 3-methylbut-1-yl, 3- methylbut-2-yl, 2-methylbut-2-yl, 2,2,2-trimethyleth-1-yl, n-hexyl, and the like. [0025] “Alkanediyl” refers to divalent alkyl groups, where alkyl is defined above, and generally having a specified number of carbon atoms (e.g., C 1-4 alkanediyl refers to an alkanediyl group having 1 to 4 (i.e., 1, 2, 3 or 4) carbon atoms, C 1-6 alkanediyl refers to an alkanediyl group having 1 to 6 carbon atoms, and so on). Examples of alkanediyl groups include methylene, ethane-1,1-diyl, ethane-1,2-diyl, propane-1,3-diyl, propane-1,2-diyl, propane-1,1-diyl, propane-2,2-diyl, butane-1,4-diyl, butane-1,3-diyl, butane-1,2-diyl, butane- 1,1-diyl, isobutane-1,3-diyl, isobutane-1,1-diyl, isobutane-1,2-diyl, and the like. [0026] “Alkenyl” refers to straight chain and branched hydrocarbon groups having one or more carbon-carbon double bonds, and generally having a specified number of carbon atoms. Examples of alkenyl groups include ethenyl, 1-propen-1-yl, 1-propen-2-yl, 2-propen-1-yl, 1- buten-1-yl, 1-buten-2-yl, 3-buten-1-yl, 3-buten-2-yl, 2-buten-1-yl, 2-buten-2-yl, 2-methyl-1- propen-1-yl, 2-methyl-2-propen-1-yl, 1,3-butadien-1-yl, 1,3-butadien-2-yl, and the like. [0027] “Alkynyl” refers to straight chain or branched hydrocarbon groups having one or more triple carbon-carbon bonds, and generally having a specified number of carbon atoms. Examples of alkynyl groups include ethynyl, 1-propyn-1-yl, 2-propyn-1-yl, 1-butyn-1-yl, 3- butyn-1-yl, 3-butyn-2-yl, 2-butyn-1-yl, and the like. [0028] “Alkoxy” refers to straight chain and branched saturated hydrocarbon groups attached through an oxygen atom, generally having a specified number of carbon atoms (e.g., C 1-4 alkoxy refers to an alkoxy group having 1 to 4 (i.e., 1, 2, 3 or 4) carbon atoms, C 1-6 alkoxy refers to an alkoxy group having 1 to 6 carbon atoms, and so on). Examples of alkoxy groups include methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, i-butoxy, t-butoxy, pent-1-yloxy, pent-2-yloxy, pent-3-yloxy, 3-methylbut-1-yloxy, 3-methylbut-2- yloxy, 2-methylbut-2-yloxy, 2,2,2-trimethyleth-1-yloxy, n-hexoxy, and the like. [0029] “Halo,” “halogen” and “halogeno” may be used interchangeably and refer to fluoro, chloro, bromo, and iodo. [0030] “Haloalkyl,” “haloalkenyl,” and “haloalkynyl,” refer, respectively, to alkyl, alkenyl, and alkynyl groups substituted with one or more halogen atoms, where alkyl, alkenyl, and alkynyl are defined above, and generally having a specified number of carbon atoms. Examples of haloalkyl groups include fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 1-fluoroethyl, 1,1-difluoroethyl, 1- chloroethyl, 1,1-dichloroethyl, 1-fluoro-1-methylethyl, 1-chloro-1-methylethyl, and the like. [0031] “Cycloalkyl” refers to saturated monocyclic and bicyclic hydrocarbon groups, generally having a specified number of carbon atoms that comprise the ring or rings (e.g., C 3-8 cycloalkyl refers to a cycloalkyl group having 3 to 8 carbon atoms as ring members). Bicyclic hydrocarbon groups may include isolated rings (two rings sharing no carbon atoms), spiro rings (two rings sharing one carbon atom), fused rings (two rings sharing two carbon atoms and the bond between the two common carbon atoms), and bridged rings (two rings sharing two carbon atoms, but not a common bond). The cycloalkyl group may be attached through any ring atom unless such attachment would violate valence requirements, and where indicated, may optionally include one or more non-hydrogen substituents unless such substitution would violate valence requirements. [0032] Examples of monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like. Examples of fused bicyclic cycloalkyl groups include bicyclo[2.1.0]pentanyl (i.e., bicyclo[2.1.0]pentan-1-yl, bicyclo[2.1.0]pentan-2-yl, and bicyclo[2.1.0]pentan-5-yl), bicyclo[3.1.0]hexanyl, bicyclo[3.2.0]heptanyl, bicyclo[4.1.0]heptanyl, bicyclo[3.3.0]octanyl, bicyclo[4.2.0]octanyl, bicyclo[4.3.0]nonanyl, bicyclo[4.4.0]decanyl, and the like. Examples of bridged cycloalkyl groups include bicyclo[2.1.1]hexanyl, bicyclo[2.2.1]heptanyl, bicyclo[3.1.1]heptanyl, bicyclo[2.2.2]octanyl, bicyclo[3.2.1]octanyl, bicyclo[4.1.1]octanyl, bicyclo[3.3.1]nonanyl, bicyclo[4.2.1]nonanyl, bicyclo[3.3.2]decanyl, bicyclo[4.2.2]decanyl, bicyclo[4.3.1]decanyl, bicyclo[3.3.3]undecanyl, bicyclo[4.3.2]undecanyl, bicyclo[4.3.3]dodecanyl, and the like. Examples of spiro cycloalkyl groups include spiro[3.3]heptanyl, spiro[2.4]heptanyl, spiro[3.4]octanyl, spiro[2.5]octanyl, spiro[3.5]nonanyl, and the like. Examples of isolated bicyclic cycloalkyl groups include those derived from bi(cyclobutane), cyclobutanecyclopentane, bi(cyclopentane), cyclobutanecyclohexane, cyclopentanecyclohexane, bi(cyclohexane), etc. [0033] “Cycloalkanediyl” refers to divalent cycloalkyl groups, where cycloalkyl is defined above, and generally having a specified number of carbon atoms (e.g., C3-4 cycloalkanediyl refers to a cycloalkanediyl group having 3 to 4 (i.e., 3 or 4) carbon atoms, C 3-6 cycloalkanediyl refers to a cycloalkanediyl group having 3 to 6 carbon atoms, and so on). Examples of cycloalkanediyl groups include cyclopropan-1,1-diyl, cyclopropan-1,2-diyl, cyclobutan-1,1-diyl, cyclobutan-1,2-diyl, and the like. [0034] “Cycloalkylidene” refers to divalent monocyclic cycloalkyl groups, where cycloalkyl is defined above, which are attached through a single carbon atom of the group, and generally having a specified number of carbon atoms that comprise the ring (e.g., C 3-6 cycloalkylidene refers to a cycloalkylidene group having 3 to 6 carbon atoms as ring members). Examples include cyclopropylidene, cyclobutylidene, cyclopentylidene, and cyclohexylidene. [0035] “Cycloalkenyl” refers to partially unsaturated monocyclic and bicyclic hydrocarbon groups, generally having a specified number of carbon atoms that comprise the ring or rings. As with cycloalkyl groups, the bicyclic cycloalkenyl groups may include isolated, spiro, fused, or bridged rings. Similarly, the cycloalkenyl group may be attached through any ring atom, and where indicated, may optionally include one or more non-hydrogen substituents unless such attachment or substitution would violate valence requirements. Examples of cycloalkenyl groups include the partially unsaturated analogs of the cycloalkyl groups described above, such as cyclobutenyl (i.e., cyclobuten-1-yl and cyclobuten-3-yl), cyclopentenyl, cyclohexenyl, bicyclo[2.2.1]hept-2-enyl, and the like. [0036] “Aryl” refers to fully unsaturated monocyclic aromatic hydrocarbons and to polycyclic hydrocarbons having at least one aromatic ring, both monocyclic and polycyclic aryl groups generally having a specified number of carbon atoms that comprise their ring members (e.g., C 6-14 aryl refers to an aryl group having 6 to 14 carbon atoms as ring members). The group may be attached through any ring atom, and where indicated, may optionally include one or more non-hydrogen substituents unless such attachment or substitution would violate valence requirements. Examples of aryl groups include phenyl, biphenyl, cyclobutabenzenyl, indenyl, naphthalenyl, benzocycloheptanyl, biphenylenyl, fluorenyl, groups derived from cycloheptatriene cation, and the like. [0037] “Arylene” refers to divalent aryl groups, where aryl is defined above. Examples of arylene groups include phenylene (i.e., benzene-1,2-diyl). [0038] “Heterocycle” and “heterocyclyl” may be used interchangeably and refer to saturated or partially unsaturated monocyclic or bicyclic groups having ring atoms composed of carbon atoms and 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. Both the monocyclic and bicyclic groups generally have a specified number of carbon atoms in their ring or rings (e.g., C 2-8 heterocyclyl refers to a heterocyclyl group having 2 to 8 carbon atoms and 1 to 4 heteroatoms as ring members). As with bicyclic cycloalkyl groups, bicyclic heterocyclyl groups may include isolated rings, spiro rings, fused rings, and bridged rings in which at least one of the rings includes one or more heteroatoms. The heterocyclyl group may be attached through any ring atom, and where indicated, may optionally include one or more non-hydrogen substituents unless such attachment or substitution would violate valence requirements or result in a chemically unstable compound. Examples of heterocyclyl groups include oxiranyl, thiiranyl, aziridinyl (e.g., aziridin-1-yl and aziridin-2-yl), oxetanyl, thietanyl, azetidinyl, tetrahydrofuranyl, tetrahydrothienyl, pyrrolidinyl, tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, 1,4-dioxanyl, 1,4-oxathianyl, morpholinyl, 1,4-dithianyl, piperazinyl, 1,4-azathianyl, oxepanyl, thiepanyl, azepanyl, 1,4-dioxepanyl, 1,4-oxathiepanyl, 1,4-oxaazepanyl, 1,4-dithiepanyl, 1,4-thiazepanyl, 1,4-diazepanyl, 3,4-dihydro-2H-pyranyl, 3,6-dihydro-2H-pyranyl, 2H-pyranyl, 1,2-dihydropyridinyl, 1,2,3,4-tetrahydropyridinyl, 1,2,5,6-tetrahydropyridinyl, 1,6-dihydropyrimidinyl, 1,2,3,4-tetrahydropyrimidinyl, and 1,2- dihydropyrazolo[1,5-d][1,2,4]triazinyl. [0039] “Heterocycle-diyl” refers to heterocyclyl groups which are attached through two ring atoms of the group, where heterocyclyl is defined above. They generally have a specified number of carbon atoms in their ring or rings (e.g., C 2-8 heterocycle-diyl refers to a heterocycle-diyl group having 2 to 8 carbon atoms and 1 to 4 heteroatoms as ring members). Examples of heterocycle-diyl groups include the multivalent analogs of the heterocycle groups described above, such as morpholine-3,4-diyl, pyrrolidine-1,2-diyl, 1-pyrrolidinyl-2- ylidene, 1-pyridinyl-2-ylidene, 1-(4H)-pyrazolyl-5-ylidene, 1-(3H)-imidazolyl-2-ylidene, 3- oxazolyl-2-ylidene, 1-piperidinyl-2-ylidene, 1-piperazinyl-6-ylidene, and the like. [0040] “Heteroaromatic” and “heteroaryl” may be used interchangeably and refer to unsaturated monocyclic aromatic groups and to polycyclic groups having at least one aromatic ring, each of the groups having ring atoms composed of carbon atoms and 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. Both the monocyclic and polycyclic groups generally have a specified number of carbon atoms as ring members (e.g., C 1-9 heteroaryl refers to a heteroaryl group having 1 to 9 carbon atoms and 1 to 4 heteroatoms as ring members) and may include any bicyclic group in which any of the above- listed monocyclic heterocycles are fused to a benzene ring. The heteroaryl group may be attached through any ring atom (or ring atoms for fused rings), and where indicated, may optionally include one or more non-hydrogen substituents unless such attachment or substitution would violate valence requirements or result in a chemically unstable compound. Examples of heteroaryl groups include monocyclic groups such as pyrrolyl (e.g., pyrrol-1-yl, pyrrol-2-yl, and pyrrol-3-yl), furanyl, thienyl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, isothiazolyl, thiazolyl, 1,2,3-triazolyl, 1,3,4-triazolyl, 1-oxa-2,3-diazolyl, 1-oxa-2,4-diazolyl, 1-oxa-2,5-diazolyl, 1-oxa-3,4-diazolyl, 1-thia-2,3-diazolyl, 1-thia-2,4-diazolyl, 1-thia-2,5- diazolyl, 1-thia-3,4-diazolyl, tetrazolyl, pyridinyl, pyridazinyl, pyrimidinyl, and pyrazinyl. [0041] Examples of heteroaryl groups also include bicyclic groups such as benzofuranyl, isobenzofuranyl, benzothienyl, benzo[c]thienyl, 1H-indolyl, 3H-indolyl, isoindolyl, 1H- isoindolyl, indolinyl, isoindolinyl, benzimidazolyl, 1H-indazolyl, 2H-indazolyl, benzotriazolyl, 1H-pyrrolo[2,3-b]pyridinyl, 1H-pyrrolo[2,3-c]pyridinyl, 1H-pyrrolo[3,2- c]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl, 3H-imidazo[4,5-b]pyridinyl, 3H-imidazo[4,5- c]pyridinyl, 1H-pyrazolo[4,3-b]pyridinyl, 1H-pyrazolo[4,3-c]pyridinyl, 1H-pyrazolo[3,4- c]pyridinyl, 1H-pyrazolo[3,4-b]pyridinyl, 7H-purinyl, indolizinyl, imidazo[1,2-a]pyridinyl, imidazo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, pyrrolo[1,2-b]pyridazinyl, imidazo[1,2- c]pyrimidinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, 1,6-naphthyridinyl, 1,7-naphthyridinyl, 1,8-naphthyridinyl, 1,5-naphthyridinyl, 2,6- naphthyridinyl, 2,7-naphthyridinyl, pyrido[3,2-d]pyrimidinyl, pyrido[4,3-d]pyrimidinyl, pyrido[3,4-d]pyrimidinyl, pyrido[2,3-d]pyrimidinyl, pyrido[2,3-b]pyrazinyl, pyrido[3,4- b]pyrazinyl, pyrimido[5,4-d]pyrimidinyl, pyrazino[2,3-b]pyrazinyl, pyrimido[4,5- d]pyrimidinyl, 1,2,3,4-tetrahydropyrido[2,3-b]pyrazinyl, 2,3-dihydrobenzo[b][1,4]dioxinyl, 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl, 2,3-dihydro-1H-benzo[d]imidazolyl, benzo[d]thiazolyl, 2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl, [1,2,4]triazolo[1,5-a]pyridinyl, 2,3-dihydro-1H-imidazo[4,5-b]pyridinyl, tetrazolo[1,5-a]pyridinyl, 7H-pyrrolo[2,3- d]pyrimidinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyrimidinyl, 4,5-dihydro-1H- pyrazolo[3,4-d]pyrimidinyl, 2,3,6,7-tetrahydro-1H-purinyl, 5H-pyrrolo[2,3-b]pyrazinyl, imidazo[1,2-a]pyrazinyl, imidazo[1,2-b]pyridazinyl, and 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrazinyl. [0042] “Heteroarylene” refers to heteroaryl groups which are attached through two ring atoms of the group, where heteroaryl is defined above. They generally have a specified number of carbon atoms in their ring or rings (e.g., C3-5 heteroarylene refers to a heteroarylene group having 3 to 5 carbon atoms and 1 to 4 heteroatoms as ring members). Examples of heteroarylene groups include the multivalent analogs of the heteroaryl groups described above, such as pyridine-2,3-diyl, pyridine-3,4-diyl, pyrazole-4,5-diyl, pyrazole-3,4- diyl, and the like. [0043] “Oxo” refers to a double bonded oxygen (=O). [0044] “Leaving group” refers to any group that leaves a molecule during a fragmentation process, including substitution reactions, elimination reactions, and addition-elimination reactions. Leaving groups may be nucleofugal, in which the group leaves with a pair of electrons that formerly served as the bond between the leaving group and the molecule, or may be electrofugal, in which the group leaves without the pair of electrons. The ability of a nucleofugal leaving group to leave depends on its base strength, with the strongest bases being the poorest leaving groups. Common nucleofugal leaving groups include nitrogen (e.g., from diazonium salts); sulfonates, including alkylsulfonates (e.g., mesylate), fluoroalkylsulfonates (e.g., triflate, hexaflate, nonaflate, and tresylate), and arylsulfonates (e.g., tosylate, brosylate, closylate, and nosylate). Others include carbonates, halide ions, carboxylate anions, phenolate ions, and alkoxides. Some stronger bases, such as NH 2 - and OH- can be made better leaving groups by treatment with an acid. Common electrofugal leaving groups include the proton, CO 2 , and metals. [0045] “Opposite enantiomer” refers to a molecule that is a non-superimposable mirror image of a reference molecule, which may be obtained by inverting all the stereogenic centers of the reference molecule. For example, if the reference molecule has S absolute stereochemical configuration, then the opposite enantiomer has R absolute stereochemical configuration. Likewise, if the reference molecule has S,S absolute stereochemical configuration, then the opposite enantiomer has R,R stereochemical configuration, and so on. [0046] “Stereoisomer” and “stereoisomers” of a compound with given stereochemical configuration refer to the opposite enantiomer of the compound and to any diastereoisomers, including geometrical isomers (Z/E) of the compound. For example, if a compound has S,R,Z stereochemical configuration, its stereoisomers would include its opposite enantiomer having R,S,Z configuration, and its diastereomers having S,S,Z configuration, R,R,Z configuration, S,R,E configuration, R,S,E configuration, S,S,E configuration, and R,R,E configuration. If the stereochemical configuration of a compound is not specified, then “stereoisomer” refers to any one of the possible stereochemical configurations of the compound. [0047] “Substantially pure stereoisomer” and variants thereof refer to a sample containing a compound having a specific stereochemical configuration and which comprises at least about 95% of the sample. [0048] “Pure stereoisomer” and variants thereof refer to a sample containing a compound having a specific stereochemical configuration and which comprises at least about 99.5% of the sample. [0049] “Subject” refers to a mammal, including a human. [0050] “Pharmaceutically acceptable” substances refer to those substances which are suitable for administration to subjects. [0051] “Treating” refers to reversing, alleviating, inhibiting the progress of, or preventing a disease, disorder or condition to which such term applies, or to reversing, alleviating, inhibiting the progress of, or preventing one or more symptoms of such disease, disorder or condition. [0052] “Treatment” refers to the act of “treating,” as defined immediately above. [0053] “Drug,” “drug substance,” “active pharmaceutical ingredient,” and the like, refer to a compound (e.g., compounds of Formula 1, including subgeneric compounds and compounds specifically named in the specification) that may be used for treating a subject in need of treatment. [0054] “Effective amount” of a drug, “therapeutically effective amount” of a drug, and the like, refer to the quantity of the drug that may be used for treating a subject and may depend on the weight and age of the subject and the route of administration, among other things. [0055] “Excipient” refers to any diluent or vehicle for a drug. [0056] “Pharmaceutical composition” refers to the combination of one or more drug substances and one or more excipients. [0057] “Drug product,” “pharmaceutical dosage form,” “dosage form,” “final dosage form” and the like, refer to a pharmaceutical composition suitable for treating a subject in need of treatment and generally may be in the form of tablets, capsules, sachets containing powder or granules, liquid solutions or suspensions, patches, films, and the like. [0058] “Condition associated with RIPK2” and similar phrases relate to a disease, disorder or condition in a subject for which inhibition of RIPK2 may provide a therapeutic or prophylactic benefit. [0059] The following abbreviations may be used in the specification: Ac (acetyl); ACN (acetonitrile); AIBN (azo-bis-isobutyronitrile); API (active pharmaceutical ingredient); aq (aqueous); B2pin2 (4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) ); BDP (4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) ); BINAP (2,2′- bis(diphenylphosphino)-1,1′-binaphthyl); Boc (tert-butoxycarbonyl); Cbz (carbobenzyloxy); CDI (1,1'-carbonyldiimidazole); dba (dibenzylideneacetone); DAST (N,N-diethylaminosulfur trifluoride); DCC (1,3-dicyclohexylcarbodiimide); DCE (1,1-dichloroethane); DCM (dichloromethane); DHP (3,4-dihydropyran); DIAD (diisopropyl azodicarboxylate); DIPEA (N,N-diisopropylethylamine, Hünig’s Base); DMA (N,N-dimethylacetamide); DMAP (4- dimethylaminopyridine); DME (1,2-dimethoxyethane); DMF (N,N-dimethylformamide); DMSO (dimethylsulfoxide); dppf (1,1′-bis(diphenylphosphino)ferrocene); DTT (dithiothreitol); EC 50 (effective concentration at half maximal response); EDA (ethoxylated dodecyl alcohol, Brj®35); EDC (N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide); EDTA (ethylenediaminetetraacetic acid); ee (enantiomeric excess); eq (equivalents); Et (ethyl); Et 3 N (triethylamine); EtOAc (ethyl acetate); EtOH (ethanol); HATU (2-(3H-[1,2,3]triazolo[4,5- b]pyridin-3-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate(V)); HEPES (4-(2- hydroxyethyl)piperazine-1-ethanesulfonic acid); HOAc (acetic acid); HOBt (1H- benzo[d][1,2,3]triazol-1-ol); IC 50 (concentration at 50% inhibition); IPA (isopropanol); IPAc (isopropyl acetate); IPE (isopropylether); KOt-Bu (potassium tertiary butoxide); LDA (lithium diisopropylamide); LiHMDS (lithium bis(trimethylsilyl)amide); mCPBA (m- chloroperoxybenzoic acid); Me (methyl); MeOH (methanol); MTBE (methyl tert-butyl ether); mp (melting point); n-BuLi (n-butyl lithium); NaOt-Bu (sodium tertiary butoxide); NBS (N-bromosuccinimide); NCS (N-chlorosuccinimide); NIS (N-iodosuccinimide); NMM (N-methylmorpholine); NMP (N-methyl-pyrrolidone); OTf (triflate); PdCl 2 (dtbpf) (dichloro[1,1’-bis(di-tert-butylphosphino)ferrocene]pallad ium(II)); PE (petroleum ether); Ph (phenyl); PyCy 3 (tricyclohexylphosphine), pEC 50 (-log 10 (EC 50 ), where EC 50 is given in molar (M) units); pIC50 (-log10(IC50), where IC50 is given in molar (M) units); Pr (propyl); c-Pr (cyclopropyl), i-Pr (isopropyl); PTFE (polytetrafluoroethylene); p-toluenesulfonic acid (PTSA); Rac (racemic); RT (room temperature, approximately 20°C to 25°C); SEM (2- (trimethylsilyl)ethoxymethyl); SEM-Cl ((2-chloromethoxyethyl)trimethylsilane); SFC (supercritical fluid chromatography); T3P (2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide); TBAF (tetrabutylammonium fluoride); TBS (tert-butyldimethylsilyl); TBSCl (tert-butylchlorodimethylsilane); TCEP (tris(2-carboxyethyl)phosphine); TFA (trifluoroacetic acid); TFAA (2,2,2-trifluoroacetic anhydride); THF (tetrahydrofuran); TLC (thin layer chromatography); TMEDA (tetramethylethylenediamine); TMS (trimethylsilyl); and Tris buffer (2-amino-2-hydroxymethyl-propane-1,3-diol buffer). [0060] As described, below, this disclosure concerns compounds of Formula 1 and their pharmaceutically acceptable salts. This disclosure also concerns materials and methods for preparing compounds of Formula 1, pharmaceutical compositions which contain them, and the use of compounds of Formula 1 and their pharmaceutically acceptable salts (optionally in combination with other pharmacologically active agents) for treating diseases, disorders or conditions associated with RIPK2. [0061] The compounds of Formula 1 include those in which: (1) (a) L 1 is a bond or -C(O)-; R 1 is selected from: (i) halo and cyano; (ii) amino having first and second substituents, wherein the first substituent is selected from hydrogen and C 1-4 alkyl, and the second substituent is selected from hydrogen, C 1-6 alkyl, C3-8 cycloalkyl, C 2-8 heterocyclyl, C 2-8 heterocyclyl-C 1-3 alkyl, C 6-14 aryl, C 1-9 heteroaryl and C 1-9 heteroaryl- C 1-3 alkyl, wherein the second substituent on amino may be hydrogen only when L 1 is -C(O)-, and wherein C 1-6 alkyl, C 3-8 cycloalkyl, C 2-8 heterocyclyl and C 2-8 heterocyclyl-C 1-3 alkyl are each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, oxo, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl; C 6-14 aryl, C 1-9 heteroaryl and C 1-9 heteroaryl-C 1-3 alkyl are each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl; and the C 1-4 alkyl, C 1-4 alkoxy and C 3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; (iii) C 1-6 alkyl and C 1-6 alkoxy, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl, wherein the C 1-4 alkoxy and C 3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy, and wherein R 1 is not C 1-6 alkoxy when L 1 is -C(O)-; (iv) C 3-8 cycloalkyl, C 2-8 heterocyclyl and C 2-8 heterocyclyl-C 1-3 alkyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, oxo, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl, wherein the C 1-4 alkyl, C 1-4 alkoxy and C 3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; and (v) C 6-14 aryl, C 1-9 heteroaryl and C 1-9 heteroaryl- C 1-3 alkyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl, wherein the C 1-4 alkyl, C 1-4 alkoxy and C 3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; R 2 is selected from hydrogen and C 1-4 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo and hydroxy; and R 3 is selected from: (i) C 1-6 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; and (ii) C 3-8 cycloalkyl, C 3-8 cycloalkyl-C 1-3 alkyl, and C 2-8 heterocyclyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl and C 1-4 alkoxy, wherein the C 1-4 alkyl and C 1-4 alkoxy optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo and hydroxy; or R 2 and R 3 , together with the nitrogen atom to which they are both attached, form a C 2-8 heterocyclyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl and C 1-4 alkoxy, wherein the C 1-4 alkyl and C 1-4 alkoxy optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo and hydroxy; or (b) L 1 is a bond; R 1 and R 2 together form a –(CH2)n-O-CH2CH2- bridge which spans the carbon and nitrogen atoms to which R 1 and R 2 are attached, wherein n is selected from 0 and 1, and wherein the (CH 2 ) n end of the bridge is attached to the carbon atom to which R 1 is attached; and R 3 is C 1-6 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; X 5 is selected from N and C(R 5 ); R 4 , R 5 , R 6 and R 7 are each independently selected from hydrogen, halo and C 1-4 alkyl; R 8 is C 1-4 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo; and R 9 is selected from C3-8 cycloalkyl, C 2-8 heterocyclyl, C 6-14 aryl and C 1-9 heteroaryl, each substituted with from 0 to 3 optional substituents independently selected from C 1-4 alkyl; wherein each of the heterocyclyl and heteroaryl moieties independently has 1 to 4 ring members which are heteroatoms, each of the heteroatoms independently selected from N, O, and S, provided when R 2 and R 3 form a heterocyclyl moiety, at least one of the heteroatoms is N. [0062] In addition to embodiment (1) in the preceding paragraph, the compounds of Formula 1 include those in which: (2) L 1 is a bond or -C(O)-; R 1 is selected from: (i) halo and cyano; (ii) amino having first and second substituents, wherein the first substituent is selected from hydrogen and C 1-4 alkyl, and the second substituent is selected from hydrogen, C 1-6 alkyl, C 3-8 cycloalkyl, C 2-8 heterocyclyl, C 2-8 heterocyclyl-C 1-3 alkyl, C 6-14 aryl, C 1-9 heteroaryl and C 1-9 heteroaryl-C 1-3 alkyl, wherein the second substituent on amino may be hydrogen only when L 1 is -C(O)-, and wherein C 1-6 alkyl, C 3-8 cycloalkyl, C 2-8 heterocyclyl and C 2-8 heterocyclyl- C 1-3 alkyl are each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, oxo, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl; C 6-14 aryl, C 1-9 heteroaryl and C 1-9 heteroaryl-C 1-3 alkyl are each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl; and the C 1-4 alkyl, C 1-4 alkoxy and C 3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; (iii) C 1-6 alkyl and C 1-6 alkoxy, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl, wherein the C 1-4 alkoxy and C 3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy, and wherein R 1 is not C 1-6 alkoxy when L 1 is -C(O)-; (iv) C 3-8 cycloalkyl, C 2-8 heterocyclyl and C 2-8 heterocyclyl- C 1-3 alkyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, oxo, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl, wherein the C 1-4 alkyl, C 1-4 alkoxy and C 3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; and (v) C 6-14 aryl, C 1-9 heteroaryl and C 1-9 heteroaryl-C 1-3 alkyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl, wherein the C 1-4 alkyl, C 1-4 alkoxy and C 3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; R 2 is selected from hydrogen and C 1-4 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo and hydroxy; and R 3 is selected from: (i) C 1-6 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; and (ii) C3-8 cycloalkyl, C3-8 cycloalkyl-C 1-3 alkyl, and C 2-8 heterocyclyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl and C 1-4 alkoxy, wherein the C 1-4 alkyl and C 1-4 alkoxy optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo and hydroxy; or R 2 and R 3 , together with the nitrogen atom to which they are both attached, form a C 2-8 heterocyclyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl and C 1-4 alkoxy, wherein the C 1-4 alkyl and C 1-4 alkoxy optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo and hydroxy. [0063] In addition to embodiment (2) in the preceding paragraph, the compounds of Formula 1 include those in which R 1 is: (3) halo; or (4) cyano. [0064] In addition to embodiment (2) above, the compounds of Formula 1 include those in which R 1 is: (5) amino having first and second substituents, wherein the first substituent is selected from hydrogen and C 1-4 alkyl, and the second substituent is selected from hydrogen, C 1-6 alkyl, C 3-8 cycloalkyl, C 2-8 heterocyclyl, C 2-8 heterocyclyl-C 1-3 alkyl, C 6-14 aryl, C 1-9 heteroaryl and C 1-9 heteroaryl- C 1-3 alkyl, wherein the second substituent on amino may be hydrogen only when L 1 is -C(O)-, and wherein C 1-6 alkyl, C3-8 cycloalkyl, C 2-8 heterocyclyl and C 2-8 heterocyclyl-C 1-3 alkyl are each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, oxo, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl; C 6-14 aryl, C 1-9 heteroaryl and C 1-9 heteroaryl-C 1-3 alkyl are each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl; and the C 1-4 alkyl, C 1-4 alkoxy and C 3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; (6) amino having first and second substituents, wherein the first substituent is selected from hydrogen and methyl, and the second substituent is selected from hydrogen, C 1-4 alkyl, C 3-6 cycloalkyl, C 2-5 heterocyclyl, C 2-5 heterocyclyl-C 1-3 alkyl, phenyl, C 1-5 heteroaryl and C 1-5 heteroaryl- C 1-3 alkyl, wherein the second substituent on amino may be hydrogen only when L 1 is -C(O)-, and wherein C 1-4 alkyl, C 3-6 cycloalkyl, C 2-5 heterocyclyl and C 2-5 heterocyclyl-C 1-3 alkyl are each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, oxo, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl; phenyl, C 1-5 heteroaryl and C 1-5 heteroaryl-C 1-3 alkyl are each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl; and the C 1-4 alkyl, C 1-4 alkoxy and C 3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; (7) amino having first and second substituents, wherein the first substituent is selected from hydrogen and methyl, and the second substituent is selected from hydrogen, C 1-4 alkyl, C 3-6 cycloalkyl, C 2-5 heterocyclyl, C 2-5 heterocyclyl-C 1-3 alkyl, C 1-5 heteroaryl and C 1-5 heteroaryl-C 1-3 alkyl, wherein the second substituent on amino may be hydrogen only when L 1 is -C(O)-, and wherein C 1-4 alkyl, C 3-6 cycloalkyl, C 2-5 heterocyclyl and C 2-5 heterocyclyl-C 1-3 alkyl are each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, oxo, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl; C 1-5 heteroaryl and C 1-5 heteroaryl-C 1-3 alkyl are each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl; and the C 1-4 alkyl, C 1-4 alkoxy and C 3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; (8) amino having first and second substituents, wherein the first substituent is selected from hydrogen and methyl, and the second substituent is selected from C 1-4 alkyl, C 3-6 cycloalkyl, C 2-5 heterocyclyl, C 2-5 heterocyclyl- C 1-3 alkyl, C 1-5 heteroaryl and C 1-5 heteroaryl-C 1-3 alkyl, and wherein C 1-4 alkyl, C 3-6 cycloalkyl, C 2-5 heterocyclyl and C 2-5 heterocyclyl-C 1-3 alkyl are each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, oxo, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl; C 1-5 heteroaryl and C 1-5 heteroaryl-C 1-3 alkyl are each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl; and the C 1-4 alkyl, C 1-4 alkoxy and C 3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; or (9) amino having first and second substituents, wherein the first substituent is selected from hydrogen and methyl, and the second substituent is selected from C 1-4 alkyl, C 3-6 cycloalkyl, C 2-5 heterocyclyl, C 2-5 heterocyclyl- C 1-3 alkyl, C 1-5 heteroaryl and C 1-5 heteroaryl-C 1-3 alkyl, and wherein C 1-4 alkyl, C 3-6 cycloalkyl, C 2-5 heterocyclyl and C 2-5 heterocyclyl-C 1-3 alkyl are each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, oxo, cyano, C 1-4 alkyl, C 1-4 alkoxy, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl; C 1-5 heteroaryl and C 1-5 heteroaryl-C 1-3 alkyl are each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl, C 1-4 alkoxy, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl; and the C 1-4 alkyl, C 1-4 alkoxy and C 3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy. [0065] In addition to embodiments (5) to (9) in the preceding paragraph, the compounds of Formula 1 include those in which: (10) each of the heterocyclyl and heteroaryl moieties for R 1 independently has 1 to 2 ring members which are heteroatoms, each of the heteroatoms independently selected from N and O. [0066] In addition to embodiment (2) above, the compounds of Formula 1 include those in which R 1 is selected from: (11) C 1-6 alkyl and C 1-6 alkoxy, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl, wherein the C 1-4 alkoxy and C 3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy, and wherein R 1 is not C 1-6 alkoxy when L 1 is -C(O)-; (12) C 1-4 alkyl and C 1-4 alkoxy, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl, wherein the C 1-4 alkoxy and C 3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy, and wherein R 1 is not C 1-6 alkoxy when L 1 is -C(O)-; (13) C 1-4 alkyl and C 1-4 alkoxy, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, methoxy, cyclopropyl, and amino which is substituted with 0 to 2 optional substituents independently selected from methyl, wherein the methoxy and cyclopropyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and methoxy, and wherein R 1 is not C 1-6 alkoxy when L 1 is -C(O)-; or (14) C 1-4 alkyl and C 1-4 alkoxy, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, methoxy, cyclopropyl, and amino which is substituted with 0 to 2 optional substituents independently selected from methyl, and wherein R 1 is not C 1-6 alkoxy when L 1 is -C(O)-. [0067] In addition to embodiment (2) above, the compounds of Formula 1 include those in which R 1 is selected from: (15) C 3-8 cycloalkyl, C 2-8 heterocyclyl and C 2-8 heterocyclyl-C 1-3 alkyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, oxo, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl, wherein the C 1-4 alkyl, C 1-4 alkoxy and C 3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; (16) C 3-6 cycloalkyl, C 2-5 heterocyclyl and C 2-5 heterocyclyl-C 1-3 alkyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, oxo, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl, wherein the C 1-4 alkyl, C 1-4 alkoxy and C 3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; (17) C 3-6 cycloalkyl, C 2-5 heterocyclyl and C 2-5 heterocyclyl-C 1-3 alkyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, oxo, cyano, C 1-4 alkyl, C 1-4 alkoxy, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl, wherein the C 1-4 alkyl and C 1-4 alkoxy optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; (18) C 3-6 cycloalkyl, C 2-5 heterocyclyl and C 2-5 heterocyclyl-C 1-3 alkyl, each substituted with 0 to 3 optional substituents independently selected from hydroxy, oxo, C 1-4 alkyl, C 1-4 alkoxy, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl; or (19) C 3-6 cycloalkyl, C 2-5 heterocyclyl and C 2-5 heterocyclyl-C 1-3 alkyl, each substituted with 0 to 3 optional substituents independently selected from hydroxy, oxo, methyl, methoxy, and amino which is substituted with 0 to 2 optional substituents independently selected from methyl. [0068] In addition to embodiments (15) to (19) in the preceding paragraph, the compounds of Formula 1 include those in which: (20) each of the heterocyclyl moieties for R 1 independently has 1 to 2 ring members which are heteroatoms, each of the heteroatoms independently selected from N and O. [0069] In addition to embodiment (2) above, the compounds of Formula 1 include those in which R 1 is selected from: (21) C 6-14 aryl, C 1-9 heteroaryl and C 1-9 heteroaryl-C 1-3 alkyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl, wherein the C 1-4 alkyl, C 1-4 alkoxy and C 3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; (22) phenyl, C 1-5 heteroaryl and C 1-5 heteroaryl-C 1-3 alkyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, and amino which is substituted with 0 to 2 optional substituents independently selected from C 1-4 alkyl, wherein the C 1-4 alkyl, C 1-4 alkoxy and C 3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; (23) phenyl, C 1-5 heteroaryl and C 1-5 heteroaryl-C 1-3 alkyl, each substituted with 0 to 3 optional substituents independently selected from C 1-4 alkyl and C 3-6 cycloalkyl, wherein the C 1-4 alkyl and C 3-6 cycloalkyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; or (24) phenyl, C 1-5 heteroaryl and C 1-5 heteroaryl-C 1-3 alkyl, each substituted with 0 to 3 optional substituents independently selected from C 1-4 alkyl and cyclopropyl, wherein the C 1-4 alkyl and cyclopropyl optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo, hydroxy, and methoxy. [0070] In addition to embodiments (21) to (24) in the preceding paragraph, the compounds of Formula 1 include those in which: (25) each of the heteroaryl moieties for R 1 independently has 1 to 3 ring members which are heteroatoms, each of the heteroatoms independently selected from N, O and S. [0071] In addition to embodiments (2) to (25) in the preceding paragraphs, the compounds of Formula 1 include those in which R 2 is selected from: (26) hydrogen and C 1-4 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo and hydroxy; (27) hydrogen and C 1-3 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo and hydroxy; (28) hydrogen, methyl and ethyl, wherein the methyl and ethyl substituents are each substituted with 0 to 3 optional substituents independently selected from halo and hydroxy; (29) hydrogen, methyl and ethyl, wherein the methyl and ethyl substituents are substituted with hydroxy; or (30) hydrogen, methyl and ethyl. [0072] In addition to embodiments (2) to (30) in the preceding paragraphs, the compounds of Formula 1 include those in which R 3 is selected from: (31) (i) C 1-6 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; and (ii) C 3-8 cycloalkyl, C 3-8 cycloalkyl-C 1-3 alkyl, and C 2-8 heterocyclyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl and C 1-4 alkoxy, wherein the C 1-4 alkyl and C 1-4 alkoxy optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo and hydroxy; (32) (i) C 1-6 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; and (ii) C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-3 alkyl, and C 2-5 heterocyclyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl and C 1-4 alkoxy, wherein the C 1-4 alkyl and C 1-4 alkoxy optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo and hydroxy; (33) (i) C 1-6 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, and C 1-4 alkoxy; and (ii) C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-3 alkyl, and C 2-5 heterocyclyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, C 1-4 alkyl and C 1-4 alkoxy, wherein the C 1-4 alkyl and C 1-4 alkoxy optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo and hydroxy; or (34) (i) C 1-6 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, and methoxy; and (ii) C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-3 alkyl, and C 2-5 heterocyclyl, each substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, methyl and methoxy, wherein the methyl and methoxy optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo and hydroxy. [0073] In addition to embodiments (31) to (34) in the preceding paragraph, the compounds of Formula 1 include those in which: (35) each of the heterocyclyl moieties for R 3 independently has 1 to 2 ring members which are heteroatoms, each of the heteroatoms independently selected from N and O; or (36) each of the heterocyclyl moieties for R 3 independently has 1 to 2 ring members which are heteroatoms, each of the heteroatoms being O. [0074] In addition to embodiments (2) to (25) above, the compounds of Formula 1 include those in which R 2 and R 3 , together with the nitrogen atom to which they are both attached, form a: (37) C 2-8 heterocyclyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl and C 1-4 alkoxy, wherein the C 1-4 alkyl and C 1-4 alkoxy optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo and hydroxy; (38) C 2-5 heterocyclyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano, C 1-4 alkyl and C 1-4 alkoxy, wherein the C 1-4 alkyl and C 1-4 alkoxy optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo and hydroxy; (39) C 2-5 heterocyclyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, C 1-3 alkyl and C 1-3 alkoxy, wherein the C 1-3 alkyl and C 1-3 alkoxy optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo and hydroxy; or (40) C 2-5 heterocyclyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, methyl and methoxy, wherein the methyl and methoxy optional substituents are each independently substituted with 0 to 3 substituents independently selected from halo and hydroxy. [0075] In addition to embodiments (37) to (40) in the preceding paragraph, the compounds of Formula 1 include those in which: (41) each of the heterocyclyl moieties formed from R 2 and R 3 has 1 to 2 ring members, each of the heteroatoms independently selected from N and O, provided at least one of the heteroatoms is N. [0076] In addition to embodiments (1) to (41) in the preceding paragraphs, the compounds of Formula 1 include those in which L 1 is: (42) a bond; or (43) -C(O)-. [0077] In addition to embodiment (1) above, the compounds of Formula 1 include those in which: (44) L 1 is a bond; R 1 and R 2 together form a –(CH 2 ) n -O-CH 2 CH 2 - bridge which spans the carbon and nitrogen atoms to which R 1 and R 2 are attached, wherein n is selected from 0 and 1, and wherein the (CH 2 ) n -end of the bridge is attached to the carbon atom to which R 1 is attached; and R 3 is C 1-6 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy. [0078] In addition to embodiment (44) in the preceding paragraph, the compounds of Formula 1 include those in which R 3 is: (45) C 1-3 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, cyano and C 1-4 alkoxy; (46) C 1-3 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, and C 1-3 alkoxy; or (47) C 1-3 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo, hydroxy, and methoxy. [0079] In addition to embodiments (44) to (47) in the preceding paragraphs, the compounds of Formula 1 include those in which: (48) n is 1; or (49) n is 0. [0080] In addition to embodiments (1) to (49) in the preceding paragraphs, the compounds of Formula 1 include those in which: (50) X 5 is C(R 5 ); or (51) X 5 is N. [0081] In addition to embodiments (1) to (50) in the preceding paragraphs, the compounds of Formula 1 include those in which R 5 is selected from: (52) hydrogen and halo; or (53) hydrogen. [0082] In addition to embodiments (1) to (53) in the preceding paragraphs, the compounds of Formula 1 include those in which R 4 and R 7 are each independently selected from: (54) hydrogen and halo; or (55) hydrogen. [0083] In addition to embodiments (1) to (55) in the preceding paragraphs, the compounds of Formula 1 include those in which R 6 is selected from: (56) hydrogen and halo. [0084] In addition to embodiments (1) to (56) in the preceding paragraphs, the compounds of Formula 1 include those in which R 8 is: (57) C 1-3 alkyl which is substituted with 0 to 3 optional substituents independently selected from halo; (58) methyl which is substituted with 0 to 3 optional substituents independently selected from halo; or (59) methyl. [0085] In addition to embodiments (1) to (59) in the preceding paragraphs, the compounds of Formula 1 include those in which R 9 is selected from: (60) C 3-6 cycloalkyl, C 2-5 heterocyclyl, phenyl and C 1-5 heteroaryl, each substituted with from 0 to 3 optional substituents independently selected from C 1-4 alkyl; or (61) C 3-6 cycloalkyl, phenyl and C 1-5 heteroaryl, each substituted with from 0 to 3 optional substituents independently selected from C 1-4 alkyl; or (62) cyclopropyl, phenyl and C 1-5 heteroaryl, each substituted with from 0 to 3 optional substituents selected from methyl. [0086] In addition to embodiments (60) to (62) in the preceding paragraphs, the compounds of Formula 1 include those in which: (63) each of the heterocyclyl and heteroaryl moieties for R 9 independently has 1 to 2 ring members which are heteroatoms, each of the heteroatoms independently selected from N, O and S. [0087] Compounds of Formula 1 include embodiments (1) to (63) described in the preceding paragraphs and all compounds specifically named in the examples, and may exist as salts, complexes, solvates, hydrates, and liquid crystals. Likewise, compounds of Formula 1 that are salts may exist as complexes, solvates, hydrates, and liquid crystals. [0088] Compounds of Formula 1 may form pharmaceutically acceptable complexes, salts, solvates and hydrates. These salts include acid addition salts (including di-acids) and base salts. Pharmaceutically acceptable acid addition salts include salts derived from inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, hydrofluoric acid, and phosphorous acids, as well nontoxic salts derived from 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. Such salts include acetate, adipate, aspartate, benzoate, besylate, bicarbonate, carbonate, bisulfate, sulfate, borate, camsylate, citrate, cyclamate, edisylate, esylate, formate, fumarate, gluceptate, gluconate, glucuronate, hexafluorophosphate, hibenzate, hydrochloride/chloride, hydrobromide/bromide, hydroiodide/iodide, isethionate, lactate, malate, maleate, malonate, mesylate, methylsulfate, naphthylate, 2-napsylate, nicotinate, nitrate, orotate, oxalate, palmitate, pamoate, phosphate, hydrogen phosphate, dihydrogen phosphate, pyroglutamate, saccharate, stearate, succinate, tannate, tartrate, tosylate, trifluoroacetate and xinofoate salts. [0089] Pharmaceutically acceptable base salts include salts derived from bases, including metal cations, such as an alkali or alkaline earth metal cation, as well as amines. Examples of suitable metal cations include sodium, potassium, magnesium, calcium, zinc, and aluminum. Examples of suitable amines include arginine, N,N′-dibenzylethylenediamine, chloroprocaine, choline, diethylamine, diethanolamine, dicyclohexylamine, ethylenediamine, glycine, lysine, N-methylglucamine, olamine, 2-amino-2-hydroxymethyl-propane-1,3-diol, and procaine. For a discussion of useful acid addition and base salts, see S. M. Berge et al., J. Pharm. Sci. (1977) 66:1-19; see also Stahl and Wermuth, Handbook of Pharmaceutical Salts: Properties, Selection, and Use (2002). [0090] Pharmaceutically acceptable salts may be prepared using various methods. For example, a compound of Formula 1 may be reacted with an appropriate acid or base to give the desired salt. Alternatively, a precursor of the compound of Formula 1 may be reacted with an acid or base to remove an acid- or base-labile protecting group or to open a lactone or lactam group of the precursor. Additionally, a salt of the compound of Formula 1 may be converted to another salt (or free form) through treatment with an appropriate acid or base or through contact with an ion exchange resin. Following reaction, the salt may be isolated by filtration if it precipitates from solution, or by evaporation to recover the salt. The degree of ionization of the salt may vary from completely ionized to almost non-ionized. [0091] Compounds of Formula 1 may exist in a continuum of solid states ranging from fully amorphous to fully crystalline. The term “amorphous” refers to a state in which the material lacks long range order at the molecular level and, depending upon temperature, may exhibit the physical properties of a solid or a liquid. Typically, such materials do not give distinctive X-ray diffraction patterns and, while exhibiting the properties of a solid, are more formally described as a liquid. Upon heating, a change from solid to liquid properties occurs which is characterized by a change of state, typically second order (“glass transition”). The term “crystalline” refers to a solid phase in which the material has a regular ordered internal structure at the molecular level and gives a distinctive X-ray diffraction pattern with defined peaks. Such materials when heated sufficiently will also exhibit the properties of a liquid, but the change from solid to liquid is characterized by a phase change, typically first order (“melting point”). [0092] Compounds of Formula 1 may also exist in unsolvated and solvated forms. The term “solvate” describes a molecular complex comprising the compound and one or more pharmaceutically acceptable solvent molecules (e.g., ethanol). The term “hydrate” is a solvate in which the solvent is water. Pharmaceutically acceptable solvates include those in which the solvent may be isotopically substituted (e.g., D2O, acetone-d6, DMSO-d6). [0093] A currently accepted classification system for solvates and hydrates of organic compounds is one that distinguishes between isolated site, channel, and metal-ion coordinated solvates and hydrates. See, e.g., K. R. Morris (H. G. Brittain ed.) Polymorphism in Pharmaceutical Solids (1995). Isolated site solvates and hydrates are ones in which the solvent (e.g., water) molecules are isolated from direct contact with each other by intervening molecules of the organic compound. In channel solvates, the solvent molecules lie in lattice channels where they are next to other solvent molecules. In metal-ion coordinated solvates, the solvent molecules are bonded to the metal ion. [0094] When the solvent or water is tightly bound, the complex will have a well-defined stoichiometry independent of humidity. When, however, the solvent or water is weakly bound, as in channel solvates and in hygroscopic compounds, the water or solvent content will depend on humidity and drying conditions. In such cases, non-stoichiometry will typically be observed. [0095] Compounds of Formula 1 may also exist as multi-component complexes (other than salts and solvates) in which the compound (drug) and at least one other component are present in stoichiometric or non-stoichiometric amounts. Complexes of this type include clathrates (drug-host inclusion complexes) and co-crystals. The latter are typically defined as crystalline complexes of neutral molecular constituents which are bound together through non-covalent interactions but could also be a complex of a neutral molecule with a salt. Co- crystals may be prepared by melt crystallization, by recrystallization from solvents, or by physically grinding the components together. See, e.g., O. Almarsson and M. J. Zaworotko, Chem. Commun. (2004) 17:1889-1896. For a general review of multi-component complexes, see J. K. Haleblian, J. Pharm. Sci. (1975) 64(8):1269-88. [0096] When subjected to suitable conditions, compounds of Formula 1 may exist in a mesomorphic state (mesophase or liquid crystal). The mesomorphic state lies between the true crystalline state and the true liquid state (either melt or solution). Mesomorphism arising as the result of a change in temperature is described as “thermotropic” and mesomorphism resulting from the addition of a second component, such as water or another solvent, is described as “lyotropic.” Compounds that have the potential to form lyotropic mesophases are described as “amphiphilic” and include molecules which possess a polar ionic moiety (e.g., -COOˉNa + , -COOˉK + , -SO3ˉNa + ) or polar non-ionic moiety (such as -NˉN + (CH3)3). See, e.g., N. H. Hartshorne and A. Stuart, Crystals and the Polarizing Microscope (4th ed, 1970). [0097] Each compound of Formula 1 may exist as polymorphs, stereoisomers, tautomers, or some combination thereof, may be isotopically-labeled, may result from the administration of a prodrug, or form a metabolite following administration. [0098] “Prodrugs” refer to compounds having little or no pharmacological activity that can, when metabolized in vivo, undergo conversion to compounds having desired pharmacological activity. Prodrugs may be prepared by replacing appropriate functionalities present in pharmacologically active compounds with “pro-moieties” as described, for example, in H. Bundgaar, Design of Prodrugs (1985). Examples of prodrugs include ester, ether or amide derivatives of compounds of Formula 1 having carboxylic acid, hydroxy, or amino functional groups, respectively. For further discussions of prodrugs, see e.g., T. Higuchi and V. Stella “Pro-drugs as Novel Delivery Systems,” ACS Symposium Series 14 (1975) and E. B. Roche ed., Bioreversible Carriers in Drug Design (1987). [0099] “Metabolites” refer to compounds formed in vivo upon administration of pharmacologically active compounds. Examples include hydroxymethyl, hydroxy, secondary amino, primary amino, phenol, and carboxylic acid derivatives of compounds of Formula 1 having methyl, alkoxy, tertiary amino, secondary amino, phenyl, and amide groups, respectively. [0100] Compounds of Formula 1 may exist as stereoisomers that result from the presence of one or more stereogenic centers, one or more double bonds, or both. The stereoisomers may be pure, substantially pure, or mixtures. Such stereoisomers may also result from acid addition or base salts in which the counter-ion is optically active, for example, when the counter-ion is D-lactate or L-lysine. [0101] Compounds of Formula 1 may exist as tautomers, which are isomers resulting from tautomerization. Tautomeric isomerism includes, for example, imine-enamine, keto-enol, oxime-nitroso, and amide-imidic acid tautomerism. [0102] Compounds of Formula 1 may exhibit more than one type of isomerism. [0103] Geometrical (cis/trans) isomers may be separated by conventional techniques such as chromatography and fractional crystallization. [0104] Conventional techniques for preparing or isolating a compound having a specific stereochemical configuration include chiral synthesis from a suitable optically pure precursor or resolution of the racemate (or the racemate of a salt or derivative) using, for example, chiral high-pressure liquid chromatography (HPLC). Alternatively, the racemate (or a racemic precursor) may be reacted with a suitable optically active compound, for example, an alcohol, or, in the case where the compound of Formula 1 contains an acidic or basic moiety, an acid or base such as tartaric acid or 1-phenylethylamine. The resulting diastereomeric mixture may be separated by chromatography, fractional crystallization, etc., and the appropriate diastereoisomer converted to the compound having the requisite stereochemical configuration. For a further discussion of techniques for separating stereoisomers, see E. L. Eliel and S. H. Wilen, Stereochemistry of Organic Compounds (1994). [0105] Compounds of Formula 1 may possess isotopic variations, in which at least one atom is replaced by an atom having the same atomic number, but an atomic mass different from the atomic mass usually found in nature. Isotopes suitable for inclusion in compounds of Formula 1 include, for example, isotopes of hydrogen, such as 2 H and 3 H; isotopes of carbon, such as 11 C, 13 C and 14 C; isotopes of nitrogen, such as 13 N and 15 N; isotopes of oxygen, such as 15 O, 17 O and 18 O; isotopes of sulfur, such as 35 S; isotopes of fluorine, such as 18 F; isotopes of chlorine, such as 36 Cl, and isotopes of iodine, such as 123 I and 125 I. Use of isotopic variations (e.g., deuterium, 2 H) may afford certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements. Additionally, certain isotopic variations of the disclosed compounds may incorporate a radioactive isotope (e.g., tritium, 3 H, or 14 C), which may be useful in drug and/or substrate tissue distribution studies. Substitution with positron emitting isotopes, such as 11 C, 18 F, 15 O and 13 N, may be useful in Positron Emission Topography (PET) studies for examining substrate receptor occupancy. Isotopically-labeled compounds may be prepared by processes analogous to those described elsewhere in the disclosure using an appropriate isotopically-labeled reagent in place of a non-labeled reagent. [0106] Isotopically-labeled compounds may be prepared by processes analogous to those described elsewhere in the disclosure using an appropriate isotopically-labeled reagent in place of a non-labeled reagent. Thus, for example, the compounds of Formula 1 include those in which one or more R 1 and R 3 may include a substituent having one or more hydrogen atoms that are deuterium. Unless otherwise stated, when a substituent is designated specifically as “D” or “deuterium,” it is understood to have deuterium at an abundance that is at least 3000 times greater than the natural abundance of deuterium, which is 0.015% (i.e., at least 45% incorporation of deuterium). [0107] The compounds of Formula 1 may be prepared using the techniques described below. Some of the schemes and examples may omit details of common reactions, including oxidations, reductions, and so on, separation techniques (extraction, evaporation, precipitation, chromatography, filtration, trituration, crystallization, and the like), and analytical procedures, which are known to persons of ordinary skill in the art of organic chemistry. The details of such reactions and techniques can be found in several treatises, including Richard Larock, Comprehensive Organic Transformations (1999), and the multi- volume series edited by Michael B. Smith and others, Compendium of Organic Synthetic Methods (1974 et seq.). Starting materials and reagents may be obtained from commercial sources or may be prepared using literature methods. Some of the reaction schemes may omit minor products resulting from chemical transformations (e.g., an alcohol from the hydrolysis of an ester, CO 2 from the decarboxylation of a di-acid, etc.). In addition, in some instances, reaction intermediates may be used in subsequent steps without isolation or purification (i.e., in situ). [0108] In some of the reaction schemes and examples below, certain compounds can be prepared using protecting groups, which prevent undesirable chemical reaction at otherwise reactive sites. Protecting groups may also be used to enhance solubility or otherwise modify physical properties of a compound. For a discussion of protecting group strategies, a description of materials and methods for installing and removing protecting groups, and a compilation of useful protecting groups for common functional groups, including amines, carboxylic acids, alcohols, ketones, aldehydes, and so on, see T. W. Greene and P. G. Wuts, Protecting Groups in Organic Chemistry (1999) and P. Kocienski, Protective Groups (2000). [0109] Generally, the chemical transformations described throughout the specification may be carried out using substantially stoichiometric amounts of reactants, though certain reactions may benefit from using an excess of one or more of the reactants. Additionally, many of the reactions disclosed throughout the specification may be carried out at about room temperature (RT) and ambient pressure, but depending on reaction kinetics, yields, and so on, some reactions may be run at elevated pressures or employ higher temperatures (e.g., reflux conditions) or lower temperatures (e.g., -78°C to 0°C). Any reference in the disclosure and claims to a stoichiometric range, a temperature range, a pH range, etc., whether expressly using the word “range,” also includes the indicated endpoints. [0110] Many of the chemical transformations may also employ one or more compatible solvents, which may influence the reaction rate and yield. Depending on the nature of the reactants, the one or more solvents may be polar protic solvents (including water), polar aprotic solvents, non-polar solvents, or some combination. Representative solvents include saturated aliphatic hydrocarbons (e.g., n-pentane, n-hexane, n-heptane, n-octane, cyclohexane, methylcyclohexane); aromatic hydrocarbons (e.g., benzene, toluene, xylenes); halogenated hydrocarbons (e.g., methylene chloride, chloroform, carbon tetrachloride); aliphatic alcohols (e.g., methanol, ethanol, propan-1-ol, propan-2-ol, butan-1-ol, 2-methyl- propan-1-ol, butan-2-ol, 2-methyl-propan-2-ol, pentan-1-ol, 3-methyl-butan-1-ol, hexan-1-ol, 2-methoxy-ethanol, 2-ethoxy-ethanol, 2-butoxy-ethanol, 2-(2-methoxy-ethoxy)-ethanol, 2-(2- ethoxy-ethoxy)-ethanol, 2-(2-butoxy-ethoxy)-ethanol); ethers (e.g., diethyl ether, di-isopropyl ether, dibutyl ether, 1,2-dimethoxy-ethane, 1,2-diethoxy-ethane, 1-methoxy-2-(2-methoxy- ethoxy)-ethane, 1-ethoxy-2-(2-ethoxy-ethoxy)-ethane, tetrahydrofuran, 1,4-dioxane); ketones (e.g., acetone, methyl ethyl ketone); esters (methyl acetate, ethyl acetate); nitrogen-containing solvents (e.g., formamide, N,N-dimethylformamide, acetonitrile, N-methyl-pyrrolidone, pyridine, quinoline, nitrobenzene); sulfur-containing solvents (e.g., carbon disulfide, dimethyl sulfoxide, tetrahydro-thiophene-1,1,-dioxide); and phosphorus-containing solvents (e.g., hexamethylphosphoric triamide). [0111] In the schemes, below, substituent identifiers (L 1 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , X 5 ) are as defined above for Formula 1. As mentioned earlier, however, some of the starting materials and intermediates may include protecting groups, which are removed prior to the final product. In such cases, the substituent identifier refers to moieties defined in Formula 1 and to those moieties with appropriate protecting groups (unless explicitly shown). For example, a starting material or intermediate in the schemes may include R 1 substituent having a potentially reactive hydroxy group. In such cases, R 1 would include the moiety with or without, say, a TBS or Ac group attached to the oxygen atom. [0112] Schemes A and B show general methods for preparing compounds of Formula 1. As indicated in Scheme A, a heteroaromatic halide (A-1 in which, e.g., X is Cl, Br or I) is reacted with an aromatic boronic acid or ester (A-2 in which, e.g., each R 10 is H or C 1-4 alkyl) in the presence of a palladium catalyst (e.g., XPhos Pd G3, Pd(dppf)Cl2, PdCl2(dtbpf), etc.), a base (e.g., K 2 CO 3 , Na 2 CO 3 , KF, etc.) and one or more polar solvents (e.g., dioxane, DMF, water, etc.). The palladium catalyzed cross-coupling reaction is carried out at elevated temperature (e.g., 80-130°C) and gives the compound of Formula 1 directly or indirectly, e.g., after removal of protecting groups, further elaboration of functional groups, etc.

[0113] Alternatively, as shown in Scheme B, a heteroaromatic boronic acid or ester (B-1) is reacted with an aromatic halide (B-2), in the presence of a palladium catalyst, base and solvent as noted above for Scheme A. Like Scheme A, the cross-coupling reaction in Scheme B gives the compound of Formula 1 directly or indirectly. [0114] Scheme C shows a general method for preparing heteroaromatic halide (C-1) and heteroaromatic boronic acid or ester (C-2) which correspond, respectively, to compounds (A- 1) and (B-1) when L 1 is a bond and R 1 = NHR 1N . In accordance with the method, nitro- substituted starting material (C-3) is reacted with an amine (C-4) in the presence of a base (e.g., DIPEA) and solvent (e.g., ACN, DMSO, etc.) at elevated temperature (e.g., 80°C) to give a nitro-substituted heteroaromatic amine (C-5). The amine (C-5) is subsequently reduced (via e.g., catalytic hydrogenation, treatment with iron metal and NH 4 Cl in EtOH and water, etc.) to provide a heteroaromatic diamine (C-6). The diamine (C-6) is treated with base (e.g., NaH, K 2 CO 3 , etc.) in solvent (e.g., DMF, ACN, etc.) and then reacted with an alkyl halide (C-7, R 1N is optionally substituted alkyl, X is Br, I, etc.) at elevated temperature (80-130°C) to give the heteroaromatic halide (C-1). If desired, the halide (C-1) may be reacted with diboronic acid or ester (C-8) in the presence of a palladium catalyst (e.g., Pd(dppf)Cl2, Pd(dppf)Cl 2 .CH 2 Cl 2 , etc.), base (KOAc, potassium phenoxide, etc.) and solvent (e.g., dioxane) at elevated temperature (e.g., 80-100°C) to provide the heteroaromatic boronic acid or ester (C-2). [0115] Scheme D shows a general method for preparing heteroaromatic halide (D-1) and heteroaromatic boronic acid or ester (D-2) which correspond, respectively, to compounds (A- 1) and (B-1) when L 1 is a bond and R 1 = NHC(O)R 1C . In accordance with the method, diamine (C-6) is reacted with an acid chloride (D-3) in the presence of a non-nucleophilic base (e.g., DIPEA) and a polar solvent (THF) with cooling (e.g., 0-15°C) to obtain the heteroaromatic halide (D-1). If desired, the halide (D-1) may be reacted with diboronic acid or ester (C-8) in the presence of a palladium catalyst (e.g., Pd(dppf)Cl2, Pd(dppf)Cl2.CH2Cl2, etc.), base (e.g., KOAc, potassium phenoxide, etc.) and solvent (e.g., dioxane) at elevated temperature (e.g., 80-100°C) to provide the heteroaromatic boronic acid or ester (D-2). O 3 Scheme D [0116] Scheme E shows a general method for preparing heteroaromatic halide (E-1) and boronic acid or ester (E-2) which correspond, respectively, to compounds (A-1) and (B-1) when L 1 is a bond. In accordance with the method, a 3-bromo-5-chloro-2-fluoropyridine derivative or analog (E-3) is reacted with an amine (C-4) in the presence of a base (e.g., DIPEA) and solvent (e.g., ACN, DMSO, etc.) at elevated temperature (e.g., 80°C) to give a heteroaromatic amine (E-4). The amine (E-4) is subsequently reacted with a diboronic acid or ester (E-5) in the presence of a palladium catalyst (e.g., Pd(dppf)Cl 2 , Pd(dppf)Cl 2 .CH 2 Cl 2 , etc.), base (e.g., KOAc, potassium phenoxide, etc.) and solvent (e.g., dioxane) at elevated temperature (e.g., 80-100°C) to provide the heteroaromatic halide (E-1). Alternatively, the amine (E-4) is reacted with an organostannane (E-6, R 12 is, e.g., butyl) in the presence of a palladium catalyst (e.g., Pd(PPh3)4) and nonpolar solvent (e.g., toluene) at elevated temperature (e.g., 100°C) to give the heteroaromatic halide (E-1). If desired, the halide (E-1) may be reacted with diboronic acid or ester (C-8) under Suzuki coupling conditions to give the heteroaromatic boronic acid or ester (E-2). nt 2 [0117] Scheme F shows a general method for preparing aromatic boronic acid or ester (A- 2) or halide (B-2). In accordance with the method, a carboxylic acid (F-1) is treated with thionyl chloride in a solvent (e.g., DMF) at elevated temperature (e.g., 60-80°C). The resulting acid chloride (F-2) is reacted with an R 9 -substituted amine (F-3) in a solvent (e.g., DCM) with cooling (0-15°C) to give the aromatic halide (B-2). Alternatively, the carboxylic acid (F-1) may be reacted with the amine (F-3) using an amide coupling agent (e.g., HATU, DCC, EDC hydrochloride, T3P or 2-chloro-1-methylpyridin-1-ium iodide) in the presence of a non-nucleophilic base (e.g., Et 3 N, DIPEA) and one or more compatible polar solvents (e.g. DCM, DMA, DMF, THF). The amide coupling may be carried out at temperatures which range from room temperature to about 80°C. HOBt may be used to facilitate the reaction. If desired, the halide (B-2) may be reacted with diboronic acid or ester (C-8) in the presence of a palladium catalyst (e.g., Pd(dppf)Cl 2 , Pd(dppf)Cl 2 .CH 2 Cl 2 , etc.), base (e.g., KOAc, potassium phenoxide, etc.) and solvent (e.g., dioxane) at elevated temperature (e.g., 80- 100°C) to provide the heteroaromatic boronic acid or ester (A-2).

[0118] Scheme G shows a general method for preparing heteroaromatic halide (G-1) and boronic acid or ester (G-2) which correspond, respectively, to compounds (A-1) and (B-1) when L 1 is a -C(O)- and R 1 = NHR 1N . In accordance with the method, a nitrile (G-3) is reacted with an amine (C-4) in the presence of a base (e.g., DIPEA) and solvent (e.g., ACN, DMSO, etc.) at elevated temperature (e.g., 80°C) to give a heteroaromatic amine (G-4). The amine (G-4) is subsequently treated with aqueous NaOH under reflux conditions, which following acid work-up, gives a carboxylic acid (G-5). The carboxylic acid (G-5) is reacted with an amine (G-6) using an amide coupling agent (e.g., HATU, DCC, EDC hydrochloride, T3P or 2-chloro-1-methylpyridin-1-ium iodide) in the presence of a non-nucleophilic base (e.g., Et3N, DIPEA) and one or more compatible polar solvents (e.g. DCM, DMA, DMF, THF). The amide coupling may be carried out at temperatures which range from room temperature to about 80°C. HOBt may be used to facilitate the reaction. If desired, the halide (G-1) may be reacted with diboronic acid or ester (C-8) in the presence of a palladium catalyst (e.g., Pd(dppf)Cl2, Pd(dppf)Cl2.CH2Cl2, etc.), base (e.g., KOAc, potassium phenoxide, etc.) and solvent (e.g., dioxane) at elevated temperature (e.g., 80-100°C) to provide the heteroaromatic boronic acid or ester (G-2).

Scheme G

[0119] The methods depicted in the schemes may be varied as desired. For example, protecting groups may be added or removed, and intermediates or products may be further elaborated via, for example, alkylation, acylation, halogenation, hydrolysis, oxidation, reduction, amidation, sulfonation, alkynation, transition metal catalyzed cross-coupling reactions, and the like to give the desired final product. Furthermore, any intermediate or final product which comprises mixture of stereoisomers may be optionally purified by chiral column chromatography (e.g., supercritical fluid chromatography) or by derivatization with optically-pure reagents as described above to give a desired stereoisomer.

[0120] Compounds of Formula 1, which include compounds named above, and their pharmaceutically acceptable complexes, salts, solvates and hydrates, should be assessed for their biopharmaceutical properties, such as solubility and solution stability across pH, permeability, and the like, to select an appropriate dosage form and route of administration. Compounds that are intended for pharmaceutical use may be administered as crystalline or amorphous products, and may be obtained, for example, as solid plugs, powders, or films by methods such as precipitation, crystallization, freeze drying, spray drying, evaporative drying, microwave drying, or radio frequency drying.

[0121] Compounds of Formula 1 may be administered alone or in combination with one another or with one or more pharmacologically active compounds which are different than the compounds of Formula 1. Generally, one or more of these compounds are administered as a pharmaceutical composition (a formulation) in association with one or more pharmaceutically acceptable excipients. The choice of excipients depends on the mode of administration, the effect of the excipient on solubility and stability, and the nature of the dosage form, among other things. Useful pharmaceutical compositions and methods for their preparation may be found, for example, in A. R. Gennaro (ed.), Remington: The Science and Practice of Pharmacy (20th ed., 2000). [0122] Compounds of Formula 1 may be administered orally. Oral administration may involve swallowing in which case the compound enters the bloodstream via the gastrointestinal tract. Alternatively, or additionally, oral administration may involve mucosal administration (e.g., buccal, sublingual, supralingual administration) such that the compound enters the bloodstream through the oral mucosa. [0123] Formulations suitable for oral administration include solid, semi-solid and liquid systems such as tablets; soft or hard capsules containing multi- or nano-particulates, liquids, or powders; lozenges which may be liquid-filled; chews; gels; fast dispersing dosage forms; films; ovules; sprays; and buccal or mucoadhesive patches. Liquid formulations include suspensions, solutions, syrups and elixirs. Such formulations may be employed as fillers in soft or hard capsules (made, e.g., from gelatin or hydroxypropylmethylcellulose) and typically comprise a carrier (e.g., water, ethanol, polyethylene glycol, propylene glycol, methylcellulose, or a suitable oil) and one or more emulsifying agents, suspending agents or both. Liquid formulations may also be prepared by the reconstitution of a solid (e.g., from a sachet). [0124] Compounds of Formula 1 may also be used in fast-dissolving, fast-disintegrating dosage forms such as those described in Liang and Chen, Expert Opinion in Therapeutic Patents (2001) 11(6):981-986. [0125] For tablet dosage forms, depending on dose, the active pharmaceutical ingredient (API) may comprise from about 1 wt% to about 80 wt% of the dosage form or more typically from about 5 wt% to about 60 wt% of the dosage form. In addition to the API, tablets may include one or more disintegrants, binders, diluents, surfactants, glidants, lubricants, anti- oxidants, colorants, flavoring agents, preservatives, and taste-masking agents. Examples of disintegrants include sodium starch glycolate, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, croscarmellose sodium, crospovidone, polyvinylpyrrolidone, methyl cellulose, microcrystalline cellulose, C 1-6 alkyl-substituted hydroxypropylcellulose, starch, pregelatinized starch, and sodium alginate. Generally, the disintegrant will comprise from about 1 wt% to about 25 wt% or from about 5 wt% to about 20 wt% of the dosage form. [0126] Binders are generally used to impart cohesive qualities to a tablet formulation. Suitable binders include microcrystalline cellulose, gelatin, sugars, polyethylene glycol, natural and synthetic gums, polyvinylpyrrolidone, pregelatinized starch, hydroxypropylcellulose and hydroxypropylmethylcellulose. Tablets may also contain diluents, such as lactose (monohydrate, spray-dried monohydrate, anhydrous), mannitol, xylitol, dextrose, sucrose, sorbitol, microcrystalline cellulose, starch and dibasic calcium phosphate dihydrate. [0127] Tablets may also include surface active agents, such as sodium lauryl sulfate and polysorbate 80, and glidants such as silicon dioxide and talc. When present, surface active agents may comprise from about 0.2 wt% to about 5 wt% of the tablet, and glidants may comprise from about 0.2 wt% to about 1 wt% of the tablet. [0128] Tablets may also contain lubricants such as magnesium stearate, calcium stearate, zinc stearate, sodium stearyl fumarate, and mixtures of magnesium stearate with sodium lauryl sulfate. Lubricants may comprise from about 0.25 wt% to about 10 wt% or from about 0.5 wt% to about 3 wt% of the tablet. [0129] Tablet blends may be compressed directly or by roller compaction to form tablets. Tablet blends or portions of blends may alternatively be wet-, dry-, or melt-granulated, melt congealed, or extruded before tableting. If desired, prior to blending one or more of the components may be sized by screening or milling or both. The final dosage form may comprise one or more layers and may be coated, uncoated, or encapsulated. Exemplary tablets may contain up to about 80 wt% of API, from about 10 wt% to about 90 wt% of binder, from about 0 wt% to about 85 wt% of diluent, from about 2 wt% to about 10 wt% of disintegrant, and from about 0.25 wt% to about 10 wt% of lubricant. For a discussion of blending, granulation, milling, screening, tableting, coating, as well as a description of alternative techniques for preparing drug products, see A. R. Gennaro (ed.), Remington: The Science and Practice of Pharmacy (20th ed., 2000); H. A. Lieberman et al. (ed.), Pharmaceutical Dosage Forms: Tablets, Vol.1-3 (2d ed., 1990); and D. K. Parikh & C. K. Parikh, Handbook of Pharmaceutical Granulation Technology, Vol.81 (1997). [0130] Consumable oral films for human or veterinary use are pliable water-soluble or water-swellable thin film dosage forms which may be rapidly dissolving or mucoadhesive. In addition to the API, a typical film includes one or more film-forming polymers, binders, solvents, humectants, plasticizers, stabilizers or emulsifiers, viscosity-modifying agents, and solvents. Other film ingredients may include anti-oxidants, colorants, flavorants and flavor enhancers, preservatives, salivary stimulating agents, cooling agents, co-solvents (including oils), emollients, bulking agents, anti-foaming agents, surfactants, and taste-masking agents. Some components of the formulation may perform more than one function. [0131] In addition to dosing requirements, the amount of API in the film may depend on its solubility. If water soluble, the API would typically comprise from about 1 wt% to about 80 wt% of the non-solvent components (solutes) in the film or from about 20 wt% to about 50 wt% of the solutes in the film. A less soluble API may comprise a greater proportion of the composition, typically up to about 88 wt% of the non-solvent components in the film. [0132] The film-forming polymer may be selected from natural polysaccharides, proteins, or synthetic hydrocolloids and typically comprises from about 0.01 wt% to about 99 wt% or from about 30 wt% to about 80 wt% of the film. [0133] Film dosage forms are typically prepared by evaporative drying of thin aqueous films coated onto a peelable backing support or paper, which may be carried out in a drying oven or tunnel (e.g., in a combined coating-drying apparatus), in lyophilization equipment, or in a vacuum oven. [0134] Useful solid formulations for oral administration may include immediate release formulations and modified release formulations. Modified release formulations include delayed-, sustained-, pulsed-, controlled-, targeted-, and programmed-release. For a general description of suitable modified release formulations, see US Patent No.6,106,864. For details of other useful release technologies, such as high energy dispersions and osmotic and coated particles, see Verma et al, Pharmaceutical Technology On-line (2001) 25(2):1-14. [0135] Compounds of Formula 1 may also be administered directly into the blood stream, muscle, or an internal organ of the subject. Suitable techniques for parenteral administration include intravenous, intraarterial, intraperitoneal, intrathecal, intraventricular, intraurethral, intrasternal, intracranial, intramuscular, intrasynovial, and subcutaneous administration. Suitable devices for parenteral administration include needle injectors, including microneedle injectors, needle-free injectors, and infusion devices. [0136] Parenteral formulations are typically aqueous solutions which may contain excipients such as salts, carbohydrates and buffering agents (e.g., pH of from about 3 to about 9). For some applications, however, compounds of Formula 1 may be more suitably formulated as a sterile non-aqueous solution or as a dried form to be used in conjunction with a suitable vehicle such as sterile, pyrogen-free water. The preparation of parenteral formulations under sterile conditions (e.g., by lyophilization) may be readily accomplished using standard pharmaceutical techniques. [0137] The solubility of compounds which are used in the preparation of parenteral solutions may be increased through appropriate formulation techniques, such as the incorporation of solubility-enhancing agents. Formulations for parenteral administration may be formulated to be immediate or modified release. Modified release formulations include delayed, sustained, pulsed, controlled, targeted, and programmed release. Thus, compounds of Formula 1 may be formulated as a suspension, a solid, a semi-solid, or a thixotropic liquid for administration as an implanted depot providing modified release of the active compound. Examples of such formulations include drug-coated stents and semi-solids and suspensions comprising drug-loaded poly(DL-lactic-coglycolic)acid (PGLA) microspheres. [0138] Compounds of Formula 1 may also be administered topically, intradermally, or transdermally to the skin or mucosa. Typical formulations for this purpose include gels, hydrogels, lotions, solutions, creams, ointments, dusting powders, dressings, foams, films, skin patches, wafers, implants, sponges, fibers, bandages and microemulsions. Liposomes may also be used. Typical carriers may include alcohol, water, mineral oil, liquid petrolatum, white petrolatum, glycerin, polyethylene glycol and propylene glycol. Topical formulations may also include penetration enhancers. See, e.g., Finnin and Morgan, J. Pharm. Sci. 88(10):955-958 (1999). [0139] Other means of topical administration include delivery by electroporation, iontophoresis, phonophoresis, sonophoresis and microneedle or needle-free (e.g. Powderject™ and Bioject™) injection. Formulations for topical administration may be formulated to be immediate or modified release as described above. [0140] Compounds of Formula 1 may also be administered intranasally or by inhalation, typically in the form of a dry powder, an aerosol spray, or nasal drops. An inhaler may be used to administer the dry powder, which comprises the API alone, a powder blend of the API and a diluent, such as lactose, or a mixed component particle that includes the API and a phospholipid, such as phosphatidylcholine. For intranasal use, the powder may include a bioadhesive agent, e.g., chitosan or cyclodextrin. A pressurized container, pump, sprayer, atomizer, or nebulizer, may be used to generate the aerosol spray from a solution or suspension comprising the API, one or more agents for dispersing, solubilizing, or extending the release of the API (e.g., EtOH with or without water), one or more solvents (e.g., 1,1,1,2- tetrafluoroethane or 1,1,1,2,3,3,3-heptafluoropropane) which serve as a propellant, and an optional surfactant, such as sorbitan trioleate, oleic acid, or an oligolactic acid. An atomizer using electrohydrodynamics may be used to produce a fine mist. [0141] Prior to use in a dry powder or suspension formulation, the drug product is usually comminuted to a particle size suitable for delivery by inhalation (typically 90% of the particles, based on volume, having a largest dimension less than 5 microns). This may be achieved by any appropriate size reduction method, such as spiral jet milling, fluid bed jet milling, supercritical fluid processing, high pressure homogenization, or spray drying. [0142] Capsules, blisters and cartridges (made, for example, from gelatin or hydroxypropylmethyl cellulose) for use in an inhaler or insufflator may be formulated to contain a powder mixture of the active compound, a suitable powder base such as lactose or starch, and a performance modifier such as L-leucine, mannitol, or magnesium stearate. The lactose may be anhydrous or monohydrated. Other suitable excipients include dextran, glucose, maltose, sorbitol, xylitol, fructose, sucrose, and trehalose. [0143] A suitable solution formulation for use in an atomizer using electrohydrodynamics to produce a fine mist may contain from about 1 μg to about 20 mg of the API per actuation and the actuation volume may vary from about 1 μL to about 100 μL. A typical formulation may comprise one or more compounds of Formula 1, propylene glycol, sterile water, EtOH, and NaCl. Alternative solvents, which may be used instead of propylene glycol, include glycerol and polyethylene glycol. [0144] Formulations for inhaled administration, intranasal administration, or both, may be formulated to be immediate or modified release using, for example, PGLA. Suitable flavors, such as menthol and levomenthol, or sweeteners, such as saccharin or sodium saccharin, may be added to formulations intended for inhaled/intranasal administration. [0145] In the case of dry powder inhalers and aerosols, the dosage unit is determined by means of a valve that delivers a metered amount. Units are typically arranged to administer a metered dose or “puff” containing from about 10 μg to about 1000 μg of the API. The overall daily dose will typically range from about 100 μg to about 10 mg which may be administered in a single dose or, more usually, as divided doses throughout the day. [0146] The active compounds may be administered rectally or vaginally, e.g., in the form of a suppository, pessary, or enema. Cocoa butter is a traditional suppository base, but various alternatives may be used as appropriate. Formulations for rectal or vaginal administration may be formulated to be immediate or modified release as described above. [0147] Compounds of Formula 1 may also be administered directly to the eye or ear, typically in the form of drops of a micronized suspension or solution in isotonic, pH-adjusted, sterile saline. Other formulations suitable for ocular and aural administration include ointments, gels, biodegradable implants (e.g. absorbable gel sponges, collagen), non- biodegradable implants (e.g. silicone), wafers, lenses, and particulate or vesicular systems, such as niosomes or liposomes. The formulation may include one or more polymers and a preservative, such as benzalkonium chloride. Typical polymers include crossed-linked polyacrylic acid, polyvinylalcohol, hyaluronic acid, cellulosic polymers (e.g., hydroxypropylmethylcellulose, hydroxyethylcellulose, methyl cellulose), and heteropolysaccharide polymers (e.g., gelan gum). Such formulations may also be delivered by iontophoresis. Formulations for ocular or aural administration may be formulated to be immediate or modified release as described above. [0148] To improve their solubility, dissolution rate, taste-masking, bioavailability, or stability, compounds of Formula 1 may be combined with soluble macromolecular entities, including cyclodextrin and its derivatives and polyethylene glycol-containing polymers. For example, API-cyclodextrin complexes are generally useful for most dosage forms and routes of administration. Both inclusion and non-inclusion complexes may be used. As an alternative to direct complexation with the API, the cyclodextrin may be used as an auxiliary additive, i.e. as a carrier, diluent, or solubilizer. Alpha-, beta- and gamma-cyclodextrins are commonly used for these purposes. See, e.g., WO 91/11172, WO 94/02518, and WO 98/55148. [0149] As noted above, one or more compounds of Formula 1, including compounds specifically named above, and their pharmaceutically active complexes, salts, solvates and hydrates, may be combined with each other or with one or more other active pharmaceutically active compounds to treat various diseases, conditions and disorders. In such cases, the active compounds may be combined in a single dosage form as described above or may be provided in the form of a kit which is suitable for coadministration of the compositions. The kit comprises (1) two or more different pharmaceutical compositions, at least one of which contains a compound of Formula 1; and (2) a device for separately retaining the two pharmaceutical compositions, such as a divided bottle or a divided foil packet. An example of such a kit is the familiar blister pack used for the packaging of tablets or capsules. The kit is suitable for administering different types of dosage forms (e.g., oral and parenteral) or for administering different pharmaceutical compositions at separate dosing intervals, or for titrating the different pharmaceutical compositions against one another. To assist with patient compliance, the kit typically comprises directions for administration and may be provided with a memory aid. [0150] For administration to human patients, the total daily dose of the claimed and disclosed compounds is typically in the range of about 0.1 mg to about 3000 mg depending on the route of administration. For example, oral administration may require a total daily dose of from about 1 mg to about 3000 mg, while an intravenous dose may only require a total daily dose of from about 0.1 mg to about 300 mg. The total daily dose may be administered in single or divided doses and, at the physician’s discretion, may fall outside of the typical ranges given above. Although these dosages are based on an average human subject having a mass of about 60 kg to about 70 kg, the physician will be able to determine the appropriate dose for a patient (e.g., an infant) whose mass falls outside of this weight range. [0151] As noted above, the compounds of Formula 1 may be used to treat diseases, disorders or conditions for which inhibition of RIPK2 is indicated. Such diseases, disorders or conditions generally relate to any unhealthy or abnormal state in a subject for which the inhibition of RIPK2 provides a therapeutic benefit. More particularly, such diseases, disorders or conditions may involve the immune system and inflammation, including Type I hypersensitivity (allergic) reactions (allergic rhinitis, allergic asthma, and atopic dermatitis); autoimmune diseases (rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, psoriasis, lupus nephritis, immune thrombocytopenic purpura, Sjögren’s syndrome, ankylosing spondylitis, and Behcet’s disease); inflammatory bowel disease; inflammation of the lung (chronic obstructive pulmonary disease), atherosclerosis, thrombosis, and myocardial infarction. The compounds of Formula 1 may also be used to treat diseases, disorders or conditions related to abnormal cell growth, including hematological malignancies, such as acute myeloid leukemia, B-cell chronic lymphocytic leukemia, B-cell lymphoma (e.g., mantle cell lymphoma), T-cell lymphoma (e.g., peripheral T-cell lymphoma), and multiple myeloma, as well as epithelial cancers (i.e., carcinomas), such as lung cancer (small cell lung cancer and non-small cell lung cancer), pancreatic cancer, colorectal cancer, gastric cancer and bladder cancer. [0152] In addition to the hematological malignancies and epithelial cancers noted above, the compounds of Formula 1 may also be used to treat other types of cancer, including leukemia (chronic myelogenous leukemia and chronic lymphocytic leukemia); breast cancer, genitourinary cancer, skin cancer, bone cancer, prostate cancer, and liver cancer; brain cancer; cancer of the larynx, gall bladder, rectum, parathyroid, thyroid, adrenal, neural tissue, bladder, head, neck, mouth, stomach, bronchi, and kidneys; basal cell carcinoma, squamous cell carcinoma, metastatic skin carcinoma, osteosarcoma, Ewing’s sarcoma, veticulum cell sarcoma, and Kaposi’s sarcoma; myeloma, giant cell tumor, islet cell tumor, acute and chronic lymphocytic and granulocytic tumors, hairy-cell tumor, adenoma, medullary carcinoma, pheochromocytoma, mucosal neuromas, intestinal ganglioneuromas, hyperplastic corneal nerve tumor, marfanoid habitus tumor, Wilms’ tumor, seminoma, ovarian tumor, leiomyomater tumor, cervical dysplasia, neuroblastoma, retinoblastoma, myelodysplastic syndrome, rhabdomyosarcoma, astrocytoma, non-Hodgkin’s lymphoma, malignant hypercalcemia, polycythermia vera, adenocarcinoma, glioblastoma multiforma, glioma, lymphomas, and malignant melanomas, among others. [0153] In addition to cancer, the compounds of Formula 1 may also be used to treat other diseases, disorders or conditions related to abnormal cell growth, including non-malignant proliferative diseases such as benign prostatic hypertrophy, restinosis, hyperplasia, synovial proliferation disorder, idiopathic plasmacytic lymphadenopathy, retinopathy or other neovascular disorders of the eye, among others. [0154] The compounds of Formula 1 may also be used to treat autoimmune diseases, disorders or conditions in addition to those listed above. Such diseases, disorders or conditions include Crohn’s disease, dermatomyositis, diabetes mellitus type 1, Goodpasture’s syndrome, Graves’ disease, Guillain-Barré syndrome, Hashimoto’s disease, mixed connective tissue damage, myasthenia gravis, narcolepsy, pemphigus vulgaris, pernicious anemia, polymyositis, primary biliary cirrhosis, temporal arteritis, ulcerative colitis, vasculitis, and Wegener’s granulomatosis, among others. [0155] The compounds of Formula 1 may be used to treat inflammatory diseases, disorders or conditions including asthma, chronic inflammation, chronic prostatitis, glomerulonephritis, hypersensitivities, inflammatory bowel diseases (ulcerative colitis in addition to Crohn’s disease), pelvic inflammatory disease, reperfusion injury, transplant rejection, vasculitis, and systemic inflammatory response syndrome. [0156] The compounds of Formula 1 may also be used to treat specific diseases or conditions that may fall within one or more general disorders described above, including arthritis. In addition to rheumatoid arthritis, Sjögren’s syndrome, systemic lupus erythematosus, SLE in children and adolescents, compounds of Formula 1 may also be used to treat other arthritis diseases, including ankylosing spondylitis, avascular necrosis, Behcet’s disease, bursitis, calcium pyrophosphate dihyrate crystal deposition disease (pseudo gout), carpal tunnel syndrome, Ehlers-Danlos syndrome, fibromyalgia, Fifth disease, giant cell arteritis, gout, juvenile dermatomyositis, juvenile rheumatoid arthritis, juvenile spondyloarthopathy, Lyme disease, Marfan syndrome, myositis, osteoarthritis, osteogenesis imperfect, osteoporosis, Paget’s disease, psoriatic arthritis, Raynaud’s phenomenon, reactive arthritis, reflex sympathetic dystrophy syndrome, scleroderma, spinal stenosis, Still’s disease, and tendinitis, among others. [0157] The claimed and disclosed compounds may be combined with one or more other pharmacologically active compounds or therapies for the treatment of one or more diseases, disorders or conditions for which RIPK2 is indicated, including those involving the immune system, inflammation, and abnormal cell growth. For example, compounds of Formula 1, which include compounds specifically named in the examples, and their pharmaceutically acceptable complexes, salts, solvates and hydrates, may be administered simultaneously, sequentially or separately in combination with one or more compounds or therapies for treating arthritis, including rheumatoid arthritis and osteoarthritis, or for treating cancer, including hematological malignancies, such as acute myeloid leukemia, B-cell chronic lymphocytic leukemia, B-cell lymphoma, T-cell lymphoma, multiple myeloma, and carcinomas, such as lung cancer, pancreatic cancer, colorectal cancer, gastric cancer and bladder cancer. Such combinations may offer significant therapeutic advantages, including fewer side effects, improved ability to treat underserved patient populations, or synergistic activity. [0158] For example, when used to treat arthritis, the compounds of Formula 1 may be combined with one or more nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics, corticosteroids, biological response modifiers, and protein-A immunoadsorption therapy. Alternatively, or additionally, when treating rheumatoid arthritis, the compounds of Formula 1 may be combined with one or more disease modifying antirheumatic drugs (DMARDs), and when treating osteoarthritis, the compounds of Formula 1 may be combined with one or more osteoporosis agents. [0159] Representative NSAIDs include apazone, aspirin, celecoxib, diclofenac (with and without misoprostol), diflunisal, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, meclofenamate sodium, mefenamic acid, meloxicam, nabumetone, naproxen, oxaprozin, phenylbutazone, piroxicam, choline and magnesium salicylates, salsalate, and sulindac. Representative analgesics include acetaminophen and morphine sulfate, as well as codeine, hydrocodone, oxycodone, propoxyphene, and tramadol, all with or without acetaminophen. Representative corticosteroids include betamethasone, cortisone acetate, dexamethasone, hydrocortisone, methylprednisolone, prednisolone, and prednisone. Representative biological response modifiers include TNF-α inhibitors, such as adalimumab, etanercept, and infliximab; selective B-cell inhibitors, such as rituximab; IL-1 inhibitors, such as anakinra, and selective costimulation modulators, such as abatacept. [0160] Representative DMARDs include auranofin (oral gold), azathioprine, chlorambucil, cyclophosamide, cyclosporine, gold sodium thiomalate (injectable gold), hydroxychloroquine, leflunomide, methotrexate, minocycline, myophenolate mofetil, penicillamine, sulfasalazine, and JAK3 inhibitor (e.g., tofacitinib). Representative osteoporosis agents include bisphosphonates, such as alendronate, ibandronate, risedronate, and zoledronic acid; selective estrogen receptor modulators, such as droloxifene, lasofoxifene, and raloxifene; hormones, such as calcitonin, estrogens, and parathyroid hormone; and immunosuppressant agents such as azathioprine, cyclosporine, and rapamycin. [0161] Particularly useful combinations for treating rheumatoid arthritis include a compound of Formula 1 and methotrexate; a compound of Formula 1 and one or more biological response modifiers, such as lefluonomide, etanercept, adalimumab, and infliximab; or a compound of Formula 1, methotrexate, and one or more biological response modifiers, such as lefluonomide, etanercept, adalimumab, and infliximab. [0162] For the treatment of thrombis and restensosis, the compounds of Formula 1 may be combined with one or more cardiovascular agents such as calcium channel blockers, statins, fibrates, beta-blockers, ACE inhibitors, and platelet aggregation inhibitors. [0163] The compounds of Formula 1 may also be combined with one or more compounds or therapies for treating cancer. These include chemotherapeutic agents (i.e., cytotoxic or antineoplastic agents) such as alkylating agents, antibiotics, antimetabolic agents, plant- derived agents, and topoisomerase inhibitors, as well as molecularly targeted drugs which block the growth and spread of cancer by interfering with specific molecules involved in tumor growth and progression. Molecularly targeted drugs include both small molecules and biologics. [0164] Representative alkylating agents include bischloroethylamines (nitrogen mustards, e.g., chlorambucil, cyclophosphamide, ifosfamide, mechlorethamine, melphalan, and uracil mustard); aziridines (e.g., thiotepa); alkyl alkone sulfonates (e.g., busulfan); nitrosoureas (e.g., carmustine, lomustine, and streptozocin); nonclassical alkylating agents (e.g., altretamine, dacarbazine, and procarbazine); and platinum compounds (e.g., carboplatin, cisplatin, nedaplatin, oxaliplatin, satraplatin, and triplatin tetranitrate). [0165] Representative antibiotic agents include anthracyclines (e.g., aclarubicin, amrubicin, daunorubicin, doxorubicin, epirubicin, idarubicin, pirarubicin, valrubicin, and zorubicin); anthracenediones (e.g., mitoxantrone and pixantrone); and streptomyces (e.g., actinomycin, bleomycin, dactinomycin, mitomycin C, and plicamycin). [0166] Representative antimetabolic agents include dihydrofolate reductase inhibitors (e.g., aminopterin, methotrexate, and pemetrexed); hymidylate synthase inhibitors (e.g., raltitrexed and pemetrexed); folinic acid (e.g., leucovorin); adenosine deaminase inhibitors (e.g., pentostatin); halogenated/ribonucleotide reductase inhibitors (e.g., cladribine, clofarabine, and fludarabine); thiopurines (e.g., thioguanine and mercaptopurine); thymidylate synthase inhibitors (e.g., fluorouracil, capecitabine, tegafur, carmofur, and floxuridine); DNA polymerase inhibitors (e.g., cytarabine); ribonucleotide reductase inhibitors (e.g., gemcitabine); hypomethylating agent (e.g., azacitidine and decitabine); and ribonucleotide reductase inhibitor (e.g., hydroxyurea); and an asparagine depleter (e.g., asparaginase) [0167] Representative plant-derived agents include vinca alkaloids (e.g., vincristine, vinblastine, vindesine, vinzolidine, and vinorelbine), podophyllotoxins (e.g., etoposide and teniposide), and taxanes (e.g., docetaxel, larotaxel, ortataxel, paclitaxel, and tesetaxel). [0168] Representative type I topoisomerase inhibitors include camptothecins, such as belotecan, irinotecan, rubitecan, and topotecan. Representative type II topoisomerase inhibitors include amsacrine, etoposide, etoposide phosphate, and teniposide, which are derivatives of epipodophyllotoxins. [0169] Molecularly targeted therapies include biologic agents such as cytokines and other immune-regulating agents. Useful cytokines include interleukin-2 (IL-2, aldesleukin), interleukin 4 (IL-4), interleukin 12 (IL-12), and interferon, which includes more than 23 related subtypes. Other cytokines include granulocyte colony stimulating factor (CSF) (e.g., filgrastim) and granulocyte macrophage colony stimulating factor (GM-CSF or CSF2) (e.g., sargramostim, namimulab). Other immuno-modulating agents include bacillus Calmette- Guerin, levamisole, and octreotide; monoclonal antibodies against tumor antigens, such as trastruzumab and rituximab; and cancer vaccines, which induce an immune response to tumors. [0170] In addition, molecularly targeted drugs that interfere with specific molecules involved in tumor growth and progression include inhibitors of epidermal growth factor (EGF), transforming growth factor-alpha (TGF ^ ), TGF ^ , heregulin, insulin-like growth factor (IGF), fibroblast growth factor (FGF), keratinocyte growth factor (KGF), colony stimulating factor (CSF), erythropoietin (EPO), interleukin-2 (IL-2), nerve growth factor (NGF), platelet- derived growth factor (PDGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), angiopoietin, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), HER4, insulin-like growth factor 1 receptor (IGF1R), IGF2R, fibroblast growth factor 1 receptor (FGF1R), FGF2R, FGF3R, FGF4R, vascular endothelial growth factor receptor (VEGFR), tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2 (Tie-2), platelet-derived growth factor receptor (PDGFR), Abl, Bcr-Abl, Raf, FMS-like tyrosine kinase 3 (FLT3), c-Kit, Src, protein kinase c (PKC), tropomyosin receptor kinase (Trk), Ret, mammalian target of rapamycin (mTOR), Aurora kinase, polo-like kinase (PLK), mitogen activated protein kinase (MAPK), mesenchymal-epithelial transition factor (c-MET), cyclin-dependent kinase (CDK), Akt, extracellular signal-regulated kinases (ERK), poly(ADP) ribose polymerase (PARP), and the like. [0171] Specific molecularly targeted drugs include selective estrogen receptor modulators, such as tamoxifen, toremifene, fulvestrant, and raloxifene; antiandrogens, such as bicalutamide, nilutamide, megestrol, and flutamide; and aromatase inhibitors, such as exemestane, anastrozole, and letrozole. Other specific molecularly targeted drugs include agents which inhibit signal transduction, such as imatinib, dasatinib, nilotinib, trastuzumab, gefitinib, erlotinib, cetuximab, lapatinib, panitumumab, and temsirolimus; agents that induce apoptosis, such as bortezomib; agents that block angiogenesis, such as bevacizumab, sorafenib, and sunitinib; agents that help the immune system destroy cancel cells, such as rituximab and alemtuzumab; and monoclonal antibodies which deliver toxic molecules to cancer cells, such as gemtuzumab ozogamicin, tositumomab, 131I-tositumoab, and ibritumomab tiuxetan. [0172] BIOLOGICAL ACTIVITY [0173] One may determine the activity of the compounds of Formula 1 using a variety of methods, including in vitro and in vivo methods. A LanthaScreen® Eu Kinase Binding Assay (Invitrogen®) is optimized to screen the compounds of Formula 1 for RIPK2 inhibition. LanthaScreen® Eu Kinase Binding Assays are based on the binding and displacement of a proprietary ATP-competitive kinase inhibitor scaffold (kinase-199 tracer) to a kinase of interest. In this case, the assay detects binding of the Kinase Tracer-199, which is labeled with Alexa Fluor® 647, to RIPK2 using a europium-labeled anti-tag antibody, which binds to the RIPK2 kinase. Simultaneous binding of both the tracer and the antibody to RIPK2 results in a high degree of fluorescence resonance energy transfer (FRET) from the europium (Eu) donor fluorophore to the Alexa Fluor® 647 acceptor fluorophore on the kinase tracer. Binding of a test compound to RIPK2 competes for binding with the tracer, resulting in a loss of FRET. [0174] The compound screening assay is carried out using Complete Binding Assay Buffer: 50 mM HEPES, 100 mM NaCl, 1 mM DTT, 10 mM MgCl 2 , 1.15 mM CHEGA11, 0.1 mg/mL BSA, 2 nM RIPK2, 50nM Kinase Tracer-199, and 2nM Eu-Anti-His Antibody at pH 7.3. The Eu-Anti-His Antibody and Kinase Tracer-199 are purchased from Invitrogen, and human RIPK2 protein (8-317 aa, N-terminal His-tag, R171C, 38.3KDa) may be obtained as described below. [0175] RIPK2 DNA encoding residues 8-317 of the human protein is cloned into pFastBac vector (Invitrogen®) which incorporates a 6-histidine tag at the N-terminus followed by a rTEV cleavage site. A R171C mutant is generated by site-directed mutagenesis. Recombinant baculovirus incorporating the RIPK2 construct is generated by transposition using the Bac-to- Bac system (Invitrogen®). High-titer viral stock is generated by infection of Spodoptera frugiperda Sf9 cells; the expression of recombinant protein is carried out by infection of Spodoptera frugiperda Sf9 (Invitrogen®) for 48 hours in a wave bag. [0176] Recombinant RIPK2 protein is isolated from cellular extracts by binding with Probond Nickel resin (Life Technology®). The resin is washed with buffer containing 25 mM HEPES pH 7.6, 0.5 M NaCl and 20 mM imidazole, and then eluted with the elution buffer 50 mM HEPES pH 7.6, 250 mM imidazole, 150 mM NaCl, 5% glycerol and 0.5 mM TCEP. Partially purified protein is then dephosphorylated by adding 0.05 mM MnCl2 and λ- phosphatase and incubating in room temperature for 4 hours. The dephosphorylated RIPK2 protein is then purified through a Superdex® 75 column in the buffer containing 10 mM HEPES pH 7.5, 150 mM NaCl, 5% glycerol, 2 mM DTT, 1 mM TCEP, 5 mM L-Arg, and 5 mM L-Glu. The protein is stored at –80°C in small aliquots. [0177] The compounds of Formula 1 are tested for RIPK2 inhibition as follows. Test compounds are prepared in 100% DMSO and are dispensed in duplicate to individual wells of a multiplate, starting at 10 µM with 2.5 x series dilution. Next 10 µL of Complete Binding Assay Buffer is added to each of the test compounds using a Multidrop™ Combi Reagent Dispenser. The wells are covered with aluminum sealer, shaken for 2 minutes at 900 rpm, spun down for 10 seconds at 1000 rpm, incubated at RT for 60 minutes, shaken for 2 minutes at 900 rpm, and spun down for 10 seconds at 1000 rpm before reading. Samples are read on an instrument capable of measuring fluorescent polarization. The ratio 665 nM/620 nM is determined using a PHERAstar plate reader. Test compound inhibition is expressed as percent (%) inhibition of internal assay controls. For concentration response experiments, normalized data are fit and pIC50s determined using conventional techniques. The pIC50s are averaged to determine a mean value for a minimum of two experiments. EXAMPLES [0178] The following examples are intended to be illustrative and non-limiting and represent specific embodiments of the present invention. [0179] 1 H Nuclear magnetic resonance (NMR) spectra were obtained for many of the compounds in the following examples. Characteristic chemical shifts (δ) are given in parts- per-million downfield from tetramethylsilane using conventional abbreviations for designation of major peaks, including s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), and br (broad). The following abbreviations are used for common solvents: CDCl 3 (deuterochloroform), DMSO-d 6 (deuterodimethylsulfoxide), CD 3 OD (deuteromethanol), CD3CN (deuteroacetonitrile), and THF-d8 (deuterotetrahydrofuran). The mass spectra (m/z for [M+H] + ) were recorded using either electrospray ionization (ESI-MS) or atmospheric pressure chemical ionization (APCI-MS) mass spectrometry. [0180] Where indicated, products of certain preparations and examples are purified by mass-triggered HPLC, flash chromatography, preparative TLC or SFC. Reverse phase chromatography is typically carried out on a column (e.g., Gemini™ 5μm C18110Å, Axia™, 30 x 75 mm, 5 μm) under acidic conditions (“acid mode”) eluting with ACN and water mobile phases containing 0.035% and 0.05% trifluoroacetic acid (TFA), respectively, or under basic conditions (“basic mode”) eluting with water and 20/80 (v/v) water/acetonitrile mobile phases, both containing 10 mM NH4HCO3. Preparative TLC is typically carried out on silica gel 60 F 254 plates. The preparations and examples may employ SFC to separate enantiomers. After isolation by chromatography, the solvent is removed and the product is obtained by drying in a centrifugal evaporator (e.g., GeneVac™), rotary evaporator, evacuated flask, etc. Reactions in an inert (e.g., nitrogen) or reactive (e.g., H2) atmosphere are typically carried out at a pressure of about 1 atmosphere (14.7 psi). [0181] PREPARATION 1: 5-bromo-2-fluoro-4-methylbenzoic acid [0182] To a mixture of 2-fluoro-4-methylbenzoic acid (100 g, 648.77 mmol) in H 2 SO 4 (600 mL) was added NBS (127.02 g, 713.65 mmol) in portions at 0-5°C under N2. The mixture was stirred at 0°C for 2 hours. The reaction mixture was poured into ice water (15 L) slowly and filtered. The filter cake was concentrated under reduced pressure to give a residue. The residue was added to water (3 L) and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to give the title compound as a white solid (905 g, 69.2%). 1 H NMR (400 MHz, CDCl3) δ ppm 2.45 (s, 3 H) 7.07 (d, J=11.2 Hz, 1 H) 8.17 (d, J=6.8 Hz, 1 H) 10.84 (s, 1 H); ESI-MS m/z [M+H] + =233.0. [0183] PREPARATION 2: 5-bromo-2-fluoro-4-methylbenzoyl chloride [0184] To a mixture of 5-bromo-2-fluoro-4-methylbenzoic acid (200 g, 792.16 mmol) in toluene (860 mL) was added SOCl 2 (471.22 g, 3.96 mol) and DMF (5.79 g, 79.22 mmol) in one portion under N2. The mixture was stirred at 70°C for 3 hours and then concentrated under reduced pressure to give the title compound as a brown oil (600 g, crude). ESI-MS m/z [M-6] + =246.9 [0185] PREPARATION 3: 5-bromo-N-cyclopropyl-2-fluoro-4-methylbenzamide [0186] To a mixture of cyclopropanamine (81.73 g, 1.43 mol) in DCM (1200 mL) was added Et 3 N (482.85 g, 4.77 mol) in one portion at 0°C under N 2 . The mixture was stirred at 0°C for 30 min, then was added a solution of 5-bromo-2-fluoro-4-methylbenzoyl chloride (300 g, 1.19 mol) in DCM (900 mL) dropwise at 0°C and stirred at 0°C for 2 hours. The reaction mixture was poured into water and extracted with DCM. The combined organic layers were washed with brine, dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to give a residue. The residue was added into a solution of (EtOAc/Petroleum ether 10%) and stirred at 25°C for 2 hours. The mixture was filtered, and the filter cake was concentrated under reduced pressure to give the title compound as a white solid (795 g, 91.7%). 1 H NMR (400 MHz, CDCl3) δ ppm 0.57 - 0.65 (m, 2 H) 0.83 - 0.92 (m, 2 H) 2.39 (s, 3 H) 2.85 - 2.96 (m, 1 H) 6.76 (d, J=11.6 Hz, 1 H) 6.98 (d, J=12.2 Hz, 1 H) 8.21 (d, J=7.6 Hz, 1 H); ESI-MS m/z [M+H] + =271.9. [0187] PREPARATION 4: N-cyclopropyl-2-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2 - dioxaborolan-2-yl)benzamide [0188] To a mixture of 5-bromo-N-cyclopropyl-2-fluoro-4-methylbenzamide (75 g, 274.52 mmol) and 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (73.20 g, 288.24 mmol) in dioxane (750 mL) were added KOAc (80.83 g, 823.55 mmol) and Pd(dppf)Cl2 (10.04 g, 13.73 mmol) in one portion under N 2 . The mixture was stirred at 90°C for 12 hours and then filtered through silica gel. The filtrate was diluted with water and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to give a residue. The residue was triturated with EtOAc/Petroleum ether (10%) at 25°C for 12 hours. The mixture was filtered, and the filter cake was concentrated under reduced pressure to give the title compound as a brown solid (277 g, 76.9%). 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.56 - 0.65 (m, 2 H) 0.81 - 0.92 (m, 2 H) 1.33 (s, 12 H) 2.54 (s, 3 H) 2.92 (m, 1 H) 6.68 (d, J=11.4 Hz, 1 H) 6.87 (d, J=13.4 Hz, 1 H) 8.44 (d, J=9.4 Hz, 1 H); ESI-MS m/z [M+H] + =320.0. [0189] PREPARATION 5: 2-((3-bromo-5-chloropyridin-2-yl)amino)ethan-1-ol [0190] To a mixture of 3-bromo-5-chloro-2-fluoropyridine (250 g, 1.19 mol) and 2- aminoethanol (79.83 g, 1.31 mol) in DMSO (1250 mL) was added DIPEA (460.64 g, 3.56 mol) in one portion under N 2 . The reaction mixture was stirred at 160°C for 4 hours and then diluted with water and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to give a residue, which was purified by column chromatography (SiO2, EtOAc/Petroleum ether 5% to 50%). The title compound was obtained as a white solid (239 g, 80.0%). ESI-MS m/z [M+H] + =253.0 [0191] PREPARATION 6: 2-((5-chloro-3-(1-methyl-1H-pyrazol-4-yl)pyridin-2- yl)amino)ethan-1-ol [0192] To a mixture of 2-((3-bromo-5-chloropyridin-2-yl)amino)ethan-1-ol (50 g, 198.80 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H- pyrazole (45.50 g, 218.68 mmol) in dioxane (500 mL) and H2O (50 mL) were added K2CO3 (54.95 g, 397.60 mmol) and Pd(dppf)Cl 2 (7.27 g, 9.94 mmol) in one portion under N 2 . The mixture was stirred at 90°C for 6 hours and then filtered. The filtrate was diluted with water and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to give a residue, which was purified by column chromatography (SiO 2 , EtOAc/Petroleum ether 20% to 200%). The pure title compound was obtained as a brown solid (300 g, 70.3%) and the crude title compound was obtained as a brown solid (65 g, 11%). 1 H NMR (400 MHz, CDCl3) δ ppm 3.48 - 3.61 (m, 2 H) 3.75 - 3.83 (m, 2 H) 3.97 (s, 3 H) 4.30 (s, 1 H) 5.21 (t, J=4.8 Hz, 1 H) 7.30 (d, J=2.4 Hz, 1 H) 7.54 (s, 1 H) 7.63 (s, 1 H) 7.95 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =253.0. [0193] PREPARATION 7: 5-bromo-2-fluoro-N-(isoxazol-3-yl)-4-methylbenzamide [0194] To a solution of isoxazol- , 1 mmol) in DCM (1 mL) was added pyridine (5 mL).The mixture was stirred at 0°C for 0.5 hours. Next, a solution of 5- bromo-2-fluoro-4-methylbenzoyl chloride (1 g, 3.98 mmol) in DCM (1 mL) was added drop- wise. The reaction mixture was stirred at 0°C for 2 hours and then diluted with DCM, washed with H2O and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO 2 , EtOAc/Petroleum ether 5% to 25%). The title compound was obtained as a white solid (900 mg, 83.2%). 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 2.40 (s, 3 H) 7.00 (s, 1 H) 7.43 (d, J=10.8 Hz, 1 H) 7.90 (d, J=6.8 Hz, 1 H) 8.86 (s, 1 H) 11.52 (s, 1 H); ESI-MS m/z [M+H] + =300.9. [0195] PREPARATION 8: 2-((3-bromo-5-chloropyridin-2-yl)amino)-2-methylpropan-1-ol [0196] To a solution of 3-bromo-5-chloro-2-fluoropyridine (2 g, 9.50 mmol) and 2-amino- 2-methylpropan-1-ol (931.89 mg, 10.45 mmol, 997.74 µL) in DMSO (20 mL) was added DIPEA (1.84 g, 14.26 mmol, 2.48 mL) at 15°C. The mixture was stirred at 120°C for 3 hours and then diluted with H2O and extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na 2 SO 4 , filtered, concentrated under reduced pressure and purified by column chromatography (SiO2, EtOAc/Petroleum ether 5% to 10%). The title compound was obtained as a yellow oil (2 g). 1 H NMR (400 MHz, CDCl3) δ ppm 1.39 (s, 6 H) 3.69 (s, 2 H) 5.12 (s, 1 H) 5.71 (s, 1 H) 7.66 (d, J=2.4 Hz, 1H) 7.94 (d, J=2.4 Hz, 1H). [0197] PREPARATION 9: N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)benzamide [0198] STEP A: 3-bromo-N-cyclopropyl-4-methylbenzamide [0199] To a solution of 3-bromo-4-methylbenzoic acid (3.6 g, 16.74 mmol) and cyclopropanamine (955.80 mg, 16.74 mmol) in DMF (20 mL) was added HATU (7.00 g, 18.41 mmol) and Et3N (5.08 g, 50.22 mmol). The reaction mixture was stirred at 30°C for 16 hours and then diluted with water (40 mL). The aqueous phase was extracted with EtOAc. The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate, filtered, concentrated under vacuum and purified by silica gel column chromatography (EtOAc/petroleum ether 10% to 30%). The title compound was obtained as a white solid (4.7 g, 99%). 1 H NMR (400 MHz, CDCl3) δ ppm 0.63 (dd, J=1.6, 3.6 Hz, 2 H) 0.85 (dd, J=1.6, 3.6 Hz, 2 H) 2.43 (s, 3 H) 2.86 - 2.92 (m, 1 H) 6.23 (s, 1 H) 7.27 (s, 1 H) 7.58 (dd, J=1.6, 8.0 Hz, 1 H) 7.90 (d, J=1.6 Hz, 1 H). [0200] STEP B: N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxabor olan-2- yl)benzamide [0201] A mixture of 3-bromo-N-cyclopropyl-4-methylbenzamide (4.8 g, 18.89 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (5.04 g, 19.83 mmol), KOAc (5.56 g, 56.67 mmol) and Pd(dppf)Cl2 (829.26 mg, 1.13 mmol) in dioxane (80 mL) was degassed and purged with N 2 (3 x). The reaction mixture was stirred at 80°C for 1 hour under N 2 and then diluted with water (40 mL). The aqueous phase was extracted with EtOAc. The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The resulting residue was purified by silica gel column chromatography (EtOAc/petroleum ether 10% to 30%), triturated with 10% Petroleum ether/EtOAc (30 mL) and filtered to give the title compound as a white solid (5.5 g, 97%). 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.55 - 0.70 (m, 2 H) 0.73 - 0.94 (m, 2 H), 1.28 - 1.43 (m, 12 H) 2.51 - 2.60 (m, 3 H) 2.87 (td, J=3.6, 7.2 Hz, 1 H) 6.31 - 6.55 (m, 1 H) 7.17 - 7.24 (m, 1 H) 7.77 - 7.85 (m, 1 H) 7.98 (s, 1 H). [0202] PREPARATION 10: 3-bromo-N-(1-((tert-butyldimethylsilyl)oxy)-2-methylpropan- 2-yl)-5-chloropyridin-2-amine [0203] To a solution of 2-(( 3-bromo-5-chloropyridin-2-yl)amino)-2-methylpropan-1-ol (1.2 g, 4.29 mmol) in DCM (20 mL) were added imidazole (584.44 mg, 8.58 mmol) and TBSCl (776.36 mg, 5.15 mmol, 631.18 µL) at 0°C. The mixture was stirred at 25°C for 3 hours and then diluted with H 2 O and extracted with DCM. The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the title compound as a yellow oil (1.6 g, crude). 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.04 (s, 6 H) 0.91 (s, 9 H) 1.42 (s, 6 H) 3.59 (s, 2 H) 7.57 (d, J=2.4 Hz, 1H) 7.97 (d, J=2.0 Hz, 1H). [0204] PREPARATION 11: 5-bromo-2-((1-hydroxy-2-methylpropan-2-yl)amino)nicotinic acid [0205] STEP A: 5-bromo-2-((1-hydroxy-2-methylpropan-2-yl)amino)nicotinonitr ile [0206] To a solution of 5-bromo-2-chloro-pyridine-3-carbonitrile (10 g, 45.99 mmol) and 2-amino-2-methyl-propan-1-ol (8.20 g, 91.98 mmol, 8.78 mL) in ACN (150 mL) was added Cs 2 CO 3 (29.97 g, 91.98 mmol). The mixture was stirred at 82°C for 12 hours and then filtered. The filtrate was concentrated and purified by column chromatography (SiO2, EtOAc/Petroleum ether 4% to 10%). The title compound was obtained as a yellow solid (3.6 g, 29%). 1 H NMR (400 MHz, CDCl3) δ ppm 1.41 (s, 6 H) 3.68 (d, J=6.4 Hz, 2 H) 5.24 (s, 1 H) 7.76 (d, J=2.4 Hz, 1 H) 8.24 (d, J=2.4 Hz, 1 H). [0207] STEP B: 5-bromo-2-((1-hydroxy-2-methylpropan-2-yl)amino)nicotinic acid [0208] To a solution of 5-bromo-2-((1-hydroxy-2-methylpropan-2-yl)amino)nicotinonitr ile (2.5 g, 9.25 mmol) in H 2 O (10 mL) was added NaOH (370.17 mg, 9.25 mmol, 24.68 µL). The reaction mixture was stirred at 100°C for 4 hours and then poured into water (20 ml), adjusted to pH 3 with HCl (1M) and filtered. The filter cake was dried under vacuum to give the title compound as a yellow solid (2.5 g, 93%). 1 H NMR (400 MHz, DMSO-d6) δ ppm 1.34 (s, 6 H) 3.50 (d, J=6.4 Hz, 2 H) 4.96 (s, 1 H) 8.09 (d, J=2.8 Hz, 1 H) 8.28 (d, J=2.8 Hz, 1 H) 8.35 (s, 1 H). [0209] PREPARATION 12: 2-((3-(dimethylcarbamoyl)-5-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)pyridin-2-yl)amino)-2-methylpropyl acetate [0210] STEP A: 5-bromo-2-((1-hydroxy-2-methylpropan-2-yl)amino)-N,N- dimethylnicotinamide [0211] To a solution of 5-bromo-2-((1-hydroxy-2-methylpropan-2-yl)amino)nicotinic acid (3.77 g, 13.02 mmol) and N-methylmethanamine (2.94 g, 65.11 mmol, 3.30 mL) in DMF (15 mL) was added HATU (7.43 g, 19.53 mmol) and DIPEA (5.05 g, 39.07 mmol, 6.80 mL). The reaction mixture was stirred at 15°C for 12 hours and then diluted with water (30 mL). The aqueous phase was extracted with EtOAc. The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate, filtered, concentrated under vacuum and purified by column chromatography (SiO 2 , EtOAc/Petroleum ether 6% to 50%). The title compound was obtained as a white solid (2.74 g, 66.7%). 1 H NMR (400 MHz, DMSO-d6) δ ppm 1.31 (s, 6 H) 2.93 (s, 6 H) 3.40 (d, J=5.2 Hz, 2 H) 5.06 (t, J=5.2 Hz 1 H) 5.97 (s, 1 H) 7.59 (d, J=2.4 Hz, 1 H) 8.14 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =318.1. [0212] STEP B: 2-((5-bromo-3-(dimethylcarbamoyl)pyridin-2-yl)amino)-2-methy lpropyl acetate [0213] A solution of 5-bromo-2-((1-hydroxy-2-methylpropan-2-yl)amino)-N,N- dimethylnicotinamide (2.1 g, 6.64 mmol) and Ac2O (1.36 g, 13.28 mmol, 1.24 mL) in pyridine (5 mL) was stirred at 80°C for 12 hours. The reaction mixture was concentrated under reduced pressure to remove solvent and then poured into water (20 mL). The aqueous phase was extracted with EtOAc. The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate, filtered, concentrated under vacuum and purified by column chromatography (SiO2, EtOAc/Petroleum ether 10% to 50%). The title compound was obtained as a yellow oil (1.95 g, 82.1%). ESI-MS m/z [M+H] + =360.0. [0214] STEP C: 2-((3-(dimethylcarbamoyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxa borolan-2- yl)pyridin-2-yl)amino)-2-methylpropyl acetate [0215] To a solution of 2-((5-bromo-3-(dimethylcarbamoyl)pyridin-2-yl)amino)-2- methylpropyl acetate (1.9 g, 5.30 mmol) and 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1,3,2-dioxaborolane (2.02 g, 7.96 mmol) in dioxane (3 mL) were added Pd(dppf)Cl2 (388.09 mg, 530.39 µmol) and KOAc (1.56 g, 15.91 mmol). The reaction mixture was stirred at 90°C for 3 hours and then poured into water (30 mL). The aqueous phase was extracted with EtOAc. The organic layers were combined, washed with brine, dried over anhydrous Na 2 SO 4 , filtered, concentrated under vacuum and purified by column chromatography (SiO2, EtOAc/Petroleum ether 0% to 5%). The product was triturated with (EtOAc/Petroleum ether 10%) and filtered to give the title compound as a white solid (1.65 g, 76.8%). 1 H NMR (400 MHz, CDCl3) δ ppm 1.30 (s, 12 H) 1.45 (s, 6 H) 2.05 (s, 3 H) 3.05 (s, 6 H) 4.42 (s, 2 H) 6.19 (s, 1 H) 7.65 (s, 1 H) 8.46 (s, 1 H). [0216] PREPARATION 13: 3-bromo-N-(isoxazol-3-yl)-4-methylbenzamide [0217] STEP A: 3-bromo-4-methylbenzoyl chloride [0218] To a solution of 3-bromo-4-methylbenzoic acid (40 g, 186.01 mmol) in toluene (200 mL) were added SOCl 2 (110.65 g, 930.04 mmol, 67.47 mL) and DMF (two drops). The reaction mixture was stirred at 70°C for 3 hours and then concentrated under vacuum to give the title compound as a yellow solid (45.5 g, crude). [0219] STEP B: 3-bromo-N-(isoxazol-3-yl)-4-methylbenzamide [0220] A mixture of isoxazol-3-amine (350 mg, 4.16 mmol, 307.02 µL) in pyridine (5 mL) and 3-bromo-4-methylbenzoyl chloride (1.07 g, 4.58 mmol) in DCM (1 mL) was added to 3- bromo-4-methylbenzoyl chloride (45.5 g). The reaction mixture was stirred at 20°C for 1 hour and then concentrated under reduced pressure. Water (40 mL) was added and the aqueous phase was extracted with EtOAc. The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The resulting residue was triturated with 10% petroleum ether/EtOAc and filtered to give the title compound as a white solid (1.05 g, 89.7%). 1 H NMR (400 MHz, DMSO-d6) δ ppm 2.39 - 2.46 (m, 3 H), 7.04 (d, J=1.6 Hz, 1 H), 7.49 - 7.55 (m, 1 H), 7.95 (dd, J=1.8, 7.9 Hz, 1 H), 8.26 (d, J=1.6 Hz, 1 H), 8.87 (d, J=1.5 Hz, 1 H), 11.52 (s, 1 H); ESI-MS m/z [M+H] + =281.0/283.1. [0221] PREPARATION 14: 3-bromo-N-(isothiazol-3-yl)-4-methylbenzamide [0222] STEP A: 3-bromo-4-methylbenzamide [0223] A mixture of 3-bromo-4-methylbenzoic acid (1 g, 4.65 mmol), NH4Cl (298.50 mg, 5.58 mmol), DIPEA (1.80 g, 13.95 mmol), EDCI (1.34 g, 6.98 mmol) and HOBt (628.35 mg, 4.65 mmol) in DMF (2 mL) was degassed and purged with N2 (3 x) and stirred at 15°C for 2 hours under N2. The reaction mixture was then poured into water and filtered. The filter cake was dried under reduced pressure to give the title compound as a white solid (835 mg, 83.9%). 1 H NMR (400 MHz, DMSO-d6) δ ppm 2.38 (s, 3 H) 7.41 (br s, 1 H) 7.43 (d, J=8.0 Hz, 1 H) 7.78 (dd, J=8.0, 1.6 Hz, 1 H) 8.01 (br s, 1 H) 8.07 (d, J=2.0 Hz, 1 H). [0224] STEP B: 3-bromo-N-(isothiazol-3-yl)-4-methylbenzamide [0225] To a solution of 3-bromo-4-methylbenzamide (78.30 mg, 365.80 µmol) in dioxane (2 mL) was added 3-bromoisothiazole (50 mg, 304.83 µmol), CuI (11.61 mg, 60.97 µmol), (1R,2R)-cyclohexane-1,2-diamine (6.96 mg, 60.97 µmol) and K 2 CO 3 (84.26 mg, 609.67 µmol). The reaction mixture was stirred at 120°C for 12 hours and then poured into H2O and extracted with EtOAc. The organic layer was washed with brine, dried over Na 2 SO 4 , concentrated under reduce pressure and purified by column chromatography (EtOAc/Petroleum ether 5% to 10%). The title compound was obtained as a yellow solid (40 mg, 44%). 1 H NMR (400 MHz, DMSO-d6) δ ppm 2.43 (s, 3 H) 7.51 (d, J=8.0 Hz, 1 H) 7.87 (d, J=4.8 Hz, 1 H) 7.96 (dd, J=8.0, 2.0 Hz, 1 H) 8.18 - 8.38 (m, 1 H) 9.07 (d, J=4.8 Hz, 1 H) 11.55 (s, 1 H); ESI-MS m/z [M+H] + =297.0. [0226] PREPARATION 15: 5-bromo-2-fluoro-N-(isothiazol-3-yl)-4-methylbenzamide [0227] STEP A: 5-bromo-2-fluoro-4-methylbenzamide [0228] A mixture of 5-bromo-2-fluoro-4-methylbenzoic acid (1 g, 4.29 mmol), NH4Cl (275.45 mg, 5.15 mmol), DIPEA (1.66 g, 12.87 mmol), EDCI (1.23 g, 6.44 mmol) and HOBt (579.83 mg, 4.29 mmol) in DMF (10 mL) was stirred at 15°C for 16 hours under N2. The reaction mixture was poured into water and filtered. The filter cake was collected and dried to give the title compound as a white solid (860 mg, 81%). 1 H NMR (400 MHz, DMSO-d6) δ ppm 2.35 (s, 3 H) 7.26 - 7.39 (m, 1 H) 7.69 (d, J=12.4 Hz, 2 H) 7.80 (d, J=6.8 Hz, 1 H); ESI- MS m/z [M+H] + =231.7. [0229] STEP B: 5-bromo-2-fluoro-N-(isothiazol-3-yl)-4-methylbenzamide [0230] A mixture of 5-bromo-2-fluoro-4-methylbenzamide (300 mg, 1.29 mmol), 3- bromoisothiazole (212.05 mg, 1.29 mmol), CuI (49.24 mg, 258.57 µmol), K 2 CO 3 (357.35 mg, 2.59 mmol) and (1R,2R)-cyclohexane-1,2-diamine (29.53 mg, 258.57 µmol) in dioxane (4 mL) was degassed and purged with N 2 (3 x). The mixture was stirred at 120°C for 16 hours under N2 and then diluted with H2O and extracted with EtOAc. The organic layers were combined, washed with brine, dried over Na 2 SO 4 , concentrated under reduced pressure and purified by column chromatography (SiO2, EtOAc/Petroleum ether 0 to 20%). The title compound was obtained as a white solid (150 mg, 59.6%). 1 H NMR (400 MHz, DMSO-d6) δ ppm 2.47 (s, 3 H) 7.12 (d, J=12.4 Hz, 1 H) 8.03 (d, J=4.8 Hz, 1 H) 8.34 (d, J=7.6 Hz, 1 H) 8.67 (d, J=4.8 Hz, 1 H) 9.32 (d, J=13.6 Hz, 1 H); ESI-MS m/z [M+H] + =314.8. [0231] PREPARATION 16: 2-chloro-N-cyclopropyl-4-methyl-5-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)benzamide [0232] STEP A: 5-bromo-2-chloro-4-methylbenzoic acid [0233] To a solution of 2-chloro-4-methylbenzoic acid (1 g, 5.86 mmol) in H2SO4 (20 mL) was added NBS (1.20 g, 6.74 mmol). The mixture was stirred at 0°C for 2 hours and then diluted with water (200 mL) and filtered. The filter cake was collected and co-evaporated with toluene (5 x) to remove water. The title compound was obtained as a white solid (1.6 g, crude). 1 H NMR (400 MHz, CD3OD) δ ppm 2.41 (s, 3 H) 7.44 (s, 1 H) 8.01 (s, 1 H); ESI-MS m/z [M+2] + =250.9. [0234] STEP B: 5-bromo-2-chloro-4-methylbenzoyl chloride [0235] To a solution of 5-bromo-2-chloro-4-methylbenzoic acid (1.6 g, 6.41 mmol) in toluene (15 mL) was added SOCl2 (3.81 g, 32.07 mmol) and DMF (46.88 mg, 641.31 µmol). The resulting mixture was stirred at 70°C for 3 hours and then concentrated under reduced pressure to give the title compound as a yellow oil (1.6 g, crude). ESI-MS m/z [M+2] + =267.0. STEP C: 5-bromo-2-chloro-N-cyclopropyl-4-methylbenzamide [0236] To a solution of cyclopropanamine (409.13 mg, 7.17 mmol) in DCM (20 mL) was added Et3N (2.42 g, 23.89 mmol). The mixture was stirred at 0°C for 0.5 hours. Next, a solution of 5-bromo-2-chloro-4-methylbenzoyl chloride (1.6 g, 5.97 mmol) in DCM (20 mL) was added drop-wise. The mixture was stirred at 0°C for 1 hour and then diluted with water and extracted with DCM. The organic layers were combined, dried over anhydrous Na 2 SO 4 , filtered, concentrated under reduced pressure and purified by column chromatography (SiO2, EtOAc/Petroleum ether 10% to 20%). The title compound was obtained as a yellow solid (1.4 g, 81%). 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.51 - 0.53 (m, 2 H) 0.65 - 0.69 (m, 2 H) 2.34 (s, 3 H) 2.76 - 2.79 (m, 1 H) 7.51 (s, 1 H) 7.59 (s, 1 H) 8.49 (d, J=3.6 Hz, 1 H); ESI-MS m/z [M+H] + =289.9. [0237] STEP D: 2-chloro-N-cyclopropyl-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2 - dioxaborolan-2-yl)benzamide [0238] To a mixture of 5-bromo-2-chloro-N-cyclopropyl-4-methylbenzamide (0.7 g, 2.43 mmol), KOAc (714.21 mg, 7.28 mmol) and B2Pin2 (739.20 mg, 2.91 mmol) in dioxane (25 mL) was added Pd(dppf)Cl 2 (177.50 mg, 242.58 µmol). The resulting mixture was degassed with N2 several times and then heated to 85°C for 12 hours under N2. The reaction mixture was subsequently diluted with water and extracted with ethyl acetate. The organic layers were combined, dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure and purified by column chromatography (SiO 2 , EtOAc/Petroleum ether 5% to 20%). The title compound was obtained as a yellow solid (850 mg, crude). 1 H NMR (400 MHz, CD3OD) δ ppm 0.61 - 0.64 (m, 2 H) 0.79 - 0.81 (m, 2 H) 1.34 (s, 12 H) 2.51 (s, 3 H) 2.82 - 2.86 (m, 1 H) 7.26 (s, 1 H) 7.70 (s, 1 H); ESI-MS m/z [M+H] + =336.1. [0239] PREPARATION 17: 2-fluoro-4-methyl-N-(1H-pyrazol-3-yl)-5-(4,4,5,5-tetramethyl - 1,3,2-dioxaborolan-2-yl)benzamide [0240] STEP A: 5-bromo-2-fluoro-4-methyl-N-(1H-pyrazol-3-yl)benzamide [0241] To a solution of tert-butyl 3-amino-1H-pyrazole-1-carboxylate (30 g, 163.75 mmol) and triethylamine (82.85 g, 818.74 mmol) in DCM (300 mL) was added dropwise a solution of 5-bromo-2-fluoro-4-methylbenzoyl chloride (41.18 g, 163.75 mmol) in DCM (100 mL) at 0°C. The reaction mixture was stirred at 0°C for 2 hours and then poured into H 2 O and extracted with DCM. The organic layer was washed with brine, dried over anhydrous Na 2 SO 4 , concentrated under reduce pressure and purified by column chromatography (SiO 2 , EtOAc/Petroleum ether 10% to 50%) to give tert-butyl 3-(5-bromo-2-fluoro-4- methylbenzamido)-1H-pyrazole-1-carboxylate as a yellow solid (12 g) and 5-bromo-2-fluoro- 4-methyl-N-(1H-pyrazol-3-yl)benzamide. The latter compound was re-purified by reversed- phase flash chromatography to give the title compound as a yellow solid (1 g, 2.05%). ESI- MS m/z [M+H] + =297.9. [0242] STEP B: 2-fluoro-4-methyl-N-(1H-pyrazol-3-yl)-5-(4,4,5,5-tetramethyl -1,3,2- dioxaborolan-2-yl)benzamide [0243] To a solution of 5-bromo-2-fluoro-4-methyl-N-(1H-pyrazol-3-yl)benzamide (1 g, 3.35 mmol) in dioxane (10 mL) were added 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2- dioxaborolane) (937.00 mg, 3.69 mmol), KOAc (987.62 mg, 10.06 mmol) and Pd(dppf)Cl2 (245.45 mg, 335.45 µmol). The reaction mixture was stirred at 90°C for 6 hours and then poured into H2O and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous Na 2 SO 4 , concentrated under reduce pressure and purified by column chromatography (SiO2, EtOAc/Petroleum ether 10% to 25%). The title compound was obtained as a yellow oil (600 mg, crude). ESI-MS m/z [M+H] + =346.1. [0244] PREPARATION 18: 5-bromo-2-((2-hydroxyethyl)(methyl)amino)nicotinonitrile [0245] To a mixture of 5-bromo-2-chloronicotinonitrile (500 mg, 2.299 mmol) in DMA (2 mL) were added 2-(methylamino)ethan-1-ol (185 µL, 2.299 mmol) and DIPEA (803 µL, 4.60 mmol). The reaction mixture was stirred at 70°C for 4 hours and then diluted with water and extracted EtOAc. The organic phase was concentrated to give the title compound, which was used without further purification. [0246] PREPARATION 19: 2-fluoro-N-(isoxazol-3-yl)-4-methyl-5-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)benzamide [0247] A mixture of 5-brom o 2 fluoro N (isoxazol 3 yl) 4 methylbenzamide (18 g, 60.18 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (22.92 g, 90.27 mmol), Pd(dppf)Cl 2 (4.40 g, 6.02 mmol) and KOAc (17.72 g, 180.54 mmol) in dioxane (180 mL) was degassed and purged with N2 (3 x). The reaction mixture was stirred at 90°C for 5 hours under N 2 atmosphere and then diluted with ethyl acetate and water. The organic layer was separated, and the aqueous phase was extracted with EtOAc. The organic layers were combined, washed with brine, dried over Na 2 SO 4 , filtered, concentrated under reduced pressure and purified by column chromatography (SiO2, EtOAc/Petroleum ether 5% to 100%). The title compound was obtained as a brown solid (10.33 g, 49.59%). 1 H NMR (400 MHz, CDCl3) δ ppm 1.34 (s, 12 H) 2.59 (s, 3 H) 7.01 (d, J=13.6 Hz, 1 H) 7.21 (d, J=1.6 Hz, 1 H) 8.34 (d, J=1.6 Hz, 1 H) 8.54 (d, J=9.6 Hz, 1 H) 9.11 (d, J=13.6 Hz, 1 H); ESI-MS m/z [M+H] + =347.2. [0248] EXAMPLE 1: 5-(5-cyano-6-((cis-3-methoxytetrahydro-2H-pyran-4- yl)amino)pyridin-3-yl)-2-fluoro-4-methyl-N-(1H-pyrazol-3-yl) benzamide [0249] STEP A: 5-bromo-2-((cis-3-methoxytetrahydro-2H-pyran-4- yl)amino)nicotinonitrile [0250] To a solution of 5-bromo-2-chloronicotinonitrile (346 mg, 1.593 mmol) in DMA (2ml) were added cis-3-methoxytetrahydro-2H-pyran-4-amine (209mg, 1.593 mmol) and DIPEA (557 µL, 3.19 mmol). The reaction mixture was stirred at 70°C for 4 hours and then diluted with water and extracted with EtOAc. The organic layer was washed by water and brine, dried over anhydrous Na 2 SO 4 , filtered, and concentrated. The resulting residue was purified by SFC to give the title compound (258mg). [0251] STEP B: 5-(5-cyano-6-((cis-3-methoxytetrahydro-2H-pyran-4-yl)amino)p yridin-3- yl)-2-fluoro-4-methyl-N-(1H-pyrazol-3-yl)benzamide [0252] To a mixture of 5-bromo-2-((cis-3-methoxytetrahydro-2H-pyran-4- yl)amino)nicotinonitrile (258 mg, 0.828 mmol) and 2-fluoro-4-methyl-N-(1H-pyrazol-3-yl)- 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (200 mg, 0.579 mmol) in 1,4- dioxane (3 mL) was added Na2CO3 (2 M) (1242 µL, 2.483 mmol). The mixture was purged with N 2 and Pd(dppf)Cl 2 -CH 2 Cl 2 adduct (67.6 mg, 0.083 mmol) was added. The reaction mixture was heated at 110°C in a microwave reactor for 1 hour and then diluted with EtOAc and filtered. The filtrate was washed with water and brine, dried over anhydrous Na 2 SO 4 , filtered, concentrated and purified by SFC. The title compound was obtained as a white solid (5 mg). ESI-MS m/z [M+H] + =451.4. [0253] EXAMPLE 2: 5-(5-cyano-6-((2-hydroxyethyl)(methyl)amino)pyridin-3-yl)-2- fluoro-4-methyl-N-(1H-pyrazol-3-yl)benzamide [0254] To a mixture of 5-bromo-2-((2-hydroxyethyl)(methyl)amino)nicotinonitrile (0.589 g, 2.299 mmol) and 2-fluoro-4-methyl-N-(1H-pyrazol-3-yl)-5-(4,4,5,5-tetramethyl -1,3,2- dioxaborolan-2-yl)benzamide (0.556 g, 1.609 mmol) in 1,4-dioxane (2 mL) were added Na 2 CO 3 (3.45 mL, 6.90 mmol). The mixture was purged with N 2 and Pd(dppf)Cl 2 -CH 2 Cl 2 adduct (0.188 g, 0.230 mmol) was added. The reaction mixture was heated at 110°C in microwave reactor for 1 hour and then filtered and purified by HPLC. The title compound was obtained as a tan solid (15 mg, 1.7%).1H NMR (400 MHz, CD 3 OD) δ ppm 2.29 - 2.41 (m, 3 H) 3.43 - 3.52 (m, 3 H) 3.84 - 3.98 (m, 4 H) 6.64 - 6.77 (m, 1 H) 7.19 - 7.30 (m, 1 H) 7.53 - 7.64 (m, 1 H) 7.66 - 7.74 (m, 1 H) 7.83 - 7.95 (m, 1 H) 8.26 - 8.36 (m, 1 H); ESI-MS m/z [M+H] + =395.3. [0255] Examples 3 to 7, below, were prepared like Examples 1 and 2. [0256] EXAMPLE 3: 5-(5-cyano-6-(((3R,4S)-3-methoxytetrahydro-2H-pyran-4- yl)amino)pyridin-3-yl)-2-fluoro-4-methyl-N-(1H-pyrazol-3-yl) benzamide [0257] 1 H NMR (400 MHz, CD 3 OD) δ ppm 1.68 - 1.80 (m, 1 H) 2.07 - 2.20 (m, 1 H) 2.36 (s, 3 H) 3.15 - 3.30 (m, 1 H) 3.44 - 3.54 (m, 5 H) 3.88 - 3.97 (m, 1 H) 4.18 (dd, J=11.19, 4.59 Hz, 1 H) 4.28 - 4.37 (m, 1 H) 6.69 (d, J=2.02 Hz, 1 H) 7.58 - 7.70 (m, 2 H) 7.87 (d, J=2.29 Hz, 1 H) 8.27 (d, J=2.38 Hz, 1 H); ESI-MS m/z [M+H] + =451.3. [0258] EXAMPLE 4: 5-(5-cyano-6-((tetrahydrofuran-3-yl)amino)pyridin-3-yl)-2-fl uoro-4- methyl-N-(1H-pyrazol-3-yl)benzamide [0259] 1 H NMR (400 MHz, CD3OD) δ ppm 2.05 (br d, J=5.59 Hz, 1 H) 2.36 (s, 3 H) 3.76 (dd, J=9.08, 4.31 Hz, 1 H) 3.82 - 3.92 (m, 1 H) 3.99 - 4.11 (m, 2 H) 4.72 - 4.79 (m, 1 H) 6.69 (br s, 1 H) 7.25 (d, J=11.74 Hz, 1 H) 7.57 - 7.72 (m, 2 H) 7.89 (d, J=2.38 Hz, 1 H) 8.31 (d, J=2.29 Hz, 1 H); ESI-MS m/z [M+H] + =407.2. [0260] EXAMPLE 5: (S)-5-(5-cyano-6-(3-hydroxy-3-methylpyrrolidin-1-yl)pyridin- 3-yl)- 2-fluoro-4-methyl-N-(1H-pyrazol-3-yl)benzamide [0261] 1 H NMR (400 MHz, CD3OD) δ ppm 1.50 (s, 3 H) 2.07 (br d, J=7.79 Hz, 2 H) 2.36 (s, 3 H) 3.73 (d, J=11.37 Hz, 1 H) 3.85 (d, J=11.19 Hz, 1 H) 3.92 - 4.07 (m, 2 H) 6.68 (br s, 1 H) 7.25 (br d, J=11.65 Hz, 1 H) 7.61 (br s, 1 H) 7.67 (br d, J=7.34 Hz, 1 H) 7.88 (d, J=2.02 Hz, 1 H) 8.29 (d, J=1.93 Hz, 1 H)"; ESI-MS m/z [M+H] + =421.4. [0262] EXAMPLE 6: 5-(5-cyano-6-(ethyl(2-hydroxyethyl)amino)pyridin-3-yl)-2-flu oro-4- methyl-N-(1H-pyrazol-3-yl)benzamide [0263] 1 H NMR (400 MHz, CD3OD) δ ppm 1.35 (t, J=7.02 Hz, 3 H) 2.37 (s, 3 H) 3.82 - 4.00 (m, 1 H) 3.84 - 3.95 (m, 4 H) 3.98 - 4.04 (m, 1 H) 6.56 - 6.77 (m, 1 H) 7.25 (d, J=11.74 Hz, 1 H) 7.61 (d, J=2.02 Hz, 1 H) 7.68 (d, J=7.61 Hz, 1 H) 7.90 (d, J=2.48 Hz, 1 H) 8.33 (d, J=2.38 Hz, 1 H); ESI-MS m/z [M+H] + =409.3. [0264] EXAMPLE 7: 5-(5-cyano-6-((2-hydroxyethyl)amino)pyridin-3-yl)-2-fluoro-4 - methyl-N-(1H-pyrazol-3-yl)benzamide [0265] 1 H NMR (400 MHz, CD 3 OD) δ ppm 2.36 (s, 3 H) 3.68 (t, J=5.69 Hz, 2 H) 3.78 (t, J=5.59 Hz, 2 H) 6.65 - 6.72 (m, 1 H) 7.20 - 7.27 (m, 1 H) 7.59 - 7.70 (m, 2 H) 7.87 (d, J=2.38 Hz, 1 H) 8.27 (d, J=2.11 Hz, 1 H); ESI-MS m/z [M+H] + =381.3. [0266] EXAMPLE 8: N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2- yl)amino)-5-(2-methyl-2H-1,2,3-triazol-4-yl)pyridin-3-yl)-4- methylbenzamide and [0267] EXAMPLE 9: N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2- yl)amino)-5-(1-methyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl)-4- methylbenzamide [0268] STEP A: 2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3-triazole [0269] To a solution of 2H-1,2,3-triazole (6.52 g, 94.40 mmol) in DCM (300 mL) were added DHP (9.53 g, 113.28 mmol) and PTSA (162.57 mg, 944.04 µmol) at 25°C. The mixture was stirred at 25°C for 18 hours. Solid sodium hydride (38 mg) was added and the mixture was stirred at 25°C for 1 hour. The mixture was filtered, and the filtrate was concentrated to give a residue. The residue was purified by column chromatography (SiO 2 , EtOAc/Petroleum ether 17% to 50%) to give the title compound (10 g, 69%) and by-product, 1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,3-triazole (5 g), as colorless oils. 1 H NMR (400 MHz, CDCl 3 ) δ ppm 1.73 - 1.75 (m, 3 H) 2.05 - 2.12 (m, 2 H) 2.42 - 2.46 (m, 1 H) 3.74 - 3.78 (m, 1 H) 4.02 - 4.06 (m, 1 H) 5.73 - 5.76 (m, 1 H) δ 7.68 (s, 2 H); ESI-MS m/z [M+Na] + =176.2. 1 H NMR (400 MHz, CDCl 3 ) δ ppm 1.68 - 1.70 (m, 3 H) 2.05 - 2.15 (m, 1 H) 2.16 - 2.18 (m, 2 H) 3.73 - 3.78 (m, 1 H) 4.00 - 402 (m, 1 H) 5.74 - 5.77 (m, 1 H) 7.73 (s, 1 H) 7.76 (s, 1 H); ESI-MS m/z [M+Na] + =176.2. [0270] STEP B: 2-(tetrahydro-2H-pyran-2-yl)-4-(tributylstannyl)-2H-1,2,3-tr iazole [0271] A solution of n-BuLi (2.5 M, 24.69 mL, 1.05 eq) in hexane was added to a stirred solution of 2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3-triazole (9 g, 58.75 mmol) in THF (270 mL) over a period of 15 minutes under N2 at -78°C. The resulting solution was stirred at - 78°C for 30 minutes. Next, n-Bu 3 SnCl (22.95 g, 70.51 mmol) was added dropwise at -78°C and the mixture was stirred at -78°C for 1 hour and then warmed to 0°C over 1 hour. The solution was quenched with a saturated solution of ammonium chloride (200 mL). Ethyl acetate (500 mL) was added and the solution was stirred for 10 minutes. The organic layer was washed with ice-water, dried over anhydrous Na 2 SO 4 and concentrated to give a residue. The residue was purified by column chromatography (SiO2, EtOAc/Petroleum ether 0% to 2%). The title compound was obtained as a colorless oil (20 g, 55%). 1 H NMR (400 MHz, CDCl3) δ ppm 1.32 - 1.38 (m, 21 H) 1.40-1.65 (m, 6 H) 1.65-1.75 (m, 3 H) 2.09 - 2.14 (m, 2 H) 2.45 - 2.49 (m, 1 H) 3.72 - 3.78 (m, 1 H) 4.03 - 4.07 (m, 1 H) 5.78 - 5.81 (m, 1 H) 7.64 (s, 1 H). [0272] STEP C: 5-chloro-2-fluoro-3-(2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3-t riazol-4- yl)pyridine [0273] A mixture of 2-(tetrahydro-2H-pyran-2-yl)-4-(tributylstannyl)-2H-1,2,3-tr iazole (6.90 g, 11.31 mmol), 3-bromo-5-chloro-2-fluoropyridine (2.57 g, 12.21 mmol) and Pd(PPh 3 ) 4 (653.26 mg, 565.32 µmol) in toluene (100 mL) was de-gassed and then heated to 110°C for 3 hours under N2. The reaction mixture was quenched with a saturated solution of NH 4 Cl (100 mL) at 25°C. The mixture was extracted with ethyl acetate and the organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to give a residue. The residue was purified by column chromatography (SiO 2 , EtOAc/Petroleum ether 10% to 25%). The title compound was obtained as a white solid (2.3 g, 66%). 1 H NMR (400 MHz, CDCl 3 ) δ ppm 1.71 - 1.78 (m, 2 H) 2.10 - 2.18 (m, 2 H) 2.44 - 2.50 (m, 1 H) 3.72 - 3.81 (m, 2 H) 4.04 - 4.08 (m, 1 H) 5.56 - 5.79 (m, 1 H) 8.08 (d, J=4.4 Hz, 1 H) 8.13 (s, 1 H) 8.47 (dd, J=8.0, 2.4 Hz, 1 H ); ESI-MS m/z [M+H] + =283.1 [0274] STEP D: 2-((5-chloro-3-(2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3-triazo l-4- yl)pyridin-2-yl)amino)-2-methylpropan-1-ol [0275] To a solution of 5-chloro-2-fluoro-3-(2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3- triazol-4-yl)pyridine (1.8 g, 5.80 mmol) and 2-amino-2-methylpropan-1-ol (619.98 mg, 6.96 mmol) in DMSO (18 mL) was added DIPEA (1.50 g, 11.59 mmol). The mixture was stirred at 170°C for 6 hours. The mixture was poured into ice-water and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to give a residue. The residue was purified by column chromatography (SiO 2 , EtOAc/Petroleum ether 10% to 25%). The title compound was obtained as a brown solid (660 mg, 24.6%). 1 H NMR (400 MHz, CDCl 3 ) δ ppm 1.47 (s, 6 H) 1.81 - 1.75 (m, 2 H) 2.20 - 2.13 (m, 2 H) 2.47 - 2.38 (m, 1 H) 3.71 (s, 1 H) 3.81 - 3.78 (m, 1 H) 4.05 - 4.02 (m, 1 H) 5.77 (dd, J=8.8, 2.4 Hz,1 H) 7.78 (d, J=1.6 Hz, 1 H) 7.89 (s, 1H) 8.00 (d, J=1.6 Hz, 2H ); ESI-MS m/z [M+H] + =352.1. [0276] STEP E: N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2-yl) amino)-5- (2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3-triazol-4-yl)pyridin- 3-yl)-4-methylbenzamide [0277] To a solution of 2-((5-chloro-3-(2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3-triazo l-4- yl)pyridin-2-yl)amino)-2-methylpropan-1-ol (600 mg, 1.29 mmol) and N-cyclopropyl-2- fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)benzamide (495.38 mg, 1.55 mmol) in dioxane (15 mL) and H2O (1.5 mL) was added XPhos Pd G3 (54.74 mg, 64.67 µmol) and Cs 2 CO 3 (1.05 g, 3.23 mmol). The mixture was stirred at 80°C for 6 hours under N2. Then the reaction was heated to 95°C and stirred for 6 hours. The reaction solution was diluted with ethyl acetate and washed with water. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to give a residue. The residue was purified by column chromatography (SiO 2 , EtOAc/Petroleum ether 25% to 50%). The title compound was obtained as a yellow solid (0.45 g, 68%). 1 H NMR (400 MHz, CDCl3) δ ppm 0.66 - 0.61 (m, 2 H) 0.91 - 0.86 (m, 2 H) 1.47 (s, 6 H) 1.83 - 1.66 (m, 5 H) 2.20 - 2.15 (m, 2 H) 2.33 (s, 1 H) 2.49 - 2.42 (m, 1 H) 2.95 - 2.93 (m, 1 H) 3.73 (s, 1 H) 3.80 - 3.79 (m, 1 H) 4.09 - 4.02 (m, 1 H) 5.77 (dd, J=8.6, 2.2 Hz, 1 H) 6.83 (d, J=13.2 Hz, 1 H) 7.03 (d, J=12.8 Hz, 1 H) 7.75 (d, J=2.0 Hz, 1 H) 8.01 - 7.92 (m, 4 H ); ESI-MS m/z [M+H] + =309.2. [0278] STEP F: N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2-yl) amino)-5- (2H-1,2,3-triazol-4-yl)pyridin-3-yl)-4-methylbenzamide

[0279] A solution of N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2- yl)amino)-5-(2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3-triazol-4 -yl)pyridin-3-yl)-4- methylbenzamide (0.45 g, 884.81 µmol) and PTSA (15.24 mg, 88.48 µmol) in MeOH (10 mL) was heated at 60°C and stirred for 3.5 hours. The solution was cooled to 25°C and HCl/MeOH (4 M, 1 mL) was added. The mixture was stirred at 60°C for 2 hours and then was concentrated, dissolved in ethyl acetate and washed with saturated aqueous NaHCO 3 solution and brine. The organic layer was filtered, dried over anhydrous Na2SO4 and concentrated to give a residue. The residue was purified by column chromatography (SiO 2 , EtOAc/Petroleum ether 33% to 67%). The title compound was obtained as a yellow solid (350 mg, crude). ESI-MS m/z [M+H] + =425.1 [0280] STEP G: N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2-yl) amino)-5- (2-methyl-2H-1,2,3-triazol-4-yl)pyridin-3-yl)-4-methylbenzam ide and N-cyclopropyl-2- fluoro-5-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(1-meth yl-1H-1,2,3-triazol-4- yl)pyridin-3-yl)-4-methylbenzamide [0281] To a solution of N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2- yl)amino)-5-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)-4-methylben zamide (0.2 g, 471.18 µmol) and MeI (8.74 g, 61.58 mmol) in CH3CN (2 mL) was added K2CO3 (130.24 mg, 942.35 µmol). The mixture was stirred at 20°C for 12 hours and then poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous Na 2 SO 4 and concentrated to give a residue. The residue was purified by preparative HPLC to give the title compounds as white solids. EXAMPLE 9 (21.7 mg): 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.62 - 0.66 (m, 2 H) 0.86 - 0.91 (m, 2 H) 1.49 (s, 6 H) 2.35 (s, 3 H) 2.93 - 2.96 (m, 1 H) 3.72 (s, 2 H) 4.19 (s, 3 H) 6.84 (d, J=12.8 Hz, 1 H) 7.03 (d, J=12.0 Hz, 1 H) 7.56 (d, J=2.4 Hz, 1 H) 7.80 (s, 1 H) 7.86 (s, 1 H) 7.94 - 7.96 (m, 2 H) 8.49 (s, 1H); ESI-MS m/z [M+H] + =439.2. EXAMPLE 8 (57.35 mg): 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.66 - 0.62 (m, 2 H) 0.86 - 0.91 (m, 2H) 1.48 (s, 6 H) 2.34 (s, 3 H) 2.93 - 2.96 (m, 1 H) 3.73 (s, 2 H) 4.28( s, 3 H) 6.84 (d, J=12.0 Hz, 1 H) 7.04 (d, J=12.8 Hz, 1 H) 7.73 (d, J=2.0 Hz, 1 H) 7.82 (s, 1 H) 7.90 (s, 1 H) 7.96 - 7.98 (m, 2 H); ESI-MS m/z [M+H] + =439.2. [0282] EXAMPLE 10: N-cyclopropyl-2-fluoro-5-(6-((2-hydroxyethyl)amino)-5-(1-met hyl- 1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide [0283] To a mixture of 2-((5-chloro-3-(1-methyl-1H-pyrazol-4-yl)pyridin-2- yl)amino)ethan-1-ol (50 g, 190.94 mmol) and N-cyclopropyl-2-fluoro-4-methyl-5-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (75.16 g, 229.13 mmol) in dioxane (1000 mL) and H2O (100 mL) were added K3PO4 (101.32 g, 477.35 mmol), Pd2(dba)3 (8.74 g, 9.55 mmol) and XPhos (18.20 g, 38.19 mmol) in one portion under N 2 . The reaction mixture was stirred at 110°C for 12 hours and then diluted with water and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to give a residue, which was purified by column chromatography (SiO 2 , EtOAc/Petroleum ether 10% to 100%) and (SiO 2 , MeOH/DCM 2% to 10%) to give crude product as a brown oil (180 g, 88.30%). The crude product was combined with product from other batches (243.8 g total) and was purified by preparative HPLC. The title compound was obtained as an off-white solid (202 g). 1 H NMR (400 MHz, CDCl3) δ ppm 0.58 - 0.67 (m, 2 H) 0.84 - 0.93 (m, 2 H) 2.33 (s, 3 H) 2.94 (m, 1 H) 3.56 - 3.67 (m, 2 H) 3.82 - 3.89 (m, 2 H) 3.99 (s, 3 H) 5.11 (s, 1 H) 5.32 (t, J=5.4 Hz, 1 H) 6.82 (d, J=11.8 Hz, 1 H) 7.01 (d, J=12.8 Hz, 1 H) 7.29 (d, J=2.4 Hz, 1 H) 7.56 (s, 1 H) 7.66 (d, J=0.6 Hz, 1 H) 7.97 - 7.92 (m, 2 H); ESI-MS m/z [M+H] + =410.1. [0284] EXAMPLE 11: (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino )-5- (1-methyl-1H-pyrazol-3-yl)pyridin-3-yl)-4-methylbenzamide [0285] STEP A: (S)-2-((3-bromo-5-chloropyridin-2-yl)amino)propan-1-ol [0286] A mixture of 3-bromo-5-chloro-2-fluoropyridine (25 g, 118.80 mmol), (S)-2- aminopropan-1-ol (10.71 g, 142.56 mmol) and DIPEA (30.71 g, 237.60 mmol) in DMSO (150 mL) was degassed and purged with N 2 (3 x) and then stirred at 150°C for 6 hours under N2. The reaction mixture was partitioned between H2O and EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue, which was purified by column chromatography (SiO 2 , EtOAc/Petroleum ether 10% to 100%). The title compound was obtained as a yellow oil (28.5 g, 82.76%); ESI-MS m/z [M+H] + =267.0. [0287] STEP B: (S)-2-((5-chloro-3-(1-methyl-1H-pyrazol-3-yl)pyridin-2-yl)am ino)propan- 1-ol [0288] To a mixture of (S)-2-((3-bromo-5-chloropyridin-2-yl)amino)propan-1-ol (250 mg, 941.50 µmol) and 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H- pyrazole (215.48 mg, 1.04 mmol) in dioxane (5 mL) and H2O (0.5 mL) were added K2CO3 (260.24 mg, 1.88 mmol) and Pd(dppf)Cl 2 (68.89 mg, 94.15 µmol) in one portion under N 2 . The reaction mixture was stirred at 90°C for 6 hours and then diluted with water and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to give a residue, which was purified by column chromatography (SiO 2 , EtOAc/Petroleum ether 10% to 100%). The title compound was obtained as a light yellow solid (256 mg, 95.4%); ESI-MS m/z [M+H] + =267.0. [0289] STEP C: (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino )-5-(1- methyl-1H-pyrazol-3-yl)pyridin-3-yl)-4-methylbenzamide [0290] To a mixture of (S)-2-((5-chloro-3-(1-methyl-1H-pyrazol-3-yl)pyridin-2- yl)amino)propan-1-ol (256 mg, 898.36 µmol) and N-cyclopropyl-2-fluoro-4-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (344.08 mg, 1.08 mmol) in dioxane (5 mL) and H 2 O (0.5 mL) were added K 2 CO 3 (248.32 mg, 1.80 mmol) and Xphos-Pd-G3 (38.02 mg, 44.92 µmol) in one portion under N2. The mixture was stirred at 95°C for 12 hours and then diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue, which was purified by column chromatography (SiO 2 , MeOH/DCM 1% to 4%). The resulting brown solid (350 mg) was further purified by preparative HPLC to give the title compound as a white solid (125.11 mg, 33.89%). 1 H NMR (400 MHz, CDCl3) δ ppm 0.59 - 0.69 (m, 2 H) 0.84 - 0.91 (m, 2 H) 1.38 (d, J=6.8 Hz, 4 H) 2.33 (s, 3H) 2.94 (m, 1 H) 3.70 (m, 1 H) 3.84 (dd, J=2.4, 10.8 Hz, 1 H) 3.97 (s, 3 H) 4.29 (m, 1 H) 6.59 (d, J=2.4 Hz, 1 H) 6.83 (d, J=12.2 Hz, 1 H) 7.02 (d, J=12.8 Hz, 1 H) 7.41 (d, J=2.4 Hz, 1 H) 7.69 (d, J=2.2 Hz, 1 H) 7.92 (d, J=2.2 Hz, 1 H) 7.97 (d, J=8.4 Hz, 1 H) 8.31 (d, J=4.8 Hz, 1 H); ESI-MS m/z [M+H] + =424.1. [0291] EXAMPLE 12: (R)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino )-5- (1-methyl-1H-pyrazol-3-yl)pyridin-3-yl)-4-methylbenzamide [0292] STEP A: (R)-2-((3-bromo-5-chloropyridin-2-yl)amino)propan-1-ol [0293] To a mixture of 3-bromo-5-chloro-2-fluoropyridine (10 g, 47.52 mmol) and (R)-2- aminopropan-1-ol (4.28 g, 57.03 mmol) in DMSO (50 mL) was added DIPEA (12.28 g, 95.04 mmol) in one portion under N 2 . The reaction mixture was stirred at 150°C for 6 hours and then poured into ice-water and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous Na 2 SO 4 , filtered, concentrated and purified by column chromatography (SiO2, EtOAc/Petroleum ether 25% to 33%). The title compound was obtained as a colorless oil (12 g, 95%). 1 H NMR (400 MHz, CDCl 3 ) δ ppm 1.28 (d, J=6.8 Hz, 3 H) 3.41 (s, 1 H) 3.62 - 3.65 (m, 1 H) 3.65 - 3.75 (m, 1 H) 4.11 - 4.20 (m, 1 H) 5.07 (d, J=3.2 Hz, 1H) 7.63 (d, J=2.0 Hz, 1 H) 7.96 (d, J=2.0 Hz, 1 H); ESI-MS m/z [M+H] + =267.0. [0294] STEP B: (R)-2-((5-chloro-3-(1-methyl-1H-pyrazol-3-yl)pyridin-2-yl)am ino)propan- 1-ol [0295] To a mixture of (R)-2-((3-bromo-5-chloropyridin-2-yl)amino)propan-1-ol (0.23 g, 866.18 µmol) and 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H- pyrazole (198.24 mg, 952.80 µmol) in dioxane (5 mL) and H 2 O (0.5 mL) were added Pd(dppf)Cl 2 (31.69 mg, 43.31 µmol) and K2CO3 (239.43 mg, 1.73 mmol) in one portion under N2. The reaction mixture was stirred at 90°C for 6 hours and then diluted with EtOAc and filtered. The filtrate was washed with water and brine, dried over anhydrous Na2SO4, concentrated and purified by column chromatography (SiO 2 , EtOAc/Petroleum ether 25% to 33%). The title compound was obtained as a yellow oil (0.22 g, 95%). 1 H NMR (400 MHz, CDCl3) δ ppm 1.32 (d, J=6.8 Hz, 3 H) 3.65 (dd, J=10.8, 7.6 Hz, 1 H) 3.79 (dd, J=10.8, 2.8 Hz, 1 H) 3.95 (s, 3 H) 4.18 - 4.26 (m, 1 H) 6.57 (d, J=2.4 Hz, 1 H) 7.41 (d, J=2.4 Hz, 1 H) 7.68 (d, J=2.4 Hz, 1 H) 7.92 (d, J=2.8 Hz, 1 H) 8.21 (d, J=4.4 Hz, 1 H); ESI-MS m/z [M+H] + =267.1. [0296] STEP C: (R)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino )-5-(1- methyl-1H-pyrazol-3-yl)pyridin-3-yl)-4-methylbenzamide [0297] To a mixture of (R)-2-((5-chloro-3-(1-methyl-1H-pyrazol-3-yl)pyridin-2- yl)amino)propan-1-ol (0.22 g, 824.82 µmol) and N-cyclopropyl-2-fluoro-4-methyl-5-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (315.92 mg, 989.78 µmol) in dioxane (8 mL) and H 2 O (0.8 mL) were added K 2 CO 3 (228.00 mg, 1.65 mmol) and XPhos Pd G3 (34.91 mg, 41.24 µmol) under N2. The mixture was stirred at 95°C for 12 hours and then diluted with EtOAc and filtered. The filtrate was washed with water and brine, dried over anhydrous Na2SO4, filtered, concentrated and purified by preparative HPLC. The title compound was obtained as a white solid (140.65 mg). 1 H NMR (400 MHz, CDCl3) δ ppm 0.61 - 0.66 (m, 2 H) 0.86 - 0.91 (m, 2 H) 1.37 (d, J=6.8 Hz, 3 H) 2.33 (s, 3 H) 2.91 - 2.98 (m, 1 H) 3.70 (dd, J=10.8, 8.0 Hz, 1 H) 3.84 (dd, J=10.8, 2.8 Hz, 1 H) 3.97 (s,3 H) 4.24 - 4.33 (m, 1 H) 5.89 (s, 1 H) 6.59 (d, J=2.8 Hz, 1 H) 6.83 (d, J=12.8 Hz, 1 H) 7.02 (d, J=12.8 Hz, 1 H) 7.41 (d, J=2.4 Hz, 1 H) 7.69 (d, J=2.4 Hz, 1 H) 7.92 (d, J=2.0 Hz, 1 H) 7.97 (d, J=8.4 Hz, 1 H) 8.31 (d, J=4.8 Hz, 1 H); ESI-MS m/z [M+H] + =424.2. [0298] EXAMPLE 13: N-cyclopropyl-2-fluoro-5-(6-((1- (hydroxymethyl)cyclopropyl)(methyl)amino)-5-(1-methyl-1H-pyr azol-4-yl)pyridin-3-yl)-4- methylbenzamide [0299] STEP A: (1-aminocyclopropyl)methanol [0300] To a mixture of LiAlH4 (2.50 g, 65.97 mmol) in THF (60 mL) was added methyl 1- aminocyclopropanecarboxylate (5 g, 32.98 mmol, HCl) in portions at 0°C under N 2 . The reaction mixture was stirred at 25°C for 2 hours and then quenched by addition of Na2SO4.10 H2O (5 g) in portions at 0-5°C. The mixture was stirred at 25°C for 0.5 hours and filtered. The filter cake was washed with MeOH/DCM (20 mL, 15%). The filtrate was concentrated under reduced pressure to give the title compound as a colorless oil (3 g, crude). 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.45 - 0.50 (m, 2 H) 0.51 - 0.56 (m, 2 H) 3.39 (s, 2 H). [0301] STEP B: (1-((3-bromo-5-chloropyridin-2-yl)amino)cyclopropyl)methanol [0302] To a mixture of 3-bromo-5-chloro-2-fluoropyridine (6.5 g, 30.89 mmol) and (1- aminocyclopropyl)methanol (2.96 g, 33.98 mmol) in DMSO (65 mL) was added DIPEA (11.98 g, 92.67 mmol) in one portion under N2. The reaction mixture was stirred at 150°C for 3 hours and then diluted with water (100 mL) and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue, which was purified by column chromatography (SiO 2 , EtOAc/Petroleum ether 5% to 25%). The title compound was obtained as a brown solid (3.5 g, 39%). ESI-MS m/z [M+H] + =278.8. [0303] STEP C: (1-((5-chloro-3-(1-methyl-1H-pyrazol-4-yl)pyridin-2- yl)amino)cyclopropyl)methanol [0304] To a solution of (1-((3-bromo-5-chloropyridin-2-yl)amino)cyclopropyl)methanol (500 mg, 1.80 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H- pyrazole (412.31 mg, 1.98 mmol) in dioxane (10 mL) and H 2 O (1 mL) were added K 2 CO 3 (497.96 mg, 3.60 mmol) and Pd(dppf)Cl2 (131.82 mg, 180.15 µmol) in one portion under N2. The reaction mixture was stirred at 90°C for 16 hours and then diluted with ethyl acetate (30 mL), washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography (SiO2, EtOAc/Petroleum ether 9% to 100%). The title compound was obtained as a brown oil (450 mg, 60.0%). ESI-MS m/z [M+H] + =279.0. [0305] STEP D: (1-((5-chloro-3-(1-methyl-1H-pyrazol-4-yl)pyridin-2- yl)amino)cyclopropyl)methyl acetate [0306] A solution of (1-((5-chloro-3-(1-methyl-1H-pyrazol-4-yl)pyridin-2- yl)amino)cyclopropyl)methanol (450 mg, 1.08 mmol) and Ac 2 O (220.85 mg, 2.16 mmol) in pyridine (5 mL) was stirred at 80°C for 4 hours and then concentrated. The resulting residue was dissolved with EtOAc and washed with water. The organic layer was dried over anhydrous Na2SO4, filtered, concentrated and purified by column chromatography (SiO2, EtOAc/Petroleum ether 5% to 50%). The title compound was obtained as a yellow oil (230 mg, 62.0%). ESI-MS m/z [M+H] + =321.1. [0307] STEP E: (1-((5-chloro-3-(1-methyl-1H-pyrazol-4-yl)pyridin-2- yl)(methyl)amino)cyclopropyl)methyl acetate [0308] To a solution of (1-((5-chloro-3-(1-methyl-1H-pyrazol-4-yl)pyridin-2- yl)amino)cyclopropyl)methyl acetate (230 mg, 670.41 µmol) in DMF (8 mL) was added NaH (53.63 mg, 1.34 mmol, 60% purity) at 0°C. The mixture was stirred at 0°C for 0.5 hours and then iodomethane (1.90 g, 13.41 mmol) was added. The reaction mixture was stirred at 25°C for 12 hours and then quenched with water, diluted with EtOAc and washed with water and brine. The organic layer was dried over Na 2 SO 4 , filtered and concentrated to give the title compound as a black brown oil (300 mg, crude). ESI-MS m/z [M+H] + =335.0. [0309] STEP F: (1-((5-chloro-3-(1-methyl-1H-pyrazol-4-yl)pyridin-2- yl)(methyl)amino)cyclopropyl)methanol [0310] A mixture of (1-((5-chloro-3-(1-methyl-1H-pyrazol-4-yl)pyridin-2- yl)(methyl)amino)cyclopropyl)methyl acetate (220 mg, 197.13 µmol) and K 2 CO 3 (54.49 mg, 394.27 µmol) in MeOH (10 mL) was stirred at 60°C for 1 hour and then concentrated under reduced pressure. Ethyl acetate (20 mL) and water (20 mL) were added and organic layer was separated. The aqueous phase was extracted with EtOAc and the combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography (SiO 2 , EtOAc/Petroleum ether 9% to 25%). The title compound was obtained as a yellow oil (55 mg, 94%). ESI-MS m/z [M+H] + =293.0. [0311] STEP G: N-cyclopropyl-2-fluoro-5-(6-((1- (hydroxymethyl)cyclopropyl)(methyl)amino)-5-(1-methyl-1H-pyr azol-4-yl)pyridin-3-yl)-4- methylbenzamide [0312] To a solution of (1-((5-chloro-3-(1-methyl-1H-pyrazol-4-yl)pyridin-2- yl)(methyl)amino)cyclopropyl)methanol (70 mg, 234.65 µmol) and N-cyclopropyl-2-fluoro- 4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benz amide (82.39 mg, 258.12 µmol) in dioxane (5 mL) and H2O (0.5 mL) were added K2CO3 (64.86 mg, 469.31 µmol) and XPhos Pd G3 (19.86 mg, 23.47 µmol) in one portion under N 2 . The mixture was stirred at 95°C for 12 hours and then diluted with H2O (30 mL) and extracted with EtOAc. The combined organic layers were dried over Na 2 SO 4 , filtered, concentrated under reduced pressure and purified by preparative HPLC. The title compound was obtained as a white solid (30.14 mg). 1 H NMR (400 MHz, CDCl3) δ ppm 0.61-0.66 (m, 2 H) 0.80 (s, 2 H) 0.86 - 0.92 (m, 2 H) 0.92 - 0.99 (m, 2 H) 2.34 (s, 3 H) 2.72 (s, 3H) 2.95 (dt, J=3.6, 7.2 Hz, 1 H) 3.73 (s, 2 H) 3.96 (s, 3 H) 6.82 (d, J=12.0 Hz, 1 H) 7.04 (d, J=12.8 Hz, 1 H) 7.47 - 7.51 (m, 2 H) 7.59 (s, 1 H) 7.96 (d, J=8.0 Hz, 1 H) 8.04 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =450.1. [0313] EXAMPLE 14: N-cyclopropyl-2-fluoro-5-(6-((2-hydroxyethyl)amino)-5-(1H- pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide [0314] STEP A: 2-((5-chloro-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl )pyridin-2- yl)amino)ethan-1-ol [0315] To a solution of 2-((3-bromo-5-chloropyridin-2-yl)amino)ethan-1-ol (1 g, 3.98 mmol), 1-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-di oxaborolan-2-yl)-1H- pyrazole (1.22 g, 4.37 mmol) in dioxane (10 mL) and H2O (1 mL) were added K2CO3 (1.10 g, 7.95 mmol) and Pd(dppf)Cl 2 (145.46 mg, 198.80 µmol) in one portion under N 2 . The reaction mixture was stirred at 90°C for 12 hours and then partitioned between H2O (100 mL) and ethyl acetate. The combined organic layers were washed with brine, dried over Na 2 SO 4 , filtered, concentrated under reduced pressure and purified by column chromatography (SiO2, EtOAc/Petroleum ether 20% to 25%). The title compound was obtained as a brown oil (1 g, 76%). ESI-MS m/z [M+H] + =323.1. [0316] STEP B: N-cyclopropyl-2-fluoro-5-(6-((2-hydroxyethyl)amino)-5-(1-(te trahydro- 2H-pyran-2-yl)-1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzami de [0317] To a solution of 2-((5-chloro-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4- yl)pyridin-2-yl)amino)ethan-1-ol (500 mg, 1.55 mmol) and N-cyclopropyl-2-fluoro-4-methyl- 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (593.29 mg, 1.86 mmol) in dioxane (5 mL) and H 2 O (0.5 mL) were added K 3 PO 4 (822.00 mg, 3.87 mmol), XPhos (147.69 mg, 309.80 µmol) and Pd2(dba)3 (70.92 mg, 77.45 µmol) in one portion under N2. The reaction mixture was stirred at 110°C for 12 hours and then partitioned between H 2 O and ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered, concentrated under reduced pressure and purified by column chromatography (SiO 2 , EtOAc/Petroleum ether 30% to 100%). The title compound was obtained as a yellow solid (600 mg, 71.2%). ESI-MS m/z [M+H] + =480.1. [0318] STEP C: N-cyclopropyl-2-fluoro-5-(6-((2-hydroxyethyl)amino)-5-(1H-py razol-4- yl)pyridin-3-yl)-4-methylbenzamide [0319] A mixture of N-cyclopropyl-2-fluoro-5-(6-((2-hydroxyethyl)amino)-5-(1- (tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)pyridin-3-yl)-4-m ethylbenzamide (100 mg, 183.72 µmol) and HCl/dioxane (4 M, 1 mL) in EtOH (2 mL) was degassed and purged with N2 (3 x). The reaction mixture was stirred at 25°C for 1 hour under N2 atmosphere and then concentrated under reduced pressure and purified by preparative HPLC. The title compound was obtained as a yellow solid (10 mg). 1 H NMR (400 MHz, CD3OD) δ ppm 0.60 - 0.67 (m, 2 H) 0.78 - 0.86 (m, 2 H) 2.33 (s, 3 H) 2.82 - 2.87 (m, 1 H) 3.52 - 3.61 (m, 2 H) 3.77 (t, J=5.2 Hz, 2 H) 7.15 (d, J=11.6 Hz, 1 H) 7.46 (d, J=2.4 Hz, 1 H) 7.52 (d, J=7.6 Hz, 1 H) 7.88 (d, J=2.4 Hz, 1 H) 7.91 (s, 2 H); ESI-MS m/z [M+H] + =396.2. [0320] Examples 15 to 69, below, were prepared like Examples 8 to 14. [0321] EXAMPLE 15: N-cyclopropyl-5-(5-ethoxy-6-((1-hydroxy-2-methylpropan-2- yl)amino)pyridin-3-yl)-2-fluoro-4-methylbenzamide [0322] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.51 - 0.57 (m, 2 H) 0.64 - 0.71 (m, 2 H) 1.31 - 1.39 (m, 9 H) 2.29 (s, 3 H) 2.78 - 2.86 (m, 1 H) 3.48 (s, 2 H) 4.04 - 4.11 (m, 2 H) 5.33 (s, 1 H) 5.40 (s, 1 H) 6.98 (d, J=1.6 Hz, 1 H) 7.20 (d, J=11.6 Hz, 1 H) 7.35 (d, J=7.6 Hz, 1 H) 7.54 (d, J=1.6 Hz, 1 H) 8.28 (d, J=4.0 Hz, 1 H); ESI-MS m/z [M+H] + =402.3. [0323] EXAMPLE 16: N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2- yl)amino)-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-4-methyl benzamide [0324] 1 H NMR (400 MHz, CDCl3) δ ppm 0.61 – 0.65 (m, 2 H) 0.86 – 0.91 (m, 2 H) 1.36 (s, 6 H) 2.34 (s, 3 H) 2.92 – 2.97 (m, 1 H) 3.67 (s, 2 H) 3.99 (s, 3 H) 4.97 (s, 1 H) 6.82 (d, J=11.6 Hz, 1 H) 7.03 (d, J=12.8 Hz, 1 H) 7.28 (d, J=2.4 Hz, 1 H) 7.52 (s, 1 H) 7.65 (s, 1 H) 7.67 (s, 1 H) 7.90 (d, J=2.4 Hz, 1 H) 7.94 (d, J=8.0 Hz, 1 H); ESI-MS m/z [M+H] + =438.2. [0325] EXAMPLE 17: N-cyclopropyl-5-(5-(ethylamino)-6-((1-hydroxy-2-methylpropan -2- yl)amino)pyridin-3-yl)-2-fluoro-4-methylbenzamide [0326] Title compound was obtained as a formic acid salt. 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.53 - 0.55 (m, 2 H) 0.67 - 0.69 (m, 2 H) 1.24 (t, J=7.2 Hz, 3 H) 1.43 (s, 6 H) 2.29 (s, 3 H) 2.79 - 2.84 (m, 1 H) 3.14 - 3.19 (m, 2 H) 3.66 (s, 2 H) 6.83 (s, 1 H) 7.26 (d, J=11.2 Hz, 1 H) 7.42 - 7.45 (m, 2 H) 7.55 (s, 1 H) 8.34 (d, J=3.6 Hz, 1 H): ESI-MS m/z [M+H] + =401.2. [0327] EXAMPLE 18: N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2-yl- 1,1- d2)amino)-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-4-methyl benzamide [0328] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.48 - 0.56 (m, 2 H) 0.63 - 0.73 (m, 2 H) 1.38 (s, 6 H) 2.30 (s, 3 H) 2.81 (tq, J=7.6, 4.0 Hz, 1 H) 3.88 (s, 3 H) 5.21 (s, 1 H) 5.42 (s, 1 H) 7.20 (d, J=11.6 Hz, 1 H) 7.34 - 7.39 (m, 2 H) 7.72 (s, 1 H) 7.93 (d, J=2.4 Hz, 1 H) 8.00 (s, 1 H) 8.25 (d, J=4.0 Hz, 1 H); ESI-MS m/z [M+H] + =440.3. [0329] EXAMPLE 19: 5-(5-(cyclopropylcarbamoyl)-4-fluoro-2-methylphenyl)-2-((1- hydroxy-2-methylpropan-2-yl-1,1-d 2 )amino)-N,N-dimethylnicotinamide [0330] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.53 - 0.55 (m, 2 H) 0.66 - 0.79 (m, 2 H) 1.36 (s, 6 H) 2.23 (s, 3 H) 2.80 - 2.82 (m, 1 H) 2.97 (s, 6 H) 5.13 (s, 1 H) 6.08 (s, 1 H) 7.23 (d, J=11.6 Hz, 1 H) 7.36 (d, J=7.2 Hz, 1 H) 7.46 (d, J=2.4 Hz, 1 H) 8.08 (d, J=2.4 Hz, 1 H) 8.31 (d, J=4.0 Hz, 1 H); ESI-MS m/z [M+H] + =431.2. [0331] EXAMPLE 20: N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2- yl)amino)-5-isopropoxypyridin-3-yl)-4-methylbenzamide [0332] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.51 - 0.57 (m, 2 H) 0.65 - 0.71 (m, 2 H) 1.28 (d, J=6.0 Hz, 6 H) 1.37 (s, 6 H) 2.29 (s, 3 H) 2.78 - 2.85 (m, 1 H) 3.47 (s, 2 H) 4.59 - 4.66 (m, 1 H) 5.40 (s, 2 H) 7.02 (d, J=1.6 Hz, 1 H) 7.20 (d, J=11.6 Hz, 1 H) 7.35 (d, J=7.6 Hz, 1 H) 7.54 (d, J=2.0 Hz, 1 H) 8.27 (d, J=4.0 Hz, 1 H); ESI-MS m/z [M+H] + =416.2. [0333] EXAMPLE 21: N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2-yl- 1,1- d2)amino)-5-isopropoxypyridin-3-yl)-4-methylbenzamide [0334] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.52 - 0.55 (m, 2 H) 0.66 - 0.70 (m, 2 H) 1.28 (d, J=6.0 Hz, 6 H) 1.36 (s, 6 H) 2.29 (s, 3 H) 2.78 - 2.85 (m, 1 H) 4.59 - 4.65 (m, 1 H) 5.39 (s, 1 H) 7.02 (d, J=1.6 Hz, 1 H) 7.20 (d, J=11.2 Hz, 1 H) 7.35 (d, J=7.6 Hz, 1 H) 7.54 (d, J=1.6 Hz, 1 H) 8.29 (d, J=4.0 Hz, 1 H); ESI-MS m/z [M+H] + =418.2. [0335] EXAMPLE 22: N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5- (1- methyl-1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide [0336] 1 H NMR (400 MHz, CDCl3) δ ppm 0.58 - 0.69 (m, 2 H) 0.82 - 0.92 (m, 2 H) 1.24 (d, J=6.8 Hz, 3 H) 2.33 (s, 3 H) 2.94 (m, 1 H) 3.61 (dd, J=7.8, 10.8 Hz, 1 H) 3.81 (dd, J=2.7, 10.8 Hz, 1 H) 4.00 (s, 3 H) 4.24 (d, J=5.0 Hz, 1 H) 4.96 (d, J=5.0 Hz, 1 H) 6.81 (d, J=13.6 Hz, 1 H) 7.02 (d, J=12.8 Hz, 1 H) 7.29 - 7.33 (m, 1 H) 7.56 (s, 1 H) 7.67 (s, 1 H) 7.91 - 7.97 (m, 2 H); ESI-MS m/z [M+H] + =424.3. [0337] EXAMPLE 23: N-cyclopropyl-2-fluoro-5-(6-((1- (hydroxymethyl)cyclopropyl)amino)-5-(1-methyl-1H-pyrazol-4-y l)pyridin-3-yl)-4- methylbenzamide [0338] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.60 - 0.66 (m, 2 H) 0.78 - 0.83 (m, 2 H) 0.88 (m, 2 H) 1.00 - 1.06 (m, 2 H) 2.33 (s, 3 H) 2.94 (m, 1 H) 3.70 (s, 2 H) 3.98 (s, 3 H) 5.28 - 5.35 (m, 1 H) 6.77 - 6.88 (m, 1 H) 7.02 (d, J=12.8 Hz, 1 H) 7.50 (s, 1 H) 7.59 (s, 1 H) 7.93 (d, J=8.2 Hz, 1 H) 7.98 (d, J=2.0 Hz, 1 H); ESI-MS m/z [M+H] + =436.3. [0339] EXAMPLE 24: N-cyclopropyl-2-fluoro-5-(6-((2-(hydroxymethyl)propan-2-yl- 1,1,1,3,3,3-d 6 )amino)-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-4-me thylbenzamide [0340] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.51 - 0.57 (m, 2 H) 0.65 - 0.71 (m, 2 H) 2.31 (s, 3 H) 2.82 (tq, J=8.0, 4.0 Hz, 1 H) 3.46 (s, 2 H) 3.89 (s, 3 H) 5.42 (s, 1 H) 7.21 (d, J=11.6 Hz, 1 H) 7.33 - 7.40 (m, 2 H) 7.73 (s, 1 H) 7.94 (d, J=2.4 Hz, 1 H) 8.01 (s, 1 H) 8.27 (d, J=4.0 Hz, 1 H); ESI-MS m/z [M+H] + =444.3. [0341] EXAMPLE 25: N-cyclopropyl-2-fluoro-5-(6-((2-hydroxyethyl-1,1,2,2-d 4 )amino)-5- (1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide [0342] 1 H NMR (500 MHz, DMSO-d 6 ) δ ppm 0.55 (dd, J=3.93, 2.36 Hz, 2 H) 0.68 (dd, J=7.07, 2.36 Hz, 2 H) 2.30 (s, 3 H) 2.75 - 2.89 (m, 1 H) 3.90 (s, 3 H) 4.69 (s, 1 H) 5.80 (s, 1 H) 7.20 (d, J=11.32 Hz, 1 H) 7.38 (d, J=7.23 Hz, 1 H) 7.40 (d, J=2.20 Hz, 1 H) 7.73 - 7.76 (m, 1 H) 7.95 (d, J=2.20 Hz, 1 H) 8.04 (s, 1 H) 8.24 - 8.29 (m, 1 H); ESI-MS m/z [M+H] + =414.2. [0343] EXAMPLE 26: N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2- yl)amino)-5-(4H-1,2,4-triazol-4-yl)pyridin-3-yl)-4-methylben zamide [0344] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.62 - 0.64 (m, 2 H) 0.86 - 0.90 (m, 2 H) 1.37 (s, 6 H) 2.35 (s, 3 H) 2.96 -2.93 (m, 1 H) 3.67 (s, 2 H) 4.32 (s, 1 H) 6.81 (d, J=12.0 Hz, 1 H) 7.05 (d, J=12.8 Hz, 1 H) 7.35 (d, J=2.4 Hz, 1 H) 7.94 (d, J=8.0 Hz, 1 H) 8.15 (d, J=2.0 Hz, 1 H) 8.37 (s, 2 H); ESI-MS m/z [M+H] + =425.3. [0345] EXAMPLE 27: N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2- yl)amino)-5-(1-methyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl)-4- methylbenzamide [0346] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.62 - 0.66 (m, 2 H) 0.86 - 0.91 (m, 2 H) 1.49 (s, 6 H) 2.35 (s, 3 H) 2.93 -2.96 (m, 1 H) 3.72 (s, 2 H) 4.19 (s, 3 H) 6.84 (d, J=12.8 Hz, 1 H) 7.03 (d, J=12.0 Hz, 1 H) 7.56 (d, J=2.4 Hz, 1 H) 7.80 (s, 1 H) 7.86 (s, 1 H) 7.94 - 7.96 (m, 2 H) 8.49 (s, 1H); ESI-MS m/z [M+H] + =439.2. [0347] EXAMPLE 28: N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2- yl)amino)-5-(1H-imidazol-1-yl)pyridin-3-yl)-4-methylbenzamid e [0348] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.61 - 0.65 (m, 2 H) 0.86 - 0.91 (m, 2 H) 1.33 (s, 6 H) 2.35 (s, 3 H) 2.92 -2.96 (m, 1 H) 3.67 (s, 2 H) 4.44 (s, 1 H) 5.32 (s, 1 H) 6.81 (d, J=11.2 Hz, 1 H) 7.04 (d, J=12.8 Hz, 1 H) 7.13 (s, 1 H) 7.33 (s, 1 H) 7.37 (d, J=2.0 Hz, 1 H) 7.70 (s, 1 H) 7.94 (d, J=8.0 Hz, 1 H) 8.08 (d, J=2.0 Hz, 1 H); ESI-MS m/z [M+H] + =424.2. [0349] EXAMPLE 29: N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2- yl)amino)-5-(1H-pyrazol-1-yl)pyridin-3-yl)-4-methylbenzamide [0350] 1 H NMR (400 MHz, CDCl3) δ ppm 0.63 - 0.66 (m, 2 H) 0.87 - 0.91 (m, 2 H) 1.40 (s, 6 H) 2.35 (s, 3 H) 2.93 - 2.96 (m, 1 H) 3.70 (s, 2 H) 6.50 (t, J=2.0 Hz, 1 H) 6.82 (d, J=12.8 Hz, 1 H) 7.02 (d, J=12.8 Hz, 1 H) 7.30 (s, 1 H) 7.38 (d, J=2.4 Hz, 1 H) 7.77 (d, J=2.4 Hz, 1 H) 7.79 (d, J=1.6 Hz, 1 H) 7.95 - 7.98 (m, 2 H); ESI-MS m/z [M+H] + =424.2. [0351] EXAMPLE 30: N-cyclopropyl-2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2- yl)amino)-5-(1-(methyl-d 3 )-1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide [0352] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.53 - 0.55 (m, 2 H) 0.67 - 0.69 (m, 2 H) 1.39 (s, 6 H) 2.31 (s, 3 H) 2.80 - 2.83 (m, 1 H) 5.43 (s, 1 H) 7.22 (d, J=11.2 Hz, 1 H) 7.37 - 7.38 (m, 2 H) 7.73 (s, 1 H) 7.95 (d, J=2.4 Hz, 1 H) 8.01 (s, 1 H) 8.27 (d, J=3.6 Hz, 1 H); ESI- MS m/z [M+H] + =441.3. [0353] EXAMPLE 31: N-cyclopropyl-2-fluoro-5-(6-((2-(hydroxymethyl)propan-2-yl- 1,1,1,3,3,3-d 6 )amino)-5-(1-(methyl-d 3 )-1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide [0354] 1 H NMR (400 MHz, CDCl3) δ ppm 0.59 - 0.66 (m, 2 H) 0.85 - 0.91 (m, 2 H) 2.34 (s, 3 H) 2.94 (tq, J=7.2, 3.6 Hz, 1 H) 3.66 (s, 2 H) 4.96 (s, 1 H) 6.81 (d, J=12.8 Hz, 1 H) 7.01 (d, J=12.8 Hz, 1 H) 7.28 (d, J=2.4 Hz, 1 H) 7.52 (s, 1 H) 7.64 (s, 1 H) 7.90 (d, J=2.4 Hz, 1 H) 7.93 (d, J=8.0 Hz, 1 H); ESI-MS m/z [M+H] + =447.2. [0355] EXAMPLE 32: N-cyclopropyl-2-fluoro-5-(4-(2-hydroxyethyl)-3,4-dihydro-2H- pyrido[3,2-b][1,4]oxazin-7-yl)-4-methylbenzamide [0356] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.50 - 0.57 (m, 2 H) 0.65 - 0.74 (m, 2 H) 2.27 (s, 3 H) 2.80 - 2.82 (m, 1 H) 3.55 - 3.69 (m, 6 H) 4.20 (t, J=3.6 Hz, 2 H) 4.75 (s, 1 H) 6.98 (d, J=1.6 Hz, 1 H) 7.20 (d, J=11.6 Hz, 1 H) 7.32 (d, J=7.6 Hz, 1 H) 7.62 (d, J=1.6 Hz, 1 H) 8.28 (d, J=3.6 Hz, 1 H); ESI-MS m/z [M+H] + =372.2. [0357] EXAMPLE 33: (R)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino )-5- (1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide [0358] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 7.93-7.91 (m, 2H) 7.66 (s, 1H) 7.55 (s, 1H) 7.27 (d, J=2.4 Hz, 1H) 7.01 (d, J=12.4 Hz, 1H) 6.82 (d, J=13.6 Hz, 1H) 5.28 (s, 1H) 4.90 (d, J=4.8 Hz, 1H) 4.20-4.16 (m, 1H) 3.99 (s, 3H) 3.79 (dd, J=10.8, 2.4 Hz, 1H) 3.63-3.60 (m, 1H) 2.95-2.92 (m, 1H) 2.32 (s, 3H) 1.23 (J=6.8 Hz, 3H) 0.90-0.86 (m, 2H) 0.65-0.62 (m, 2H); ESI-MS m/z [M+H] + =424.5. [0359] EXAMPLE 34: (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino )-5- (1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide [0360] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 8.27 (d, J=4.4 Hz, 1 H) 8.02 (s, 1 H) 7.94 (d, J=2.4Hz, 1 H) 7.73 (s, 1 H) 7.39 – 7.37 (m, 2 H) 7.23 (d, J=12.0 Hz, 1 H) 5.39 (d, J=8.0 Hz, 1 H) 4.79 (t, J=5.6 Hz, 1 H) 4.19 – 4.14 (m, 1 H) 3.89 (s, 3 H) 3.52 – 3.42 (m, 1 H) 2.85 – 2.78 (m, 1 H) 2.30 (s, 3 H) 1.16 (d, J=6.8 Hz, 3 H) 0.70– 0.65 (m, 2 H) 0.56 – 0.52 (m, 2 H); ESI-MS m/z [M+H] + =424.5. [0361] EXAMPLE 35: N-cyclopropyl-5-(1-ethyl-1,2,3,5-tetrahydropyrido[2,3- e][1,4]oxazepin-7-yl)-2-fluoro-4-methylbenzamide [0362] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.60 - 0.67 (m, 2 H) 0.78 - 0.84 (m, 2 H) 1.26 (t, J=7.2 Hz, 3 H) 2.31 (s, 3 H) 2.82 - 2.88 (m, 1 H) 3.35 - 3.37 (m, 2 H) 3.62 (q, J=7.2 Hz, 2 H) 3.86 - 3.91 (m, 2 H) 4.59 (s, 2 H) 7.14 (d, J=11.6 Hz, 1 H) 7.45 (d, J=2.4 Hz, 1 H) 7.49 (d, J=7.6 Hz, 1 H) 8.03 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =370.2. [0363] EXAMPLE 36: N-cyclopropyl-2-fluoro-5-(6-((1- (hydroxymethyl)cyclopropyl)amino)-5-(1-methyl-1H-pyrazol-3-y l)pyridin-3-yl)-4- methylbenzamide [0364] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.62 – 0.66 (m, 2 H) 0.86 – 0.91 (m, 4 H) 1.04 – 1.07 (m, 2 H) 2.33 (s, 3 H) 2.93 – 2.97 (m, 1 H) 3.77 (s, 2 H) 3.96 (s, 3 H) 6.57 (d, J=2.4 Hz, 1 H) 6.81 – 6.91 (m, 2 H) 7.04 (d, J=12.8 Hz, 1 H) 7.39 (d, J=2.4 Hz, 1 H) 7.67 (d, J=2.0 Hz, 1 H) 7.95 – 7.97 (m, 2 H) 8.61 (s, 1 H); ESI-MS m/z [M+H] + =436.2. [0365] EXAMPLE 37: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (isoxazol-5-yl)pyridin-3-yl)-4-methylbenzamide [0366] 1 H NMR (400 MHz, CDCl3) δ ppm 0.58 - 0.68 (m, 2 H) 0.85 - 0.92 (m, 2 H) 1.47 (s, 6 H) 2.35 (s, 3 H) 2.92 (m, 1 H) 3.73 (s, 2 H) 6.21 (s, 1 H) 6.25 (s, 1 H) 6.52 (d, J=1.8 Hz, 1 H) 7.03 (m, 1 H) 7.35 (d, J=8.0 Hz, 1 H) 7.59 (d, J=1.8 Hz, 1 H) 7.64 (m, 1 H) 7.74 (d, J=2.4 Hz, 1 H) 8.10 (d, J=2.4 Hz, 1 H) 8.36 (d, J=2.0 Hz, 1 H); ESI-MS m/z [M+H] + =407.2. [0367] EXAMPLE 38: (S)-N-cyclopropyl-5-(5-(1-ethyl-1H-pyrazol-4-yl)-6-((1- hydroxypropan-2-yl)amino)pyridin-3-yl)-2-fluoro-4-methylbenz amide [0368] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.60 – 0.64 (m, 2 H) 0.85 – 0.89 (m, 2 H) 1.22 – 1.24 (m, 3 H) 1.55 (t, J=7.2 Hz, 3 H) 2.32 (s, 3 H) 2.90 – 2.96 (m, 1 H) 3.59 – 3.63 (m, 1 H) 3.76 – 3.80 (m, 1 H) 4.15 – 4.20 (m, 1 H) 4.22 – 4.27 (m, 2 H) 4.93 (d, J=5.2 Hz, 1 H) 5.36 (s, 1 H) 6.84 (d, J=11.2 Hz, 1 H) 7.01 (d, J=12.8 Hz, 1 H) 7.29 (d, J=2.4 Hz, 1 H) 7.58 (s, 1 H) 7.68 (s, 1 H) 7.91 – 7.93 (m, 2 H); ESI-MS m/z [M+H] + =438.2. [0369] EXAMPLE 39: (R)-N-cyclopropyl-5-(5-(1-ethyl-1H-pyrazol-4-yl)-6-((1- hydroxypropan-2-yl)amino)pyridin-3-yl)-2-fluoro-4-methylbenz amide [0370] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.61 - 0.65 (m, 2 H) 0.85 - 0.91 (m, 2 H) 1.24 (d, J=7.2 Hz, 3 H) 1.56 (t, J=7.4 Hz, 3 H) 2.33 (s, 3 H) 2.92-2.91 (m, 1 H) 3.62 (dd, J=10.8, 7.6 Hz, 1 H) 3.79 (dd, J=10.8, 2.4 Hz, 1 H) 4.15 - 4.22 (m, 1 H) 4.26 (q, J=7.2 Hz, 2 H) 4.92 (d, J=5.2 Hz, 1 H) 5.34 (s, 1 H) 6.82 (d, J=13.2 Hz, 1 H) 7.01 (d, J=12.8 Hz, 1 H) 7.29 (d, J=2.4 Hz, 1 H) 7.59 (s, 1 H) 7.69 (s, 1 H) 7.91 - 7.95 (m, 2 H); ESI-MS m/z [M+H] + =438.2. [0371] EXAMPLE 40: N-cyclopropyl-5-(5-(1-ethyl-1H-pyrazol-4-yl)-6-((1- (hydroxymethyl)cyclopropyl)amino)pyridin-3-yl)-2-fluoro-4-me thylbenzamide [0372] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.62 - 0.64 (m, 2 H) 0.79 - 0.82 (m, 2 H) 0.86 - 0.91 (m, 2 H) 1.02 - 1.05 (m, 2 H) 1.54 (t, J=7.2 Hz, 3 H) 2.33 (s, 3 H) 2.92 - 2.96 (m, 1 H) 3.70 (s, 2 H) 4.22 - 4.27 (m, 2 H) 5.31 (s, 1 H) 6.46 (s, 1 H) 6.79 (d, J=12.8 Hz, 1 H) 6.99 (d, J=12.4 Hz, 1 H) 7.28 (d, J=2.4 Hz, 1 H) 7.53 (s, 1 H) 7.61 (s, 1 H) 7.93 (d, J=8.4 Hz, 1 H) 7.97 (d, J=2.0 Hz, 1 H); ESI-MS m/z [M+H] + =450.1. [0373] EXAMPLE 41: (S)-N-cyclopropyl-2-fluoro-5-(5-(1-(2-hydroxyethyl)-1H-pyraz ol-4- yl)-6-((1-hydroxypropan-2-yl)amino)pyridin-3-yl)-4-methylben zamide [0374] 1 H NMR (400 MHz, CDCl3) δ ppm 061 – 0.65 (m, 2 H) 0.85 – 0.90 (m, 2 H) 1.25 (d, J=6.8 Hz, 3 H) 2.32 (s, 3 H) 2.91 – 2.96 (m, 1 H) 3.15 (s, 1 H) 3.59 – 3.63 (m, 1 H) 3.78 – 3.80 (m, 1 H) 4.07 (d, J=4.4 Hz, 2 H) 4.31 – 4.34 (m, 2 H) 4.94 (d, J=5.6 Hz, 1 H) 5.20 (s, 1 H) 6.84 (d, J=12.8 Hz, 1 H) 7.02 (d, J=12.8 Hz, 1 H) 7.29 (d, J=2.4 Hz, 1 H) 7.67 (s, 1 H) 7.70 (s, 1 H) 7.91 – 7.93 (m, 2 H); ESI-MS m/z [M+H] + =454.2. [0375] EXAMPLE 42: (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino )-5- (1-(2-methoxyethyl)-1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbe nzamide [0376] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.61 - 0.65 (m, 2 H) 0.86 - 0.91 (m, 2 H) 1.20 (d, J=6.8 Hz, 3 H) 2.33 (s, 3 H) 2.93 - 2.95 (m, 1 H) 3.37 (s, 3 H) 3.59 (dd, J=7.6, 10.8 Hz, 1 H) 3.77 - 3.81 (m, 3 H) 4.17 - 4.19 (m, 1 H) 4.35 (t, J=5.2 Hz, 2 H) 4.92 (d, J=5.2 Hz, 1 H) 5.38 (s, 1 H) 6.79 (d, J=12.4 Hz, 1 H) 6.99 (d, J=12.8 Hz, 1 H) 7.30 (d, J=2.4 Hz, 1 H) 7.68 (s, 2 H) 7.91 - 7.95 (m, 2 H); ESI-MS m/z [M+H] + =468.1. [0377] EXAMPLE 43: (R)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino )-5- (2-methyl-2H-1,2,3-triazol-4-yl)pyridin-3-yl)-4-methylbenzam ide [0378] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.62 - 0.66 (m, 2 H) 0.86 - 0.91 (m, 2 H) 1.38 (d, J=6.8 Hz, 3 H) 2.34 (s, 3 H) 2.93 - 2.98 (m, 1 H) 3.70 (dd, J=10.4, 7.6 Hz, 1 H) 3.85 (dd, J=10.4, 2.4 Hz, 1 H) 4.28 (s, 3 H) 4.30 - 4.37 (m, 1 H) 5.29 (s, 1 H) 6.83 (d, J=13.6 Hz, 1 H) 7.03 (d, J=12.8 Hz, 1 H) 7.62 (d, J=5.6 Hz, 1 H) 7.71 (d, J=2.4 Hz, 1 H) 7.90 (s, 1 H) 7.97 (d, J=8.4 Hz, 1 H) 7.99 (d, J=2.0 Hz, 1 H); ESI-MS m/z [M+H] + =425.0. [0379] EXAMPLE 44: (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino )-5- (oxazol-5-yl)pyridin-3-yl)-4-methylbenzamide [0380] 1 H NMR (400 MHz, CD3OD) δ ppm 0.60 - 0.66 (m, 2 H) 0.78 - 0.84 (m, 2 H) 1.30 (d, J=6.4 Hz, 3 H) 2.33 (s, 3 H) 2.83 - 2.88 (m, 1 H) 3.65 - 3.71 (m, 2 H) 4.30 - 4.40 (m, 1 H) 7.15 (d, J=11.6 Hz, 1 H) 7.53 (t, J=3.6 Hz, 2 H) 7.76 (d, J=2.4 Hz, 1 H) 8.05 (d, J=2.4 Hz, 1 H) 8.33 (s, 1 H); ESI-MS m/z [M+H] + =411.1. [0381] EXAMPLE 45: (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino )-5- (2-methylthiazol-5-yl)pyridin-3-yl)-4-methylbenzamide [0382] 1 H NMR (400 MHz, CDCl 3 ) δ 0.62 - 0.65 (m, 2 H) 0.87 - 0.91 (m, 2 H) 1.25 (d, J=6.8 Hz, 3 H) 2.32 (s, 3 H) 2.78 (s, 3 H) 2.93 - 2.95 (m, 1 H) 3.62 (dd, J=10.8, 7.2 Hz, 1 H) 3.79 (dd, J=10.8, 2.8 Hz, 1 H) 4.21 - 4.27 (m, 1 H) 4.94 (d, J=5.2 Hz, 1 H) 6.81 (d, J=12.8 Hz, 1 H) 7.02 (d, J=12.4 Hz, 1 H) 7.36 (d, J=2.4 Hz, 1 H) 7.70 (s, 1 H) 7.93 (d, J=8.4 Hz, 1 H) 8.01 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =441.1. [0383] EXAMPLE 46: (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino )-5- (1-methyl-1H-imidazol-2-yl)pyridin-3-yl)-4-methylbenzamide [0384] 1 H NMR (400 MHz, CDCl3) δ ppm 0.63 - 0.66 (m, 2 H) 0.86 - 0.91 (m, 2 H) 1.29 (d, J=6.8 Hz, 3 H) 2.34 (s, 3 H) 2.92 - 2.96 (m, 1 H) 3.60 - 3.65 (m, 1 H) 3.75 (s, 3 H) 3.82 (dd, J=10.8, 2.8 Hz, 1 H) 4.25 - 4.29 (m, 1 H) 6.85 (d, J=11.6 Hz, 1 H) 7.01 - 7.05 (m, 2 H) 7.20 (d, J=1.2 Hz, 1 H) 7.41 (d, J=2.4 Hz, 1 H) 7.94 (d, J=8.4 Hz, 1 H) 8.04 (d, J=2.4 Hz, 1 H) 8.10 (s, 1 H); ESI-MS m/z [M+H] + =424.1. [0385] EXAMPLE 47: (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino )-5- (2-methyl-2H-1,2,3-triazol-4-yl)pyridin-3-yl)-4-methylbenzam ide [0386] 1 H NMR (400 MHz, CDCl3) δ ppm 0.62 – 0.66 (m, 2 H) 0.86 – 0.91 (m, 2 H) 1.39 (d, J=6.8 Hz, 3 H) 2.33 (s, 3 H) 2.93 – 2.97 (m, 1 H) 3.68 – 3.72 (m, 1 H) 3.83 – 3.87 (m, 1 H) 4.28 (s, 3 H) 4.31 – 4.36 (m, 1 H) 5.30 (s, 1 H) 6.85 (d, J=12.8 Hz, 1 H) 7.05 (d, J=12.8 Hz, 1 H) 7.63 (d, J=5.2 Hz, 1 H) 7.67 (s, 1 H) 7.71 (d, J=2.0 Hz, 1 H) 7.90 (s, 1 H) 7.96 – 7.99 (m, 2 H); ESI-MS m/z [M+H] + =425.1. [0387] EXAMPLE 48: N-cyclopropyl-2-fluoro-5-(6-((1- (hydroxymethyl)cyclopropyl)amino)-5-(2-methyl-2H-1,2,3-triaz ol-4-yl)pyridin-3-yl)-4- methylbenzamide [0388] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.62 - 0.66 (m, 2 H) 0.86 - 0.92 (m, 4 H) 1.07 - 1.10 (m, 2 H) 2.34 (s, 3 H) 2.93 - 2.97 (m, 1 H) 3.78 (s, 2 H) 4.27 (s, 3 H) 6.51 (s, 1 H) 6.81 (d, J=12.4 Hz, 1 H) 7.02 (d, J=12.8 Hz, 1 H) 7.70 (d, J=2.0 Hz, 1 H) 7.88 (s, 1 H) 7.96 - 7.98 (m, 2 H) 8.04 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =437.1. [0389] EXAMPLE 49: N-cyclopropyl-2-fluoro-5-(6-((2-hydroxyethyl)amino)-5-(2-met hyl- 2H-1,2,3-triazol-4-yl)pyridin-3-yl)-4-methylbenzamide [0390] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.60 - 0.69 (m, 2 H) 0.85 - 0.93 (m, 2 H) 2.34 (s, 3 H) 2.90 - 3.01 (m, 1 H) 3.76 - 3.84 (m, 2 H) 3.92 (m, 2 H) 4.29 (s, 3 H) 6.84 (d, J=12.0 Hz, 1 H) 7.04 (d, J=13.0 Hz, 1 H) 7.72 (d, J=2.4 Hz, 1 H) 7.87 - 7.92 (m, 2 H) 7.98 (d, J=8.2 Hz, 1 H) 8.02 (d, J=2.4 Hz, 1 H). ESI-MS m/z [M+H] + =411.1. [0391] EXAMPLE 50: (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino )-5- (thiazol-5-yl)pyridin-3-yl)-4-methylbenzamide [0392] 1 H NMR (400 MHz, CD3OD) δ ppm 0.59 - 0.66 (m, 2 H) 0.78 - 0.85 (m, 2 H) 1.23 (d, J=6.8 Hz, 3 H) 2.33 (s, 3 H) 2.83 - 2.88 (m, 1 H) 3.67 - 3.58 (m, 2 H) 4.21 - 4.34 (m, 1 H) 7.14 (d, J=11.6 Hz, 1 H) 7.47 - 7.56 (m, 2 H) 8.00 - 8.11 (m, 2 H) 9.11 (s, 1 H); ESI-MS m/z [M+H] + =427.1. [0393] EXAMPLE 51: (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino )-5- (isothiazol-4-yl)pyridin-3-yl)-4-methylbenzamide [0394] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.61 - 0.65 (m, 2 H) 0.78 - 0.83 (m, 2 H) 1.22 (d, J=6.4 Hz, 3 H) 2.34 (s, 3 H) 2.84 - 2.87 (m, 1 H) 3.57 - 3.66 (m, 2 H) 4.23 - 4.27 (m, 1 H) 7.13 (d, J=11.6 Hz, 1 H) 7.46 (d, J=2.4 Hz, 1 H) 7.53 (d, J=7.6 Hz, 1 H) 8.00 (d, J=2.4 Hz, 1 H) 8.71 (s, 1 H) 9.08 (s, 1H); ESI-MS m/z [M+H] + =427.0. [0395] EXAMPLE 52: (R)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2- yl)(methyl)amino)-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)- 4-methylbenzamide [0396] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.60 - 0.67 (m, 2 H) 0.85 - 0.92 (m, 2 H) 1.23 (d, J=7.2 Hz, 3 H) 2.33 (s, 3 H) 2.63 (s, 3 H) 2.91 - 2.98 (m, 1 H) 3.69 - 3.75 (m, 1 H) 3.77 - 3.85 (m, 1 H) 3.97 (s, 3 H) 4.20 - 4.33 (m, 1 H) 6.38 (s, 1 H) 6.82 (d, J=12.8 Hz, 1 H) 7.03 (d, J=12.8 Hz, 1 H) 7.51 (d, J=2.4 Hz, 1 H) 7.65 (s, 1 H) 7.76 (s, 1 H) 7.95 (d, J=8.0 Hz, 1 H) 7.98 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =438.2. [0397] EXAMPLE 53: (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino )-5- (2-methyloxazol-5-yl)pyridin-3-yl)-4-methylbenzamide [0398] 1 H NMR (400 MHz, CD3OD) δ ppm 0.61 - 0.66 (m, 2 H) 0.78 - 0.84 (m, 2 H) 1.30 (d, J=6.4 Hz, 3 H) 2.33 (s, 3 H) 2.54 (s, 3 H) 2.84 - 2.88 (m, 1 H) 3.64 - 3.73 (m, 2 H) 4.27 - 4.37 (m, 1 H) 7.15 (d, J=11.6 Hz, 1 H) 7.37 (s, 1 H) 7.52 (d, J=7.2 Hz, 1 H) 7.71 (d, J=2.0 Hz, 1 H) 8.02 (d, J=2.0 Hz, 1 H); ESI-MS m/z [M+H] + =425.2. [0399] EXAMPLE 54: (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino )-5- (isothiazol-5-yl)pyridin-3-yl)-4-methylbenzamide [0400] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.62 - 0.64 (m, 2 H) 0.87 - 0.89(m, 2 H) 1.27 (d, J=6.8 Hz, 3 H) 2.34 (s, 3 H) 2.91 - 2.97 (m, 1 H) 3.64 (dd, J=10.8, 3.2 Hz 1 H) 3.81 (dd, J=10.8, 2.8 Hz, 1 H) 4.97 (d, J=5.6 Hz, 1 H) 6.79 - 6.83 (m, 1 H) 7.03 (d, J=12.8 Hz, 1 H) 7.42 - 7.43 (m, 2 H) 7.95 (d, J=8.0 Hz, 1 H) 8.06 (d, J=2.4 Hz, 1 H) 8.59 (d, J=2.0 Hz, 1 H); ESI-MS m/z [M+H] + =427.1. [0401] EXAMPLE 55: (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino )-5- (3-methylisothiazol-5-yl)pyridin-3-yl)-4-methylbenzamide [0402] 1 H NMR (400 MHz, CDCl3) δ ppm 0.62 - 0.66 (m, 2 H) 0.86 - 0.90 (m, 2 H) 1.27 (d, J=6.8 Hz, 3 H) 2.33 (s, 3 H) 2.58 (s, 3 H) 2.90 - 2.99 (m, 1 H) 3.64 (dd, J=10.8, 7.2 Hz, 1 H) 3.81 (dd, J=10.8, 2.8 Hz, 1 H) 4.25 - 4.30 (m, 1 H) 5.01 (d, J=6.0 Hz, 1 H) 6.77 - 6.85 (m, 1 H) 7.03 (d, J=12.8 Hz, 1 H) 7.17 (s, 1 H) 7.41 (d, J=2.4 Hz, 1 H) 7.94 (d, J=8.0 Hz, 1 H) 8.05 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =441.2. [0403] EXAMPLE 56: N-cyclopropyl-2-fluoro-5-(6-((2-hydroxyethyl)amino)-5-(1-met hyl- 1H-pyrazol-3-yl)pyridin-3-yl)-4-methylbenzamide [0404] 1 H NMR (400 MHz, CDCl3) δ ppm 0.61 - 0.65 (m, 2 H) 0.86 - 0.91 (m, 2 H) 2.33 (s, 3 H) 2.92 - 2.96 (m, 1 H) 3.75 - 3.79 (m, 2 H) 3.89 - 3.92 (m, 2 H) 3.98 (s, 3 H) 5.58 - 5.64 (m, 1 H) 6.59(d, J=2.4 Hz, 1 H) 6.80 (d, J=13.2 Hz, 1 H) 7.00 (d, J=12.8 Hz, 1 H) 7.40 (d, J=2.4 Hz, 1 H) 7.69 (d, J=2.0 Hz, 1 H) 7.95 (d, J=2.0 Hz, 1 H) 7.96 (d, J=8.4 Hz, 1 H) 8.50 (t, J=6.0 Hz, 1 H); ESI-MS m/z [M+H] + =410.2. [0405] EXAMPLE 57: (S)-N-cyclopropyl-5-(5-(1,3-dimethyl-1H-pyrazol-4-yl)-6-((1- hydroxypropan-2-yl)amino)pyridin-3-yl)-2-fluoro-4-methylbenz amide [0406] 1 H NMR (400 MHz, CDCl3) δ ppm 0.61 - 0.65 (m, 2 H) 0.86 - 0.91 (m, 2 H) 1.20 (d, J=6.8 Hz, 3 H) 2.21 (s, 3 H) 2.33 (s, 3 H) 2.92 - 2.96 (m, 1 H) 3.58 (dd, J=8.0, 10.4 Hz, 1 H) 3.76 (dd, J=2.8, 10.4 Hz, 1 H) 3.92 (s, 3 H) 4.15 - 4.21 (m, 1 H) 4.60 (d, J=5.2 Hz, 1 H) 6.79 (d, J=12.8 Hz, 1 H) 6.99 (d, J=13.2 Hz, 1 H) 7.20 (d, J=2.4 Hz, 1 H) 7.38 (s, 1 H) 7.92 - 7.95 (m, 2 H); ESI-MS m/z [M+H] + =438.1. [0407] EXAMPLE 58: (S)-N-cyclopropyl-5-(5-(1,5-dimethyl-1H-pyrazol-4-yl)-6-((1- hydroxypropan-2-yl)amino)pyridin-3-yl)-2-fluoro-4-methylbenz amide [0408] 1 H NMR (400 MHz, CDCl3) δ ppm 0.61 - 0.65 (m, 2 H) 0.86 - 0.90 (m, 2 H) 1.55(d, J=6.8 Hz, 3 H) 2.23 (s, 3 H) 2.33 (s, 3 H) 2.91 - 2.97 (m, 1 H) 3.59 (dd, J=7.6, 10.4 Hz, 1 H) 3.75 (dd, J=2.4, 10.8 Hz, 1 H) 3.88 (s, 3 H) 4.15 - 4.20 (m, 1 H) 4.68 (d, J=4.8 Hz, 1 H) 5.38 - 5.41 (m, 1 H) 6.79 (d, J=12.8 Hz, 1 H) 6.99 (d, J=12.8 Hz, 1 H) 7.17 (d, J=2.0 Hz, 1 H) 7.51 (s, 1 H) 7.92 - 7.94 (m, 2 H); ESI-MS m/z [M+H] + =438.1. [0409] EXAMPLE 59: (S)-N-cyclopropyl-2-fluoro-5-(6-((1-hydroxypropan-2- yl)(methyl)amino)-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)- 4-methylbenzamide [0410] 1 H NMR (400 MHz, CDCl3) δ ppm 0.61 – 0.65 (m, 2 H) 0.86 – 0.91 (m, 2 H) 1.24 (d, J=6.8 Hz, 3 H) 2.34 (s, 3 H) 2.63 (s, 3 H) 2.91 – 2.97 (m, 1 H) 3.70 – 3.74 (m, 1 H) 3.78 – 3.83 (m, 1 H) 3.97 (s, 3 H) 4.26 – 4.31 (m, 1 H) 6.35 (s, 1 H) 6.84 (d, J=12.8 Hz, 1 H) 7.05 (d, J=12.8 Hz, 1 H) 7.51 (d, J=2.4 Hz, 1 H) 7.65 (s, 1 H) 7.76 (s, 1 H) 7.96 (d, J=8.4 Hz, 1 H) 7.99 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =438.2. [0411] EXAMPLE 60: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (oxazol-4-yl)pyridin-3-yl)-4-methylbenzamide [0412] 1 H NMR (400 MHz, CD3OD) δ ppm0.58 - 0.68 (m, 2 H) 0.75 - 0.85 (m, 2 H) 1.54 (s, 6 H) 2.35 (s, 3 H) 2.80 -2.90 (m, 1 H) 4.72 (s, 2 H) 7.43 (d, J=8.0 Hz, 1 H) 7.68 - 7.72 (m, 2 H) 7.75 (dd, J=1.6, 8.0 Hz, 1 H) 8.18 (s, 2 H) 8.34 (s, 1 H) 8.52 (s, 1 H); ESI-MS m/z [M+H] + =407.2. [0413] EXAMPLE 61: N-cyclopropyl-2-fluoro-5-(5-(3-(hydroxymethyl)-2-methyl-2H- pyrrol-4-yl)-6-(((S)-1-hydroxypropan-2-yl)amino)pyridin-3-yl )-4-methylbenzamide [0414] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.59 - 0.66 (m, 2 H) 0.84 - 0.92 (m, 2 H) 1.19 (d, J=6.8 Hz, 3 H) 2.34 (s, 3 H) 2.88 - 2.97 (m, 1 H) 3.53 - 3.61 (m, 1 H) 3.84 - 3.91 (m, 1 H) 4.24 - 4.34 (m, 1 H) 4.53 - 4.62 (m, 2 H) 4.81 (d, J=6.8 Hz, 1 H) 6.84 (d, J=13.2 Hz, 1 H) 7.01 (d, J=12.8 Hz, 1 H) 7.23 (d, J=2.4 Hz, 1 H) 7.48 (s, 1 H) 7.90 (d, J=8.0 Hz, 1 H) 7.98 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =454.2. [0415] EXAMPLE 62: N-cyclopropyl-5-(5-(1-ethyl-1H-pyrazol-4-yl)-6-((2- hydroxyethyl)amino)pyridin-3-yl)-2-fluoro-4-methylbenzamide [0416] 1 H NMR (400 MHz, CDCl3) δ ppm 0.60 - 0.64 (m, 2 H) 0.85 - 0.90 (m, 2 H) 1.55(t, J=7.2 Hz, 3 H) 2.33 (s, 3 H) 2.91 - 2.97 (m, 1 H) 3.59 (dd, J=5.2, 9.2 Hz, 2 H) 3.84 (dd, J=4.4, 4.8 Hz, 2 H) 4.22 - 4.27 (m, 2 H) 5.34(t, J=5.2 Hz, 1 H) 6.80 (d, J=12.8 Hz, 1 H) 6.99 (d, J=12.8 Hz, 1 H) 7.20 (d, J=2.4 Hz, 1 H) 7.59 (s, 1 H) 7.68 (d, J=0.4 Hz, 1 H) 7.92 - 7.94 (m, 2 H); ESI-MS m/z [M+H] + =424.1. [0417] EXAMPLE 63: N-cyclopropyl-2-fluoro-5-(5-(1-(2-hydroxyethyl)-1H-pyrazol-4 -yl)- 6-((2-hydroxyethyl)amino)pyridin-3-yl)-4-methylbenzamide [0418] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.58 - 0.67 (m, 2 H) 0.84 - 0.91 (m, 2 H) 2.32 (s, 3 H) 2.88 - 3.00 (m, 1 H) 3.18 - 3.39 (s, 1 H) 3.57 - 3.64 (m, 2 H) 3.80 - 3.87 (m, 2 H) 4.01 - 4.10 (m, 2 H) 4.26 - 4.35 (m, 2 H) 5.36 (t, J=5.4 Hz, 1 H) 6.84 (m, 1H) 7.01 (d, J=12.8 Hz, 1 H) 7.29 (d, J=2.2 Hz, 1 H) 7.69 (d, J=3.2 Hz, 2 H) 7.91 (d, J=8.2 Hz, 1 H) 7.94 (d, J=2.2 Hz, 1 H); ESI-MS m/z [M+H] + =440.2. [0419] EXAMPLE 64: N-cyclopropyl-2-fluoro-5-(6-((2-methoxyethyl)amino)-5-(1-met hyl- 1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide [0420] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.48 - 0.59 (m, 2 H) 0.64 - 0.75 (m, 2 H) 2.31 (s, 3 H) 2.80 - 2.84 (m, 1 H) 3.28 (s, 3 H) 3.50 - 3.55 (m, 2 H) 3.56 - 3.58 (m, 2 H) 3.90 (s, 3 H) 5.82 (t, J=5.4 Hz, 1 H) 7.21 (d, J=11.6 Hz, 1 H) 7.39 (d, J=7.6 Hz, 1 H) 7.42 (d, J=2.4Hz, 1 H) 7.73 (s, 1 H) 7.97 (d, J=2.4 Hz, 1 H) 8.03 (s, 1 H) 8.31 (d, J=4.0 Hz, 1 H); ESI-MS m/z [M+H] + =366.2. [0421] EXAMPLE 65: N-cyclopropyl-2-fluoro-5-(6-((2-hydroxyethyl)amino)-5-(2- methyloxazol-5-yl)pyridin-3-yl)-4-methylbenzamide [0422] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.50 - 0.59 (m, 2 H) 0.65 - 0.73 (m, 2 H) 2.29 (s, 3 H) 2.49 (s, 3 H) 2.77 - 2.86 (m, 1 H) 3.49 - 3.57 (m, 2 H) 3.58 - 3.66 (m, 2 H) 4.83 (s, 1 H) 6.19 (t, J=5.6 Hz, 1 H) 7.23 (d, J=11.6 Hz, 1 H) 7.38 (d, J=7.6 Hz, 1 H) 7.48 (s, 1 H) 7.66 (d, J=2.4Hz, 1 H) 8.07 (d, J=2.4 Hz, 1 H) 8.32 (d, J=4.0 Hz, 1 H); ESI-MS m/z [M+H] + =410.9. [0423] EXAMPLE 66: (S)-N-cyclopropyl-2-fluoro-5-(5-(3-(hydroxymethyl)-1-methyl- 1H- pyrazol-4-yl)-6-((1-hydroxypropan-2-yl)amino)pyridin-3-yl)-4 -methylbenzamide [0424] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.58 - 0.65 (m, 2 H) 0.83 - 0.92 (m, 2 H) 1.19 (d, J=6.8 Hz, 3 H) 2.34 (s, 3 H) 2.88 - 2.98 (m, 1 H) 3.52 - 3.60 (m, 1 H) 3.73 (s, 1 H) 3.82 (dd, J=11.2, 2.8 Hz, 1 H) 3.95 (s, 3 H) 4.23 - 4.37 (m, 1 H) 4.49 - 4.67 (m, 2 H) 4.79 (s, 1 H) 4.94 (d, J=14.0, 6.8 Hz,, 1 H) 6.82 (dd, J=13.2, 2.0 Hz, 1 H) 7.24 (d, J=12.8 Hz, 1 H) 7.40 (s, 1 H) 7.92 (d, J=8.0 Hz, 1 H) 7.96 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =454.2. [0425] EXAMPLE 67: N-cyclopropyl-2-fluoro-5-(6-((2-hydroxyethyl)amino)-5-(3- methylisothiazol-5-yl)pyridin-3-yl)-4-methylbenzamide [0426] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.50 - 0.58 (m, 2 H) 0.65 - 0.73 (m, 2 H) 2.30 (s, 3 H) 2.49 (s, 3 H) 2.75 - 2.82(m, 1 H) 3.45 - 3.53 (m, 2 H) 3.55 - 3.61 (m, 2 H) 4.73 (s, 1 H) 6.15 (t, J=5.6 Hz, 1 H) 7.23 (d, J=11.2 Hz, 1 H) 7.39 (d, J=7.6 Hz, 1 H) 7.50 (s, 1 H) 7.54 (d, J=2.4 Hz, 1 H) 8.12 (d, J=2.0 Hz, 1 H) 8.30 (d, J=4.0 Hz, 1 H); ESI-MS m/z [M+H] + =426.9. [0427] EXAMPLE 68: N-cyclopropyl-2-fluoro-5-(6-((2-hydroxyethyl)amino)-5- (isothiazol-5-yl)pyridin-3-yl)-4-methylbenzamide [0428] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.50 - 0.57 (m, 2 H) 0.65 - 0.73 (m, 2 H) 2.31 (s, 3 H) 2.82 - 2.76 (m, 1 H) 3.48 (q, J=5.6 Hz, 2 H) 3.54 - 3.65 (m, 2 H) 4.78 (s, 1 H) 6.15 (t, J=5.6 Hz, 1 H) 7.24 (d, J=11.6 Hz, 1 H) 7.40 (d, J=7.6 Hz, 1 H) 7.59 (d, J=2.4 Hz, 1 H) 7.73 (d, J=1.6 Hz, 1 H) 8.14 (d, J=2.4 Hz, 1 H) 8.30 (d, J=4.0 Hz, 1 H) 8.67 (d, J=1.6 Hz, 1 H); ESI-MS m/z [M+H] + =412.9. [0429] EXAMPLE 69: N-cyclopropyl-2-fluoro-5-(6-((2-hydroxyethyl)amino)-5-(oxazo l-5- yl)pyridin-3-yl)-4-methylbenzamide [0430] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.52 - 0.58 (m, 2 H) 0.65 - 0.72 (m, 2 H) 2.30 (s, 3 H) 2.75 - 2.83 (m,1 H) 3.52 - 3.58 (m, 2 H) 3.58 - 3.59 (m, 2 H) 3.59 - 3.64 (m, 2 H) 4.82 (s, 1 H) 6.27 (t, J=5.2 Hz, 1 H) 7.24 (d, J=11.6 Hz, 1 H) 7.40 (d, J=7.6 Hz, 1 H) 7.67 (s, 1 H) 7.74 (d, J=2.4 Hz, 1 H) 8.11 (d, J=2.4 Hz, 1 H) 8.31 (d, J=4.0 Hz, 1 H) 8.52 (s, 1 H); ESI-MS m/z [M+H] + =396.9. [0431] EXAMPLE 70: 5-(5-cyano-6-((2-hydroxyethyl)(methyl)amino)pyridin-3-yl)-2- fluoro-N-(isoxazol-3-yl)-4-methylbenzamide [0432] To a mixture of 5-bromo-2-((2-hydroxyethyl)(methyl)amino)nicotinonitrile (74.0 mg, 0.289 mmol) and 2-fluoro-N-(isoxazol-3-yl)-4-methyl-5-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)benzamide (150mg, 0.433 mmol) in 1,4-Dioxane (2 mL) was added Na2CO3 (433 µL, 0.867 mmol). The mixture was purged with N2 and then Pd(dppf)Cl2- CH 2 Cl 2 adduct (236 mg, 0.289 mmol) was added. The reaction mixture was heated at 110°C in a microwave reactor for 1 hour and then filtered and purified by HPLC. The title compound was obtained as a white solid (65 mg, 57%). 1 H NMR (400 MHz, CD 3 OD) δ ppm 2.37 (s, 3 H) 3.46 (s, 3 H) 3.83 - 3.96 (m, 4 H) 7.05 (d, J=1.65 Hz, 1 H) 7.26 (d, J=11.46 Hz, 1 H) 7.64 (d, J=7.34 Hz, 1 H) 7.91 (d, J=2.48 Hz, 1 H) 8.32 (d, J=2.48 Hz, 1 H) 8.60 (d, J=1.74 Hz, 1 H); ESI-MS m/z [M+H] + =396.3. [0433] EXAMPLE 71: 5-(5-cyano-6-((2-hydroxyethyl)amino)pyridin-3-yl)-2-fluoro-N - (isoxazol-3-yl)-4-methylbenzamide [0434] STEP A: 5-bromo-2-((2-hydroxyethyl)amino)nicotinonitrile [0435] To a mixture of 5-bromo-2-chloronicotinonitrile (150 mg, 0.690 mmol) in DMA (2 mL) were added 2-aminoethan-1-ol (42.1 mg, 0.690 mmol) and DIPEA (241 µL, 1.380 mmol). The reaction mixture was stirred at 70°C for 4 hours and then diluted with water and extracted with EtOAc. The organic phase was concentrated to give the title compound, which was used without further purification. [0436] STEP B: 5-(5-cyano-6-((2-hydroxyethyl)(methyl)amino)pyridin-3-yl)-2- fluoro-N- (isoxazol-3-yl)-4-methylbenzamide [0437] To a mixture of 5-bromo-2-((2-hydroxyethyl)amino)nicotinonitrile (20.98 mg, 0.087 mmol) and 2-fluoro-N-(isoxazol-3-yl)-4-methyl-5-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)benzamide (20 mg, 0.058 mmol) in 1,4-dioxane (2 mL) was added Na 2 CO 3 (87 µL, 0.173 mmol). The mixture was purged with N 2 and Pd(dppf)Cl 2 -CH 2 Cl 2 adduct (47.2 mg, 0.058 mmol) was added. The reaction mixture was heated at 100°C in microwave reactor for 1 hour and then filtered and purified by SFC to give the title compound (5 mg, 23%). 1 H NMR (400 MHz, CD3OD) δ ppm 2.36 (s, 3 H) 3.69 (d, J=5.50 Hz, 2 H) 3.77 (d, J=5.50 Hz, 2 H) 7.05 (d, J=1.74 Hz, 1 H) 7.25 (d, J=11.55 Hz, 1 H) 7.62 (d, J=7.34 Hz, 1 H) 7.87 (d, J=2.38 Hz, 1 H) 8.27 (d, J=2.38 Hz, 1 H) 8.60 (d, J=1.74 Hz, 1 H); ESI-MS m/z [M+H] + =382.2. [0438] Examples 72 to 79, below, were prepared like Examples 70 and 71. [0439] EXAMPLE 72: (S)-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(1-methyl- 1H- pyrazol-4-yl)pyridin-3-yl)-N-(isoxazol-3-yl)-4-methylbenzami de [0440] 1 H NMR (400 MHz, CDCl3) δ ppm 1.25 (d, J=6.4 Hz, 3 H) 2.38 (s, 3 H) 3.60 – 3.64 (m, 1 H) 3.79 – 3.82 (m, 1 H) 3.99 (s, 3 H) 4.18 – 4.24 (m, 1 H) 4.94 (d, J=5.2 Hz, 1 H) 5.21 (s, 1 H) 7.15 (d, J=2.8 Hz, 1 H) 7.19 (d, J=1.6 Hz, 1 H) 7.30 (d, J=2.4 Hz, 1 H) 7.56 (s, 1 H) 7.67 (s, 1 H) 7.95 (d, J=2.4 Hz, 1 H) 7.99 (d, J=8.0 Hz, 1 H) 8.35 (d, J=1.6 Hz, 1 H) 9.14 (d, J=15.2 Hz, 1 H); ESI-MS m/z [M+H] + =451.2. [0441] EXAMPLE 73: 5-(5-cyano-6-(((3R,4S)-3-methoxytetrahydro-2H-pyran-4- yl)amino)pyridin-3-yl)-2-fluoro-N-(isoxazol-3-yl)-4-methylbe nzamide [0442] 1 H NMR (400 MHz, CD 3 OD) δ ppm 1.75 (br dd, J=13.25, 4.54 Hz, 1 H) 2.08 - 2.19 (m, 1 H) 2.36 (s, 3 H) 3.21 (dd, J=11.19, 9.63 Hz, 1 H) 3.41 - 3.56 (m, 5 H) 3.88 - 3.97 (m, 1 H) 4.18 (dd, J=11.28, 4.86 Hz, 1 H) 4.29 - 4.37 (m, 1 H) 4.85 - 5.05 (m, 2 H) 7.05 (d, J=1.65 Hz, 1 H) 7.23 (s, 1 H) 7.26 (s, 1 H) 7.63 (d, J=7.34 Hz, 1 H) 7.87 (d, J=2.38 Hz, 1 H) 8.27 (d, J=2.48 Hz, 1 H) 8.57 - 8.61 (m, 1 H); ESI-MS m/z [M+H] + =452.3. [0443] EXAMPLE 74: 5-(5-cyano-6-(((3R,4R)-3-methoxytetrahydro-2H-pyran-4- yl)amino)pyridin-3-yl)-2-fluoro-N-(isoxazol-3-yl)-4-methylbe nzamide [0444] 1 H NMR (400 MHz, CD3OD) δ ppm 1.80 - 1.89 (m, 1 H) 1.92 - 2.05 (m, 1 H) 2.36 (s, 3 H) 3.43 - 3.53 (m, 5 H) 3.58 (td, J=11.74, 2.38 Hz, 1 H) 3.92 - 4.01 (m, 1 H) 4.23 (dd, J=12.98, 2.06 Hz, 1 H) 4.43 - 4.49 (m, 1 H) 7.04 (d, J=1.56 Hz, 1 H) 7.25 (d, J=11.46 Hz, 1 H) 7.62 (d, J=7.34 Hz, 1 H) 7.90 (d, J=2.38 Hz, 1 H) 8.29 (d, J=2.38 Hz, 1 H) 8.57 - 8.60 (m, 1 H); ESI-MS m/z [M+H] + =452.3. [0445] EXAMPLE 75: (S)-5-(5-cyano-6-(3-hydroxy-3-methylpyrrolidin-1-yl)pyridin- 3-yl)- 2-fluoro-N-(isoxazol-3-yl)-4-methylbenzamide [0446] 1 H NMR (400 MHz, CD 3 OD) δ ppm 1.50 (s, 3 H) 2.02 - 2.11 (m, 2 H) 2.34 - 2.37 (m, 3 H) 3.69 - 3.77 (m, 1 H) 3.82 - 3.88 (m, 1 H) 3.91 - 4.07 (m, 2 H) 7.00 - 7.05 (m, 1 H) 7.19 - 7.25 (m, 1 H) 7.59 - 7.63 (m, 1 H) 7.86 - 7.89 (m, 1 H) 8.28 (d, J=2.29 Hz, 1 H) 8.57 (d, J=1.56 Hz, 1 H); ESI-MS m/z [M+H] + =422.3. [0447] EXAMPLE 76: (S)-5-(5-cyano-6-(3-hydroxypyrrolidin-1-yl)pyridin-3-yl)-2-f luoro- N-(isoxazol-3-yl)-4-methylbenzamide [0448] 1 H NMR (400 MHz, CD3OD) δ ppm 2.04 - 2.22 (m, 2 H) 2.36 (s, 3 H) 3.77 - 3.84 (m, 1 H) 3.89 - 4.02 (m, 3 H) 4.51 - 4.61 (m, 1 H) 7.05 (d, J=1.47 Hz, 1 H) 7.25 (d, J=11.65 Hz, 1 H) 7.60 - 7.65 (m, 1 H) 7.89 (d, J=2.38 Hz, 1 H) 8.29 (d, J=2.38 Hz, 1 H) 8.59 (d, J=1.74 Hz, 1 H); ESI-MS m/z [M+H] + =408.3. [0449] EXAMPLE 77: (S)-5-(5-cyano-6-(3-hydroxypyrrolidin-1-yl)pyridin-3-yl)-2-f luoro- 4-methyl-N-(1H-pyrazol-3-yl)benzamide [0450] 1 H NMR (400 MHz, CD 3 OD) δ ppm 2.15 (s, 2 H) 2.36 (s, 3 H) 3.77 - 3.87 (m, 1 H) 3.89 - 4.02 (m, 3 H) 4.52 - 4.59 (m, 1 H) 6.69 (br s, 1 H) 7.24 (d, J=11.83 Hz, 1 H) 7.61 (d, J=2.20 Hz, 1 H) 7.68 (d, J=7.43 Hz, 1 H) 7.89 (d, J=2.29 Hz, 1 H) 8.30 (d, J=2.38 Hz, 1 H); ESI-MS m/z [M+H] + =407.4. [0451] EXAMPLE 78: (S)-5-(5-cyano-6-((tetrahydrofuran-3-yl)amino)pyridin-3-yl)- 2- fluoro-N-(isoxazol-3-yl)-4-methylbenzamide [0452] 1 H NMR (400 MHz, CD3OD) δ ppm 1.97 - 2.22 (m, 1 H) 2.32 - 2.45 (m, 1 H) 2.36 (s, 3 H) 3.75 (dd, J=9.17, 4.22 Hz, 1 H) 3.87 (td, J=8.18, 6.28 Hz, 1 H) 3.99 - 4.10 (m, 2 H) 4.74 (br dd, J=7.29, 6.01 Hz, 1 H) 7.01 - 7.10 (m, 1 H) 7.22 - 7.30 (m, 1 H) 7.62 (d, J=7.34 Hz, 2 H) 7.88 (d, J=2.29 Hz, 1 H) 8.30 (d, J=2.29 Hz, 1 H) 8.60 (d, J=1.56 Hz, 1 H); ESI-MS m/z [M+H] + =408.3. [0453] EXAMPLE 79: 5-(5-cyano-6-(ethyl(2-hydroxyethyl)amino)pyridin-3-yl)-2-flu oro- N-(isoxazol-3-yl)-4-methylbenzamide [0454] 1 H NMR (400 MHz, CD 3 OD) δ ppm 1.31 - 1.38 (m, 3 H) 2.37 (s, 3 H) 3.80 - 3.96 (m, 6 H) 6.92 - 7.12 (m, 1 H) 7.26 (br s, 1 H) 7.60 - 7.68 (m, 1 H) 7.84 - 7.93 (m, 1 H) 8.25 - 8.36 (m, 1 H) 8.60 (d, J=1.01 Hz, 1 H); ESI-MS m/z [M+H] + =410.3. [0455] EXAMPLE 80: 5-(5-cyano-6-((2-hydroxyethyl)(methyl)amino)pyridin-3-yl)-N- cyclopropyl-2-fluoro-4-methylbenzamide [0456] To a mixture of 5-bromo-2-((2-hydroxyethyl)(methyl)amino)nicotinonitrile (110 mg, 0.430 mmol) and N-cyclopropyl-2-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2 - dioxaborolan-2-yl)benzamide (137 mg, 0.430 mmol) in dioxane (2 mL) was added aq Na2CO3 (2 M, 537 µL, 1.074 mmol) and Pd(dppf)Cl2 (35.1 mg, 0.043 mmol). The reaction mixture was stirred at 90°C for 16 hours. The reaction mixture was worked up with EtOAc and brine and the crude product was purified by flash chromatography (12 g SiO2 column, EtOAc/heptane 10-70%). The title compound was obtained as a beige solid (51.7 mg, 32.7%). 1 H NMR (400 MHz, CD3OD) δ ppm 0.60 - 0.68 (m, 2 H) 0.78 - 0.87 (m, 2 H) 2.32 (s, 3 H) 2.82 - 2.92 (m, 1 H) 3.45 (s, 3 H) 3.81 - 3.89 (m, 2 H) 3.89 - 3.95 (m, 2 H) 7.13 - 7.21 (m, 1 H) 7.48 - 7.56 (m, 1 H) 7.83 - 7.89 (m, 1 H) 8.25 - 8.32 (m, 1 H); ESI-MS m/z=369.3. [0457] EXAMPLE 81: 5-(5-cyano-6-(ethyl(2-hydroxyethyl)amino)pyridin-3-yl)-N- cyclopropyl-2-fluoro-4-methylbenzamide [0458] STEP A: 5-bromo-2-(ethyl(2-hydroxyethyl)amino)nicotinonitrile [0459] To a mixture of 5-bromo-2-chloronicotinonitrile (410 mg, 1.88 mmol) and 2- (ethylamino)ethan-1-ol (184 µL, 1.88 mmol) was added N-ethyl-N-isopropylpropan-2-amine (985 µL, 5.66 mmol) in anhydrous DMF (8 mL). The mixture was stirred at 70°C for 16 hours and then diluted with EtOAc (20 mL) and water. The aqueous layer was extracted EtOAc (2 x). The organic layers were combined, dried over sodium sulfate, filtered and concentrated to give the title compound, which was used without further purification. ESI- MS m/z [M+H] + =270.0-272.1. [0460] STEP B: 5-(5-cyano-6-(ethyl(2-hydroxyethyl)amino)pyridin-3-yl)-N-cyc lopropyl-2- fluoro-4-methylbenzamide [0461] To a mixture of 5-bromo-2-(ethyl(2-hydroxyethyl)amino)nicotinonitrile (300 mg, 1.11 mmol), N-cyclopropyl-2-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2 -dioxaborolan-2- yl)benzamide (354 mg, 1.11 mmol) in dioxane (5 mL) was added aq Na2CO3 (2 M, 1.4 mL, 2.78 mmol) and Pd(dppf)Cl 2 (91 mg, 0.111 mmol). The reaction mixture was stirred at 90°C for 16 hours. The reaction mixture was worked up with EtOAc and brine, and the crude product was purified by flash chromatography (24 g SiO 2 column, EtOAc/heptane 10-70%) and then re-purified by preparative HPLC (basic mode). The title compound was obtained as an off-white solid (49.9 mg, 11.8%). 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.62 - 0.68 (m, 2 H) 0.80 - 0.86 (m, 2 H) 1.34 (t, J=6.97 Hz, 3 H) 2.33 (s, 3 H) 2.84 - 2.92 (m, 1 H) 3.86 (s, 4 H) 3.88 - 3.95 (m, 2 H) 7.16 (d, J=11.55 Hz, 1 H) 7.49 - 7.55 (m, 1 H) 7.86 (d, J=2.38 Hz, 1 H) 8.30 (d, J=2.38 Hz, 1 H); ESI-MS m/z=383.3. [0462] EXAMPLE 82: 5-(5-cyano-6-morpholinopyridin-3-yl)-N-cyclopropyl-2-fluoro- 4- methylbenzamide [0463] In a 40 mL vial were combined 5-bromo-2-morpholinonicotinonitrile (123 mg, 0.459 mmol), N-cyclopropyl-2-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2 -dioxaborolan-2- yl)benzamide (146 mg, 0.459 mmol), aq Na 2 CO 3 (2 M, 0.573 mL, 1.147 mmol) and Pd(dppf)Cl2 (37.5 mg, 0.046 mmol) in dioxane (1.5 mL). The reaction mixture was stirred at 90°C overnight and then diluted with EtOAc (10 mL) and brine (10 mL) and extracted with EtOAc (2 x 10 mL). The combined organic layers were dried over sodium sulfate, concentrated and purified by flash chromatography (12 g SiO 2 column, EtOAc/heptane 10- 70% over 60 minutes). The product-containing fractions were combined and evaporated to give the title compound as a white solid (51 mg, 29%). 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.62 - 0.67 (m, 1 H) 0.79 - 0.86 (m, 1 H) 2.32 (s, 2 H) 2.85 - 2.91 (m, 1 H) 3.73 - 3.79 (m, 3 H) 3.81 - 3.91 (m, 3 H) 5.50 (s, 1 H) 7.18 (d, J=11.74 Hz, 1 H) 7.54 (d, J=7.34 Hz, 1 H) 7.98 (d, J=2.57 Hz, 1 H) 8.38 (d, J=2.38 Hz, 1 H); ESI-MS m/z [M+H] + =381.4. [0464] Examples 83 to 106, below, were prepared like Examples 80 to 82. [0465] EXAMPLE 83: 5-(5-cyano-6-((2-hydroxyethyl)(3-hydroxypropyl)amino)pyridin -3- yl)-N-cyclopropyl-2-fluoro-4-methylbenzamide [0466] 1 H NMR (400 MHz, CD3OD) δ ppm 0.65 (br d, J=2.57 Hz, 2 H) 0.79 - 0.86 (m, 2 H) 1.95 - 2.03 (m, 2 H) 2.33 (s, 3 H) 2.84 - 2.92 (m, 1 H) 3.68 (s, 2 H) 3.85 - 3.96 (m, 6 H) 7.16 (d, J=11.74 Hz, 1 H) 7.52 (d, J=7.34 Hz, 1 H) 7.83 - 7.89 (m, 1 H) 8.30 (d, J=2.57 Hz, 1 H); ESI-MS m/z [M+H] + =413.4. [0467] EXAMPLE 84: 5-(5-cyano-6-((2-hydroxy-2-methylpropyl)(methyl)amino)pyridi n- 3-yl)-N-cyclopropyl-2-fluoro-4-methylbenzamide [0468] 1 H NMR (400 MHz, CD3OD) δ ppm 0.62 - 0.68 (m, 2 H) 0.79 - 0.86 (m, 2 H) 1.25 (s, 6 H) 2.28 - 2.34 (m, 3 H) 2.83 - 2.92 (m, 1 H) 3.54 (s, 3 H) 3.88 - 3.93 (m, 2 H) 7.12 - 7.18 (m, 1 H) 7.49 - 7.55 (m, 1 H) 7.83 - 7.89 (m, 1 H) 8.22 - 8.28 (m, 1 H); ESI-MS m/z [M+H] + =397.3. [0469] EXAMPLE 85: (S)-5-(5-cyano-6-((2-hydroxypropyl)(methyl)amino)pyridin-3-y l)- N-cyclopropyl-2-fluoro-4-methylbenzamide [0470] 1 H NMR (400 MHz, CD3OD) δ ppm 0.62 - 0.68 (m, 2 H) 0.83 (d, J=5.32 Hz, 2 H) 1.23 (d, J=6.42 Hz, 3 H) 2.32 (s, 3 H) 2.84 - 2.92 (m, 1 H) 3.47 (s, 3 H) 3.61 - 3.70 (m, 1 H) 3.86 - 3.94 (m, 1 H) 4.14 - 4.24 (m, 1 H) 7.13 - 7.20 (m, 1 H) 7.49 - 7.54 (m, 1 H) 7.84 - 7.88 (m, 1 H) 8.25 - 8.31 (m, 1 H); ESI-MS m/z [M+H] + =383.3. [0471] EXAMPLE 86: (S)-5-(5-cyano-6-((1-hydroxypropan-2-yl)amino)pyridin-3-yl)- N- cyclopropyl-2-fluoro-4-methylbenzamide [0472] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.61 - 0.68 (m, 2 H) 0.79 - 0.86 (m, 2 H) 1.31 (d, J=6.60 Hz, 3 H) 2.27 - 2.36 (m, 3 H) 2.83 - 2.91 (m, 1 H) 3.64 - 3.69 (m, 2 H) 4.35 - 4.43 (m, 1 H) 7.13 - 7.20 (m, 1 H) 7.48 - 7.54 (m, 1 H) 7.79 - 7.85 (m, 1 H) 8.21 - 8.27 (m, 1 H); ESI-MS m/z [M+H] + =369.3. [0473] EXAMPLE 87: 5-(5-cyano-6-(3-fluoro-4-hydroxypyrrolidin-1-yl)pyridin-3-yl )-N- cyclopropyl-2-fluoro-4-methylbenzamide [0474] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.49 - 0.57 (m, 2 H) 0.63 - 0.72 (m, 2 H) 2.28 (s, 3 H) 2.83 (td, J=7.34, 3.58 Hz, 1 H) 3.74 - 4.16 (m, 3 H) 3.80 (d, J=11.83 Hz, 1 H) 4.37 - 4.43 (m, 1 H) 5.19 (br s, 1 H) 5.06 (br s, 1 H) 5.66 (d, J=3.21 Hz, 1 H) 7.26 (s, 1 H) 7.23 (s, 1 H) 7.41 (d, J=7.43 Hz, 1 H) 8.05 (d, J=2.38 Hz, 1 H) 8.29 (br d, J=3.85 Hz, 1 H) 8.38 (d, J=2.48 Hz, 1 H); ESI-MS m/z [M+H] + =399.3. [0475] EXAMPLE 88: 5-(5-cyano-6-(3-hydroxy-3-methylpyrrolidin-1-yl)pyridin-3-yl )-N- cyclopropyl-2-fluoro-4-methylbenzamide [0476] 1 H NMR (400 MHz, CD3OD) δ ppm 0.61 - 0.68 (m, 2 H) 0.79 - 0.86 (m, 2 H) 1.50 (s, 3 H) 2.01 - 2.11 (m, 2 H) 2.32 (s, 3 H) 2.84 - 2.92 (m, 1 H) 3.69 - 3.76 (m, 1 H) 3.81 - 3.88 (m, 1 H) 3.92 - 4.06 (m, 2 H) 7.16 (d, J=11.74 Hz, 1 H) 7.48 - 7.54 (m, 1 H) 7.85 (d, J=2.38 Hz, 1 H) 8.26 (d, J=2.38 Hz, 1 H); ESI-MS m/z [M+H] + =395.4. [0477] EXAMPLE 89: 5-(6-(bis(2-hydroxyethyl)amino)-5-cyanopyridin-3-yl)-N- cyclopropyl-2-fluoro-4-methylbenzamide [0478] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.62 - 0.68 (m, 2 H) 0.79 - 0.86 (m, 2 H) 2.32 (s, 3 H) 2.83 - 2.92 (m, 1 H) 3.85 - 3.92 (m, 4 H) 3.97 - 4.04 (m, 4 H) 7.16 (d, J=11.55 Hz, 1 H) 7.49 - 7.55 (m, 1 H) 7.83 - 7.89 (m, 1 H) 8.27 - 8.33 (m, 1 H); ESI-MS m/z [M+H] + =399.4. [0479] EXAMPLE 90: 5-(5-cyano-6-(3-hydroxypyrrolidin-1-yl)pyridin-3-yl)-N- cyclopropyl-2-fluoro-4-methylbenzamide [0480] 1 H NMR (400 MHz, CD3OD) δ ppm 0.65 (dd, J=3.85, 2.20 Hz, 2 H) 0.78 - 0.86 (m, 2 H) 2.04 - 2.21 (m, 2 H) 2.31 (s, 3 H) 2.83 - 2.91 (m, 1 H) 3.76 - 3.83 (m, 1 H) 3.86 - 4.01 (m, 3 H) 4.51 - 4.58 (m, 1 H) 7.09 - 7.18 (m, 1 H) 7.51 (d, J=7.52 Hz, 1 H) 7.83 (d, J=2.38 Hz, 1 H) 8.21 - 8.26 (m, 1 H); ESI-MS m/z [M+H] + =381.3. [0481] EXAMPLE 91: 5-(5-cyano-6-((2,3-dihydroxypropyl)(methyl)amino)pyridin-3-y l)- N-cyclopropyl-2-fluoro-4-methylbenzamide [0482] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.57 - 0.73 (m, 2 H) 0.75 - 0.91 (m, 2 H) 2.33 (s, 3 H) 2.88 (tt, J=7.35, 3.79 Hz, 1 H) 3.36 - 3.39 (m, 1H) 3.50 (s, 3 H) 3.53 - 3.67 (m, 2 H) 3.74 - 3.82 (m, 1 H) 3.88 - 4.00 (m, 1 H) 4.00 - 4.08 (m, 1 H) 7.15 (s, 1 H) 7.52 (d, J=7.43 Hz, 1 H) 7.88 (d, J=2.48 Hz, 1 H) 8.28 (d, J=2.48 Hz, 1 H); ESI-MS m/z [M+H] + =399.4. [0483] EXAMPLE 92: 5-(5-cyano-6-(2-(hydroxymethyl)morpholino)pyridin-3-yl)-N- cyclopropyl-2-fluoro-4-methylbenzamide [0484] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.48 - 0.61 (m, 2 H) 0.63 - 0.72 (m, 2 H) 2.29 (s, 3 H) 2.83 (tq, J=7.42, 3.86 Hz, 1 H) 2.92 (dd, J=12.93, 10.09 Hz, 1 H) 3.08 - 3.24 (m, 1 H) 3.38 - 3.60 (m, 2 H) 3.64 (td, J=11.49, 2.52 Hz, 1 H) 4.04 (br d, J=7.34 Hz, 1 H) 4.31 (br d, J=13.02 Hz, 1 H) 4.82 (t, J=5.64 Hz, 1 H) 7.28 (s, 1 H) 7.25 (s, 1 H) 7.43 (d, J=7.34 Hz, 1 H) 8.15 (d, J=2.29 Hz, 1 H) 8.29 (br d, J=3.94 Hz, 1 H) 8.44 (d, J=2.38Hz, 1 H); ESI-MS m/z [M+H] + =411.3. [0485] EXAMPLE 93: 5-(5-cyano-6-((1,3-dihydroxypropan-2-yl)amino)pyridin-3-yl)- N- cyclopropyl-2-fluoro-4-methylbenzamide [0486] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.49 - 0.57 (m, 2 H) 0.64 - 0.72 (m, 2 H) 2.28 (s, 3 H) 2.83 (tq, J=7.46, 3.89 Hz, 1 H) 3.51 - 3.65 (m, 4 H) 4.17 - 4.25 (m, 1 H) 4.78 (t, J=5.50 Hz, 2 H) 6.33 (d, J=7.79 Hz, 1 H) 7.24 (d, J=11.37 Hz, 1 H) 7.39 (d, J=7.43 Hz, 1 H) 8.00 (d, J=2.38 Hz, 1 H) 8.27 (d, J=4.52 Hz, 1 H) 8.29 (s, 1 H); ESI-MS m/z [M+H] + =385.4. [0487] EXAMPLE 94: (S)-5-(5-cyano-6-((3-hydroxy-3-methylbutan-2-yl)amino)pyridi n-3- yl)-N-cyclopropyl-2-fluoro-4-methylbenzamide [0488] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.51 - 0.57 (m, 2 H) 0.65 - 0.72 (m, 2 H) 1.13 - 1.20 (m, 9 H) 2.28 (s, 3 H) 2.82 (td, J=7.34, 3.85 Hz, 1 H) 4.13 - 4.23 (m, 1 H) 4.78 (s, 1 H) 6.16 (d, J=8.62 Hz, 1 H) 7.23 (d, J=11.46 Hz, 1 H) 7.39 (d, J=7.43 Hz, 1 H) 8.00 (d, J=2.38 Hz, 1 H) 8.27 (d, J=4.46 Hz, 1 H) 8.29 (s, 1 H); ESI-MS m/z [M+H] + =397.5. [0489] EXAMPLE 95: 5-(5-cyano-6-((2-hydroxypropyl)amino)pyridin-3-yl)-N- cyclopropyl-2-fluoro-4-methylbenzamide [0490] 1 H NMR (400 MHz, CD3OD) δ ppm 0.62 - 0.69 (m, 2 H) 0.79 - 0.86 (m, 2 H) 1.21 - 1.26 (m, 3 H) 2.31 (s, 3 H) 2.82 - 2.92 (m, 1 H) 3.39 - 3.47 (m, 1 H) 3.60 - 3.67 (m, 1 H) 3.98 - 4.08 (m, 1 H) 7.11 - 7.18 (m, 1 H) 7.48 - 7.53 (m, 1 H) 7.82 (d, J=2.38 Hz, 1 H) 8.22 (d, J=2.38 Hz, 1 H); ESI-MS m/z [M+H] + =369.3. [0491] EXAMPLE 96: 5-(5-cyano-6-(oxetan-3-ylamino)pyridin-3-yl)-N-cyclopropyl-2 - fluoro-4-methylbenzamide [0492] 1 H NMR (400 MHz, CD3OD) δ ppm 0.65 (dd, J=3.85, 2.20 Hz, 2 H) 0.83 (dd, J=7.06, 1.74 Hz, 2 H) 2.31 (s, 3 H) 2.84 - 2.91 (m, 1 H) 4.71 - 4.76 (m, 2 H) 4.97 (s, 2 H) 5.13 - 5.22 (m, 1 H) 7.13 - 7.20 (m, 1 H) 7.46 - 7.53 (m, 1 H) 7.84 - 7.91 (m, 1 H) 8.23 (d, J=2.20 Hz, 1 H); ESI-MS m/z [M+H] + =367.2. [0493] EXAMPLE 97: 5-(5-cyano-6-((tetrahydrofuran-3-yl)amino)pyridin-3-yl)-N- cyclopropyl-2-fluoro-4-methylbenzamide [0494] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.65 (dd, J=3.94, 2.29 Hz, 2 H) 0.83 (dd, J=7.06, 1.93 Hz, 2 H) 2.05 (br d, J=5.69 Hz, 1 H) 2.32 (s, 3 H) 2.34 - 2.42 (m, 1 H) 2.84 - 2.92 (m, 1 H) 3.72 - 3.78 (m, 1 H) 3.83 - 3.92 (m, 1 H) 3.99 - 4.09 (m, 2 H) 4.68 - 4.76 (m, 1 H) 7.16 (d, J=11.74 Hz, 1 H) 7.51 (d, J=7.52 Hz, 1 H) 7.85 (s, 1 H) 8.24 - 8.31 (m, 1 H); ESI-MS m/z [M+H] + =381.4. [0495] EXAMPLE 98: 5-(5-cyano-6-((3-hydroxy-2-methoxypropyl)amino)pyridin-3-yl) -N- cyclopropyl-2-fluoro-4-methylbenzamide [0496] 1 H NMR (400 MHz, CD3OD) δ ppm 0.61 - 0.68 (m, 2 H) 0.79 - 0.86 (m, 2 H) 2.29 - 2.34 (m, 3 H) 2.84 - 2.91 (m, 1 H) 3.48 - 3.52 (m, 3 H) 3.53 - 3.58 (m, 1 H) 3.60 - 3.69 (m, 2 H) 3.70 - 3.78 (m, 2 H) 7.12 - 7.19 (m, 1 H) 7.48 - 7.53 (m, 1 H) 7.81 - 7.85 (m, 1 H) 8.23 - 8.27 (m, 1 H); ESI-MS m/z [M+H] + =399.4. [0497] EXAMPLE 99: 5-(5-cyano-6-((3R,4S)-3,4-dihydroxypyrrolidin-1-yl)pyridin-3 -yl)- N-cyclopropyl-2-fluoro-4-methylbenzamide [0498] 1H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.52 - 0.59 (m, 1 H) 0.63 - 0.72 (m, 2 H) 2.28 (s, 3 H) 2.83 (tq, J=7.46, 3.89 Hz, 1 H) 3.64 (d, J=11.55 Hz, 2H) 3.89 (dd, J=11.60, 3.53 Hz, 2 H) 4.02 - 4.13 (m, 3 H) 5.24 (s, 2 H) 7.24 (d, J=11.37 Hz, 1 H) 7.40 (d, J=7.43 Hz, 1 H) 7.99 (d, J=2.38 Hz, 1 H) 8.28 (br d, J=4.13 Hz, 1 H) 8.34 (d, J=2.38 Hz, 1 H); ESI- MS m/z [M+H] + =397.3. [0499] EXAMPLE 100: 5-(5-cyano-6-((2-hydroxy-2-methylpropyl)amino)pyridin-3-yl)- N- cyclopropyl-2-fluoro-4-methylbenzamide [0500] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.51 - 0.57 (m, 2 H) 0.65 - 0.72 (m, 2 H) 1.15 (s, 6 H) 2.27 (s, 3 H) 2.82 (td, J=7.38, 3.85 Hz, 1 H) 3.42 - 3.49 (m, 4 H) 4.76 (s, 1 H) 6.54 (t, J=5.69 Hz, 1 H) 7.23 (d, J=11.55 Hz, 1 H) 7.39 (d, J=7.43 Hz, 1 H) 8.01 (d, J=2.38 Hz, 1 H) 8.28 (d, J=2.29 Hz, 2 H); ESI-MS m/z [M+H] + =383.3. [0501] EXAMPLE 101: 5-(5-cyano-6-(((3R,4S)-4-hydroxytetrahydrofuran-3- yl)(methyl)amino)pyridin-3-yl)-N-cyclopropyl-2-fluoro-4-meth ylbenzamide [0502] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.49 - 0.57 (m, 2 H) 0.65 - 0.72 (m, 2 H) 2.29 (s, 3 H) 2.79 - 2.86 (m, 1 H) 3.16 - 3.23 (m, 4 H) 3.25 (br d, J=1.47 Hz, 1 H) 3.46 - 3.79 (m, 3 H) 3.91 - 4.17 (m, 1 H) 3.95 - 4.17 (m, 1 H) 4.42 - 4.48 (m, 1 H) 4.85 - 4.90 (m, 1 H) 5.32 (d, J=4.68 Hz, 1 H) 7.25 (d, J=11.46 Hz, 1 H) 7.42 (d, J=7.52 Hz, 1 H) 8.09 (d, J=2.48 Hz, 1 H) 8.29 (br d, J=4.04 Hz, 1 H) 8.39 (d, J=2.48 Hz, 1 H); ESI-MS m/z [M+H] + =411.4. [0503] EXAMPLE 102: 5-(5-cyano-6-((2-hydroxyethyl)amino)pyridin-3-yl)-N- cyclopropyl-2-fluoro-4-methylbenzamide [0504] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.48 - 0.61 (m, 2 H) 0.63 - 0.73 (m, 2 H) 2.27 (s, 3 H) 2.82 (tq, J=7.42, 3.89 Hz, 1 H) 3.15 - 3.20 (m, 1 H) 3.46 - 3.55 (m, 2 H) 3.55 - 3.60 (m, 2 H) 4.75 (t, J=5.36 Hz, 1 H) 7.05 (t, J=5.41 Hz, 1 H) 7.22 (s, 1H) 7.25 (s, 1 H) 7.38 (d, J=7.43 Hz, 1 H) 7.97 (d, J=2.38 Hz, 1 H) 8.25 - 8.31 (m, 2 H); ESI-MS m/z [M+H] + =355.3. [0505] EXAMPLE 103: 5-(5-cyano-6-(3-methoxy-3-methylpyrrolidin-1-yl)pyridin-3-yl )- N-cyclopropyl-2-fluoro-4-methylbenzamide [0506] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.61 - 0.69 (m, 2 H) 0.83 (dd, J=6.88, 1.56 Hz, 2 H) 1.46 (s, 3 H) 1.90 - 2.01 (m, 1 H) 2.31 (s, 4 H) 2.83 - 2.92 (m, 1 H) 3.30 (s, 3 H) 3.60 - 3.67 (m, 1 H) 3.87 - 3.94 (m, 2 H) 3.95 - 4.03 (m, 1 H) 7.11 - 7.19 (m, 1 H) 7.47 - 7.55 (m, 1 H) 7.80 - 7.87 (m, 1 H) 8.21 - 8.28 (m, 1 H); ESI-MS m/z [M+H] + =409.4. [0507] EXAMPLE 104: 5-(5-cyano-6-(3-hydroxyazetidin-1-yl)pyridin-3-yl)-N- cyclopropyl-2-fluoro-4-methylbenzamide [0508] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.48 - 0.61 (m, 2 H) 0.63 - 0.73 (m, 2 H) 2.26 (s, 3 H) 2.82 (tq, J=7.40, 3.93 Hz, 1 H) 3.97 - 4.07 (m, 2 H) 4.49 (dd, J=9.49, 6.83 Hz, 2 H) 4.55 - 4.66 (m, 1 H) 5.77 (d, J=6.24 Hz, 1 H) 7.19 - 7.29 (m, 1 H) 7.38 (d, J=7.43 Hz, 1 H) 8.01 (d, J=2.38 Hz, 1 H) 8.28 (br d, J=3.76 Hz, 1 H) 8.32 (d, J=2.38 Hz, 1 H); ESI-MS m/z [M+H] + =367.4. [0509] EXAMPLE 105: 5-(5-cyano-6-((2-methoxyethyl)(methyl)amino)pyridin-3-yl)-N- cyclopropyl-2-fluoro-4-methylbenzamide [0510] 1 H NMR (400 MHz, CD3OD) δ ppm 0.60 - 0.68 (m, 2 H) 0.76 - 0.91 (m, 2 H) 2.33 (s, 3 H) 2.88 (tt, J=7.28, 3.68 Hz, 1 H) 3.37 - 3.43 (m, 5H) 3.72 (t, J=5.59 Hz, 2 H) 3.98 (t, J=5.55 Hz, 2 H) 7.18 (d, J=11.65 Hz, 1 H) 7.53 (d, J=7.34 Hz,1H) 7.88 (s, 1 H) 8.29 - 8.31 (m, 1 H); ESI-MS m/z [M+H] + =383.3. [0511] EXAMPLE 106: (R)-5-(5-cyano-6-((2-hydroxybutyl)amino)pyridin-3-yl)-N- cyclopropyl-2-fluoro-4-methylbenzamide [0512] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.61 - 0.69 (m, 2 H) 0.78 - 0.87 (m, 2 H) 0.99 - 1.07 (m, 3 H) 1.45 - 1.55 (m, 1 H) 1.56 - 1.68 (m, 1 H) 2.32 (s, 3 H) 2.83 - 2.93 (m, 1 H) 3.37 - 3.47 (m, 1 H) 3.66 - 3.79 (m, 2 H) 7.12 - 7.21 (m, 1 H) 7.47 - 7.55 (m, 1 H) 7.79 - 7.86 (m, 1 H) 8.20 - 8.27 (m, 1 H); ESI-MS m/z [M+H] + =383.3. [0513] EXAMPLE 107: 2-fluoro-5-(6-((2-hydroxyethyl)amino)-5-(1-methyl-1H-pyrazol -4- yl)pyridin-3-yl)-N-(isoxazol-3-yl)-4-methylbenzamide [0514] To a mixture of 2-((5-chloro-3-(1-methyl-1H-pyrazol-4-yl)pyridin-2- yl)amino)ethan-1-ol (0.2 g, 791 µmol) and 2-fluoro-N-(isoxazol-3-yl)-4-methyl-5-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (411 mg, 1.19 mmol) in THF (8 mL) were added K 3 PO 4 (1.5 M, 1.58 mL) and cataCXium A Pd G3 (28.8 mg, 39.6 µmol) under N 2 . The reaction mixture was stirred at 60°C for 12 hours and then diluted with ethyl acetate and filtered. The filtrate was washed with water, dried over anhydrous Na 2 SO 4 , filtered, concentrated and purified by column chromatography (SiO2, EtOAc/Petroleum ether 50% to 100% and MeOH/EtOAc 10%) followed by preparative HPLC. The title compound was obtained as a yellow solid (4.32 mg, 1.21%). 1 H NMR (400 MHz, CDCl3) δ ppm 2.38 (s, 3 H) 3.60 - 3.66 (m, 2 H) 3.83 - 3.88 (m, 2 H) 3.99 (s, 3 H) 5.34 - 5.37 (m, 1 H) 7.13 (d, J=12.8 Hz, 1 H) 7.19 (s,1 H) 7.31(d, J=2.0 Hz, 1 H) 7.58 (s, 1 H) 7.67 (s, 1 H) 7.8 - 8.1 (m, 2 H) 8.34 (s, 1 H) 9.14 (d, J=15.2 Hz, 1 H); ESI-MS m/z [M+H] + =437.2. [0515] Examples 108 to 110, below, were prepared like Example 107. [0516] EXAMPLE 108: (S)-2-((1-hydroxypropan-2-yl)amino)-5-(5-(isoxazol-3- ylcarbamoyl)-2-methylphenyl)-N,N-dimethylnicotinamide [0517] The title compound was obtained as a formic acid salt. 1 H NMR (400 MHz, DMSO- d6) δ ppm 1.17 (d, J=6.4 Hz, 3 H) 2.37 (s, 3 H) 2.99 (s, 6 H) 3.38 - 3.45 (m, 1 H) 3.46 - 3.53 (m, 1 H) 4.14 - 4.24 (m, 1 H) 6.09 (d, J=7.6 Hz, 1 H) 7.05 (d, J=1.6 Hz, 1 H) 7.40 - 7.57 (m, 2 H) 7.82 - 7.95 (m, 2 H) 8.18 (d, J=2.4 Hz, 1 H) 8.35 (s, 1 H) 8.84 (d, J=1.6 Hz, 1 H) 11.40 (s, 1 H); ESI-MS m/z [M+H] + =424.1. [0518] EXAMPLE 109: (R)-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(1-methyl- 1H-pyrazol-4-yl)pyridin-3-yl)-N-(isoxazol-3-yl)-4-methylbenz amide F CH 3 N H N N N CH3 O O N NH OH H 3 C [0519] 1 H NMR (400 MHz, DMSO-d6) δ ppm 1.16 (d, J=7.6 Hz, 3 H) 2.34 (s, 3 H) 3.45 - 3.55 (m, 2 H) 3.88 (s, 3 H) 4.10 - 4.23 (m, 1 H) 4.82 (t, J=5.2 Hz, 1 H) 5.41 (d, J=7.6 Hz, 1 H) 7.01 (d, J=1.6 Hz, 1 H) 7.29 (d, J=11.6 Hz, 1 H) 7.44 (d, J=2.0 Hz, 1 H) 7.53 (d, J=7.2Hz, 1 H) 7.73 (s, 1 H) 8.00 (d, J=2.4 Hz, 1 H) 8.02 (s, 1 H) 8.84 (d, J=1.6 Hz, 1 H) 11.42 (s, 1 H); ESI-MS m/z [M+H] + =451.2. [0520] EXAMPLE 110: 2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(1- methyl-1H-pyrazol-4-yl)pyridin-3-yl)-N-(isoxazol-3-yl)-4-met hylbenzamide [0521] 1 H NMR (400 MHz, CDCl3) δ ppm 1.36 (s, 6 H) 2.39 (s, 3 H) 3.68 (s, 2 H) 4.00 (s, 3 H) 5.00 (s, 1 H) 7.10 - 7.18 (m, 1 H) 7.19 (s, 1 H) 7.29 (d, J=2.4 Hz, 1 H) 7.53 (s, 1 H) 7.65 (s, 1 H) 7.92 (d, J=2.4 Hz, 1 H) 7.98 (d, J=8.0 Hz, 1 H) 8.34 (d, J=1.6 Hz, 1 H) 9.13 (d, J=15.2 Hz, 1 H); ESI-MS m/z [M+H] + =465.2. [0522] EXAMPLE 111: 2-fluoro-5-(6-((2-hydroxyethyl)amino)-5-(1-methyl-1H-pyrazol -4- yl)pyridin-3-yl)-4-methyl-N-(1H-pyrazol-3-yl)benzamide [0523] To a mixture of 2-((5-chloro-3-(1-methyl-1H-pyrazol-4-yl)pyridin-2- yl)amino)ethan-1-ol (200 mg, 791 µmol) and 2-fluoro-4-methyl-N-(1H-pyrazol-3-yl)-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (328 mg, 950 µmol) in dioxane (10 mL) and H2O (1 mL) were added XPhos (75.5mg, 158 µmol), Pd2(dba)3 (36.2 mg, 39.6 µmol) and K 3 PO 4 (504 mg, 2.37 mmol) under N 2 . The reaction mixture was stirred at 110°C for 10 hours and then diluted with ethyl acetate and filtered. The filtrate was washed with water and brine, dried over anhydrous Na 2 SO 4 , filtered, concentrated and purified by column chromatography (SiO 2 , EtOAc/Petroleum ether 50% to 100% and MeOH/EtOAc 10%) followed by preparative HPLC. The title compound was obtained as a white solid (130.29 mg). 1 H NMR (400 MHz, CDCl 3 ) δ ppm 3.55 - 3.65 (m, 2 H) 2.83 - 3.90 (m, 2 H) 3.98 (s, 3 H) 6.77 (d, J=2.0 Hz, 1 H) 7.09 (d, J=12.8 Hz, 1 H) 7.32 (d, J=2.4 Hz, 1 H) 7.53 (d, J=2.4 Hz, 1 H) 7.58 (s, 1 H) 7.67 (s, 1 H) 7.94 - 8.04 (m, 2 H) 9.11 (d, J=14.0 Hz, 1 H); ESI-MS m/z [M+H] + =436.2. [0524] Examples 112 to 114, below, were prepared like Example 111. [0525] EXAMPLE 112: (R)-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(1-methyl- 1H-pyrazol-4-yl)pyridin-3-yl)-4-methyl-N-(1H-pyrazol-3-yl)be nzamide [0526] 1 H NMR (400 MHz, CDCl3) δ ppm 1.24 (d, J=6.8 Hz, 3 H) 2.37 (s, 3 H) 3.59 - 3.66 (m, 1 H) 3.77 - 3.83 (m, 1 H) 4.00 (s, 3 H) 4.15 - 4.25 (m, 1 H) 4.92 (d, J=4.8 Hz, 1 H) 6.78 (s, 1 H) 7.11 (d, J=12.8 Hz, 1 H) 7.31 (d, J=2.0 Hz, 1 H) 7.53 (d, J=2.4 Hz, 1 H) 7.56 (s, 1 H) 7.68 (s, 1 H) 7.95 (d, J=2.4 Hz, 1 H) 8.01 (d, J=8.4 Hz, 1 H) 9.01 (d, J=14.4 Hz, 1 H); ESI- MS m/z [M+H] + =450.2. [0527] EXAMPLE 113: (S)-2-fluoro-5-(6-((1-hydroxypropan-2-yl)amino)-5-(1-methyl- 1H- pyrazol-4-yl)pyridin-3-yl)-4-methyl-N-(1H-pyrazol-3-yl)benza mide [0528] 1 H NMR (400 MHz, DMSO-d6) δ ppm 1.17 (d, J=6.4 Hz, 3 H) 2.33 (s, 3 H) 3.43 – 3.52 (m, 2 H) 3.89 (s, 3 H) 4.12 – 4.22 (m, 1 H) 4.79 (s, 1 H) 5.40 (d, J=7.6 Hz, 1 H) 6.59 (d, J=1.6 Hz, 1 H) 7.27 (d, J=11.2 Hz, 1 H) 7.45 (d, J=2.0 Hz, 1 H) 7.51 (d, J=7.2 Hz, 1 H) 7.64 (d, J=2.0 Hz, 1 H) 7.74 (s, 1 H) 8.00 (d, J=2.4 Hz, 1 H) 8.03 (s, 1 H) 10.70 (s, 1 H) 12.36 (s, 1 H); ESI-MS m/z [M+H] + =450.2. [0529] EXAMPLE 114: 2-fluoro-5-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(1- methyl-1H-pyrazol-4-yl)pyridin-3-yl)-4-methyl-N-(1H-pyrazol- 3-yl)benzamide [0530] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 1.36 (s, 6 H) 2.38 (s, 3 H) 3.68 (s, 2 H) 4.00 (s, 3 H) 4.99 (s, 1 H) 6.77 (s, 1 H) 7.10 (d, J=12.8 Hz, 1 H) 7.31 (d, J=2.2 Hz, 1 H) 7.53 (s, 2 H) 7.65 (s, 1 H) 7.93 (d, J=2.2 Hz, 1 H) 8.01 (d, J=8.2 Hz, 1 H) 9.04 (d, J=14.6 Hz, 1 H); ESI- MS m/z [M+H] + =464.1. [0531] EXAMPLE 115: N-cyclopropyl-2-fluoro-5-(5-((1- (hydroxymethyl)cyclopropyl)amino)-6-(2-methyl-2H-1,2,3-triaz ol-4-yl)pyrazin-2-yl)-4- methylbenzamide [0532] STEP A: (1-((5-bromopyrazin-2-yl)amino)cyclopropyl)methanol [0533] To a solution of 2,5-dibromopyrazine (1 g, 4.20 mmol) and (1- aminocyclopropyl)methanol (439.48 mg, 5.04 mmol) in DMSO (10 mL) was added DIPEA (1.63 g, 12.61 mmol, 2.20 mL). The reaction mixture was stirred at 120°C for 12 hours and then diluted with H 2 O and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure and purified by preparative TLC (EtOAc/Petroleum ether 50%) The title compound was obtained as a yellow oil. ESI-MS m/z [M+H] + =244.1. [0534] STEP B: N-cyclopropyl-2-fluoro-5-(5-((1- (hydroxymethyl)cyclopropyl)amino)pyrazin-2-yl)-4-methylbenza mide [0535] A mixture of (1-((5-bromopyrazin-2-yl)amino)cyclopropyl)methanol (0.28 g, 1.15 mmol), N-cyclopropyl-2-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2 -dioxaborolan-2- yl)benzamide (420.00 mg, 1.32 mmol), Pd(dppf)Cl 2 (64.19 mg, 87.73 µmol) and Na 2 CO 3 (278.94 mg, 2.63 mmol) in dioxane (10 mL) and H2O (2 mL) was degassed and purged with N 2 (3 x). The reaction mixture was stirred at 80°C for 2 hours under N 2 and then diluted with H2O and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous Na 2 SO 4 , filtered, concentrated under reduced pressure and purified by preparative TLC (SiO2, EtOAc/Petroleum ether 100%). The title compound was obtained as a yellow oil (80 mg, 20%). ESI-MS m/z [M+H] + =357.1. [0536] STEP C: 5-(6-bromo-5-((1-(hydroxymethyl)cyclopropyl)amino)pyrazin-2- yl)-N- cyclopropyl-2-fluoro-4-methylbenzamide [0537] To a solution of N-cyclopropyl-2-fluoro-5-(5-((1- (hydroxymethyl)cyclopropyl)amino)pyrazin-2-yl)-4-methylbenza mide (80 mg, 0.18 mmol, 80% purity) in DMSO (5 mL) was added NBS (47.94 mg, 0.27 mmol). The reaction mixture was stirred at 25°C for 12 hours and then diluted with H2O and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous Na 2 SO 4 , filtered, concentrated under reduced pressure and purified by preparative TLC (SiO2, EtOAc/Petroleum ether 100%). The title compound was obtained as a colorless oil (16 mg, 14%). ESI-MS m/z [M+H] + =435.0. [0538] STEP D: N-cyclopropyl-2-fluoro-5-(5-((1-(hydroxymethyl)cyclopropyl)a mino)-6- (2-methyl-2H-1,2,3-triazol-4-yl)pyrazin-2-yl)-4-methylbenzam ide [0539] A mixture of 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H- 1,2,3- triazole (15.37 mg, 73.51 µmol), 5-(6-bromo-5-((1- (hydroxymethyl)cyclopropyl)amino)pyrazin-2-yl)-N-cyclopropyl -2-fluoro-4- methylbenzamide (16 mg, 36.76 µmol), XPhos-Pd-G3 (3.11 mg, 3.68 µmol) and K2CO3 (15.24 mg, 0.11 mmol) in dioxane (5 mL) and H 2 O (1 mL) was degassed and purged with N 2 (3 x). The reaction mixture was stirred at 80°C for 12 hours under N2 atmosphere and then concentrated under reduced pressure. The resulting residue was purified by preparative TLC (SiO2, EtOAc/Petroleum ether 100%) followed by preparative HPLC. The title compound was obtained as a white solid (3.3 mg). 1 H NMR (400 MHz, CD3OD) δ ppm 0.63 - 0.67 (m, 2 H) 0.80 - 0.85 (m, 2 H) 0.90 - 0.95 (m, 2 H) 0.96 - 1.01 (m, 2 H) 2.47 (s, 3 H) 2.85 - 2.91 (m, 1 H) 3.76 (s, 2 H) 4.30 (s, 3 H) 7.17 (d, J=11.6 Hz, 1 H) 7.76 (d, J=7.6 Hz, 1 H) 8.20 (s, 1 H) 8.22 (s, 1 H) 8.28 (s, 1 H); ESI-MS m/z [M+H] + =438.1. [0540] EXAMPLE 116: 5-(6-bromo-5-((2-hydroxyethyl)amino)pyrazin-2-yl)-N- cyclopropyl-2-fluoro-4-methylbenzamide [0541] To a mixture of N-cyclopropyl-2-fluoro-5-(5-((2-hydroxyethyl)amino)pyrazin-2 -yl)- 4-methylbenzamide (50 mg, 0.151 mmol) in DMSO (2 mL) was added 1-bromopyrrolidine- 2,5-dione (26.9 mg, 0.151 mmol). The mixture was stirred at RT for 18 hours. Some starting material remained so more 1-bromopyrrolidine-2,5-dione (0.5 eq) was added. The mixture was stirred for 4 hours and then diluted with EtOAc (10 mL), washed with brine (20 mL), dried over Na2SO4, filtered and concentrated. The crude residue was purified by flash chromatography (4 g silica column, EtOAc/heptane 10 to 100% over 60 minutes). The product-containing fractions were combined and concentrated to give the title compound as a white solid (32 mg, 52%). 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.61 - 0.70 (m, 2 H) 0.79 - 0.86 (m, 2 H) 2.42 (s, 3 H) 2.88 (dt, J=7.31, 3.54 Hz, 1 H) 3.62 - 3.67 (m, 2 H) 3.75 - 3.82 (m, 2 H) 7.12 - 7.20 (m, 1 H) 7.70 (d, J=7.52 Hz, 1 H) 8.13 (s, 1 H); ESI-MS m/z [M+H] + =409.3. [0542] EXAMPLE 117: N-cyclopropyl-2-fluoro-5-(5-((2-hydroxyethyl)amino)-6-(1- methyl-1H-pyrazol-4-yl)pyrazin-2-yl)-4-methylbenzamide [0543] To a mixture of 5-(6-bromo-5-((2-hydroxyethyl)amino)pyrazin-2-yl)-N- cyclopropyl-2-fluoro-4-methylbenzamide (85 mg, 0.208 mmol) and 1-methyl-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (43.2 mg, 0.208 mmol) in 1,4-dioxane (3 ml) and water (0.3 mL) were added potassium carbonate (57.4 mg, 0.415 mmol) and Xphos- Pd-G3 (8.79 mg, 10.38 µmol) at room temperature. The suspension was purged with N2 and heated to 100°C for 2 hours in a microwave reactor. The reaction mixture was diluted with EtOAc (10 mL) and washed with water (10 mL) and brine (10 mL). The organic phase was dried over Na 2 SO4, filtered and concentrated. The crude residue was purified by SFC. The product-containing fractions were combined and concentrated to give the title compound (4.4mg, 5.2%). 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.60 - 0.69 (m, 2 H) 0.79 - 0.85 (m, 2 H) 2.45 (s, 3 H) 2.84 - 2.92 (m, 1 H) 3.60 - 3.68 (m, 2 H) 3.78 - 3.85 (m, 2 H) 4.00 (s, 3 H) 7.10 - 7.23 (m, 1 H) 7.73 (d, J=7.61 Hz, 1 H) 8.01 (s, 1 H) 8.04 (s, 1 H) 8.19 (s, 1 H); ESI-MS m/z [M+H] + =411.4. [0544] EXAMPLE 118: (S)-N-cyclopropyl-2-fluoro-5-(5-((1-hydroxypropan-2-yl)amino )- 6-(1-methyl-1H-pyrazol-4-yl)pyrazin-2-yl)-4-methylbenzamide [0545] To a mixture of (S)-5-(6-bromo-5-((1-hydroxypropan-2-yl)amino)pyrazin-2-yl)- N- cyclopropyl-2-fluoro-4-methylbenzamide (100 mg, 0.236 mmol) and 1-methyl-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (49.2 mg, 0.236 mmol) in 1,4-dioxane (3 mL) and water (0.3 mL) were added potassium carbonate (65.3 mg, 0.472 mmol) and Xphos- Pd-G3 (10.00 mg, 0.012 mmol) at room temperature. The suspension was purged withN 2 and heated to 100°C for 2 hours. The reaction mixture was then diluted with EtOAc (10 mL) and washed with water (10 mL) and brine (10 mL). The organic phrase was dried over Na2SO4, filtered and concentrated. The crude residue was purified by SFC. The product-containing fractions were combined and concentrated to give the title compound as a white solid (28 mg, 28%). 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.54 - 0.70 (m, 2 H) 0.77 - 0.96 (m, 2 H) 1.30 (d, J=6.60 Hz, 3 H) 2.44 (s, 3 H) 2.88 (tt, J=7.31, 3.78 Hz, 1 H) 3.61 - 3.80 (m, 2 H) 3.99 (s, 3 H) 4.17 - 4.42 (m, 1 H) 7.14 (d, J=11.74 Hz, 1 H) 7.73 (d, J=7.61 Hz, 1 H) 7.93 - 8.09 (m, 2 H) 8.16 (s, 1 H); ESI-MS m/z [M+H] + =425.4. [0546] Examples 119 to 121, below, were prepared like Examples 115 to 118. [0547] EXAMPLE 119: 6-(5-(cyclopropylcarbamoyl)-4-fluoro-2-methylphenyl)-3-((1- hydroxy-2-methylpropan-2-yl)amino)-N,N-dimethylpyrazine-2-ca rboxamide [0548] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.52 - 0.53 (m, 2 H) 0.54 - 0.55 (m, 2 H) 1.38 (s, 6 H) 2.57(s, 3 H) 2.81 - 2.82 (m, 1 H) 2.95(d, J=8.0 Hz, 6 H) 3.47 (s, 3 H) 5.04(s, 1 H) 6.86 (s, 1 H) 7.22 (d, J=8.0 Hz, 1 H) 7.55 (d, J=8.0 Hz, 1 H) 8.29 - 8.31 (m, 2 H); ESI-MS m/z [M+H] + =430.2. [0549] EXAMPLE 120: (S)-N-cyclopropyl-2-fluoro-5-(5-((1-hydroxypropan-2-yl)amino )- 6-(2-methyl-2H-1,2,3-triazol-4-yl)pyrazin-2-yl)-4-methylbenz amide [0550] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.64 - 0.66 (m, 2 H) 0.86 - 0.91 (m, 2 H) 1.41 (d, J=6.8 Hz, 3 H) 2.48 (s, 3 H) 2.95 - 2.97 (m, 1 H) 3.74 (dd, J=10.8, 6.8 Hz, 1 H) 3.87 (dd, J=10.8, 3.2 Hz, 1 H) 4.30 (s, 3 H) 4.36 - 4.44 (m, 1 H) 6.83 (d, J=13.6 Hz, 1 H) 7.04 (d, J=12.8 Hz, 1 H) 7.74 (d, J=6.0 Hz, 1 H) 8.13 (s, 1 H) 8.18 (d, J=8.0 Hz, 1 H) 8.27 (s, 1 H); ESI-MS m/z [M+H] + =426.1. [0551] EXAMPLE 121: (R)-N-cyclopropyl-2-fluoro-5-(5-((1-hydroxypropan-2-yl)amino )- 6-(2-methyl-2H-1,2,3-triazol-4-yl)pyrazin-2-yl)-4-methylbenz amide [0552] 1 H NMR (400 MHz, CDCl3) δ ppm 0.64 - 0.68 (m, 2 H) 0.88 - 0.92 (m, 2 H) 1.43 (d, J=6.8 Hz, 3 H) 2.49 (s, 3 H) 2.94 - 2.99 (m, 1 H) 3.73 (dd, J=6.4, 10.4 Hz, 1 H) 3.87 (dd, J=3.2, 10.8 Hz, 1 H) 4.31 (s, 3 H) 4.38 - 4.44 (m, 1 H) 6.83 (d, J=13.2 Hz, 1 H) 7.07 (d, J=8.0 Hz, 1 H) 7.74 (d, J=6.0 Hz, 1 H) 8.13 (s, 1 H) 8.18 (d, J=8.4 Hz, 1 H) 8.28 (s, 1 H); ESI-MS m/z [M+H] + =426.1. [0553] EXAMPLE 122: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (oxazol-2-yl)pyridin-3-yl)-4-methylbenzamide [0554] STEP A: N-(1-((tert-butyldimethylsilyl)oxy)-2-methylpropan-2-yl)-5-c hloro-3- (oxazol-2-yl)pyridin-2-amine [0555] A mixture of 3-bromo-N-(1-((tert-butyldimethylsilyl)oxy)-2-methylpropan-2 -yl)-5- chloropyridin-2-amine (0.5 g, 1.27 mmol), 2-(tributylstannyl)oxazole (909.31 mg, 2.54 mmol) and Pd(PPh3)4 (73.36 mg, 63.48 µmol) in toluene (5 mL) was degassed and purged with N 2 (3 x). The reaction mixture was stirred at 110°C for 12 hours under N 2 atmosphere and then concentrated under reduced pressure and purified by column chromatography (SiO2, EtOAc/Petroleum ether 0% to 5%). The title compound was obtained as a yellow oil (0.4 g, 82%). 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.01 (s, 6 H) 0.87 (s, 9 H) 1.48 (s, 6 H) 3.75 (s, 2 H) 7.22 (s, 1 H) 7.67 (s, 1 H) 8.01 (d, J=2.8 Hz, 1 H) 8.10 (d, J=2.8 Hz, 1 H) 8.54 (s, 1 H). [0556] STEP B: 2-((5-chloro-3-(oxazol-2-yl)pyridin-2-yl)amino)-2-methylprop an-1-ol [0557] To a solution of N-(1-((tert-butyldimethylsilyl)oxy)-2-methylpropan-2-yl)-5-c hloro- 3-(oxazol-2-yl)pyridin-2-amine (0.4 g, 1.05 mmol) in DCM (5 mL) was added HCl/dioxane (4 M, 1 mL) at 0°C. The reaction mixture was stirred at 25°C for 0.5 hours and then concentrated under reduced pressure. The concentrate was adjusted to pH 8 with saturated NaHCO3 and extracted with EtOAc. The combined organic layers were dried over anhydrous Na 2 SO 4 , filtered and concentrated under reduced pressure to give the title compound as a yellow oil (0.3 g, crude). [0558] STEP C: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (oxazol- 2-yl)pyridin-3-yl)-4-methylbenzamide [0559] A mixture of 2-((5-chloro-3-(oxazol-2-yl)pyridin-2-yl)amino)-2-methylprop an-1-ol (0.1 g, 373.54 µmol), N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxabor olan-2- yl)benzamide (112.50 mg, 373.54 µmol), Pd2(dba)3 (34.21 mg, 37.35 µmol), PCy3 (10.48 mg, 37.35 µmol, 12.11 µL) and K 3 PO 4 (237.87 mg, 1.12 mmol) in THF (1 mL) and H 2 O (0.1 mL) was degassed and purged with N2 (3 x). The reaction mixture was stirred at 70°C for 12 hours under N 2 and then diluted with H 2 O and extracted with EtOAc. The combined organic layers were dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure and purified by preparative HPLC. The title compound was obtained as a white solid (17.96 mg, 11.46%). 1 H NMR (400 MHz, CDCl3) δ ppm 0.64 (s, 2 H) 0.87 (s, 2 H) 1.51 (s, 6 H) 2.36 (s, 3 H) 2.91 - 2.92 (m, 1 H) 3.74 (s, 2 H) 6.22 (s, 1 H) 7.28 (s, 1 H) 7.34 (d, J=8.0 Hz, 1 H) 7.59 (s, 1 H) 7.65 (d, J=8.0 Hz, 1 H) 7.70 (s, 1 H) 8.07 (s, 1 H) 8.14 (s, 1 H) 8.83 (s, 1 H); ESI- MS m/z [M+H] + =407.2. [0560] EXAMPLE 123: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (oxazol-5-yl)pyridin-3-yl)-4-methylbenzamide

[0561] STEP A: N-(1-((tert-butyldimethylsilyl)oxy)-2-methylpropan-2-yl)-5-c hloro-3- (oxazol-5-yl)pyridin-2-amine [0562] A mixture of 3-bromo-N-(1-((tert-butyldimethylsilyl)oxy)-2-methylpropan-2 -yl)-5- chloropyridin-2-amine (0.8 g, 2.03 mmol), oxazole (420.87 mg, 6.09 mmol, 389.70 µL), Pd(OAc)2 (9.12 mg, 40.63 µmol), dppf (45.05 mg, 81.26 µmol) and K2CO3 (561.50 mg, 4.06 mmol) in toluene (8 mL) was degassed and purged with N 2 (3 x) at 15°C. The reaction mixture was stirred at 100°C for 12 hours under N2 and then diluted with H2O and extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO 4 , filtered, concentrated under reduced pressure and purified by column chromatography (SiO2, EtOAc/Petroleum ether 2% to 20%). The title compound was obtained as a yellow oil (0.07 g, crude). 1 H NMR (400 MHz, CDCl3) δ ppm 0.05 (s, 6 H) 0.88 (s, 9 H) 1.46 (s, 6 H) 3.61 (s, 2 H) 5.55 (s, 1 H) 7.35 (s, 1 H) 7.63 (d, J=2.4 Hz, 1 H) 7.95 (s, 1 H) 8.07 (d, J=2.8 Hz, 1 H). [0563] STEP B: 2-((5-chloro-3-(oxazol-5-yl)pyridin-2-yl)amino)-2-methylprop an-1-ol [0564] To a solution of N-(1-((tert-butyldimethylsilyl)oxy)-2-methylpropan-2-yl)-5-c hloro- 3-(oxazol-5-yl)pyridin-2-amine (70.00 mg, 183.26 µmol) in DCM (3 mL) was added HCl/dioxane (4 M, 45.81 µL) at 0°C. The mixture was stirred at 15°C for 1 hour and then filtered and concentrated under vacuum. The concentrate was diluted with H 2 O (20 mL) and extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO 4 , filtered and concentrated under reduced pressure to give the title compound as a yellow oil (0.06 g, crude). [0565] STEP C: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (oxazol- 5-yl)pyridin-3-yl)-4-methylbenzamide [0566] A mixture of 2-((5-chloro-3-(oxazol-5-yl)pyridin-2-yl)amino)-2-methylprop an-1-ol (0.06 g, 224.12 µmol), N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxabor olan-2- yl)benzamide (74.25 mg, 246.53 µmol), Pd2(dba)3 (20.52 mg, 22.41 µmol), K3PO4 (95.15 mg, 448.24 µmol) and PCy 3 (6.29 mg, 22.41 µmol, 7.27 µL) in H 2 O (0.2 mL) and THF (2 mL) was degassed and purged with N2 (3 x). The reaction mixture was stirred at 90°C for 13 hours under N 2 and then diluted with H 2 O and extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered, concentrated under reduced pressure and purified by preparative HPLC. The title compound was obtained as a yellow solid (3.25 mg). 1 H NMR (400 MHz, CDCl3) δ ppm 0.55 (s, 2 H) 0.79 - 0.81 (m, 2 H) 1.37 (s, 6 H) 2.27 (s, 3 H) 2.84 (s, 1 H) 3.65 (s, 2 H) 5.35 (s, 1 H) 6.18 (s, 1 H) 7.19 (s, 1 H) 7.25 (s, 1 H) 7.51 (s, 1 H) 7.56 (d, J=7.2 Hz, 1 H) 7.60 (s, 1 H) 7.94 (s, 1 H) 7.96 (s, 1 H); ESI-MS m/z [M+H] + =407.4. [0567] Examples 124 to 176, below, were prepared like Examples 122 and 123. [0568] EXAMPLE 124: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- methoxypyridin-3-yl)-4-methylbenzamide [0569] 1 H NMR (400 MHz, CD3OD) δ ppm 0.62 - 0.69 (m, 2 H) 0.77 - 0.85 (m, 2 H) 1.41 (s, 6 H) 2.36 (s, 3 H) 2.80 - 2.91 (m, 1 H) 3.64 - 3.69 (m, 2 H) 3.90 (s, 3 H) 7.01 - 7.06 (m, 1 H) 7.33 - 7.40 (m, 1 H) 7.52 - 7.57 (m, 1 H) 7.64 - 7.73 (m, 2 H); ESI-MS m/z [M+H] + =370.4. [0570] EXAMPLE 125: N-cyclopropyl-3-(6-((2-hydroxyethyl)amino)-5-methoxypyridin- 3- yl)-4-methylbenzamide [0571] 1 H NMR (400 MHz, CD3OD) δ ppm 0.62 - 0.68 (m, 2 H) 0.78 - 0.85 (m, 2 H) 2.35 (s, 3 H) 2.82 - 2.90 (m, 1 H) 3.55 - 3.61 (m, 2 H) 3.76 - 3.80 (m, 2 H) 3.91 (s, 3 H) 7.00 - 7.03 (m, 1 H) 7.34 - 7.39 (m, 1 H) 7.52 - 7.56 (m, 1 H) 7.65 - 7.71 (m, 2 H); ESI-MS m/z [M+H] + =342.4. [0572] EXAMPLE 126: N-cyclopropyl-3-(6-((1-hydroxypropan-2-yl)amino)-5- methoxypyridin-3-yl)-4-methylbenzamide [0573] 1 H NMR (400 MHz, CD3OD) δ ppm 0.62 - 0.69 (m, 2 H) 0.77 - 0.86 (m, 2 H) 1.29 (d, J=6.60 Hz, 3 H) 2.36 (s, 3 H) 2.82 - 2.91 (m, 1 H) 3.65 (d, J=4.95 Hz, 2 H) 3.91 (s, 3 H) 4.13 - 4.22 (m, 1 H) 6.99 - 7.05 (m, 1 H) 7.33 - 7.39 (m, 1 H) 7.54 (d, J=1.83 Hz, 1 H) 7.67 (s, 2 H); ESI-MS m/z [M+H] + =356.4. [0574] EXAMPLE 127: 3-(5-(azetidine-1-carbonyl)-6-((1-hydroxy-2-methylpropan-2- yl)amino)pyridin-3-yl)-N-cyclopropyl-4-methylbenzamide [0575] 1 H NMR (400 MHz, CD3OD) δ ppm 0.49 - 0.57 (m, 2 H) 0.65 - 0.75 (m, 2 H) 1.32 (s, 6 H) 2.25 (s, 5 H) 2.71 - 2.78 (m, 1 H) 3.61 (s, 2 H) 4.04 - 4.35 (m, 4 H) 7.23 - 7.31 (m, 1 H) 7.44 - 7.49 (m, 1 H) 7.50 - 7.54 (m, 2 H) 7.56 - 7.62 (m, 1 H) 7.96 - 8.02 (m, 1 H); ESI- MS m/z [M+H] + =423.5. [0576] EXAMPLE 128: N-cyclopropyl-3-(5-ethoxy-6-((1-hydroxy-2-methylpropan-2- yl)amino)pyridin-3-yl)-4-methylbenzamide [0577] 1 H NMR (400 MHz, CD3OD) δ ppm 0.61 - 0.69 (m, 2 H) 0.73 - 0.82 (m, 2 H) 1.40 (s, 6 H) 1.45 (t, J=7.2 Hz, 3 H) 2.34 (s, 3 H) 2.81 - 2.87 (m, 1 H) 3.66 (s, 2 H) 4.09 - 4.14 (m, 2 H) 7.01 (d, J=2.0 Hz, 1 H) 7.35 (d, J=7.6 Hz, 1 H) 7.52 (d, J=2.0 Hz, 1 H) 7.68 - 7.64 (m, 2 H); ESI-MS m/z [M+H] + =384.3. [0578] EXAMPLE 129: N-cyclopropyl-3-(5-(cyclopropylmethoxy)-6-((1-hydroxy-2- methylpropan-2-yl)amino)pyridin-3-yl)-4-methylbenzamide [0579] 1 H NMR (400 MHz, CD3OD) δ ppm 0.36 - 0.40 (m, 2 H) 0.59 - 0.69 (m, 4 H) 0.75 - 0.82 (m, 2 H) 1.26 - 1.35 (m, 1 H) 1.41 (s, 6 H) 2.33 (s, 3 H) 2.81 - 2.86 (m, 1 H) 3.66 (s, 2 H) 3.90 (d, J=6.8 Hz, 2 H) 7.01 (d, J=1.6 Hz, 1 H) 7.34 (d, J=8.0 Hz, 1 H) 7.53 (d, J=1.6 Hz, 1 H) 7.63 - 7.68 (m, 2 H); ESI-MS m/z [M+H] + =410.4. [0580] EXAMPLE 130: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- isopropoxypyridin-3-yl)-4-methylbenzamide [0581] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.60 - 0.66 (m, 2 H) 0.75 - 0.82 (m, 2 H) 1.35 - 1.41 (m, 12 H) 2.34 (s, 3 H) 2.81 - 2.87 (m, 1 H) 3.65 (s, 2 H) 4.59 - 4.69 (m, 1 H) 7.04 (d, J=1.6 Hz, 1 H) 7.35 (d, J=8.0 Hz, 1 H) 7.52 (d, J=1.6 Hz, 1 H) 7.62 - 7.70 (m, 2 H); ESI-MS m/z [M+H] + =398.4. [0582] EXAMPLE 131: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide [0583] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.53 - 0.58 (m, 2 H) 0.64 - 0.70 (m, 2 H) 1.40 (s, 6 H) 2.32 (s, 3 H) 2.81 - 2.87(m, 1 H) 3.47 (s, 2 H) 3.89 (s, 3 H) 5.43 (s, 1 H) 7.35 (d, J=7.6 Hz, 1 H) 7.41 (d, J=2.0 Hz, 1 H) 7.67 - 7.71 (m, 2 H) 7.73 (s, 1 H) 7.97 (d, J=2.0 Hz, 1 H) 8.01 (s, 1 H) 8.36 (d, J=4.0 Hz, 1 H); ESI-MS m/z [M+H] + =420.3. [0584] EXAMPLE 132: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide [0585] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.51 - 0.61 (m, 2 H) 0.62 - 0.71 (m, 2 H) 1.40 (s, 6 H) 2.33 (s, 3 H) 2.79 - 2.89 (m, 1 H) 3.46 (s, 2 H) 5.28 (s, 1 H) 5.45 (s, 1 H) 7.35 (d, J=8.4 Hz, 1 H) 7.44 (d, J=2.4 Hz, 1 H) 7.66 - 7.72 (m, 2 H) 7.80 - 8.10 (m, 3 H) 8.36 (d, J=4.0 Hz, 1 H) 13.14 (s, 1 H); ESI-MS m/z [M+H] += 406.2. [0586] EXAMPLE 133: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (5-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide [0587] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.62 - 0.64 (m, 2 H) 0.87 - 0.91 (m, 2 H) 1.35 (s, 6 H) 2.31 (s, 3 H) 2.38 (s, 3 H) 2.90 - 2.94 (m, 1 H) 3.67 (s, 2 H) 4.66 (s, 1 H) 6.23 (s, 1 H) 7.33 (d, J=8.0 Hz, 1 H) 7.58 - 7.63 (m, 3 H) 7.97 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =420.3 [0588] EXAMPLE 134: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- phenylpyridin-3-yl)-4-methylbenzamide [0589] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.60 - 0.64 (m, 2 H) 0.86 - 0.90 (m, 2 H) 1.32 (s, 6 H) 2.38 (s, 3 H) 2.90 - 2.93 (m, 1 H) 3.66 (s, 2 H) 4.80 (s, 1 H) 6.23 (s, 1 H) 7.31 - 7.33 (m, 2 H) 7.41 - 7.44 (m, 3 H) 7.48 - 7.52 (m, 2 H) 7.57 (d, J=2.0 Hz, 1 H) 7.65 (dd, J=8.0, 2.0 Hz, 1 H) 7.99 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =416.3. [0590] EXAMPLE 135: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- methylpyridin-3-yl)-4-methylbenzamide [0591] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.59 - 0.63 (m, 2 H) 0.84 - 0.89 (m, 2 H) 1.42 (s, 6 H) 2.13 (s, 3 H) 2.31 (s, 3 H) 2.88 - 2.93 (m, 1 H) 3.69 (s , 2 H) 6.26 (s, 1 H) 7.30 (d, J=8.0 Hz, 3 H) 7.51 (s, 1 H) 7.62 (dd, J=1.6, 7.6 Hz, 1 H) 7.85 (d, J=2.0 Hz, 1 H) 8.09 (s, 1 H); ESI-MS m/z [M+H] + =354.3. [0592] EXAMPLE 136: N-cyclopropyl-3-(5-ethyl-6-((1-hydroxy-2-methylpropan-2- yl)amino)pyridin-3-yl)-4-methylbenzamide [0593] 1 H NMR (400 MHz, CDCl3) δ ppm 0.60 - 0.65 (m, 2 H) 0.85 - 0.90 (m, 2 H) 1.29 (t, J=7.6 Hz, 3 H) 1.43 (s, 6 H) 2.33 (s, 3 H) 2.46 (q, J=7.2 Hz, 2 H) 2.89 - 2.93 (m, 1 H) 3.70 (s, 2 H) 6.21 (s, 1 H) 7.28 - 7.29 (m, 1 H) 7.32 (d, J=8.0 Hz, 1 H) 7.54 (d, J=2.0 Hz, 1 H) 7.64 (dd, J=2.0, 8.0 Hz, 1 H) 7.87 (d, J=2.0 Hz, 1 H); ESI-MS m/z [M+H] + =368.3. [0594] EXAMPLE 137: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- propylpyridin-3-yl)-4-methylbenzamide [0595] 1 H NMR (400 MHz, CDCl3) δ ppm 0.58 - 0.66 (m, 2 H) 0.83 - 0.89 (m, 2 H) 1.03 (t, J=5.4 Hz, 3 H) 1.42 (s, 6 H) 1.63 - 1.73 (m, 2 H) 2.32 (s, 3 H) 2.40 (t, J=7.6 Hz, 2 H) 2.93 - 2.89 (m, 1 H) 3.68 (s, 2 H) 4.38 (s, 1 H) 6.22 (s, 1 H) 7.24 (d, J=2.0 Hz, 1 H) 7.31 (d, J=8.0 Hz, 1 H) 7.53 (d, J=1.6 Hz, 1 H) 7.63 (dd, J=2.0, 8.0 Hz, 1 H) 7.86 (d, J=2.0 Hz, 1 H); ESI- MS m/z [M+H] + =382.1. [0596] EXAMPLE 138: 3-(5-cyclohexyl-6-((1-hydroxy-2-methylpropan-2- yl)amino)pyridin-3-yl)-N-cyclopropyl-4-methylbenzamide [0597] 1 H NMR (400 MHz, CDCl3) δ ppm 0.62 - 0.64 (m, 2 H) 0.85 - 0.88 (m, 2 H) 1.27 - 1.29 (m, 2 H) 1.32 - 1.38 (m, 3 H) 1.42 (s, 6 H) 1.82 (d, J=13.2 Hz, 2 H) 1.92 (d, J=11.2 Hz, 4 H) 2.31 (s, 3 H) 2.90 - 2.94 (m, 1 H) 3.68 (s, 2 H) 6.20 (s, 1 H) 7.29 (d, J=2.4 Hz, 1 H) 7.31 (d, J=8.0 Hz, 1 H) 7.53 (d, J=1.6 Hz, 1 H) 7.62 (d, J=7.6 Hz, 1 H) 7.85 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =422.3. [0598] EXAMPLE 139: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (piperidin-4-yl)pyridin-3-yl)-4-methylbenzamide [0599] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.55 - 0.56 (m, 2 H) 0.65 - 0.69 (m, 2 H) 1.40 (s, 6 H) 1.74 - 1.77 (m, 2 H) 1.88 - 1.91 (m, 2 H) 2.30 (s, 3 H) 2.81 - 2.88 (m, 2 H) 2.93 - 2.99 (m, 2 H) 3.27 (d, J=11.6 Hz, 1 H) 3.53 (s, 2 H) 5.26 (s, 1 H) 7.28 (d, J=2.4 Hz, 1 H) 7.34 (d, J=8.0 Hz, 1 H) 7.66 - 7.70 (m, 2 H) 7.94 (d, J=2.4 Hz, 1 H) 8.42 - 8.47 (m, 2 H); ESI-MS m/z [M+H] + =423.4. [0600] EXAMPLE 140: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (methylamino)pyridin-3-yl)-4-methylbenzamide [0601] The title compound was obtained as a formic acid salt. 1 H NMR (400 MHz, CDCl3) δ ppm 0.62 - 0.65 (m, 2 H) 0.80 - 0.89 (m, 2 H) 1.42 (s, 6 H) 2.33 (s, 3 H) 2.84(s, 3 H) 2.89 - 2.94 (m, 1 H) 3.69 (s, 2 H) 6.37 (s, 1 H) 6.76 (s, 1 H) 7.31 - 7.33 (m, 1 H) 7.47 (s, 1 H) 7.56 (s, 1 H) 7.63 - 7.65 (m, 1 H) 8.17 (s, 1 H); ESI-MS m/z [M+H] + =369.2. [0602] EXAMPLE 141: N-cyclopropyl-3-(5-(dimethylamino)-6-((1-hydroxy-2- methylpropan-2-yl)amino)pyridin-3-yl)-4-methylbenzamide [0603] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.61 - 0.64 (m, 2 H) 0.85 - 0.90 (m, 2 H) 1.41 (s, 6 H) 2.34 (s, 3 H) 2.65 (s, 6 H) 2.88 - 2.94 (m, 1 H) 3.69 (s, 2 H) 5.46 (s, 1 H) 6.22 (s, 1 H) 7.13 (d, J=2.0 Hz, 1 H) 7.32 - 7.34 (m, 1 H) 7.54 (d, J=1.6 Hz, 1 H) 7.61 (d, J=2.0 Hz, 1 H) 7.69 (d, J=2.0 Hz, 1 H); ESI-MS m/z [M+H] + =383.3. [0604] EXAMPLE 142: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (pyrrolidin-1-yl)pyridin-3-yl)-4-methylbenzamide [0605] The title compound was obtained as an HCL salt. 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.56 (s, 2 H) 0.67 - 0.71 (m, 2 H) 1.46 (s, 6 H) 1.92 (s, 4 H) 2.33 (s, 3 H) 2.82 - 2.88 (m, 1 H) 3.17 (s, 4 H) 3.62 (s, 2 H) 6.80 (s, 1 H) 7.39 - 7.41 (m, 1 H) 7.51 (s, 1 H) 7.72 (s, 1 H) 7.77 - 7.79 (m, 2 H) 8.44 (s, 1 H); ESI-MS m/z [M+H] + =409.3. [0606] EXAMPLE 143: N-cyclopropyl-3-(2-((1-hydroxy-2-methylpropan-2-yl)amino)-4' - methyl-[3,3'-bipyridin]-5-yl)-4-methylbenzamide [0607] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.62 (d, J=2.0 Hz ,2 H) 0.87 (d, J=5.6 Hz ,2 H) 1.28 (d, J=19.6 Hz ,6 H) 2.46 (s, 3 H) 2.37 (s, 3 H) 2.90 - 2.92 (m, 1 H) 3.64 (s, 2 H) 4.09 (s, 1 H) 6.21 (s, 1 H) 7.28 - 7.29 (m, 2 H) 7.32 (d, J=8.0 Hz, 1 H) 7.61 - 7.63 (m, 2 H) 8.06 (d, J=2.0 Hz, 1 H) 8.43 (s, 1 H) 8.56 (d, J=4.8 Hz, 1 H); ESI-MS m/z [M+H] + =431.2. [0608] EXAMPLE 144: N-cyclopropyl-3-(2-((1-hydroxy-2-methylpropan-2-yl)amino)- [3,3'-bipyridin]-5-yl)-4-methylbenzamide [0609] 1 H NMR (400 MHz, CDCl3) δ ppm 0.61 - 0.64 (m, 2 H) 0.85 - 0.88 (m, 2 H) 1.33 (s, 6 H) 2.37 (s, 3 H) 2.90 - 2.92 (m, 1 H) 3.66 (s, 2 H) 4.57 (s, 1 H) 6.22 (s, 1 H) 7.32 - 7.34 (m, 2 H) 7.44 - 7.47 (m, 1 H) 7.58 - 7.64 (m, 2 H) 7.77 (d, J=8.0 Hz, 1 H) 8.04 (d, J=2.0 Hz, 1 H) 8.69 (d, J=6.0 Hz, 2 H); ESI-MS m/z [M+H] + =417.1. [0610] EXAMPLE 145: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (thiazol-4-yl)pyridin-3-yl)-4-methylbenzamide [0611] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.60 - 0.64 (m, 2 H) 0.85 - 0.89 (m, 2 H) 1.45 (s, 6 H) 2.36 (s, 3 H) 2.89 - 2.93 (m, 1 H) 3.71 (s, 2 H) 6.25 (s, 1 H) 7.33 (d, J=8.0 Hz, 1 H) 7.55 (d, J=2.0 Hz, 2 H) 7.59 (d, J=1.6 Hz, 1 H) 7.64 (dd, J=1.6, 2.0 Hz, 1 H) 7.74 (d, J=2.4 Hz, 1 H) 7.99 (d, J=2.4 Hz, 1 H) 8.32 (s, 1 H) 8.94 (d, J=2.0 Hz, 1 H); ESI-MS m/z [M+H] + =423.3. [0612] EXAMPLE 146: N-cyclopropyl-3-(2-((1-hydroxy-2-methylpropan-2-yl)amino)- [3,4'-bipyridin]-5-yl)-4-methylbenzamide [0613] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.52 - 0.57 (m, 2 H) 0.64 - 0.70 (m, 2 H) 1.39 (s, 6 H) 2.34 (s, 3 H) 2.79 - 2.87 (m, 1 H) 3.43 (s, 2 H) 5.17 (s, 1 H) 5.35 (s, 1 H) 7.34 - 7.38 (m, 1 H) 7.44 (d, J=2.4 Hz, 1 H) 7.54 (d, J=6.0 Hz, 2 H) 7.70 (dd, J=2.0, 3.6 Hz, 2 H) 8.13 (d, J=2.4 Hz, 1 H) 8.38 (d, J=4.0 Hz, 1 H) 8.67 (d, J=6.0 Hz, 2 H); ESI-MS m/z [M+H] + =417.3. [0614] EXAMPLE 147: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (piperidin-1-yl)pyridin-3-yl)-4-methylbenzamide [0615] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.62 - 0.64 (m, 2 H) 0.77 - 0.80 (m, 2 H) 1.40 (s, 6 H) 1.56 - 1.61 (m, 2 H) 1.75 (s, 4 H) 2.33 (s, 3 H) 2.80 - 2.86 (m, 5 H) 3.66 (s, 2 H) 7.24 (d, J=2.0 Hz, 1 H) 7.35 (d, J=8.0 Hz, 1 H) 7.62 (d, J=1.6 Hz, 1 H) 7.64 (dd, J=2.0, 8.0 Hz, 1 H) 7.69 (d, J=2.0 Hz, 1 H); ESI-MS m/z [M+H] + =423.3. [0616] EXAMPLE 148: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- morpholinopyridin-3-yl)-4-methylbenzamide [0617] 1 H NMR (400 MHz, CDCl3) δ ppm 0.60 - 0.64 (m, 2 H) 0.85 - 0.90 (m, 2 H) 1.41 (s, 6 H) 2.32 (s, 3 H) 3.87 - 3.93 (m, 5 H) 3.68 (s, 2 H) 3.86 (s, 4 H) 5.53 (s, 1 H) 6.22 (s, 1 H) 7.15 (d, J=2.0 Hz, 1 H) 7.31 - 7.33 (m, 1 H) 7.55 (s, 1 H) 7.60 - 7.63 (m, 1 H) 7.74 (d, J=1.6 Hz, 1 H); ESI-MS m/z [M+H] + =425.2. [0618] EXAMPLE 150: N-cyclopropyl-3-(2'-((1-hydroxy-2-methylpropan-2-yl)amino)- [2,3'-bipyridin]-5'-yl)-4-methylbenzamide [0619] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.58 - 0.67 (m, 2 H) 0.82 - 0.94 (m, 2 H) 1.46 (s, 6 H) 2.38 (s, 3 H) 2.89 - 2.95 (m, 1 H) 3.72 (s, 2 H) 6.25 (s, 1 H) 7.26 (d, J=1.2 Hz, 1 H) 7.29 (d, J=1.2 Hz, 1 H) 7.34 (d, J=8.0 Hz, 1 H) 7.61 (d, J=2.0 Hz, 1 H) 7.65 (dd, J=8.0, 2.0 Hz, 1 H) 7.71 - 7.75 (m, 1 H) 7.78 - 7.83 (m, 1 H) 7.84 (d, J=2.0 Hz, 1 H) 8.03 (d, J=2.4 Hz, 1 H) 8.63 - 8.64 (m, 1 H) 9.57 (s, 1 H); ESI-MS m/z [M+H] + =417.3. [0620] EXAMPLE 151: N-cyclopropyl-3-(5-(1-ethyl-1H-pyrazol-4-yl)-6-((1-hydroxy-2 - methylpropan-2-yl)amino)pyridin-3-yl)-4-methylbenzamide [0621] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.54 - 0.56 (m, 2 H) 0.65 - 0.70 (m, 2 H) 1.39 - 1.43 (m, 9 H) 2.32 (s, 3 H) 2.81 - 2.86 (m, 1 H) 3.47 (d, J=5.2 Hz, 2 H) 4.17 (q, J=7.2 Hz, 2 H) 5.28 (t, J=4.8 Hz, 1 H) 5.47 (s, 1 H) 7.35 (d, J=8.0 Hz, 1 H) 7.43 (s, 1 H) 7.69 - 7.70 (m, 2 H) 7.74 (s, 1 H) 7.96 (d, J=2.0 Hz, 1 H) 8.06 (s, 1 H) 8.37 (d, J=4.0 Hz, 1 H); ESI-MS m/z [M+H] + =434.2. [0622] EXAMPLE 152: N-cyclopropyl-3-(5-(ethylamino)-6-((1-hydroxy-2-methylpropan - 2-yl)amino)pyridin-3-yl)-4-methylbenzamide [0623] 1 H NMR (400 MHz, CDCl3) δ ppm 0.62 - 0.64 (m, 2 H) 0.85 - 0.90 (m, 2 H) 1.33 (t, J=6.4 Hz, 3 H) 1.43 (s, 6 H) 2.33 (s, 3 H) 2.89 - 2.92 (m, 1 H) 3.09 - 3.14 (m, 2 H) 3.69 (s, 2 H) 6.26 (s, 1 H) 6.78 (d, J=1.6 Hz, 1 H) 7.32 (d, J=8.0 Hz, 1 H) 7.50 (s, 1 H) 7.55 (d, J=2.0 Hz, 1 H) 7.65 (dd, J=1.6, 7.6 Hz, 1 H) 8.06 (s, 1 H); ESI-MS m/z [M+H] + =383.3. [0624] EXAMPLE 153: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (isothiazol-4-yl)pyridin-3-yl)-4-methylbenzamide [0625] 1 H NMR (400 MHz, CDCl3) δ ppm 0.61 - 0.64 (m, 2 H) 0.85 - 0.90 (m, 2 H) 1.36 (s, 6 H) 2.36 (s, 3 H) 2.89 - 2.93 (m, 1 H) 3.68 (s, 2 H) 4.66 (s, 1 H) 6.22 (s, 1 H) 7.32 - 7.34 (m, 1 H) 7.38 (d, J=2.0 Hz, 1 H) 7.58 (s, 1 H) 7.61 - 7.63 (m, 1 H) 8.03 (d, J=2.4 Hz, 1 H) 8.63 (s, 1 H) 8.75 (s, 1 H); ESI-MS m/z [M+H] + =423.2. [0626] EXAMPLE 154: N-cyclopropyl-3-(1-ethyl-1,2,3,5-tetrahydropyrido[2,3- e][1,4]oxazepin-7-yl)-4-methylbenzamide [0627] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.55 - 0.56 (m, 2 H) 0.66 - 0.70 (m, 2 H) 1.19 (t, J=6.8 Hz, 3 H) 2.29 (s, 3 H) 2.83 - 2.85 (m, 1 H) 3.33 - 3.35 (m, 3 H) 3.56 - 3.80 (m, 2 H) 3.81 (t, J=4.4 Hz, 2 H) 4.55 (s, 2 H) 7.36 (d, J=8.0 Hz, 1 H) 7.52 (d, J=2.4 Hz, 1 H) 7.66 - 7.72 (m, 2 H) 8.10 (d, J=2.4 Hz, 1 H) 8.35 (d, J=4.0 Hz, 1 H); ESI-MS m/z [M+H] + =352.1. [0628] EXAMPLE 155: N-cyclopropyl-4-methyl-3-(1-propyl-1,2,3,5-tetrahydropyrido[ 2,3- e][1,4]oxazepin-7-yl)benzamide [0629] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.76 (s, 2 H) 0.88 (d, J=5.6 Hz, 2 H) 1.11 (t, J=7.2 Hz, 3 H) 1.79 - 1.90 (m, 2 H) 2.70 (s, 3 H) 3.00 - 3.13 (m, 1 H) 3.57 (s, 2 H) 3.70 (t, J=6.8 Hz, 2 H) 4.02 (s, 2 H) 4.77 (s, 2 H) 7.56 (d, J=7.6 Hz, 1 H) 7.72 (s, 1 H) 7.86 - 7.96 (m, 2 H) 8.31 (s, 1 H) 8.42 (s, 1 H) 8.58 (d, J=2.8 Hz, 1 H); ESI-MS m/z [M+H] + =366.2. [0630] EXAMPLE 156: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl-1,1- d 2 )amino)-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-4-me thylbenzamide [0631] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.53 - 0.57 (m, 2 H) 0.65 - 0.70 (m, 2 H) 1.39 (s, 6 H) 2.32 (s, 3 H) 2.80 - 2.86 (m, 1 H) 3.89 (s, 3 H) 5.44 (s, 1 H) 7.36 (d, J=8.0 Hz, 1 H) 7.41 (s, 1 H) 7.68 - 7.70 (m, 2 H) 7.73 (s, 1 H) 7.97 (s, 1 H) 8.01(s, 1 H) 8.39 (d, J=4.0 Hz, 1 H); ESI-MS m/z [M+H] + =422.2. [0632] EXAMPLE 157: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (thiazol-5-yl)pyridin-3-yl)-4-methylbenzamide [0633] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.60 - 0.63 (m, 2 H) 0.85 - 0.90 (m, 2 H) 1.37 (s, 6 H) 2.35 (s, 3 H) 2.88 - 2.93 (m, 1 H) 3.68 (s, 2 H) 4.93 (s, 1 H) 6.19 (s, 1 H) 7.32 (d , J=8.4 Hz, 1 H) 7.43 (d, J=2.4 Hz, 1 H) 7.57 (d, J=2.0 Hz, 1 H) 7.62 (dd, J=2.0, 7.6 Hz, 1 H) 7.98 (s, 1 H) 8.03 (d, J=2.4 Hz, 1 H) 8.92 (s, 1 H); ESI-MS m/z [M+H] + =423.2. [0634] EXAMPLE 158: N-cyclopropyl-4-methyl-3-(1-methyl-1,2,3,5- tetrahydropyrido[2,3-e][1,4]oxazepin-7-yl)benzamide [0635] 1 H NMR (400 MHz, CD3OD) δ ppm 0.63 - 0.65 (m, 2 H) 0.76 - 0.86 (m, 2 H) 2.36 (s, 3 H) 2.79 - 2.91 (m, 1 H) 3.38 (s, 3 H) 3.99 - 4.00 (m, 2 H) 4.09 - 4.17 (m, 2 H) 4.89 (s, 2 H) 7.43 (d, J=8.0 Hz, 1 H) 7.68 - 7.81 (m, 2 H) 7.89 (d, J=2.0 Hz, 1 H) 7.96 (d, J=1.8 Hz, 1 H); ESI-MS m/z [M+H] + =338.3. [0636] EXAMPLE 159: N-cyclopropyl-3-(1-(2-methoxyethyl)-1,2,3,5- tetrahydropyrido[2,3-e][1,4]oxazepin-7-yl)-4-methylbenzamide [0637] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.56 (s, 2 H) 0.68 (d, J=5.2 Hz, 2 H) 2.30 (s, 3 H) 2.85 (d, J=3.8 Hz, 1 H) 3.29 (s, 3 H) 3.47 (s, 2 H) 3.61 (t, J=5.8 Hz, 2 H) 3.69 - 3.78 (m, 2 H) 3.82 (s, 2 H) 4.58 (s, 2 H) 7.36 (d, J=7.9 Hz, 1 H) 7.52 (s, 1 H) 7.62 - 7.76 (m, 2 H) 8.09 (s, 1 H) 8.33 - 8.47 (m, 1 H); ESI-MS m/z [M+H] + =382.3. [0638] EXAMPLE 160: N-cyclopropyl-3-(1-(2-hydroxyethyl)-1,2,3,5- tetrahydropyrido[2,3-e][1,4]oxazepin-7-yl)-4-methylbenzamide [0639] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.52 - 0.73 (m, 4 H) 2.29 (s, 3 H) 2.84 (qt, J=3.8, 7.4 Hz, 1 H) 3.43 - 3.52 (m, 2 H), 3.66 (s, 4 H) 3.76 - 3.93 (m, 2 H) 4.58 (s, 2 H) 7.36 (d, J=8.0 Hz, 1 H) 7.52 (d, J=2.0 Hz, 1 H) 7.63 - 7.75 (m, 2 H) 8.07 (d, J=2.0 Hz, 1 H) 8.37 (d, J=4.0 Hz, 1 H); ESI-MS m/z [M+H] + =368.2. [0640] EXAMPLE 161: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (thiazol-2-yl)pyridin-3-yl)-4-methylbenzamide [0641] The title compound was obtained as a formic acid salt. 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.62 - 0.66 (m, 2 H) 0.85 - 0.91 (m, 2 H) 1.50 (s, 6 H) 2.37 (s, 3 H) 2.90 - 2.96 (m, 1 H) 3.74 (s, 2 H) 6.26 (s, 1 H) 7.32 (d, J=3.6 Hz, 1 H) 7.35 (d, J=7.6 Hz, 1 H) 7.60 (d, J=2.0 Hz, 1 H) 7.66 (dd, J=2.0, 7.6 Hz, 1 H) 7.85 (d, J=3.6 Hz, 1 H) 7.89 (d, J=2.0 Hz, 1 H) 8.04 (d, J=2.0 Hz, 1 H) 9.46 (s, 1 H); ESI-MS m/z [M+H] + =423.2. [0642] EXAMPLE 162: N-cyclopropyl-3-(5-(1-ethyl-1H-imidazol-4-yl)-6-((1-hydroxy- 2- methylpropan-2-yl)amino)pyridin-3-yl)-4-methylbenzamide [0643] 1 H NMR (400 MHz, CDCl3) δ ppm 0.63 - 0.65 (m, 2 H) 0.85 - 0.86 (m, 2 H) 1.46 (s, 6 H) 1.52 (t, J=7.2 Hz, 3 H) 2.36 (s, 3 H) 2.90 - 2.92 (m, 1 H) 3.71 (s, 2 H) 4.05 (q, J=7.2 Hz, 2 H) 6.25 (s, 1 H) 7.24 (s, 1 H) 7.31 - 7.33 (m, 1 H) 7.55 - 7.57 (m, 3 H) 7.62 - 7.64 (m, 1 H) 7.87 (d, J=2.0 Hz, 1 H) 8.87 (s, 1 H). ESI-MS m/z [M+H] + =434.3. [0644] EXAMPLE 163: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (1-methyl-1H-imidazol-2-yl)pyridin-3-yl)-4-methylbenzamide [0645] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.61 - 0.65 (m, 2 H) 0.81 - 0.92 (m, 2 H) 1.41 (s, 6 H) 2.34 (s, 3 H) 2.88 - 2.92 (m, 1 H) 3.68 (s, 2 H) 3.73 (s, 3 H) 6.49 (s, 1 H) 7.00 (s, 1 H) 7.18 (s, 1 H) 7.31 (d, J=8.0 Hz, 1 H) 7.42 (d, J=1.6 Hz, 1 H) 7.59 (s, 1 H) 7.63 (d, J=8.0 Hz, 1 H) 7.73 (s, 1 H) 7.95 (d, J=2.0 Hz, 1 H); ESI-MS m/z [M+H] + =420.4. [0646] EXAMPLE 164: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (1-methyl-1H-imidazol-4-yl)pyridin-3-yl)-4-methylbenzamide [0647] The title compound was obtained as a formic acid salt. 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.55 - 0.65 (m, 2 H) 0.66 - 0.68 (m, 2 H) 1.38 (s, 6 H) 2.33 (s, 3 H) 2.87 - 2.80 (m, 1 H) 3.61 (s, 2 H) 3.70 (s, 3 H) 7.35 (d, J=2.4 Hz, 1 H) 7.69 - 7.70 (m, 2 H) 7.73 - 7.74 (m, 2 H) 7.75 - 7.76 (m, 1 H) 7.89 (d, J=2.4 Hz, 1H) 8.30 - 8.40 (m, 1 H) 8.91 (s, 1 H); ESI-MS m/z [M+H] + =420.3. [0648] EXAMPLE 165: N-cyclopropyl-3-(5-(1-ethyl-1H-imidazol-2-yl)-6-((1-hydroxy- 2- methylpropan-2-yl)amino)pyridin-3-yl)-4-methylbenzamide [0649] The title compound was obtained as a formic acid salt. 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.61 - 0.65 (m, 2 H) 0.85 - 0.90 (m, 2 H) 1.39 (s, 6 H) 1.44 (t, J=7.2 Hz, 3 H) 2.36 (s, 3 H) 2.89 - 2.93 (m, 1 H) 3.68 (s, 2 H) 4.03 (q, J=7.2 Hz, 2 H) 6.36 (s, 1 H) 7.09 (s, 1 H) 7.17 (s, 1 H) 7.22 (s, 1 H) 7.32 - 7.34 (m, 1 H) 7.39 (d, J=2.0 Hz, 1 H) 7.58 (s, 1 H) 7.63 - 7.65 (m, 1 H) 8.01 (d, J=2.0 Hz, 1 H); ESI-MS m/z [M+H] + =434.3. [0650] EXAMPLE 166: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-3-yl)-4-methylb enzamide [0651] 1 H NMR (400 MHz, CDCl3) δ ppm 0.60 - 0.67 (m, 2 H) 0.84 - 0.91 (m, 2 H) 1.38 (s, 6 H) 2.35 (s, 3 H) 2.89 - 2.93 (m, 1 H) 3.69 (s, 2 H) 4.70 (s, 1 H) 6.22 (s, 1 H) 7.33 (d, J=7.6 Hz, 1 H) 7.36 (d, J=2.4 Hz, 1 H) 7.57 (d, J=2.0 Hz, 1 H) 7.62 (dd, J=2.0, 8.0 Hz, 1 H) 7.95 (s, 1 H) 7.99 (s, 1 H) 8.01 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =474.4. [0652] EXAMPLE 167: N-cyclopropyl-3-(5-(1-cyclopropyl-1H-pyrazol-4-yl)-6-((1- hydroxy-2-methylpropan-2-yl)amino)pyridin-3-yl)-4-methylbenz amide [0653] 1 H NMR (400 MHz, CDCl3) δ ppm 0.60 - 0.64 (m, 2 H) 0.85 - 0.88 (m, 2 H) 1.07 - 1.12 (m, 2 H) 1.22 - 1.25 (m, 2 H) 1.37 (s, 6 H) 2.35 (s, 3 H) 2.89 - 2.93 (m, 1 H) 3.65 - 3.70 (m, 3 H) 4.96 (s, 1 H) 6.21 (s, 1 H) 7.31 - 7.33 (m, 2 H) 7.56 (s, 1 H) 7.62 (d, J=9.6 Hz, 3 H) 7.92 (d, J=2.0 Hz, 1 H); ESI-MS m/z [M+H] + =446.4. [0654] EXAMPLE 168: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (isothiazol-3-yl)pyridin-3-yl)-4-methylbenzamide [0655] 1 H NMR (400 MHz, CDCl3) δ ppm 0.61 - 0.65 (m, 2 H) 0.85 - 0.90 (m, 2 H) 1.49 (s, 6 H) 2.36 (s, 3 H) 2.89 - 2.93 (m, 1 H) 3.74 (s, 2 H) 6.23 (s, 1 H) 7.34 (d, J=8.0 Hz, 1 H) 7.66 - 7.60 (m, 3 H) 7.90 (s, 1 H) 8.03 (s, 1 H) 8.71 (d, J=4.8 Hz, 1 H) 9.22 (s, 1 H); ESI-MS m/z [M+H] + =423.2. [0656] EXAMPLE 169: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (5-methyl-1H-imidazol-2-yl)pyridin-3-yl)-4-methylbenzamide [0657] 1 H NMR (400 MHz, CDCl3) δ ppm 0.58 - 0.62 (m, 2 H) 0.75 (d, J=6.4 Hz, 2 H) 1.47 (s, 6 H) 2.25 (s, 3 H) 2.34 (s, 3 H) 2.76 (d, J=3.2 Hz, 1 H) 3.72 (s, 2 H) 6.87 (s, 1 H) 7.09 (d, J=8.4 Hz, 1 H) 7.42 - 7.46(m, 2 H) 7.59 (s, 1 H) 8.04 (s, 1 H); ESI-MS m/z [M+H] + =420.2. [0658] EXAMPLE 170: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (1H-imidazol-2-yl)pyridin-3-yl)-4-methylbenzamide [0659] 1 H NMR (400 MHz, CDCl3) δ ppm 0.58 - 0.60 (m, 2 H) 0.79 - 0.82 (m, 2 H) 1.50 (s, 6 H) 2.33 (s, 3 H) 2.76 - 2.87 (m, 1 H) 3.72 (s, 2 H) 6.37 (s, 1 H) 7.17 (s, 1 H) 7.21 (s, 1 H) 7.23 (s, 1 H) 7.47 (s, 1 H) 7.50 (dd, J=1.6, 8.0 Hz, 1 H) 7.80 (d, J=2.0 Hz, 1 H) 7.89 (d, J=2.0 Hz, 1 H) 9.62 (s, 1 H) 10.75 (s, 1 H); ESI-MS m/z [M+H] + =406.2. [0660] EXAMPLE 171: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (1H-imidazol-4-yl)pyridin-3-yl)-4-methylbenzamide [0661] 1 H NMR (400 MHz, CDCl3) δ ppm 0.63 - 0.66 (m, 2 H) 0.83 - 0.89 (m, 2 H) 1.46 (s, 6 H) 2.29 (s, 3 H) 2.89 - 2.92 (m, 1 H) 3.71 (s, 2 H) 6.51 (s, 1 H) 7.21 (s, 1 H) 7.29 (d, J=7.6 Hz, 1 H) 7.51 (d, J=2.0 Hz, 1 H) 7.54 (d, J=2.0 Hz, 1 H) 7.55 (dd, J=2.0, 8.0 Hz, 1 H) 7.70 (s, 1 H) 7.80 (d, J=2.0 Hz, 1 H) 8.88 (s, 1 H); ESI-MS m/z [M+H] + =406.2. [0662] EXAMPLE 172: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (isothiazol-5-yl)pyridin-3-yl)-4-methylbenzamide [0663] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.56 - 0.65 (m, 2 H) 0.86 - 0.90 (m, 2 H) 1.39 (s, 6 H) 2.36 (s, 3 H) 2.89 - 2.93 (m, 1 H) 3.69 (s, 2 H) 5.01 (s, 1 H) 6.24 (s, 1 H) 7.34 (d, J=8.0 Hz, 1 H) 7.40 (d, J=0.8 Hz, 1 H) 7.47 (d, J=2.4 Hz, 1 H) 7.58 (s, 1 H) 7.63 (d, J=8.0 Hz, 1 H) 8.06 (d, J=2.0 Hz, 1 H) 8.59 (s, 1 H); ESI-MS m/z [M+H] + =423.4. [0664] EXAMPLE 173: N-cyclopropyl-3-(5-(1,5-dimethyl-1H-imidazol-2-yl)-6-((1- hydroxy-2-methylpropan-2-yl)amino)pyridin-3-yl)-4-methylbenz amide [0665] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.61 - 0.65 (m, 2 H) 0.86 - 0.90 (m, 2 H) 1.26 (s, 1 H) 1.41 (s, 6 H) 2.29 (s, 3 H) 2.36 (s, 3 H) 2.89 - 2.94 (m, 1 H) 3.58 (s, 3 H) 3.69 (s, 2 H) 6.24 (s, 1 H) 6.94 (d, J=0.8 Hz, 1 H) 7.34 (d, J=7.6 Hz, 1 H) 7.39 (d, J=2.0 Hz, 1 H) 7.58 (d, J=1.6 Hz, 1 H) 7.64 (dd, J=2.0, 8.0 Hz, 1 H) 7.76 (s, 1 H) 7.98 (d, J=2.4 Hz, 1 H); ESI- MS m/z [M+H] + =434.3. [0666] EXAMPLE 174: N-cyclopropyl-3-(5-(1,4-dimethyl-1H-imidazol-2-yl)-6-((1- hydroxy-2-methylpropan-2-yl)amino)pyridin-3-yl)-4-methylbenz amide [0667] 1 H NMR (400 MHz, CDCl3) δ ppm 0.61 - 0.65 (m, 2 H) 0.85 - 0.90 (m, 2 H) 1.42 (s, 6 H) 2.27 (s, 3 H) 2.34 (s, 3 H) 2.89 - 2.93 (m, 1 H) 3.67 (s, 3 H) 3.69 (s, 2 H) 6.34 (s, 1 H) 6.70 (s, 1 H) 7.33 (d, J=7.6 Hz, 1 H) 7.40 (d, J=2.0 Hz, 1 H) 7.58 (s, 1 H) 7.62 - 7.64 (m, 2 H) 7.94 (d, J=2.0 Hz, 1 H) 8.04 (s, 1 H); ESI-MS m/z [M+H] + =434.3. [0668] EXAMPLE 175: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (methoxymethyl)pyridin-3-yl)-4-methylbenzamide [0669] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.55 - 0.57 (m, 2 H) 0.67 - 0.69 (m, 2 H) 1.39 (s, 6 H) 2.30 (s, 3 H) 2.82 - 2.87 (m, 1 H) 3.29 (s, 3 H) 3.50 (s, 2 H) 4.39 (s, 2 H) 5.34 (s, 1 H) 5.68 (s, 1 H) 7.36 (d, J=8.0 Hz, 1 H) 7.43 (s, 1 H) 7.66 (s, 1 H) 7.71 (d, J=8.0 Hz, 1 H) 8.01 (s, 1 H) 8.39 (d, J=4.4 Hz, 1 H) ESI-MS m/z [M+H] + =384.1. [0670] EXAMPLE 176: N-cyclopropyl-4-methyl-3-(1-(2,2,2-trifluoroethyl)-1,2,3,5- tetrahydropyrido[2,3-e][1,4]oxazepin-7-yl)benzamide [0671] 1 H NMR (400 MHz, CDCl3) δ ppm 0.58 - 0.66 (m, 2 H) 0.83 - 0.92 (m, 2 H) 2.32 (s, 3 H) 2.85 - 2.97 (m, 1 H) 3.42 - 3.51 (m, 2 H) 3.90 - 3.97 (m, 2 H) 4.45 (q, J=9.2 Hz, 2 H) 4.61 (s, 2 H) 6.22 (s, 1 H) 7.34 (d, J=8.0 Hz, 1 H) 7.44 (d, J=2.0 Hz, 1 H) 7.55 (d, J=2.0 Hz, 1 H) 7.65 (dd, J=8.0, 2.0 Hz, 1 H) 8.14 (d, J=2.0 Hz, 1 H); ESI-MS m/z [M+H] + =406.1. [0672] EXAMPLE 177: 2-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(5-(isoxazol-3- ylcarbamoyl)-2-methylphenyl)-N,N-dimethylnicotinamide [0673] STEP A: 2-((3-(dimethylcarbamoyl)-5-(5-(isoxazol-3-ylcarbamoyl)-2- methylphenyl)pyridin-2-yl)amino)-2-methylpropyl acetate [0674] To a solution of 3-bromo-N-(isoxazol-3-yl)-4-methylbenzamide (100 mg, 355.74 µmol) and 2-((3-(dimethylcarbamoyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxa borolan-2- yl)pyridin-2-yl)amino)-2-methylpropyl acetate (173.02 mg, 426.89 µmol) in dioxane (3 mL) and H2O (0.3 mL) were added Na2CO3 (113.11 mg, 1.07 mmol) and Pd(dppf)Cl2 (26.03 mg, 35.57 µmol). The reaction mixture was stirred at 90°C for 3 hours under N 2 and then poured into water (20 mL). The aqueous phase was extracted with EtOAc. The organic layers were combined, washed with brine, dried over anhydrous Na2SO4, filtered, concentrated under vacuum and purified by preparative TLC (EtOAc/Petroleum ether 50%). The title compound was obtained as a yellow oil (154 mg, 90.3%). ESI-MS m/z [M+H] + =480.3. [0675] STEP B: 2-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(5-(isoxazol-3- ylcarbamoyl)-2-methylphenyl)-N,N-dimethylnicotinamide [0676] To a solution of 2-((3-(dimethylcarbamoyl)-5-(5-(isoxazol-3-ylcarbamoyl)-2- methylphenyl)pyridin-2-yl)amino)-2-methylpropyl acetate (75 mg, 156.40 µmol) in MeOH (3 mL) was added K2CO3 (64.85 mg, 469.21 µmol). The reaction mixture was stirred at 50°C for 1 hour and then adjusted to pH 7 with HCl (1M), concentrated under vacuum and purified by preparative HPLC. The title compound was obtained as a white solid (22 mg). 1 H NMR (400 MHz, CDCl 3 ) δ ppm 1.40 (s, 6 H) 2.37 (s, 3 H) 3.10 (s, 6 H) 3.67 (d, J=5.2 Hz, 2 H) 6.21 (s, 1 H) 7.08 (t, J=5.6 Hz, 1 H) 7.21 (d, J=2.0 Hz, 1 H) 7.38 (d, J=2.4 Hz, 1 H) 7.42 (d, J=8.0 Hz, 1 H) 7.76 (d, J=2.0 Hz, 1 H) 7.80 (dd, J=1.6, 8.0 Hz, 1 H) 8.04 (d, J=2.4 Hz, 1 H) 8.32 (d, J=1.6 Hz, 1 H) 9.16 (s, 1 H); ESI-MS m/z [M+H] + =438.2. [0677] EXAMPLE 178: 5-(4-fluoro-5-(isoxazol-3-ylcarbamoyl)-2-methylphenyl)-2-((1 - hydroxy-2-methylpropan-2-yl)amino)-N,N-dimethylnicotinamide [0678] STEP A: 2-((3-(dimethylcarbamoyl)-5-(4-fluoro-5-(isoxazol-3-ylcarbam oyl)-2- methylphenyl)pyridin-2-yl)amino)-2-methylpropyl acetate [0679] A mixture of 5-bromo-2-fluoro-N-(isoxazol-3-yl)-4-methylbenzamide (110 mg, 367.78 µmol), 2-((3-(dimethylcarbamoyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxa borolan-2- yl)pyridin-2-yl)amino)-2-methylpropyl acetate (163.96 mg, 404.55 µmol), K2CO3 (101.66 mg, 735.55 µmol) and Pd(dppf)Cl 2 (13.46 mg, 18.39 µmol) in dioxane (2.5 mL) and H 2 O (0.5 mL) was stirred at 90°C for 5 hours under N2. The reaction mixture was then diluted with EtOAc, washed with H 2 O and brine, dried over Na 2 SO 4 , filtered, concentrated under reduced pressure and purified by column chromatography (SiO2, EtOAc/Petroleum ether 5% to 30%). The title compound was obtained as a white solid (110 mg, 60.1%). ESI-MS m/z [M+H] + =498.2. [0680] STEP B: 5-(4-fluoro-5-(isoxazol-3-ylcarbamoyl)-2-methylphenyl)-2-((1 -hydroxy-2- methylpropan-2-yl)amino)-N,N-dimethylnicotinamide [0681] A mixture of 2-((3-(dimethylcarbamoyl)-5-(4-fluoro-5-(isoxazol-3-ylcarbam oyl)-2- methylphenyl)pyridin-2-yl)amino)-2-methylpropyl acetate (110 mg, 221.10 µmol) and K2CO3 (61.11 mg, 442.20 µmol) in MeOH (5 mL) was stirred at 50°C for 2 hours under N2. The reaction mixture was then diluted with EtOAc, washed with H 2 O and brine, dried over Na2SO4, filtered, concentrated under reduced pressure and purified by preparative HPLC. The title compound was obtained as a white solid (21.21 mg). 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 1.38 (s, 6 H) 2.35 (s, 3 H) 2.98 (s, 6 H) 3.46 (s, 2 H) 5.18 (s, 1 H) 6.07 (s, 1H) 7.02 (d, J=1.6 Hz, 1 H) 7.32 (d, J=11.6 Hz, 1 H) 7.52 (d, J=2.4 Hz, 1 H) 7.56 (d, J=7.2 Hz, 1 H) 8.15 (d, J=2.4 Hz, 1 H) 8.86 (d, J=2.0 Hz, 1 H) 11.40 (s, 1 H); ESI-MS m/z [M+H] + =456.2. [0682] EXAMPLE 179: (S)-5-(4-fluoro-5-(isoxazol-3-ylcarbamoyl)-2-methylphenyl)-2 - ((1-hydroxypropan-2-yl)amino)-N,N-dimethylnicotinamide [0683] STEP A: (S)-5-bromo-2-((1-hydroxypropan-2-yl)amino)nicotinic acid [0684] A mixture of 5-bromo-2-fluoro-pyridine-3-carboxylic acid (1.4 g, 6.36 mmol), DIPEA (3.33 mL, 19.09 mmol) and (S)-2-aminopropan-1-ol (955.96 mg, 12.73 mmol) in DMSO (8 mL) was stirred at 180°C for 2 hours. The reaction mixture was diluted with EtOAc and washed with H2O and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was triturated with 20% Petroleum ether/EtOAc to give the title compound as a white solid (1.6 g, 91%). ESI-MS m/z [M+H] + =275.0. [0685] STEP B: (S)-5-bromo-2-((1-hydroxypropan-2-yl)amino)-N,N-dimethylnico tinamide [0686] To a solution of (S)-5-bromo-2-((1-hydroxypropan-2-yl)amino)nicotinic acid (1.58 g, 5.74 mmol) in DMF (15 mL) were added EDCI (1.65 g, 8.62 mmol), HOBt (1.16 g, 8.62 mmol) and DIPEA (6.00 mL 34.46 mmol). N-methylmethanamine (936.68 mg, 11.49 mmol) was added. The reaction mixture was stirred at 15°C for 12 hours and then diluted with EtOAc, washed with H2O and brine, dried over Na2SO4, filtered, concentrated under reduced pressure and purified by column chromatography (SiO 2 , EtOAc/Petroleum ether 50% to 100%). The title compound was obtained as a yellow oil (686 mg, 39.5%). 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 1.23 - 1.25 (m, 3 H) 3.08 (s, 6 H) 3.60 (dd, J=6.8, 10.4 Hz, 1 H) 3.60 (dd, J=3.2, 10.8 Hz, 1 H) 4.15 - 4.18 (m, 1 H) 5.99 (d, J=5.6 Hz, 1 H) 7.44 (d, J=2.4 Hz, 1 H) 8.12 (d, J=2.8 Hz, 1 H); ESI-MS m/z [M+H] + =302.1. [0687] STEP C: (S)-2-((5-bromo-3-(dimethylcarbamoyl)pyridin-2-yl)amino)prop yl acetate [0688] To a solution of (S)-5-bromo-2-((1-hydroxypropan-2-yl)amino)-N,N- dimethylnicotinamide (500 mg, 1.65 mmol) in pyridine (4 mL) was added Ac2O (309.96 µL, 3.31 mmol) at 20°C. The reaction mixture was stirred at 80°C for 12 hours and then diluted with EtOAc, washed with H2O and brine, dried over Na2SO4, filtered and concentrated under reduced pressure to give the title compound as a yellow oil (530 mg, 93.1%). 1 H NMR (400 MHz, DMSO-d6) δ ppm 1.26 (d, J=6.8 Hz, 3 H) 2.07 (s, 3 H) 3.07 (s, 6 H) 4.14 (dd, J=2.4, 5.6 Hz, 2 H) 4.40 - 4.46 (m, 1 H) 5.88 (d, J=7.6 Hz, 1 H) 7.43 (d, J=2.4Hz, 1 H) 8.17 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =344.1. [0689] STEP D: (S)-2-((3-(dimethylcarbamoyl)-5-(4,4,5,5-tetramethyl-1,3,2-d ioxaborolan- 2-yl)pyridin-2-yl)amino)propyl acetate [0690] To a solution of (S)-2-((5-bromo-3-(dimethylcarbamoyl)pyridin-2-yl)amino)prop yl acetate (530 mg, 1.54 mmol) and 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1,3,2-dioxaborolane (430.11 mg, 1.69 mmol) in dioxane (10 mL) were added Pd(dppf)Cl 2 (56.33 mg, 76.99 µmol) and KOAc (377.79 mg, 3.85 mmol). The reaction mixture was stirred at 90°C for 3 hours and then concentrated under reduced pressure and purified by column chromatography (SiO 2 , EtOAc/Petroleum ether 3% to 10%). The title compound was obtained as a brown oil (750 mg, crude). ESI-MS m/z [M+H] + =392.1. [0691] STEP E: (S)-2-((3-(dimethylcarbamoyl)-5-(4-fluoro-5-(isoxazol-3-ylca rbamoyl)-2- methylphenyl)pyridin-2-yl)amino)propyl acetate [0692] A mixture of 5-bromo-2-fluoro-N-(isoxazol-3-yl)-4-methylbenzamide (129.00 mg, 431.29 µmol), (S)-2-((3-(dimethylcarbamoyl)-5-(4,4,5,5-tetramethyl-1,3,2-d ioxaborolan-2- yl)pyridin-2-yl)amino)propyl acetate (270 mg, 690.06 µmol), K2CO3 (119.21 mg, 862.58 µmol) and Pd(dppf)Cl 2 (15.78 mg, 21.56 µmol) in dioxane (5 mL) and H 2 O (1 mL) was stirred at 90°C for 5 hours. The reaction mixture was then filtered, and the filtrate was poured into H 2 O and extracted with ethyl acetate. The organic layer was washed with brine, dried over Na2SO4, concentrated under reduce pressure and purified by column chromatography (SiO2, EtOAc/Petroleum ether 10% to 60%). The title compound was obtained as a yellow solid (150 mg, 71.9%). ESI-MS m/z [M+H] + =484.3. [0693] STEP F: (S)-5-(4-fluoro-5-(isoxazol-3-ylcarbamoyl)-2-methylphenyl)-2 -((1- hydroxypropan-2-yl)amino)-N,N-dimethylnicotinamide [0694] To a solution of (S)-2-((3-(dimethylcarbamoyl)-5-(4-fluoro-5-(isoxazol-3- ylcarbamoyl)-2-methylphenyl)pyridin-2-yl)amino)propyl acetate (150 mg, 310.24 µmol) in MeOH (5 mL) was added K2CO3 (85.76 mg, 620.49 µmol). The reaction mixture was stirred at 50°C for 2 hours and then concentrated under reduced pressure and purified by preparative HPLC. The title compound was obtained as a white solid (9.01 mg). 1 H NMR (400 MHz, CDCl 3 ) δ ppm 1.21 - 1.23 (d, J=6.8 Hz, 3 H) 2.29 (s, 3 H) 3.04 (s, 6 H) 3.55 (dd, J=7.6, 10.8 Hz, 1 H) 3.72 (dd, J=2.8, 10.8 Hz, 1 H) 4.12 - 4.21 (m, 1 H) 6.06 (d, J=5.6 Hz, 1 H) 7.09 (d, J=12.8 Hz, 1 H) 7.12 (d, J=1.6 Hz, 1 H) 7.28 (d, J=2.4 Hz, 1 H) 7.90 (d, J=8.4 Hz, 1 H) 7.99 (d, J=2.4 Hz, 1 H) 8.28 (d, J=1.6 Hz, 1 H) 9.06 (d, J=14.8 Hz, 1 H); ESI-MS m/z [M+H] + =442.1. [0695] EXAMPLE 180: 5-(5-(azetidine-1-carbonyl)-6-((1-hydroxy-2-methylpropan-2- yl)amino)pyridin-3-yl)-N-cyclopropyl-2-fluoro-4-methylbenzam ide [0696] STEP A: 5-(5-(cyclopropylcarbamoyl)-4-fluoro-2-methylphenyl)-2-((1-h ydroxy-2- methylpropan-2-yl)amino)nicotinic acid [0697] To a solution of N-cyclopropyl-2-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2 - dioxaborolan-2-yl)benzamide (401.43 mg, 1.26 mmol), 5-bromo-2-((1-hydroxy-2- methylpropan-2-yl)amino)nicotinic acid (400 mg, 1.38 mmol) and K 2 CO 3 (347.65 mg, 2.52 mmol) in dioxane (5 mL) and H2O (1 mL) was added Pd(dppf)Cl2 (46.01 mg, 62.89 µmol) under N 2 . The reaction mixture was stirred at 90°C for 16 hours and then poured into water and extracted with EtOAc. The aqueous layer was adjusted to pH=3 with 1 N HCl aqueous solution and extracted with EtOAc. The combined organic layers were dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to afford the title compound as a yellow solid (420 mg, 75.4%). ESI-MS m/z [M+H] + =402.3. [0698] STEP B: 5-(5-(azetidine-1-carbonyl)-6-((1-hydroxy-2-methylpropan-2- yl)amino)pyridin-3-yl)-N-cyclopropyl-2-fluoro-4-methylbenzam ide [0699] To a solution of 5-(5-(cyclopropylcarbamoyl)-4-fluoro-2-methylphenyl)-2-((1- hydroxy-2-methylpropan-2-yl)amino)nicotinic acid (100 mg, 225.64 µmol), HATU (128.69 mg, 338.46 µmol) and DIPEA (87.49 mg, 676.93 µmol, 117.91 µL) in DMF (2 mL) was added azetidine (32.21 mg, 564.11 µmol, 38.07 µL). The mixture was stirred at 25°C for 16 hours and then diluted with EtOAc and washed with aqueous NaCl. The combined organic phase was dried over anhydrous Na2SO4, filtered, concentrated under vacuum and purified by preparative TLC (MeOH/EtOAc 5%) followed by preparative HPLC. The title compound was obtained as a white solid (33.39 mg). 1 H NMR (400 MHz, CD3OD) δ ppm 0.62-0.64 (m, 2 H) 0.80-0.84 (m, 2 H) 1.42 (s, 6 H) 2.31-2.39 (m, 5 H) 2.84-2.88 (m, 1 H) 3.71 (s, 2 H) 4.20-4.39 (m, 4 H) 7.15 (d, J=11.6 Hz, 1 H) 7.49 (d, J=7.2 Hz, 1 H) 7.59 (d, J=2.4 Hz, 1 H) 8.06 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =441.3. [0700] EXAMPLE 181: 2-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(5-(isothiazol-3- ylcarbamoyl)-2-methylphenyl)-N,N-dimethylnicotinamide [0701] STEP A: 2-((3-(dimethylcarbamoyl)-5-(5-(isothiazol-3-ylcarbamoyl)-2- methylphenyl)pyridin-2-yl)amino)-2-methylpropyl acetate [0702] A mixture of 3-bromo-N-(isothiazol-3-yl)-4-methylbenzamide (80 mg, 269.21 µmol), 2-((3-(dimethylcarbamoyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxa borolan-2-yl)pyridin-2- yl)amino)-2-methylpropyl acetate (174.57 mg, 430.73 µmol), Pd(dppf)Cl2 (19.70 mg, 26.92 µmol) and K 2 CO 3 (93.01 mg, 673.01 µmol) in dioxane (5 mL) and H 2 O (0.5 mL) was degassed and purged with N2 (3 x). The reaction mixture was stirred at 90°C for 8 hours under N 2 and then diluted with water (20 mL) and extracted with EtOAc. The organic layers were combined, washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to give the title compound as a brown oil (100 mg, crude). ESI-MS m/z [M+H] + =496.3. [0703] STEP B: 2-((1-hydroxy-2-methylpropan-2-yl)amino)-5-(5-(isothiazol-3- ylcarbamoyl)-2-methylphenyl)-N,N-dimethylnicotinamide [0704] To a solution of 2-((3-(dimethylcarbamoyl)-5-(5-(isothiazol-3-ylcarbamoyl)-2- methylphenyl)pyridin-2-yl)amino)-2-methylpropyl acetate (100 mg, 201.78 µmol) in MeOH (1 mL) was added K 2 CO 3 (27.89 mg, 201.78 µmol). The reaction mixture was stirred at 50°C for 15 minutes and then filtered and concentrated under reduced pressure. The resulting residue was purified by preparative HPLC. The product-containing fractions were collected, concentrated and lyophilized to give the title compound as a yellow solid (18.88 mg, 20.12%). 1 H NMR (400 MHz, CDCl 3 ) ppm 1.39 (s, 6 H) 2.28 - 2.44 (m, 3 H) 3.00 (s, 6 H) 3.47 (s, 2 H) 5.13 - 5.28 (m, 1 H) 6.09 (s, 1 H) 7.44 (d, J=8.0 Hz, 1 H) 7.57 (d, J=2.4 Hz, 1 H) 7.98 - 7.82 (m, 3 H) 8.22 (d, J=2.4 Hz, 1 H) 9.05 (d, J=4.8 Hz, 1 H) 11.50 (s, 1 H). ESI- MS m/z [M+H] + =454.2. [0705] EXAMPLE 182: 5-(4-fluoro-5-(isothiazol-3-ylcarbamoyl)-2-methylphenyl)-2-( (1- hydroxy-2-methylpropan-2-yl)amino)-N,N-dimethylnicotinamide [0706] STEP A: 2-((3-(dimethylcarbamoyl)-5-(4-fluoro-5-(isothiazol-3-ylcarb amoyl)-2- methylphenyl)pyridin-2-yl)amino)-2-methylpropyl acetate [0707] A mixture of 5-bromo-2-fluoro-N-(isothiazol-3-yl)-4-methylbenzamide (160 mg, 507.68 µmol), 2-((3-(dimethylcarbamoyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxa borolan-2- yl)pyridin-2-yl)amino)-2-methylpropyl acetate (246.91 mg,609.21 µmol), Na 2 CO 3 (107.62 mg, 1.02 mmol) and Pd(dppf)Cl2 (37.15 mg, 50.77 µmol) in dioxane (2 mL) and H2O (0.4 mL) was degassed and purged with N 2 (3 x). The mixture was stirred at 90°C for 6 hours under N2 and then concentrated under reduced pressure and purified by column chromatography (SiO 2 , EtOAc/Petroleum ether 20% to 50%). The title compound was obtained as a white oil (190 mg, 72.9%). ESI-MS m/z [M+H] + =514.1. [0708] STEP B: 5-(4-fluoro-5-(isothiazol-3-ylcarbamoyl)-2-methylphenyl)-2-( (1-hydroxy- 2-methylpropan-2-yl)amino)-N,N-dimethylnicotinamide [0709] To a solution of 2-((3-(dimethylcarbamoyl)-5-(4-fluoro-5-(isothiazol-3- ylcarbamoyl)-2-methylphenyl)pyridin-2-yl)amino)-2-methylprop yl acetate (190 mg, 369.95 µmol) in MeOH (2 mL) was added K 2 CO 3 (51.13 mg, 369.95 µmol). The mixture was stirred at 50°C for 15 minutes and then purified by preparative HPLC. The title compound was obtained as a white solid (66 mg, 38%). 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 1.38 (s, 6 H) 2.36 (s, 3 H) 2.99 (s, 6 H) 3.46 (s, 2 H) 5.19 (s, 1 H) 6.08 (s, 1 H) 7.32 (d, J=11.6 Hz, 1 H) 7.53 (d, J=2.4 Hz, 1 H) 7.56 (d, J=7.6 Hz, 1 H) 7.87 (d, J=4.8 Hz, 1 H) 8.16 (d, J=2.4 Hz, 1 H) 9.07 (d, J=4.8 Hz, 1 H) 11.46 (s, 1 H); ESI-MS m/z [M+H] + =472.2. [0710] Examples 183 to 247, below, were prepared like Examples 177 to 182. [0711] EXAMPLE 183: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)nicotinamide [0712] 1 H NMR (400 MHz, CD3OD) δ ppm 0.62 - 0.69 (m, 2 H) 0.79 - 0.85 (m, 2 H) 1.44 (s, 6 H) 2.37 (s, 3 H) 2.83 - 2.90 (m, 1 H) 3.73 (s, 2 H) 7.36 - 7.42 (m, 1 H) 7.67 - 7.73 (m, 2 H) 7.97 - 8.01 (m, 1 H) 8.13 - 8.17 (m, 1 H); ESI-MS m/z [M+H] + =383.4. [0713] EXAMPLE 184: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-methylnicotinamide [0714] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.62 - 0.69 (m, 2 H) 0.77 - 0.86 (m, 2 H) 1.44 (s, 6 H) 2.36 (s, 3 H) 2.82 - 2.87 (m, 1 H) 2.88 (s, 3 H) 3.72 (s, 2 H) 7.38 (d, J=7.70 Hz, 1 H) 7.66 - 7.74 (m, 2 H) 7.87 (d, J=2.20 Hz, 1 H) 8.12 (d, J=2.20 Hz, 1 H); ESI-MS m/z [M+H] + =397.5. [0715] EXAMPLE 185: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-(3,3,3-trifluoropropyl)nicotinami de [0716] 1 H NMR (400 MHz, CD3OD) δ ppm 0.66 (br d, J=2.57 Hz, 2 H) 0.79 - 0.86 (m, 2 H) 1.45 (s, 6 H) 2.36 (s, 3 H) 2.45 - 2.58 (m, 2 H) 2.83 - 2.91 (m, 1 H) 3.56 - 3.63 (m, 2 H) 3.73 (s, 2 H) 7.37 - 7.43 (m, 1 H) 7.66 - 7.74 (m, 2 H) 7.86 - 7.90 (m, 1 H) 8.13 - 8.17 (m, 1 H); ESI-MS m/z [M+H] + =479.5. [0717] EXAMPLE 186: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1- (hydroxymethyl)cyclopropyl)amino)-N-methylnicotinamide [0718] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.50 - 0.56 (m, 2 H) 0.66 - 0.76 (m, 4 H) 0.83 - 0.89 (m, 2 H) 2.24 (s, 3 H) 2.76 (s, 4 H) 3.60 (s, 2 H) 7.25 - 7.31 (m, 1 H) 7.54 - 7.63 (m, 2 H) 7.73 - 7.78 (m, 1 H) 8.06 (d, J=1.10 Hz, 1 H); ESI-MS m/z [M+H] + =395.5. [0719] EXAMPLE 187: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-N-ethyl-2-((1- hydroxy-2-methylpropan-2-yl)amino)nicotinamide [0720] 1 H NMR (400 MHz, CD3OD) δ ppm 0.62 - 0.69 (m, 2 H) 0.78 - 0.86 (m, 2 H) 1.17 - 1.25 (m, 3 H) 1.44 (s, 6 H) 2.37 (s, 3 H) 2.82 - 2.91 (m, 1 H) 3.35 - 3.43 (m, 2 H) 3.72 (s, 2 H) 7.36 - 7.42 (m, 1 H) 7.67 - 7.74 (m, 2 H) 7.89 (d, J=2.20 Hz, 1 H) 8.10 - 8.15 (m, 1 H); ESI-MS m/z [M+H] + =411.5. [0721] EXAMPLE 188: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-(2-hydroxyethyl)nicotinamide [0722] 1 H NMR (400 MHz, CD3OD) δ ppm 0.60 - 0.70 (m, 2 H) 0.82 (br d, J=5.87 Hz, 2 H) 1.44 (s, 6 H) 2.37 (s, 3 H) 2.81 - 2.92 (m, 1 H) 3.48 (s, 2 H) 3.62 - 3.78 (m, 4 H) 7.39 (d, J=7.70 Hz, 1 H) 7.66 - 7.75 (m, 2 H) 7.94 (d, J=1.65 Hz, 1 H) 8.14 (s, 1 H); ESI-MS m/z [M+H] + =427.4. [0723] EXAMPLE 189: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-(oxetan-3-yl)nicotinamide [0724] 1 H NMR (400 MHz, CD3OD) δ ppm 0.49 - 0.57 (m, 2 H) 0.66 - 0.75 (m, 2 H) 1.32 (s, 6 H) 2.26 (s, 3 H) 2.71 - 2.80 (m, 1 H) 3.60 (s, 2 H) 4.54 - 4.61 (m, 2 H) 4.80 (s, 2 H) 4.93 - 5.02 (m, 1 H) 7.24 - 7.32 (m, 1 H) 7.59 (s, 2 H) 7.87 - 7.92 (m, 1 H) 8.01 - 8.07 (m, 1 H); ESI-MS m/z [M+H] + =439.5. [0725] EXAMPLE 190: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1- hydroxypropan-2-yl)amino)-N-methylnicotinamide [0726] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.62 - 0.69 (m, 2 H) 0.78 - 0.86 (m, 2 H) 1.30 (d, J=6.79 Hz, 3 H) 2.36 (s, 3 H) 2.83 - 2.88 (m, 1 H) 2.89 (s, 3 H) 3.65 (t, J=5.14 Hz, 2 H) 4.24 - 4.35 (m, 1 H) 7.35 - 7.43 (m, 1 H) 7.66 - 7.74 (m, 2 H) 7.85 (d, J=2.20 Hz, 1 H) 8.11 - 8.17 (m, 1 H); ESI-MS m/z [M+H] + =383.4. [0727] EXAMPLE 191: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-(1-hydroxypropan-2-yl)nicotinamid e [0728] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.61 - 0.70 (m, 2 H) 0.78 - 0.86 (m, 2 H) 1.19 - 1.26 (m, 3 H) 1.44 (s, 6 H) 2.37 (s, 3 H) 2.83 - 2.91 (m, 1 H) 3.59 (d, J=5.69 Hz, 2 H) 3.72 (s, 2 H) 4.13 - 4.23 (m, 1 H) 7.35 - 7.42 (m, 1 H) 7.67 - 7.74 (m, 2 H) 7.92 - 7.96 (m, 1 H) 8.09 - 8.15 (m, 1 H); ESI-MS m/z [M+H] + =441.5. [0729] EXAMPLE 192: N-cyclopropyl-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2- ((1-hydroxy-2-methylpropan-2-yl)amino)nicotinamide [0730] 1 H NMR (400 MHz, CD3OD) δ ppm 0.58 - 0.69 (m, 4 H) 0.81 (s, 4 H) 1.45 (s, 6 H) 2.35 (s, 3 H) 2.77 - 2.90 (m, 2 H) 3.73 (s, 2 H) 7.38 (d, J=7.89 Hz, 1 H) 7.65 - 7.74 (m, 2 H) 7.86 (d, J=2.02 Hz, 1 H) 8.10 - 8.16 (m, 1 H); ESI-MS m/z [M+H] + =423.5. [0731] EXAMPLE 193: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-(tetrahydrofuran-3-yl)nicotinamid e [0732] 1 H NMR (400 MHz, CD3OD) δ ppm 0.62 - 0.70 (m, 2 H) 0.82 (br d, J=5.87 Hz, 2 H) 1.45 (s, 6 H) 1.93 - 2.03 (m, 1 H) 2.24 - 2.34 (m, 1 H) 2.36 (s, 3 H) 2.82 - 2.91 (m, 1 H) 3.67 - 3.76 (m, 3 H) 3.82 (br d, J=6.05 Hz, 1 H) 3.91 - 4.01 (m, 2 H) 4.52 - 4.61 (m, 1 H) 7.39 (d, J=7.89 Hz, 1 H) 7.67 - 7.75 (m, 2 H) 7.94 (d, J=1.47 Hz, 1 H) 8.10 - 8.17 (m, 1 H); ESI-MS m/z [M+H] + =453.5. [0733] EXAMPLE 194: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-(1-methylpyrrolidin-3-yl)nicotina mide [0734] 1 H NMR (400 MHz, CD3OD) δ ppm 0.61 - 0.70 (m, 2 H) 0.77 - 0.87 (m, 2 H) 1.44 (s, 6 H) 1.81 - 1.95 (m, 1 H) 2.37 (s, 4 H) 2.45 (s, 3 H) 2.53 - 2.63 (m, 1 H) 2.68 - 2.77 (m, 1 H) 2.82 - 2.96 (m, 3 H) 3.72 (s, 2 H) 4.49 - 4.61 (m, 1 H) 7.35 - 7.44 (m, 1 H) 7.66 - 7.76 (m, 2 H) 7.96 (d, J=2.02 Hz, 1 H) 8.14 (d, J=2.02 Hz, 1 H); ESI-MS m/z [M+H] + =466.5. [0735] EXAMPLE 195: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-(1-methyl-5-oxopyrrolidin-3-yl)ni cotinamide [0736] 1 H NMR (400 MHz, CD3OD) δ ppm 0.60 - 0.69 (m, 2 H) 0.82 (br d, J=5.87 Hz, 2 H) 1.45 (s, 6 H) 2.36 (s, 3 H) 2.42 - 2.53 (m, 1 H) 2.76 - 2.84 (m, 1 H) 2.85 - 2.91 (m, 4 H) 3.37 - 3.44 (m, 1 H) 3.73 (s, 2 H) 3.82 - 3.91 (m, 1 H) 4.61 - 4.70 (m, 1 H) 7.40 (s, 1 H) 7.69 (s, 2 H) 7.95 (s, 1 H) 8.11 - 8.18 (m, 1 H); ESI-MS m/z [M+H] + =480.5. [0737] EXAMPLE 196: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N,N-dimethylnicotinamide [0738] 1 H NMR (400 MHz, CD3OD) δ ppm 0.61 - 0.70 (m, 2 H) 0.77 - 0.86 (m, 2 H) 1.44 (s, 6 H) 2.36 (s, 3 H) 2.82 - 2.91 (m, 1 H) 3.11 (s, 6 H) 3.69 (s, 2 H) 7.35 - 7.41 (m, 1 H) 7.48 - 7.54 (m, 1 H) 7.63 - 7.68 (m, 1 H) 7.68 - 7.74 (m, 1 H) 8.08 - 8.14 (m, 1 H) 8.45 - 8.55 (m, 1 H); ESI-MS m/z [M+H] + =411.5. [0739] EXAMPLE 197: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-isopropylnicotinamide [0740] 1 H NMR (400 MHz, CD3OD) δ ppm 0.61 - 0.70 (m, 2 H) 0.82 (br d, J=6.24 Hz, 2 H) 1.24 (d, J=6.42 Hz, 6 H) 1.44 (s, 6 H) 2.36 (s, 3 H) 2.87 (s, 1 H) 3.72 (s, 2 H) 4.12 - 4.25 (m, 1 H) 7.34 - 7.44 (m, 1 H) 7.70 (s, 2 H) 7.86 - 7.95 (m, 1 H) 8.11 (s, 1 H); ESI-MS m/z [M+H] + =425.5. [0741] EXAMPLE 198: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-((1-methylazetidin-3-yl)methyl)ni cotinamide [0742] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.61 - 0.70 (m, 2 H) 0.78 - 0.88 (m, 2 H) 1.44 (s, 6 H) 2.37 (s, 3 H) 2.44 (s, 3 H) 2.76 - 2.84 (m, 1 H) 2.85 - 2.91 (m, 1 H) 3.19 - 3.27 (m, 2 H) 3.48 - 3.55 (m, 2 H) 3.56 - 3.63 (m, 2 H) 3.73 (s, 2 H) 7.39 (d, J=7.89 Hz, 1 H) 7.66 - 7.75 (m, 2 H) 7.89 (d, J=1.10 Hz, 1 H) 8.15 (d, J=1.10 Hz, 1 H); ESI-MS m/z [M+H] + =466.5. [0743] EXAMPLE 199: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-(2-methoxycyclopropyl)nicotinamid e [0744] 1 H NMR (400 MHz, CD3OD) δ ppm 0.61 - 0.69 (m, 2 H) 0.82 (br d, J=6.24 Hz, 2 H) 0.92 (br d, J=6.24 Hz, 1 H) 1.05 - 1.15 (m, 1 H) 1.45 (s, 6 H) 2.31 - 2.40 (m, 3 H) 2.80 - 2.91 (m, 2 H) 3.28 - 3.32 (m, 1 H) 3.47 (s, 3 H) 3.73 (s, 2 H) 7.35 - 7.42 (m, 1 H) 7.64 - 7.74 (m, 2 H) 7.82 - 7.87 (m, 1 H) 8.11 - 8.17 (m, 1 H); ESI-MS m/z [M+H] + =453.5. [0745] EXAMPLE 200: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-(1-methylazetidin-3-yl)nicotinami de [0746] 1 H NMR (400 MHz, CD3OD) δ ppm 0.49 - 0.57 (m, 2 H) 0.66 - 0.74 (m, 2 H) 1.33 (s, 6 H) 1.74 - 1.93 (m, 3 H) 2.25 (s, 3 H) 2.72 - 2.79 (m, 1 H) 2.84 - 2.91 (m, 2 H) 3.55 - 3.63 (m, 2 H) 3.65 - 3.70 (m, 1 H) 3.85 - 3.93 (m, 1 H) 4.17 - 4.25 (m, 1 H) 7.24 - 7.32 (m, 1 H) 7.47 - 7.64 (m, 3 H) 8.09 - 8.17 (m, 1 H); ESI-MS m/z [M+H] + =452.5. [0747] EXAMPLE 201: N-(1-cyanopropyl)-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl )- 2-((1-hydroxy-2-methylpropan-2-yl)amino)nicotinamide [0748] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.62 - 0.70 (m, 2 H) 0.79 - 0.86 (m, 2 H) 1.08 - 1.16 (m, 3 H) 1.46 (s, 6 H) 1.90 - 2.02 (m, 2 H) 2.37 (s, 3 H) 2.83 - 2.91 (m, 1 H) 3.75 (s, 2 H) 4.87 - 4.92 (m, 1 H) 7.37 - 7.43 (m, 1 H) 7.68 - 7.75 (m, 2 H) 7.96 (s, 1 H) 8.17 - 8.22 (m, 1 H); ESI-MS m/z [M+H] + =450.5. [0749] EXAMPLE 202: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-(oxetan-3-ylmethyl)nicotinamide [0750] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.61 - 0.69 (m, 2 H) 0.82 (br d, J=6.42 Hz, 2 H) 1.44 (s, 6 H) 2.36 (s, 3 H) 2.83 - 2.91 (m, 1 H) 3.22 - 3.30 (m, 1 H) 3.61 - 3.68 (m, 2 H) 3.69 - 3.76 (m, 2 H) 4.50 (s, 2 H) 4.77 - 4.81 (m, 1 H) 7.39 (d, J=7.89 Hz, 1 H) 7.66 - 7.74 (m, 2 H) 7.89 (d, J=1.28 Hz, 1 H) 8.11 - 8.17 (m, 1 H); ESI-MS m/z [M+H] + =453.5. [0751] EXAMPLE 203: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-(1-methoxy-2-methylpropan-2-yl)ni cotinamide [0752] 1 H NMR (400 MHz, CD3OD) δ ppm 0.49 - 0.57 (m, 2 H) 0.66 - 0.74 (m, 2 H) 1.31 (d, J=13.39 Hz, 12 H) 2.25 (s, 3 H) 2.71 - 2.79 (m, 1 H) 3.27 (s, 3 H) 3.44 - 3.50 (m, 2 H) 3.58 - 3.65 (m, 2 H) 7.25 - 7.31 (m, 1 H) 7.58 (s, 3 H) 7.72 - 7.79 (m, 1 H) 7.95 - 8.02 (m, 1 H) 8.32 - 8.41 (m, 1 H); ESI-MS m/z [M+H] + =469.5. [0753] EXAMPLE 204: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-(tetrahydro-2H-pyran-4-yl)nicotin amide [0754] 1 H NMR (400 MHz, CD3OD) δ ppm 0.63 - 0.68 (m, 2 H) 0.79 - 0.85 (m, 2 H) 1.44 (s, 6 H) 1.60 - 1.72 (m, 2 H) 1.85 - 1.91 (m, 2 H) 2.36 (s, 3 H) 2.83 - 2.90 (m, 1 H) 3.53 (s, 2 H) 3.72 (s, 2 H) 3.96 - 4.02 (m, 2 H) 4.05 - 4.15 (m, 1 H) 7.36 - 7.42 (m, 1 H) 7.68 - 7.73 (m, 2 H) 7.92 (s, 1 H) 8.12 - 8.15 (m, 1 H); ESI-MS m/z [M+H] + =467.6. [0755] EXAMPLE 205: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (morpholine-4-carbonyl)pyridin-3-yl)-4-methylbenzamide [0756] 1 H NMR (400 MHz, CD3OD) δ ppm 0.50 - 0.56 (m, 2 H) 0.70 (br d, J=6.05 Hz, 2 H) 1.33 (s, 6 H) 2.22 - 2.27 (m, 3 H) 2.71 - 2.78 (m, 1 H) 3.53 (br s, 4 H) 3.58 (s, 2 H) 3.59 - 3.66 (m, 4 H) 7.27 (d, J=8.07 Hz, 1 H) 7.37 (d, J=2.02 Hz, 1 H) 7.54 (s, 1 H) 7.56 - 7.62 (m, 1 H) 7.99 - 8.04 (m, 1 H); ESI-MS m/z [M+H] + =453.4. [0757] EXAMPLE 206: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-(2-methylcyclopropyl)nicotinamide [0758] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.54 - 0.61 (m, 1 H) 0.62 - 0.69 (m, 2 H) 0.76 - 0.86 (m, 3 H) 0.94 - 1.03 (m, 1 H) 1.14 (d, J=6.05 Hz, 3 H) 1.45 (s, 6 H) 2.35 (s, 3 H) 2.46 - 2.52 (m, 1 H) 2.83 - 2.91 (m, 1 H) 3.73 (s, 2 H) 7.35 - 7.42 (m, 1 H) 7.64 - 7.74 (m, 2 H) 7.81 - 7.88 (m, 1 H) 8.13 (s, 1 H); ESI-MS m/z [M+H] + =437.5. [0759] EXAMPLE 207: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-N-(1,1- difluoropropan-2-yl)-2-((1-hydroxy-2-methylpropan-2-yl)amino )nicotinamide [0760] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.62 - 0.69 (m, 2 H) 0.82 (br d, J=5.69 Hz, 2 H) 1.31 (d, J=7.15 Hz, 3 H) 1.45 (s, 6 H) 2.37 (s, 3 H) 2.83 - 2.91 (m, 1 H) 3.73 (s, 2 H) 4.38 - 4.52 (m, 1 H) 5.76 - 6.07 (m, 1 H) 7.39 (d, J=7.89 Hz, 1 H) 7.67 - 7.75 (m, 2 H) 7.92 - 7.98 (m, 1 H) 8.12 - 8.18 (m, 1 H); ESI-MS m/z [M+H] + =461.3. [0761] EXAMPLE 208: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (2-methylmorpholine-4-carbonyl)pyridin-3-yl)-4-methylbenzami de [0762] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.50 - 0.57 (m, 2 H) 0.66 - 0.74 (m, 2 H) 1.06 (br d, J=6.05 Hz, 3 H) 1.33 (s, 6 H) 2.25 (s, 3 H) 2.69 - 2.81 (m, 2 H) 2.99 - 3.16 (m, 2 H) 3.45 - 3.55 (m, 2 H) 3.57 (s, 2 H) 3.76 - 3.88 (m, 2 H) 5.60 - 5.68 (m, 1 H) 7.24 - 7.30 (m, 1 H) 7.35 - 7.40 (m, 1 H) 7.51 - 7.55 (m, 1 H) 7.56 - 7.62 (m, 1 H) 7.99 - 8.05 (m, 1 H); ESI- MS m/z [M+H] + =467.5. [0763] EXAMPLE 209: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-N-ethyl-2-((1- hydroxy-2-methylpropan-2-yl)amino)-N-methylnicotinamide [0764] 1 H NMR (400 MHz, CD3OD) δ ppm 0.49 - 0.57 (m, 2 H) 0.66 - 0.73 (m, 2 H) 1.06 - 1.16 (m, 3 H) 1.32 (s, 6 H) 2.24 (s, 3 H) 2.71 - 2.79 (m, 1 H) 2.96 (s, 3 H) 3.35 - 3.45 (m, 2 H) 3.57 (s, 2 H) 5.43 - 5.50 (m, 1 H) 7.24 - 7.29 (m, 1 H) 7.33 - 7.38 (m, 1 H) 7.52 - 7.56 (m, 1 H) 7.57 - 7.63 (m, 1 H) 7.97 - 8.02 (m, 1 H); ESI-MS m/z [M+H] + =425.5. [0765] EXAMPLE 210: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (4-methylpiperazine-1-carbonyl)pyridin-3-yl)-4-methylbenzami de [0766] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.53 (dd, J=3.21, 1.74 Hz, 2 H) 0.69 (s, 2 H) 1.33 (s, 6 H) 2.24 (d, J=6.97 Hz, 6 H) 2.40 (br s, 4 H) 2.71 - 2.79 (m, 1 H) 3.57 (s, 6 H) 5.57 - 5.63 (m, 1 H) 7.27 (d, J=8.07 Hz, 1 H) 7.36 (s, 1 H) 7.54 (s, 1 H) 7.59 (br d, J=8.07 Hz, 1 H) 8.02 (s, 1 H); ESI-MS m/z [M+H] + =466.5. [0767] EXAMPLE 211: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (3-hydroxy-3-methylazetidine-1-carbonyl)pyridin-3-yl)-4-meth ylbenzamide [0768] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.62 - 0.69 (m, 2 H) 0.79 - 0.86 (m, 2 H) 1.45 (s, 6 H) 1.50 (s, 3 H) 2.37 (s, 3 H) 2.83 - 2.91 (m, 1 H) 3.71 - 3.76 (m, 2 H) 4.05 - 4.25 (m, 4 H) 7.37 - 7.43 (m, 1 H) 7.62 - 7.68 (m, 2 H) 7.69 - 7.74 (m, 1 H) 8.11 - 8.15 (m, 1 H); ESI- MS m/z [M+H] + =453.5. [0769] EXAMPLE 212: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (2-methylazetidine-1-carbonyl)pyridin-3-yl)-4-methylbenzamid e [0770] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.62 - 0.68 (m, 2 H) 0.78 - 0.86 (m, 2 H) 1.44 (s, 9 H) 1.87 - 1.99 (m, 2 H) 2.36 (s, 3 H) 2.48 - 2.60 (m, 1 H) 2.82 - 2.92 (m, 1 H) 3.72 (s, 2 H) 4.06 - 4.16 (m, 1 H) 4.37 (br dd, J=1.74, 1.01 Hz, 1 H) 4.65 - 4.78 (m, 1 H) 7.36 - 7.42 (m, 1 H) 7.61 - 7.66 (m, 2 H) 7.71 (d, J=7.89 Hz, 1 H) 8.09 - 8.14 (m, 1 H; ESI-MS m/z [M+H] + =437.5. [0771] EXAMPLE 213: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-methyl-N-(oxetan-3-yl)nicotinamid e [0772] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.50 - 0.57 (m, 2 H) 0.70 (br d, J=6.24 Hz, 2 H) 1.32 (s, 6 H) 2.26 (s, 3 H) 2.71 - 2.78 (m, 1 H) 3.10 (s, 3 H) 3.57 (s, 2 H) 4.72 - 4.72 (m, 2 H) 5.03 - 5.12 (m, 2 H) 5.74 - 5.81 (m, 1 H) 7.27 (d, J=7.70 Hz, 1 H) 7.33 - 7.38 (m, 1 H) 7.53 - 7.56 (m, 1 H) 7.57 - 7.61 (m, 1 H) 8.00 - 8.04 (m, 1 H); ESI-MS m/z [M+H] + =453.6. [0773] EXAMPLE 214: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (3-hydroxyazetidine-1-carbonyl)pyridin-3-yl)-4-methylbenzami de [0774] 1 H NMR (400 MHz, CD3OD) δ ppm 0.48 - 0.57 (m, 2 H) 0.66 - 0.75 (m, 2 H) 1.32 (s, 6 H) 2.25 (s, 3 H) 2.71 - 2.78 (m, 1 H) 3.61 (s, 2 H) 3.86 - 4.01 (m, 2 H) 4.31 - 4.44 (m, 2 H) 4.46 - 4.53 (m, 1 H) 7.25 - 7.31 (m, 1 H) 7.45 - 7.55 (m, 2 H) 7.56 - 7.62 (m, 1 H) 8.01 (d, J=2.02 Hz, 1 H); ESI-MS m/z [M+H] + =439.5. [0775] EXAMPLE 215: N-cyclopropyl-3-(6-((1-hydroxy-2-methylpropan-2-yl)amino)-5- (2-methylaziridine-1-carbonyl)pyridin-3-yl)-4-methylbenzamid e [0776] 1 H NMR (400 MHz, CD3OD) δ ppm 0.49 - 0.57 (m, 3 H) 0.65 - 0.74 (m, 3 H) 1.17 - 1.21 (m, 1 H) 1.21 - 1.27 (m, 3 H) 1.34 (s, 6 H) 2.20 - 2.27 (m, 3 H) 2.72 - 2.78 (m, 2 H) 3.60 - 3.66 (m, 2 H) 7.25 - 7.29 (m, 1 H) 7.52 - 7.56 (m, 1 H) 7.57 - 7.62 (m, 1 H) 7.87 - 7.91 (m, 1 H) 7.98 - 8.03 (m, 1 H) 9.09 - 9.13 (m, 1 H); ESI-MS m/z [M+H] + =423.5. [0777] EXAMPLE 216: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-(2-methoxyethyl)-N-methylnicotina mide [0778] 1 H NMR (400MHz, CDCl3) δ ppm 0.59 (m, 2 H) 0.78 - 0.91 (m, 2 H) 1.40 (s, 6 H) 2.32 (s, 3 H) 2.90 (m, 1 H) 3.09 (s, 3 H) 3.34 (s, 3 H) 3.52 - 3.69 (m, 4 H) 3.70 (s, 2 H) 6.00 (s, 1 H) 6.34 (s, 1 H) 7.31 (d, J=8.0 Hz, 1 H) 7.54 (m, 2 H) 7.67 (m, 1 H) 7.99 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =455.2. [0779] EXAMPLE 217: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-(2-methoxyethyl)-N-methylnicotina mide [0780] 1 H NMR (400MHz, CDCl 3 ) δ ppm 0.59 (m, 2 H) 0.78 - 0.91 (m, 2 H) 1.40 (s, 6 H) 2.32 (s, 3 H) 2.90 (m, 1 H) 3.09 (s, 3 H) 3.34 (s, 3 H) 3.52 - 3.69 (m, 4 H) 3.70 (s, 2 H) 6.00 (s, 1 H) 6.34 (s, 1 H) 7.31 (d, J=8.0 Hz, 1 H) 7.54 (m, 2 H) 7.67 (m, 1 H) 7.99 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =455.2. [0781] EXAMPLE 218: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((2- hydroxyethyl)amino)-N-methylnicotinamide [0782] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.54 - 0.59 (m, 2 H) 0.66 - 0.72 (m, 2 H) 2.31 (s, 3 H) 2.75 (d, J=4.4 Hz, 3 H) 2.80 - 2.85 (m, 1 H) 3.48 - 3.55 (m, 2 H) 3.55 - 3.62 (m, 2 H) 4.81 (s, 1 H) 7.34 - 7.41 (m, 1 H) 7.67 - 7.76 (m, 2 H) 7.93 (d, J=2.4 Hz, 1 H) 8.18 (d, J=2.0 Hz, 1 H) 8.40 (d, J=4.0 Hz, 1 H) 8.50 (d, J=4.4 Hz, 1 H) 8.63 (t, J=5.2 Hz, 1 H); ESI- MS m/z [M+H] + =369.3. [0783] EXAMPLE 219: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-(oxazol-2-ylmethyl)nicotinamide [0784] 1 H NMR (400MHz, CDCl3) δ ppm 0.59 - 0.68 (m, 2 H) 0.79 - 0.86 (m, 2 H) 1.28 - 1.33 (m, 6 H) 2.30 (s, 3 H) 2.86 (dd, J=3.6, 7.4 Hz, 1 H) 3.54 (s, 2 H) 4.71 (d, J=5.6 Hz, 2 H) 6.82 (s, 1 H) 7.00 (s, 1 H) 7.26 - 7.30 (m, 2 H) 7.65 (s, 1 H) 7.67 (d, J=9.0 Hz, 1 H) 7.97 – 8.04 (m, 2 H) 8.57 (s, 1 H) 8.85 (s, 1 H); ESI-MS m/z [M+H] + =464.2. [0785] EXAMPLE 220: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1- (hydroxymethyl)cyclopentyl)amino)-N-methylnicotinamide [0786] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.54 - 0.58 (m, 2 H) 0.66 - 0.71 (m, 2 H) 1.60 (d, J=7.2 Hz, 2 H) 1.67 - 1.84 (m, 4 H) 1.88 - 1.97 (m, 2 H) 2.32 (s, 3 H) 2.74 (d, J=4.0 Hz, 3 H) 2.85 (d, J=4.0 Hz, 1 H) 3.67 (d, J=5.6 Hz, 2 H) 5.09 (t, J=5.6 Hz, 1 H) 7.37 (d, J=8.4 Hz, 1 H) 7.71 (s, 1 H) 7.72 (d, J=7.6Hz, 2 H) 7.93 (d, J=2.4 Hz, 1 H) 8.15 (d, J=2.4 Hz, 1 H) 8.39 (d, J=4.0 Hz, 1 H) 8.50 (d, J=5.6 Hz, 1 H) 8.79 (s, 1 H); ESI-MS m/z [M+H] + =423.2. [0787] EXAMPLE 221: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((3- (hydroxymethyl)tetrahydrofuran-3-yl)amino)-N-methylnicotinam ide [0788] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.48 - 0.61 (m, 2 H) 0.63 - 0.75 (m, 2 H) 2.13 (t, J=6.8 Hz, 2 H) 2.32 (s, 3 H) 2.75 (d, J=4.4 Hz, 2 H) 2.73 - 2.77 (m, 1 H) 2.80 - 2.91 (m, 1 H) 3.68 - 3.90 (m, 6 H) 7.38 (d, J=7.8 Hz, 1 H) 7.63 - 7.83 (m, 2 H) 7.97 (d, J=2.0 Hz, 1 H) 8.17 (d, J=2.4 Hz, 1 H) 8.32 - 8.48 (m, 1 H) 8.56 (d, J=4.4 Hz, 1 H) 8.92 (s, 1 H); ESI- MS m/z [M+H] + =425.2. [0789] EXAMPLE 222: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1- hydroxybutan-2-yl)amino)-N,N-dimethylnicotinamide [0790] 1H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.54 - 0.56 (m, 2 H) 0.67 - 0.68 (m, 2 H) 6.05 (t, J=7.6 Hz, 1 H) 1.49 - 1.52 (m, 1 H) 1.67 - 1.69 (m, 1 H) 2.31 (s, 3 H) 2.82 - 2.84 (m, 1 H) 2.98 (s, 6 H) 3.41 (dd, J=10.8, 5.2 Hz, 1 H) 3.53 (dd, J=10.8, 4.4 Hz, 1 H) 4.01 - 4.05 (m, 1 H) 6.05 (d, J=8.4 Hz, 1 H) 7.34 (d, J=8.0 Hz, 1 H) 7.46 (d, J=2.0 Hz, 1 H) 7.67 - 7.71 (m, 2 H) 8.09 (d, J=2.4 Hz, 1 H) 8.38 (d, J=3.6 Hz, 1 H); ESI-MS m/z [M+H] + =411.2. [0791] EXAMPLE 223: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((3- (hydroxymethyl)oxetan-3-yl)amino)-N-methylnicotinamide [0792] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 0.48 - 0.59 (m, 2 H) 0.63 - 0.75 (m, 2 H) 2.31 (s, 3 H) 2.75 - 2.87 (m, 4 H) 3.49 (s, 4 H) 4.24 (s, 2 H) 7.37 (d, J=8.0 Hz, 1 H) 7.67 - 7.75 (m, 2 H) 8.04 (s, 1 H) 8.08 (s, 1 H) 8.31 (s, 1 H) 8.49 (d, J=4.0 Hz, 1 H) 9.65 (d, J=4.0 Hz, 1 H); ESI-MS m/z [M+H] + =328.1. [0793] EXAMPLE 224: 5-(5-(cyclopropylcarbamoyl)-4-fluoro-2-methylphenyl)-2-((1- hydroxy-2-methylpropan-2-yl)amino)-N,N-dimethylnicotinamide

[0794] 1 H NMR (400MHz, CDCl3) δ ppm 0.50 - 0.55 (m, 2 H) 0.65 - 0.70 (m, 2 H) 1.36 (s, 6 H) 2.29 (s, 3 H) 2.81 (m, 1 H) 2.97 (s, 6 H) 3.44 (s, 2 H) 5.16 (s, 1 H) 6.07 (s, 1 H) 7.21 (d, J=11.2 Hz, 1 H) 7.35 (d, J=7.6 Hz, 1 H) 7.44 (d, J=2.4 Hz, 1 H) 8.07 (d, J=2.4 Hz, 1 H) 8.28 (d, J=3.9 Hz, 1 H); ESI-MS m/z [M+H] + =429.3. [0795] EXAMPLE 225: (R)-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1- hydroxypropan-2-yl)amino)-N,N-dimethylnicotinamide [0796] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.43 - 0.60 (m, 2 H) 0.63 - 0.72 (m, 2 H) 1.15 (d, J=6.8 Hz, 3 H) 2.31 (s, 3 H) 2.86 - 2.81 (m, 1 H) 2.97 (s, 6 H) 3.46 - 3.40 (m, 1 H) 3.47 - 3.49 (m, 1 H) 4.15 - 4.18 (m, 1 H) 6.09 (d, J=8.0 Hz, 1 H) 7.35 (d, J=8.0 Hz, 1 H) 7.47 (d, J=2.4 Hz, 1 H) 7.61 (s, 1 H) 7.71 - 7.68 (dd, J=2.4, 8.0 Hz, 1 H) 8.11 (d, J=2.4 Hz, 1 H) 8.39 (d, J=4.0 Hz, 1 H); ESI-MS m/z [M+H] + =397.3. [0797] EXAMPLE 226: (S)-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1- hydroxypropan-2-yl)amino)-N,N-dimethylnicotinamide [0798] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.55 - 0.58 (m, 2 H) 0.67 - 0.69 (m, 2 H) 1.16 (d, J=6.8 Hz, 3 H) 2.33 (s, 3 H) 2.80 - 2.86 (m, 1 H) 2.98 (s, 6 H) 3.48 - 3.53 (m, 2 H) 4.09 - 4.30 (m, 1 H) 4.82 (s, 1 H) 6.10 (d, J=7.6 Hz, 1 H) 7.36 (d, J=8.0 Hz, 1 H) 7.47 (d, J=2.4 Hz, 1 H) 7.61 - 7.77 (m, 2 H) 8.11 (d, J=2.4 Hz, 1 H) 8.40 (d, J=4.0 Hz, 1 H); ESI-MS m/z [M+H] + =397.3. [0799] EXAMPLE 227: 2-((1-hydroxy-2-methylpropan-2-yl)amino)-N-methyl-5-(2- methyl-5-(phenylcarbamoyl)phenyl)nicotinamide [0800] 1 H NMR (400 MHz, DMSO-d6) δ ppm δ 1.39 (s, 6 H) 2.36 (s, 3 H) 2.74 (d, J=4.0 Hz, 3 H) 3.57 (s, 2 H) 7.10 (t, J=7.2 Hz, 1 H) 7.35 (t, J=7.6 Hz, 2 H) 7.46 (d, J=8.0 Hz, 1 H) 7.77 (d, J=8.0 Hz, 2 H) 7.84 - 7.92 (m, 2 H) 7.99 (s, 1 H) 8.23 (s, 1 H) 8.54 (s, 1 H) 8.86 (s, 1 H) 10.18 (s, 1 H); ESI-MS m/z [M+H] + =433.2. [0801] EXAMPLE 228: 5-(5-((1H-pyrazol-3-yl)carbamoyl)-2-methylphenyl)-2-((1- hydroxy-2-methylpropan-2-yl)amino)-N,N-dimethylnicotinamide [0802] 1 H NMR (400MHz, CDCl 3 ) δ ppm 1.38 (s, 6 H) 2.32 (s, 3 H) 3.07 (s, 6 H) 3.67 (s, 2 H) 6.18 (s, 1 H) 6.76 (s, 1 H) 7.32 - 7.38 (m, 2 H) 7.48 (d, J=2.0 Hz, 1 H) 7.71 - 7.79 (m, 2 H) 7.96 (d, J=2.4 Hz, 1 H) 9.44 (s, 1 H); ESI-MS m/z [M+H] + =437.2. [0803] EXAMPLE 229: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1- (hydroxymethyl)cyclobutyl)amino)-N-methylnicotinamide [0804] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.49 - 0.59 (m, 2 H) 0.66 - 0.73 (m, 2 H) 1.72 - 1.82 (m, 1 H) 1.83 - 1.93 (m, 1 H) 2.15 - 2.24 (m, 3 H) 2.31 (s, 3 H) 2.75 (d, J=4.4 Hz, 3 H) 2.81 - 2.88 (m, 1 H) 3.73 (s, 2 H) 4.94 (s, 1 H) 7.37 (d, J=8.0 Hz, 1 H) 7.69 - 7.79 (m, 2 H) 7.94 (d, J=2.0 Hz, 1 H) 8.14 (d, J=2.0 Hz, 1 H) 8.39 ( d, J=4.0 Hz, 1 H) 8.51 (d, J=4.4 Hz, 1 H) 8.75 (s, 1 H); ESI-MS m/z [M+H] + =409.1. [0805] EXAMPLE 230: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-(1-(oxazol-2-yl)ethyl)nicotinamid e [0806] 1 H NMR (400MHz, CDCl3) δ ppm 0.59 - 0.71 (m, 2 H) 0.85 (d, J=6.8 Hz, 2 H) 1.37 (d, J=17.2 Hz, 6 H) 1.66 (d, J=7.2 Hz, 3 H) 2.31 (s, 3 H) 2.88 - 2.90 (m, 1 H) 3.62 (s, 2 H) 5.43 - 5.36 (m, 1 H) 6.59 (s, 1 H) 7.01 (s, 1 H) 7.30 (d, J=8.0 Hz, 1 H) 7.45 (s, 1 H) 7.61 - 7.67 (m, 2 H) 7.90 (s, 1 H) 8.03 (s, 1 H) 8.77 (s, 1 H); ESI-MS m/z [M+H] + =478.2. [0807] EXAMPLE 231: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1- (hydroxymethyl)cyclopropyl)amino)-N,N-dimethylnicotinamide [0808] 1 H NMR (400 MHz, CDCl3) δ ppm 0.61 - 0.64 (m, 2 H) 0.83 - 0.85 (m, 4 H) 0.99 - 1.02 (m, 2 H) 2.31 (s, 3 H) 2.87 - 2.92 (m, 1 H) 3.06 (s, 6 H) 3.69 (s, 2 H) 6.44 - 6.46 (m, 2 H) 7.31 (d, J=8.0 Hz, 1 H) 7.34 (d, J=2.4 Hz, 1 H) 7.54 (s, 1 H) 7.63 (d, J=7.6 Hz, 1 H) 8.06 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =409.3. [0809] EXAMPLE 232: 2-((1-hydroxy-2-methylpropan-2-yl)amino)-N,N-dimethyl-5-(2- methyl-5-(thiazol-4-ylcarbamoyl)phenyl)nicotinamide [0810] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 1.43 (s, 6 H) 2.39 (s, 3 H) 3.10 (s, 6 H) 3.68 (s, 2 H) 7.45 (d, J=8.0 Hz, 1 H) 7.42 - 7.48 (m, 1 H) 7.55 (d, J=2.4 Hz, 1 H) 7.82 (dd, J=2.0, 4.8 Hz, 2 H) 7.87 (dd, J=2.0, 8.0 Hz, 1 H) 8.15 (d, J=2.4 Hz, 1 H) 8.84 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =454.1. [0811] EXAMPLE 233: N-(2-aminoethyl)-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl) - 2-((1-hydroxy-2-methylpropan-2-yl)amino)nicotinamide [0812] The title compound was obtained as an HCL salt. 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.66 (d, J=5.6 Hz, 4 H) 1.45 (s, 6 H) 2.36 (s, 3 H) 2.86 - 2.89 (m, 1 H) 2.95 - 3.02 (m, 2 H) 3.40 (s, 2 H) 3.48 - 3.55 (m, 3 H) 3.59 (s, 2 H) 7.38 (d, J=8.0 Hz, 1 H) 7.75 (dd, J=1.6, 6.0 Hz, 1 H) 7.96 (s, 1 H) 8.12 (s, 3 H) 8.28 (d, J=2.0 Hz, 1 H) 8.50 (s, 1 H) 8.65 (d, J=4.4 Hz, 1 H) 9.34 (s, 1 H); ESI-MS m/z [M+H] + =426.2. [0813] EXAMPLE 234: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-N-(2- (dimethylamino)ethyl)-2-((1-hydroxy-2-methylpropan-2-yl)amin o)nicotinamide [0814] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.52 - 0.59 (m, 2 H) 0.65 - 0.73 (m, 2 H) 1.38 (s, 6 H) 2.22 (s, 6 H) 2.32(s, 3 H) 2.43 - 2.47 (m, 2 H) 2.80- 2.89 (m, 1 H) 3.34 - 3.36 (m, 2 H) 3.56 (d, J=1.8 Hz, 2 H) 5.13 (s, 1 H) 7.37 (d, J=8.8 Hz, 1 H) 7.70 - 7.76 (m, 2 H) 7.94 (d, J=2.4 Hz, 1 H) 8.15 (d, J=2.4 Hz, 1 H) 8.39 (d, J=4.0 Hz, 1 H) 8.46 (t, J=2.8 Hz, 1 H) 8.71 (s, 1 H); ESI-MS m/z [M+H] + =454.3. [0815] EXAMPLE 235: 5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-2-((1-hydroxy-2- methylpropan-2-yl)amino)-N-(2-(methylamino)ethyl)nicotinamid e [0816] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.67 - 0.68 (m, 4 H) 1.15 (s, 6 H) 2.37 (s, 3 H) 2.56 (t, J=5.2 Hz, 3 H) 2.87 - 2.89 (m, 1 H) 3.03 - 3.10 (m, 2 H) 3.55 - 3.60 (m, 4 H) 7.40 (d, J=8.0 Hz, 1 H) 7.75 -7.77 (m, 1 H) 8.00 (d, J=1.2 Hz, 1 H) 8.30 (d, J=2.4 Hz, 1 H) 8.52 (s, 1 H) 8.67 (d, J=4.4 Hz, 1 H) 9.00 (s, 2 H) 9.39 (s, 1 H); ESI-MS m/z [M+H] + =440.4. [0817] EXAMPLE 236: 2-((1-cyclopropyl-2-hydroxyethyl)amino)-5-(5- (cyclopropylcarbamoyl)-2-methylphenyl)-N,N-dimethylnicotinam ide [0818] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.42 - 0.43 (m, 2 H) 0.60 - 0.64 (m, 4 H) 0.84 - 0.87 (m, 2 H) 0.99 - 1.04 (m, 1 H) 2.31 (m, 3 H) 2.87 - 2.91 (m, 1 H) 3.11 (s, 6 H) 3.27 (s, 1 H) 3.73 - 3.78 (m, 1 H) 3.97 - 4.00 (m, 1 H) 6.30 - 6.34 (m, 2 H) 7.31 (d, J=7.6 Hz, 1 H) 7.36 (d, J=2.4 Hz, 1 H) 7.54 (d, J=2.0 Hz, 1 H) 7.62 (dd, J=2.0, 8.0 Hz, 1 H) 8.01 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =423.2. [0819] EXAMPLE 237: 3-(5-acetamido-6-((1-hydroxy-2-methylpropan-2- yl)amino)pyridin-3-yl)-N-cyclopropyl-4-methylbenzamide [0820] 1 H NMR (400 MHz, CDCl 3 ) δ ppm 0.54 - 0.57 (m, 2 H) 0.66 - 0.69 (m, 2 H) 1.37 (s, 6 H) 2.07 (s, 3 H) 2.30 (s, 3 H) 2.80 - 2.86 (m, 1 H) 3.56 (d, J=5.6 Hz, 2 H) 5.26 (t, J=5.6 Hz, 1 H) 5.45 (s, 1 H) 7.34 (d, J=8.0 Hz, 1 H) 7.55 (d, J=2.0 Hz, 1 H) 7.64 (s, 1 H) 7.66 - 7.71 (m, 1 H) 7.87 (d, J=2.00 Hz, 1 H) 8.37 (d, J=4.00 Hz, 1 H) 9.38 (s, 1 H); ESI-MS m/z [M+H] + = 397.2. [0821] EXAMPLE 238: (S)-5-(5-(cyclopropylcarbamoyl)-4-fluoro-2-methylphenyl)-2-( (1- hydroxypropan-2-yl)amino)-N,N-dimethylnicotinamide [0822] 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.47 - 0.58 (m, 2 H) 0.63 - 0.72 (m, 2 H) 1.15 (d, J=6.4 Hz, 3 H) 2.29 (s, 3 H) 2.74 - 2.86 (m, 1 H) 2.97 (s, 6 H) 3.33 - 3.53 (m, 2 H) 4.16 (dt, J=12.4, 6.4 Hz, 1 H) 4.78 (s, 1 H) 6.07 (d, J=7.6 Hz, 1 H) 7.21 (d, J=11.6 Hz, 1 H) 7.35 (d, J=7.6 Hz, 1 H) 7.43 (d, J=2.4 Hz, 1 H) 8.07 (d, J=2.4 Hz, 1 H) 8.27 (d, J=4.0 Hz, 1 H); ESI-MS m/z [M+H] + =415.2. [0823] EXAMPLE 239: (S)-2-((1-hydroxypropan-2-yl)amino)-N,N-dimethyl-5-(2-methyl - 5-((1-methyl-1H-pyrazol-3-yl)carbamoyl)phenyl)nicotinamide [0824] 1 H NMR (400 MHz, CDCl3) δ ppm 1.32 (d, J=6.4 Hz, 3 H) 2.37 (s, 3 H) 3.14 (s, 6 H) 3.49 - 3.60 (m, 1 H) 3.87 (s, 4 H) 4.27 - 4.39 (m, 1 H) 6.93 (d, J=1.6 Hz, 1 H) 7.36 (d, J=2.4 Hz, 1 H) 7.44 (d, J=8.0 Hz, 1 H) 7.72 (d, J=1.2 Hz, 1 H) 7.81 (s, 1 H) 7.90 (d, J=8.0 Hz, 1 H) 8.08 (s, 1 H) 9.92 (s, 1 H); ESI-MS m/z [M+H] + =437.3. [0825] EXAMPLE 240: 5-(4-fluoro-2-methyl-5-((1-methyl-1H-pyrazol-3- yl)carbamoyl)phenyl)-2-((1-hydroxy-2-methylpropan-2-yl)amino )-N,N-dimethylnicotinamide [0826] 1 H NMR (400 MHz, DMSO-d6) δ ppm 1.37 (s, 6 H) 2.33 (s, 3 H) 2.98 (s, 6 H) 3.45 (s, 2 H) 3.76 (s, 3 H) 5.16 (s, 1 H) 6.06 (s, 1 H) 6.55 (s, 1 H) 7.27 (d, J=11.2 Hz, 1 H) 7.49 (d, J=7.2 Hz, 1 H) 7.50 (s, 1 H) 7.59 (s, 1 H) 8.13 (s, 1 H) 10.68 (s,1 H); ESI-MS m/z [M+H] + =469.2. [0827] EXAMPLE 241: 5-(5-((1H-imidazol-4-yl)carbamoyl)-2-methylphenyl)-2-((1- hydroxy-2-methylpropan-2-yl)amino)-N,N-dimethylnicotinamide [0828] 1 H NMR (400MHz, CDCl 3 ) δ ppm 1.41 (s, 6 H) 2.35 (s, 3 H) 3.10 (s, 6 H) 3.69 (s, 2 H) 6.15 (s, 1 H) 7.32 -7.41 (m, 3 H) 7.59 (s, 1 H) 7.74 (s, 1 H) 7.85 (d, J=8.8 Hz, 1 H) 8.02 (d, J=2.0 Hz, 1 H) 9.97 (s, 1 H); ESI-MS m/z [M+H] + =437.2. [0829] EXAMPLE 242: 5-(4-fluoro-2-methyl-5-((1-methyl-1H-pyrazol-3- yl)carbamoyl)phenyl)-2-((1-hydroxypropan-2-yl)amino)-N,N-dim ethylnicotinamide [0830] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 1.30 (d, J=6.8 Hz, 3 H) 2.33 (s, 3 H) 3.11 (s, 6 H) 3.65 (dd, J=7.6, 10.8 Hz, 1 H) 3.80 (dd, J=2.8, 10.8 Hz, 1 H) 3.84 (s, 3 H) 4.23 (s, 1 H) 6.13 (d, J=4.4 Hz, 1 H) 6.81 (d, J=2.0 Hz, 1 H) 7.11 (d, J=12.8 Hz, 1 H) 7.30 (d, J=2.0 Hz, 1 H) 7.36 (d, J=2.4 Hz, 1 H) 7.97 (d, J=8.0 Hz, 1 H) 8.06 (d, J=2.4 Hz, 1 H) 9.00 (d, J=14.4 Hz, 1 H); ESI-MS m/z [M+H] + =455.2. [0831] EXAMPLE 243: 5-(5-(cyclopropylcarbamoyl)-4-fluoro-2-methylphenyl)-2-((1- hydroxy-2-methylpropan-2-yl)amino)-N-methyl-N-(oxetan-3-yl)n icotinamide [0832] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.62 - 0.65 (m, 2 H) 0.80 - 0.83 (m, 2 H) 1.41 (s, 6 H) 2.34 (s, 3 H) 2.84 - 2.88 (m, 1 H) 3.20 (s, 3 H) 3.66 (s, 2 H) 4.80 - 4.86 (m, 4 H) 5.15 - 5.19 (m, 1 H) 7.15 (d, J=11.6 Hz, 1 H) 7.43 (s, 1 H) 7.52 (d, J=7.2 Hz, 1 H) 8.09 (d, J=2.8 Hz, 1 H); ESI-MS m/z [M+H] + =471.3. [0833] EXAMPLE 244: 5-(5-(cyclopropylcarbamoyl)-4-fluoro-2-methylphenyl)-2-((1- hydroxy-2-methylpropan-2-yl)amino)-N-(2-methoxyethyl)-N-meth ylnicotinamide [0834] 1 H NMR (400 MHz, CD3OD) δ ppm 0.62 - 0.64 (m, 2 H) 0.78 - 0.83 (m, 2 H) 1.41 (s, 6 H) 2.32 (s, 3 H) 2.82 - 2.88 (m, 1 H) 3.08 (s, 3 H) 3.35 (s, 3 H) 3.65 (s, 6 H) 7.13 (d, J=11.6 Hz, 1 H) 7.48 - 7.51 (m, 2 H) 8.05 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =473.3. [0835] EXAMPLE 245: 5-(5-(cyclopropylcarbamoyl)-4-fluoro-2-methylphenyl)-2-((2- hydroxyethyl)(methyl)amino)-N,N-dimethylnicotinamide [0836] 1 H NMR (400 MHz, CD3OD) δ ppm 0.61 - 0.65 (m, 2 H) 0.79 - 0.83 (m, 2 H) 2.31 (s, 3 H) 2.84 - 2.88 (m, 1 H) 3.02 (d, J=12.0 Hz, 6 H) 3.11 (s, 3 H) 3.68 - 3.81 (m, 4 H) 7.13 (d, J=12.0 Hz, 1 H) 7.46 - 7.52 (m, 2 H) 8.12 (d, J=4.0 Hz, 1 H); ESI-MS m/z [M+H] + =415.2. [0837] EXAMPLE 246: 5-(5-(cyclopropylcarbamoyl)-4-fluoro-2-methylphenyl)-2-((1- (hydroxymethyl)cyclopropyl)(methyl)amino)-N,N-dimethylnicoti namide [0838] 1 H NMR (400 MHz, CD 3 OD) δ ppm 0.56 - 0.87 (m, 8 H) 2.29 (s, 3 H) 2.79 (s, 4 H) 2.94 (d, J=10.4 Hz, 6 H) 3.69 (d, J=10.8 Hz, 2 H) 5.20 (s, 1 H) 7.23 (d, J=11.2 Hz, 1 H) 7.37 (d, J=7.2 Hz, 1 H) 7.44 (s, 1 H) 8.17 (d, J=2.0 Hz, 1 H) 8.31 (d, J=3.6 Hz, 1 H); ESI-MS m/z [M+H] + =441.2. [0839] EXAMPLE 247: 5-(5-(cyclopropylcarbamoyl)-2-(fluoromethyl)phenyl)-2-((1- hydroxy-2-methylpropan-2-yl)amino)-N,N-dimethylnicotinamide [0840] 1 H NMR (400MHz, CDCl3) δ ppm 0.61 - 0.68 (m, 2 H) 0.85 - 0.92 (m, 2 H) 1.39 (s, 6 H) 2.86 - 2.94 (m, 1 H) 3.09 (s, 6 H) 3.66 (s, 2 H) 5.20 - 5.39 (m, 2 H) 6.33 (s, 1 H) 6.38 (s, 1 H) 7.44 (d, J=2.4 Hz, 1 H) 7.59 (d, J=8.0 Hz, 1 H) 7.65 (s, 1 H) 7.76 (d, J=8.0 Hz, 1 H) 8.02 (d, J=2.4 Hz, 1 H); ESI-MS m/z [M+H] + =429.3. [0841] EXAMPLE 248: 2-chloro-N-cyclopropyl-5-(6-((2-hydroxyethyl)amino)-5-(1- methyl-1H-pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide [0842] STEP A: 2-((5-bromo-3-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)e than-1-ol [0843] To a solution of 2-((5-bromo-3-iodopyridin-2-yl)amino)ethan-1-ol (500 mg, 1.46 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyra zole (303.34 mg, 1.46 mmol) in dioxane (5 mL) and H2O (0.5 mL) were added K2CO3 (402.98 mg, 2.92 mmol) and Pd(dppf)Cl2 (106.68 mg, 145.79 µmol) in one portion under N2. The mixture was stirred at 90°C for 6 hours and then diluted with water and extracted with ethyl acetate. The organic layers were combined, dried over anhydrous Na 2 SO 4 , filtered, concentrated under reduced pressure and purified by column chromatography (SiO2, MeOH/DCM 0% to 5%). The title compound was obtained as a brown oil (200 mg, 42.9%). ESI-MS m/z [M+H] + =298.9. [0844] STEP B: 2-chloro-N-cyclopropyl-5-(6-((2-hydroxyethyl)amino)-5-(1-met hyl-1H- pyrazol-4-yl)pyridin-3-yl)-4-methylbenzamide [0845] To a solution of 2-((5-bromo-3-(1-methyl-1H-pyrazol-4-yl)pyridin-2- yl)amino)ethan-1-ol (30 mg, 93.89 µmol) and 2-chloro-N-cyclopropyl-4-methyl-5-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (31.51 mg, 93.89 µmol) in dioxane (5 mL) and H 2 O (0.5 mL) were added K 2 CO 3 (25.95 mg, 187.78 µmol) and Pd(dppf)Cl 2 (6.87 mg, 9.39 µmol) in one portion under N2. The mixture was stirred at 90°C for 12 hours and then diluted with water and extracted with ethyl acetate. The organic layers were combined, dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure and purified by preparative HPLC. The title compound was obtained as a white solid (9.25 mg). 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.50 - 0.51 (m, 2 H) 0.64 - 0.69 (m, 2 H) 2.29 (s, 3 H) 2.77 - 2.80 (m, 1H) 5.76 (q, J=5.6 Hz, 2 H) 3.58 (q, J=5.2 Hz, 2 H) 3.89 (s, 3 H) 5.76 (t, J=5.2 Hz, 1 H) 5.86 (t, J=5.2 Hz, 1 H) 7.22 (s, 1 H) 7.39 (d, J=2.4 Hz, 1 H) 7.42 (s, 1 H) 7.72 (s, 1 H) 7.95 (d, J=2.4 Hz, 1 H) 8.03 (s, 1 H) 8.41 (d, J=4.4 Hz, 1 H); ESI-MS m/z [M+H] + =426.1. [0846] TABLE 1, below, lists RIPK2 inhibition data for the compounds described in the examples, where larger pIC 50 values represent higher potency. The compounds were tested in accordance with the assay described in the section entitled Biological Activity, above. [0847] TABLE 1: RIPK2 Inhibition (pIC50) for Example Compounds Ex# pIC50 Ex# pIC50 Ex# pIC50 Ex# pIC50 Ex# pIC50 Ex# pIC 50 Ex# pIC 50 Ex# pIC 50 Ex# pIC 50 Ex# pIC 50 [0848] As used in this specification and the appended claims, singular articles such as “a,” “an,” and “the,” may refer to a single object or to a plurality of objects unless the context clearly indicates otherwise. Thus, for example, reference to a composition containing “a compound” may include a single compound or two or more compounds. The above description is intended to be illustrative and not restrictive. Many embodiments will be apparent to those of skill in the art upon reading the above description. Therefore, the scope of the invention should be determined with reference to the appended claims and includes the full scope of equivalents to which such claims are entitled. The disclosures of all articles and references cited in the disclosure, including patents, patent applications and publications, are herein incorporated by reference in their entirety and for all purposes.




 
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