Substituted 1-Arylaminocarbonyl-1’-Heteroaryl Compounds, Substituted 1- Heteroarylaminocarbonyl-1’-Heteroaryl Compounds and Methods Using Same CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Patent Application No.63/410,766, filed September 28, 2022, which is incorporated herein by reference in its entirety. BACKGROUND Hepatitis B virus (HBV) is a noncytopathic, liver tropic DNA virus belonging to Hepadnaviridae family. HBV infection is one of the world's most prevalent diseases, being listed by National Institute of Allergy and Infectious Diseases (NIAID) as a High Priority Area of Interest. Although most individuals resolve the infection following acute symptoms, approximately 30% of cases become chronic.350-400 million people worldwide are estimated to have chronic hepatitis B, leading to 0.5-1 million deaths per year, due largely to the development of hepatocellular carcinoma, cirrhosis and/or other complications. A limited number of drugs are currently approved for the management of chronic hepatitis B, including two formulations of alpha-interferon (standard and pegylated) and five nucleoside/nucleotide analogues (lamivudine, adefovir, entecavir, telbivudine, and tenofovir) that inhibit HBV DNA polymerase. At present, the first-line treatment choices are entecavir, tenofovir and/or peg-interferon alfa-2a. However, peg-interferon alfa-2a achieves desirable serological milestones in only one third of treated patients, and is frequently associated with severe side effects. Entecavir and tenofovir are potent HBV inhibitors, but require long-term or possibly lifetime administration to continuously suppress HBV replication, and may eventually fail due to emergence of drug-resistant viruses. There is thus a pressing need for the introduction of novel, safe and effective therapies for chronic hepatitis B. Hepatitis D virus (HDV) is a small circular enveloped RNA virus that can propagate only in the presence of HBV. In particular, HDV requires the HBV surface antigen protein to propagate itself. Infection with both HBV and HDV results in more severe complications compared to infection with HBV alone. These complications include a greater likelihood of experiencing liver failure in acute infections and a rapid progression to liver cirrhosis, with an increased chance of developing liver cancer in chronic infections. In combination with hepatitis B virus, hepatitis D has the highest mortality rate of all the hepatitis infections. The routes of transmission of HDV are similar to those for HBV. Infection is largely restricted to persons at high risk of HBV infection, particularly injecting drug users and persons receiving clotting factor concentrates. Currently, there is no effective antiviral therapy available for the treatment of acute or chronic type D hepatitis. Interferon-alfa, given weekly for 12 to 18 months, is the only licensed treatment for hepatitis D. Response to this therapy is limited-in only about one- quarter of patients is serum HDV RNA undetectable 6 months post therapy. There is a need in the art for the identification of novel compounds that can be used to treat, ameliorate, and/or prevent HBV infection in a subject. In certain embodiments, the novel compounds can be used in patients that are HBV infected, patients who are at risk of becoming HBV infected, and/or patients that are infected with drug-resistant HBV. In other embodiments, the HBV-infected subject is further HDV-infected. The present disclosure addresses this need. BRIEF SUMMARY The present disclosure provides certain compounds of formula (I), or a salt, solvate, geometric isomer, isotopologue, stereoisomer, or tautomer thereof, or any mixtures thereof, wherein the substituents in (I) are defined elsewhere herein: (I). The present disclosure further provides pharmaceutical compositions comprising at least one compound of the present disclosure and at least one pharmaceutically acceptable carrier. In certain embodiments, the pharmaceutical composition further comprises at least one additional agent that treats, ameliorates, and/or prevents hepatitis virus infection. The present disclosure further provides methods of treating, ameliorating, and/or preventing hepatitis virus infection in a subject. In certain embodiments, the method comprises administering to the subject in need thereof a therapeutically effective amount of at least one compound of the present disclosure and/or at least one pharmaceutical composition of the present disclosure. In certain embodiments, the subject is infected with hepatitis B virus (HBV). In certain embodiments, the subject is infected with hepatitis D virus (HDV). In certain embodiments, the subject is infected with HBV and HDV. The present disclosure further provides methods of treating, ameliorating, and/or preventing cancer in a subject. In certain embodiments, the method comprises administering to the subject in need thereof a therapeutically effective amount of at least one compound of the present disclosure and/or at least one pharmaceutically acceptable composition of the present disclosure. In certain embodiments, the cancer is amenable to treatment by inhibiting PD-1, PD-L1, or the PD-1/PD-L1 interaction. In certain embodiments, the cancer is at least one of pancreatic cancer, bladder cancer, colorectal cancer, breast cancer, prostate cancer, renal cancer, hepatocellular cancer, lung cancer, ovarian cancer, cervical cancer, gastric cancer, esophageal cancer, head and neck cancer, melanoma, neuroendocrine cancer, CNS cancer, brain cancer, bone cancer, soft tissue sarcoma, non-small cell lung cancer, small-cell lung cancer, or colon cancer. In certain embodiments, the cancer is at least one of acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), myelodysplastic syndrome (MDS), myeloproliferative disease (MPD), chronic myeloid leukemia (CML), multiple myeloma (MM), non-Hodgkin's lymphoma (NHL), mantle cell lymphoma (MCL), follicular lymphoma, Waldestrom's macroglobulinemia (WM), T-cell lymphoma, B-cell lymphoma and diffuse large B-cell lymphoma (DLBCL). DETAILED DESCRIPTION The present disclosure relates, in certain aspects, to the discovery of certain substituted 1-arylaminocarbonyl-1'-heteroaryl or substituted 1-heteroarylaminocarbonyl-1'- heteroaryl compounds. In one aspect, the compounds of the present disclosure are useful to treat, ameliorate, and/or prevent hepatitis B virus (HBV) infection and/or hepatitis B virus- hepatitis D virus (HBV-HDV) infection and related conditions in a subject. In certain embodiments, these compounds are administered along with at least one additional agent useful for treating, ameliorating, and/or preventing the viral infection. In other embodiments, the subject is infected with HBV. In yet other embodiments, the HBV-infected subject is further infected with HDV. In another aspect, the compounds of the disclosure are useful to treat, ameliorate and/or prevent cancer and related conditions in a subject. Definitions As used herein, each of the following terms has the meaning associated with it in this section. Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Generally, the nomenclature used herein and the laboratory procedures in animal pharmacology, pharmaceutical science, separation science and organic chemistry are those well-known and commonly employed in the art. It should be understood that the order of steps or order for performing certain actions is immaterial, so long as the present teachings remain operable. Moreover, two or more steps or actions can be conducted simultaneously or not. As used herein, the articles "a" and "an" refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, "an element" means one element or more than one element. As used herein, the term "alkenyl," employed alone or in combination with other terms, means, unless otherwise stated, a stable monounsaturated or diunsaturated straight chain or branched chain hydrocarbon group having the stated number of carbon atoms. Examples include vinyl, propenyl (or allyl), crotyl, isopentenyl, butadienyl, 1,3-pentadienyl, 1,4-pentadienyl, and the higher homologs and isomers. A functional group representing an alkene is exemplified by -CH ₂ -CH=CH ₂ . As used herein, the term "alkoxy" employed alone or in combination with other terms means, unless otherwise stated, an alkyl group having the designated number of carbon atoms, as defined elsewhere herein, connected to the rest of the molecule via an oxygen atom, such as, for example, methoxy, ethoxy, 1-propoxy, 2-propoxy (or isopropoxy) and the higher homologs and isomers. A specific example is (C ₁ -C ₃ )alkoxy, such as, but not limited to, ethoxy and methoxy. As used herein, the term "alkyl" by itself or as part of another substituent means, unless otherwise stated, a straight or branched chain hydrocarbon having the number of carbon atoms designated (i.e., C ₁ -C ₁₀ means one to ten carbon atoms) and includes straight, branched chain, or cyclic substituent groups. Examples include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, neopentyl, hexyl, and cyclopropylmethyl. A specific embodiment is (C ₁ -C ₆ ) alkyl, such as, but not limited to, ethyl, methyl, isopropyl, isobutyl, n-pentyl, n-hexyl and cyclopropylmethyl. As used herein, the term "alkynyl" employed alone or in combination with other terms means, unless otherwise stated, a stable straight chain or branched chain hydrocarbon group with a triple carbon-carbon bond, having the stated number of carbon atoms. Non-limiting examples include ethynyl and propynyl, and the higher homologs and isomers. The term "propargylic" refers to a group exemplified by -CH ₂ -C≡CH. The term "homopropargylic" refers to a group exemplified by -CH ₂ CH ₂ -C≡CH. As used herein, the term "aromatic" refers to a carbocycle or heterocycle with one or more polyunsaturated rings and having aromatic character, i.e., having (4n+2) delocalized π (pi) electrons, where 'n' is an integer. As used herein, the term "aryl" employed alone or in combination with other terms means, unless otherwise stated, a carbocyclic aromatic system containing one or more rings (typically one, two or three rings) wherein such rings may be attached together in a pendent manner, such as a biphenyl, or may be fused, such as naphthalene. Examples include phenyl, anthracyl and naphthyl. Aryl groups also include, for example, phenyl or naphthyl rings fused with one or more saturated or partially saturated carbon rings (e.g., bicyclo[4.2.0]octa-1,3,5- trienyl, or indanyl), which can be substituted at one or more carbon atoms of the aromatic and/or saturated or partially saturated rings. As used herein, the term "aryl-(C ₁ -C ₆ )alkyl" refers to a functional group wherein a one to six carbon alkylene chain is attached to an aryl group, e.g., -CH ₂ CH ₂ -phenyl or -CH ₂ - phenyl (or benzyl). Specific examples are aryl-CH ₂ - and aryl-CH(CH ₃ )-. The term "substituted aryl-(C ₁ -C ₆ )alkyl" refers to an aryl-(C ₁ -C ₆ )alkyl functional group in which the aryl group is substituted. A specific example is substituted aryl(CH ₂ )-. Similarly, the term "heteroaryl-(C ₁ -C ₆ )alkyl" refers to a functional group wherein a one to three carbon alkylene chain is attached to a heteroaryl group, e.g., -CH ₂ CH ₂ -pyridyl. A specific example is heteroaryl-(CH ₂ )-. The term "substituted heteroaryl-(C ₁ -C ₆ )alkyl" refers to a heteroaryl-(C ₁ -C ₆ )alkyl functional group in which the heteroaryl group is substituted. A specific example is substituted heteroaryl-(CH ₂ )-. In one aspect, the terms "co-administered" and "co-administration" as relating to a subject refer to administering to the subject a compound and/or composition of the disclosure along with a compound and/or composition that may also treat or prevent a disease or disorder contemplated herein. In certain embodiments, the co-administered compounds and/or compositions are administered separately, or in any kind of combination as part of a single therapeutic approach. The co-administered compound and/or composition may be formulated in any kind of combinations as mixtures of solids and liquids under a variety of solid, gel, and liquid formulations, and as a solution. As used herein, the term "cycloalkyl" by itself or as part of another substituent refers to, unless otherwise stated, a cyclic chain hydrocarbon having the number of carbon atoms designated (i.e.,C ₃ -C ₆ refers to a cyclic group comprising a ring group consisting of three to six carbon atoms) and includes straight, branched chain or cyclic substituent groups. Examples of (C ₃ -C ₆ )cycloalkyl groups are cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. Cycloalkyl rings can be optionally substituted. Non-limiting examples of cycloalkyl groups include: cyclopropyl, 2-methyl-cyclopropyl, cyclopropenyl, cyclobutyl, 2,3-dihydroxycyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclopentadienyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctanyl, decalinyl, 2,5-dimethylcyclopentyl, 3,5- dichlorocyclohexyl, 4-hydroxycyclohexyl, 3,3,5-trimethylcyclohex-1-yl, octahydropentalenyl, octahydro-1H-indenyl, 3a,4,5,6,7,7a-hexahydro-3H-inden-4-yl, decahydroazulenyl; bicyclo[6.2.0]decanyl, decahydronaphthalenyl, and dodecahydro-1H- fluorenyl. The term "cycloalkyl" also includes bicyclic hydrocarbon rings, non-limiting examples of which include, bicyclo-[2.1.1]hexanyl, bicyclo[2.2.1]heptanyl, bicyclo[3.1.1]heptanyl, 1,3-dimethyl[2.2.1] heptan-2-yl, bicyclo[2.2.2]octanyl, and bicyclo[3.3.3]undecanyl. As used herein, the term "DCM" refers to dichloromethane. As used herein, a "disease" is a state of health of a subject wherein the subject cannot maintain homeostasis, and wherein if the disease is not ameliorated then the subject's health continues to deteriorate. As used herein, a "disorder" in a subject is a state of health in which the subject is able to maintain homeostasis, but in which the subject's state of health is less favorable than it would be in the absence of the disorder. Left untreated, a disorder does not necessarily cause a further decrease in the subject's state of health. As used herein, the term "halide" refers to a halogen atom bearing a negative charge. The halide anions are fluoride (F ⁻ ), chloride (Cl ⁻ ), bromide (Br ⁻ ), and iodide (I ⁻ ). As used herein, the term "halo" or "halogen" alone or as part of another substituent refers to, unless otherwise stated, a fluorine, chlorine, bromine, or iodine atom. As used herein, the term "Hepatitis B virus" (or HBV) refers to a virus species of the genus Orthohepadnavirus, which is a part of the Hepadnaviridae family of viruses, and that is capable of causing liver inflammation in humans. As used herein, the term "Hepatitis D virus" (or HDV) refers to a virus species of the genus Deltaviridae, which is capable of causing liver inflammation in humans. The HDV particle comprises an envelope, which is provided by HBV and surrounds the RNA genome and the HDV antigen. The HDV genome is a single, negative stranded, circular RNA molecule nearly 1.7 kb in length. The genome contains several sense and antisense open reading frames (ORFs), only one of which is functional and conserved. The RNA genome is replicated through an RNA intermediate, the antigenome. The genomic RNA and its complement, the antigenome, can function as ribozymes to carry out self-cleavage and self- ligation reactions. A third RNA present in the infected cell, also complementary to the genome, but 800 bp long and polyadenylated, is the mRNA for the synthesis of the delta antigen (HDAg). As used herein, the term "heteroalkenyl" by itself or in combination with another term refers to, unless otherwise stated, a stable straight or branched chain monounsaturated or diunsaturated hydrocarbon group consisting of the stated number of carbon atoms and one or two heteroatoms selected from the group consisting of O, N, and S, and wherein the nitrogen and sulfur atoms may optionally be oxidized and the nitrogen heteroatom may optionally be quaternized. Up to two heteroatoms may be placed consecutively. Examples include - CH=CH-O-CH ₃ , -CH=CH-CH ₂ -OH, -CH ₂ -CH=N-OCH ₃ , -CH=CH-N(CH ₃ )-CH ₃ , and -CH ₂ - CH=CH-CH ₂ -SH. As used herein, the term "heteroalkyl" by itself or in combination with another term refers to, unless otherwise stated, a stable straight or branched chain alkyl group consisting of the stated number of carbon atoms and one or two heteroatoms selected from the group consisting of O, N, and S, and wherein the nitrogen and sulfur atoms may be optionally oxidized and the nitrogen heteroatom may be optionally quaternized. The heteroatom(s) may be placed at any position of the heteroalkyl group, including between the rest of the heteroalkyl group and the fragment to which it is attached, as well as attached to the most distal carbon atom in the heteroalkyl group. Examples include: -OCH ₂ CH ₂ CH ₃ , - CH ₂ CH ₂ CH ₂ OH, -CH ₂ CH ₂ NHCH ₃ , -CH ₂ SCH ₂ CH ₃ , and -CH ₂ CH ₂ S(=O)CH ₃ . Up to two heteroatoms may be consecutive, such as, for example, -CH ₂ NH-OCH ₃ , or -CH ₂ CH ₂ SSCH ₃ . As used herein, the term "heteroaryl" or "heteroaromatic" refers to a heterocycle having aromatic character. A polycyclic heteroaryl may include one or more rings that are partially saturated. Examples include tetrahydroquinoline and 2,3-dihydrobenzofuryl. As used herein, the term "heterocycle" or "heterocyclyl" or "heterocyclic" by itself or as part of another substituent refers to, unless otherwise stated, an unsubstituted or substituted, stable, mono- or multi-cyclic heterocyclic ring system that comprises carbon atoms and at least one heteroatom selected from the group consisting of N, O, and S, and wherein the nitrogen and sulfur heteroatoms may be optionally oxidized, and the nitrogen atom may be optionally quaternized. The heterocyclic system may be attached, unless otherwise stated, at any heteroatom or carbon atom that affords a stable structure. A heterocycle may be aromatic or non-aromatic in nature. In certain embodiments, the heterocycle is a heteroaryl. Examples of non-aromatic heterocycles include monocyclic groups such as aziridine, oxirane, thiirane, azetidine, oxetane, thietane, pyrrolidine, pyrroline, imidazoline, pyrazolidine, dioxolane, sulfolane, 2,3-dihydrofuran, 2,5-dihydrofuran, tetrahydrofuran, thiophane, piperidine, 1,2,3,6-tetrahydropyridine, 1,4-dihydropyridine, piperazine, morpholine, thiomorpholine, pyran, 2,3-dihydropyran, tetrahydropyran, 1,4-dioxane, 1,3- dioxane, homopiperazine, homopiperidine, 1,3-dioxepane, 4,7-dihydro-1,3-dioxepin and hexamethyleneoxide. Examples of heteroaryl groups include pyridyl, pyrazinyl, pyrimidinyl (such as, but not limited to, 2- and 4-pyrimidinyl), pyridazinyl, thienyl, furyl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, pyrazolyl, isothiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,3,4-triazolyl, tetrazolyl, 1,2,3-thiadiazolyl, 1,2,3-oxadiazolyl, 1,3,4-thiadiazolyl and 1,3,4-oxadiazolyl. Examples of polycyclic heterocycles include indolyl (such as, but not limited to, 3-, 4- , 5-, 6- and 7-indolyl), indolinyl, quinolyl, tetrahydroquinolyl, isoquinolyl (such as, but not limited to, 1- and 5-isoquinolyl), 1,2,3,4-tetrahydroisoquinolyl, cinnolinyl, quinoxalinyl (such as, but not limited to, 2- and 5-quinoxalinyl), quinazolinyl, phthalazinyl, 1,8-naphthyridinyl, 1,4-benzodioxanyl, coumarin, dihydrocoumarin, 1,5-naphthyridinyl, benzofuryl (such as, but not limited to, 3-, 4-, 5-, 6- and 7-benzofuryl), 2,3-dihydrobenzofuryl, 1,2-benzisoxazolyl, benzothienyl (such as, but not limited to, 3-, 4-, 5-, 6-, and 7-benzothienyl), benzoxazolyl, benzothiazolyl (such as, but not limited to, 2-benzothiazolyl and 5-benzothiazolyl), purinyl, benzimidazolyl, benztriazolyl, thioxanthinyl, carbazolyl, carbolinyl, acridinyl, pyrrolizidinyl, and quinolizidinyl. The aforementioned listing of heterocyclyl and heteroaryl moieties is intended to be representative and not limiting. As described herein, the term "PD-L1 inhibitor" includes any compound that is capable of inhibiting the expression and/or function of the protein Programmed Death-Ligand 1 (PD-L1) either directly or indirectly. PD-L1, also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1), is a type 1 transmembrane protein that plays a major role in suppressing the adaptive arm of immune system during pregnancy, tissue allograft transplants, autoimmune disease, and hepatitis. PD-L1 binds to its receptor, the inhibitory checkpoint molecule PD-1 (which is found on activated T cells, B cells, and myeloid cells) so as to modulate activation or inhibition of the adaptive arm of immune system. In certain embodiments, the PD-L1 inhibitor inhibits the expression and/or function of PD-L1 by at least 5%, at least 10%, at least 20%, at least 50%, at least 75%, or at least 90%. As used herein, the term "pharmaceutical composition" or "composition" refers to a mixture of at least one compound useful within the disclosure with a pharmaceutically acceptable carrier. The pharmaceutical composition facilitates administration of the compound to a subject. As used herein, the term "pharmaceutically acceptable" refers to a material, such as a carrier or diluent, which does not abrogate the biological activity or properties of the compound useful within the disclosure, and is relatively non-toxic, i.e., the material may be administered to a subject without causing undesirable biological effects or interacting in a deleterious manner with any of the components of the composition in which it is contained. As used herein, the term "pharmaceutically acceptable carrier" means a pharmaceutically acceptable material, composition or carrier, such as a liquid or solid filler, stabilizer, dispersing agent, suspending agent, diluent, excipient, thickening agent, solvent or encapsulating material, involved in carrying or transporting a compound useful within the disclosure within or to the subject such that it may perform its intended function. Typically, such constructs are carried or transported from one organ, or portion of the body, to another organ, or portion of the body. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation, including the compound useful within the disclosure, and not injurious to the subject. Some examples of materials that may serve as pharmaceutically acceptable carriers include: sugars, such as lactose, glucose and sucrose; starches, such as corn starch and potato starch; cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients, such as cocoa butter and suppository waxes; oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols, such as propylene glycol; polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffering agents, such as magnesium hydroxide and aluminum hydroxide; surface active agents; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol; phosphate buffer solutions; and other non-toxic compatible substances employed in pharmaceutical formulations. As used herein, "pharmaceutically acceptable carrier" also includes any and all coatings, antibacterial and antifungal agents, and absorption delaying agents, and the like that are compatible with the activity of the compound useful within the disclosure, and are physiologically acceptable to the subject. Supplementary active compounds may also be incorporated into the compositions. The "pharmaceutically acceptable carrier" may further include a pharmaceutically acceptable salt of the compound useful within the disclosure. Other additional ingredients that may be included in the pharmaceutical compositions used in the practice of the disclosure are known in the art and described, for example in Remington's Pharmaceutical Sciences (Genaro, Ed., Mack Publishing Co., 1985, Easton, PA), which is incorporated herein by reference. As used herein, the language "pharmaceutically acceptable salt" refers to a salt of the administered compound prepared from pharmaceutically acceptable non-toxic acids and/or bases, including inorganic acids, inorganic bases, organic acids, inorganic bases, solvates (including hydrates) and clathrates thereof. As used herein, a "pharmaceutically effective amount," "therapeutically effective amount," or "effective amount" of a compound is that amount of compound that is sufficient to provide a beneficial effect to the subject to which the compound is administered. The term "prevent," "preventing," or "prevention" as used herein means avoiding or delaying the onset of symptoms associated with a disease or condition in a subject that has not developed such symptoms at the time the administering of an agent or compound commences. Disease, condition and disorder are used interchangeably herein. By the term "specifically bind" or "specifically binds" as used herein is meant that a first molecule preferentially binds to a second molecule (e.g., a particular receptor or enzyme), but does not necessarily bind only to that second molecule. As used herein, the terms "subject" and "individual" and "patient" can be used interchangeably and may refer to a human or non-human mammal or a bird. Non-human mammals include, for example, livestock and pets, such as ovine, bovine, porcine, canine, feline and murine mammals. In certain embodiments, the subject is human. As used herein, the term "substituted" refers to that an atom or group of atoms has replaced hydrogen as the substituent attached to another group. As used herein, the term "substituted alkyl," "substituted cycloalkyl," "substituted alkenyl," or "substituted alkynyl" refers to alkyl, cycloalkyl, alkenyl or alkynyl, as defined elsewhere herein, substituted by one, two or three substituents independently selected from the group consisting of halogen, -OH, alkoxy, tetrahydro-2-H-pyranyl, -NH ₂ , -NH(C ₁ -C ₆ alkyl), -N(C ₁ -C ₆ alkyl) ₂ , 1-methyl-imidazol-2-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, - C(=O)OH, -C(=O)O(C ₁ -C ₆ )alkyl, trifluoromethyl, -C≡N, -C(=O)NH ₂ , -C(=O)NH(C ₁ - C ₆ )alkyl, -C(=O)N((C ₁ -C ₆ )alkyl) ₂ , -SO ₂ NH ₂ , -SO ₂ NH(C ₁ -C ₆ alkyl), -SO ₂ N(C ₁ -C ₆ alkyl) ₂ , - C(=NH)NH ₂ , and -NO ₂ , in certain embodiments containing one or two substituents independently selected from halogen, -OH, alkoxy, -NH ₂ , trifluoromethyl, -N(CH ₃ ) ₂ , and - C(=O)OH, in certain embodiments independently selected from halogen, alkoxy and -OH. Examples of substituted alkyls include, but are not limited to, 2,2-difluoropropyl, 2- carboxycyclopentyl and 3-chloropropyl. For aryl, aryl-(C ₁ -C ₃ )alkyl and heterocyclyl groups, the term "substituted" as applied to the rings of these groups refers to any level of substitution, namely mono-, di-, tri-, tetra-, or penta-substitution, where such substitution is permitted. The substituents are independently selected, and substitution may be at any chemically accessible position. In certain embodiments, the substituents vary in number between one and four. In other embodiments, the substituents vary in number between one and three. In yet another embodiments, the substituents vary in number between one and two. In yet other embodiments, the substituents are independently selected from the group consisting of C ₁ -C ₆ alkyl, -OH, C ₁ -C ₆ alkoxy, halo, amino, acetamido and nitro. As used herein, where a substituent is an alkyl or alkoxy group, the carbon chain may be branched, straight or cyclic. In certain embodiments, each occurrence of alkyl or cycloalkyl is independently optionally substituted with at least one substituent selected from the group consisting of C ₁ - C ₆ alkyl, halo, -OR, phenyl (thus yielding, in non-limiting examples, optionally substituted phenyl-(C ₁ -C ₃ alkyl), such as, but not limited to, benzyl or substituted benzyl) and -N(R)(R), wherein each occurrence of R is independently H, C ₁ -C ₆ alkyl or C ₃ -C ₈ cycloalkyl. In other embodiments, each occurrence of aryl or heteroaryl is independently optionally substituted with at least one substituent selected from the group consisting of C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ haloalkoxy, halo, -CN, -OR, -N(R)(R), -NO ₂ , -S(=O) ₂ N(R)(R), acyl, and C ₁ - C ₆ alkoxycarbonyl, wherein each occurrence of R is independently H, C ₁ -C ₆ alkyl or C ₃ -C ₈ cycloalkyl. In yet other embodiments, each occurrence of aryl or heteroaryl is independently optionally substituted with at least one substituent selected from the group consisting of C ₁ - C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ haloalkoxy, halo, -CN, -OR, -N(R)(R), and C ₁ -C ₆ alkoxycarbonyl, wherein each occurrence of R is independently H, C ₁ -C ₆ alkyl or C ₃ -C ₈ cycloalkyl. Unless otherwise noted, when two substituents are taken together to form a ring having a specified number of ring atoms (e.g., R ² and R ³ taken together with the nitrogen to which they are attached to form a ring having from 3 to 7 ring members), the ring can have carbon atoms and optionally one or more (e.g., 1 to 3) additional heteroatoms independently selected from nitrogen, oxygen, or sulfur. The ring can be saturated or partially saturated, and can be optionally substituted with one or more substituents, non-limiting examples including a carbonyl (C=O). Whenever a term or either of their prefix roots appear in a name of a substituent the name is to be interpreted as including those limitations provided herein. For example, whenever the term "alkyl" or "aryl" or either of their prefix roots appear in a name of a substituent (e.g., arylalkyl, alkylamino) the name is to be interpreted as including those limitations given elsewhere herein for "alkyl" and "aryl" respectively. In certain embodiments, substituents of compounds are disclosed in groups or in ranges. It is specifically intended that the description include each and every individual subcombination of the members of such groups and ranges. For example, the term "C _1-6 alkyl" is specifically intended to individually disclose C ₁ , C ₂ , C ₃ , C ₄ , C ₅ , C ₆ , C ₁ -C ₆ , C ₁ -C ₅ , C ₁ -C ₄ , C ₁ -C ₃ , C ₁ -C ₂ ,C ₂ -C ₆ , C ₂ -C ₅ , C ₂ -C ₄ , C ₂ - C ₃ , C ₃ -C ₆ , C ₃ -C ₅ , C ₃ -C ₄ , C ₄ -C ₆ , C ₄ -C ₅ , and C ₅ -C ₆ alkyl. The terms "treat," "treating," and "treatment," as used herein, means reducing the frequency or severity with which symptoms of a disease or condition are experienced by a subject by virtue of administering an agent or compound to the subject. Ranges: throughout this disclosure, various aspects of the disclosure can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all the possible sub-ranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual and partial numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the breadth of the range. Compounds Programmed death-ligand 1 (PD-L1), which is also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1), is a human transmembrane protein that plays a major role in suppressing the immune system as needed. Generally, the presence of a foreign antigen in the body triggers proliferation of antigen-specific CD8+ T cells in the lymph nodes. However, binding of PD-L1 to the receptor programmed cell death protein 1 (PD-1) or B7.1 membrane protein (both of which are found on activated T cells, B cells, and myeloid cells), transmits an inhibitory signal, which reduces proliferation of the CD8+ T cells in the lymph nodes. Such interaction effectively suppresses the immune response and avoids detection and destruction of the antigens. In certain embodiments, small-molecule immunomodulators targeting the PD-1/PD- L1 signaling pathway are used to treat, ameliorate, and/or prevent hepatitis B virus (HBV) infection and related conditions in a subject. In other embodiments, inhibition of PDL-1 enhances the immune response to at least one HBV antigen. The disclosure includes a compound of formula (I), or a salt, solvate, prodrug, stereoisomer (such as, in a non-limiting example, an enantiomer or diastereoisomer, and any mixtures thereof, such as, in a non-limiting example, mixtures in any proportion of enantiomers and/or diastereoisomers thereof), tautomer, and/or geometric isomer, and any mixtures thereof. It should be noted that the absolute stereochemistry of the chiral center(s) represented in any structure depicted herein and/or compound named herein is merely illustrative and non-limiting. In one aspect, the present disclosure provides a compound formula (I), or a salt, solvate, geometric isomer, isotopologue, stereoisomer, or tautomer thereof: (I), wherein: X ¹ is selected from the group consisting of CR ^2a and N; X ² is selected from the group consisting of CR ^2b and N; X ³ is selected from the group consisting of CR ^2c and N; X ⁴ is selected from the group consisting of CR ^2d and N; X ⁵ is selected from the group consisting of CR ^2e and N; X ⁶ is selected from the group consisting of CR ^2f and N; wherein one to four selected from the group consisting of X ¹ , X ² , X ³ , X ⁴ , X ⁵ , and X ⁶ are N; R ^1a and R ^1b are each independently selected from the group consisting of H, halogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₁ -C ₆ alkoxy, CN, NO ₂ , optionally substituted C ₁ -C ₆ haloalkyl, and optionally substituted C ₁ -C ₆ haloalkoxy; R ^1c is selected from the group consisting of and ; R ^1d is selected from the group consisting of , , , , , , , and ; R ^2a , R ^2b , R ^2c , R ^2d , R ^2e , and R ^2f , if present, are each independently selected from the group consisting of H, halogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₁ -C ₆ alkoxy, CN, NO ₂ , optionally substituted C ₁ -C ₆ haloalkyl, and optionally substituted C ₁ -C ₆ haloalkoxy; R ^3a , if present, is selected from the group consisting of H, -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₁ -C ₆ alkyl), -(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocylyl), -(CH ₂ ) _{1- 3} N(R ⁸ )(optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _1-3 N(R ⁸ )(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _1-3 N(R ⁸ )C(=O)O(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₃ -C ₈ cycloalkyl), optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ alkoxy, optionally substituted C ₁ -C ₆ hydroxyalkyl, optionally substituted C ₂ -C ₉ heterocyclyl, C(=O)R ^I , C(=O)OR ^I , C(=O)N(R ^I )(R ^II ), N(R ^I )C(=O)R ^II , and S(=O) ₂ R ^I ; R ^3b , if present, is selected from the group consisting of H, -(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocylyl), C(=O)O(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _{1- 3} N(R ⁸ )(optionally substituted C ₁ -C ₆ alkyl), optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ hydroxyalkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₂ -C ₉ heterocyclyl, C(=O)R ^I , C(=O)OR ^I , C(=O)N(R ^I )(R ^II ), and S(=O) ₂ R ^I ; R ^3c , if present, is selected from the group consisting of -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₁ -C ₆ alkyl), -(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _{1- 3} N(R ⁸ )(optionally substituted C ₃ -C ₈ cycloalkyl), -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₂ -C ₉ heterocyclyl), and -(CH ₂ ) _1-3 N(R ⁸ )(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl); R ^3d , if present, is selected from the group consisting of H, -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₁ -C ₆ alkyl), -(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocylyl), -(CH ₂ ) _{1- 3} N(R ⁸ )(optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _1-3 N(R ⁸ )(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _1-3 N(R ⁸ )C(=O)O(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₃ -C ₈ cycloalkyl), optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ alkoxy, optionally substituted C ₁ -C ₆ hydroxyalkyl, optionally substituted C ₂ -C ₉ heterocyclyl, C(=O)R ^I , C(=O)OR ^I , C(=O)N(R ^I )(R ^II ), N(R ^I )C(=O)R ^II , and S(=O) ₂ R ^I ; R ^3e , if present, is selected from the group consisting of H, -(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocylyl), C(=O)O(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _{1- 3} N(R ⁸ )(optionally substituted C ₁ -C ₆ alkyl), optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ hydroxyalkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₂ -C ₉ heterocyclyl, C(=O)R ^I , C(=O)OR ^I , C(=O)N(R ^I )(R ^II ), and S(=O) ₂ R ^I ; R ^4a , R ^4b , R ^4c , R ^4d , and R ^4e , if present, are each independently selected from the group consisting of H, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₁ -C ₆ alkoxy, cyano, halogen, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ haloalkoxy, C(=O)R ^I , C(=O)OR ^I , C(=O)N(R ^I )(R ^II ), N(R ^I )C(=O)R ^II , and S(=O) ₂ R ^I ; R ^5a , R ^5b , R ^5c , R ^5d , R ^5e , R ^5f , R ^5g , R ^5h , R ⁵ⁱ , R ^5j , R ^5k , and R ^5l , if present, are each independently selected from the group consisting of H, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₁ -C ₆ alkoxy, CN, NO ₂ , halogen, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ haloalkoxy, C(=O)R ^I , C(=O)OR ^I , C(=O)N(R ^I )(R ^II ), N(R ^I )C(=O)R ^II , and S(=O) ₂ R ^I ; R ^6a , R ^6b , R ^6c , R ^6d , and R ^6e , if present, are each independently selected from the group consisting of H, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₁ -C ₆ alkoxy, CN, NO ₂ , halogen, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ haloalkoxy, C(=O)R ^I , C(=O)OR ^I , C(=O)N(R ^I )(R ^II ), N(R ^I )C(=O)R ^II , and S(=O) ₂ R ^I , wherein two vicinal substituents selected from the group consisting of R ^6a , R ^6b , R ^6c , R ^6d , and R ^6e can combine with the atoms to which they are bound to form an optionally substituted C ₄ -C ₈ cycloalkyl; each occurrence of R ^7a and R ^7b , if present, is independently selected from the group consisting of H, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₂ -C ₈ heterocycloalkyl, optionally substituted C ₇ -C ₁₂ aralkyl, optionally substituted C ₆ -C ₁₀ aryl, and optionally substituted C ₂ -C ₁₂ heteroaryl; each occurrence of R ⁸ is independently selected from the group consisting of H, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₂ -C ₈ heterocycloalkyl, optionally substituted C7-C ₁₂ aralkyl, optionally substituted C ₆ -C ₁₀ aryl, and optionally substituted C ₂ -C ₁₂ heteroaryl; each occurrence of R ^I and R ^II , if present, is independently selected from the group consisting of H, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₂ -C ₈ heterocycloalkyl, optionally substituted C7-C ₁₂ aralkyl, optionally substituted C ₆ -C ₁₀ aryl, and optionally substituted C ₂ -C ₁₂ heteroaryl; each occurrence of CH ₂ in R ^3a , R ^3b , R ^3c , and R ^3d , if present, is independently optionally substituted with at least one substituent selected from the group consisting of C ₁ -C ₃ alkyl, C ₃ - C ₈ cycloalkyl, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkyl, C ₁ -C ₃ haloalkoxy, and halogen; and each occurrence of Y is independently selected from the group consisting of O, S, and NR ^7b ; Z ¹ , if present, is selected from the group consisting of CR ^4d and N; Z ² , if present, is selected from the group consisting of CR ^4e and N; Z ³ , if present, is selected from the group consisting of CR ^6d and N; Z ⁴ , if present, is selected from the group consisting of CR ^6e and N. In certain embodiments, the compound of Formula (I) is not a compound selected from the group consisting of: N-(3-(3-chloro-2-(4-(((2-hydroxyethyl)amino)methyl)-3-methox yphenyl)pyridin-4-yl)-2- methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)picolinamide; N-(2-chloro-3-(3-chloro-2-(4-(((2-hydroxyethyl)amino)methyl) -3- methoxyphenyl)pyridin-4-yl)phenyl)-5-(((2-hydroxyethyl)amino )methyl)picolinamide; N-(3-(2-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-3-methoxy phenyl)-3-chloropyridin-4- yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)picolin amide; N-(3-(3-chloro-2-(3-methoxy-4-(((tetrahydro-2H-pyran-4- yl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(2-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-3-methoxy phenyl)-3-chloropyridin-4- yl)-2-chlorophenyl)-5-(((2-hydroxyethyl)amino)methyl)picolin amide; (S)-N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((7-oxo-2,6-diazaspiro[3.4]oct an-2- yl)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(2-chloro-3-(3-chloro-2-(3-methoxy-4-((7-oxo-2,6-diazaspir o[3.4]octan-2- yl)methyl)phenyl)pyridin-4-yl)phenyl)-5-(((2-hydroxyethyl)am ino)methyl)picolinamide; N-(3-(2-(4-((6-acetyl-2,6-diazaspiro[3.3]heptan-2-yl)methyl) -3-methoxyphenyl)-3- chloropyridin-4-yl)-2-chlorophenyl)-5-(((2-hydroxyethyl)amin o)methyl)picolinamide; N-(3-(3-chloro-2-(3-fluoro-4-(((2-hydroxyethyl)amino)methyl) -5- methoxyphenyl)pyridin-4-yl)-2-methylphenyl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((tetrahydro-2H-pyran-4-yl)amin o)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)picolinamide; N-(2-chloro-3-(3-chloro-2-(3-methoxy-4-(((tetrahydro-2H-pyra n-4- yl)amino)methyl)phenyl)pyridin-4-yl)phenyl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)picolin amide; (S)-N-(3-(3-chloro-2-(3-(difluoromethoxy)-4-((((5-oxopyrroli din-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((7-oxo-2,6-diazaspiro[3.4]oct an-2- yl)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)-5-((7-oxo-2,6 -diazaspiro[3.4]octan-2- yl)methyl)picolinamide; 5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(2-(4-(((1-ac etylpiperidin-4- yl)amino)methyl)-3-methoxyphenyl)-3-chloropyridin-4-yl)-2-me thylphenyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-(((tetrahydro-2H-pyran-4- yl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)-5-(((te trahydro-2H-pyran-4- yl)amino)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamide; 5-((6-acetyl-2,6-diazaspiro[3.3]heptan-2-yl)methyl)-N-(3-(2- (4-((6-acetyl-2,6- diazaspiro[3.3]heptan-2-yl)methyl)-3-methoxyphenyl)-3-chloro pyridin-4-yl)-2- methylphenyl)picolinamide; N-(3-(3-chloro-2-(4-((((S)-2-hydroxypropyl)amino)methyl)-3-m ethoxyphenyl)pyridin-4- yl)-2-methylphenyl)-5-((((S)-2-hydroxypropyl)amino)methyl)pi colinamide; N-(2-chloro-3-(3-chloro-2-(3-methoxy-4-((7-oxo-2,6-diazaspir o[3.4]octan-2- yl)methyl)phenyl)pyridin-4-yl)phenyl)-5-((7-oxo-2,6-diazaspi ro[3.4]octan-2- yl)methyl)picolinamide; 5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(2-(4-(((1-ac etylpiperidin-4- yl)amino)methyl)-3-methoxyphenyl)-3-chloropyridin-4-yl)-2-ch lorophenyl)picolinamide; N-(2-chloro-3-(3-chloro-2-(3-methoxy-4-(((tetrahydro-2H-pyra n-4- yl)amino)methyl)phenyl)pyridin-4-yl)phenyl)-5-(((tetrahydro- 2H-pyran-4- yl)amino)methyl)picolinamide; N-(2-chloro-3-(3-chloro-2-(3-methoxy-4-(((((S)-5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)phenyl)-5-(((((S) -5-oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamide; 5-((6-acetyl-2,6-diazaspiro[3.3]heptan-2-yl)methyl)-N-(3-(2- (4-((6-acetyl-2,6- diazaspiro[3.3]heptan-2-yl)methyl)-3-methoxyphenyl)-3-chloro pyridin-4-yl)-2- chlorophenyl)picolinamide; N-(2-chloro-3-(3-chloro-2-(4-((((S)-2-hydroxypropyl)amino)me thyl)-3- methoxyphenyl)pyridin-4-yl)phenyl)-5-((((S)-2-hydroxypropyl) amino)methyl)picolinamide; N-(2-chloro-3-(3-chloro-2-(3-methoxy-4-((methylamino)methyl) phenyl)pyridin-4- yl)phenyl)-5-((methylamino)methyl)picolinamide; 5-(((2-oxaspiro[3.3]heptan-6-yl)amino)methyl)-N-(3-(2-(4-((( 2-oxaspiro[3.3]heptan-6- yl)amino)methyl)-3-methoxyphenyl)-3-chloropyridin-4-yl)-2-ch lorophenyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((methylamino)methyl)phenyl)py ridin-4-yl)-2- methylphenyl)-5-((methylamino)methyl)picolinamide; 5-((2-oxa-6-azaspiro[3.3]heptan-6-yl)methyl)-N-(3-(2-(4-((2- oxa-6-azaspiro[3.3]heptan- 6-yl)methyl)-3-methoxyphenyl)-3-chloropyridin-4-yl)-2-chloro phenyl)picolinamide; N-(2-chloro-3-(3-chloro-2-(4-(((3-fluoropropyl)amino)methyl) -3-methoxyphenyl)pyridin- 4-yl)phenyl)-5-(((3-fluoropropyl)amino)methyl)picolinamide; 5-(((2-acetyl-2-azaspiro[3.3]heptan-6-yl)amino)methyl)-N-(3- (2-(4-(((2-acetyl-2- azaspiro[3.3]heptan-6-yl)amino)methyl)-3-methoxyphenyl)-3-ch loropyridin-4-yl)-2- chlorophenyl)picolinamide; N-(3-(3-chloro-2-(3-(difluoromethoxy)-4-(((((S)-5-oxopyrroli din-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(3-chloro-2-(3-fluoro-5-methoxy-4-(((((S)-5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamide; (S)-N-(3-(2-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-3-met hoxyphenyl)-3- chloropyridin-4-yl)-2-methylphenyl)-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamide; (S)-N-(3-(3-chloro-2-(3-methoxy-4-(((tetrahydro-2H-pyran-4- yl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)-5-((((5 -oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamide; (S)-N-(3-(3-chloro-2-(4-(((3-fluoropropyl)amino)methyl)-3-me thoxyphenyl)pyridin-4- yl)-2-methylphenyl)-5-((((5-oxopyrrolidin-2-yl)methyl)amino) methyl)picolinamide; (S)-N-(2-chloro-3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)phenyl)-5-((methy lamino)methyl)picolinamide; (S)-N-(2-chloro-3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)phenyl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)picolinamide; (S)-N-(3-(3-chloro-2-(4-(((2-hydroxyethyl)amino)methyl)-3-me thoxyphenyl)pyridin-4- yl)-2-methylphenyl)-5-((((5-oxopyrrolidin-2-yl)methyl)amino) methyl)picolinamide; and (S)-N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5- ((methylamino)methyl)picolinamide. In certain embodiments, the compound of formula (I) is a compound of formula (Ia): (Ia). In certain embodiments, the compound of formula (I) is a compound of formula (Ib): (Ib). In certain embodiments, the compound of formula (I) is a compound of formula (Ic): (Ic). In certain embodiments, the compound of formula (I) is a compound of formula (Id): (Id). In certain embodiments, the compound of formula (I) is a compound of formula (Ie): (Ie). In certain embodiments, the compound of formula (I) is a compound of formula (If): (If). In certain embodiments, the compound of formula (I) is a compound of formula (Ig): (Ig). In certain embodiments, the compound of formula (I) is a compound of formula (Ih): (Ih). In certain embodiments, the compound of formula (I) is a compound of formula (Ii): (Ii). In certain embodiments, the compound of formula (I) is a compound of formula (Ij): (Ij). In certain embodiments, the compound of formula (I) is a compound of formula (Ik): (Ik). In certain embodiments, the compound of formula (I) is a compound of formula (Il): (Il). In certain embodiments, the compound of formula (I) is a compound of formula (Im): (Im). In certain embodiments, the compound of formula (I) is a compound of formula (In): (In). In certain embodiments, the compound of formula (I) is a compound of formula (Io): (Io). In certain embodiments, each of R ^2b , R ^2c , R ^2d , R ^2e , and R ^2f is independently H. In certain embodiments, each of R ^2a , R ^2c , R ^2d , R ^2e , and R ^2f is independently H. In certain embodiments, each of R ^2a , R ^2b , R ^2d , R ^2e , and R ^2f is independently H. In certain embodiments, each of R ^2a , R ^2b , R ^2c , R ^2e , and R ^2f is independently H. In certain embodiments, each of R ^2a , R ^2b , R ^2c , R ^2d , and R ^2f is independently H. In certain embodiments, each of R ^2a , R ^2b , R ^2c , R ^2d , and R ^2e is independently H. In certain embodiments, each of R ^2b , R ^2c , R ^2e , and R ^2f is independently H. In certain embodiments, each of R ^2b , R ^2c , R ^2d , and R ^2f is independently H. In certain embodiments, each of R ^2b , R ^2c , R ^2d , and R ^2e is independently H. In certain embodiments, each of R ^2a , R ^2c , R ^2e , and R ^2f is independently H. In certain embodiments, each of R ^2a , R ^2c , R ^2d , and R ^2f is independently H. In certain embodiments, each of R ^2a , R ^2c , R ^2d , and R ^2e is independently H. In certain embodiments, each of R ^2a , R ^2b , R ^2e , and R ^2f is independently H. In certain embodiments, each of R ^2a , R ^2b , R ^2d , and R ^2f is independently H. In certain embodiments, each of R ^2a , R ^2b , R ^2d , and R ^2e is independently H. In certain embodiments, R ^1a is Me. In certain embodiments, R ^1a is Cl. In certain embodiments, R ^1a is H. In certain embodiments, R ^1a is F. In certain embodiments, R ^1a is OMe. In certain embodiments, R ^1b is Me. In certain embodiments, R ^1b is Cl. In certain embodiments, R ^1b is H. In certain embodiments, R ^1b is F. In certain embodiments, R ^1b is OMe. In certain embodiments, R ^1a and R ^1b are identical. In certain embodiments, Z ¹ is N. In certain embodiments, Z ¹ is CH. In certain embodiments, Z ² is N. In certain embodiments, Z ² is CH. In certain embodiments, R ^4a is H. In certain embodiments, R ^4a is F. In certain embodiments, R ^4a is Me. In certain embodiments, R ^4a is Et. In certain embodiments, R ^4a is OMe. In certain embodiments, R ^4a is OCHF ₂ . In certain embodiments, R ^4b is H. In certain embodiments, R ^4b is F. In certain embodiments, R ^4b is Me. In certain embodiments, R ^4b is Et. In certain embodiments, R ^4b is OMe. In certain embodiments, R ^4b is OCHF ₂ . In certain embodiments, R ^4c is H. In certain embodiments, R ^4c is F. In certain embodiments, R ^4c is Me. In certain embodiments, R ^4c is Et. In certain embodiments, R ^4c is OMe. In certain embodiments, R ^4c is OCHF ₂ . In certain embodiments, R ^4d is H. In certain embodiments, R ^4d is F. In certain embodiments, R ^4d is Me. In certain embodiments, R ^4d is Et. In certain embodiments, R ^4d is OMe. In certain embodiments, R ^4d is OCHF ₂ . In certain embodiments, R ^4e is H. In certain embodiments, R ^4e is F. In certain embodiments, R ^4e is Me. In certain embodiments, R ^4e is Et. In certain embodiments, R ^4e is OMe. In certain embodiments, R ^4e is OCHF ₂ . In certain embodiments, R ^3a is -(CH ₂ ) _1-3 NH(CH ₂ ) _1-3 (optionally substituted 5- oxopyrrolidin-2-yl). In certain embodiments, R ^3a is -(CH ₂ )NH(optionally substituted C ₁ -C ₆ haloalkyl). In certain embodiments, R ^3a is -(CH ₂ ) _1-3 (optionally substituted 2,6- diazaspiro[3.4]octan-2-yl). In certain embodiments, R ^3a is -(CH ₂ ) _1-3 (optionally substituted 7- oxa-2-azaspiro[3.5]nonan-2-yl). In certain embodiments, R ^3a is -(CH ₂ ) _1-3 (optionally substituted pyrrolidinyl). In certain embodiments, R ^3a is -(CH ₂ ) _1-3 NH(optionally substituted 2-azaspiro[3.3]heptan-6-yl). In certain embodiments, R ^3a is -(CH ₂ ) _1-3 NH(optionally substituted piperidin-4-yl). In certain embodiments, R ^3a is -(CH ₂ ) _1-3 NHC(=O)O(CH ₂ ) _{1- 3} (optionally substituted 5-oxopyrrolidin-2-yl). In certain embodiments, R ^3a is -(CH ₂ ) _{1- 3} N(CH ₃ )(CH ₂ ) _1-3 (optionally substituted 5-oxopyrrolidin-2-yl). In certain embodiments, R ^3a is -(CH ₂ ) _1-3 NH(CH ₂ ) _1-3 (optionally substituted oxetanyl). In certain embodiments, R ^3a is -(CH ₂ ) _{1- 3} NH(CH ₂ ) _1-3 (optionally substituted piperidinyl). In certain embodiments, R ^3a is -(CH ₂ ) _{1- 3} NH(CH ₂ ) _0-2 C(CH ₃ ) ₂ (CH ₂ ) _0-2 C(=O)OH. In certain embodiments, R ^3a is -(CH ₂ ) _1-3 (optionally substituted azetidinyl). In certain embodiments, R ^3a is -(CH ₂ ) _1-3 (optionally substituted 2,5- diazaspiro[3.4]octan-2-yl). In certain embodiments, R ^3a is -(CH ₂ ) _1-3 (optionally substituted piperidinyl). In certain embodiments, R ^3a is -(CH ₂ ) _1-3 NH(optionally substituted pyrrolidinyl). In certain embodiments, R ^3a is -(CH ₂ ) _1-3 N(CH ₃ )(optionally substituted piperidin-4-yl). In certain embodiments, R ^3a is -(CH ₂ ) _1-3 NH(optionally substituted piperidin-3-yl). In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, R ^3a is . In certain embodiments, at least one of R ^5a , R ^5b , R ^5c , R ^5d , R ^5e , and R ^5f is H. In certain embodiments, at least two of R ^5a , R ^5b , R ^5c , R ^5d , R ^5e , and R ^5f are H. In certain embodiments, at least three of R ^5a , R ^5b , R ^5c , R ^5d , R ^5e , and R ^5f are H. In certain embodiments, at least four of R ^5a , R ^5b , R ^5c , R ^5d , R ^5e , and R ^5f are H. In certain embodiments, at least five of R ^5a , R ^5b , R ^5c , R ^5d , R ^5e , and R ^5f are H. In certain embodiments, each of R ^5a , R ^5b , R ^5c , R ^5d , R ^5e , and R ^5f are H. In certain embodiments, R ^3b is -(CH ₂ ) _1-3 CH(CH ₃ )(OH). In certain embodiments, R ^3b is -(CH ₂ ) _1-3 (optionally substituted 5-oxopyrrolidin-2-yl). In certain embodiments, R ^3b is . In certain embodiments, R ^3b is . In certain embodiments, R ^3b is . In certain embodiments, R ^3b is . In certain embodiments, R ^3b is . In certain embodiments, R ^3b is . In certain embodiments, R ^1c is , R ^1d is , R ^1a and R ^1b are identical, R ^3a and R ^3c are not identical, and R ^3c is -(CH ₂ ) _1-3 N(R ⁸ )(C ₁ -C ₆ haloalkyl). In certain embodiments, R ^1c is , R ^1d is , R ^3a and R ^3c are not identical, and R ^3c is selected from the group consisting of -(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₃ -C ₈ cycloalkyl), and -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₂ -C ₉ heterocyclyl). In certain embodiments, R ^1c is , R ^1d is , R ^3a and R ^3c are not identical, R ^3c is -(CH ₂ ) _1-3 N(R ⁸ )(C ₁ -C ₆ alkyl), and R ^3a is selected from the group consisting of H, -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₁ -C ₆ alkyl), -(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocylyl), -(CH ₂ ) _1-3 N(R ⁸ )C(=O)O(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₃ -C ₈ cycloalkyl), optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ alkoxy, optionally substituted C ₁ -C ₆ hydroxyalkyl, optionally substituted C ₂ -C ₉ heterocyclyl, C(=O)R ^I , C(=O)OR ^I , C(=O)N(R ^I )(R ^II ), N(R ^I )C(=O)R ^II , and S(=O) ₂ R ^I . In certain embodiments, R ^1c is , R ^1d is , R ^3a and R ^3c are not identical, and at least one of R ^4a , R ^4b , R ^4d , and R ^4e is selected from the group consisting of C ₁ -C ₆ alkyl and halogen. In certain embodiments, R ^1c is , R ^1d is , R ^3a and R ^3c are not identical, R ^1a and R ^1b are identical, and R ^3c is optionally substituted 2- azaspiro[3.3]heptanyl. In certain embodiments, R ^1c is , R ^1d is , and R ^3a is 7- oxa-2-azaspiro[3.5]nonanyl. In certain embodiments, R ^1c is , R ^1d is , and R ^3c is - (CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₁ -C ₆ alkyl), wherein R ⁸ is selected from the group consisting of optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₂ -C ₈ heterocycloalkyl, optionally substituted C7-C ₁₂ aralkyl, optionally substituted C ₆ -C10 aryl, and optionally substituted C ₂ -C ₁₂ heteroaryl. In certain embodiments, R ^1c is , R ^1d is , and R ^3c is - (CH ₂ ) _1-3 N(R ⁸ )(C ₁ -C ₆ alkoxy). In certain embodiments, R ^1c is , R ^1d is , and R ^3c is - (CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₃ -C ₆ hydroxyalkyl). In certain embodiments, R ^1c is , R ^1d is , and at least one of R ^3a and R ^3c is -(CH ₂ ) _1-3 (optionally substituted pyrrolidin-1-yl). In certain embodiments, R ^1c is , R ^1d is , X ³ is N, and at least one of R ^4a , R ^4b , R ^4d , and R ^4e is C ₁ -C ₆ haloalkoxy. In certain embodiments, R ^1c is , R ^1d is , X ³ is N, and R ^1a and R ^1b are identical. In certain embodiments, R ^1c is , R ^1d is , X ³ is N, and R ^3c is -(CH ₂ ) _1-3 N(R ⁸ )(C ₁ -C ₆ hydroxyalkyl), wherein the hydroxyalkyl in R ^3c is substituted at any position with at least one C ₁ -C ₆ alkyl. In certain embodiments, R ^1c is , R ^1d is , X ³ is N, and R ^3c is -(CH ₂ ) _1-3 N(R ⁸ )(C ₁ -C ₆ haloalkyl). In certain embodiments, R ^1c is , R ^1d is , X ³ is N, and R ^3c is -(CH ₂ ) _1-3 N(R ⁸ )(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl). In certain embodiments, R ^1c is , R ^1d is , X ³ is N, and R ^3c is -(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl). In certain embodiments, R ^1c is , R ^1d is , X ³ is N, and R ^3a is selected from the group consisting of H, -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₁ -C ₆ alkyl), -(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocylyl), -(CH ₂ ) _1-3 N(R ⁸ )C(=O)O(CH ₂ ) _{1- 3} (optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₃ -C ₈ cycloalkyl), optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ alkoxy, optionally substituted C ₁ -C ₆ hydroxyalkyl, optionally substituted C ₂ -C ₉ heterocyclyl, C(=O)R ^I , C(=O)OR ^I , C(=O)N(R ^I )(R ^II ), N(R ^I )C(=O)R ^II , and S(=O) ₂ R ^I . In certain embodiments, R ^1c is , R ^1d is , and Z ² is N. In certain embodiments, R ^1c is , R ^1d is , and Z ³ is CR ^6d . In certain embodiments, R ^1c is , R ^1d is , Z ³ is N, and at least one of R ^6a , R ^6c , and R ^6e is selected from the group consisting of C ₁ -C ₆ alkyl, hydroxy, C ₁ -C ₆ alkoxy, and halogen. In certain embodiments, R ^1c is , R ^1d is , and Z ⁴ is N. In certain embodiments, R ^1c is , R ^1d is , R ³ is -(CH ₂ ) _{1- 3} N(R ⁸ )(CH ₂ ) _1-3 (1-methyl-5-oxopyrrolidinyl) or R ^3c is -(CH ₂ ) _1-3 (optionally substituted pyrrolidinyl). In certain embodiments, R ^1c is , R ^1d is , Z ¹ is N and R ^3c is -(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl). In certain embodiments, R ^1c is , R ^1d is , Z ¹ is N and R ^3a and R ^3c are identical. In certain embodiments, R ^1c is , R ^1d is , Z ¹ is N, R ^3a is –(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl), and R ^3c is -(CH ₂ ) _1-3 N(R ⁸ )(CH ₂ ) _1- 3(optionally substituted C ₂ -C ₀ heterocyclyl). In certain embodiments, R ^1c is , R ^1d is , at least one of R ^1a and R ^1b is F or OMe. In certain embodiments, R ^1c is , R ^1d is , R ^1a and R ^1b are Cl, and R ^3c is CH ₂ N(R ⁸ )(C ₁ -C ₆ haloalkyl). In certain embodiments, R ^1c is , R ^1d is , R ^3a and R ^3c are not identical, and at least one of R ^4a , R ^4b , R ^4d , and R ^4e is selected from the group consisting of Me, Et, F, and Cl. In certain embodiments, R ^1c is , R ^1d is , and R ^3c is CH ₂ N(R ⁸ )(methoxyethyl). In certain embodiments, R ^1c is , R ^1d is , R ^3c is CH ₂ N(CH ₃ )(C ₁ -C ₆ hydroxyalkyl). In certain embodiments, R ^1c is , R ^1d is , and R ^3c is CH ₂ N(R ⁸ )(optionally substituted hydroxypropyl). In certain embodiments, R ^1c is , R ^1d is , X ³ is N, and at least one of R ^4a , R ^4b , R ^4d , and R ^4e is OCHF ₂ . In certain embodiments, R ^1c is , R ^1d is , X ³ is N, and R ^1a and R ^1b are Cl. In certain embodiments, R ^1c is , R ^1d is , X ³ is N, and R ^3c is CH ₂ N(R ⁸ )(C ₁ -C ₆ hydroxyalkyl), wherein the hydroxyalkyl in R ^3c is substituted at any position with at least one selected from the group consisting of methyl and isopropyl. In certain embodiments, R ^1c is , R ^1d is , X ³ is N, and R ^3c is CH ₂ N(R ⁸ )(C ₁ -C ₆ fluoroalkyl). In certain embodiments, R ^1c is , R ^1d is , X ³ is N, and R ^3c is CH ₂ N(R ⁸ )CH ₂ (optionally substituted C ₂ -C ₉ heterocyclyl). In certain embodiments, R ^1c is , R ^1d is , X ³ is N, and R ^1a and R ^1b are identical. In certain embodiments, R ^1c is , R ^1d is , X ³ is N, and R ^3a is -(CH ₂ ) _1-3 N(R ⁸ )C(=O)O(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl). In certain embodiments, R ^1c is , R ^1d is , Z ³ is N, and at least one of R ^6a , R ^6c , and R ^6e is selected from the group consisting of Me, OMe, and F. In certain embodiments, R ^1c is , R ^1d is , and Z ³ is CF. In certain embodiments, R ^3c is -(CH ₂ ) _1-3 NH(C ₁ -C ₆ alkyl). In certain embodiments, R ^3c is -(CH ₂ ) _1-3 NH(optionally substituted C ₁ -C ₆ haloalkyl). In certain embodiments, R ^3c is - (CH ₂ ) _1-3 NH(optionally substituted C ₁ -C ₆ hydroxyalkyl). In certain embodiments, R ^3c is - (CH ₂ ) _1-3 N(C ₁ -C ₆ alkyl)(optionally substituted C ₁ -C ₆ hydroxyalkyl). In certain embodiments, R ^3c is -(CH ₂ ) _1-3 NH(optionally substituted C ₁ -C ₆ alkoxy). In certain embodiments, R ^3c is - (CH ₂ ) _1-3 NHCH ₂ C(CH ₃ )(OH). In certain embodiments, R ^3c is -(CH ₂ ) _1-3 NHCH ₂ C(CH ₃ ) ₂ (OH). In certain embodiments, R ^3c is -(CH ₂ ) _1-3 NHCH(CH(CH ₃ ) ₂ )CH ₂ OH. In certain embodiments, R ^3c is -(CH ₂ ) _1-3 (optionally substituted azetidin-1-yl). In certain embodiments, R ^3c is -(CH ₂ ) _1- 3(optionally substituted pyrrolidin-1-yl). In certain embodiments, R ^3c is -(CH ₂ ) _{1- 3} NH(optionally substituted cyclopropyl). In certain embodiments, R ^3c is -(CH ₂ ) _{1- 3} NH(optionally substituted 2-azaspiro[3.3]heptan-2-yl). In certain embodiments, R ^3c is - (CH ₂ ) _1-3 N(optionally substituted piperidin-4-yl). In certain embodiments, R ^3c is -(CH ₂ ) _{1- 3} NH(CH ₂ ) _1-3 (optionally substituted oxetan-2-yl). In certain embodiments, R ^3c is -(CH ₂ ) _{1- 3} NH(optionally substituted cyclobutyl). In certain embodiments, R ^3c is -(CH ₂ ) _1-3 NH(CH ₂ ) _1- 3(optionally substituted cyclopropylenyl)(CH ₂ ) _1-3 OH. In certain embodiments, R ^3c is -(CH ₂ ) _{1- 3} NH(CH ₂ ) _1-3 (C(CH ₃ ) ₂ ) _0-1 (CH ₂ ) _1-3 C(=O)OH. In certain embodiments, R ^3c is -(CH ₂ ) _1- 3C(=O)NH ₂ . In certain embodiments, R ^3c is -(CH ₂ ) _1-3 (optionally substituted piperidinyl). In certain embodiments, R ^3c is -(CH ₂ ) _1-3 NH(optionally substituted cyclohexyl). In certain embodiments, R ^3c is -(CH ₂ ) _1-3 NH(CH ₂ ) _1-3 (optionally substituted 5-oxopyrrolidin-2-yl). In certain embodiments, R ^3c is -(CH ₂ ) _1-3 NH(CH ₂ ) _1-3 (optionally substituted bicyclo[2.2.1]heptanyl). In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c . In certain embodiments, R ^3c is . In certain embodiments, R ^3c . In certain embodiments, R ^3c . In certain embodiments, R ^3c . In certain embodiments, R ^3c . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3c is . In certain embodiments, R ^3d is -(CH ₂ ) _1-3 NH(C ₁ -C ₆ hydroxyalkyl). In certain embodiments, R ^3d is -(CH ₂ ) _1-3 N(C ₁ -C ₆ alkyl)(C ₁ -C ₆ haloalkyl). In certain embodiments, R ^3d is . In certain embodiments, R ^3d is . In certain embodiments, R ^3d is . In certain embodiments, R ^3d is . In certain embodiments, R ^3d is . In certain embodiments, R ^3d is . In certain embodiments, R ^3d is . In certain embodiments, R ^3d is . In certain embodiments, R ^3d is . In certain embodiments, R ^3d is . In certain embodiments, R ^3d is . In certain embodiments, R ^3d is . In certain embodiments, R ^3d is . In certain embodiments, R ^3d is . In certain embodiments, R ^3d is . In certain embodiments, at least one of R ^5g , R ^5h , R ⁵ⁱ , R ^5j , R ^5k , and R ^5l is H. In certain embodiments, at least two of R ^5g , R ^5h , R ⁵ⁱ , R ^5j , R ^5k , and R ^5l are H. In certain embodiments, at least three of R ^5g , R ^5h , R ⁵ⁱ , R ^5j , R ^5k , and R ^5l are H. In certain embodiments, at least four of R ^5g , R ^5h , R ⁵ⁱ , R ^5j , R ^5k , and R ^5l are H. In certain embodiments, at least five of R ^5g , R ^5h , R ⁵ⁱ , R ^5j , R ^5k , and R ^5l are H. In certain embodiments, each of R ^5g , R ^5h , R ⁵ⁱ , R ^5j , R ^5k , and R ^5l are H. In certain embodiments, R ^1c is selected from the group consisting of , , , , , , , , ,

wherein: R ^9a and R ^9b , if present, are each independently selected from the group consisting of C ₁ - C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₁ -C ₆ haloalkoxy, and halogen; and R ^10a and R ^10b , if present, are each independently selected from the group consisting of H, C ₁ -C ₆ alkyl, and C(=O)(C ₁ -C ₆ alkyl). In certain embodiments, R ^9a is methyl. In certain embodiments, R ^9a is ethyl. In certain embodiments, R ^9a is methoxy. In certain embodiments, R ^9a is fluoro. In certain embodiments, R ^9a is chloro. In certain embodiments, R ^9a is difluoromethoxy. In certain embodiments, R ^9b is methyl. In certain embodiments, R ^9b is ethyl. In certain embodiments, R ^9b is methoxy. In certain embodiments, R ^9b is fluoro. In certain embodiments, R ^9b is chloro. In certain embodiments, R ^9b is difluoromethoxy. In certain embodiments, R ^10a is H. In certain embodiments, R ^10a is C(=O)CH ₃ . In certain embodiments, R ^10a is CH ₃ . In certain embodiments, R ^10b is H. In certain embodiments, R ^10b is C(=O)CH ₃ . In certain embodiments, R ^10b is CH ₃ . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1c is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is , In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . . In certain embodiments, R ^1d is . . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is In certain embodiments, R ^1d is In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, each occurrence of R ^11a , R ^11b , and R ^11c , if present, is independently selected from the group consisting of H, C ₁ -C ₆ alkyl, and C(=O)(C ₁ -C ₆ alkyl); and each occurrence of R ¹² , if present, is independently selected from the group consisting of C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, hydroxy, and halogen. In certain embodiments, R ^11a is H. In certain embodiments, R ^11a is methyl. In certain embodiments, R ^11a is C(=O)CH ₃ . In certain embodiments, R ^11a is CH ₃ . In certain embodiments, R ^11b is H. In certain embodiments, R ^11b is methyl. In certain embodiments, R ^11b is C(=O)CH ₃ . In certain embodiments, R ^11b is CH ₃ . In certain embodiments, R ^11c is H. In certain embodiments, R ^11c is methyl. In certain embodiments, R ^11c is C(=O)CH ₃ . In certain embodiments, R ^11c is CH ₃ . In certain embodiments, R ¹² is methyl. In certain embodiments, R ¹² is methoxy. In certain embodiments, R ¹² is fluoro. In certain embodiments, R ¹² is methyl. In certain embodiments, R ¹² is hydroxy. In certain embodiments, R ^7a is H. In certain embodiments, R ^7b is H. In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is In certain embodiments, R ^1d is In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is , In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, R ^1d is . In certain embodiments, each occurrence of optionally substituted alkyl, optionally substituted alkoxy, optionally substituted haloalkyl, optionally substituted haloalkoxy, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl is independently optionally substituted with at least one substituent selected from the group consisting of C ₁ -C ₆ alkyl, C ₃ -C ₈ cycloalkyl, C ₂ -C ₁₂ heterocycloalkyl, C ₁ -C ₆ hydroxyalkyl, halogen, CN, NO ₂ OR’, N(R’)(R”), C ₁ -C ₆ haloalkoxy, C ₃ -C ₈ halocycloalkoxy, aryl, heteroaryl, (C ₁ -C ₆ alkylenyl)C(=O)N(R’)(R”), (C ₁ -C ₆ alkylenyl)C(=O)OR’, O(C ₁ -C ₃ alkylenyl)C(=O)OR’, O(C ₁ -C ₃ alkylenyl)C(=O)N(R’)(R’), C(=O)R’, C(=O)OR’, OC(=O)R’, OC(=O)OR’, SR’, S(=O)R’, S(=O) ₂ R’, S(=O) ₂ N(R’)(R”), S(=O) ₂ NR’C(=O)NHR”, N(R’)S(=O) ₂ R”, N(R’)C(=O)R”, and C(=O)NR’R”, wherein R’ and R” are each independently selected from the group consisting of H, -C(=O)(C ₁ -C ₆ alkyl), C ₁ - C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl, C ₃ -C ₈ cycloalkyl, C ₂ -C ₁₂ heterocycloalkyl, C ₇ - C ₁₂ aralkyl, aryl, and heteroaryl. In certain embodiments, each occurrence of optionally substituted C ₃ -C ₆ hydroxyalkyl, optionally substituted 5-oxopyrrolidin-2-yl, optionally substituted 2,6- diazaspiro[3.4]octan-2-yl, optionally substituted 7-oxa-2-azaspiro[3.5]nonan-2-yl, optionally substituted pyrrolidinyl, optionally substituted 2-azaspiro[3.3]heptan-6-yl, optionally substituted piperidin-4-yl, optionally substituted 5-oxopyrrolidin-2-yl, optionally substituted pyrrolidin-1-yl, optionally substituted azetidin-1-yl, optionally substituted cyclopropyl, and optionally substituted oxetan-2-yl is independently optionally substituted with at least one substituent selected from the group consisting of C ₁ -C ₆ alkyl, C ₃ -C ₈ cycloalkyl, C ₂ -C ₁₂ heterocycloalkyl, C ₁ -C ₆ hydroxyalkyl, halogen, CN, NO ₂ OR’, N(R’)(R”), C ₁ -C ₆ haloalkoxy, C ₃ -C ₈ halocycloalkoxy, aryl, heteroaryl, (C ₁ -C ₆ alkylenyl)C(=O)N(R’)(R”), (C ₁ -C ₆ alkylenyl)C(=O)OR’, O(C ₁ -C ₃ alkylenyl)C(=O)OR’, O(C ₁ -C ₃ alkylenyl)C(=O)N(R’)(R’), C(=O)R’, C(=O)OR’, OC(=O)R’, OC(=O)OR’, SR’, S(=O)R’, S(=O) ₂ R’, S(=O) ₂ N(R’)(R”), S(=O) ₂ NR’C(=O)NHR”, N(R’)S(=O) ₂ R”, N(R’)C(=O)R”, and C(=O)NR’R”, wherein R’ and R” are each independently selected from the group consisting of H, -C(=O)(C ₁ -C ₆ alkyl), C ₁ - C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl, C ₃ -C ₈ cycloalkyl, C ₂ -C ₁₂ heterocycloalkyl, C7- C ₁₂ aralkyl, aryl, and heteroaryl. In certain embodiments, the compound is selected from the group consisting of: N-(3-(3-chloro-2-(3-fluoro-5-methoxy-4-((((5-oxopyrrolidin-2 - yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; (S)-N-(3-(3-chloro-2-(3-fluoro-5-methoxy-4-((((5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; (R)-N-(3-(3-chloro-2-(3-fluoro-5-methoxy-4-((((5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(2-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-3-methoxy phenyl)-3-chloropyridin-4- yl)-2-methylphenyl)-5-((methylamino)methyl)picolinamide; N-(3-(3-chloro-2-(4-(((3-fluoropropyl)amino)methyl)-3-methox yphenyl)pyridin-4-yl)-2- methylphenyl)-5-((methylamino)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- methoxyethyl)amino)methyl)picolinamide; (S)-N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- methoxyethyl)amino)methyl)picolinamide; (R)-N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- methoxyethyl)amino)methyl)picolinamide; N-(3-(2-(4-((7-oxa-2-azaspiro[3.5]nonan-2-yl)methyl)-3-metho xyphenyl)-3- chloropyridin-4-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amin o)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-((3-hydroxypyrrolidin-1- yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((S)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((R)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-(((((R)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((S)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-(((((R)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((R)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(2-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-3-methoxy phenyl)-3-chloropyridin-4- yl)-2-methylphenyl)-5-((3-hydroxypyrrolidin-1-yl)methyl)pico linamide; (S)-N-(3-(2-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-3-met hoxyphenyl)-3- chloropyridin-4-yl)-2-methylphenyl)-5-((3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; (R)-N-(3-(2-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-3-met hoxyphenyl)-3- chloropyridin-4-yl)-2-methylphenyl)-5-((3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(3-chloro-2-(4-((3-hydroxypyrrolidin-1-yl)methyl)-3-met hoxyphenyl)pyridin-4-yl)- 2-methylphenyl)-5-((3-hydroxypyrrolidin-1-yl)methyl)picolina mide; N-(3-(3-chloro-2-(4-(((S)-3-hydroxypyrrolidin-1-yl)methyl)-3 -methoxyphenyl)pyridin-4- yl)-2-methylphenyl)-5-(((S)-3-hydroxypyrrolidin-1-yl)methyl) picolinamide; N-(3-(3-chloro-2-(4-(((S)-3-hydroxypyrrolidin-1-yl)methyl)-3 -methoxyphenyl)pyridin-4- yl)-2-methylphenyl)-5-(((R)-3-hydroxypyrrolidin-1-yl)methyl) picolinamide; N-(3-(3-chloro-2-(4-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-3 -methoxyphenyl)pyridin-4- yl)-2-methylphenyl)-5-(((S)-3-hydroxypyrrolidin-1-yl)methyl) picolinamide; N-(3-(3-chloro-2-(4-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-3 -methoxyphenyl)pyridin-4- yl)-2-methylphenyl)-5-(((R)-3-hydroxypyrrolidin-1-yl)methyl) picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)(methyl)amino)methyl)picolinamide; (S)-N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)(methyl)amino)methyl)picolinamide; (R)-N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)(methyl)amino)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((7-oxo-2,6-diazaspiro[3.4]oct an-2- yl)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)-5-((3-hydroxy pyrrolidin-1- yl)methyl)picolinamide; (S)-N-(3-(3-chloro-2-(3-methoxy-4-((7-oxo-2,6-diazaspiro[3.4 ]octan-2- yl)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)-5-((3-hydroxy pyrrolidin-1- yl)methyl)picolinamide; (R)-N-(3-(3-chloro-2-(3-methoxy-4-((7-oxo-2,6-diazaspiro[3.4 ]octan-2- yl)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)-5-((3-hydroxy pyrrolidin-1- yl)methyl)picolinamide; N-(3-(2-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-3-methoxy phenyl)-3-chloropyridin-4- yl)-2-methylphenyl)-5-(((2-hydroxyethyl)(methyl)amino)methyl )picolinamide; N-(3-(2-(4-(((2-acetyl-2-azaspiro[3.3]heptan-6-yl)amino)meth yl)-3-methoxyphenyl)-3- chloropyridin-4-yl)-2-chlorophenyl)-5-(((2-hydroxyethyl)amin o)methyl)picolinamide; 5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3-(3-c hloro-2-(3-methoxy-4-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)phenyl)pyridin-4-yl)p henyl)picolinamide; (S)-5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3-chloro-2-(3-methoxy-4- ((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)phenyl)pyridin- 4-yl)phenyl)picolinamide; 5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3-(3-c hloro-2-(3-methoxy-4-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)phenyl)pyridin-4-yl)p henyl)picolinamide; N-(2-chloro-3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2 - yl)methyl)amino)methyl)phenyl)pyridin-4-yl)phenyl)-5-(((3- fluoropropyl)amino)methyl)picolinamide; (S)-N-(2-chloro-3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)phenyl)-5-(((3- fluoropropyl)amino)methyl)picolinamide; (R)-N-(2-chloro-3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)phenyl)-5-(((3- fluoropropyl)amino)methyl)picolinamide; 5-(((2-acetyl-2-azaspiro[3.3]heptan-6-yl)amino)methyl)-N-(2- chloro-3-(3-chloro-2-(3- methoxy-4-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)pheny l)pyridin-4- yl)phenyl)picolinamide; (S)-5-(((2-acetyl-2-azaspiro[3.3]heptan-6-yl)amino)methyl)-N -(2-chloro-3-(3-chloro-2- (3-methoxy-4-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)ph enyl)pyridin-4- yl)phenyl)picolinamide; (R)-5-(((2-acetyl-2-azaspiro[3.3]heptan-6-yl)amino)methyl)-N -(2-chloro-3-(3-chloro-2- (3-methoxy-4-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)ph enyl)pyridin-4- yl)phenyl)picolinamide; N-(3-(3-chloro-2-(3-methyl-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; (S)-N-(3-(3-chloro-2-(3-methyl-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; (R)-N-(3-(3-chloro-2-(3-methyl-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(3-chloro-2-(3-ethyl-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; (S)-N-(3-(3-chloro-2-(3-ethyl-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; (R)-N-(3-(3-chloro-2-(3-ethyl-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(3-chloro-2-(3-fluoro-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; (S)-N-(3-(3-chloro-2-(3-fluoro-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; (R)-N-(3-(3-chloro-2-(3-fluoro-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(3-chloro-2-(3-chloro-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; (S)-N-(3-(3-chloro-2-(3-chloro-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; (R)-N-(3-(3-chloro-2-(3-chloro-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(3'-chloro-4-fluoro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl) amino)methyl)picolinamide; (S)-N-(3-(3'-chloro-4-fluoro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide; (R)-N-(3-(3'-chloro-4-fluoro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-(difluoromethoxy)-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl) amino)methyl)picolinamide; (S)-N-(3-(3'-chloro-6-(difluoromethoxy)-5-((((5-oxopyrrolidi n-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide; (R)-N-(3-(3'-chloro-6-(difluoromethoxy)-5-((((5-oxopyrrolidi n-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 2-fluoro-4-(((2- hydroxyethyl)amino)methyl)benzamide; (S)-N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 2-fluoro-4-(((2- hydroxyethyl)amino)methyl)benzamide; (R)-N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 2-fluoro-4-(((2- hydroxyethyl)amino)methyl)benzamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((2-hydroxyethyl)amino)met hyl)picolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 2- hydroxyethyl)amino)methyl)picolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 2- hydroxyethyl)amino)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((S)-3-hydroxypyrrolidin-1 -yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( S)-3-hydroxypyrrolidin-1- yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( R)-3-hydroxypyrrolidin-1- yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( S)-3-hydroxypyrrolidin-1- yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( R)-3-hydroxypyrrolidin-1- yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((2-methoxyethyl)amino)met hyl)picolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 2- methoxyethyl)amino)methyl)picolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 2- methoxyethyl)amino)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((3-fluoropropyl)amino)met hyl)picolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 3- fluoropropyl)amino)methyl)picolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 3- fluoropropyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxypyrrolidin-1- yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-hydroxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-hydroxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-hydroxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-hydroxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxypyrrolidin-1- yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-hydroxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-hydroxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-hydroxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-hydroxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxypropyl)amino )methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((S)-2-hydroxypropyl)a mino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((R)-2-hydroxypropyl)a mino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((S)-2-hydroxypropyl)a mino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((R)-2-hydroxypropyl)a mino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((3-fluoropropyl)amino) methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((3-fluoropropyl)amino) methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((3-fluoropropyl)amino) methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxypropyl)amino )methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((S)-2-hydroxypropyl)a mino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((R)-2-hydroxypropyl)a mino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((S)-2-hydroxypropyl)a mino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((R)-2-hydroxypropyl)a mino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxy-2- methylpropyl)amino)methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxy-2- methylpropyl)amino)methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxy-2- methylpropyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)(methy l)amino)methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)(methy l)amino)methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)(methy l)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-methoxyethyl)amino) methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-methoxyethyl)amino) methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-methoxyethyl)amino) methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((oxetan-2-ylmethyl)ami no)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((oxetan-2-ylmethyl)ami no)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((oxetan-2-ylmethyl)ami no)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((3-hydroxy-3- methylcyclobutyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((1r,3s)-3-hydroxy-3- methylcyclobutyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((1r,3s)-3-hydroxy-3- methylcyclobutyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((1r,3r)-3-hydroxy-3- methylcyclobutyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((1r,3r)-3-hydroxy-3- methylcyclobutyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-(hydroxymethyl)azeti din-1-yl)methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-(hydroxymethyl)azeti din-1-yl)methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-(hydroxymethyl)azeti din-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((3-hydroxypropyl)amino )methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((3-hydroxypropyl)amino )methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((3-hydroxypropyl)amino )methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((1-hydroxy-3-methylbut an-2- yl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((S)-1-hydroxy-3-methy lbutan-2- yl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((R)-1-hydroxy-3-methy lbutan-2- yl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((S)-1-hydroxy-3-methy lbutan-2- yl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((R)-1-hydroxy-3-methy lbutan-2- yl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-methoxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-methoxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-methoxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-methoxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-methoxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-6- methoxypicolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-6- methoxypicolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-6- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)thiazole-2- carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)thiazole-2- carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)thiazole-2- carboxamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-1-methyl-1H- imidazole-2-carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-1-methyl-1H- imidazole-2-carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-1-methyl-1H- imidazole-2-carboxamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)pyrazine-2- carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)pyrazine-2- carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)pyrazine-2- carboxamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)thiazole-2- carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)thiazole-2- carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)thiazole-2- carboxamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-3-(2-((3-fluoropropyl)(methyl )amino)ethyl)-1H-pyrazole-5- carboxamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-3-(2- ((3- fluoropropyl)(methyl)amino)ethyl)-1H-pyrazole-5-carboxamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-3-(2- ((3- fluoropropyl)(methyl)amino)ethyl)-1H-pyrazole-5-carboxamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-3- methoxypicolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-3- methoxypicolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-3- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-3-methylpicolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-3-methylpicolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-3-methylpicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)picolinamide; N-(3-(3-chloro-2-(2-(2-hydroxypropyl)-8-methoxy-1,2,3,4-tetr ahydroisoquinolin-6- yl)pyridin-4-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)m ethyl)picolinamide; (S)-N-(3-(3-chloro-2-(2-(2-hydroxypropyl)-8-methoxy-1,2,3,4- tetrahydroisoquinolin-6- yl)pyridin-4-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)m ethyl)picolinamide; (R)-N-(3-(3-chloro-2-(2-(2-hydroxypropyl)-8-methoxy-1,2,3,4- tetrahydroisoquinolin-6- yl)pyridin-4-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)m ethyl)picolinamide; N-(3-(3-chloro-2-(8-methoxy-2-((5-oxopyrrolidin-2-yl)methyl) -1,2,3,4- tetrahydroisoquinolin-6-yl)pyridin-4-yl)-2-methylphenyl)-5-( ((2- hydroxyethyl)amino)methyl)picolinamide; (S)-N-(3-(3-chloro-2-(8-methoxy-2-((5-oxopyrrolidin-2-yl)met hyl)-1,2,3,4- tetrahydroisoquinolin-6-yl)pyridin-4-yl)-2-methylphenyl)-5-( ((2- hydroxyethyl)amino)methyl)picolinamide; (R)-N-(3-(3-chloro-2-(8-methoxy-2-((5-oxopyrrolidin-2-yl)met hyl)-1,2,3,4- tetrahydroisoquinolin-6-yl)pyridin-4-yl)-2-methylphenyl)-5-( ((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(3-chloro-4-(6-methoxy-5-((((5-oxopyrrolidin-2-yl)methy l)amino)methyl)pyrazin-2- yl)pyridin-2-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)m ethyl)picolinamide; (S)-N-(3-(3-chloro-4-(6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)pyrazin-2-yl)pyridin-2-yl)-2-methylph enyl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide; and (R)-N-(3-(3-chloro-4-(6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)pyrazin-2-yl)pyridin-2-yl)-2-methylph enyl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide. (5-oxopyrrolidin-2-yl)methyl ((3'-chloro-2'-(2-chloro-3-(5-(((2- hydroxyethyl)amino)methyl)picolinamido)phenyl)-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)carbamate; (S)-(5-oxopyrrolidin-2-yl)methyl ((3'-chloro-2'-(2-chloro-3-(5-(((2- hydroxyethyl)amino)methyl)picolinamido)phenyl)-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)carbamate; (R)-(5-oxopyrrolidin-2-yl)methyl ((3'-chloro-2'-(2-chloro-3-(5-(((2- hydroxyethyl)amino)methyl)picolinamido)phenyl)-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)carbamate; 5-(((2-hydroxyethyl)amino)methyl)-N-(3-(4-(6-methoxy-5-((((5 -oxopyrrolidin-2- yl)methyl)amino)methyl)pyrazin-2-yl)-3-methylpyridin-2-yl)-2 -methylphenyl)picolinamide; (S)-5-(((2-hydroxyethyl)amino)methyl)-N-(3-(4-(6-methoxy-5-( (((5-oxopyrrolidin-2- yl)methyl)amino)methyl)pyrazin-2-yl)-3-methylpyridin-2-yl)-2 -methylphenyl)picolinamide; (R)-5-(((2-hydroxyethyl)amino)methyl)-N-(3-(4-(6-methoxy-5-( (((5-oxopyrrolidin-2- yl)methyl)amino)methyl)pyrazin-2-yl)-3-methylpyridin-2-yl)-2 -methylphenyl)picolinamide; N-(3-(3-chloro-4-(6-methoxy-5-((((5-oxopyrrolidin-2-yl)methy l)amino)methyl)pyrazin-2- yl)pyridin-2-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)m ethyl)pyrazine-2- carboxamide; (S)-N-(3-(3-chloro-4-(6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)pyrazin-2-yl)pyridin-2-yl)-2-methylph enyl)-5-(((2- hydroxyethyl)amino)methyl)pyrazine-2-carboxamide; (R)-N-(3-(3-chloro-4-(6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)pyrazin-2-yl)pyridin-2-yl)-2-methylph enyl)-5-(((2- hydroxyethyl)amino)methyl)pyrazine-2-carboxamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-6-methylpicolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-6-methylpicolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-6-methylpicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-4-methylpicolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-4-methylpicolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-4-methylpicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((3-fluoropropyl)amino)met hyl)thiazole-2-carboxamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 3- fluoropropyl)amino)methyl)thiazole-2-carboxamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 3- fluoropropyl)amino)methyl)thiazole-2-carboxamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((3-hydroxypyrrolidin-1-yl) methyl)thiazole-2-carboxamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( S)-3-hydroxypyrrolidin-1- yl)methyl)thiazole-2-carboxamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( R)-3-hydroxypyrrolidin-1- yl)methyl)thiazole-2-carboxamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( S)-3-hydroxypyrrolidin-1- yl)methyl)thiazole-2-carboxamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( R)-3-hydroxypyrrolidin-1- yl)methyl)thiazole-2-carboxamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((2-hydroxyethyl)amino)met hyl)thiazole-2-carboxamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 2- hydroxyethyl)amino)methyl)thiazole-2-carboxamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 2- hydroxyethyl)amino)methyl)thiazole-2-carboxamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-3-hydroxy-5-(((2- hydroxyethyl)amino)methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-3-hydroxy-5-(((2- hydroxyethyl)amino)methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-3-hydroxy-5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-1H-imidazole-2- carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-1H-imidazole-2- carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-1H-imidazole-2- carboxamide; 5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3-(3'- chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)thiazole-2- carboxamide; (S)-5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3'-chloro-6-methoxy-5- ((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridi n]-2'-yl)phenyl)thiazole-2- carboxamide; (R)-5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3'-chloro-6-methoxy-5- ((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridi n]-2'-yl)phenyl)thiazole-2- carboxamide; 1-((2-((2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidi n-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)carbam oyl)thiazol-5- yl)methyl)piperidine-4-carboxylic acid; (S)-1-((2-((2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrro lidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)carbam oyl)thiazol-5- yl)methyl)piperidine-4-carboxylic acid; (R)-1-((2-((2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrro lidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)carbam oyl)thiazol-5- yl)methyl)piperidine-4-carboxylic acid; 5-(((2-hydroxyethyl)amino)methyl)-N-(3-(6-methoxy-3'-methyl- 5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)picolinamide; (S)-5-(((2-hydroxyethyl)amino)methyl)-N-(3-(6-methoxy-3'-met hyl-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2- methylphenyl)picolinamide; (R)-5-(((2-hydroxyethyl)amino)methyl)-N-(3-(6-methoxy-3'-met hyl-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2- methylphenyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(2-hydroxyethyl)-5,6,7,8 -tetrahydro-2,7-naphthyridine- 3-carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(2-hydroxyethyl)-5,6,7,8 -tetrahydro-2,7-naphthyridine- 3-carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(2-hydroxyethyl)-5,6,7,8 -tetrahydro-2,7-naphthyridine- 3-carboxamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-1-methyl-1H- imidazole-2-carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-1-methyl-1H- imidazole-2-carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-1-methyl-1H- imidazole-2-carboxamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)thiazol e-2-carboxamide; 1-((3'-chloro-2'-(3-(5-(((2-hydroxyethyl)amino)methyl)thiazo le-2-carboxamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)piperid ine-4-carboxylic acid; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-methoxyazetidin-1-yl )methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-methoxyazetidin-1-yl )methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-methoxyazetidin-1-yl )methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-(methoxymethyl)azeti din-1-yl)methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-(methoxymethyl)azeti din-1-yl)methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-(methoxymethyl)azeti din-1-yl)methyl)picolinamide; N-(3-(3'-chloro-5-((3-hydroxypyrrolidin-1-yl)methyl)-6-metho xy-[2,4'-bipyridin]-2'-yl)- 2-methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)thiazole-2- carboxamide; (S)-N-(3-(3'-chloro-5-((3-hydroxypyrrolidin-1-yl)methyl)-6-m ethoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)thiazol e-2-carboxamide; (R)-N-(3-(3'-chloro-5-((3-hydroxypyrrolidin-1-yl)methyl)-6-m ethoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)thiazol e-2-carboxamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-4- methoxypicolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-4- methoxypicolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-4- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-5- methoxypicolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-5- methoxypicolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-5- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxypyrrolidin-1- yl)methyl)-1-methyl-1H- imidazole-2-carboxamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-hydroxypyrrolidi n-1-yl)methyl)-1-methyl-1H- imidazole-2-carboxamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-hydroxypyrrolidi n-1-yl)methyl)-1-methyl-1H- imidazole-2-carboxamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-hydroxypyrrolidi n-1-yl)methyl)-1-methyl-1H- imidazole-2-carboxamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-hydroxypyrrolidi n-1-yl)methyl)-1-methyl-1H- imidazole-2-carboxamide; 5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chloro-6- methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-1-methyl- 1H-imidazole-2-carboxamide; (S)-5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chlor o-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-1-methyl- 1H-imidazole-2-carboxamide; (R)-5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chlor o-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-1-methyl- 1H-imidazole-2-carboxamide; N-(3-(3-chloro-2-(3-methoxy-4-((((1-methyl-5-oxopyrrolidin-2 - yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-((3-hydroxypyrrolidin-1- yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-(((((S)-1-methyl-5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((S)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-(((((S)-1-methyl-5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((R)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-(((((R)-1-methyl-5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((S)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-(((((R)-1-methyl-5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((R)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; 3-(((3'-chloro-2'-(3-(5-(((2-hydroxyethyl)amino)methyl)thiaz ole-2-carboxamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)amino)- 2,2-dimethylpropanoic acid; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-2-(2-hydroxyethyl)-2,3-dih ydro-1H-pyrrolo[3,4- c]pyridine-6-carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-2-(2-hydroxyethyl)-2,3-dih ydro-1H-pyrrolo[3,4- c]pyridine-6-carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-2-(2-hydroxyethyl)-2,3-dih ydro-1H-pyrrolo[3,4- c]pyridine-6-carboxamide; N-(3-(3'-chloro-6-methoxy-5-((7-oxo-2,6-diazaspiro[3.4]octan -2-yl)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-6-(2-hydroxyethyl)-5,6,7,8 -tetrahydro-2,6-naphthyridine- 3-carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-6-(2-hydroxyethyl)-5,6,7,8 -tetrahydro-2,6-naphthyridine- 3-carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-6-(2-hydroxyethyl)-5,6,7,8 -tetrahydro-2,6-naphthyridine- 3-carboxamide; 4-(((2-hydroxyethyl)amino)methyl)-N-(3-(6-methoxy-3'-methyl- 5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)picolinamide; (S)-4-(((2-hydroxyethyl)amino)methyl)-N-(3-(6-methoxy-3'-met hyl-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2- methylphenyl)picolinamide; (R)-4-(((2-hydroxyethyl)amino)methyl)-N-(3-(6-methoxy-3'-met hyl-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2- methylphenyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-6,7-dihydro-5H- cyclopenta[c]pyridine-1-carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-6,7-dihydro-5H- cyclopenta[c]pyridine-1-carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-6,7-dihydro-5H- cyclopenta[c]pyridine-1-carboxamide; N-(3-(3'-chloro-5-((3-hydroxyazetidin-1-yl)methyl)-6-methoxy -[2,4'-bipyridin]-2'-yl)-2- methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picolinamide ; N-(3-(5-(((1-acetylpyrrolidin-3-yl)amino)methyl)-3'-chloro-6 -methoxy-[2,4'-bipyridin]- 2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)pic olinamide; (S)-N-(3-(5-(((1-acetylpyrrolidin-3-yl)amino)methyl)-3'-chlo ro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide; (R)-N-(3-(5-(((1-acetylpyrrolidin-3-yl)amino)methyl)-3'-chlo ro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide; N-(3-(5-((((1-acetylpiperidin-4-yl)methyl)amino)methyl)-3'-c hloro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((oxetan-2-ylmethyl)amino)methy l)-[2,4'-bipyridin]-2'-yl)- 2-methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picolinami de; (S)-N-(3-(3'-chloro-6-methoxy-5-(((oxetan-2-ylmethyl)amino)m ethyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picoli namide; (R)-N-(3-(3'-chloro-6-methoxy-5-(((oxetan-2-ylmethyl)amino)m ethyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picoli namide; N-(3-(3'-chloro-6-methoxy-5-((((1-methyl-5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidi n-1-yl)methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((1-methyl-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-((3-hydroxyazetidin-1- yl)methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((1-methyl-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-((3-hydroxyazetidin-1- yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((6-oxo-2,5-diazaspiro[3.4]octan -2-yl)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide; 5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chloro-6- methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-4- methoxypicolinamide; (S)-5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chlor o-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-4- methoxypicolinamide; (R)-5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chlor o-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-4- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((3-fluoropropyl)amino) methyl)-4- methoxypicolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((3-fluoropropyl)amino) methyl)-4- methoxypicolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((3-fluoropropyl)amino) methyl)-4- methoxypicolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)(methyl)amino)methyl)-3'-c hloro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((methyl((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-((3-hydroxypyrrolidin-1- yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((methyl(((S)-5-oxopyrrolidin- 2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((S)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((methyl(((S)-5-oxopyrrolidin- 2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((R)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((methyl(((R)-5-oxopyrrolidin- 2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((S)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((methyl(((R)-5-oxopyrrolidin- 2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((R)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-((3-(methoxyme thyl)azetidin-1- yl)methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-((3-(methoxyme thyl)azetidin-1- yl)methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-((3-(methoxyme thyl)azetidin-1- yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxypyrrolidin-1- yl)methyl)-4- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-hydroxypyrrolidi n-1-yl)methyl)-4- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-hydroxypyrrolidi n-1-yl)methyl)-4- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-hydroxypyrrolidi n-1-yl)methyl)-4- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-hydroxypyrrolidi n-1-yl)methyl)-4- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-((((5-oxopyrro lidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-(((((S)-5-oxop yrrolidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-(((((R)-5-oxop yrrolidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-(((((S)-5-oxop yrrolidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-(((((R)-5-oxop yrrolidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((methyl((5-oxopyrrolidin-2-yl)m ethyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidi n-1-yl)methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((methyl((5-oxopyrrolidin-2- yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidi n-1-yl)methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((methyl((5-oxopyrrolidin-2- yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidi n-1-yl)methyl)picolinamide; 4-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chloro-6- methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5- methoxypicolinamide; (S)-4-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chlor o-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5- methoxypicolinamide; (R)-4-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chlor o-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((3-fluoropropyl)amino) methyl)-5- methoxypicolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((3-fluoropropyl)amino) methyl)-5- methoxypicolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((3-fluoropropyl)amino) methyl)-5- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-((3-hydroxypyrrolidin-1- yl)methyl)-5- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((S)-3-hydroxypyrrolidi n-1-yl)methyl)-5- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((R)-3-hydroxypyrrolidi n-1-yl)methyl)-5- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((S)-3-hydroxypyrrolidi n-1-yl)methyl)-5- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((R)-3-hydroxypyrrolidi n-1-yl)methyl)-5- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-methoxy-4-((3-(methoxyme thyl)azetidin-1- yl)methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-methoxy-4-((3-(methoxyme thyl)azetidin-1- yl)methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-methoxy-4-((3-(methoxyme thyl)azetidin-1- yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((oxetan-2-yl)methyl)amino)met hyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-((((oxetan-2-yl)methyl)amino)methyl)pi colinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-oxetan-2-yl)methyl)amino )methyl)-[2,4'-bipyridin]- 2'-yl)-2-methylphenyl)-5-(((((S)-oxetan-2-yl)methyl)amino)me thyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-oxetan-2-yl)methyl)amino )methyl)-[2,4'-bipyridin]- 2'-yl)-2-methylphenyl)-5-(((((R)-oxetan-2-yl)methyl)amino)me thyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-oxetan-2-yl)methyl)amino )methyl)-[2,4'-bipyridin]- 2'-yl)-2-methylphenyl)-5-(((((S)-oxetan-2-yl)methyl)amino)me thyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-oxetan-2-yl)methyl)amino )methyl)-[2,4'-bipyridin]- 2'-yl)-2-methylphenyl)-5-(((((R)-oxetan-2-yl)methyl)amino)me thyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-methoxy-4-((((5-oxopyrro lidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-methoxy-4-(((((S)-5-oxop yrrolidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-methoxy-4-(((((R)-5-oxop yrrolidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-methoxy-4-(((((S)-5-oxop yrrolidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-methoxy-4-(((((R)-5-oxop yrrolidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(5-(((1-acetylpiperidin-3-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picoli namide; (S)-N-(3-(5-(((1-acetylpiperidin-3-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide; (R)-N-(3-(5-(((1-acetylpiperidin-3-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide; N-(3-(3'-chloro-5-((3-hydroxyazetidin-1-yl)methyl)-6-methoxy -[2,4'-bipyridin]-2'-yl)-2- methylphenyl)-5-(((oxetan-2-ylmethyl)amino)methyl)picolinami de; (S)-N-(3-(3'-chloro-5-((3-hydroxyazetidin-1-yl)methyl)-6-met hoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-(((oxetan-2-ylmethyl)amino)methyl)pico linamide; (R)-N-(3-(3'-chloro-5-((3-hydroxyazetidin-1-yl)methyl)-6-met hoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-(((oxetan-2-ylmethyl)amino)methyl)pico linamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(3-fluoropropyl)-5,6,7,8 -tetrahydro-2,7-naphthyridine-3- carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(3-fluoropropyl)-5,6,7,8 -tetrahydro-2,7-naphthyridine-3- carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(3-fluoropropyl)-5,6,7,8 -tetrahydro-2,7-naphthyridine-3- carboxamide; 3-(2-((2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)carbam oyl)thiazol-5-yl)propanoic acid; (S)-3-(2-((2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrol idin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)carbam oyl)thiazol-5-yl)propanoic acid; (R)-3-(2-((2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrol idin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)carbam oyl)thiazol-5-yl)propanoic acid; 5-(2-aminoethyl)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5- oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)thiazo le-2-carboxamide; (S)-5-(2-aminoethyl)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-(( ((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)thiazo le-2-carboxamide; (R)-5-(2-aminoethyl)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-(( ((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)thiazo le-2-carboxamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-((5-oxopyrrolidin-2-yl)m ethyl)-5,6,7,8-tetrahydro-2,7- naphthyridine-3-carboxamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(((S)-5-oxopyrrolidin-2- yl)methyl)-5,6,7,8-tetrahydro- 2,7-naphthyridine-3-carboxamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(((R)-5-oxopyrrolidin-2- yl)methyl)-5,6,7,8-tetrahydro- 2,7-naphthyridine-3-carboxamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(((S)-5-oxopyrrolidin-2- yl)methyl)-5,6,7,8-tetrahydro- 2,7-naphthyridine-3-carboxamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(((R)-5-oxopyrrolidin-2- yl)methyl)-5,6,7,8-tetrahydro- 2,7-naphthyridine-3-carboxamide; 4-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3-(3'- chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-5- methoxypicolinamide; (S)-4-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3'-chloro-6-methoxy-5- ((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridi n]-2'-yl)phenyl)-5- methoxypicolinamide; (R)-4-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3'-chloro-6-methoxy-5- ((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridi n]-2'-yl)phenyl)-5- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-methoxy-4-((((5-oxopyrrolid in-2- yl)methyl)amino)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-met hoxy-4-(((((S)-5-oxopyrrolidin- 2-yl)methyl)amino)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-met hoxy-4-(((((R)-5-oxopyrrolidin- 2-yl)methyl)amino)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-met hoxy-4-(((((S)-5-oxopyrrolidin- 2-yl)methyl)amino)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-met hoxy-4-(((((R)-5-oxopyrrolidin- 2-yl)methyl)amino)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-((3-hydroxypyrrolidin-1-yl) methyl)-5-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-((( S)-3-hydroxypyrrolidin-1- yl)methyl)-5-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-((( R)-3-hydroxypyrrolidin-1- yl)methyl)-5-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-((( S)-3-hydroxypyrrolidin-1- yl)methyl)-5-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-((( R)-3-hydroxypyrrolidin-1- yl)methyl)-5-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-(((2-hydroxyethyl)(methyl)a mino)methyl)-5- methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-((( 2- hydroxyethyl)(methyl)amino)methyl)-5-methoxypicolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-((( 2- hydroxyethyl)(methyl)amino)methyl)-5-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-(((2-hydroxyethyl)amino)met hyl)-5-methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-((( 2-hydroxyethyl)amino)methyl)- 5-methoxypicolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-((( 2-hydroxyethyl)amino)methyl)- 5-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-methoxy-4-((3-(methoxymethy l)azetidin-1- yl)methyl)picolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-met hoxy-4-((3- (methoxymethyl)azetidin-1-yl)methyl)picolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-met hoxy-4-((3- (methoxymethyl)azetidin-1-yl)methyl)picolinamide; 5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3-(3'- chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-4- methoxypicolinamide; (S)-5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3'-chloro-6-methoxy-5- ((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridi n]-2'-yl)phenyl)-4- methoxypicolinamide; (R)-5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3'-chloro-6-methoxy-5- ((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridi n]-2'-yl)phenyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((2-hydroxyethyl)amino)met hyl)-4-methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 2-hydroxyethyl)amino)methyl)- 4-methoxypicolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 2-hydroxyethyl)amino)methyl)- 4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-(((3-fluoropropyl)amino)met hyl)-5-methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-((( 3-fluoropropyl)amino)methyl)-5- methoxypicolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-((( 3-fluoropropyl)amino)methyl)-5- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((3-hydroxypyrrolidin-1-yl) methyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( S)-3-hydroxypyrrolidin-1- yl)methyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( R)-3-hydroxypyrrolidin-1- yl)methyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( S)-3-hydroxypyrrolidin-1- yl)methyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( R)-3-hydroxypyrrolidin-1- yl)methyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-methoxy-5-((((5-oxopyrrolid in-2- yl)methyl)amino)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-(((((S)-5-oxopyrrolidin- 2-yl)methyl)amino)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-(((((R)-5-oxopyrrolidin- 2-yl)methyl)amino)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-(((((S)-5-oxopyrrolidin- 2-yl)methyl)amino)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-(((((R)-5-oxopyrrolidin- 2-yl)methyl)amino)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-methoxy-5-((3-(methoxymethy l)azetidin-1- yl)methyl)picolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-((3- (methoxymethyl)azetidin-1-yl)methyl)picolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-((3- (methoxymethyl)azetidin-1-yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((2-hydroxyethyl)(methyl)a mino)methyl)-4- methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 2- hydroxyethyl)(methyl)amino)methyl)-4-methoxypicolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 2- hydroxyethyl)(methyl)amino)methyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((3-fluoropropyl)amino)met hyl)-4-methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 3-fluoropropyl)amino)methyl)-4- methoxypicolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 3-fluoropropyl)amino)methyl)-4- methoxypicolinamide; 7-(1-acetylpiperidin-4-yl)-N-(3-(3'-chloro-6-methoxy-5-((((5 -oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5,6,7,8-tetrahydro-2,7- naphthyridine-3-carboxamide; (S)-7-(1-acetylpiperidin-4-yl)-N-(3-(3'-chloro-6-methoxy-5-( (((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5,6,7,8-tetrahydro-2,7- naphthyridine-3-carboxamide; (R)-7-(1-acetylpiperidin-4-yl)-N-(3-(3'-chloro-6-methoxy-5-( (((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5,6,7,8-tetrahydro-2,7- naphthyridine-3-carboxamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(oxetan-3-ylmethyl)-5,6, 7,8-tetrahydro-2,7- naphthyridine-3-carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(oxetan-3-ylmethyl)-5,6, 7,8-tetrahydro-2,7- naphthyridine-3-carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(oxetan-3-ylmethyl)-5,6, 7,8-tetrahydro-2,7- naphthyridine-3-carboxamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-fluorophenyl)-5-(((2-hydroxyethyl)amino) methyl)-4- methoxypicolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-fluorophenyl)-5-(((2-hydroxyethyl)amino) methyl)-4- methoxypicolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-fluorophenyl)-5-(((2-hydroxyethyl)amino) methyl)-4- methoxypicolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)-4-meth oxypicolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-4-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamide; (S)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-((((5-oxopyrro lidin-2- yl)methyl)amino)methyl)picolinamide; (R)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-((((5-oxopyrro lidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-fluorophenyl)-5-(((2-hydroxyethyl)amino) methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-fluorophenyl)-5-(((2-hydroxyethyl)amino) methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-fluorophenyl)-5-(((2-hydroxyethyl)amino) methyl)picolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-(((2-hydroxypropyl)amino)methyl)-4-met hoxypicolinamide; (S)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxypropyl)amino )methyl)-4- methoxypicolinamide; (R)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxypropyl)amino )methyl)-4- methoxypicolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-((3-hydroxypyrrolidin-1-yl)methyl)-4-m ethoxypicolinamide; (S)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxypyrrolidin-1- yl)methyl)-4- methoxypicolinamide; (R)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxypyrrolidin-1- yl)methyl)-4- methoxypicolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-((3-(hydroxymethyl)azetidin-1-yl)methy l)-4-methoxypicolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'- yl)-2-chlorophenyl)-5-(((2-hydroxyethyl)amino)methyl)-4-meth oxypicolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-4-methoxy-5-((3-(methoxymethyl)azetidin- 1-yl)methyl)picolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'- yl)-2-chlorophenyl)-4-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamide; (S)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)-4-methoxy-5-((((5-oxopyrro lidin-2- yl)methyl)amino)methyl)picolinamide; (R)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)-4-methoxy-5-((((5-oxopyrro lidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'- yl)-2-chlorophenyl)-5-((3-hydroxypyrrolidin-1-yl)methyl)-4-m ethoxypicolinamide; (S)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)-5-((3-hydroxypyrrolidin-1- yl)methyl)-4- methoxypicolinamide; (R)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)-5-((3-hydroxypyrrolidin-1- yl)methyl)-4- methoxypicolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'- yl)-2-chlorophenyl)-5-((3-(hydroxymethyl)azetidin-1-yl)methy l)-4-methoxypicolinamide; 1-((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlo ro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)carbamoyl)-4-methoxypyridin -3-yl)methyl)piperidine-4- carboxylic acid; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'- yl)-2-chlorophenyl)-4-methoxy-5-((3-(methoxymethyl)azetidin- 1-yl)methyl)picolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'- yl)-2-chlorophenyl)-5-(((2-hydroxypropyl)amino)methyl)-4-met hoxypicolinamide; (S)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)-5-(((2-hydroxypropyl)amino )methyl)-4- methoxypicolinamide; (R)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)-5-(((2-hydroxypropyl)amino )methyl)-4- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methoxyphenyl)-5-(((2-hydroxyethyl)amino )methyl)-4- methoxypicolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methoxyphenyl)-5-(((2-hydroxyethyl)amino )methyl)-4- methoxypicolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methoxyphenyl)-5-(((2-hydroxyethyl)amino )methyl)-4- methoxypicolinamide; 1-((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlo ro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3-yl)methyl)piperidine-4- carboxylic acid; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methoxyphenyl)-5-(((2-hydroxyethyl)amino )methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methoxyphenyl)-5-(((2-hydroxyethyl)amino )methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methoxyphenyl)-5-(((2-hydroxyethyl)amino )methyl)picolinamide; 3-(((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chl oro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3-yl)methyl)amino)-2,2- dimethylpropanoic acid; 4-(((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chl oro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3- yl)methyl)amino)cyclohexane-1-carboxylic acid; (1s,4s)-4-(((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl )-3'-chloro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3- yl)methyl)amino)cyclohexane-1-carboxylic acid; (1r,4r)-4-(((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl )-3'-chloro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3- yl)methyl)amino)cyclohexane-1-carboxylic acid; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((2-hydroxypropyl)amino)me thyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (S)-2- hydroxypropyl)amino)methyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (R)-2- hydroxypropyl)amino)methyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (S)-2- hydroxypropyl)amino)methyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (R)-2- hydroxypropyl)amino)methyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((3-hydroxypropyl)amino)me thyl)-4-methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 3- hydroxypropyl)amino)methyl)-4-methoxypicolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 3- hydroxypropyl)amino)methyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((((1-hydroxycyclopropyl)me thyl)amino)methyl)-4- methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (1- hydroxycyclopropyl)methyl)amino)methyl)-4-methoxypicolinamid e; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (1- hydroxycyclopropyl)methyl)amino)methyl)-4-methoxypicolinamid e; 3-(((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chl oro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3-yl)methyl)amino)propanoic acid; ((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro -6-methoxy-[2,4'-bipyridin]- 2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin-3-yl)methy l)glycine; 4-(((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chl oro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3-yl)methyl)amino)butanoic acid; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((((1-(hydroxymethyl)cyclop ropyl)methyl)amino)methyl)-4- methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (1- (hydroxymethyl)cyclopropyl)methyl)amino)methyl)-4-methoxypic olinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (1- (hydroxymethyl)cyclopropyl)methyl)amino)methyl)-4-methoxypic olinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((3-hydroxyazetidin-1-yl)me thyl)-4-methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((3 -hydroxyazetidin-1-yl)methyl)- 4-methoxypicolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((3 -hydroxyazetidin-1-yl)methyl)- 4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((3-(hydroxymethyl)azetidin -1-yl)methyl)-4- methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((3 -(hydroxymethyl)azetidin-1- yl)methyl)-4-methoxypicolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((3 -(hydroxymethyl)azetidin-1- yl)methyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((4-hydroxypiperidin-1-yl)m ethyl)-4-methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((4 -hydroxypiperidin-1-yl)methyl)- 4-methoxypicolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((4 -hydroxypiperidin-1-yl)methyl)- 4-methoxypicolinamide; 1-((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlo ro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3-yl)methyl)pyrrolidine-3- carboxylic acid; (S)-1-((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'- chloro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3-yl)methyl)pyrrolidine-3- carboxylic acid; (R)-1-((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'- chloro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3-yl)methyl)pyrrolidine-3- carboxylic acid; 4-((((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-ch loro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3- yl)methyl)amino)methyl)bicyclo[2.2.1]heptane-1-carboxylic acid; 1-((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlo ro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3-yl)methyl)azetidine-3- carboxylic acid; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-methoxy-5-((3-methoxyazetid in-1-yl)methyl)picolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-((3-methoxyazetidin-1- yl)methyl)picolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-((3-methoxyazetidin-1- yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-methoxy-5-(((2-methoxyethyl )amino)methyl)picolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-(((2- methoxyethyl)amino)methyl)picolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-(((2- methoxyethyl)amino)methyl)picolinamide; 5-(((2-amino-2-oxoethyl)amino)methyl)-N-(2-chloro-3-(3'-chlo ro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-4- methoxypicolinamide; (S)-5-(((2-amino-2-oxoethyl)amino)methyl)-N-(2-chloro-3-(3'- chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-4- methoxypicolinamide; (R)-5-(((2-amino-2-oxoethyl)amino)methyl)-N-(2-chloro-3-(3'- chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-methoxy-5-((3-methoxypyrrol idin-1-yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-(((S)-3- methoxypyrrolidin-1-yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-(((R)-3- methoxypyrrolidin-1-yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-(((S)-3- methoxypyrrolidin-1-yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-(((R)-3- methoxypyrrolidin-1-yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((3-(hydroxymethyl)pyrrolid in-1-yl)methyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( S)-3-(hydroxymethyl)pyrrolidin- 1-yl)methyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( R)-3-(hydroxymethyl)pyrrolidin- 1-yl)methyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( S)-3-(hydroxymethyl)pyrrolidin- 1-yl)methyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( R)-3-(hydroxymethyl)pyrrolidin- 1-yl)methyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((3-hydroxycyclobutyl)amin o)methyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (1s,3s)-3- hydroxycyclobutyl)amino)methyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (1r,3r)-3- hydroxycyclobutyl)amino)methyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (1s,3s)-3- hydroxycyclobutyl)amino)methyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (1r,3r)-3- hydroxycyclobutyl)amino)methyl)-4-methoxypicolinamide; 5-((4-acetamidopiperidin-1-yl)methyl)-N-(2-chloro-3-(3'-chlo ro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-4- methoxypicolinamide; (S)-5-((4-acetamidopiperidin-1-yl)methyl)-N-(2-chloro-3-(3'- chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-4- methoxypicolinamide; and (R)-5-((4-acetamidopiperidin-1-yl)methyl)-N-(2-chloro-3-(3'- chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-4- methoxypicolinamide. The compounds of the disclosure may possess one or more stereocenters, and each stereocenter may exist independently in either the (R) or (S) configuration. In certain embodiments, compounds described herein are present in optically active or racemic forms. The compounds described herein encompass racemic, optically active, regioisomeric and stereoisomeric forms, or combinations thereof that possess the therapeutically useful properties described herein. Preparation of optically active forms is achieved in any suitable manner, including by way of non-limiting example, by resolution of the racemic form with recrystallization techniques, synthesis from optically active starting materials, chiral synthesis, or chromatographic separation using a chiral stationary phase. A compound illustrated herein by the racemic formula further represents either of the two enantiomers or mixtures thereof, or in the case where two or more chiral center are present, all diastereomers or mixtures thereof. In certain embodiments, the compounds of the disclosure exist as tautomers. All tautomers are included within the scope of the compounds recited herein. Compounds described herein also include isotopically labeled compounds wherein one or more atoms is replaced by an atom having the same atomic number, but an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes suitable for inclusion in the compounds described herein include and are not limited to ² H, ³ H, ¹¹ C, ¹³ C, ¹⁴ C, ³⁶ Cl, ¹⁸ F, ¹²³ I, ¹²⁵ I, ¹³ N, ¹⁵ N, ¹⁵ O, ¹⁷ O, ¹⁸ O, ³² P, and ³⁵ S. In certain embodiments, substitution with heavier isotopes such as deuterium affords greater chemical stability. Isotopically labeled compounds are prepared by any suitable method or by processes using an appropriate isotopically labeled reagent in place of the non-labeled reagent otherwise employed. In certain embodiments, the compounds described herein are labeled by other means, including, but not limited to, the use of chromophores or fluorescent moieties, bioluminescent labels, or chemiluminescent labels. In all of the embodiments provided herein, examples of suitable optional substituents are not intended to limit the scope of the claimed disclosure. The compounds of the disclosure may contain any of the substituents, or combinations of substituents, provided herein. Salts The compounds described herein may form salts with acids or bases, and such salts are included in the present disclosure. The term "salts" embraces addition salts of free acids or bases that are useful within the methods of the disclosure. The term "pharmaceutically acceptable salt" refers to salts that possess toxicity profiles within a range that affords utility in pharmaceutical applications. In certain embodiments, the salts are pharmaceutically acceptable salts. Pharmaceutically unacceptable salts may nonetheless possess properties such as high crystallinity, which have utility in the practice of the present disclosure, such as for example utility in process of synthesis, purification or formulation of compounds useful within the methods of the disclosure. Suitable pharmaceutically acceptable acid addition salts may be prepared from an inorganic acid or from an organic acid. Examples of inorganic acids include sulfate, hydrogen sulfate, hydrochloric, hydrobromic, hydriodic, nitric, carbonic, sulfuric, and phosphoric acids (including hydrogen phosphate and dihydrogen phosphate). Appropriate organic acids may be selected from aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic, carboxylic and sulfonic classes of organic acids, examples of which include formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucuronic, maleic, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic, 4-hydroxybenzoic, phenylacetic, mandelic, embonic (or pamoic), methanesulfonic, ethanesulfonic, benzenesulfonic, pantothenic, sulfanilic, 2-hydroxyethanesulfonic, trifluoromethanesulfonic, p-toluenesulfonic, cyclohexylaminosulfonic, stearic, alginic, β-hydroxybutyric, salicylic, galactaric, galacturonic acid, glycerophosphonic acids and saccharin (e.g., saccharinate, saccharate). Salts may be comprised of a fraction of one, one or more than one molar equivalent of acid or base with respect to any compound of the disclosure. Suitable pharmaceutically acceptable base addition salts of compounds of the disclosure include, for example, ammonium salts and metallic salts including alkali metal, alkaline earth metal and transition metal salts such as, for example, calcium, magnesium, potassium, sodium and zinc salts. Pharmaceutically acceptable base addition salts also include organic salts made from basic amines such as, for example, N,N'-dibenzylethylene- diamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine (or N- methylglucamine) and procaine. All of these salts may be prepared from the corresponding compound by reacting, for example, the appropriate acid or base with the compound. Combination Therapies In one aspect, the compounds of the disclosure are useful within the methods of the disclosure in combination with one or more additional agents useful for treating HBV and/or HDV infections. These additional agents may comprise compounds or compositions identified herein, or compounds (e.g., commercially available compounds) known to treat, prevent, or reduce the symptoms of HBV and/or HDV infections. Non-limiting examples of one or more additional agents useful for treating HBV and/or HDV infections include: (a) reverse transcriptase inhibitors; (b) capsid inhibitors; (c) cccDNA formation inhibitors; (d) RNA destabilizers; (e) oligomeric nucleotides targeted against the HBV genome; (f) immunostimulators, such as checkpoint inhibitors (e.g., PD-L1 inhibitors); (g) GalNAc-siRNA conjugates targeted against an HBV gene transcript; and (h) therapeutic vaccines. (a) Reverse Transcriptase Inhibitors In certain embodiments, the reverse transcriptase inhibitor is a reverse-transcriptase inhibitor (NARTI or NRTI). In other embodiments, the reverse transcriptase inhibitor is a nucleotide analog reverse-transcriptase inhibitor (NtARTI or NtRTI). Reported reverse transcriptase inhibitors include, but are not limited to, entecavir, clevudine, telbivudine, lamivudine, adefovir, and tenofovir, tenofovir disoproxil, tenofovir alafenamide, adefovir dipovoxil, (1R,2R,3R,5R)-3-(6-amino-9H-9-purinyl)-2-fluoro-5- (hydroxymethyl)-4-methylenecyclopentan-1-ol (described in U.S. Patent No.8,816,074, incorporated herein in its entirety by reference), emtricitabine, abacavir, elvucitabine, ganciclovir, lobucavir, famciclovir, penciclovir, and amdoxovir. Reported reverse transcriptase inhibitors further include, but are not limited to, entecavir, lamivudine, and (1R,2R,3R,5R)-3-(6-amino-9H-9-purinyl)-2-fluoro-5- (hydroxymethyl)-4-methylenecyclopentan-1-ol. Reported reverse transcriptase inhibitors further include, but are not limited to, a covalently bound phosphoramidate or phosphonamidate moiety of the above-mentioned reverse transcriptase inhibitors, or as described in for example U.S. Patent No.8,816,074, US Patent Application Publications No. US 2011/0245484 A1, and US 2008/0286230A1, all of which incorporated herein in their entireties by reference. Reported reverse transcriptase inhibitors further include, but are not limited to, nucleotide analogs that comprise a phosphoramidate moiety, such as, for example, methyl ((((1R,3R,4R,5R)-3-(6-amino-9H-purin-9-yl)-4-fluoro-5-hydrox y-2-methylenecyclopentyl) methoxy)(phenoxy) phosphoryl)-(D or L)-alaninate and methyl ((((1R,2R,3R,4R)-3-fluoro-2- hydroxy-5-methylene-4-(6-oxo-1,6-dihydro-9H-purin-9-yl)cyclo pentyl)methoxy)(phenoxy) phosphoryl)-(D or L)-alaninate. Also included are the individual diastereomers thereof, which include, for example, methyl ((R)-(((1R,3R,4R,5R)-3-(6-amino-9H-purin-9-yl)-4-fluoro-5- hydroxy-2-methylenecyclopentyl)methoxy)(phenoxy)phosphoryl)- (D or L)-alaninate and methyl ((S)-(((1R,3R,4R,5R)-3-(6-amino-9H-purin-9-yl)-4-fluoro-5-hy droxy-2- methylenecyclopentyl) methoxy)(phenoxy)phosphoryl)-(D or L)-alaninate. Reported reverse transcriptase inhibitors further include, but are not limited to, compounds comprising a phosphonamidate moiety, such as, for example, tenofovir alafenamide, as well as those described in U.S. Patent Application Publication No. US 2008/0286230 A1, incorporated herein in its entirety by reference. Methods for preparing stereoselective phosphoramidate or phosphonamidate containing actives are described in, for example, U.S. Patent No.8,816,074, as well as U.S. Patent Application Publications No. US 2011/0245484 A1 and US 2008/0286230 A1, all of which incorporated herein in their entireties by reference. (b) Capsid Inhibitors As described herein, the term "capsid inhibitor" includes compounds that are capable of inhibiting the expression and/or function of a capsid protein either directly or indirectly. For example, a capsid inhibitor may include, but is not limited to, any compound that inhibits capsid assembly, induces formation of non-capsid polymers, promotes excess capsid assembly or misdirected capsid assembly, affects capsid stabilization, and/or inhibits encapsidation of RNA (pgRNA). Capsid inhibitors also include any compound that inhibits capsid function in a downstream event(s) within the replication process (e.g., viral DNA synthesis, transport of relaxed circular DNA (rcDNA) into the nucleus, covalently closed circular DNA (cccDNA) formation, virus maturation, budding and/or release, and the like). For example, in certain embodiments, the inhibitor detectably inhibits the expression level or biological activity of the capsid protein as measured, e.g., using an assay described herein. In certain embodiments, the inhibitor inhibits the level of rcDNA and downstream products of viral life cycle by at least 5%, at least 10%, at least 20%, at least 50%, at least 75%, or at least 90%. Reported capsid inhibitors include, but are not limited to, compounds described in International Patent Applications Publication Nos WO 2013006394, WO 2014106019, and WO ₂ 014089296, all of which incorporated herein in their entireties by reference. Reported capsid inhibitors also include, but are not limited to, the following compounds and pharmaceutically acceptable salts and/or solvates thereof: Bay-41-4109 (see Int’l Patent Application Publication No. WO 2013144129), AT-61 (see Int’l Patent Application Publication No. WO 1998033501; and King, et al., 1998, Antimicrob. Agents Chemother.42(12):3179–3186), DVR-01 and DVR-23 (see Int’l Patent Application Publication No. WO 2013006394; and Campagna, et al., 2013, J. Virol.87(12):6931, all of which incorporated herein in their entireties by reference. In addition, reported capsid inhibitors include, but are not limited to, those generally and specifically described in U.S. Patent Application Publication Nos. US 2015/0225355, US 2015/0132258, US 2016/0083383, US 2016/0052921, US 2019/0225593, and Int’l Patent Application Publication Nos. WO 2013096744, WO 2014165128, WO 2014033170, WO 2014033167, WO 2014033176, WO 2014131847, WO 2014161888, WO 2014184350, WO 2014184365, WO 2015059212, WO 2015011281, WO 2015118057, WO 2015109130, WO 2015073774, WO 2015180631, WO 2015138895, WO 2016089990, WO 2017015451, WO 2016183266, WO 2017011552, WO 2017048950, WO ₂ 017048954, WO 2017048962, WO 2017064156, WO 2018052967, WO 2018172852, WO 2020023710, WO ₂ 020123674, and are incorporated herein in their entirety by reference. (c) cccDNA Formation Inhibitors Covalently closed circular DNA (cccDNA) is generated in the cell nucleus from viral rcDNA and serves as the transcription template for viral mRNAs. As described herein, the term "cccDNA formation inhibitor" includes compounds that are capable of inhibiting the formation and/or stability of cccDNA either directly or indirectly. For example, a cccDNA formation inhibitor may include, but is not limited to, any compound that inhibits capsid disassembly, rcDNA entry into the nucleus, and/or the conversion of rcDNA into cccDNA. For example, in certain embodiments, the inhibitor detectably inhibits the formation and/or stability of the cccDNA as measured, e.g., using an assay described herein. In certain embodiments, the inhibitor inhibits the formation and/or stability of cccDNA by at least 5%, at least 10%, at least 20%, at least 50%, at least 75%, or at least 90%. Reported cccDNA formation inhibitors include, but are not limited to, compounds described in Int’l Patent Application Publication No. WO 2013130703, and are incorporated herein in their entirety by reference. In addition, reported cccDNA formation inhibitors include, but are not limited to, those generally and specifically described in U.S. Patent Application Publication No. US 2015/0038515 A1, and are incorporated herein in their entirety by reference. (d) RNA Destabilizer As used herein, the term "RNA destabilizer" refers to a molecule, or a salt or solvate thereof, that reduces the total amount of HBV RNA in mammalian cell culture or in a live human subject. In a non-limiting example, an RNA destabilizer reduces the amount of the RNA transcript(s) encoding one or more of the following HBV proteins: surface antigen, core protein, RNA polymerase, and e antigen. In certain embodiments, the RNA destabilizer reduces the total amount of HBV RNA in mammalian cell culture or in a live human subject by at least 5%, at least 10%, at least 20%, at least 50%, at least 75%, or at least 90%. Reported RNA destabilizers include compounds described in U.S. Patent No. 8,921,381, as well as compounds described in U.S. Patent Application Publication Nos. US 2015/0087659 and US 2013/0303552, all of which are incorporated herein in their entireties by reference. In addition, reported RNA destabilizers include, but are not limited to, those generally and specifically described in Int’l Patent Application Publication Nos. WO 2015113990, WO 2015173164, US 2016/0122344, WO 2016107832, WO 2016023877, WO 2016128335, WO 2016177655, WO 2016071215, WO 2017013046, WO 2017016921, WO 2017016960, WO 2017017042, WO 2017017043, WO 2017102648, WO 2017108630, WO 2017114812, WO 2017140821, WO 2018085619, and are incorporated herein in their entirety by reference. (e) Oligomeric Nucleotides Targeted Against the HBV Genome Reported oligomeric nucleotides targeted against the HBV genome include, but are not limited to, Arrowhead-ARC-520 (see U.S. Patent No.8,809,293; and Wooddell et al., 2013, Molecular Therapy 21(5):973–985, all of which incorporated herein in their entireties by reference). In certain embodiments, the oligomeric nucleotides can be designed to target one or more genes and/or transcripts of the HBV genome. Oligomeric nucleotide targeted to the HBV genome also include, but are not limited to, isolated, double stranded, siRNA molecules, that each include a sense strand and an antisense strand that is hybridized to the sense strand. In certain embodiments, the siRNA target one or more genes and/or transcripts of the HBV genome. (f) Immunostimulators Checkpoint Inhibitors As described herein, the term "checkpoint inhibitor" includes any compound that is capable of inhibiting immune checkpoint molecules that are regulators of the immune system (e.g., stimulate or inhibit immune system activity). For example, some checkpoint inhibitors block inhibitory checkpoint molecules, thereby stimulating immune system function, such as stimulation of T cell activity against cancer cells. A non-limiting example of a checkpoint inhibitor is a PD-L1 inhibitor. As described herein, the term "PD-L1 inhibitor" includes any compound that is capable of inhibiting the expression and/or function of the protein Programmed Death-Ligand 1 (PD-L1) either directly or indirectly. PD-L1, also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1), is a type 1 transmembrane protein that plays a major role in suppressing the adaptive arm of immune system during pregnancy, tissue allograft transplants, autoimmune disease, and hepatitis. PD-L1 binds to its receptor, the inhibitory checkpoint molecule PD-1 (which is found on activated T cells, B cells, and myeloid cells) so as to modulate activation or inhibition of the adaptive arm of immune system. In certain embodiments, the PD-L1 inhibitor inhibits the expression and/or function of PD-L1 by at least 5%, at least 10%, at least 20%, at least 50%, at least 75%, or at least 90%. Reported PD-L1 inhibitors include, but are not limited to, compounds recited in one of the following patent application publications: US 2018/0057455; US 2018/0057486; WO 2017/106634; WO 2018/026971; WO 2018/045142; WO 2018/118848; WO 2018/119221; WO 2018/119236; WO 2018/119266; WO 2018/119286; WO 2018/121560; WO 2019/076343; WO 2019/087214; and are incorporated herein in their entirety by reference. (g) GalNAc-siRNA Conjugates Targeted Against an HBV Gene Transcript "GalNAc" is the abbreviation for N-acetylgalactosamine, and "siRNA" is the abbreviation for small interfering RNA. An siRNA that targets an HBV gene transcript is covalently bonded to GalNAc in a GalNAc-siRNA conjugate useful in the practice of the present disclosure. While not wishing to be bound by theory, it is believed that GalNAc binds to asialoglycoprotein receptors on hepatocytes thereby facilitating the targeting of the siRNA to the hepatocytes that are infected with HBV. The siRNA enter the infected hepatocytes and stimulate destruction of HBV gene transcripts by the phenomenon of RNA interference. Examples of GalNAc-siRNA conjugates useful in the practice of this aspect of the present disclosure are set forth in published international application PCT/CA2017/050447 (PCT Application Publication number WO/2017/177326, published on October 19, 2017) which is hereby incorporated by reference in its entirety. (h) Therapeutic Vaccines In certain embodiments, administration of a therapeutic vaccine is useful in the practice of the present disclosure for the treatment of a viral disease in a subject. In certain embodiments, the viral disease is a hepatitis virus. In certain embodiments, the hepatitis virus is at least one selected from the group consisting of hepatitis B virus (HBV) and hepatitis D virus (HDV). In certain embodiments, the subject is a human. A synergistic effect may be calculated, for example, using suitable methods such as, for example, the Sigmoid-E _max equation (Holford & Scheiner, 1981, Clin. Pharmacokinet. 6:429-453), the equation of Loewe additivity (Loewe & Muischnek, 1926, Arch. Exp. Pathol Pharmacol.114: 313-326) and the median-effect equation (Chou & Talalay, 1984, Adv. Enzyme Regul.22:27-55). Each equation referred to elsewhere herein may be applied to experimental data to generate a corresponding graph to aid in assessing the effects of the drug combination. The corresponding graphs associated with the equations referred to elsewhere herein are the concentration-effect curve, isobologram curve and combination index curve, respectively. Synthesis The present disclosure further provides methods of preparing the compounds of the present disclosure. Compounds of the present teachings can be prepared in accordance with the procedures outlined herein, from commercially available starting materials, compounds known in the literature, or readily prepared intermediates, by employing standard synthetic methods and procedures known to those skilled in the art. Standard synthetic methods and procedures for the preparation of organic molecules and functional group transformations and manipulations can be readily obtained from the relevant scientific literature or from standard textbooks in the field. It is appreciated that where typical or preferred process conditions (i.e., reaction temperatures, times, mole ratios of reactants, solvents, pressures, and so forth) are given, other process conditions can also be used unless otherwise stated. Optimum reaction conditions can vary with the particular reactants or solvent used, but such conditions can be determined by one skilled in the art by routine optimization procedures. Those skilled in the art of organic synthesis will recognize that the nature and order of the synthetic steps presented can be varied for the purpose of optimizing the formation of the compounds described herein. The processes described herein can be monitored according to any suitable method known in the art. For example, product formation can be monitored by spectroscopic means, such as nuclear magnetic resonance spectroscopy (e.g., ¹ H or ¹³ C), infrared spectroscopy, spectrophotometry (e.g., UV-visible), mass spectrometry, or by chromatography such as high pressure liquid chromatograpy (HPLC), gas chromatography (GC), gel-permeation chromatography (GPC), or thin layer chromatography (TLC). Preparation of the compounds can involve protection and deprotection of various chemical groups. The need for protection and deprotection and the selection of appropriate protecting groups can be readily determined by one skilled in the art. The chemistry of protecting groups can be found, for example, in Greene, et al., Protective Groups in Organic Synthesis, 2d. Ed. (Wiley & Sons, 1991), the entire disclosure of which is incorporated by reference herein for all purposes. The reactions or the processes described herein can be carried out in suitable solvents that can be readily selected by one skilled in the art of organic synthesis. Suitable solvents typically are substantially nonreactive with the reactants, intermediates, and/or products at the temperatures at which the reactions are carried out, i.e., temperatures that can range from the solvent's freezing temperature to the solvent's boiling temperature. A given reaction can be carried out in one solvent or a mixture of more than one solvent. Depending on the particular reaction step, suitable solvents for a particular reaction step can be selected. A compound of formula (I) can be prepared, for example, according to the synthetic methods outlined in Schemes 1-12. In Schemes 1-12, R ^a1 and R ^a2 are each independently selected from the group consisting of H, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₁ -C ₆ alkoxy, cyano, halogen, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ haloalkoxy, C(=O)R ^I , C(=O)OR ^I , C(=O)N(R ^I )(R ^II ), N(R ^I )C(=O)R ^II , and S(=O) ₂ R ^I ; R ^b1 and R ^b2 are each independently selected from the group consisting of H, C ₁ -C ₃ alkyl, C ₃ -C ₈ cycloalkyl, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkyl, C ₁ -C ₃ haloalkoxy, and halogen; R ^c1 , R ^c2 , R ^c3 , and R ^c4 are each independently selected from the group consisting of H, -(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocylyl), C(=O)O(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₁ -C ₆ alkyl), optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ hydroxyalkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₂ -C ₉ heterocyclyl, C(=O)R ^I , C(=O)OR ^I , C(=O)N(R ^I )(R ^II ), and S(=O) ₂ R ^I , wherein R ^a1 can combine with any one of R ^c1 or R ^c2 to form an optionally substituted C ₃ -C ₈ heterocycloalkyl; n is an integer selected from the group consisting of 0, 1, 2, 3, and 4; M independently B(OH) ₂ or Bpin; Hal is a halogen; each occurrence of R is independently H or optionally substituted C ₁ - C ₆ alkyl; and R, R ^I , R ^II , R ^1a , R ^1b , R ⁸ , X ¹ , X ² , X ³ , X ⁴ , X ⁵ , X ⁶ , Y, Z ¹ , Z ² , and Z ³ are defined within the scope of the present invention. A synthesis of compounds of formula (I) is shown in Scheme 1. An aromatic amine compound 1-1 is coupled with a carboxylic acid (or corresponding lithium salt) compound 1- 2 under amide coupling conditions (e.g. using a suitable coupling agent such as HATU, 1,1'- carbonyldiimidazole or 2-chloro-1-methylpyridinium iodide (Mukaiyama reagent) and a suitable base such as N,N-diisopropylethylamine) to provide compound 1-3. Hydrolysis of the acetal or ketal (e.g. under acidic conditions with aqueous hydrochloric acid or trifluoroacetic acid) in compound 1-3 provides compound 1-4. Reductive amination of compound 1-4 with an amine 1-5 (e.g. using a suitable reducing agent such as sodium cyanoborohydride or sodium triacetoxyborohydride optionally in the presence of acetic acid or sodium acetate) provides compound 1-6. When compound 1-6 contains a secondary amine, the amine can optionally be protected with a tert-butyloxycarbonyl (Boc) protecting group (e.g. by reaction with di-tert-butyl dicarbonate in the presence of a tertiary amine such as triethylamine). Compound 1-6 is then coupled with a boronic acid or boronic acid pinacol ester compound 1-7 under standard metal-catalyzed coupling conditions (e.g. using a suitable palladium catalyst and a suitable base) to give compound 1-8. Compound 1-8 is then further coupled with a boronic acid or boronic acid pinacol ester compound 1-9 under standard metal-catalyzed coupling conditions (e.g. using a suitable palladium catalyst and a suitable base) to give compound 1-10. Reaction of compound 1-10 with amine compound 1-11 under reductive amination conditions (e.g. using a suitable reducing agent such as sodium cyanoborohydride or sodium triacetoxyborohydride optionally in the presence of acetic acid or sodium acetate) then gives compound 1-12. If intermediate 1-6 was protected as the Boc amine, the Boc protecting group can be removed by treatment with trifluoroacetic acid in dichloromethane or hydrochloric acid in 1,4-dioxane. Scheme 1. An alternative synthesis of compound 2-5 is shown in Scheme 2. Aromatic amine compound 2-1 is coupled with a carboxylic acid (or corresponding lithium salt) compound 2- 2 under amide coupling conditions (e.g. using a suitable coupling agent such as HATU, 1,1'- carbonyldiimidazole or 2-chloro-1-methylpyridinium iodide (Mukaiyama reagent) and a suitable base such as N,N-diisopropylethylamine) to provide compound 2-3. Reduction of the carboxylic ester group (e.g. using a suitable reducing agent such as sodium borohydride in methanol, or diisobutylaluminium hydride in inert solvent) in compound 2-3 provides alcohol compound 2-4 (where R ³ = H). Compound 2-4 is then oxidized (e.g. using a suitable reducing agent such as manganese dioxide or Dess-Martin periodinane in inert solvent) to give compound 2-5 (where R ³ = H). Scheme 2. An alternative synthesis of compounds of formula (I) is shown in Scheme 3. Reaction of compound 3-1 with amine compound 3-2 under reductive amination conditions (e.g. using a suitable reducing agent such as sodium cyanoborohydride or sodium triacetoxyborohydride optionally in the presence of acetic acid or sodium acetate) gives compound 3-3. When compound 3-3 contains a secondary amine, the amine can optionally be protected with a tert- butyloxycarbonyl (Boc) protecting group (e.g. by reaction with di-tert-butyl dicarbonate in the presence of a tertiary amine such as triethylamine). Borylation of compound 3-3 (e.g. under Miyaura borylation conditions using a palladium catalyst, a suitable borylating agent such as bis(pinacolato)diboron and a suitable base such as potassium acetate) gives compound 3-4. Compound 3-4 is then coupled with a boronic acid or boronic acid pinacol ester compound 3-5 under standard metal-catalyzed coupling conditions (e.g. using a suitable palladium catalyst and a suitable base) to give compound 3-6. If intermediate 3-3 was protected as the Boc amine, the Boc protecting group can be removed by treatment with trifluoroacetic acid in dichloromethane or hydrochloric acid in 1,4-dioxane.

Scheme 3. An alternative synthesis of compounds of formula (I) is shown in Scheme 4. The alcohol in compound 4-1 is derivatized using a suitable protecting group to give compound 4- 2 (PG = protecting group). For example, the alcohol can be converted to a tert- butyldimethylsilyl ether (PG = TBS) on treatment with tert-butyldimethylsilyl chloride with imidazole as base in DMF as solvent. Compound 4-2 is then coupled with a boronic acid or boronic acid pinacol ester compound 4-3 under standard metal-catalyzed coupling conditions (e.g. using a suitable palladium catalyst and a suitable base) to give compound 4-4. Compound 4-4 is then further coupled with a boronic acid or boronic acid pinacol ester compound 4-5 under standard metal-catalyzed coupling conditions (e.g. using a suitable palladium catalyst and a suitable base) to give compound 4-6. The alcohol protecting group in 4-6 is removed (e.g. when P = TBS, on treatment with tetrabutylammonium fluoride in THF or aqueous hydrochloric acid) and the resulting alcohol is then oxidized (e.g. using a suitable reducing agent such as manganese dioxide or Dess-Martin periodinane in inert solvent) to give compound 4-7 (where R ³ = H). Reaction of compound 4-7 with amine compound 4-8 under reductive amination conditions (e.g. using a suitable reducing agent such as sodium cyanoborohydride or sodium triacetoxyborohydride optionally in the presence of acetic acid or sodium acetate) then gives compound 4-9. Scheme 4. An alternative synthesis of compound 5-6 is shown in Scheme 5. Compound 5-1 is coupled with a boronic acid or boronic acid pinacol ester compound 5-2 under standard metal-catalyzed coupling conditions (e.g. using a suitable palladium catalyst and a suitable base) to give compound 5-3. Compound 5-4 is borylated (e.g. under Miyaura borylation conditions using a palladium catalyst, a suitable borylating agent such as bis(pinacolato)diboron and a suitable base such as potassium acetate) to give compound 5-5. Compound 5-3 is then coupled with the boronic acid or boronic acid pinacol ester compound 5-5 under standard metal-catalyzed coupling conditions (e.g. using a suitable palladium catalyst and a suitable base) to give compound 5-6. Scheme 5. An alternative synthesis of compounds of formula (I) is shown in Scheme 6. Reaction of compound 6-1 with amine compound 6-2 under reductive amination conditions (e.g. using a suitable reducing agent such as sodium cyanoborohydride or sodium triacetoxyborohydride optionally in the presence of acetic acid or sodium acetate) gives compound 6-3. When compound 6-3 contains a secondary amine, the amine can optionally be protected with a tert- butyloxycarbonyl (Boc) protecting group (e.g. by reaction with di-tert-butyl dicarbonate in the presence of a tertiary amine such as triethylamine). Compound 6-3 is then coupled with the boronic acid or boronic acid pinacol ester compound 6-4 under standard metal-catalyzed coupling conditions (e.g. using a suitable palladium catalyst and a suitable base) to give compound 6-5. If intermediate 6-3 was protected as the Boc amine, the Boc protecting group can be removed by treatment with trifluoroacetic acid in dichloromethane or hydrochloric acid in 1,4-dioxane.

Scheme 6. An alternative synthesis of compounds of formula (I) is shown in Scheme 7. Reaction of compound 7-1 with amine compound 7-2 under reductive amination conditions (e.g. using a suitable reducing agent such as sodium cyanoborohydride or sodium triacetoxyborohydride optionally in the presence of acetic acid or sodium acetate) gives compound 7-3. When compound 7-3 contains a secondary amine, the amine can optionally be protected with a tert- butyloxycarbonyl (Boc) protecting group (e.g. by reaction with di-tert-butyl dicarbonate in the presence of a tertiary amine such as triethylamine). Aromatic amine compound 7-4 is coupled with a carboxylic acid (or corresponding lithium salt) compound 7-5 under amide coupling conditions (e.g. using a suitable coupling agent such as HATU, 1,1'- carbonyldiimidazole or 2-chloro-1-methylpyridinium iodide (Mukaiyama reagent) and a suitable base such as N,N-diisopropylethylamine). Hydrolysis of the acetal or ketal (e.g. under acidic conditions with aqueous hydrochloric acid or trifluoroacetic acid) provides compound 7-6. Compound 7-3 is then coupled with the boronic acid or boronic acid pinacol ester compound 7-6 under standard metal-catalyzed coupling conditions (e.g. using a suitable palladium catalyst and a suitable base) to give compound 7-7. Reaction of compound 7-7 with amine compound 7-8 under reductive amination conditions (e.g. using a suitable reducing agent such as sodium cyanoborohydride or sodium triacetoxyborohydride optionally in the presence of acetic acid or sodium acetate) then gives compound 7-9. If intermediate 7-3 was protected as the Boc amine, the Boc protecting group can be removed by treatment with trifluoroacetic acid in dichloromethane or hydrochloric acid in 1,4-dioxane.

Scheme 7. An alternative synthesis of compounds of formula (I) is shown in Scheme 8. Compound 8-1 is coupled with the boronic acid or boronic acid pinacol ester compound 8-2 under standard metal-catalyzed coupling conditions (e.g. using a suitable palladium catalyst and a suitable base) to give compound 8-3. Compound 8-4 is reacted with amine compound 8-5 under reductive amination conditions (e.g. using a suitable reducing agent such as sodium cyanoborohydride or sodium triacetoxyborohydride optionally in the presence of acetic acid or sodium acetate) to give amine compound 8-6. When compound 8-6 contains a secondary amine, the amine can optionally be protected with a tert-butyloxycarbonyl (Boc) protecting group (e.g. by reaction with di-tert-butyl dicarbonate in the presence of a tertiary amine such as triethylamine). Hydrolysis (e.g. using lithium hydroxide in aqueous alcoholic solvent) of the carboxylic ester in 8-6 affords carboxylic acid compound 8-7. Aromatic amine compound 8-3 is then coupled with the carboxylic acid (or corresponding lithium salt) compound 8-7 under amide coupling conditions (e.g. using a suitable coupling agent such as HATU, 1,1'- carbonyldiimidazole or 2-chloro-1-methylpyridinium iodide (Mukaiyama reagent) and a suitable base such as N,N-diisopropylethylamine) to provide compound 8-8. If intermediate 8-6 was protected as the Boc amine, the Boc protecting group can be removed by treatment with trifluoroacetic acid in dichloromethane or hydrochloric acid in 1,4-dioxane. Scheme 8. An alternative synthesis of compounds of formula (I) is shown in Scheme 9. Aromatic amine compound 9-1 is coupled with a carboxylic acid (or corresponding lithium salt) compound 9-2 under amide coupling conditions (e.g. using a suitable coupling agent such as HATU, 1,1'-carbonyldiimidazole or 2-chloro-1-methylpyridinium iodide (Mukaiyama reagent) and a suitable base such as N,N-diisopropylethylamine) to provide compound 9-3. Compound 9-3 is then coupled with a vinyl boronic acid or boronic acid pinacol ester under standard metal-catalyzed coupling conditions (e.g. using a suitable palladium catalyst and a suitable base) to give compound 9-4. Oxidative cleavage (e.g. using osmium tetroxide in the presence of sodium periodate or ozone followed by triphenylphosphine) of the alkene in compound 9-4 then gives aldehyde compound 9-5. Reaction of compound 9-5 with amine compound 9-6 under reductive amination conditions (e.g. using a suitable reducing agent such as sodium cyanoborohydride or sodium triacetoxyborohydride optionally in the presence of acetic acid or sodium acetate) then gives compound 9-7. If intermediate 9-1 was protected as the Boc amine, the Boc protecting group can be removed by treatment with trifluoroacetic acid in dichloromethane or hydrochloric acid in 1,4-dioxane. Scheme 9. An alternative synthesis of compounds of formula (I) is shown in Scheme 10. Reaction of compound 10-1 with amine compound 10-2 under reductive amination conditions (e.g. using a suitable reducing agent such as sodium cyanoborohydride or sodium triacetoxyborohydride optionally in the presence of acetic acid or sodium acetate) gives compound 10-3. When compound 10-3 contains a secondary amine, the amine can optionally be protected with a tert-butyloxycarbonyl (Boc) protecting group (e.g. by reaction with di- tert-butyl dicarbonate in the presence of a tertiary amine such as triethylamine). Hydrolysis (e.g. using lithium hydroxide in aqueous alcoholic solvent) of the carboxylic ester in 10-3 affords carboxylic acid compound 10-4. Coupling of carboxylic acid (or corresponding lithium salt) compound 10-4 with aromatic amine compound 10-5 under amide coupling conditions (e.g. using a suitable coupling agent such as HATU, 1,1'-carbonyldiimidazole or 2-chloro-1-methylpyridinium iodide (Mukaiyama reagent) and a suitable base such as N,N- diisopropylethylamine) then gives compound 10-6. If intermediates 10-3 or 10-5 were protected as the Boc amine, the Boc protecting group/s can be removed by treatment with trifluoroacetic acid in dichloromethane or hydrochloric acid in 1,4-dioxane.

Scheme 10. An alternative synthesis of compounds of formula (I) is shown in Scheme 11. Aromatic amine compound 11-1 is coupled with a carboxylic acid (or corresponding lithium salt) compound 11-2 under amide coupling conditions (e.g. using a suitable coupling agent such as HATU, 1,1'-carbonyldiimidazole or 2-chloro-1-methylpyridinium iodide (Mukaiyama reagent) and a suitable base such as N,N-diisopropylethylamine) to provide compound 11-3. The alcohol group in compound 11-3 is then oxidized (e.g. using a suitable reducing agent such as manganese dioxide or Dess-Martin periodinane in inert solvent) to give an aldehyde or ketone. Reductive amination with amine compound 11-4 (e.g. using a suitable reducing agent such as sodium cyanoborohydride or sodium triacetoxyborohydride optionally in the presence of acetic acid or sodium acetate) gives compound 11-5. If intermediate 11-1 was protected as the Boc amine, the Boc protecting group can be removed by treatment with trifluoroacetic acid in dichloromethane or hydrochloric acid in 1,4-dioxane. Scheme 11.

Scheme 12. An alternative synthesis of compounds of formula (I) is shown in Scheme 12. Aromatic amine compound 12-1 is coupled with a carboxylic acid (or corresponding lithium salt) compound 12-2 under amide coupling conditions (e.g., using a suitable coupling agent such as HATU, 1,1'-carbonyldiimidazole or 2-chloro-1-methylpyridinium iodide (Mukaiyama reagent) and a suitable base such as N,N-diisopropylethylamine) to provide compound 12-3. Compound 12-3 is then coupled with a vinyl boronic acid or boronic acid pinacol ester under standard metal-catalyzed coupling conditions (e.g., using a suitable palladium catalyst and a suitable base) to give compound 12-4. Oxidative cleavage (e.g., using osmium tetroxide in the presence of sodium periodate or ozone followed by triphenylphosphine) of the alkene in compound 12-4 then gives aldehyde compound 12-5. Reaction of compound 12-5 with amine compound 12-6 under reductive amination conditions (e.g., using a suitable reducing agent such as sodium cyanoborohydride or sodium triacetoxyborohydride optionally in the presence of acetic acid or sodium acetate) then gives compound 12-7. If intermediate 12-1 was protected as the Boc amine, the Boc protecting group can be removed by treatment with trifluoroacetic acid in dichloromethane or hydrochloric acid in 1,4-dioxane. Methods The disclosure provides a method of treating, ameliorating, and/or preventing hepatitis virus infection in a subject. In certain embodiments, the infection comprises hepatitis B virus (HBV) and/or hepatitis D virus (HDV) infection. In other embodiments, the infection comprises hepatitis B virus (HBV) infection. In yet other embodiments, the infection comprises hepatitis D virus (HDV) infection. In yet other embodiments, the method comprises administering to the subject in need thereof a therapeutically effective amount of at least one compound of the disclosure. In yet other embodiments, the compound of the disclosure is the only antiviral agent administered to the subject. In yet other embodiments, the at least one compound is administered to the subject in a pharmaceutically acceptable composition. In yet other embodiments, the subject is further administered at least one additional agent useful for treating the hepatitis virus infection. In yet other embodiments, the at least one additional agent comprises at least one selected from the group consisting of reverse transcriptase inhibitors; capsid inhibitors; cccDNA formation inhibitors; RNA destabilizers; oligomeric nucleotides targeted against the HBV genome; immunostimulators; GalNAc-siRNA conjugates targeted against an HBV gene transcript; and therapeutic vaccines. In yet other embodiments, the subject is co-administered the at least one compound and the at least one additional agent. In yet other embodiments, the at least one compound and the at least one additional agent are coformulated. The disclosure further provides a method of treating, ameliorating, and/or preventing cancer in a subject. In certain embodiments, the method comprises administering to the subject in need thereof a therapeutically effective amount of at least one compound of the disclosure. In other embodiments, the compound of the disclosure is the only anticancer agent administered to the subject. In yet other embodiments, the at least one compound is administered to the subject in a pharmaceutically acceptable composition. In yet other embodiments, the subject is further administered at least one additional agent or therapy useful for treating, ameliorating, or preventing the cancer. In yet other embodiments, the additional anticancer agent or therapy comprises nivolumab, pembrolizumab, atezolizumab, ipilimumab, chemotherapy, radiation therapy, and/or resection therapy. In yet other embodiments, the additional anticancer agent or therapy comprises rituximab, doxorubicin, gemcitabine, nivolumab, pembrolizumab, and/or ipilimumab. In certain embodiments, the cancer is amenable to treatment by inhibiting PD-1, PD- L1 or the PD-1/PD-L1 interaction. In other embodiments, the cancer is at least one of pancreatic cancer, bladder cancer, colorectal cancer, breast cancer, prostate cancer, renal cancer, hepatocellular cancer, lung cancer, ovarian cancer, cervical cancer, gastric cancer, esophageal cancer, head and neck cancer, melanoma, neuroendocrine cancer, CNS cancer, brain cancer, bone cancer, soft tissue sarcoma, non-small cell lung cancer, small-cell lung cancer, or colon cancer. In yet other embodiments, the cancer is at least one of lymphoma, multiple myeloma, or leukemia. In yet other embodiments, the cancer is at least one of acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), myelodysplastic syndrome (MDS), myeloproliferative disease (MPD), chronic myeloid leukemia (CML), multiple myeloma (MM), non-Hodgkin's lymphoma (NHL), mantle cell lymphoma (MCL), follicular lymphoma, Waldestrom's macroglobulinemia (WM), T-cell lymphoma, B-cell lymphoma and diffuse large B-cell lymphoma (DLBCL). In certain embodiments, the subject is a mammal. In other embodiments, the mammal is a human. Pharmaceutical Compositions and Formulations The disclosure provides pharmaceutical compositions comprising at least one compound of the disclosure or a salt or solvate thereof, which are useful to practice methods of the disclosure. Such a pharmaceutical composition may consist of at least one compound of the disclosure or a salt or solvate thereof, in a form suitable for administration to a subject, or the pharmaceutical composition may comprise at least one compound of the disclosure or a salt or solvate thereof, and one or more pharmaceutically acceptable carriers, one or more additional ingredients, or some combination of these. At least one compound of the disclosure may be present in the pharmaceutical composition in the form of a physiologically acceptable salt, such as in combination with a physiologically acceptable cation or anion, as is well known in the art. In certain embodiments, the pharmaceutical compositions useful for practicing the method of the disclosure may be administered to deliver a dose of between 1 ng/kg/day and 100 mg/kg/day. In other embodiments, the pharmaceutical compositions useful for practicing the disclosure may be administered to deliver a dose of between 1 ng/kg/day and 1,000 mg/kg/day. The relative amounts of the active ingredient, the pharmaceutically acceptable carrier, and any additional ingredients in a pharmaceutical composition of the disclosure will vary, depending upon the identity, size, and condition of the subject treated and further depending upon the route by which the composition is to be administered. By way of example, the composition may comprise between 0.1% and 100% (w/w) active ingredient. Pharmaceutical compositions that are useful in the methods of the disclosure may be suitably developed for nasal, inhalational, oral, rectal, vaginal, pleural, peritoneal, parenteral, topical, transdermal, pulmonary, intranasal, buccal, ophthalmic, epidural, intrathecal, intravenous or another route of administration. A composition useful within the methods of the disclosure may be directly administered to the brain, the brainstem, or any other part of the central nervous system of a mammal or bird. Other contemplated formulations include projected nanoparticles, microspheres, liposomal preparations, coated particles, polymer conjugates, resealed erythrocytes containing the active ingredient, and immunologically- based formulations. In certain embodiments, the compositions of the disclosure are part of a pharmaceutical matrix, which allows for manipulation of insoluble materials and improvement of the bioavailability thereof, development of controlled or sustained release products, and generation of homogeneous compositions. By way of example, a pharmaceutical matrix may be prepared using hot melt extrusion, solid solutions, solid dispersions, size reduction technologies, molecular complexes (e.g., cyclodextrins, and others), microparticulate, and particle and formulation coating processes. Amorphous or crystalline phases may be used in such processes. The route(s) of administration will be readily apparent to the skilled artisan and will depend upon any number of factors including the type and severity of the disease being treated, the type and age of the veterinary or human patient being treated, and the like. The formulations of the pharmaceutical compositions described herein may be prepared by any method known or hereafter developed in the art of pharmacology and pharmaceutics. In general, such preparatory methods include the step of bringing the active ingredient into association with a carrier or one or more other accessory ingredients, and then, if necessary or desirable, shaping or packaging the product into a desired single-dose or multi-dose unit. As used herein, a "unit dose" is a discrete amount of the pharmaceutical composition comprising a predetermined amount of the active ingredient. The amount of the active ingredient is generally equal to the dosage of the active ingredient that would be administered to a subject or a convenient fraction of such a dosage such as, for example, one-half or one- third of such a dosage. The unit dosage form may be for a single daily dose or one of multiple daily doses (e.g., about 1 to 4 or more times per day). When multiple daily doses are used, the unit dosage form may be the same or different for each dose. Although the descriptions of pharmaceutical compositions provided herein are principally directed to pharmaceutical compositions suitable for ethical administration to humans, it will be understood by the skilled artisan that such compositions are generally suitable for administration to animals of all sorts. Modification of pharmaceutical compositions suitable for administration to humans in order to render the compositions suitable for administration to various animals is well understood, and the ordinarily skilled veterinary pharmacologist can design and perform such modification with merely ordinary, if any, experimentation. Subjects to which administration of the pharmaceutical compositions of the disclosure is contemplated include, but are not limited to, humans and other primates, mammals including commercially relevant mammals such as cattle, pigs, horses, sheep, cats, and dogs. In certain embodiments, the compositions of the disclosure are formulated using one or more pharmaceutically acceptable excipients or carriers. In certain embodiments, the pharmaceutical compositions of the disclosure comprise a therapeutically effective amount of at least one compound of the disclosure and a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers, which are useful, include, but are not limited to, glycerol, water, saline, ethanol, recombinant human albumin (e.g., RECOMBUMIN®), solubilized gelatins (e.g., GELOFUSINE®), and other pharmaceutically acceptable salt solutions such as phosphates and salts of organic acids. Examples of these and other pharmaceutically acceptable carriers are described in Remington's Pharmaceutical Sciences (1991, Mack Publication Co., New Jersey). The carrier may be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), recombinant human albumin, solubilized gelatins, suitable mixtures thereof, and vegetable oils. The proper fluidity may be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms may be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In many cases, isotonic agents, for example, sugars, sodium chloride, or polyalcohols such as mannitol and sorbitol, are included in the composition. Prolonged absorption of the injectable compositions may be brought about by including in the composition an agent that delays absorption, for example, aluminum monostearate or gelatin. Formulations may be employed in admixtures with conventional excipients, i.e., pharmaceutically acceptable organic or inorganic carrier substances suitable for oral, parenteral, nasal, inhalational, intravenous, subcutaneous, transdermal enteral, or any other suitable mode of administration, known to the art. The pharmaceutical preparations may be sterilized and if desired mixed with auxiliary agents, e.g., lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure buffers, coloring, flavoring and/or fragrance-conferring substances and the like. They may also be combined where desired with other active agents, e.g., other analgesic, anxiolytics or hypnotic agents. As used herein, "additional ingredients" include, but are not limited to, one or more ingredients that may be used as a pharmaceutical carrier. The composition of the disclosure may comprise a preservative from about 0.005% to 2.0% by total weight of the composition. The preservative is used to prevent spoilage in the case of exposure to contaminants in the environment. Examples of preservatives useful in accordance with the disclosure include but are not limited to those selected from the group consisting of benzyl alcohol, sorbic acid, parabens, imidurea and combinations thereof. One such preservative is a combination of about 0.5% to 2.0% benzyl alcohol and 0.05% to 0.5% sorbic acid. The composition may include an antioxidant and a chelating agent which inhibit the degradation of the compound. Antioxidants for some compounds are BHT, BHA, alpha- tocopherol and ascorbic acid in the exemplary range of about 0.01% to 0.3%, or BHT in the range of 0.03% to 0.1% by weight by total weight of the composition. The chelating agent may be present in an amount of from 0.01% to 0.5% by weight by total weight of the composition. Exemplary chelating agents include edetate salts (e.g. disodium edetate) and citric acid in the weight range of about 0.01% to 0.20%, or in the range of 0.02% to 0.10% by weight by total weight of the composition. The chelating agent is useful for chelating metal ions in the composition that may be detrimental to the shelf life of the formulation. While BHT and disodium edetate are exemplary antioxidant and chelating agent, respectively, for some compounds, other suitable and equivalent antioxidants and chelating agents may be substituted therefore as would be known to those skilled in the art. Liquid suspensions may be prepared using conventional methods to achieve suspension of the active ingredient in an aqueous or oily vehicle. Aqueous vehicles include, for example, water, and isotonic saline. Oily vehicles include, for example, almond oil, oily esters, ethyl alcohol, vegetable oils such as arachis, olive, sesame, or coconut oil, fractionated vegetable oils, and mineral oils such as liquid paraffin. Liquid suspensions may further comprise one or more additional ingredients including, but not limited to, suspending agents, dispersing or wetting agents, emulsifying agents, demulcents, preservatives, buffers, salts, flavorings, coloring agents, and sweetening agents. Oily suspensions may further comprise a thickening agent. Known suspending agents include, but are not limited to, sorbitol syrup, hydrogenated edible fats, sodium alginate, polyvinylpyrrolidone, gum tragacanth, gum acacia, and cellulose derivatives such as sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethyl cellulose. Known dispersing or wetting agents include, but are not limited to, naturally-occurring phosphatides such as lecithin, condensation products of an alkylene oxide with a fatty acid, with a long chain aliphatic alcohol, with a partial ester derived from a fatty acid and a hexitol, or with a partial ester derived from a fatty acid and a hexitol anhydride (e.g., polyoxyethylene stearate, heptadecaethyleneoxycetanol, polyoxyethylene sorbitol monooleate, and polyoxyethylene sorbitan monooleate, respectively). Known emulsifying agents include, but are not limited to, lecithin, acacia, and ionic or non ionic surfactants. Known preservatives include, but are not limited to, methyl, ethyl, or n-propyl para-hydroxybenzoates, ascorbic acid, and sorbic acid. Known sweetening agents include, for example, glycerol, propylene glycol, sorbitol, sucrose, and saccharin. Liquid solutions of the active ingredient in aqueous or oily solvents may be prepared in substantially the same manner as liquid suspensions, the primary difference being that the active ingredient is dissolved, rather than suspended in the solvent. As used herein, an "oily" liquid is one which comprises a carbon-containing liquid molecule and which exhibits a less polar character than water. Liquid solutions of the pharmaceutical composition of the disclosure may comprise each of the components described with regard to liquid suspensions, it being understood that suspending agents will not necessarily aid dissolution of the active ingredient in the solvent. Aqueous solvents include, for example, water, and isotonic saline. Oily solvents include, for example, almond oil, oily esters, ethyl alcohol, vegetable oils such as arachis, olive, sesame, or coconut oil, fractionated vegetable oils, and mineral oils such as liquid paraffin. Powdered and granular formulations of a pharmaceutical preparation of the disclosure may be prepared using known methods. Such formulations may be administered directly to a subject, used, for example, to form tablets, to fill capsules, or to prepare an aqueous or oily suspension or solution by addition of an aqueous or oily vehicle thereto. Each of these formulations may further comprise one or more of dispersing or wetting agent, a suspending agent, ionic and non-ionic surfactants, and a preservative. Additional excipients, such as fillers and sweetening, flavoring, or coloring agents, may also be included in these formulations. A pharmaceutical composition of the disclosure may also be prepared, packaged, or sold in the form of oil-in-water emulsion or a water-in-oil emulsion. The oily phase may be a vegetable oil such as olive or arachis oil, a mineral oil such as liquid paraffin, or a combination of these. Such compositions may further comprise one or more emulsifying agents such as naturally occurring gums such as gum acacia or gum tragacanth, naturally- occurring phosphatides such as soybean or lecithin phosphatide, esters or partial esters derived from combinations of fatty acids and hexitol anhydrides such as sorbitan monooleate, and condensation products of such partial esters with ethylene oxide such as polyoxyethylene sorbitan monooleate. These emulsions may also contain additional ingredients including, for example, sweetening or flavoring agents. Methods for impregnating or coating a material with a chemical composition are known in the art, and include, but are not limited to methods of depositing or binding a chemical composition onto a surface, methods of incorporating a chemical composition into the structure of a material during the synthesis of the material (i.e., such as with a physiologically degradable material), and methods of absorbing an aqueous or oily solution or suspension into an absorbent material, with or without subsequent drying. Methods for mixing components include physical milling, the use of pellets in solid and suspension formulations and mixing in a transdermal patch, as known to those skilled in the art. Administration/Dosing The regimen of administration may affect what constitutes an effective amount. The therapeutic formulations may be administered to the patient either prior to or after the onset of a disease or disorder. Further, several divided dosages, as well as staggered dosages may be administered daily or sequentially, or the dose may be continuously infused, or may be a bolus injection. Further, the dosages of the therapeutic formulations may be proportionally increased or decreased as indicated by the exigencies of the therapeutic or prophylactic situation. Administration of the compositions of the present disclosure to a patient, such as a mammal, such as a human, may be carried out using known procedures, at dosages and for periods of time effective to treat a disease or disorder contemplated herein. An effective amount of the therapeutic compound necessary to achieve a therapeutic effect may vary according to factors such as the activity of the particular compound employed; the time of administration; the rate of excretion of the compound; the duration of the treatment; other drugs, compounds or materials used in combination with the compound; the state of the disease or disorder, age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well-known in the medical arts. Dosage regimens may be adjusted to provide the optimum therapeutic response. For example, several divided doses may be administered daily or the dose may be proportionally reduced as indicated by the exigencies of the therapeutic situation. A non-limiting example of an effective dose range for a therapeutic compound of the disclosure is from about 0.01 mg/kg to 100 mg/kg of body weight/per day. One of ordinary skill in the art would be able to study the relevant factors and make the determination regarding the effective amount of the therapeutic compound without undue experimentation. The compound may be administered to an animal as frequently as several times daily, or it may be administered less frequently, such as once a day, once a week, once every two weeks, once a month, or even less frequently, such as once every several months or even once a year or less. It is understood that the amount of compound dosed per day may be administered, in non-limiting examples, every day, every other day, every 2 days, every 3 days, every 4 days, or every 5 days. For example, with every other day administration, a 5 mg per day dose may be initiated on Monday with a first subsequent 5 mg per day dose administered on Wednesday, a second subsequent 5 mg per day dose administered on Friday, and so on. The frequency of the dose is readily apparent to the skilled artisan and depends upon a number of factors, such as, but not limited to, type and severity of the disease being treated, and type and age of the animal. Actual dosage levels of the active ingredients in the pharmaceutical compositions of this disclosure may be varied so as to obtain an amount of the active ingredient that is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient. A medical doctor, e.g., physician or veterinarian, having ordinary skill in the art may readily determine and prescribe the effective amount of the pharmaceutical composition required. For example, the physician or veterinarian could start doses of the compounds of the disclosure employed in the pharmaceutical composition at levels lower than that required in order to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved. In particular embodiments, it is especially advantageous to formulate the compound in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the patients to be treated; each unit containing a predetermined quantity of therapeutic compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical vehicle. The dosage unit forms of the disclosure are dictated by and directly dependent on (a) the unique characteristics of the therapeutic compound and the particular therapeutic effect to be achieved, and (b) the limitations inherent in the art of compounding/formulating such a therapeutic compound for the treatment of a disease or disorder in a patient. In certain embodiments, the compositions of the disclosure are administered to the patient in dosages that range from one to five times per day or more. In other embodiments, the compositions of the disclosure are administered to the patient in range of dosages that include, but are not limited to, once every day, every two days, every three days to once a week, and once every two weeks. It will be readily apparent to one skilled in the art that the frequency of administration of the various combination compositions of the disclosure will vary from subject to subject depending on many factors including, but not limited to, age, disease or disorder to be treated, gender, overall health, and other factors. Thus, the disclosure should not be construed to be limited to any particular dosage regime and the precise dosage and composition to be administered to any patient will be determined by the attending physician taking all other factors about the patient into account. Compounds of the disclosure for administration may be in the range of from about 1 μg to about 7,500 mg, about 20 μg to about 7,000 mg, about 40 μg to about 6,500 mg, about 80 μg to about 6,000 mg, about 100 μg to about 5,500 mg, about 200 μg to about 5,000 mg, about 400 μg to about 4,000 mg, about 800 μg to about 3,000 mg, about 1 mg to about 2,500 mg, about 2 mg to about 2,000 mg, about 5 mg to about 1,000 mg, about 10 mg to about 750 mg, about 20 mg to about 600 mg, about 30 mg to about 500 mg, about 40 mg to about 400 mg, about 50 mg to about 300 mg, about 60 mg to about 250 mg, about 70 mg to about 200 mg, about 80 mg to about 150 mg, and any and all whole or partial increments there-in- between. In some embodiments, the dose of a compound of the disclosure is from about 0.5 μg and about 5,000 mg. In some embodiments, a dose of a compound of the disclosure used in compositions described herein is less than about 5,000 mg, or less than about 4,000 mg, or less than about 3,000 mg, or less than about 2,000 mg, or less than about 1,000 mg, or less than about 800 mg, or less than about 600 mg, or less than about 500 mg, or less than about 200 mg, or less than about 50 mg. Similarly, in some embodiments, a dose of a second compound as described herein is less than about 1,000 mg, or less than about 800 mg, or less than about 600 mg, or less than about 500 mg, or less than about 400 mg, or less than about 300 mg, or less than about 200 mg, or less than about 100 mg, or less than about 50 mg, or less than about 40 mg, or less than about 30 mg, or less than about 25 mg, or less than about 20 mg, or less than about 15 mg, or less than about 10 mg, or less than about 5 mg, or less than about 2 mg, or less than about 1 mg, or less than about 0.5 mg, and any and all whole or partial increments thereof. In certain embodiments, the present disclosure is directed to a packaged pharmaceutical composition comprising a container holding a therapeutically effective amount of a compound of the disclosure, alone or in combination with a second pharmaceutical agent; and instructions for using the compound to treat, prevent, or reduce one or more symptoms of a disease or disorder in a patient. The term "container" includes any receptacle for holding the pharmaceutical composition or for managing stability or water uptake. For example, in certain embodiments, the container is the packaging that contains the pharmaceutical composition, such as liquid (solution and suspension), semisolid, lyophilized solid, solution and powder or lyophilized formulation present in dual chambers. In other embodiments, the container is not the packaging that contains the pharmaceutical composition, i.e., the container is a receptacle, such as a box or vial that contains the packaged pharmaceutical composition or unpackaged pharmaceutical composition and the instructions for use of the pharmaceutical composition. Moreover, packaging techniques are well known in the art. It should be understood that the instructions for use of the pharmaceutical composition may be contained on the packaging containing the pharmaceutical composition, and as such the instructions form an increased functional relationship to the packaged product. However, it should be understood that the instructions may contain information pertaining to the compound's ability to perform its intended function, e.g., treating, preventing, or reducing a disease or disorder in a patient. Administration Routes of administration of any of the compositions of the disclosure include inhalational, oral, nasal, rectal, parenteral, sublingual, transdermal, transmucosal (e.g., sublingual, lingual, (trans)buccal, (trans)urethral, vaginal (e.g., trans- and perivaginally), (intra)nasal, and (trans)rectal), intravesical, intrapulmonary, intraduodenal, intragastrical, intrathecal, epidural, intrapleural, intraperitoneal, subcutaneous, intramuscular, intradermal, intra-arterial, intravenous, intrabronchial, inhalation, and topical administration. Suitable compositions and dosage forms include, for example, tablets, capsules, caplets, pills, gel caps, troches, emulsions, dispersions, suspensions, solutions, syrups, granules, beads, transdermal patches, gels, powders, pellets, magmas, lozenges, creams, pastes, plasters, lotions, discs, suppositories, liquid sprays for nasal or oral administration, dry powder or aerosolized formulations for inhalation, compositions and formulations for intravesical administration and the like. It should be understood that the formulations and compositions that would be useful in the present disclosure are not limited to the particular formulations and compositions that are described herein. Oral Administration For oral application, particularly suitable are tablets, dragees, liquids, drops, capsules, caplets and gelcaps. Other formulations suitable for oral administration include, but are not limited to, a powdered or granular formulation, an aqueous or oily suspension, an aqueous or oily solution, a paste, a gel, toothpaste, a mouthwash, a coating, an oral rinse, or an emulsion. The compositions intended for oral use may be prepared according to any method known in the art and such compositions may contain one or more agents selected from the group consisting of inert, non-toxic, generally recognized as safe (GRAS) pharmaceutically excipients which are suitable for the manufacture of tablets. Such excipients include, for example an inert diluent such as lactose; granulating and disintegrating agents such as cornstarch; binding agents such as starch; and lubricating agents such as magnesium stearate. Tablets may be non-coated or they may be coated using known methods to achieve delayed disintegration in the gastrointestinal tract of a subject, thereby providing sustained release and absorption of the active ingredient. By way of example, a material such as glyceryl monostearate or glyceryl distearate may be used to coat tablets. Further by way of example, tablets may be coated using methods described in U.S. Patents Nos.4,256,108; 4,160,452; and 4,265,874 to form osmotically controlled release tablets. Tablets may further comprise a sweetening agent, a flavoring agent, a coloring agent, a preservative, or some combination of these in order to provide for pharmaceutically elegant and palatable preparation. Hard capsules comprising the active ingredient may be made using a physiologically degradable composition, such as gelatin. The capsules comprise the active ingredient, and may further comprise additional ingredients including, for example, an inert solid diluent such as calcium carbonate, calcium phosphate, or kaolin. Hard capsules comprising the active ingredient may be made using a physiologically degradable composition, such as gelatin. Such hard capsules comprise the active ingredient, and may further comprise additional ingredients including, for example, an inert solid diluent such as calcium carbonate, calcium phosphate, or kaolin. Soft gelatin capsules comprising the active ingredient may be made using a physiologically degradable composition, such as gelatin from animal-derived collagen or from a hypromellose, a modified form of cellulose, and manufactured using optional mixtures of gelatin, water and plasticizers such as sorbitol or glycerol. Such soft capsules comprise the active ingredient, which may be mixed with water or an oil medium such as peanut oil, liquid paraffin, or olive oil. For oral administration, the compounds of the disclosure may be in the form of tablets or capsules prepared by conventional means with pharmaceutically acceptable excipients such as binding agents; fillers; lubricants; disintegrates; or wetting agents. If desired, the tablets may be coated using suitable methods and coating materials such as OPADRY® film coating systems available from Colorcon, West Point, Pa. (e.g., OPADRY® OY Type, OYC Type, Organic Enteric OY-P Type, Aqueous Enteric OY-A Type, OY-PM Type and OPADRY® White, 32K18400). It is understood that similar type of film coating or polymeric products from other companies may be used. A tablet comprising the active ingredient may, for example, be made by compressing or molding the active ingredient, optionally with one or more additional ingredients. Compressed tablets may be prepared by compressing, in a suitable device, the active ingredient in a free-flowing form such as a powder or granular preparation, optionally mixed with one or more of a binder, a lubricant, an excipient, a surface active agent, and a dispersing agent. Molded tablets may be made by molding, in a suitable device, a mixture of the active ingredient, a pharmaceutically acceptable carrier, and at least sufficient liquid to moisten the mixture. Pharmaceutically acceptable excipients used in the manufacture of tablets include, but are not limited to, inert diluents, granulating and disintegrating agents, binding agents, and lubricating agents. Known dispersing agents include, but are not limited to, potato starch and sodium starch glycolate. Known surface-active agents include, but are not limited to, sodium lauryl sulphate. Known diluents include, but are not limited to, calcium carbonate, sodium carbonate, lactose, microcrystalline cellulose, calcium phosphate, calcium hydrogen phosphate, and sodium phosphate. Known granulating and disintegrating agents include, but are not limited to, corn starch and alginic acid. Known binding agents include, but are not limited to, gelatin, acacia, pre-gelatinized maize starch, polyvinylpyrrolidone, and hydroxypropyl methylcellulose. Known lubricating agents include, but are not limited to, magnesium stearate, stearic acid, silica, and talc. Granulating techniques are well known in the pharmaceutical art for modifying starting powders or other particulate materials of an active ingredient. The powders are typically mixed with a binder material into larger permanent free-flowing agglomerates or granules referred to as a "granulation." For example, solvent-using "wet" granulation processes are generally characterized in that the powders are combined with a binder material and moistened with water or an organic solvent under conditions resulting in the formation of a wet granulated mass from which the solvent must then be evaporated. Melt granulation generally consists in the use of materials that are solid or semi-solid at room temperature (i.e., having a relatively low softening or melting point range) to promote granulation of powdered or other materials, essentially in the absence of added water or other liquid solvents. The low melting solids, when heated to a temperature in the melting point range, liquefy to act as a binder or granulating medium. The liquefied solid spreads itself over the surface of powdered materials with which it is contacted, and on cooling, forms a solid granulated mass in which the initial materials are bound together. The resulting melt granulation may then be provided to a tablet press or be encapsulated for preparing the oral dosage form. Melt granulation improves the dissolution rate and bioavailability of an active (i.e., drug) by forming a solid dispersion or solid solution. U.S. Patent No.5,169,645 discloses directly compressible wax-containing granules having improved flow properties. The granules are obtained when waxes are admixed in the melt with certain flow improving additives, followed by cooling and granulation of the admixture. In certain embodiments, only the wax itself melts in the melt combination of the wax(es) and additives(s), and in other cases both the wax(es) and the additives(s) will melt. The present disclosure also includes a multi-layer tablet comprising a layer providing for the delayed release of one or more compounds useful within the methods of the disclosure, and a further layer providing for the immediate release of one or more compounds useful within the methods of the disclosure. Using a wax/pH-sensitive polymer mix, a gastric insoluble composition may be obtained in which the active ingredient is entrapped, ensuring its delayed release. Liquid preparation for oral administration may be in the form of solutions, syrups or suspensions. The liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (e.g., sorbitol syrup, methyl cellulose or hydrogenated edible fats); emulsifying agent (e.g., lecithin or acacia); non- aqueous vehicles (e.g., almond oil, oily esters or ethyl alcohol); and preservatives (e.g., methyl or propyl para-hydroxy benzoates or sorbic acid). Liquid formulations of a pharmaceutical composition of the disclosure which are suitable for oral administration may be prepared, packaged, and sold either in liquid form or in the form of a dry product intended for reconstitution with water or another suitable vehicle prior to use. Parenteral Administration As used herein, "parenteral administration" of a pharmaceutical composition includes any route of administration characterized by physical breaching of a tissue of a subject and administration of the pharmaceutical composition through the breach in the tissue. Parenteral administration thus includes, but is not limited to, administration of a pharmaceutical composition by injection of the composition, by application of the composition through a surgical incision, by application of the composition through a tissue-penetrating non-surgical wound, and the like. In particular, parenteral administration is contemplated to include, but is not limited to, subcutaneous, intravenous, intraperitoneal, intramuscular, intrasternal injection, and kidney dialytic infusion techniques. Formulations of a pharmaceutical composition suitable for parenteral administration comprise the active ingredient combined with a pharmaceutically acceptable carrier, such as sterile water or sterile isotonic saline. Such formulations may be prepared, packaged, or sold in a form suitable for bolus administration or for continuous administration. Injectable formulations may be prepared, packaged, or sold in unit dosage form, such as in ampules or in multidose containers containing a preservative. Injectable formulations may also be prepared, packaged, or sold in devices such as patient-controlled analgesia (PCA) devices. Formulations for parenteral administration include, but are not limited to, suspensions, solutions, emulsions in oily or aqueous vehicles, pastes, and implantable sustained-release or biodegradable formulations. Such formulations may further comprise one or more additional ingredients including, but not limited to, suspending, stabilizing, or dispersing agents. In one embodiment of a formulation for parenteral administration, the active ingredient is provided in dry (i.e., powder or granular) form for reconstitution with a suitable vehicle (e.g., sterile pyrogen-free water) prior to parenteral administration of the reconstituted composition. The pharmaceutical compositions may be prepared, packaged, or sold in the form of a sterile injectable aqueous or oily suspension or solution. This suspension or solution may be formulated according to the known art, and may comprise, in addition to the active ingredient, additional ingredients such as the dispersing agents, wetting agents, or suspending agents described herein. Such sterile injectable formulations may be prepared using a non- toxic parenterally acceptable diluent or solvent, such as water or 1,3-butanediol, for example. Other acceptable diluents and solvents include, but are not limited to, Ringer's solution, isotonic sodium chloride solution, and fixed oils such as synthetic mono- or di-glycerides. Other parentally-administrable formulations which are useful include those which comprise the active ingredient in microcrystalline form in a recombinant human albumin, a fluidized gelatin, in a liposomal preparation, or as a component of a biodegradable polymer system. Compositions for sustained release or implantation may comprise pharmaceutically acceptable polymeric or hydrophobic materials such as an emulsion, an ion exchange resin, a sparingly soluble polymer, or a sparingly soluble salt. Topical Administration An obstacle for topical administration of pharmaceuticals is the stratum corneum layer of the epidermis. The stratum corneum is a highly resistant layer comprised of protein, cholesterol, sphingolipids, free fatty acids and various other lipids, and includes cornified and living cells. One of the factors that limit the penetration rate (flux) of a compound through the stratum corneum is the amount of the active substance that can be loaded or applied onto the skin surface. The greater the amount of active substance which is applied per unit of area of the skin, the greater the concentration gradient between the skin surface and the lower layers of the skin, and in turn the greater the diffusion force of the active substance through the skin. Therefore, a formulation containing a greater concentration of the active substance is more likely to result in penetration of the active substance through the skin, and more of it, and at a more consistent rate, than a formulation having a lesser concentration, all other things being equal. Formulations suitable for topical administration include, but are not limited to, liquid or semi-liquid preparations such as liniments, lotions, oil-in-water or water-in-oil emulsions such as creams, ointments or pastes, and solutions or suspensions. Topically administrable formulations may, for example, comprise from about 1% to about 10% (w/w) active ingredient, although the concentration of the active ingredient may be as high as the solubility limit of the active ingredient in the solvent. Formulations for topical administration may further comprise one or more of the additional ingredients described herein. Enhancers of permeation may be used. These materials increase the rate of penetration of drugs across the skin. Typical enhancers in the art include ethanol, glycerol monolaurate, PGML (polyethylene glycol monolaurate), dimethylsulfoxide, and the like. Other enhancers include oleic acid, oleyl alcohol, ethoxydiglycol, laurocapram, alkanecarboxylic acids, dimethylsulfoxide, polar lipids, or N-methyl-2-pyrrolidone. One acceptable vehicle for topical delivery of some of the compositions of the disclosure may contain liposomes. The composition of the liposomes and their use are known in the art (i.e., U.S. Patent No.6,323,219). In alternative embodiments, the topically active pharmaceutical composition may be optionally combined with other ingredients such as adjuvants, anti-oxidants, chelating agents, surfactants, foaming agents, wetting agents, emulsifying agents, viscosifiers, buffering agents, preservatives, and the like. In other embodiments, a permeation or penetration enhancer is included in the composition and is effective in improving the percutaneous penetration of the active ingredient into and through the stratum corneum with respect to a composition lacking the permeation enhancer. Various permeation enhancers, including oleic acid, oleyl alcohol, ethoxydiglycol, laurocapram, alkanecarboxylic acids, dimethylsulfoxide, polar lipids, or N-methyl-2-pyrrolidone, are known to those of skill in the art. In another aspect, the composition may further comprise a hydrotropic agent, which functions to increase disorder in the structure of the stratum corneum, and thus allows increased transport across the stratum corneum. Various hydrotropic agents such as isopropyl alcohol, propylene glycol, or sodium xylene sulfonate, are known to those of skill in the art. The topically active pharmaceutical composition should be applied in an amount effective to affect desired changes. As used herein "amount effective" shall mean an amount sufficient to cover the region of skin surface where a change is desired. An active compound should be present in the amount of from about 0.0001% to about 15% by weight volume of the composition. For example, it should be present in an amount from about 0.0005% to about 5% of the composition; for example, it should be present in an amount of from about 0.001% to about 1% of the composition. Such compounds may be synthetically-or naturally derived. Buccal Administration A pharmaceutical composition of the disclosure may be prepared, packaged, or sold in a formulation suitable for buccal administration. Such formulations may, for example, be in the form of tablets or lozenges made using conventional methods, and may contain, for example, 0.1 to 20% (w/w) of the active ingredient, the balance comprising an orally dissolvable or degradable composition and, optionally, one or more of the additional ingredients described herein. Alternately, formulations suitable for buccal administration may comprise a powder or an aerosolized or atomized solution or suspension comprising the active ingredient. Such powdered, aerosolized, or aerosolized formulations, when dispersed, may have an average particle or droplet size in the range from about 0.1 to about 200 nanometers, and may further comprise one or more of the additional ingredients described herein. The examples of formulations described herein are not exhaustive and it is understood that the disclosure includes additional modifications of these and other formulations not described herein, but which are known to those of skill in the art. Rectal Administration A pharmaceutical composition of the disclosure may be prepared, packaged, or sold in a formulation suitable for rectal administration. Such a composition may be in the form of, for example, a suppository, a retention enema preparation, and a solution for rectal or colonic irrigation. Suppository formulations may be made by combining the active ingredient with a non-irritating pharmaceutically acceptable excipient which is solid at ordinary room temperature (i.e., about 20 ^C) and which is liquid at the rectal temperature of the subject (i.e., about 37 ^C in a healthy human). Suitable pharmaceutically acceptable excipients include, but are not limited to, cocoa butter, polyethylene glycols, and various glycerides. Suppository formulations may further comprise various additional ingredients including, but not limited to, antioxidants, and preservatives. Retention enema preparations or solutions for rectal or colonic irrigation may be made by combining the active ingredient with a pharmaceutically acceptable liquid carrier. As is well known in the art, enema preparations may be administered using, and may be packaged within, a delivery device adapted to the rectal anatomy of the subject. Enema preparations may further comprise various additional ingredients including, but not limited to, antioxidants, and preservatives. Additional Administration Forms Additional dosage forms of this disclosure include dosage forms as described in U.S. Patents Nos.6,340,475, 6,488,962, 6,451,808, 5,972,389, 5,582,837, and 5,007,790. Additional dosage forms of this disclosure also include dosage forms as described in U.S. Patent Applications Nos.20030147952, 20030104062, 20030104053, 20030044466, 20030039688, and 20020051820. Additional dosage forms of this disclosure also include dosage forms as described in PCT Applications Nos. WO 03/35041, WO 03/35040, WO 03/35029, WO 03/35177, WO 03/35039, WO 02/96404, WO 02/32416, WO 01/97783, WO 01/56544, WO 01/32217, WO 98/55107, WO 98/11879, WO 97/47285, WO 93/18755, and WO 90/11757. Controlled Release Formulations and Drug Delivery Systems: In certain embodiments, the compositions and/or formulations of the present disclosure may be, but are not limited to, short-term, rapid-offset, as well as controlled, for example, sustained release, delayed release and pulsatile release formulations. The term sustained release is used in its conventional sense to refer to a drug formulation that provides for gradual release of a drug over an extended period of time, and that may, although not necessarily, result in substantially constant blood levels of a drug over an extended time period. The period of time may be as long as a month or more and should be a release which is longer that the same amount of agent administered in bolus form. For sustained release, the compounds may be formulated with a suitable polymer or hydrophobic material which provides sustained release properties to the compounds. As such, the compounds for use the method of the disclosure may be administered in the form of microparticles, for example, by injection or in the form of wafers or discs by implantation. In certain embodiments of the disclosure, the compounds useful within the disclosure are administered to a subject, alone or in combination with another pharmaceutical agent, using a sustained release formulation. The term delayed release is used herein in its conventional sense to refer to a drug formulation that provides for an initial release of the drug after some delay following drug administration and that may, although not necessarily, include a delay of from about 10 minutes up to about 12 hours. The term pulsatile release is used herein in its conventional sense to refer to a drug formulation that provides release of the drug in such a way as to produce pulsed plasma profiles of the drug after drug administration. The term immediate release is used in its conventional sense to refer to a drug formulation that provides for release of the drug immediately after drug administration. As used herein, short-term refers to any period of time up to and including about 8 hours, about 7 hours, about 6 hours, about 5 hours, about 4 hours, about 3 hours, about 2 hours, about 1 hour, about 40 minutes, about 20 minutes, or about 10 minutes and any or all whole or partial increments thereof after drug administration after drug administration. As used herein, rapid-offset refers to any period of time up to and including about 8 hours, about 7 hours, about 6 hours, about 5 hours, about 4 hours, about 3 hours, about 2 hours, about 1 hour, about 40 minutes, about 20 minutes, or about 10 minutes, and any and all whole or partial increments thereof after drug administration. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, numerous equivalents to the specific procedures, embodiments, claims, and examples described herein. Such equivalents were considered to be within the scope of this disclosure and covered by the claims appended hereto. For example, it should be understood, that modifications in reaction conditions, including but not limited to reaction times, reaction size/volume, and experimental reagents, such as solvents, catalysts, pressures, atmospheric conditions, e.g., nitrogen atmosphere, and reducing/oxidizing agents, with art- recognized alternatives and using no more than routine experimentation, are within the scope of the present application. It is to be understood that, wherever values and ranges are provided herein, the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosure. Accordingly, all values and ranges encompassed by these values and ranges are meant to be encompassed within the scope of the present disclosure. Moreover, all values that fall within these ranges, as well as the upper or lower limits of a range of values, are also contemplated by the present application. The description of a range should be considered to have specifically disclosed all the possible sub-ranges as well as individual numerical values within that range and, when appropriate, partial integers of the numerical values within ranges. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the breadth of the range. The following examples further illustrate aspects of the present disclosure. However, they are in no way a limitation of the teachings or disclosure of the present disclosure as set forth herein.

EXAMPLES The disclosure is now described with reference to the following Examples. These Examples are provided for the purpose of illustration only, and the disclosure is not limited to these Examples, but rather encompasses all variations that are evident as a result of the teachings provided herein. LCMS Methods LCMS Method A: Waters Acquity UPLC system employing a Waters Acquity UPLC BEH C18, 1.7 μm, 50 x 2.1 mm column with an aqueous acetonitrile based solvent gradient of 2-98% CH ₃ CN/H ₂ O (0.05 % TFA) over 9.5 mins. Flow rate = 0.8 mL/min. LCMS Method B: Waters Acquity UPLC system employing a Waters Acquity UPLC BEH C18, 1.7 μm, 50 x 2.1 mm column with an aqueous acetonitrile based solvent gradient of 2-98% CH ₃ CN/H ₂ O (0.05 % TFA) over 1.0 mins. Flow rate = 0.8 mL/min. LCMS Method C: Shimadzu UFLC system employing an ACE UltraCore Super PhenylHexyl, 2.5 μm, 50 x 2.1 mm column with an aqueous acetonitrile based solvent gradient of 5-100% CH ₃ CN/H ₂ O (0.05 % Formic acid) over 5.0 mins. Flow rate = 1.0 mL/min. LCMS Method D: Waters Acquity UPLC system employing a Waters Acquity UPLC BEH C18, 1.7 μm, 50 x 2.1 mm column with an aqueous acetonitrile based solvent gradient of 2-98% CH ₃ CN/H ₂ O (0.05 % TFA) over 5.0 mins. Flow rate = 0.8 mL/min. LCMS Method E: Shimadzu LC-20AD HPLC system employing a Xbridge Shield RP18 C18, 5 μm, 50 x 2.1 mm column with an aqueous acetonitrile based solvent gradient of 5-95% CH ₃ CN/H ₂ O (NH ₄ HCO ₃ ) over 2.2 mins. Flow rate = 1.5 mL/min. Preparation of Dioxaborolanes 2-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ben zaldehyde To a solution of 4-bromo-2-methoxybenzaldehyde (10 g, 46.5 mmol) and bis(pinacolato)diboron (23.6 g, 93.0 mmol) in 1,4-dioxane (100 mL) was added potassium acetate (13.7 g, 139 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1.90 g, 2.33 mmol) and the mixture stirred at 95 °C for 12 hours. The mixture was then filtered and the filtrate concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-100% EtOAc/petroleum ether) to afford a yellow solid. The solid product was further purified by recrystallization from petroleum ether / ethyl acetate (6/1, 50 mL) at -30 ^o C twice to give 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)benzaldehyde as a white solid (12 g, 98% yield). ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.40 (s, 1 H), 7.70 (d, 1 H), 7.37 (d, 2 H), 3.95 (s, 3 H), 1.32 (s, 12 H). 2-Fluoro-6-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan -2-yl)benzaldehyde A mixture of 4-bromo-2-fluoro-6-methoxybenzaldehyde (1 g, 4.29 mmol), potassium acetate (842 mg, 8.58 mmol) and bis(pinacolato)diboron (2.18 g, 8.58 mmol) in 1,4-dioxane (10 mL) was degassed and purged with N ₂ three times. [1,1′- Bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (350 mg, 0.429 mmol,) was then added and the mixture stirred at 85 °C for 12 hours under N ₂ . The mixture was then diluted with ethyl acetate (10 mL) and washed with water (2 x 15 mL) and saturated brine 20 mL (2 x 10 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (4-16% Petroleum ether/Ethyl acetate) to afford 2-fluoro-6-methoxy-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde (1 g, 99% yield) as a yellow solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 10.47 (s, 1H), 7.17-7.14 (m, 2H), 3.98 (s, 3H), 1.36 (s, 12H). 2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benz aldehyde To a solution of 4-bromo-2-methylbenzaldehyde (3 g, 15.0 mmol) and bis(pinacolato)diboron (7.65 g, 30.1 mmol) in 1,4-dioxane (40 mL) was added potassium acetate (3.70 g, 37.7 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1.23 g, 1.51 mmol) and the mixture stirred at 100 °C for 12 hours. The mixture was filtered, the filtrate concentrated and the residue purified by normal phase SiO ₂ chromatography (0-10% ethyl acetate/petroleum ether) to afford 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2-yl)benzaldehyde (1.6 g, 43% yield) as a light yellow oil. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.28 (s, 1 H), 7.82 (d, 1 H), 7.69-7.63 (m, 2 H), 2.63 (s, 3 H), 1.32 (s, 12 H). 2-Ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benza ldehyde To a solution of 4-bromo-2-ethylbenzaldehyde (500 mg, 2.35 mmol) and bis(pinacolato)diboron (1.19 g, 4.69 mmol) in 1,4-dioxane (10 mL) was added potassium acetate (576 mg, 5.87 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (192 mg, 0.24 mmol) and the mixture stirred at 100 °C for 12 hours. The mixture was filtered, the filtrate concentrated and the residue purified by normal phase SiO ₂ chromatography (0-10% ethyl acetate/petroleum ether) to afford 2-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)benzaldehyde (1 g, 55% yield) as a yellow oil. 2-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benz aldehyde To a solution of 4-bromo-2-fluorobenzaldehyde (500 mg, 2.46 mmol) and bis(pinacolato)diboron (938 mg, 3.69 mmol) in 1,4-dioxane (8 mL) was added potassium acetate (965 mg, 9.83 mmol), 1,1′-ferrocenediyl-bis(diphenylphosphine) (205 mg, 0.37 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II ) (270 mg, 0.37 mmol) and the mixture stirred at 85 °C for 12 hours. The mixture was filtered, the filtrate concentrated and the residue purified by normal phase SiO ₂ chromatography (0-10% ethyl acetate/petroleum ether) to afford 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)benzaldehyde (498 mg, 80% yield) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.33 (s, 1H), 7.78 (t, 1H), 7.60 (d, 1H), 7.51 (d, 1H), 1.29 (s, 12H). 2-Chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benz aldehyde To a solution of 4-bromo-2-chlorobenzaldehyde (510 mg, 2.32 mmol) and bis(pinacolato)diboron (640 mg, 2.52 mmol) in 1,4-dioxane (5 mL) was added potassium acetate (0.7 g, 7.13 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (94.9 mg, 0.12 mmol) and the mixture stirred at 100 °C for 3 hours. The mixture was filtered, washed with ethyl acetate (50 mL) and the filtrate concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-8% ethyl acetate/petroleum ether) to afford 2-chloro-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde (256 mg, 31% yield) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.42 (s, 1H), 7.94 (d, 1H), 7.83-7.81 (m, 2H), 1.38 (s, 12H). 2-Chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anil ine To a mixture of 3-bromo-2-chloroaniline (10 g, 48.4 mmol) and bis(pinacolato)diboron (14.8 g, 58 mmol) in 1,4-dioxane (240 mL) was added potassium acetate (14.3 g, 145 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (3.9 g, 4.8 mmol) and the mixture was stirred at 100 °C for 3 hours under N ₂ . The mixture was filtered and the filtrate was concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-20 % ethyl acetate/petroleum ether) to afford 2-chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anil ine (7.5 g, 61% yield) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 7.00 (t, 1H), 6.87 (d, 1H), 6.78 (d, 1H), 5.26 (s, 2H), 1.29 (s, 12H). 2-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anil ine To a mixture of 3-bromo-2-methylaniline (10 g, 53.8 mmol) and bis(pinacolato)diboron (20.5 g, 80.6 mmol) in 1,4-dioxane (150 mL) was added potassium acetate (15.8 g, 161 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (4.39 g, 5.37 mmol), and the mixture stirred at 100 °C for 12 hours under N ₂ . water (50 mL) was added and the mixture extracted with ethyl acetate (3 x 50 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (5-20% ethyl acetate/petroleum ether) to afford 2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)aniline (7.5 g, 60% yield) as a brown solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 7.23 (d, 1H), 7.05 (t, 1H), 6.78 (d, 1H), 3.61 (s, 2H), 2.39 (s, 3H), 1.36 (s, 12H). 2-Fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anil ine To a mixture of 3-bromo-2-fluoroaniline (5 g, 26.3 mmol) and bis(pinacolato)diboron (10.0 g, 39.4 mmol) in 1,4-dioxane (80 mL) was added potassium acetate (7.75 g, 78.9 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1.07 g, 1.32 mmol), and the mixture stirred at 110 °C for 2 hours under N ₂ . The mixture was combined with another batch at the 1 g scale, the combined mixture was filtered and the filtrate concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-15 % ethyl acetate / petroleum ether) to afford the semi-purified product. The semi-purified product was triturated with petroleum ether / ethyl acetate (10:1 v/v, 20 mL) at room temperature for 0.5 hours. The mixture was filtered and the solid product dried under vacuum to afford of 2-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anil ine (7 g) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 6.89-6.86 (m, 2H), 6.78-6.76 (m, 1H), 5.03 (s, 2H), 1.29 (s, 12H). 2-Methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ani line To a mixture of 3-bromo-2-methoxyaniline (5 g, 24.7 mmol) and bis(pinacolato)diboron (15.7 g, 61.9 mmol) in 1,4-dioxane (100 mL) was added potassium acetate (7.29 g, 74.2 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1.01 g, 1.24 mmol), and the mixture stirred at 120 °C for 6 hours under N ₂ . The mixture was concentrated, water (300 mL) added, and the mixture extracted with ethyl acetate (2 x 300 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure The residue was purified by normal phase SiO ₂ chromatography (0-10 % ethyl acetate / petroleum ether) to afford 2-methoxy-3-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (4.2 g, 64.7% yield) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 6.81-6.75 (m, 3H), 4.81 (s, 2H), 3.65 (s, 3H), 1.30 (s, 12H). Example 1: (S)-N-(3-(3-chloro-2-(3-fluoro-5-methoxy-4-((((5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide (a) Methyl 6-((3-bromo-2-methylphenyl)carbamoyl)nicotinate To a mixture of 5-(methoxycarbonyl)picolinic acid (3 g, 16.6 mmol) in DMF (2 mL) was added 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyri dinium 3-oxide hexafluorophosphate HATU (9.45 g, 24.84 mmol) and N,N-diisopropylethylamine (7.21 mL, 41.40 mmol). After 0.2 hours, 3-bromo-2-methylaniline (2.24 mL, 18.2 mmol) was added and the reaction was stirred for 12 hours at room temperature. To the reaction was added water (60 mL) and the mixture stirred for 1 hour. The mixture was then filtered, and the filter cake washed with water (100 mL) to give an off-white solid. The solid was dried under reduced pressure to give methyl 6-((3-bromo-2-methylphenyl)carbamoyl)nicotinate (4.71 g, 81% yield) as an off-white solid that was used into the next step without further purification. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.64 (s, 1 H), 9.15 (s, 1 H), 8.51 (dd, 1 H), 8.24 (d, 1 H), 7.54 (d, 1 H), 7.49 (d, 1 H), 7.16 (t, 1 H), 3.91 (s, 3 H), 2.29 (s, 3 H). (b) N-(3-Bromo-2-methylphenyl)-5-(hydroxymethyl)picolinamide To a mixture of methyl 6-((3-bromo-2-methylphenyl)carbamoyl)nicotinate (4.1 g, 11.7 mmol) in methanol/THF (1/1, 300 mL) was added sodium borohydride (1.78 g, 47.0 mmol) at 0 °C under N ₂ and the mixture stirred at room temperature for 12 hours. Water (20 mL) was then added and the mixture concentrated. The residue was partitioned between ethyl acetate (200 mL) and water (200 mL), and the aqueous phase back extracted with ethyl acetate (200 mL). The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0- 100% ethyl acetate /petroleum ether) to afford N-(3-bromo-2-methylphenyl)-5- (hydroxymethyl)picolinamide (2.66 g, 70% yield) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.50 (s, 1 H), 8.69 (s, 1 H), 8.14 (d, 1 H), 8.00 (dd, 1 H), 7.69 (d, 1 H), 7.51 (d, 1 H), 7.21 (t, 1 H), 5.54 (t, 1 H), 4.68 (d, 2 H), 2.36 (s, 3 H). (c) N-(3-Bromo-2-methylphenyl)-5-formylpicolinamide To a solution of N-(3-bromo-2-methylphenyl)-5-(hydroxymethyl)picolinamide (2.6 g, 8.10 mmol) in dichloromethane (40 mL) was added Dess-Martin periodinane (8.58 g, 20.2 mmol) and the mixture stirred at room temperature for 2 hours. The mixture was then concentrated and the residue purified by normal phase SiO ₂ chromatography (20-30% ethyl acetate/petroleum ether) to afford N-(3-bromo-2-methylphenyl)-5-formylpicolinamide (2 g, 77% yield) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.73 (s, 1 H), 10.30 (s, 1 H), 9.28 (s, 1 H), 8.58-8.55 (m, 1 H), 8.39 (d 1 H), 7.66 (d, 1 H), 7.69 (d, 1 H), 7.27 (t, 1 H), 2.40 (s, 3 H). (d) tert-Butyl ((6-((3-bromo-2-methylphenyl)carbamoyl)pyridin-3-yl)methyl)( 2- hydroxyethyl)carbamate To a mixture of N-(3-bromo-2-methylphenyl)-5-formylpicolinamide (1 g, 3.13 mmol) and 2-aminoethanol (383 mg, 6.27 mmol) in methanol (80 mL) was added sodium acetate (771 mg, 9.40 mmol) and the mixture stirred for 12 hours. Sodium cyanoborohydride (591 mg, 9.40 mmol) was then added, and the mixture was stirred for an additional 2 hours at room temperature. Additional sodium cyanoborohydride (4 eq) was added and stirring continued for another 6 hours. Di-tert-butyl dicarbonate (1.71 g, 7.82 mmol) and triethylamine (1.31 mL, 9.39 mmol) were then added, and the mixture stirred for 2 hours at room temperature. To the mixture was added saturated aqueous brine solution (30 mL) and the mixture extracted with dichloromethane (40 mL x 3). The combined organic layers were concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether) to afford tert-butyl ((6-((3-bromo-2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)c arbamate (1.2 g, 71% yield) as a yellow oil. LCMS: m/z found 464 and 466 [M+H] ⁺ . (e) tert-Butyl ((6-((3-(2,3-dichloropyridin-4-yl)-2-methylphenyl)carbamoyl) pyridin- 3-yl)methyl)(2-hydroxyethyl)carbamate To a mixture of tert-butyl ((6-((3-bromo-2-methylphenyl)carbamoyl)pyridin-3- yl)methyl)(2-hydroxyethyl)carbamate (400 mg, 0.86 mmol, 3 batches) and 2,3-dichloro-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (519 mg, 1.90 mmol) in 1,4- dioxane/water (5/1, 24 mL) was added potassium phosphate (549 mg, 2.58 mmol) and [1,1′- bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) (56 mg, 0.09 mmol) in one portion under N ₂ and the mixture was stirred at 85 °C for 6 hours. Water (20 mL) was added and the mixture extracted with ethyl acetate (100 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and the filtrate concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether) to afford tert- butyl ((6-((3-(2,3-dichloropyridin-4-yl)-2-methylphenyl)carbamoyl) pyridin-3-yl)methyl)(2- hydroxyethyl)carbamate (340 mg, 16% yield) as a red oil. LCMS: m/z found 531 [M+H] ⁺ . (f) tert-Butyl ((6-((3-(3-chloro-2-(3-fluoro-4-formyl-5-methoxyphenyl)pyrid in-4-yl)- 2-methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl )carbamate To a mixture of tert-butyl ((6-((3-(2,3-dichloropyridin-4-yl)-2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)c arbamate (200 mg, 0.38 mmol) and 2-fluoro-6-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan -2-yl)benzaldehyde (137 mg, 0.49 mmol) in 1,4-dioxane/water (10:1 v/v, 6.6 mL) was added potassium carbonate (156 mg, 1.13 mmol) and tetrakis(triphenylphosphine)palladium(0) (43.5 mg, 0.04 mmol) in one portion under N ₂ and the mixture was stirred at 110 °C for 12 hours. Saturated aqueous brine solution (10 mL) was added and the mixture extracted with ethyl acetate (80 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-80% ethyl acetate/petroleum ether) to afford tert-butyl ((6-((3-(3-chloro-2-(3-fluoro-4-formyl-5- methoxyphenyl)pyridin-4-yl)-2-methylphenyl)carbamoyl)pyridin -3-yl)methyl)(2- hydroxyethyl)carbamate (150 mg, 53% yield) as a yellow solid. LCMS: m/z found 649 [M+H] ⁺ . (g) tert-Butyl (S)-((6-((3-(3-chloro-2-(3-fluoro-5-methoxy-4-((((5-oxopyrro lidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)c arbamoyl)pyridin-3- yl)methyl)(2-hydroxyethyl)carbamate To a mixture of tert-butyl ((6-((3-(3-chloro-2-(3-fluoro-4-formyl-5- methoxyphenyl)pyridin-4-yl)-2-methylphenyl)carbamoyl)pyridin -3-yl)methyl)(2- hydroxyethyl)carbamate (140 mg, 0.22 mmol) and (S)-5-(aminomethyl)pyrrolidin-2-one hydrochloride salt (48.7 mg, 0.32 mmol) in methanol (3 mL) was added sodium acetate (53.1 mg, 0.65 mmol) and the mixture stirred at room temperature for 3 hours. Sodium cyanoborohydride (40.7 mg, 0.65 mmol) was added and the mixture was stirred for another 10 hours at room temperature. The reaction mixture was concentrated under reduced pressure and the residue purified by normal phase SiO ₂ chromatography (0~50% methanol/ethyl acetate) to afford tert-butyl (S)-((6-((3-(3-chloro-2-(3-fluoro-5-methoxy-4-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)phenyl)pyridin-4-yl)- 2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)c arbamate (150 mg, 69% yield) as a yellow oil. LCMS: m/z found 747 [M +H] ⁺ . (h) (S)-N-(3-(3-Chloro-2-(3-fluoro-5-methoxy-4-((((5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide A mixture of tert-butyl (S)-((6-((3-(3-chloro-2-(3-fluoro-5-methoxy-4-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)phenyl)pyridin-4-yl)- 2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)c arbamate (145 mg, 0.19 mmol) and trifluoroacetic acid (1 mL, 13 mmol) in dichloromethane (3 mL) was stirred for 0.5 hours at room temperature. The mixture was concentrated under reduced pressure and the residue purified by reverse phase HPLC to afford (S)-N-(3-(3-chloro-2-(3-fluoro-5-methoxy- 4-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)phenyl)pyridi n-4-yl)-2-methylphenyl)-5- (((2-hydroxyethyl)amino)methyl)picolinamide (49.9 mg, 39% yield) as a white solid. LCMS: m/z found 647 [M+H] ⁺ , retention time = 2.90 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.72 (d, 1H), 8.64 (d, 1H), 8.23 (d, 1H), 8.05 (dd, 1H), 8.01 (d, 1H), 7.44- 7.40 (m, 2H), 7.18 (s, 1H), 7.14-7.10 (m, 2H), 3.97-3.94 (m, 7H), 3.87-3.82 (m, 1H), 3.71 (t, 1H), 2.78 (t, 2H), 2.73-2.64 (m, 2H), 2.36-2.25 (m, 3H), 2.19 (s, 3 H), 1.84-1.75 (m, 1H). Example 2: N-(3-(2-(4-(((1-Acetylpiperidin-4-yl)amino)methyl)-3-methoxy phenyl)-3- chloropyridin-4-yl)-2-methylphenyl)-5-((methylamino)methyl)p icolinamide (a) tert-Butyl ((6-((3-bromo-2-methylphenyl)carbamoyl)pyridin-3- yl)methyl)(methyl)carbamate To a mixture of N-(3-bromo-2-methylphenyl)-5-formylpicolinamide (Example 1, step (c)) (1 g, 3.13 mmol) and methylamine hydrochloride salt (317 mg, 4.70 mmol) in methanol/dichloromethane (1/1, 30 mL) was added sodium acetate (771 mg, 9.40 mmol) and the mixture stirred for 12 hours at room temperature. Sodium cyanoborohydride (591 mg, 9.40 mmol) was then added and the mixture was stirred for another 1 hour at room temperature. Triethylamine (1.31 mL, 9.43 mmol) and di-tert-butyl decarbonate (1.37 g, 6.28 mmol) were then added and the reaction stirred for 12 hours at room temperature. Saturated aqueous brine solution (15 mL) was added, and the mixture extracted with ethyl acetate (40 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-50% ethyl acetate/petroleum ether) to afford tert-butyl ((6-((3-bromo-2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(methyl)carbamate (1 g, 73% yield) as a white solid. ¹ H NMR (400 MHz, Chloroform-d): δ 10.07 (s, 1H), 8.50 (s, 1H), 8.25 (d, 1H), 8.15 (d, 1H), 7.70 (br s, 1H), 7.38 (d, 1H), 7.11 (t, 1H), 4.51 (s, 2H), 2.90-2.85 (m, 3H), 2.49 (s, 3H), 1.48 (s, 9H). (b) tert-Butyl ((6-((3-(2,3-dichloropyridin-4-yl)-2-methylphenyl)carbamoyl) pyridin- 3-yl)methyl)(methyl)carbamate To a mixture of tert-butyl ((6-((3-bromo-2-methylphenyl)carbamoyl)pyridin-3- yl)methyl)(methyl)carbamate (200 mg, 0.46 mmol) and 2,3-dichloro-4-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)pyridine (290 mg, 1.06 mmol) in 1,4-dioxane/water (5:1, 12 mL) was added potassium phosphate (293 mg, 1.38 mmol) and [1,1′-bis(di-tert- butylphosphino)ferrocene]dichloropalladium(II) (30.0 mg, 0.05 mmol) in one portion under N ₂ and the mixture stirred at 85 °C for 6 hours. Additional 2,3-dichloro-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (150 mg) was added and the mixture stirred for another 12 hours at 85 °C. The mixture combined with another batch at 20 mg scale. Water (50 mL) was added and the mixture extracted with ethyl acetate (200 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether) to afford tert-butyl ((6-((3-(2,3-dichloropyridin-4-yl)-2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(methyl)carbamate (250 mg ,79% yield) as a yellow oil. LCMS: m/z found 501 [M+H] ⁺ . (c) tert-Butyl ((6-((3-(3-chloro-2-(4-formyl-3-methoxyphenyl)pyridin-4-yl)- 2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(methyl)carbamate To a mixture of tert-butyl ((6-((3-(2,3-dichloropyridin-4-yl)-2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(methyl)carbamate (600 mg, 1.20 mmol) and 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ben zaldehyde (408 mg, 1.56 mmol) in 1,4-dioxane/water (5:1 v/v, 18 mL) was added potassium carbonate (496 mg, 3.59 mmol) and tetrakis(triphenylphosphine)palladium(0) (138 mg, 0.12 mmol) in one portion under N ₂ and the mixture stirred at 95 °C for 3 hours. The mixture combined with another batch at 100 mg scale. Water (20 mL) was added and the mixture extracted with ethyl actetate (100 mL). The organic layer was dried over sodium sulfate, filtered and the filtrate was concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether) to afford tert-butyl ((6-((3-(3-chloro-2-(4-formyl-3- methoxyphenyl)pyridin-4-yl)-2-methylphenyl)carbamoyl)pyridin -3- yl)methyl)(methyl)carbamate (380 mg, 47% yield) as a yellow solid. LCMS: m/z found 601 [M+H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d): δ 10.56 (s, 1H), 10.17 (s, 1H), 8.69 (d, 1H), 8.54 (s, 1H), 8.39 (d, 1H), 8.32 (d, 1H), 7.96 (d, 1H), 7.83 (s, 1H), 7.46-7.41 (m, 3H), 7.04 (d, 1H), 4.56 (s, 2H), 4.04 (s, 3H), 2.93-2.90 (m, 3H), 2.24 (s, 3H), 1.51 (s, 9H). (d) tert-Butyl ((6-((3-(2-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-3- methoxyphenyl)-3-chloropyridin-4-yl)-2-methylphenyl)carbamoy l)pyridin-3- yl)methyl)(methyl)carbamate To a mixture of tert-butyl ((6-((3-(3-chloro-2-(4-formyl-3-methoxyphenyl)pyridin-4- yl)-2-methylphenyl)carbamoyl)pyridin-3-yl)methyl)(methyl)car bamate (180 mg, 0.30 mmol) and 1-(4-aminopiperidin-1-yl)ethan-1-one hydrochloride salt (107 mg, 0.60 mmol) in methanol (3 mL) was added sodium acetate (73.7 mg, 0.90 mmol) and the mixture stirred for 3 hours at room temperature. Sodium cyanoborohydride (56.5 mg, 0.90 mmol) was added and the mixture was stirred for another 10 hours at room temperature. The reaction mixture was concentrated to remove methanol and the residue purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether to 0-50% methanol/ethyl acetate) to afford tert-butyl ((6-((3-(2-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-3-meth oxyphenyl)-3- chloropyridin-4-yl)-2-methylphenyl)carbamoyl)pyridin-3-yl)me thyl)(methyl)carbamate (180 mg, 74% yield) as a white oil. LCMS: m/z found 727 [M+H] ⁺ . (e) N-(3-(2-(4-(((1-Acetylpiperidin-4-yl)amino)methyl)-3-methoxy phenyl)-3- chloropyridin-4-yl)-2-methylphenyl)-5-((methylamino)methyl)p icolinamide To a mixture of tert-butyl ((6-((3-(2-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-3- methoxyphenyl)-3-chloropyridin-4-yl)-2-methylphenyl)carbamoy l)pyridin-3- yl)methyl)(methyl)carbamate (175 mg, 0.24 mmol) in dichloromethane (3 mL) was added trifluoroacetic acid (1 mL, 13.5 mmol) and the mixture stirred for 0.5 hours at room temperature. The mixture was concentrated under reduced pressure and the residue purified by reverse phase HPLC twice to afford N-(3-(2-(4-(((1-acetylpiperidin-4-yl)amino)methyl)- 3-methoxyphenyl)-3-chloropyridin-4-yl)-2-methylphenyl)-5- ((methylamino)methyl)picolinamide (72.2 mg, 47% yield) as a white solid. LCMS: m/z found 627 [M+H] ⁺ , retention time = 2.93 min (Method A). ¹ H NMR (400 MHz, Methanol- d ₄ ): δ 8.65 (d, 1H), 8.58 (d, 1H), 8.18 (d, 1H), 7.99-7.95 (m, 2H), 7.41-7.36 (m, 3H), 7.27- 7.23 (m, 2H), 7.09 (d, 1H), 4.45 (d, 1H), 3.93-3.89 (m, 6H), 3.83 (s, 2H), 3.13-3.06 (m, 1H), 2.80-2.74 (m, 1H), 2.69-2.62 (m, 1H), 2.40 (s, 3H), 2.15 (s, 3H), 2.08 (s, 3H), 2.04-1.95 (m, 2H), 1.38-1.25 (m, 2H). Example 3: N-(3-(3-Chloro-2-(4-(((3-fluoropropyl)amino)methyl)-3- methoxyphenyl)pyridin-4-yl)-2-methylphenyl)-5-((methylamino) methyl)picolinamide (a) tert-Butyl ((6-((3-(3-chloro-2-(4-(((3-fluoropropyl)amino)methyl)-3- methoxyphenyl)pyridin-4-yl)-2-methylphenyl)carbamoyl)pyridin -3- yl)methyl)(methyl)carbamate To a mixture of tert-butyl ((6-((3-(3-chloro-2-(4-formyl-3-methoxyphenyl)pyridin-4- yl)-2-methylphenyl)carbamoyl)pyridin-3-yl)methyl)(methyl)car bamate (Example 2, step (c)) (180 mg, 0.30 mmol) and 3-fluoropropan-1-amine hydrochloride salt (68.0 mg, 0.59 mmol) in methanol (3 mL) was added sodium acetate (73.7 mg, 0.90 mmol) and the mixture stirred for 3 hours at room temperature. Sodium cyanoborohydride (56.5 mg, 0.90 mmol) was added and the mixture was stirred for another 10 hours at room temperature. The mixture was concentrated under reduced pressure to remove methanol and the residue was purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether to 0-50% methanol/ethyl acetate) to afford tert-butyl ((6-((3-(3-chloro-2-(4-(((3- fluoropropyl)amino)methyl)-3-methoxyphenyl)pyridin-4-yl)-2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(methyl)carbamate (180 mg, 75% yield) as a white oil. LCMS: m/z found 662 [M+H] ⁺ . (b) N-(3-(3-Chloro-2-(4-(((3-fluoropropyl)amino)methyl)-3-methox yphenyl)pyridin- 4-yl)-2-methylphenyl)-5-((methylamino)methyl)picolinamide To a mixture of tert-butyl ((6-((3-(3-chloro-2-(4-(((3-fluoropropyl)amino)methyl)-3- methoxyphenyl)pyridin-4-yl)-2-methylphenyl)carbamoyl)pyridin -3- yl)methyl)(methyl)carbamate (175 mg, 0.26 mmol) in dichloromethane (3 mL) was added trifluoroacetic acid (1 mL, 13.5 mmol) and the mixture stirred for 0.5 hours at room temperature. The mixture was concentrated under reduced pressure and the residue purified by reverse phase HPLC twice to afford N-(3-(3-chloro-2-(4-(((3- fluoropropyl)amino)methyl)-3-methoxyphenyl)pyridin-4-yl)-2-m ethylphenyl)-5- ((methylamino)methyl)picolinamide (64.7 mg, 42% yield) as a yellow solid. LCMS: m/z found 562 [M +H] ⁺ , retention time = 2.41 min (Method A). ¹ H NMR (400 MHz, Methanol- d4): δ 8.68 (d, 1H), 8.61 (d, 1H), 8.21 (d, 1H), 8.02-7.98 (m, 2H), 7.42-7.39 (m, 3H), 7.29- 7.26 (m, 2H), 7.12 (d, 1H), 4.57 (t, 1H), 4.45 (t, 1H), 3.94 (s, 3H), 3.89 (s, 2H), 3.86 (s, 2H), 2.79 (t, 2H), 2.43 (s, 3H), 2.18 (s, 3H), 1.99-1.89 (m, 2H). Example 4: (S)-N-(3-(3-Chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- methoxyethyl)amino)methyl)picolinamide (a) tert-Butyl ((6-((3-bromo-2-methylphenyl)carbamoyl)pyridin-3-yl)methyl)( 2- methoxyethyl)carbamate To a mixture of N-(3-bromo-2-methylphenyl)-5-formylpicolinamide (Example 1, step (c)) (0.5 g, 1.57 mmol) and 2-methoxyethan-1-amine (0.29 g, 3.92 mmol) in THF/methanol mixture (3:2, 5 mL) was added sodium acetate (0.26 g, 3.13 mmol) in one portion under N ₂ and the mixture stirred at 40 °C for 1 hour. Sodium cyanoborohydride (0.3 g, 4.70 mmol) was added and the mixture stirred at 40 °C for 1 hour to give N-(3-bromo-2- methylphenyl)-5-(((2-methoxyethyl)amino)methyl)picolinamide (LCMS: m/z found 378 and 380 [M+H] ⁺ ). Di-tert-butyl dicarbonate (0.93 g, 4.28 mmol) and triethylamine (0.16 g, 1.59 mmol) were then added in one portion under N ₂ and the mixture stirred at room temperature for 3 hours. Water (30 mL) was added and the mixture extracted with ethyl acetate (2 x 30 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 30 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (9-33% ethyl acetate/petroleum ether) to afford tert-butyl ((6-((3-bromo-2-methylphenyl)carbamoyl)pyridin-3-yl)methyl)( 2- methoxyethyl)carbamate (0.58 g, 59% yield) as a colorless solid. ¹ H NMR (400 MHz, Chloroform-d): δ 10.03 (s, 1H), 8.45 (s, 1H), 8.18 (d, 1H), 8.10 (d, 1H), 7.75 (s, 1H), 7.33 (d, 1H), 7.06 (t, 1H), 4.55 (s, 2H), 3.38-3.36 (m, 2H), 3.26 (s, 3H), 3.24 (s, 2H), 2.44 (s, 3H), 1.43 (s, 9H). (b) tert-Butyl ((6-((3-(2,3-dichloropyridin-4-yl)-2-methylphenyl)carbamoyl) pyridin- 3-yl)methyl)(2-methoxyethyl)carbamate To a mixture of tert-butyl ((6-((3-bromo-2-methylphenyl)carbamoyl)pyridin-3- yl)methyl)(2-methoxyethyl)carbamate (0.15 g, 0.31 mmol) and 2,3-dichloro-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.26 g, 0.94 mmol) in 1,4-dioxane/water mixture (5:1 v/v, 2.4 mL) was added [1,1′-bis(di-tert- butylphosphino)ferrocene]dichloropalladium(II) (0.02 g, 0.03 mmol) and potassium phosphate (0.2 g, 0.94 mmol) in one portion under N ₂ and the mixture stirred at 130 °C for 5 hours. The mixture was combined with another batch at 300 mg scale. Water (30 mL) and the mixture was extracted with ethyl acetate (2 x 15 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 20 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (9-25% ethyl acetate/petroleum ether) to afford tert-butyl ((6-((3-(2,3- dichloropyridin-4-yl)-2-methylphenyl)carbamoyl)pyridin-3-yl) methyl)(2- methoxyethyl)carbamate (0.2 g, 38% yield) as a brown solid. LCMS: m/z found 545 [M+H] ⁺ . (c) (S)-5-(((4-Bromo-2-methoxybenzyl)amino)methyl)pyrrolidin-2-o ne To a mixture of 4-bromo-2-methoxybenzaldehyde (3 g, 13.9 mmol) and (S)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt (2.52 g, 16.7 mmol) in methanol (40 mL) was added sodium acetate (3.43 g, 41.8 mmol) and the mixture was stirred at room temperature for 12 hours. Sodium cyanoborohydride (1.75 g, 27.9 mmol) was added and the mixture was stirred at room temperature for 0.5 hours. To the mixture was added water (50 mL) and the mixture was extracted with ethyl acetate (2 x 100 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to afford (S)-5-(((4-bromo-2- methoxybenzyl)amino)methyl)pyrrolidin-2-one as a yellow oil (4 g, crude) which was used for next step without further purification. (d) tert-Butyl (S)-(4-bromo-2-methoxybenzyl)((5-oxopyrrolidin-2- yl)methyl)carbamate A mixture of (S)-5-(((4-bromo-2-methoxybenzyl)amino)methyl)pyrrolidin-2-o ne (3.9 g, 12.5 mmol), di-tert-butyl dicarbonate (8.15 g, 37.4 mmol) and triethylamine (5.20 mL, 37.4 mmol) in dichloromethane (40 mL) was degassed and purged with nitrogen. The mixture was stirred at room temperature for 3 hours under N ₂ atmosphere. The mixture was concentrated, and the residue purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether) to afford tert-butyl (S)-(4-bromo-2-methoxybenzyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (4.2 g, 81% yield) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 7.73 (s, 1H), 7.19-7.13 (m, 2H), 6.93 (s, 1H), 4.38-4.27 (m, 2H), 3.83 (s, 3H), 3.71 (s, 1H), 3.21-3.16 (m, 2H), 2.15-1.99 (m, 3H), 1.13 (s, 1H), 1.42-1.31 (m, 9H). (e) tert-Butyl (S)-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)benzyl)((5-oxopyrrolidin-2-yl)methyl)carbamate To a mixture of tert-butyl (S)-(4-bromo-2-methoxybenzyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (4.1 g, 9.92 mmol) and bis(pinacolato)diboron (7.56 g, 29.8 mmol) in 1,4-dioxane (40 mL) was added potassium acetate (2.92 g, 29.8 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (810 mg, 0.99 mmol) and the mixture was stirred at 95 °C for 12 hours under N ₂ . The mixture was filtered, the filtrate concentrated and the residue purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether) to afford tert-butyl (S)-(2-methoxy- 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)((5-ox opyrrolidin-2- yl)methyl)carbamate (2.6 g, 56% yield) as a black solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 7.72 (s, 1H), 7.27 (d, 1H), 7.18 (s, 1H), 7.01 (d, 1H), 4.41-4.39 (m, 2H), 3.93 (s, 3H), 3.72 (s, 1H), 3.21-3.17 (m, 2H), 2.17-2.04 (m, 3H), 1.75-1.71 (m, 1H), 1.43-1.30 (m, 21H). (f) tert-Butyl (S)-((6-((3-(2-(4-(((tert-butoxycarbonyl)((5-oxopyrrolidin-2 - yl)methyl)amino)methyl)-3-methoxyphenyl)-3-chloropyridin-4-y l)-2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-methoxyethyl)c arbamate To a mixture of tert-butyl ((6-((3-(2,3-dichloropyridin-4-yl)-2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-methoxyethyl)c arbamate (0.18 g, 0.33 mmol) and tert-butyl (S)-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)benzyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (0.23 g, 0.50 mmol) in 1,4-dioxane/water mixture (5:1 v/v, 3.6 mL) was added potassium phosphate (0.21 g, 0.99 mmol) and chloro(2- dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-bip henyl)[2-(2′-amino-1,1′- biphenyl)]palladium(II) (0.03 g, 0.03 mmol) in one portion under N ₂ and the mixture stirred at 110 °C for 3 hours. Water (10 mL) was added, and the mixture extracted with ethyl acetate (2 x 10 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 10 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (9-100% ethyl acetate/petroleum ether) to afford tert-butyl (S)-((6-((3-(2-(4-(((tert-butoxycarbonyl)((5-oxopyrrolidin-2 - yl)methyl)amino)methyl)-3-methoxyphenyl)-3-chloropyridin-4-y l)-2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-methoxyethyl)c arbamate (0.3 g, 65% yield) as a yellow solid LCMS: m/z found 843 [M+H] ⁺ . (g) (S)-N-(3-(3-Chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- methoxyethyl)amino)methyl)picolinamide To a mixture of tert-butyl (S)-((6-((3-(2-(4-(((tert-butoxycarbonyl)((5-oxopyrrolidin- 2-yl)methyl)amino)methyl)-3-methoxyphenyl)-3-chloropyridin-4 -yl)-2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-methoxyethyl)c arbamate (0.29 g, 0.34 mmol) in 1,4-dioxane (2 mL) was added concentrated HCl solution (0.3 mL) in one portion under N ₂ and the mixture stirred at room temperature for 2 hours. The mixture was combined with another batch at 10 mg scale. The mixture was neutralized with saturated aqueous sodium bicarbonate solution, concentrated and the residue purified by reverse phase HPLC to afford (S)-N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- methoxyethyl)amino)methyl)picolinamide (57 mg, 24% yield) as a yellow solid. LCMS: m/z found 643 [M+H] ⁺ , retention time = 2.49 min (Method A). ¹ H NMR (400 MHz, Methanol- d ₄ ): δ 8.71 (s, 1H), 8.62 (d, 1H), 8.22 (d, 1H), 8.05-8.00 (m, 2H), 7.44-7.40 (m, 3H), 7.30- 7.27 (m, 2H), 7.13 (d, 1H), 3.95 (s, 5H), 3.90-3.82 (m, 3H), 3.55 (t, 2H), 3.38 (s, 3H), 2.82 (t, 2H), 2.75-2.66 (m, 2H), 2.36-2.26 (m, 3H), 2.20 (s, 3H), 1.85-1.77 (m, 1H). Example 5: N-(3-(2-(4-((7-Oxa-2-azaspiro[3.5]nonan-2-yl)methyl)-3-metho xyphenyl)-3- chloropyridin-4-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amin o)methyl)picolinamide (a) tert-Butyl ((6-((3-(3-chloro-2-(4-formyl-3-methoxyphenyl)pyridin-4-yl)- 2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)c arbamate To a mixture of tert-butyl ((6-((3-(2,3-dichloropyridin-4-yl)-2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)c arbamate (Example 1, step (e)) (160 mg, 0.30 mmol) and 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)benzaldehyde (94.7 mg, 0.36 mmol) in 1,4-dioxane/water (10:1 v/v, 2.2 mL) was added potassium carbonate (125 mg, 0.90 mmol) and tetrakis(triphenylphosphine)palladium(0) (34.8 mg, 0.03 mmol) in one portion under N ₂ and the mixture stirred at 110 °C for 12 hours. The reaction mixture combined with another batch at 50 mg scale. Aqueous brine solution (15 mL) was added and the mixture extracted with ethyl acetate (100 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether) to afford tert-butyl ((6-((3-(3-chloro-2-(4-formyl-3-methoxyphenyl)pyridin-4-yl)- 2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)c arbamate (120 mg, 63% yield) as a yellow oil. (b) tert-Butyl ((6-((3-(2-(4-((7-oxa-2-azaspiro[3.5]nonan-2-yl)methyl)-3- methoxyphenyl)-3-chloropyridin-4-yl)-2-methylphenyl)carbamoy l)pyridin-3- yl)methyl)(2-hydroxyethyl)carbamate To the mixture of tert-butyl ((6-((3-(3-chloro-2-(4-formyl-3-methoxyphenyl)pyridin- 4-yl)-2-methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydrox yethyl)carbamate (110 mg, 0.17 mmol) and 7-oxa-2-azaspiro[3.5]nonane hydrochloride salt (34.2 mg, 0.21 mmol) in methanol (3 mL) was added sodium acetate (42.9 mg, 0.52 mmol) and the mixture stirred for 2 hours at room temperature. Sodium cyanoborohydride (32.9 mg, 0.52 mmol) was added and the mixture was stirred for another 10 hours at room temperature. The reaction mixture was concentrated under reduced pressure and the residue purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether to 0-50% methanol/ethyl acetate) to afford tert-butyl ((6-((3-(2-(4-((7-oxa-2-azaspiro[3.5]nonan-2-yl)methyl)-3-me thoxyphenyl)- 3-chloropyridin-4-yl)-2-methylphenyl)carbamoyl)pyridin-3-yl) methyl)(2- hydroxyethyl)carbamate (110 mg, 80% yield) as an off-white solid. LCMS: m/z found 742 [M+H] ⁺ . (c) N-(3-(2-(4-((7-oxa-2-azaspiro[3.5]nonan-2-yl)methyl)-3-metho xyphenyl)-3- chloropyridin-4-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amin o)methyl)picolinamide A mixture of tert-butyl ((6-((3-(2-(4-((7-oxa-2-azaspiro[3.5]nonan-2-yl)methyl)-3- methoxyphenyl)-3-chloropyridin-4-yl)-2-methylphenyl)carbamoy l)pyridin-3-yl)methyl)(2- hydroxyethyl)carbamate (105 mg, 0.14 mmol) and trifluoroacetic acid (2.10 mL, 28.4 mmol) in dichloromethane (1 mL) was stirred for 0.5 hours at room temperature. The mixture was concentrated under reduced pressure and the residue purified by reverse phase HPLC to afford N-(3-(2-(4-((7-oxa-2-azaspiro[3.5]nonan-2-yl)methyl)-3-metho xyphenyl)-3- chloropyridin-4-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amin o)methyl)picolinamide (25.0 mg, 27% yield) as a white solid. LCMS: m/z found 642 [M+H] ⁺ , retention time = 2.81 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.72 (d, 1H), 8.62 (d, 1H), 8.23 (d, 1H), 8.05 (dd, 1H), 8.01 (d, 1H), 7.44-7.38 (m, 3H), 7.29-7.28 (m, 2H), 7.13 (d, 1H), 3.96 (s, 2H), 3.92 (s, 3H), 3.84 (s, 2H), 3.71 (t, 2H), 3.62 (t, 4H), 3.30 (s, 4H), 2.78 (t, 2H), 2.20 (s, 3H), 1.79 (t, 4H). Example 6: N-(3-(3-Chloro-2-(3-methoxy-4-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((R)-3- hydroxypyrrolidin-1-yl)methyl)picolinamide (a) Methyl 5-(dimethoxymethyl)picolinate To a solution of methyl 5-formylpicolinate (10 g, 60.6 mmol) and methanol (24.50 mL, 606 mmol, 10 eq) in toluene (100 mL) was added p-toluenesulfonic acid (1.04 g, 6.06 mmol) and the mixture stirred at 130 °C for 1 h under N ₂ using a Dean-Stark apparatus. The reaction mixture was concentrated and the residue purified by normal phase SiO ₂ chromatography (10-30% ethyl acetate / petroleum ether) to give methyl 5-(dimethoxymethyl)picolinate (10 g, 78% yield) as a yellow solid. ¹ H NMR (400 MHz, Chloroform-d): δ 8.78 (s, 1H), 8.14-8.12 (d, 1H), 7.92-7.90 (d, 1H), 5.51 (s, 1H), 4.00 (s, 3H), 3.33 (s, 6H). (b) Lithium 5-(dimethoxymethyl)picolinate To a mixture of methyl 5-(dimethoxymethyl)picolinate (5.3 g, 25.09 mmol) in THF (10 mL) and water (2 mL) was added lithium hydroxide monohydrate (2.11 g, 50.29 mmol) and the mixture stirred at 15 °C for 1 h under N ₂ . The mixture was then concentrated to give lithium 5-(dimethoxymethyl)picolinate (7 g, crude) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 8.45 (s, 1H), 8.02 (d, 1H), 7.86 (d, 1H), 5.53 (s, 1H), 3.27 (s, 6H). (c) 3-(2,3-Dichloropyridin-4-yl)-2-methylaniline To a mixture of 3-bromo-2-methylaniline (2 g, 10.75 mmol) and 2,3-dichloro-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (3.98 g, 14.51 mmol) in 1,4- dioxane/water mixture (5:1 v/v, 36 mL) was added potassium phosphate (6.85 g, 32.3 mmol) and [1,1′-bis(di-tert-butylphosphino)ferrocene]dichloropalladi um(II) (0.18 g, 0.27 mmol) in one portion under N ₂ and the mixture stirred at 100 °C for 6 hours. The mixture was concentrated, water (50 mL) and saturated aqueous brine solution (15 mL) added to the residue, and the mixture extracted with an ethyl acetate/THF mixture (1:1 v/v, 50 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (5-20% ethyl acetate/petroleum ether) to afford 3-(2,3-dichloropyridin-4-yl)-2-methylaniline (2 g, 45% yield) as a yellow solid. LCMS: m/z found 253 [M+H] ⁺ . (d) N-(3-(2,3-Dichloropyridin-4-yl)-2-methylphenyl)-5- (dimethoxymethyl)picolinamide To a mixture of 3-(2,3-dichloropyridin-4-yl)-2-methylaniline (1.35 g, 5.33 mmol) and lithium 5-(dimethoxymethyl)picolinate (1.52 g, 7.48 mmol) in DMF (30 mL) was added 1- [bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridi nium 3-oxide hexafluorophosphate (HATU) (3.04 g, 8 mmol) and N,N-diisopropylethylamine (2 mL, 10.7 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 6 hours. Additional HATU (1.01 g, 2.67 mmol) was added and stirring continued for 6 hours. The mixture was then concentrated, water (500 mL) and saturated aqueous brine solution (500 mL) added to the residue, and the mixture extracted with an ethyl acetate/THF mixture (1:1 v/v, 500 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-10% ethyl acetate/petroleum ether) to afford N-(3-(2,3-dichloropyridin-4-yl)-2-methylphenyl)-5- (dimethoxymethyl)picolinamide (1.4 g, 51% yield) as a white solid. LCMS: m/z found 432 [M+H] ⁺ . (e) N-(3-(2,3-Dichloropyridin-4-yl)-2-methylphenyl)-5-formylpico linamide To a mixture of N-(3-(2,3-dichloropyridin-4-yl)-2-methylphenyl)-5- (dimethoxymethyl)picolinamide (1.38 g, 3.19 mmol) in THF (16 mL) was added 1 N aqueous HCl solution (4 mL) in one portion under N ₂ and the mixture stirred at room temperature for 0.5 hours. The mixture was neutralized with saturated aqueous sodium bicarbonate solution, water (150 mL) and saturated aqueous brine solution (50 mL) added, and the mixture extracted with an ethyl acetate/THF mixture (1:1 v/v, 150 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated to afford N-(3-(2,3-dichloropyridin- 4-yl)-2-methylphenyl)-5-formylpicolinamide as a white solid (1.2 g, 82% yield). ¹ H NMR (400 MHz, Chloroform-d): δ 10.17 (s, 1H), 10.07 (s, 1H), 9.04 (d, 1H), 8.44 (d, 1H), 8.34 (dd, 1H), 8.30-8.29 (m, 2H), 7.33 (t, 1H), 7.11 (d, 1H), 6.91 (d, 1H), 2.11 (s, 3H). (f) (R)-N-(3-(2,3-Dichloropyridin-4-yl)-2-methylphenyl)-5-((3-hy droxypyrrolidin-1- yl)methyl)picolinamide To a mixture of N-(3-(2,3-dichloropyridin-4-yl)-2-methylphenyl)-5- formylpicolinamide (0.9 g, 2.33 mmol) and (R)-pyrrolidin-3-ol (0.3 g, 3.50 mmol) in THF/methanol mixture (1:1 v/v, 12 mL) was added sodium triacetoxyborohydride (1.48 g, 6.99 mmol) and sodium acetate (0.38 g, 4.66 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 12 hours. The mixture was combined with another batch at 150 mg scale. The mixture was concentrated, water (150 mL) and saturated aqueous brine solution (25 mL) added to the residue, and the mixture extracted with an ethyl acetate/THF mixture (1:1 v/v, 150 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0- 7% methanol/ethyl acetate) to afford (R)-N-(3-(2,3-dichloropyridin-4-yl)-2-methylphenyl)-5- ((3-hydroxypyrrolidin-1-yl)methyl)picolinamide (1 g, 80% yield) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.45 (s, 1H), 8.72-8.71 (m, 1H), 8.53 (d, 1H), 8.20 (d, 1H), 8.05 (dd, 1H), 7.98 (d, 1H), 7.51 (d, 1H), 7.45 (t, 1H), 7.15-7.13 (m, 1H), 4.79 (d, 1H), 4.32-4.27 (m, 1H), 3.84-3.73 (m, 2H), 2.79-2.75 (m, 1H), 2.72-2.66 (m, 1H), 2.54-2.48 (m, 1H), 2.43- 2.39 (m, 1H), 2.10 (s, 3H), 2.08-2.03 (m, 1H), 1.66-1.60 (m, 1H). (g) (R)-N-(3-(3-Chloro-2-(4-formyl-3-methoxyphenyl)pyridin-4-yl) -2-methylphenyl)- 5-((3-hydroxypyrrolidin-1-yl)methyl)picolinamide To a mixture of (R)-N-(3-(2,3-dichloropyridin-4-yl)-2-methylphenyl)-5-((3- hydroxypyrrolidin-1-yl)methyl)picolinamide (0.1 g, 0.22 mmol) and 2-methoxy-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde (0.07 g, 0.28 mmol) in 1,4-dioxane/water mixture (6:1 v/v, 3.5 mL) was added potassium phosphate (0.14 g, 0.66 mmol) and [1,1′- bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) (0.01 g, 0.02 mmol) in one portion under N ₂ and the mixture stirred at 110 °C for 6 hours. The mixture was combined with another batch at 500 mg scale. The mixture was concentrated, water (150 mL) and saturated aqueous brine solution (25 mL) added to the residue, and the mixture extracted with an ethyl acetate/THF mixture (1:1 v/v, 100 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-10% methanol/ethyl acetate) to afford (R)-N-(3-(3-chloro-2-(4-formyl-3- methoxyphenyl)pyridin-4-yl)-2-methylphenyl)-5-((3-hydroxypyr rolidin-1- yl)methyl)picolinamide (390 mg, 50% yield) as a yellow solid. LCMS: m/z found 557 [M+H] ⁺ . (h) N-(3-(3-Chloro-2-(3-methoxy-4-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((R)-3- hydroxypyrrolidin-1-yl)methyl)picolinamide To a mixture of (R)-N-(3-(3-chloro-2-(4-formyl-3-methoxyphenyl)pyridin-4-yl) -2- methylphenyl)-5-((3-hydroxypyrrolidin-1-yl)methyl)picolinami de (0.15 g, 0.27 mmol) and (S)-5-(aminomethyl)pyrrolidin-2-one hydrochloride salt (0.05 g, 0.35 mmol) in THF/methanol mixture (1:1 v/v, 2 mL) was added sodium acetate (0.07 g, 0.8 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 12 hours. To the mixture was added sodium cyanoborohydride (0.05 g, 0.8 mmol). The mixture was stirred at room temperature for 0.5 hours. The mixture was purified by reverse phase HPLC to afford the product as a formic salt (~40 mg). The product (~40 mg) was neutralized with saturated aqueous sodium bicarbonate solution. To the mixture was added deionized water (15 mL) and the mixture extracted with dichloromethane (3 x 5 mL). The combined organic phases were concentrated and lyophilized to afford N-(3-(3-chloro-2-(3-methoxy-4-(((((S)-5- oxopyrrolidin-2-yl)methyl)amino)methyl)phenyl)pyridin-4-yl)- 2-methylphenyl)-5-(((R)-3- hydroxypyrrolidin-1-yl)methyl)picolinamide (35.4 mg, 20% yield) as a white solid. LCMS: m/z found 655 [M+H] ⁺ , retention time = 2.43 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.71 (s, 1H), 8.62 (d, 1H), 8.21 (d, 1H), 8.11-7.96 (m, 2H), 7.44-7.40 (m, 3H), 7.30-7.27 (m, 2H), 7.13 (d, 1H), 4.40-4.37 (m, 1H), 3.95-3.76 (m, 8H), 2.84-2.55 (m, 6H), 2.36-2.12 (m, 7H), 1.87-1.75 (m, 2H). Example 7: (R)-N-(3-(2-(4-(((1-Acetylpiperidin-4-yl)amino)methyl)-3-met hoxyphenyl)- 3-chloropyridin-4-yl)-2-methylphenyl)-5-((3-hydroxypyrrolidi n-1- yl)methyl)picolinamide (a) (R)-N-(3-(2-(4-(((1-Acetylpiperidin-4-yl)amino)methyl)-3-met hoxyphenyl)-3- chloropyridin-4-yl)-2-methylphenyl)-5-((3-hydroxypyrrolidin- 1-yl)methyl)picolinamide To a mixture of (R)-N-(3-(3-chloro-2-(4-formyl-3-methoxyphenyl)pyridin-4-yl) -2- methylphenyl)-5-((3-hydroxypyrrolidin-1-yl)methyl)picolinami de (Example 6, step (g)) (0.15 g, 0.27 mmol) and 1-(4-aminopiperidin-1-yl)ethan-1-one hydrochloride salt (0.06 g, 0.35 mmol) in in THF/methanol mixture (1:1 v/v, 2 mL) was added sodium acetate (0.07 g, 0.81 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 12 hours. To the mixture was added sodium cyanoborohydride (0.05 g, 0.81 mmol) and the mixture was stirred at room temperature for 0.5 hours. The mixture was combined with another batch at 10 mg scale. The mixture was purified by reverse phase HPLC to afford the product as a formic salt (~30 mg). The product (~30 mg) was neutralized with saturated aqueous sodium bicarbonate solution. To the mixture was added deionized water (15 mL) and the mixture extracted with dichloromethane (3 x 5 mL). The combined organic phases were concentrated and lyophilized to afford (R)-N-(3-(2-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-3- methoxyphenyl)-3-chloropyridin-4-yl)-2-methylphenyl)-5-((3-h ydroxypyrrolidin-1- yl)methyl)picolinamide (28 mg, 15% yield) as a white solid. LCMS: m/z found 683 [M+H] ⁺ , retention time = 2.54 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.71 (d, 1H), 8.62 (d, 1H), 8.22 (d, 1H), 8.05-8.00 (m, 2H), 7.44-7.40 (m, 3H), 7.31-7.27 (m, 2H), 7.13 (d, 1H), 4.51-4.47 (m, 1H), 4.41-4.36 (m, 1H), 3.95-3.93 (m, 6H), 3.86-3.76 (m, 2H), 3.17-3.11 (m, 1H), 2.85-2.67 (m, 4H), 2.59-2.54 (m, 2H), 2.22-2.13 (m, 4H), 2.12 (s, 3H), 2.06-1.95 (m, 2H), 1.80-1.72 (m, 1H), 1.41-1.29 (m, 2H). Example 8: N-(3-(3-Chloro-2-(4-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-3 - methoxyphenyl)pyridin-4-yl)-2-methylphenyl)-5-(((R)-3-hydrox ypyrrolidin-1- yl)methyl)picolinamide N-(3-(3-Chloro-2-(4-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-3 - methoxyphenyl)pyridin-4-yl)-2-methylphenyl)-5-(((R)-3-hydrox ypyrrolidin-1- yl)methyl)picolinamide was prepared in a similar fashion to Example 7, replacing 1-(4- aminopiperidin-1-yl)ethan-1-one hydrochloride salt with (R)-pyrrolidin-3-ol in step (a). LCMS: m/z found 628 [M+H] ⁺ , retention time = 2.43 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.71 (d, 1H), 8.62 (d, 1H), 8.22 (d, 1H), 8.05-8.00 (m, 2H), 7.47 (d, 1H), 7.44-7.40 (m, 2H), 7.30-7.28 (m, 2H), 7.13 (d, 1H), 4.41-4.37 (m, 2H), 3.92 (s, 3H), 3.86- 3.76 (m, 4H), 2.96-2.92 (m, 1H), 2.85-2.79 (m, 3H), 2.69-2.67 (m, 1H), 2.61-2.54 (m, 3H), 2.24-2.13 (m, 5H), 1.80-1.72 (m, 2H). Example 9: (S)-N-(3-(3-Chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)(methyl)amino)methyl)picolinamide (a) N-(3-Bromo-2-methylphenyl)-5-(((tert- butyldimethylsilyl)oxy)methyl)picolinamide To a mixture of N-(3-bromo-2-methylphenyl)-5-(hydroxymethyl)picolinamide (3 g, 9.34 mmol) (Example 1, step (b)) in DMF (30 mL) was added imidazole (0.76 g, 11.2 mmol) and tert-butyldimethylsilyl chloride (2.82 g, 18.7 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 1 hour. The mixture was concentrated, water (20 mL) and saturated aqueous brine solution (30 mL) added to the residue, and the mixture extracted with ethyl acetate (100 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-10% ethyl acetate/petroleum ether) to afford N-(3-bromo-2- methylphenyl)-5-(((tert-butyldimethylsilyl)oxy)methyl)picoli namide (3.7 g, 90% yield) as a yellow solid. ¹ H NMR (400 MHz, Chloroform-d): δ 9.97 (s, 1H), 8.45 (s, 1H), 8.12 (d, 1H), 8.04 (d, 1H), 7.71 (dd, 1H), 7.25 (dd, 1H), 6.98 (t, 1H), 4.71 (s, 2H), 2.37 (s, 3H), 0.82 (s, 9H), 0.00 (s, 6H). (b) 5-(((tert-Butyldimethylsilyl)oxy)methyl)-N-(3-(2,3-dichlorop yridin-4-yl)-2- methylphenyl)picolinamide To a mixture of N-(3-bromo-2-methylphenyl)-5-(((tert- butyldimethylsilyl)oxy)methyl)picolinamide (1.2 g, 2.76 mmol) and 2,3-dichloro-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (2.26 g, 8.27 mmol) in 1,4-dioxane/water mixture (5:1 v/v, 36 mL) was added potassium phosphate (1.75 g, 8.27 mmol) and [1,1′- bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) (0.18 g, 0.28 mmol) in one portion under N ₂ and the mixture was stirred at 130 °C for 36 hours. The mixture was combined with another batch at the same scale. The mixture was concentrated, water (20 mL) and saturated aqueous brine solution (20 mL) added to the residue, and the mixture extracted with an ethyl acetate/THF mixture (1:1 v/v, 80 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (1-10% ethyl acetate/petroleum ether) to afford 5-(((tert- butyldimethylsilyl)oxy)methyl)-N-(3-(2,3-dichloropyridin-4-y l)-2- methylphenyl)picolinamide (0.65 g, 22% yield) as a white solid (0.65 g, 22% yield). ¹ H NMR (400 MHz, Chloroform-d): δ 10.02 (s, 1H), 8.44 (s, 1H), 8.24-8.20 (m, 2H), 8.15 (d, 1H), 7.73 (d, 1H), 7.23 (t, 1H), 7.03 (d, 1H), 6.79 (d, 1H), 4.72 (s, 2H), 2.02 (s, 3H), 0.82 (s, 9H), 0.00 (s, 6H). (c) tert-Butyl (S)-(4-(4-(3-(5-(((tert-butyldimethylsilyl)oxy)methyl)picoli namido)-2- methylphenyl)-3-chloropyridin-2-yl)-2-methoxybenzyl)((5-oxop yrrolidin-2- yl)methyl)carbamate To a mixture of 5-(((tert-butyldimethylsilyl)oxy)methyl)-N-(3-(2,3-dichlorop yridin-4- yl)-2-methylphenyl)picolinamide (0.65 g, 1.29 mmol) and tert-butyl (S)-(2-methoxy-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)((5-oxop yrrolidin-2- yl)methyl)carbamate (0.77 g, 1.68 mmol) (Example 4, step (e)) in 1,4-dioxane/water mixture (10:1 v/v, 22 mL) was added potassium phosphate (0.82 g, 3.88 mmol) and chloro(2- dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-bip henyl)[2-(2′-amino-1,1′- biphenyl)]palladium(II) (0.1 g, 0.13 mmol) in one portion under N ₂ and the mixture stirred at 105 °C for 5 hours. The mixture was combined with another batch at 100 mg scale. The mixture was concentrated, water (20 mL) and saturated aqueous brine solution (20 mL) added to the residue, and the mixture extracted with an ethyl acetate/THF mixture (1:1 v/v, 100 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-15% ethyl acetate/petroleum ether) to afford tert-butyl (S)-(4-(4-(3-(5-(((tert- butyldimethylsilyl)oxy)methyl)picolinamido)-2-methylphenyl)- 3-chloropyridin-2-yl)-2- methoxybenzyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (0.9 g, 75% yield) as a yellow solid. LCMS: m/z found 800 [M+H] ⁺ . (d) tert-Butyl (S)-(4-(3-chloro-4-(3-(5-(hydroxymethyl)picolinamido)-2- methylphenyl)pyridin-2-yl)-2-methoxybenzyl)((5-oxopyrrolidin -2-yl)methyl)carbamate To a mixture of tert-butyl (S)-(4-(4-(3-(5-(((tert- butyldimethylsilyl)oxy)methyl)picolinamido)-2-methylphenyl)- 3-chloropyridin-2-yl)-2- methoxybenzyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (0.88 g, 1.1 mmol) in THF (10 mL) was added 1 M tetrabutylammonium fluoride in THF solution (2.2 mL, 2.2 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 1 hour. The mixture was combined with another batch at 20 mg scale. The mixture was concentrated, water (20 mL) and saturated aqueous brine solution (20 mL) added to the residue, and the mixture was extracted with an ethyl acetate/THF mixture (3:1 v/v, 50 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated to afford the crude tert-butyl (S)-(4- (3-chloro-4-(3-(5-(hydroxymethyl)picolinamido)-2-methylpheny l)pyridin-2-yl)-2- methoxybenzyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (0.9 g, crude) as a yellow solid. ¹ H NMR (400 MHz, Methanol-d4): δ 8.63 (s, 1H), 8.54 (d, 1H), 8.15 (d, 1H), 7.96 -7.93 (m, 2H), 7.34-7.32 (m, 2H), 7.25-7.21 (m, 3H), 7.05 (d, 1H), 4.71 (s, 2H), 4.58-4.46 (m, 2H), 3.89- 3.81 (m, 4H), 3.35-3.31 (m, 2H), 2.29-2.13 (m, 3H), 2.12 (s, 3H), 1.90-1.81 (m, 1H), 1.45- 1.35 (m, 9H). (e) tert-Butyl (S)-(4-(3-chloro-4-(3-(5-formylpicolinamido)-2-methylphenyl) pyridin- 2-yl)-2-methoxybenzyl)((5-oxopyrrolidin-2-yl)methyl)carbamat e To a mixture of tert-butyl (S)-(4-(3-chloro-4-(3-(5-(hydroxymethyl)picolinamido)-2- methylphenyl)pyridin-2-yl)-2-methoxybenzyl)((5-oxopyrrolidin -2-yl)methyl)carbamate (0.3 g, 0.44 mmol) in dichloromethane (5 mL) was added manganese dioxide (0.46 g, 5.25 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 16 hours. The mixture was filtered through Celite®, and the filtrate concentrated to afford crude tert-butyl (S)-(4-(3-chloro-4-(3-(5-formylpicolinamido)-2-methylphenyl) pyridin-2-yl)-2- methoxybenzyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (260 mg, crude) as a yellow solid. LCMS: m/z found 684 [M+H] ⁺ . (f) tert-Butyl (S)-(4-(3-chloro-4-(3-(5-(((2- hydroxyethyl)(methyl)amino)methyl)picolinamido)-2-methylphen yl)pyridin-2-yl)-2- methoxybenzyl)((5-oxopyrrolidin-2-yl)methyl)carbamate To a mixture of tert-butyl (S)-(4-(3-chloro-4-(3-(5-formylpicolinamido)-2- methylphenyl)pyridin-2-yl)-2-methoxybenzyl)((5-oxopyrrolidin -2-yl)methyl)carbamate (0.26 g, 0.38 mmol) and 2-(methylamino)ethan-1-ol (0.04 g, 0.57 mmol) in THF/methanol mixture (2:1 v/v, 3 mL) was added sodium acetate (0.06 g, 0.76 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 12 hours. Sodium cyanoborohydride (0.07 g, 1.14 mmol) was then added and the mixture stirred at room temperature for 3 hours. The mixture was concentrated, water (5 mL) and saturated aqueous brine solution (5 mL) added to the residue, and the mixture extracted with dichloromethane /methanol mixture (10:1 v/v, 20 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0~30% methanol/ethyl acetate) to afford tert-butyl (S)-(4-(3-chloro-4-(3-(5-(((2- hydroxyethyl)(methyl)amino)methyl)picolinamido)-2-methylphen yl)pyridin-2-yl)-2- methoxybenzyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (80 mg, 21% yield) as a yellow solid. LCMS: m/z found 743 [M+H] ⁺ . (g) (S)-N-(3-(3-Chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)(methyl)amino)methyl)picolinamide To a mixture of tert-butyl (S)-(4-(3-chloro-4-(3-(5-(((2- hydroxyethyl)(methyl)amino)methyl)picolinamido)-2-methylphen yl)pyridin-2-yl)-2- methoxybenzyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (0.11 g, 0.15 mmol) in 1,4-dioxane (1 mL) was added concentrated HCl solution (12 M, 0.3 mL) in one portion under N ₂ and the mixture stirred at room temperature for 1 h. The mixture was neutralized with saturated aqueous sodium bicarbonate solution and purified by reverse phase HPLC to afford (S)-N-(3- (3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2-yl)methyl)ami no)methyl)phenyl)pyridin-4- yl)-2-methylphenyl)-5-(((2-hydroxyethyl)(methyl)amino)methyl )picolinamide (26.6 mg, 27% yield) as a white solid. LCMS: m/z found 643 [M+H] ⁺ , retention time = 2.40 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.70 (d, 1H), 8.62 (d, 1H), 8.22 (d, 1H), 8.05 (dd, 1H), 8.01 (d, 1H), 7.44-7.40 (m, 3H), 7.30-7.27 (m, 2H), 7.13 (d, 1H), 3.95 (s, 3H), 3.90-3.81 (m, 3H), 3.75-3.71 (m, 4H), 2.73-2.68 (m, 2H), 2.63 (t, 2H), 2.37-2.26 (m, 6H), 2.20 (s, 3H), 1.83-1.77 (m, 1H). Example 10: (R)-N-(3-(3-Chloro-2-(3-methoxy-4-((7-oxo-2,6-diazaspiro[3.4 ]octan-2- yl)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)-5-((3-hydroxy pyrrolidin-1- yl)methyl)picolinamide (R)-N-(3-(3-chloro-2-(3-methoxy-4-((7-oxo-2,6-diazaspiro[3.4 ]octan-2- yl)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)-5-((3-hydroxy pyrrolidin-1- yl)methyl)picolinamide was prepared in a similar fashion to Example 7, replacing 1-(4- aminopiperidin-1-yl)ethan-1-one hydrochloride salt with 2,6-diazaspiro[3.4]octan-7-one trifluoroacetic acid salt in step (a). LCMS: m/z found 667 [M+H] ⁺ , retention time = 2.40 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.71-8.70 (m, 1H), 8.61 (d, 1H), 8.22 (d, 1H), 8.05-8.00 (m, 2H), 7.44-7.38 (m, 3H), 7.29-7.27 (m, 2H), 7.13 (d, 1H), 4.41-4.36 (m, 1H), 3.92 (s, 3H), 3.86-3.76 (m, 4H), 3.59 (s, 2H), 3.45-3.40 (m, 4H), 2.85-2.80 (m, 2H), 2.60-2.54 (m, 4H), 2.34-2.15 (m, 4H), 1.80-1.72 (m, 1H). Example 11: N-(3-(2-(4-(((1-Acetylpiperidin-4-yl)amino)methyl)-3-methoxy phenyl)-3- chloropyridin-4-yl)-2-methylphenyl)-5-(((2- hydroxyethyl)(methyl)amino)methyl)picolinamide (a) N-(3-(2,3-Dichloropyridin-4-yl)-2-methylphenyl)-5-(((2- hydroxyethyl)(methyl)amino)methyl)picolinamide To a mixture of N-(3-(2,3-dichloropyridin-4-yl)-2-methylphenyl)-5- formylpicolinamide (0.6 g, 1.55 mmol) (Example 6, step (e)) and 2-(methylamino)ethan-1-ol (0.18 g, 2.33 mmol) in THF/methanol mixture (1:1 v/v, 6 mL) was added sodium acetate (0.38 g, 4.66 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 12 hours. Sodium cyanoborohydride (0.29 g, 4.66 mmol) was then added and the mixture stirred at room temperature for 0.5 hours. The mixture was combined with another batch at 200 mg scale. The mixture was concentrated, water (150 mL) and saturated aqueous brine solution (25 mL) added to the residue, and the mixture was extracted with an ethyl acetate/THF mixture (1:1 v/v, 100 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (50-100% ethyl acetate/petroleum ether) to afford N-(3-(2,3- dichloropyridin-4-yl)-2-methylphenyl)-5-(((2- hydroxyethyl)(methyl)amino)methyl)picolinamide (330 mg, 33% yield) as a yellow oil. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.46 (s, 1H), 8.72 (d, 1H), 8.53 (d, 1H), 8.20 (d, 1H), 8.07 (dd, 1H), 7.98 (d, 1H), 7.51 (d, 1H), 7.45 (t, 1H), 7.13 (dd, 1H), 3.73 (s, 2H), 3.59 (t, 2H), 2.53 (t, 2H), 2.26 (s, 3H), 2.10 (s, 3H). (b) N-(3-(3-Chloro-2-(4-formyl-3-methoxyphenyl)pyridin-4-yl)-2-m ethylphenyl)-5- (((2-hydroxyethyl)(methyl)amino)methyl)picolinamide To a mixture of N-(3-(2,3-dichloropyridin-4-yl)-2-methylphenyl)-5-(((2- hydroxyethyl)(methyl)amino)methyl)picolinamide (0.23 g, 0.52 mmol) and 2-methoxy-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde (0.18 g, 0.67 mmol) in 1,4- dioxane/water mixture (5:1 v/v, 3.6 mL) was added potassium phosphate (0.33 g, 1.55 mmol) and [1,1′-bis(di-tert-butylphosphino)ferrocene]dichloropalladi um(II) (0.03 g, 0.05 mmol) in one portion under N ₂ , and the mixture stirred at 110 °C for 6 hours. The mixture was combined with another batch at 100 mg scale. The mixture was concentrated, water (50 mL) and saturated aqueous brine solution (15 mL) added to the residue, and the mixture extracted with an ethyl acetate/THF mixture (1:1 v/v, 50 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-15% methanol/ethyl acetate) to afford N-(3-(3-chloro-2-(4- formyl-3-methoxyphenyl)pyridin-4-yl)-2-methylphenyl)-5-(((2- hydroxyethyl)(methyl)amino)methyl)picolinamide (200 mg, 50% yield) as a white solid. LCMS: m/z found 545 [M+H] ⁺ . (c) N-(3-(2-(4-(((1-Acetylpiperidin-4-yl)amino)methyl)-3-methoxy phenyl)-3- chloropyridin-4-yl)-2-methylphenyl)-5-(((2- hydroxyethyl)(methyl)amino)methyl)picolinamide To a mixture of N-(3-(3-chloro-2-(4-formyl-3-methoxyphenyl)pyridin-4-yl)-2- methylphenyl)-5-(((2-hydroxyethyl)(methyl)amino)methyl)picol inamide (0.19 g, 0.35 mmol) and 1-(4-aminopiperidin-1-yl)ethan-1-one hydrochloride salt (0.1 g, 0.56 mmol) in THF/methanol mixture (1:1 v/v, 2 mL) was added sodium acetate (0.14 g, 1.74 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 1 hour. Sodium cyanoborohydride (0.07 g, 1.05 mmol) was then added and the mixture stirred at room temperature for 0.5 hours. The mixture was combined with another batch at 10 mg scale. The residue was purified by reverse phase HPLC to afford the product as a formic salt (~55 mg). The product was neutralized with saturated aqueous sodium bicarbonate solution. To the mixture was added deionized water (15 mL) and the mixture extracted with dichloromethane (3 x 5 mL). The combined organic phases were concentrated and lyophilized to afford N-(3- (2-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-3-methoxypheny l)-3-chloropyridin-4-yl)-2- methylphenyl)-5-(((2-hydroxyethyl)(methyl)amino)methyl)picol inamide (49.5 mg, 18% yield) as a white solid. LCMS: m/z found 671 [M+H] ⁺ , retention time = 2.51 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.71 (d, 1H), 8.62 (d, 1H), 8.22 (d, 1H), 8.05 (dd, 1H), 8.01 (d, 1H), 7.45-7.40 (m, 3H), 7.31-7.28 (m, 2H), 7.13 (d, 1H), 4.51-4.47 (m, 1H), 3.99-3.90 (m, 6H), 3.78-3.70 (m, 4H), 3.17-3.11 (m, 1H), 2.83-2.67 (m, 2H), 2.63 (t, 2H) 2.31 (s, 3H), 2.20 (s, 3H), 2.12 (s, 3H), 2.10-1.99 (m, 2H), 1.47-1.33 (m, 2H). Example 12: N-(3-(2-(4-(((2-Acetyl-2-azaspiro[3.3]heptan-6-yl)amino)meth yl)-3- methoxyphenyl)-3-chloropyridin-4-yl)-2-chlorophenyl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide (a) tert-Butyl 6-(((benzyloxy)carbonyl)amino)-2-azaspiro[3.3]heptane-2-carb oxylate To a mixture of tert-butyl 6-amino-2-azaspiro[3.3]heptane-2-carboxylate (1 g, 4.71 mmol) and benzyl chloroformate (1.21 g, 7.07 mmol) in dichloromethane (15 mL) was added N,N-diisopropylethylamine (1.8 g, 14.1 mmol) and the mixture stirred at room temperature for 2 hours under N ₂ . Water (10 mL) was added and the mixture extracted with ethyl acetate (2 x 10 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (22-25% ethyl acetate/petroleum ether) to afford tert-butyl 6- (((benzyloxy)carbonyl)amino)-2-azaspiro[3.3]heptane-2-carbox ylate (1.4 g, crude) as a yellow oil. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 7.51-7.49 (m, 1H), 7.32-7.27 (m, 5H), 4.94 (s, 2H), 3.80-3.78 (m, 3H), 3.76-3.68 (m, 2H), 2.36-3.34 (m, 2H), 2.02-1.99 (m, 2H), 1.33 (s, 9H). (b) Benzyl (2-azaspiro[3.3]heptan-6-yl)carbamate To a solution of tert-butyl 6-(((benzyloxy)carbonyl)amino)-2-azaspiro[3.3]heptane-2- carboxylate (1 g, 2.89 mmol) in dichloromethane (5 mL) was added trifluoroacetic acid (5.56 mL, 75.0 mmol) and the mixture stirred at room temperature for 0.5 hours under N ₂ . The mixture was filtered and concentrated to afford benzyl (2-azaspiro[3.3]heptan-6-yl)carbamate (2 g, crude) as a yellow oil. LCMS: m/z found 247 [M+H] ⁺ . The crude product was used for next step without further purification. (c) Benzyl (2-acetyl-2-azaspiro[3.3]heptan-6-yl)carbamate To a mixture of benzyl (2-azaspiro[3.3]heptan-6-yl)carbamate (1.9 g, 8.00 mmol) and acetic anhydride (1.2 g, 12.0 mmol) in dichloromethane (20 mL) was added triethylamine (2.4 g, 23.9 mmol) and the mixture stirred at room temperature for 2 hours under N ₂ . The mixture was filtered and concentrated to give benzyl (2-acetyl-2-azaspiro[3.3]heptan-6- yl)carbamate (900 mg, crude) as a yellow oil. The crude product was used for next step without further purification. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 7.58-7.57 (m, 1H), 7.37-7.32 (m, 5H), 5.00 (s, 2H), 4.12 (s, 1H), 3.91 (s, 1H), 3.87-3.85 (m, 2H), 3.72 (s, 1H), 3.14 (s, 3H), 2.44-2.43 (m, 2H), 2.09-2.08 (m, 2H). (d) 1-(6-Amino-2-azaspiro[3.3]heptan-2-yl)ethan-1-one To a mixture of benzyl (2-acetyl-2-azaspiro[3.3]heptan-6-yl)carbamate (400 mg, 1.39 mmol) in ethanol/methanol (1:1 v/v, 10 mL) was added palladium on carbon (10%, 1.00 g), then the mixture was stirred at 80 °C for 12 hours under hydrogen (50 psi). The mixture was filtered and concentrated to afford 1-(6-amino-2-azaspiro[3.3]heptan-2-yl)ethan-1-one (200 mg, crude) as a white oil. LCMS: m/z found 155 [M+H] ⁺ . The crude product was used for next step without further purification. (e) 2-Chloro-3-(2,3-dichloropyridin-4-yl)aniline To a mixture of 2-chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anil ine (3.8 g, 15 mmol) and 2,3-dichloro-4-iodopyridine (3.5 g, 12.8 mmol) in 1,4-dioxane/water mixture (70:15, 85 mL) was added potassium carbonate (5.3 g, 38.3 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (0.21 g, 0.26 mmo) in one portion under N ₂ . The mixture was stirred at 110 °C for 3 hours. The mixture was concentrated, water (30 mL) and saturated aqueous brine solution (100 mL) added, and the mixture extracted with an ethyl acetate/THF mixture (1:1 v/v, 200 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-15% ethyl acetate/petroleum ether) to afford 2-chloro-3-(2,3-dichloropyridin-4-yl)aniline (2.7 g, 77% yield) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 8.26 (d, 1H), 7.19-7.07 (m, 2H), 6.79 (dd, 1H), 6.52 (dd, 1H). (f) Methyl 6-((2-chloro-3-(2,3-dichloropyridin-4-yl)phenyl)carbamoyl)ni cotinate A mixture of 5-(methoxycarbonyl)picolinic acid (0.5 g, 2.76 mmol) in thionyl chloride (4 mL) was stirred at 80°C for 3 hours under N ₂ . The mixture was concentrated to afford crude methyl 6-(chlorocarbonyl)nicotinate (0.55 g, crude) as a white solid. To a mixture of methyl 6-(chlorocarbonyl)nicotinate (0.55 g, 2.76 mmol) and 2-chloro-3-(2,3- dichloropyridin-4-yl)aniline (0.64 g, 2.34 mmol) in dichloromethane (3 mL) was added triethylamine (1.2 mL, 8.27 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 12 hours. Water (50 mL) was added to the reaction solution and the mixture was filtered. The filter cake was dried to give methyl 6-((2-chloro-3-(2,3-dichloropyridin-4- yl)phenyl)carbamoyl)nicotinate (0.65 g, 54% yield) as a white solid. LCMS: m/z found 436 and 438 [M+H] ⁺ . (g) N-(2-Chloro-3-(2,3-dichloropyridin-4-yl)phenyl)-5-(hydroxyme thyl)picolinamide To a mixture of methyl 6-((2-chloro-3-(2,3-dichloropyridin-4- yl)phenyl)carbamoyl)nicotinate (0.65 g, 1.49 mmol) in methanol/THF mixture (2:5, 70 mL) was added sodium borohydride (0.56 mg, 14.9 mmol) in portions at 0 °C under N ₂ . The mixture was stirred at room temperature for 12 hours. To the mixture was added water (20 mL) to quench sodium borohydride and the mixture was concentrated. To the residue was added water (20 mL) and saturated aqueous brine solution (5 mL) and the mixture extracted with an ethyl acetate/THF mixture (1:1 v/v, 50 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-50% (30% THF in ethyl acetate)/petroleum ether) to afford N- (2-chloro-3-(2,3-dichloropyridin-4-yl)phenyl)-5-(hydroxymeth yl)picolinamide (0.4 g, 65% yield) as a light yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.73 (s, 1H), 8.71 (d, 1H), 8.59 (d, 1H), 8.31 (d, 1H), 8.23 (d, 1H), 7.88 (dd, 1H), 7.38 (t, 1H), 7.13 (d, 1H), 6.93 (dd, 1H), 4.80 (s, 2H). (h) N-(2-Chloro-3-(2,3-dichloropyridin-4-yl)phenyl)-5-formylpico linamide To a mixture of N-(2-chloro-3-(2,3-dichloropyridin-4-yl)phenyl)-5- (hydroxymethyl)picolinamide (1 g, 2.45 mmol) in dichloromethane (10 mL) was added sodium bicarbonate (0.41 g, 4.89 mmol) and Dess-Martin periodinane (1.14 g, 2.69 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 1 hour. The mixture was purified directly without work-up by normal phase SiO ₂ chromatography (0-15% (10% THF in ethyl acetate)/petroleum ether) to afford N-(2-chloro-3-(2,3-dichloropyridin-4-yl)phenyl)- 5-formylpicolinamide (0.37 g, 22% yield) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.78 (s, 1H), 10.24 (s, 1H), 9.24 (s, 1H), 8.54-8.53 (m, 2H), 8.46-8.40 (m, 2H), 7.56 (m, 2H), 7.30 (d, 1H). (i) tert-Butyl ((6-((2-chloro-3-(2,3-dichloropyridin-4-yl)phenyl)carbamoyl) pyridin- 3-yl)methyl)(2-hydroxyethyl)carbamate To a mixture of N-(2-chloro-3-(2,3-dichloropyridin-4-yl)phenyl)-5- formylpicolinamide (0.47 g, 1.16 mmol) and 2-aminoethanol (0.08 g, 1.27 mmol) in dichloromethane/methanol mixture (2:1 v/v, 30 mL) was added sodium acetate and the mixture stirred at room temperature for 12 hours under N ₂ . Sodium cyanoborohydride (0.22 g, 3.47 mmol) was then added and the mixture stirred at room temperature for 1 hour. Di-tert- butyl dicarbonate (0.31 mL, 1.35 mmol) and triethylamine (0.14 mL, 1.04 mmol) were then added in one portion under N ₂ and the mixture was stirred at room temperature for 1 hour. Water (10 mL) was added and the mixture extracted with ethyl acetate (2 x 10 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 10 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (15-50% ethyl acetate/petroleum ether) to afford tert- butyl ((6-((2-chloro-3-(2,3-dichloropyridin-4-yl)phenyl)carbamoyl) pyridin-3-yl)methyl)(2- hydroxyethyl)carbamate (0.47 g, 52% yield) as a yellow oil. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 11.75 (s, 1H), 10.76 (s, 1H), 8.59-8.56 (m, 2H), 8.26 (d, 1H), 8.02 (d, 1H), 7.66-7.61 (m, 2H), 7.32 (dd, 1H), 4.79 (t, 1H), 4.64-4.61 (m, 2H), 3.57-3.54 (m, 2H), 3.33-3.32 (m, 2H), 1.49-1.36 (m, 9H). (j) tert-Butyl ((6-((2-chloro-3-(3-chloro-2-(4-formyl-3-methoxyphenyl)pyrid in-4- yl)phenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)carb amate To a mixture of tert-butyl ((6-((2-chloro-3-(2,3-dichloropyridin-4- yl)phenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)carb amate (0.12 g, 0.22 mmol) and 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ben zaldehyde (0.07 g, 0.28 mmol) in 1,4-dioxane /water mixture (4:1 v/v, 5 mL) was added tetrakis(triphenylphosphine)palladium(0) (0.02 g, 0.02 mmol) and potassium carbonate (0.09 g, 0.65 mmol) in one portion under N ₂ . The mixture was stirred at 110 °C for 3 hours then the mixture was combined with additional batches at 30 mg and 130 mg scale. The combined reaction mixtures were concentrated, water (20 mL) and ethyl acetate (20 mL) added to the residue and the mixture extracted with ethyl acetate (2 x 50 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 50 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-25% ethyl acetate/petroleum ether) to afford tert-butyl ((6-((2-chloro-3- (3-chloro-2-(4-formyl-3-methoxyphenyl)pyridin-4-yl)phenyl)ca rbamoyl)pyridin-3- yl)methyl)(2-hydroxyethyl)carbamate (0.24 g, 72% yield) as a white solid. LCMS: m/z found 651 [M+H] ⁺ . (k) tert-Butyl ((6-((3-(2-(4-(((2-acetyl-2-azaspiro[3.3]heptan-6-yl)amino)m ethyl)-3- methoxyphenyl)-3-chloropyridin-4-yl)-2-chlorophenyl)carbamoy l)pyridin-3- yl)methyl)(2-hydroxyethyl)carbamate To a mixture of tert-butyl ((6-((2-chloro-3-(3-chloro-2-(4-formyl-3- methoxyphenyl)pyridin-4-yl)phenyl)carbamoyl)pyridin-3-yl)met hyl)(2- hydroxyethyl)carbamate (0.08 g, 0.12 mmol) and 1-(6-amino-2-azaspiro[3.3]heptan-2- yl)ethan-1-one (0.11 g, 0.74 mmol) in dichloromethane/methanol mixture (2:1 v/v, 1.5 mL) was added sodium acetate (0.02 g, 0.25 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 1 hour. Sodium cyanoborohydride (0.02 g, 0.37 mmol) was then added and the mixture stirred at room temperature for 1 hour. Water (10 mL) was added and the mixture extracted with ethyl acetate (2 x 5 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 5 mL), dried with anhydrous sodium sulfate, filtered and concentrated to afford tert-butyl ((6-((3-(2-(4-(((2-acetyl-2- azaspiro[3.3]heptan-6-yl)amino)methyl)-3-methoxyphenyl)-3-ch loropyridin-4-yl)-2- chlorophenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)c arbamate (0.1 g, crude) as a colorless solid. LCMS: m/z found 789 [M+H] ⁺ . (l) N-(3-(2-(4-(((2-Acetyl-2-azaspiro[3.3]heptan-6-yl)amino)meth yl)-3- methoxyphenyl)-3-chloropyridin-4-yl)-2-chlorophenyl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide To a mixture of tert-butyl ((6-((3-(2-(4-(((2-acetyl-2-azaspiro[3.3]heptan-6- yl)amino)methyl)-3-methoxyphenyl)-3-chloropyridin-4-yl)-2- chlorophenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)c arbamate (0.1 g, 0.13 mmol) in 1,4-dioxane (2 mL) was added concentrated HCl solution (0.4 mL) in one portion under N ₂ and the mixture stirred at room temperature for 12 hours. The mixture was neutralized with saturated aqueous sodium bicarbonate solution and concentrated. The residue was purified by reverse phase HPLC to afford N-(3-(2-(4-(((2-acetyl-2-azaspiro[3.3]heptan-6- yl)amino)methyl)-3-methoxyphenyl)-3-chloropyridin-4-yl)-2-ch lorophenyl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide (trifluoroacetic acid salt) as a white solid (32 mg). The product was neutralized with saturated aqueous sodium bicarbonate solution. Water (5 mL) was added and the mixture extracted with dichloromethane (2 x 5 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 5 mL), concentrated and lyophilized to afford N-(3-(2-(4-(((2-acetyl-2-azaspiro[3.3]heptan-6-yl)amino)meth yl)-3- methoxyphenyl)-3-chloropyridin-4-yl)-2-chlorophenyl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide (26 mg, 29% yield) as a white solid. LCMS: m/z found 689 [M+H] ⁺ , retention time = 3.79 min (Method A). ¹ H NMR (400 MHz, Methanol- d ₄ ): δ 8.67-8.60 (m, 3H), 8.22 (d, 1H), 8.02 (dd, 1H), 7.50 (t, 1H), 7.40 (d, 1H), 7.35 (d, 1H), 7.24-7.22 (m, 2H), 7.17 (d, 1H), 4.17 (s, 1H), 4.06 (s, 1H), 3.93-3.92 (m, 3H), 3.90 (s, 3H), 3.83 (s, 1H), 3.73 (s, 2H), 3.66 (t, 2H), 3.25-3.15 (m, 1H), 2.73 (t, 2H), 2.43-2.40 (m, 2H), 2.00-1.95 (m, 2H), 1.80 (d, 3H). Example 13: (S)-5-(((1-Acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3-chloro-2- (3-methoxy-4-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)ph enyl)pyridin-4- yl)phenyl)picolinamide (a) tert-Butyl (S)-(4-bromo-2-methoxybenzyl)((5-oxopyrrolidin-2- yl)methyl)carbamate To a mixture of 4-bromo-2-methoxybenzaldehyde (3 g, 14 mmol) and (S)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt (2.31 g, 15.4 mmol) in dichloromethane / methanol mixture (2:1 v/v, 60 mL) was added sodium acetate (3.43 g, 41.9 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 1 hour. Sodium cyanoborohydride (2.63 g, 41.9 mmol) was then added and the mixture stirred at room temperature for 1 hour to give (S)-5-(((4-bromo-2-methoxybenzyl)amino)methyl)pyrrolidin- 2-one (MS: m/z found 313 and 315 [M+H] ⁺ ). Di-tert-butyl dicarbonate (3.2 mL, 14 mmol) and triethylamine (1.9 mL, 14.0 mmol) were then added in one portion under N ₂ and the mixture stirred at room temperature for 2 hours. The mixture was concentrated, water (10 mL) and saturated aqueous brine solution (10 mL) added to the residue, and the mixture extracted with ethyl acetate (20 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (16-90% ethyl acetate/petroleum ether) to afford 3.5 g of product which was further purified by reverse phase HPLC to afford tert-butyl (S)-(4-bromo-2- methoxybenzyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (2.2 g, 62% yield) as a light yellow gum. ¹ H NMR (400 MHz, Chloroform-d) δ 7.28 (s, 1H), 7.11-7.09 (m, 1H), 7.02 (s, 1H), 4.45-4.42 (m, 2H), 3.85-3.84 (m, 4H), 3.31-3.26 (m, 2H), 2.35-2.31 (m, 2H), 2.17-2.07 (m, 1H), 1.88-1.86 (m, 1H), 1.74-1.46 (m, 9H). (b) tert-Butyl (S)-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)benzyl)((5-oxopyrrolidin-2-yl)methyl)carbamate To a mixture of tert-butyl (S)-(4-bromo-2-methoxybenzyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (1.6 g, 3.87 mmol) and bis(pinacolato)diboron (2.46 g, 9.69 mmol) in 1,4-dioxane/THF mixture (4:1 v/v, 10 mL) was added potassium acetate (1.14 g, 11.6 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (0.47 g, 0.58 mmol) in one portion under N ₂ and the mixture stirred at 110 °C for 3 hours. The mixture was concentrated and the residue purified by normal phase SiO ₂ chromatography (25-90% ethyl acetate/petroleum ether) to afford tert-butyl (S)-(2-methoxy- 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)((5-ox opyrrolidin-2- yl)methyl)carbamate (1.6 g, 63% yield) as a red solid. LCMS: m/z found 405 [M+H-tBu] ⁺ . (c) tert-Butyl (S)-(4-(3-chloro-4-(2-chloro-3-(5- (hydroxymethyl)picolinamido)phenyl)pyridin-2-yl)-2-methoxybe nzyl)((5-oxopyrrolidin- 2-yl)methyl)carbamate To a mixture of N-(2-chloro-3-(2,3-dichloropyridin-4-yl)phenyl)-5- (hydroxymethyl)picolinamide (0.2 g, 0.49 mmol) (Example 12, step (g)) and tert-butyl (S)- (2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)be nzyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (0.29 g, 0.64 mmol) in 1,4-dioxane/water mixture (5:1 v/v, 3.6 mL) was added potassium phosphate (0.31 g, 1.47 mmol) and chloro(2-dicyclohexylphosphino-2′,4′,6′- triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl) ]palladium(II) (0.04 g, 0.05 mmol) in one portion under N ₂ and the mixture stirred at 110 °C for 3 hours. Water (20 mL) was added and the mixture extracted with ethyl acetate (2 x 20 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 20 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-15% ethyl acetate/petroleum ether) to afford tert-butyl (S)-(4-(3-chloro-4- (2-chloro-3-(5-(hydroxymethyl)picolinamido)phenyl)pyridin-2- yl)-2-methoxybenzyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (0.1 g, 21 % yield) as a colorless solid. LCMS: m/z found 706 [M+H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d): δ 10.76 (s, 1H), 8.71 (dd, 1H), 8.59- 8.58 (m, 2H), 8.24 (d, 1H), 7.88 (dd, 1H), 7.39 (t, 1H), 7.30 (dd, 1H), 7.24-7.21 (m, 1H), 7.16 (m, 2H), 7.01 (d, 1H), 4.79 (s, 2H), 4.55-4.41 (m, 2H), 3.84-3.80 (m, 4H), 3.29-3.21 (m, 2H), 2.26-2.22 (m, 2H), 2.12-2.05 (m, 1H), 1.72-1.63 (m, 1H), 1.49-1.35 (m, 9H). (d) tert-Butyl (S)-(4-(3-chloro-4-(2-chloro-3-(5-formylpicolinamido)phenyl) pyridin- 2-yl)-2-methoxybenzyl)((5-oxopyrrolidin-2-yl)methyl)carbamat e To a mixture of tert-butyl (S)-(4-(3-chloro-4-(2-chloro-3-(5- (hydroxymethyl)picolinamido)phenyl)pyridin-2-yl)-2-methoxybe nzyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (0.34 g, 0.48 mmol) in dichloromethane (3 mL) was added Dess-Martin periodinane (0.27 g, 0.63 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 2 hours. The mixture was purified directly by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether) to afford tert-butyl (S)-(4-(3-chloro- 4-(2-chloro-3-(5-formylpicolinamido)phenyl)pyridin-2-yl)-2-m ethoxybenzyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (0.58 g, crude) as a colorless solid. LCMS: m/z found 704 [M+H] ⁺ . (e) tert-Butyl (S)-(4-(4-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)picol inamido)-2- chlorophenyl)-3-chloropyridin-2-yl)-2-methoxybenzyl)((5-oxop yrrolidin-2- yl)methyl)carbamate To a mixture of tert-butyl (S)-(4-(3-chloro-4-(2-chloro-3-(5- formylpicolinamido)phenyl)pyridin-2-yl)-2-methoxybenzyl)((5- oxopyrrolidin-2- yl)methyl)carbamate (0.35 g, 0.5 mmol) and 1-(4-aminopiperidin-1-yl)ethan-1-one hydrochloride salt (0.12 g, 0.65 mmol) in dichloromethane /methanol mixture (3:1 v/v, 4 mL) was added sodium acetate (0.11 g, 1.49 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 1 hour. Sodium cyanoborohydride (0.09 g, 1.49 mmol) was added and the mixture stirred at room temperature for 1 hour. Water (15 mL) was added, and the mixture extracted with ethyl acetate (2 x 15 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 15 mL), dried with anhydrous sodium sulfate, filtered and concentrated to afford tert-butyl (S)-(4-(4-(3-(5-(((1-acetylpiperidin-4- yl)amino)methyl)picolinamido)-2-chlorophenyl)-3-chloropyridi n-2-yl)-2-methoxybenzyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (0.25 g, crude) as a colorless solid. LCMS: m/z found 830 [M+H] ⁺ . (f) (S)-5-(((1-Acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3-chloro-2-(3- methoxy-4-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)pheny l)pyridin-4- yl)phenyl)picolinamide To a mixture of tert-butyl (S)-(4-(4-(3-(5-(((1-acetylpiperidin-4- yl)amino)methyl)picolinamido)-2-chlorophenyl)-3-chloropyridi n-2-yl)-2-methoxybenzyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (0.24 g, 0.29 mmol) in 1,4-dioxane (2 mL) was added concentrated HCl solution (0.25 mL) in one portion under N ₂ and the mixture stirred at room temperature for 2 hours. The mixture was neutralized with saturated aqueous sodium bicarbonate solution, the mixture was concentrated and the residue purified by reverse phase HPLC to afford (S)-5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3-chloro-2-(3- methoxy-4-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)pheny l)pyridin-4- yl)phenyl)picolinamide (35.1 mg, 16% yield) as a white solid. LCMS: m/z found 730 [M+H]+ observed, retention time = 3.88 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.68 (d, 1H), 8.65-8.61 (m, 2H), 8.22 (d, 1H), 8.04 (dd, 1H), 7.51 (t, 1H), 7.41-7.38 (m, 2H), 7.26-7.24 (m, 2H), 7.17 (dd, 1H), 4.45-4.40 (m, 1H), 3.94 (s, 2H), 3.91-3.81 (m, 7H), 3.15-3.10 (m, 1H), 2.78-2.63 (m, 4H), 2.33-2.20 (m, 3H), 2.07 (s, 3H), 2.05-1.95 (m, 2H), 1.80-1.76 (m, 1H), 1.37-1.24 (m, 2H). Example 14: (S)-N-(2-Chloro-3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)phenyl)-5-(((3- fluoropropyl)amino)methyl)picolinamide (a) tert-Butyl (S)-(4-(3-chloro-4-(2-chloro-3-(5-formylpicolinamido)phenyl) pyridin- 2-yl)-2-methoxybenzyl)((5-oxopyrrolidin-2-yl)methyl)carbamat e To a mixture of tert-butyl (S)-(4-(3-chloro-4-(2-chloro-3-(5- (hydroxymethyl)picolinamido)phenyl)pyridin-2-yl)-2-methoxybe nzyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (Example 13, step (c)) (0.1 g, 0.14 mmol) in dichloromethane (4 mL) was added manganese dioxide (0.16 g, 1.84 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 2 hourx. The mixture was filtered with Celite® and the filtrate concentrated to afford tert-butyl (S)-(4-(3-chloro-4-(2-chloro-3-(5- formylpicolinamido)phenyl)pyridin-2-yl)-2-methoxybenzyl)((5- oxopyrrolidin-2- yl)methyl)carbamate (0.15 g, crude) as a colorless solid. LCMS: m/z found 704 [M+H] ⁺ . (b) tert-Butyl (S)-(4-(3-chloro-4-(2-chloro-3-(5-(((3- fluoropropyl)amino)methyl)picolinamido)phenyl)pyridin-2-yl)- 2-methoxybenzyl)((5- oxopyrrolidin-2-yl)methyl)carbamate To a mixture of tert-butyl (S)-(4-(3-chloro-4-(2-chloro-3-(5- formylpicolinamido)phenyl)pyridin-2-yl)-2-methoxybenzyl)((5- oxopyrrolidin-2- yl)methyl)carbamate (0.15 g, 0.21 mmol) and 3-fluoropropan-1-amine hydrochloride salt (0.04 g, 0.32 mmol) in THF/methanol mixture (1:1 v/v, 4 mL) was added sodium acetate (0.03 g, 0.43 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 2 hours. Sodium cyanoborohydride (0.04 g, 0.64 mmol) was then added and the mixture stirred at room temperature for 1 hour. Water (5 mL) was added and the mixture extracted with ethyl acetate (2 x 5 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 5 mL), dried with anhydrous sodium sulfate, filtered and concentrated to afford tert-butyl (S)-(4-(3-chloro-4-(2-chloro-3-(5-(((3- fluoropropyl)amino)methyl)picolinamido)phenyl)pyridin-2-yl)- 2-methoxybenzyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (0.09 g, crude) as a colorless solid. LCMS: m/z found 765 [M+H] ⁺ . (c) (S)-N-(2-Chloro-3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)phenyl)-5-(((3- fluoropropyl)amino)methyl)picolinamide To a mixture of tert-butyl (S)-(4-(3-chloro-4-(2-chloro-3-(5-(((3- fluoropropyl)amino)methyl)picolinamido)phenyl)pyridin-2-yl)- 2-methoxybenzyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (0.09 g, 0.11 mmol) in 1,4-dioxane (2 mL) was added concentrated HCl solution (0.2 mL) in one portion under N ₂ and the mixture stirred at room temperature for 1 hour. The mixture was combined with another batch at 5 mg scale. The mixture was neutralized with saturated aqueous sodium bicarbonate solution, concentrated and the residue purified by reverse phase HPLC to afford (S)-N-(2-chloro-3-(3-chloro-2-(3- methoxy-4-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)pheny l)pyridin-4-yl)phenyl)-5- (((3-fluoropropyl)amino)methyl)picolinamide (9 mg, 12% yield) as a white solid. LCMS: m/z found 665 [M+H] ⁺ , retention time = 3.22 min (Method A). ¹ H NMR (400 MHz, Methanol- d4): δ 8.71-8.65 (m, 3H), 8.26 (d, 1H), 8.06 (dd, 1H), 7.55 (t, 1H), 7.45-7.45 (m, 2H), 7.31- 7.28 (m, 2H), 7.21 (dd, 1H), 4.59 (t, 1H), 4.48 (t, 1H), 3.95 (s, 3H), 3.94 (s, 2H), 3.90-3.89 (m, 2H), 3.87-3.82 (m, 1H), 2.78 (t, 2H), 2.72-2.66 (m, 2H), 2.37-2.26 (m, 3H), 2.01-1.88 (m, 2H), 1.84-1.79 (m, 1H). Example 15: (S)-5-(((2-Acetyl-2-azaspiro[3.3]heptan-6-yl)amino)methyl)-N -(2-chloro-3- (3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)phenyl)picolinami de (S)-5-(((2-Acetyl-2-azaspiro[3.3]heptan-6-yl)amino)methyl)-N -(2-chloro-3-(3-chloro- 2-(3-methoxy-4-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl) phenyl)pyridin-4-yl)phenyl) was prepared in a similar fashion to Example 14, replacing 3-fluoropropan-1-amine hydrochloride salt with 1-(6-amino-2-azaspiro[3.3]heptan-2-yl)ethan-1-one hydrochloride salt in step (b). LCMS: m/z found 742 [M+H] ⁺ , retention time = 2.72 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.72-8.63 (m, 3H), 8.25 (d, 1H), 8.04 (dd, 1H), 7.55 (t, 1H), 7.45-7.42 (m, 2H), 7.31-7.29 (m, 2H), 7.22 (dd, 1H), 4.22 (s, 1H), 4.12 (s, 1H), 3.98- 3.94 (m, 4H), 3.90-3.83 (m, 6H), 3.27-3.21 (m, 1H), 2.72-2.66 (m, 2H), 2.52-2.48 (m, 2H), 2.36-2.28 (m, 3H), 2.07-2.01 (m, 2H), 1.85-1.80 (m, 4H). Example 16: (S)-N-(3-(3-Chloro-2-(3-methyl-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide (a) tert-Butyl ((6-((3-(3-chloro-2-(4-formyl-3-methylphenyl)pyridin-4-yl)-2 - methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)c arbamate To a mixture of tert-butyl ((6-((3-(2,3-dichloropyridin-4-yl)-2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)c arbamate (Example 1, step (e)) (140 mg, 0.26 mmol) and 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)benzaldehyde (162 mg, 0.66 mmol) in 1,4-dioxane/water (10:1 v/v, 8.8 mL) was added potassium carbonate (109 mg, 0.79 mmol) and tetrakis(triphenylphosphine)palladium(0) (30.4 mg, 0.03 mmol) in one portion under N ₂ and the mixture stirred at 110 °C for 12 hours. Additional 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benz aldehyde (50 mg) was added and the mixture stirred for another 5 hours at 110 °C. The reaction mixture combined with another batch at 50 mg scale. Saturated aqueous brine solution (15 mL) was added and the mixture extracted with ethyl acetate (100 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-70% ethyl acetate/petroleum ether) to afford tert-butyl ((6-((3-(3-chloro-2-(4-formyl-3-methylphenyl)pyridin-4-yl)-2 - methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)c arbamate (120 mg, 50% yield) as a red oil. LCMS: m/z found 615 [M+H] ⁺ . (b) tert-Butyl (S)-((6-((3-(3-chloro-2-(3-methyl-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)c arbamoyl)pyridin-3- yl)methyl)(2-hydroxyethyl)carbamate To a mixture of tert-butyl ((6-((3-(3-chloro-2-(4-formyl-3-methylphenyl)pyridin-4- yl)-2-methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxye thyl)carbamate (110 mg, 0.18 mmol) and (S)-5-(aminomethyl)pyrrolidin-2-one hydrochloride salt (40.4 mg, 0.27 mmol) in methanol (3 mL) was added sodium acetate (44.0 mg, 0.54 mmol) and the mixture stirred for 2 hours at room temperature. Sodium cyanoborohydride (33.7 mg, 0.54 mmol) was then added and the mixture stirred for another 10 hours at room temperature. The reaction mixture was concentrated under reduced pressure and the residue purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether to 0-30% methanol/ethyl acetate) to afford tert-butyl (S)-((6-((3-(3-chloro-2-(3-methyl-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)c arbamoyl)pyridin-3- yl)methyl)(2-hydroxyethyl)carbamate (115 mg, 90% yield) as an off-white solid. (c) (S)-N-(3-(3-chloro-2-(3-methyl-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide A mixture of tert-butyl (S)-((6-((3-(3-chloro-2-(3-methyl-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)c arbamoyl)pyridin-3- yl)methyl)(2-hydroxyethyl)carbamate (110 mg, 0.15 mmol) and trifluoroacetic acid (1 mL, 13.5 mmol) in dichloromethane (3 mL) was stirred for 1 hour at room temperature. The mixture was concentrated under reduced pressure and the residue purified by reverse phase HPLC to afford (S)-N-(3-(3-chloro-2-(3-methyl-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide (44.5 mg, 44% yield) as a white solid. LCMS: m/z found 613 [M +H] ⁺ , retention time = 2.42 min (Method A). ¹ H NMR (400 MHz, Methanol- d ₄ ): δ 8.70 (d, 1H), 8.58 (d, 1H), 8.21 (d, 1H), 8.04 (dd, 1H), 7.98 (d, 1H), 7.50-7.45 (m, 3H), 7.42-7.37 (m, 2H), 7.11 (d, 1H), 3.96 (s, 2H), 3.92-3.84 (m, 3H), 3.70 (t, 2H), 2.81-2.71 (m, 4H), 2.45 (s, 3H), 2.36-2.25 (m, 3H), 2.18 (s, 3H), 1.86-1.81 (m, 1H). Example 17: (S)-N-(3-(3-Chloro-2-(3-ethyl-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide (S)-N-(3-(3-chloro-2-(3-ethyl-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl) was prepared in a similar fashion to Example 16, replacing 2- methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzal dehyde with 2-ethyl-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde in step (a). LCMS: m/z found 627 [M+H] ⁺ , retention time = 2.58 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.70 (d, 1H), 8.59 (d, 1H), 8.21 (d, 1H), 8.03 (dd, 1H), 7.99 (d, 1H), 7.52-7.49 (m, 3H), 7.42-7.36 (m, 2H), 7.10 (d, 1H), 3.95 (s, 2H), 3.90 (d, 2H), 3.87-3.68 (m, 1H), 2.85-2.72 (m, 6H), 2.36-2.26 (m, 3H), 2.18 (s, 3H), 1.86-1.82 (m, 1H), 1.29 (t, 3H). Example 18: (S)-N-(3-(3-Chloro-2-(3-fluoro-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide (S)-N-(3-(3-chloro-2-(3-fluoro-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl) was prepared in a similar fashion to Example 16, replacing 2- methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzal dehyde with 2-fluoro-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde in step (a). LCMS: m/z found 617 [M+H] ⁺ , retention time = 2.30 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.69 (d, 1H), 8.60 (d, 1H), 8.20 (d, 1H), 8.03 (dd, 1H), 7.99 (d, 1H), 7.57 (t, 1H), 7.51 (dd, 1H), 7.46- 7.38 (m, 3H), 7.11 (d, 1H), 3.97-3.92 (m, 4H), 3.84-3.81 (m, 1H), 3.69 (t, 2H), 2.76 (t, 2H), 2.72-2.65 (m, 2H), 2.35-2.24 (m, 3H), 2.17 (s, 3H), 1.84-1.79 (m, 1H). Example 19: (S)-N-(3-(3-Chloro-2-(3-chloro-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide (S)-N-(3-(3-Chloro-2-(3-chloro-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide was prepared in a similar fashion to Example 16, replacing 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benz aldehyde with 2- chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzal dehyde in step (a). m/z: 633 [M+H] ⁺ , retention time = 2.80 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.70 (d, 1H), 8.61 (d, 1H), 8.21 (d, 1H), 8.03 (dd, 1H), 7.99 (d, 1H), 7.74 (s, 1H), 7.67-7.62 (m, 2H), 7.42-7.38 (m, 2H), 7.11 (d, 1H), 3.99 (d, 2H), 3.95 (s, 2 H), 3.86-3.83 (m, 1H), 3.69 (t, 2H), 2.78-2.71 (m, 4H), 2.37-2.27 (m, 3H), 2.17 (s, 3H), 1.87-1.79 (m, 1H). Example 20: (S)-N-(3-(3'-Chloro-4-fluoro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide (a) tert-Butyl (2-hydroxyethyl)((6-((2-methyl-3-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)phenyl)carbamoyl)pyridin-3-yl)methyl)carba mate To a mixture of tert-butyl ((6-((3-bromo-2-methylphenyl)carbamoyl)pyridin-3- yl)methyl)(2-hydroxyethyl)carbamate (Example 1, step (d)) (1 g, 2.15 mmol) and bis(pinacolato)diboron (1.64 g, 6.46 mmol) in 1,4-dioxane (8 mL) was added potassium acetate (634 mg, 6.46 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (176 mg, 0.22 mmol) and the mixture stirred at 110 °C for 3 hours under N ₂ . The mixture was concentrated and the residue was purified by normal phase SiO ₂ chromatography (10-50 % ethyl acetate / petroleum ether) to afford tert-butyl (2-hydroxyethyl)((6-((2-methyl-3-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamoyl)pyridin -3-yl)methyl)carbamate (800 mg, 79% yield) as a white solid. LCMS: m/z found 512 [M+H] ⁺ . (b) 2',3'-Dichloro-4-fluoro-6-methoxy-[2,4'-bipyridine]-5-carbal dehyde To a mixture of 6-chloro-4-fluoro-2-methoxynicotinaldehyde (0.80 g, 4.22 mmol) and 2,3-dichloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine (1.73 g, 6.33 mmol) in THF/water (5:1 v/v, 12 mL) was added potassium phosphate (2.69 g, 12.7 mmol) and [1,1′- bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) (0.28 mg, 0.42 mmol), and then the mixture stirred at 80 °C for 2 hours under N ₂ . Water (10 mL) was then added, and the mixture extracted with ethyl acetate (2 x 20 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-25 % ethyl acetate / petroleum ether) to afford 2',3'-dichloro-4-fluoro-6-methoxy-[2,4'-bipyridine]-5-carbal dehyde (680 mg, 53% yield) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.26 (s, 1H), 8.57 (d, 1H), 7.75 (d, 1H), 7.56 (d, 1H), 4.06 (s, 3H). (c) tert-Butyl (S)-((2',3'-dichloro-4-fluoro-6-methoxy-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate To a mixture of 2',3'-dichloro-4-fluoro-6-methoxy-[2,4'-bipyridine]-5-carbal dehyde (400 mg, 1.33 mmol) and (S)-5-(aminomethyl)pyrrolidin-2-one hydrochloride salt (400 mg, 2.66 mmol) in methanol/dichloromethane (1:1 v/v, 6 mL) was added sodium acetate (327 mg, 3.99 mmol), and then the mixture stirred at room temperature for 2.5 hours under N ₂ . Sodium cyanoborohydride (250 mg, 3.99 mmol) was then added and the mixture stirred at room temperature for 0.5 hours under N ₂ to afford (S)-5-((((2',3'-dichloro-4-fluoro-6-methoxy- [2,4'-bipyridin]-5-yl)methyl)amino)methyl)pyrrolidin-2-one (MS: m/z found 399 [M+H] ⁺ ). Di-tert-butyl dicarbonate (956 mg, 4.38 mmol) and triethylamine (0.70 mL, 5.01 mmol) were then added, and the mixture stirred at room temperature for 2 hours under N ₂ . Water (10 mL) was added, and the mixture extracted with ethyl acetate (2 x 10 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-100 % ethyl acetate / petroleum ether) to afford tert-butyl (S)-((2',3'-dichloro-4-fluoro-6-methoxy-[2,4'-bipyridin]- 5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (500 mg, 55% yield) as a yellow solid. LCMS: m/z found 499 [M+H] ⁺ . (d) tert-Butyl (S)-((6-((3-(5-(((tert-butoxycarbonyl)((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-3'-chloro-4-fluoro-6-methoxy-[2,4'-b ipyridin]-2'-yl)-2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)c arbamate To a mixture of tert-butyl (S)-((2',3'-dichloro-4-fluoro-6-methoxy-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (100 mg, 0.20 mmol) and tert-butyl (2- hydroxyethyl)((6-((2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dio xaborolan-2- yl)phenyl)carbamoyl)pyridin-3-yl)methyl)carbamate (154 mg, 0.30 mmol) in 1,4- dioxane/water (3:1 v/v, 4 mL) was added potassium carbonate (69.2 mg, 0.50 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (22 mg, 0.030 mmol), and the mixture was stirred at 100 °C for 5 hours under N ₂ . Water (15 mL) was added and the mixture extracted with EtOAc (100 mL). The organic phase was dried over anhydrous sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-100 % EtOAc / petroleum ether) to afford tert-butyl (S)-((6-((3-(5-(((tert-butoxycarbonyl)((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-3'-chloro-4-fluoro-6-methoxy-[2,4'-b ipyridin]-2'-yl)-2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)c arbamate (115 mg, 36% yield) as a yellow oil. LCMS: m/z found 848 [M+H] ⁺ . (e) (S)-N-(3-(3'-Chloro-4-fluoro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide To a mixture of tert-butyl (S)-((6-((3-(5-(((tert-butoxycarbonyl)((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-3'-chloro-4-fluoro-6-methoxy-[2,4'-b ipyridin]-2'-yl)-2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)c arbamate (90 mg, 0.11 mmol) in dichloromethane (3 mL) was added trifluoroacetic acid (1 mL, 13.5 mmol), and the mixture stirred at room temperature for 0.5 hours under N ₂ . The mixture was concentrated and the residue purified by reverse phase HPLC to afford (S)-N-(3-(3'-Chloro-4-fluoro-6- methoxy-5-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4 '-bipyridin]-2'-yl)-2- methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)picolinamide (13.0 mg, 18 % yield) as a white solid. LCMS: m/z found 648 [M+H] ⁺ , retention time = 2.28 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.71 (d, 1H), 8.66 (d, 1H), 8.22 (d, 1H), 8.08-8.04 (m, 2H), 7.76 (d, 1H), 7.43 (t, 1H), 7.33 (d, 1H), 7.21 (d, 1H), 4.09 (s, 3H), 3.96 (s, 2H), 3.92 (s, 2H), 3.85- 3.80 (m, 1H), 3.71 (t, 2H), 2.78 (t, 2H), 2.73-2.67 (m, 2H), 2.37-2.20 (m, 3H), 2.18 (s, 3H), 1.84-1.78 (m, 1H). Example 21: (S)-N-(3-(3'-Chloro-6-(difluoromethoxy)-5-((((5-oxopyrrolidi n-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide (a) Methyl 6-chloro-2-hydroxynicotinate To a mixture 6-chloro-2-hydroxynicotinic acid (3.7 g, 21.3 mmol) in MeOH (37 mL) was added concentrated sulfuric acid (2.77 mL), and the mixture stirred at 60 °C for 4 hours under N ₂ . The mixture was concentrated and the residue neutralized with saturated sodium bicarbonate solution, then extracted with EtOAc (2 x 200 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford methyl 6-chloro-2-hydroxynicotinate (2.5 g, 62% yield) as a white solid. The product was used in the next step without further purification. ¹ H NMR (400 MHz, DMSO- d6): δ 12.31 (br s, 1H), 8.14 (d, 1H), 7.04 (d, 1H), 3.82 (s, 3H). (b) Methyl 6-chloro-2-(difluoromethoxy)nicotinate To a mixture of methyl 6-chloro-2-hydroxynicotinate (1 g, 5.33 mmol) in dichloromethane (15 mL) was added potassium hydroxide (1.79 g, 32.0 mmol) in water (9 mL). (bromodifluoromethyl)trimethylsilane (2.27 g, 11.20 mmol, 2.1 eq) was then added and the mixture stirred at room temperature for 12 hours under N ₂ . Water (20 mL) was then added and the mixture extracted with EtOAc (2 x 50 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-15 % EtOAc / petroleum ether) to afford methyl 6-chloro-2-(difluoromethoxy)nicotinate (350 mg, 27% yield) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 8.38 (d, 1H), 7.73 (t, 1H), 7.55 (d, 1H), 3.88 (s, 3H). (c) (6-Chloro-2-(difluoromethoxy)pyridin-3-yl)methanol To a mixture of methyl 6-chloro-2-(difluoromethoxy)nicotinate (160 mg, 0.67 mmol) in THF/methanol (1:1 v/v, 6 mL) was added sodium borohydride (415 mg, 11.0 mmol) at 0°C, and the mixture stirred at room temperature for 6 hours under N ₂ . The mixture was combined with another two batches at the same scale. To the combined mixture was added saturated ammonium chloride solution (20 mL) and the mixture extracted with EtOAc (2 x50 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-20 % EtOAc / petroleum ether) to afford 6-chloro-2- (difluoromethoxy)pyridin-3-yl)methanol (62 mg, 61% yield) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 8.02 (d, 1H), 7.72 (t, 1H), 7.47 (d, 1H), 5.54 (t, 1H), 4.54 (d, 1H). (d) 6-Chloro-2-(difluoromethoxy)nicotinaldehyde To a mixture of 6-chloro-2-(difluoromethoxy)pyridin-3-yl)methanol (140 mg, 0.67 mmol) in dichloromethane (5 mL) was added manganese dioxide (581 mg, 6.68 mmol) and the mixture stirred at room temperature for 12 h. The mixture was filtered and washed with dichloromethane (100 mL) and the filtrat concentrated under reduce pressure to afford 6- chloro-2-(difluoromethoxy)nicotinaldehyde (100 mg, 72% yield) as a light yellow solid. The product was used in the next step without further purification.1H NMR (400 MHz, Chloroform-d): δ 10.26 (s, 1H), 8.14 (d, 1H), 7.51 (t, 1H), 7.21 (d, 1H). (e) 2',3'-Dichloro-6-(difluoromethoxy)-[2,4'-bipyridine]-5-carba ldehyde To a mixture of 6-chloro-2-(difluoromethoxy)nicotinaldehyde (65 mg, 0.313 mmol) in 1,4-dioxane/water (5:1 v/v, 2.4 mL) was added 2,3-dichloro-4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)pyridine (85.8 mg, 0.313 mmol), potassium carbonate (130 mg, 0.939 mmol) and tetrakis(triphenylphosphine)palladium(0) (36.2 mg, 0.031 mmol), and the reaction stirred at 95 °C for 4 hours under N ₂ . The mixture was combined with another batch at the 50 mg scale, water (10 mL) added and the mixture extracted with EtOAc (80 mL). The organic phase was dried over anhydrous sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-30 % EtOAc / petroleum ether) to afford 2',3'-dichloro-6-(difluoromethoxy)-[2,4'-bipyridine]-5-carba ldehyde (100 mg, 60% yield) as a white solid. ¹ H NMR (400 MHz, Chloroform-d): δ 10.45 (s, 1H), 8.44 (d, 1H), 8.41 (d, 1H), 7.67-7.27 (m, 3H). (f) tert-Butyl ((6-((3-(3'-chloro-6-(difluoromethoxy)-5-formyl-[2,4'-bipyri din]-2'-yl)- 2-methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl )carbamate To a mixture of 2',3'-dichloro-6-(difluoromethoxy)-[2,4'-bipyridine]-5-carba ldehyde (60 mg, 0.188 mmol), tert-butyl (2-hydroxyethyl)((6-((2-methyl-3-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)phenyl)carbamoyl)pyridin-3-yl)methyl)carba mate (Example 20, step (a)) (125 mg, 0.244 mmol) in THF/water (5:1 v/v, 3.6 mL) was added potassium phosphate (120 mg, 0.564 mmol), chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1 ,1′-biphenyl)[2-(2′- amino-1,1′-biphenyl)]palladium(II) (14.8 mg, 0.018 mmol), and the mixture stirred at 80 °C for 12 hours under N ₂ . The mixture was combined with another batch at the 30 mg scale. Water (5 mL) was added and the mixture extracted with EtOAc (2 x10 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by prep-TLC (SiO ₂ , EtOAc: petroleum ether = 1:0) to afford tert-butyl ((6-((3-(3'-chloro-6-(difluoromethoxy)-5-formyl-[2,4'-bipyri din]-2'- yl)-2-methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxye thyl)carbamate (70 mg, 37% yield) as a yellow oil. LCMS: m/z found 668 [M+H] ⁺ . (g) tert-Butyl (S)-((6-((3-(3'-chloro-6-(difluoromethoxy)-5-((((5-oxopyrrol idin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)carbamoyl)pyridin-3- yl)methyl)(2-hydroxyethyl)carbamate To a mixture of tert-butyl ((6-((3-(3'-chloro-6-(difluoromethoxy)-5-formyl-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)carbamoyl)pyridin-3-yl)meth yl)(2-hydroxyethyl)carbamate (65 mg, 0.097 mmol) and (S)-5-(aminomethyl)pyrrolidin-2-one hydrochloride salt (22 mg, 0.146 mmol) in dichloromethane/methanol (1:1 v/v, 6 mL) was added sodium acetate (23.9 mg, 0.292 mmol), and the mixture was stirred at room temperature for 1.5 hours under N ₂ . Sodium cyanoborohydride (18.3 mg, 0.292 mmol) was then added and the mixture stirred at room temperature for 0.5 hours under N ₂ . The mixture was then concentrated and the residue purified by prep-TLC (SiO ₂ , EtOAc:MeOH = 4:1 v/v) to afford tert-butyl (S)-((6-((3-(3'- chloro-6-(difluoromethoxy)-5-((((5-oxopyrrolidin-2-yl)methyl )amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)carbamoyl)pyridin-3-yl)meth yl)(2-hydroxyethyl)carbamate (40 mg, 53% yield) as a white solid. LCMS: m/z found 766 [M+H] ⁺ . (h) (S)-N-(3-(3'-Chloro-6-(difluoromethoxy)-5-((((5-oxopyrrolidi n-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide To a mixture of tert-butyl (S)-((6-((3-(3'-chloro-6-(difluoromethoxy)-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)c arbamate (35 mg, 0.05 mmol) in dichloromethane (3 mL) was added trifluoroacetic acid (1 mL, 13.5 mmol), and the mixture stirred at room temperature for 10 min under N ₂ . The mixture was concentrated and the residue purified by reverse phase HPLC to afford (S)-N-(3-(3'-chloro-6- (difluoromethoxy)-5-((((5-oxopyrrolidin-2-yl)methyl)amino)me thyl)-[2,4'-bipyridin]-2'-yl)-2- methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)picolinamide (10.9 mg, 35% yield) as a white solid. LCMS: m/z found 666 [M+H] ⁺ , retention time = 2.44 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.76 (s, 1H), 8.67 (d, 1H), 8.26 (d, 1H), 8.11-8.05 (m, 3H), 7.87- 7.51 (m, 3H), 7.44 (t, 1H), 7.22 (d, 1H), 4.12 (s, 2H), 3.94-3.93 (m, 2H), 3.90-3.87 (m, 1H), 3.76 (t, 1H), 2.95-2.92 (m, 2H), 2.81-2.70 (m, 2H), 2.39-2.28 (m, 3H), 2.18 (s, 3H), 1.89-1.86 (m, 1H). Example 22: (S)-N-(3-(3-Chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 2-fluoro-4-(((2- hydroxyethyl)amino)methyl)benzamide (a) Methyl 4-((3-bromo-2-methylphenyl)carbamoyl)-3-fluorobenzoate To a mixture of 2-fluoro-4-(methoxycarbonyl)benzoic acid (1.00 g, 5.05 mmol) in DMF (30 mL) was added 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5- b]pyridinium 3-oxide hexafluorophosphate (HATU) (2.88 g, 7.57 mmol) and N,N- diisopropylethylamine (1.63 g, 12.6 mmol), and the mixture stirred at room temperature for 0.5 h.3-Bromo-2-methylaniline (1.03 g, 5.55 mmol) was then added and the mixture stirred at room temperature for 12 hours under N ₂ . Water (25 mL) was added and the mixture filtered to give an off-white solid. The solid was dried under reduced pressure to afford methyl 4-((3-bromo-2-methylphenyl)carbamoyl)-3-fluorobenzoate (2.8 g, crude) as a yellow solid. The product was used in the next step without further purification. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.34 (s, 1H), 7.94-7.85 (m, 3H), 7.56 (d, 1H), 7.45 (d, 1H), 7.23-7.19 (m, 1H), 3.92 (s, 3H), 2.34 (s, 3H). (b) N-(3-Bromo-2-methylphenyl)-2-fluoro-4-(hydroxymethyl)benzami de To a mixture of methyl 4-((3-bromo-2-methylphenyl)carbamoyl)-3-fluorobenzoate (2.3 g, 6.28 mmol) in methanol/THF (1:1 v/v, 60 mL) was added sodium borohydride (2.85 g, 75.4 mmol) in portions at 0 °C under N ₂ . The mixture was then stirred at room temperature for 12 hours under N ₂ . Water (200 mL) was added and the mixture and extracted with EtOAc (2 x 300 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford N-(3-bromo-2-methylphenyl)-2- fluoro-4-(hydroxymethyl)benzamide (1.23 g, 58% yield) as a yellow solid. The product was used in the next step without further purification. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.08 (s, 1H), 7.75 (t, 1H), 7.58 (d, 1H), 7.50-7.48 (m, 1H), 7.34-7.32 (m, 2H), 7.26-7.24 (m, 1H), 5.51 (t, 1H), 4.64 (d, 2H), 2.38 (s, 3H). (c) N-(3-Bromo-2-methylphenyl)-2-fluoro-4-formylbenzamide To a mixture of N-(3-bromo-2-methylphenyl)-2-fluoro-4-(hydroxymethyl)benzami de (0.70 g, 2.07 mmol) in dichloromethane (30 mL) was added 1,1,1-Tris(acetyloxy)-1,1- dihydro-1,2-benziodoxol-3-(1H)-one (Dess-Martin periodinane) (1.05 g, 2.48 mmol), and the mixture stirred at room temperature for 12 hours under N ₂ . The mixture was combined with another batch at the 0.75 g scale. Water (100 mL) was added and the mixture extracted with EtOAc (2 x 100 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-32 % EtOAc/petroleum ether) to afford N-(3-bromo-2- methylphenyl)-2-fluoro-4-formylbenzamide (1.10 g, 76% yield) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.36 (s, 1H), 10.09 (s, 1H), 7.98-7.87 (m, 3H), 7.57 (d, 1H), 7.46 (d, 1H), 7.24-7.20 (m, 1H), 2.35 (s, 3H). (d) tert-Butyl (4-((3-bromo-2-methylphenyl)carbamoyl)-3-fluorobenzyl)(2- hydroxyethyl)carbamate To a mixture of N-(3-bromo-2-methylphenyl)-2-fluoro-4-formylbenzamide (0.80 g, 2.38 mmol) and 2-aminoethan-1-ol (436 mg, 7.14 mmol) in methanol/dichloromethane (1:1 v/v, 30 mL) was added sodium acetate (1.95 g, 23.8 mmol), and the mixture stirred at room temperature for 11.5 h. Sodium cyanoborohydride (1.79 g, 28.6 mmol) was added to the mixture and stirring continued at room temperature for 0.5 h. A solution di-tert-butyl dicarbonate (1.29 g, 5.90 mmol) in dichloromethane (5 mL) was added followed by triethylamine (0.72 g, 7.08 mmol), and the mixture stirred at room temperature for 12 hours under N ₂ . The mixture was concentrated and the residue purified by normal phase SiO ₂ chromatography (0-54 % EtOAc/petroleum ether) to afford tert-butyl (4-((3-bromo-2- methylphenyl)carbamoyl)-3-fluorobenzyl)(2-hydroxyethyl)carba mate (1.3 g, crude) as a green oil. LCMS: m/z found 503 [M+Na] ⁺ . (e) tert-Butyl (4-((3-(2,3-dichloropyridin-4-yl)-2-methylphenyl)carbamoyl)- 3- fluorobenzyl)(2-hydroxyethyl)carbamate To a mixture of tert-butyl 4-((3-bromo-2-methylphenyl)carbamoyl)-3-fluorobenzyl(2- hydroxyethyl)carbamate (1.00 g, 2.08 mmol) and 2,3-dichloro-4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)pyridine (0.85 g, 3.12 mmol) in 1,4-dioxane/water (5:1 v/v, 25 mL) was added potassium phosphate (1.32 g, 6.23 mmol) and [1,1′-bis(di-tert- butylphosphino)ferrocene]dichloropalladium(II) (0.13 g, 0.21 mmol), and the mixture stirred at 80 °C for 3 hours under N ₂ . The mixture was combined with another batch at the 0.2 g scale. The mixture was concentrated and the residue purified by normal phase SiO ₂ chromatography (0-68 % EtOAc/petroleum ether) to afford tert-butyl (4-((3-(2,3- dichloropyridin-4-yl)-2-methylphenyl)carbamoyl)-3-fluorobenz yl)(2-hydroxyethyl)carbamate (0.33 g, crude) as a yellow oil. LCMS: m/z found 492 [M+H-t-Bu] ⁺ . (f) tert-Butyl (4-((3-(3-chloro-2-(4-formyl-3-methoxyphenyl)pyridin-4-yl)-2 - methylphenyl)carbamoyl)-3-fluorobenzyl)(2-hydroxyethyl)carba mate To a mixture of tert-butyl 4-((3-(2,3-dichloropyridin-4-yl)-2- methylphenyl)carbamoyl)-3-fluorobenzyl(2-hydroxyethyl)carbam ate (200 mg, 0.36 mmol) and 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ben zaldehyde (143 mg, 0.55 mmol) in 1,4-dioxane/water (5:1 v/v, 18 mL) was added tetrakis(triphenylphosphine)palladium(0) (42.1 mg, 0.04 mmol) and potassium carbonate (151 mg, 1.09 mmol), and the mixture stirred at 110 °C for 3 hours under N ₂ . The mixture was then concentrated and the residue purified by normal phase SiO ₂ chromatography (0-88 % EtOAc/petroleum ether) to afford tert-butyl (4-((3-(3-chloro-2-(4-formyl-3- methoxyphenyl)pyridin-4-yl)-2-methylphenyl)carbamoyl)-3-fluo robenzyl)(2- hydroxyethyl)carbamate (140 mg, 59% yield) as a yellow oil. LCMS: m/z found 648 [M+H] ⁺ . (g) tert-Butyl (S)-(4-((3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)c arbamoyl)-3- fluorobenzyl)(2-hydroxyethyl)carbamate To a mixture of tert-butyl 4-((3-(3-chloro-2-(4-formyl-3-methoxyphenyl)pyridin-4- yl)-2-methylphenyl)carbamoyl)-3-fluorobenzyl(2-hydroxyethyl) carbamate (120 mg, 0.185 mmol) and (S)-5-(aminomethyl)pyrrolidin-2-one hydrochloride salt (55.8 mg, 0.37 mmol) in dichloromethane/methanol (1:1 v/v, 10 mL) was added sodium acetate (45.6 mg, 0.555 mmol), then the mixture was stirred at room temperature for 11.5 h, sodium cyanoborohydride (34.9 mg, 0.555 mmol) was added to the mixture. The mixture was stirred at room temperature for 0.5 hours under N ₂ . The mixture was then concentrated to give tert- butyl (S)-(4-((3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)c arbamoyl)-3- fluorobenzyl)(2-hydroxyethyl)carbamate (260 mg, crude) as a yellow solid. LCMS: m/z found 746 [M+H] ⁺ . The crude product was used in the next step without further purification. (h) (S)-N-(3-(3-Chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 2-fluoro-4-(((2- hydroxyethyl)amino)methyl)benzamide To a mixture of tert-butyl (S)-(4-((3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)c arbamoyl)-3- fluorobenzyl)(2-hydroxyethyl)carbamate (0.24 g, 0.32 mmol) in dichloromethane (3 mL) was added trifluoroacetic acid (2.31 g, 20.0 mmol), and the mixture stirred at room temperature for 0.5 hours under N ₂ . The mixture was concentrated and the residue purified by reverse phase HPLC to afford (S)-N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 2-fluoro-4-(((2- hydroxyethyl)amino)methyl)benzamide (53.5 mg, 25% yield) as a white solid. LCMS: m/z found 646 [M+H] ⁺ , retention time = 2.37 min (Method A). ¹ H NMR (400 MHz, Methanol- d ₄ ): δ 8.63 (d, 1H), 7.89 (t, 1H), 8.64 (d, 1H), 7.46-7.40 (m, 5H), 7.33-7.29 (m, 2H), 7.18 (d, 1H), 4.08 (s, 2H), 4.04-4.00 (m, 2H), 3.96 (s, 3H), 3.91-3.88 (m, 1H), 3.78-3.75 (m, 2H), 2.94-2.92 (m, 2H), 2.85-2.80 (m, 2H), 2.38-2.29 (m, 3H), 2.16 (s, 3H), 1.86-1.79 (m, 1H). Example 23: (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 2- hydroxyethyl)amino)methyl)picolinamide (a) 2',3'-Dichloro-6-methoxy-[2,4'-bipyridine]-5-carbaldehyde A mixture of 2,3-dichloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine (1.00 g, 3.65 mmol), 6-chloro-2-methoxy-pyridine-3-carbaldehyde (0.69 g, 4.02 mmol), potassium carbonate (1.51 g, 10.95 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.21 g, 0.18 mmol) in degassed 1,4-dioxane/water (5:1) was stirred at 80 ºC for 2 hours. The reaction mixture was cooled to room temperature, diluted with water, and extracted with dichloromethane. The combined organic phases were dried over sodium sulfate and concentrated under reduced pressure. Purification on silica gel column afforded 2',3'- dichloro-6-methoxy-[2,4'-bipyridine]-5-carbaldehyde (0.72 g, 69% yield). LCMS: m/z found 283.0 [M+H] ⁺ , retention time = 1.01 min (Method B). (b) (S)-5-((((2',3'-Dichloro-6-methoxy-[2,4'-bipyridin]-5- yl)methyl)amino)methyl)pyrrolidin-2-one A mixture of 2',3'-dichloro-6-methoxy-[2,4'-bipyridine]-5-carbaldehyde (130 mg, 0.46 mmol), (S)-5-(aminomethyl)pyrrolidin-2-one (58 mg, 0.51 mmol) and acetic acid (13 µL, 14 mg, 0.23 mmol) in MeOH/THF (1:1 v/v) was stirred for 1 hour at room temperature . Sodium cyanoborohydride (32 mg, 0.51 mmol) was added and the mixture stirred for an additional 30 minutes then quenched with water. After concentration of the mixture and extraction into dichloromethane, the organic layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure to give (S)-5-((((2',3'-dichloro-6-methoxy-[2,4'- bipyridin]-5-yl)methyl)amino)methyl)pyrrolidin-2-one. LCMS: m/z found 381.1 [M+H] ⁺ , retention time = 0.65 min (Method B). The crude product was used in the next step without further purification. (c) tert-Butyl (S)-((2',3'-dichloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl) ((5- oxopyrrolidin-2-yl)methyl)carbamate To a solution of (S)-5-((((2',3'-dichloro-6-methoxy-[2,4'-bipyridin]-5- yl)methyl)amino)methyl)pyrrolidin-2-one (140 mg, 0.37 mmol) in dichloromethane was added di-tert-butyl dicarbonate (104 mg, 0.48 mmol) and DMAP (9 mg, 0.07 mmol). The mixture was stirred for 2 hours, concentrated under reduced pressure, and purified on silica gel column using MeOH in dichloromethane (0 to 10% gradient) as eluent to afford tert-butyl (S)-((2',3'-dichloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl) ((5-oxopyrrolidin-2- yl)methyl)carbamate. LCMS: m/z found 481.1 [M+H] ⁺ , retention time = 1.01 min (Method B). (d) N-(2-Chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)p henyl)-5- (dimethoxymethyl)picolinamide To a solution of 5-(dimethoxymethyl)pyridine-2-carboxylic acid (0.93 g, 4.73 mmol) and HATU (1.80 g, 4.73 mmol) in DMF was added N,N-diisopropylethylamine (0.82 mL, 0.61 g, 4.73 mmol). After stirring 10 minutes, 2-chloro-3-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)aniline (0.30 g, 1.18 mmol) was added in portions and the reaction mixture was stirred over the weekend at room temperature. The mixture was diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by flash column chromatography to give N-(2-chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl)-5-(dimethoxymethyl)picolinamide. LCMS: m/z found 433.2 [M+H] ⁺ , retention time = 1.22 min (Method B). (e) N-(2-Chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)p henyl)-5- formylpicolinamide A mixture of N-[2-chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)p henyl]-5- (dimethoxymethyl)pyridine-2-carboxamide (100 mg, 0.23 mmol) and trifluoroacetic acid (2 mL) was stirred at room temperature for 2 hours. Excess trifluoroacetic acid was evaporated and the resulting mixture neutralized to pH=8 with saturated aqueous sodium hydrogen carbonate and extracted with dichloromethane three times. The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure to give N-(2- chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl )-5-formylpicolinamide (89 mg, 99% yield), which was used in the next step without further purification. LCMS: m/z found 387.1 [M+H] ⁺ , retention time = 1.12 min (Method B). (f) tert-Butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-formylpicolinamido)phenyl) -6- methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl) methyl)carbamate A mixture of tert-butyl (S)-((2',3'-dichloro-6-methoxy-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (180 mg, 0.37 mmol), N-(2-chloro-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-5-formy lpicolinamide (145 mg, 0.37 mmol), potassium carbonate (155 mg, 1.12 mmol) and tetrakis(triphenylphosphine)palladium(0) (86 mg, 0.07 mmol) in degassed 1,4-dioxane : water (5:1) was stirred at 120 ºC for 30 min. The reaction mixture was cooled to room temperature, diluted with water, and extracted with dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification on silica gel column afforded tert-butyl (S)-((3'-chloro-2'-(2-chloro-3-(5- formylpicolinamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)m ethyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (200 mg, 76% yield). LCMS: m/z found 705.2 [M+H] ⁺ , retention time = 1.03 min (Method B). (g) tert-butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-(((2- hydroxyethyl)amino)methyl)picolinamido)phenyl)-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate A mixture of tert-butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-formylpicolinamido)phenyl) - 6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-y l)methyl)carbamate (50 mg, 0.07 mmol), 2-aminoethanol (9 mg, 0.14 mmol) and acetic acid (3 µL, 3 mg, 0.04 mmol) in MeOH/THF (1:1 v/v) was stirred for 1 hour at room temperature. Sodium cyanoborohydride (6 mg, 0.09 mmol) was added, the mixture stirred for an additional 30 min, quenched with water, and extracted with dichloromethane three times. The combined organic extracts were concentrated to give tert-butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-(((2- hydroxyethyl)amino)methyl)picolinamido)phenyl)-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate, which was used in the next step without further purification. LCMS: m/z found 750.3 [M+H] ⁺ , retention time = 0.81 min (Method B). (h) (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 2- hydroxyethyl)amino)methyl)picolinamide A solution of crude tert-butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-(((2- hydroxyethyl)amino)methyl)picolinamido)phenyl)-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (40 mg, 0.05 mmol) in dichloromethane / trifluoroacetic acid (1:1) was stirred for 30 min, concentrated to dryness and purified by reversed phase chromatography. The combined fractions were concentrated and then converted to free base by neutralization and extraction to give (S)-N-(2-chloro-3-(3'-chloro-6- methoxy-5-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4 '-bipyridin]-2'-yl)phenyl)-5- (((2-hydroxyethyl)amino)methyl)picolinamide. LCMS: m/z found 650.2 [M+H] ⁺ , retention time = 1.50 min (Method D). ¹ H NMR (400 MHz, Methanol-d4): δ 8.72 – 8.67 (m, 2H), 8.64 (dd, 1H), 8.25 (d, 1H), 8.06 (dd, 1H), 7.82 (d, 1H), 7.80 (dd, 1H), 7.55 (dd, 1H), 7.44 (d, 1H), 7.26 (dd, 1H), 4.05 (s, 3H), 3.95 (s, 2H), 3.90 – 3.79 (m, 3H), 3.69 (t, 2H), 2.76 (t, 2H), 2.74 – 2.62 (m, 2H), 2.40 – 2.19 (m, 3H), 1.91 – 1.75 (m, 1H). Example 24: N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( S)-3-hydroxypyrrolidin-1- yl)methyl)picolinamide (a) tert-Butyl ((3'-chloro-2'-(2-chloro-3-(5-(((S)-3-hydroxypyrrolidin-1- yl)methyl)picolinamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5- yl)methyl)(((S)-5- oxopyrrolidin-2-yl)methyl)carbamate A mixture of tert-butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-formylpicolinamido)phenyl) - 6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-y l)methyl)carbamate (Example 23, step (f)) (50 mg, 0.07 mmol), (S)-pyrrolidin-3-ol (12 mg, 0.14 mmol) and acetic acid (4 µL, 4 mg, 0.07 mmol) in MeOH/THF (1:1 v/v) was stirred for 1 hour at room temperature. Sodium cyanoborohydride (9 mg, 0.14 mmol) was added, the mixture stirred for an additional 30 minutes, quenched with water, and extracted with dichloromethane three times. The combined extracts were concentrated to give tert-butyl ((3'-chloro-2'-(2-chloro-3-(5-(((S)-3- hydroxypyrrolidin-1-yl)methyl)picolinamido)phenyl)-6-methoxy -[2,4'-bipyridin]-5- yl)methyl)(((S)-5-oxopyrrolidin-2-yl)methyl)carbamate, which was used in the next step without further purification. LCMS: m/z found 776.3 [M+H] ⁺ , retention time = 0.82 min (Method B). (b) N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( S)-3-hydroxypyrrolidin-1- yl)methyl)picolinamide A solution of the crude tert-butyl ((3'-chloro-2'-(2-chloro-3-(5-(((S)-3- hydroxypyrrolidin-1-yl)methyl)picolinamido)phenyl)-6-methoxy -[2,4'-bipyridin]-5- yl)methyl)(((S)-5-oxopyrrolidin-2-yl)methyl)carbamate (40 mg, 0.05 mmol) in dichloromethane / trifluoroacetic acid (1:1) was stirred for 30 min, concentrated to dryness and purified by reversed phase chromatography. The combined fractions were concentrated and then converted to free base by neutralization and extraction to give N-(2-chloro-3-(3'- chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)methyl)amino )methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-5-(((S)-3-hydroxypyrrolidin-1-yl)methyl)picolinam ide. LCMS: m/z found 676.2 [M+H] ⁺ , retention time = 1.51 min (Method D). ¹ H NMR (400 MHz, Methanol-d4): δ 8.73 – 8.67 (m, 2H), 8.64 (dd, 1H), 8.24 (d, 1H), 8.05 (dd, 1H), 7.82 (d, 1H), 7.80 – 7.77 (m, 1H), 7.55 (t, 1H), 7.44 (d, 1H), 7.27 (dt, 1H), 4.40 – 4.33 (m, 1H), 4.05 (s, 3H), 3.91 – 3.73 (m, 5H), 2.84 – 2.76 (m, 2H), 2.76 – 2.62 (m, 2H), 2.59 – 2.49 (m, 2H), 2.38 – 2.24 (m, 3H), 2.23 – 2.11 (m, 1H), 1.88 – 1.68 (m, 2H). Example 25: (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 2- methoxyethyl)amino)methyl)picolinamide (a) tert-Butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-(((2- methoxyethyl)amino)methyl)picolinamido)phenyl)-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-2'-(2-chloro-3-(5- formylpicolinamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)m ethyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (0.3 g, 0.43 mmol) (Example 23, step (f)) and 2-methoxyethan-1-amine (0.05 g, 0.64 mmol) in THF/methanol mixture (5:1 v/v, 3 mL) was added sodium acetate (0.1 g, 1.28 mmol) in one portion under N ₂ . The mixture was stirred at room temperature for 11.5 hours then sodium cyanoborohydride (0.08 g, 1.28 mmol) added and the mixture was stirred for an additional 0.5 hours. The mixture was combined with another batch at 20 mg scale. The combined mixture was concentrated, water (15 mL) and saturated aqueous brine solution (50 mL) were added to the residue and the mixture extracted with an ethyl acetate/THF mixture (1:1 v/v, 50 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0- 15% MeOH/ethyl acetate) to afford tert-butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-(((2- methoxyethyl)amino)methyl)picolinamido)phenyl)-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (180 mg, 50% yield) as a yellow oil. LCMS: m/z found 764 [M+H] ⁺ . (b) (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 2- methoxyethyl)amino)methyl)picolinamide To a mixture of tert-butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-(((2- methoxyethyl)amino)methyl)picolinamido)phenyl)-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (0.17 g, 0.22 mmol) in 1,4-dioxane (1 mL) was added concentrated HCl solution (0.3 mL) in one portion under N ₂ and the mixture stirred at room temperature for 0.5 hours. The mixture was combined with another batch at 10 mg scale. The combined mixture was purified by reverse phase HPLC to afford (S)-N-(2- chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-(((2-methoxyethyl)amino)methyl)pi colinamide (24.9 mg, 17% yield) as a yellow solid. LCMS: m/z found 664 [M+H] ⁺ , retention time = 2.48 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.71-8.69 (m, 2H), 8.66 (d, 1H), 8.26 (d, 1H), 8.06 (dd, 1H), 7.83 (d, 1H), 7.81 (d, 1H), 7.56 (t, 1H), 7.45 (d, 1H), 7.28 (dd, 1H), 4.07 (s, 3H), 3.96 (s, 2H), 3.87-3.83 (m, 3H), 3.55 (t, 2H), 3.37 (s, 3H), 2.81 (t, 2H), 2.75-2.70 (m, 2H), 2.38-2.25 (m, 3H), 1.92-1.80 (m, 1H). Example 26: (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 3- fluoropropyl)amino)methyl)picolinamide (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 3- fluoropropyl)amino)methyl)picolinamide was prepared in a similar fashion to Example 25, replacing 2-methoxyethan-1-amine with 3-fluoropropan-1-amine hydrochloride salt in step (a). LCMS: m/z found m/z: 666 [M+H] ⁺ , retention time = 2.55 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.81-8.61 (m, 3H), 8.27-8.24 (m, 1H), 8.10-8.04 (m, 1H), 7.87- 7.77 (m, 2H), 7.58-7.53 (m, 1H), 7.48-7.43 (m, 1H), 7.32-7.26 (m, 1H), 4.60-4.58 (m, 1H), 4.51-4.45 (m, 1H), 4.11-3.86 (m, 8H), 2.82-2.68 (m, 4H), 2.36-2.26 (m, 3H), 2.01-1.79 (m, 3H). Example 27: N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((S)-3- hydroxypyrrolidin-1-yl)methyl)picolinamide (a) 5-(((tert-Butyldimethylsilyl)oxy)methyl)-N-(2-methyl-3-(4,4, 5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)phenyl)picolinamide To a mixture of N-(3-bromo-2-methylphenyl)-5-(((tert- butyldimethylsilyl)oxy)methyl)picolinamide (4.6 g, 10.5mmol) (Example 9, step (a)) and bis(pinacolato)diboron (16.1 g, 63.4 mmol) in 1,4-dioxane (80 mL) was added [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (0.86 g, 1.06 mmol) and potassium acetate (3.1 g, 31.7 mmol) in one portion under N ₂ and the mixture stirred at 130 °C for 6 hours. The mixture was combined with another batch at 4.6 g scale. The combined mixture was concentrated and the residue purified by normal phase SiO ₂ chromatography (0-5% ethyl acetate/petroleum ether) and followed by purification by reversed-phase HPLC to afford 5-(((tert-butyldimethylsilyl)oxy)methyl)-N-(2-methyl-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)picolina mide (7.3 g, 14% yield) as a white solid. LCMS: m/z found 483 [M+H] ⁺ . (b) tert-butyl (S)-((2'-(3-(5-(((tert-butyldimethylsilyl)oxy)methyl)picolin amido)-2- methylphenyl)-3'-chloro-6-methoxy-[2,4'-bipyridin]-5-yl)meth yl)((5-oxopyrrolidin-2- yl)methyl)carbamate To a mixture of 5-(((tert-butyldimethylsilyl)oxy)methyl)-N-(2-methyl-3-(4,4, 5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)picolinamide (2.2 g, 4.59 mmol) and tert-butyl (S)-((2',3'-dichloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl) ((5-oxopyrrolidin-2- yl)methyl)carbamate (1.7 g, 3.53 mmol) (Example 23, step (c)) in 1,4-dioxane / water mixture (17:3, 20 mL) was added potassium acetate (2.3 g, 10.6 mmol) and [1,1′-bis(di-tert- butylphosphino)ferrocene]dichloropalladium(II) (0.23 g, 0.35 mmol) in one portion under N ₂ and the mixture stirred at 120 °C for 10 hours. The mixture was combined with another two batches at 0.65 g and 0.13 g scale. To the mixture was added water (20 mL) and the mixture extracted with ethyl acetate (20 mL). The organic phase was washed with saturated aqueous brine solution (20 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-5% methanol / dichloromethane) to afford tert-butyl (S)-((2'-(3-(5-(((tert- butyldimethylsilyl)oxy)methyl)picolinamido)-2-methylphenyl)- 3'-chloro-6-methoxy-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te (2.5 g, 65% yield) as a yellow solid. ¹ H NMR (400 MHz, Chloroform-d): δ 10.03 (s, 1H), 8.53 (d, 1H), 8.47-8.44 (s, 1H), 8.27 (d, 1H), 8.15 (d, 1H), 7.73 (dd, 1H), 7.48 (d, 1H), 7.38-7.36 (m, 2H), 7.27-7.23 (m, 2H), 7.00 (d, 1H), 4.71 (s, 2H), 4.40-4.24 (m, 3H), 3.90 (s, 3H), 3.80-3.69 (m, 1H), 3.29-3.21 (m, 3H), 2.22-2.18 (m, 3H), 2.13-2.08 (m, 3H), 1.68-1.63 (m, 1H), 1.39-1.29 (m, 9H), 0.82 (s, 9H), 0.00 (s, 6H). (c) tert-Butyl (S)-((3'-chloro-2'-(3-(5-(hydroxymethyl)picolinamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate To a mixture of tert-butyl (S)-((2'-(3-(5-(((tert- butyldimethylsilyl)oxy)methyl)picolinamido)-2-methylphenyl)- 3'-chloro-6-methoxy-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te (0.5 g, 0.62 mmol) in THF (10 mL) was added 1.0 M tetrabutylammonium fluoride in THF (1.3 mL, 1.3 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 1 hour. Water (10 mL) was added and the mixture extracted with ethyl acetate (10 mL). The organic phase was washed with saturated aqueous brine solution (10 mL), dried with anhydrous sodium sulfate, filtered and concentrated to afford tert-butyl (S)-((3'-chloro-2'-(3-(5-(hydroxymethyl)picolinamido)- 2-methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-o xopyrrolidin-2- yl)methyl)carbamate (0.6 g, crude) as a yellow oil. LCMS: m/z found 687 [M+H] ⁺ . (d) tert-Butyl (S)-((3'-chloro-2'-(3-(5-formylpicolinamido)-2-methylphenyl) -6- methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl) methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-2'-(3-(5-(hydroxymethyl)picolinamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate (0.25 g, 0.36 mmol) in dichloromethane (10 mL) was added manganese dioxide (0.41 g, 4.73 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 5 hours. The mixture was filtered and the filtrate concentrated to afford tert- butyl (S)-((3'-chloro-2'-(3-(5-formylpicolinamido)-2-methylphenyl) -6-methoxy-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te 0.26 g, crude) as a yellow solid. LCMS: m/z found 685 [M+H] ⁺ . (e) tert-Butyl ((3'-chloro-2'-(3-(5-(((S)-3-hydroxypyrrolidin-1- yl)methyl)picolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipy ridin]-5-yl)methyl)(((S)- 5-oxopyrrolidin-2-yl)methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-2'-(3-(5-formylpicolinamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate (0.35 g, 0.51 mmol) and (S)-pyrrolidin-3-ol (0.04 g, 0.51 mmol) in THF/MeOH mixture (1:1 v/v, 10 mL) was added sodium acetate (0.08 g, 1.02 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 10 hours. Sodium cyanoborohydride (0.1 g, 1.53 mmol) was then added and the mixture stirred at room temperature for 2 hours. Water (10 mL) and saturated aqueous brine solution (10 mL) were added, and the mixture was extracted with dichloromethane/methanol mixture (10:1 v/v, 10 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-40% methanol / ethyl acetate) to afford tert-butyl ((3'-chloro-2'-(3-(5-(((S)-3-hydroxypyrrolidin-1- yl)methyl)picolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipy ridin]-5-yl)methyl)(((S)-5- oxopyrrolidin-2-yl)methyl)carbamate (0.07 g, 12% yield) as a white solid. LCMS: m/z found 756 [M+H] ⁺ . (f) N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-hydroxypyr rolidin-1- yl)methyl)picolinamide To a mixture of tert-butyl ((3'-chloro-2'-(3-(5-(((S)-3-hydroxypyrrolidin-1- yl)methyl)picolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipy ridin]-5-yl)methyl)(((S)-5- oxopyrrolidin-2-yl)methyl)carbamate (0.06 g, 0.08 mmol) in 1,4-dioxane (1 mL) was added 1 N aqueous HCl solution (0.25 mL) in one portion under N ₂ and the mixture stirred at room temperature for 0.5 hours. The mixture was combined with another batch at 10 mg scale. The mixture was neutralized with sodium hydroxide and the mixture purified by prep-HPLC to afford N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-hydroxypyr rolidin-1- yl)methyl)picolinamide (14 mg, 24% yield) as a white solid. LCMS: m/z found 656 [M+H] ⁺ , retention time = 2.16 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.70 (d, 1H), 8.64 (d, 1H), 8.22 (d, 1H), 8.08-8.03 (m, 2H), 7.83 (d, 1H), 7.76 (d, 1H), 7.45-7.41 (m, 2H), 7.21 (dd, 1H), 4.41-4.36 (m, 1H), 4.06 (s, 3H), 3.91-3.76 (m, 5H), 2.84-2.76 (m, 2H), 2.75- 2.67 (m, 2H), 2.60-2.54 (m, 2H), 2.38-2.15 (m, 7H), 1.88-1.72 (m, 2H). Example 28: N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((R)-3- hydroxypyrrolidin-1-yl)methyl)picolinamide (a) tert-Butyl ((3'-chloro-2'-(3-(5-(((R)-3-hydroxypyrrolidin-1- yl)methyl)picolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipy ridin]-5-yl)methyl)(((S)- 5-oxopyrrolidin-2-yl)methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-2'-(3-(5-formylpicolinamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate (Example 27, step (d)) (0.3 g, 0.44 mmol) and (R)-pyrrolidin-3-ol (0.06 g, 0.66 mmol) in THF/MeOH mixture (1:1 v/v, 2 mL) was added sodium acetate (0.07 g, 0.88 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 2 hours. Sodium cyanoborohydride (0.08 g, 1.31 mmol) was then added and the mixture stirred at room temperature for 3 hours. Water (10 mL) was added and the mixture extracted with dichloromethane (2 x 10 mL). The combined organic phases were washed with saturated aqueous brine solution (10 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified directly by column chromatography (silica gel, 0-30% methanol / ethyl acetate) to afford tert-butyl ((3'-chloro-2'-(3-(5-(((R)-3-hydroxypyrrolidin-1- yl)methyl)picolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipy ridin]-5-yl)methyl)(((S)-5- oxopyrrolidin-2-yl)methyl)carbamate (140 mg, 30% yield) as a brown solid. LCMS: m/z found 756 [M+H] ⁺ . (b) N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-hydroxypyr rolidin-1- yl)methyl)picolinamide To a mixture of tert-butyl ((3'-chloro-2'-(3-(5-(((R)-3-hydroxypyrrolidin-1- yl)methyl)picolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipy ridin]-5-yl)methyl)(((S)-5- oxopyrrolidin-2-yl)methyl)carbamate (0.13 g, 0.17 mmol) in 1,4-dioxane (1 mL) was added concentrated HCl solution (0.2 mL) in one portion under N ₂ and the mixture stirred at room temperature for 0.5 hours. The mixture was combined with another batch at 10 mg scale. The mixture was neutralized with sodium hydroxide and purified by prep-HPLC to afford N-(3- (3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)methyl)a mino)methyl)-[2,4'-bipyridin]- 2'-yl)-2-methylphenyl)-5-(((R)-3-hydroxypyrrolidin-1-yl)meth yl)picolinamide (21.8 mg,17% yield) as a white solid. LCMS: m/z found 656 [M+H] ⁺ , retention time = 1.35 min (Method D). ¹ H NMR (400 MHz, Methanol-d4): δ 8.71 (d, 1H), 8.64 (d, 1H), 8.22 (d, 1H), 8.08-8.03 (m, 2H), 7.83 (d, 1H), 7.76 (d, 1H), 7.45-7.41 (m, 2H), 7.21 (dd, 1H), 4.39-4.38 (m, 1H), 4.06 (s, 3H), 3.91-3.73 (m, 5H), 2.84-2.80 (m, 2H), 2.76-2.67 (m, 2H), 2.60-2.55 (m, 2H), 2.37- 2.27 (m, 3H), 2.19-2.15 (m, 4H), 1.86-1.74 (m, 2H). Example 29: N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-((((S)-2- hydroxypropyl)amino)methyl)picolinamide (a) 5-Formyl-N-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborol an-2- yl)phenyl)picolinamide To a stirred mixture of lithium 5-(dimethoxymethyl)picolinate (Example 6, step (b)) (12 mmol) and dichloromethane (5 mL) in a 40 mL vial, thionyl chloride (5 mL) was added dropwise. After stirring for 10 min at room temperature, the vial was closed with an assembled screw cap with a PTFE/silicone septum and stirred at 55 ºC for 2 hours. The mixture was cooled to room temperature, concentrated by blowing a stream of nitrogen gas and then placed under high vacuum for 1 hour. DMF (5 mL) was added followed by the addition of 2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anil ine (3 mmol). The reaction mixture was stirred for 1 h, quenched with water and extracted with dichloromethane. The combined organic extracts were concentrated, dried over anhydrous magnesium sulfate and purified on silica gel column to give 5-formyl-N-(2-methyl-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)picolina mide. LCMS: m/z found 367.1 [M+H] ⁺ , retention time = 1.08 min (Method B). (b) tert-Butyl (S)-((3'-chloro-2'-(3-(5-formylpicolinamido)-2-methylphenyl) -6- methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl) methyl)carbamate A mixture of tert-butyl (S)-((2',3'-dichloro-6-methoxy-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (Example 23, step (c)) (210 mg, 0.44 mmol), 5-formyl-N-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborol an-2- yl)phenyl)picolinamide (160 mg, 0.44 mmol), potassium carbonate (181 mg, 1.31 mmol) and tetrakis(triphenylphosphine)palladium(0) (101 mg, 0.09 mmol) in degassed 1,4-dioxane : water (5:1) was stirred at 120 ºC for 30 min. The reaction mixture was cooled to room temperature, diluted with water, and extracted with dichloromethane. The combined organics were dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification on silica gel column afforded tert-butyl (S)-((3'-chloro-2'-(3-(5- formylpicolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipyridi n]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (180 mg, 60% yield). LCMS: m/z found 685.3 [M+H] ⁺ , retention time = 0.96 min (Method B). (c) tert-Butyl ((3'-chloro-2'-(3-(5-((((S)-2- hydroxypropyl)amino)methyl)picolinamido)-2-methylphenyl)-6-m ethoxy-[2,4'- bipyridin]-5-yl)methyl)(((S)-5-oxopyrrolidin-2-yl)methyl)car bamate A mixture of tert-butyl (S)-((3'-chloro-2'-(3-(5-formylpicolinamido)-2-methylphenyl) - 6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-y l)methyl)carbamate (35 mg, 0.05 mmol), (S)-1-aminopropan-2-ol (8 mg, 0.10 mmol) and acetic acid (3 µL, 3 mg, 0.05 mmol) in MeOH/THF (1:1) was stirred for 1 hour at room temperature. Sodium cyanoborohydride (7 mg, 0.10 mmol) was added and the mixture stirred for an additional 30 min, quenched with water, concentrated and extracted with dichloromethane three times. The combined organic extracts were concentrated to give tert-butyl ((3'-chloro-2'-(3-(5-((((S)-2- hydroxypropyl)amino)methyl)picolinamido)-2-methylphenyl)-6-m ethoxy-[2,4'-bipyridin]-5- yl)methyl)(((S)-5-oxopyrrolidin-2-yl)methyl)carbamate, which was used in the next step without further purification. LCMS: m/z found 744.3 [M+H] ⁺ , retention time = 0.78 min (Method B). (d) N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((((S)-2- hydroxypropyl)amino)methyl)picolinamide A solution of crude tert-butyl ((3'-chloro-2'-(3-(5-((((S)-2- hydroxypropyl)amino)methyl)picolinamido)-2-methylphenyl)-6-m ethoxy-[2,4'-bipyridin]-5- yl)methyl)(((S)-5-oxopyrrolidin-2-yl)methyl)carbamate (25 mg, 0.03 mmol) in dichloromethane / trifluoroacetic acid (1:1) was stirred for 30 min, concentrated to dryness and purified by reversed phase chromatography. The combined fractions were concentrated and then converted to free base by neutralization and extraction to give N-(3-(3'-chloro-6- methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2- methylphenyl)-5-((((S)-2-hydroxypropyl)amino)methyl)picolina mide. LCMS: m/z found 644.3 [M+H] ⁺ , retention time = 1.38 min (Method D). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.70 (d, 1H), 8.62 (d, 1H), 8.21 (d, 1H), 8.09 – 8.00 (m, 2H), 7.84 – 7.79 (m, 1H), 7.74 (d, 1H), 7.45 – 7.38 (m, 2H), 7.20 (d, 1H), 4.04 (s, 3H), 3.94 (d, 1H), 3.86 – 3.83 (m, 3H), 2.75 – 2.63 (m, 3H), 2.62 – 2.52 (m, 2H), 2.37 – 2.24 (m, 4H), 2.17 (s, 3H), 1.87 – 1.76 (m, 1H). Example 30: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((3- fluoropropyl)amino)methyl)picolinamide (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((3-fluoropropyl) amino)methyl)picolinamide was prepared in a similar fashion to Example 28, replacing (R)-pyrrolidin-3-ol with 3- fluoropropan-1-amine hydrochloride salt in step (a). LCMS: m/z found 646 [M+H] ⁺ , retention time = 1.40 min (Method D). ¹ H NMR (400 MHz, Methanol-d ₄ ): 8.71 (d, 1H), 8.64 (d, 1H), 8.23 (d, 1H), 8.08-8.03 (m, 2H), 7.83 (d, 1H), 7.76 (d, 1H), 7.45-7.41 (m, 2H), 7.21 (d, 1H), 4.60 (t, 1H), 4.48 (t, 1H), 4.06 (s, 3H), 3.94 (s, 2H), 3.89-3.83 (m, 3H), 2.80-2.67 (m, 4H), 2.41-2.25 (m, 3H), 2.19 (s, 3H), 2.01-1.77 (m, 3H). Example 31: N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-((((R)-2- hydroxypropyl)amino)methyl)picolinamide (a) tert-Butyl ((3'-chloro-2'-(3-(5-((((R)-2- hydroxypropyl)amino)methyl)picolinamido)-2-methylphenyl)-6-m ethoxy-[2,4'- bipyridin]-5-yl)methyl)(((S)-5-oxopyrrolidin-2-yl)methyl)car bamate A mixture of tert-butyl (S)-((3'-chloro-2'-(3-(5-formylpicolinamido)-2-methylphenyl) - 6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-y l)methyl)carbamate (Example 29, step (b)) (50 mg, 0.07 mmol), (R)-1-aminopropan-2-ol (11 mg, 0.15 mmol) and acetic acid (4 µL, 4 mg, 0.07 mmol) in MeOH/THF (1:1 v/v) was stirred for 1 hour at room temperature. Sodium cyanoborohydride (9 mg, 0.15 mmol) was added and the mixture stirred for an additional 30 min, quenched with water, and directly purified by preparative HPLC to give tert-butyl ((3'-chloro-2'-(3-(5-((((R)-2-hydroxypropyl)amino)methyl)pic olinamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)(((S)-5 -oxopyrrolidin-2- yl)methyl)carbamate. LCMS: m/z found 744.3 [M+H] ⁺ , retention time = 0.78 min (Method B). (b) N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((((R)-2- hydroxypropyl)amino)methyl)picolinamide A solution of crude tert-butyl ((3'-chloro-2'-(3-(5-((((R)-2- hydroxypropyl)amino)methyl)picolinamido)-2-methylphenyl)-6-m ethoxy-[2,4'-bipyridin]-5- yl)methyl)(((S)-5-oxopyrrolidin-2-yl)methyl)carbamate (30 mg, 0.04 mmol) in dichloromethane : trifluoroacetic acid (1:1) was stirred for 30 min, concentrated to dryness and then converted to free base by neutralization and extraction to give N-(3-(3'-chloro-6- methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2- methylphenyl)-5-((((R)-2-hydroxypropyl)amino)methyl)picolina mide. LCMS: m/z found 644.3 [M+H] ⁺ , retention time = 2.21 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.69 (d, 1H), 8.62 (dd, 1H), 8.21 (d, 1H), 8.09 – 7.99 (m, 2H), 7.81 (d, 1H), 7.74 (dd, 1H), 7.41 (t, 2H), 7.25 – 7.15 (m, 1H), 4.04 (d, 3H), 3.98 – 3.77 (m, 6H), 2.79 – 2.49 (m, 4H), 2.40 – 2.24 (m, 3H), 2.17 (s, 3H), 1.88 – 1.75 (m, 1H), 1.17 (d, 3H). Example 32: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2-hydroxy-2- methylpropyl)amino)methyl)picolinamide (a) tert-Butyl (S)-((3'-chloro-2'-(3-(5-(((2-hydroxy-2- methylpropyl)amino)methyl)picolinamido)-2-methylphenyl)-6-me thoxy-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te A mixture of tert-butyl (S)-((3'-chloro-2'-(3-(5-formylpicolinamido)-2-methylphenyl) - 6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-y l)methyl)carbamate (Example 29, step (b)) (50 mg, 0.07 mmol), 1-amino-2-methyl-propan-2-ol (11 mg, 0.15 mmol) and acetic acid (4 µL, 4 mg, 0.07 mmol) in MeOH/THF (1:1 v/v) was stirred for 1 hour at room temperature. Sodium cyanoborohydride (9 mg, 0.15 mmol) was added and the mixture stirred for an additional 30 min, quenched with water, and directly purified by preparative HPLC to give tert-butyl (S)-((3'-chloro-2'-(3-(5-(((2-hydroxy-2- methylpropyl)amino)methyl)picolinamido)-2-methylphenyl)-6-me thoxy-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate. LCMS: m/z found 758.3 [M+H] ⁺ , retention time = 0.79 min (Method B). (b) (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxy-2- methylpropyl)amino)methyl)picolinamide A solution of tert-butyl (S)-((3'-chloro-2'-(3-(5-(((2-hydroxy-2- methylpropyl)amino)methyl)picolinamido)-2-methylphenyl)-6-me thoxy-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (35 mg, 0.05 mmol) in dichloromethane : trifluoroacetic acid (1:1) was stirred for 30 min, concentrated to dryness and converted to free base by neutralization and extraction to give (S)-N-(3-(3'-chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-(((2- hydroxy-2-methylpropyl)amino)methyl)picolinamide. LCMS: m/z found 658.3 [M+H] ⁺ , retention time = 2.24 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.70 (s, 1H), 8.62 (d, 1H), 8.20 (d, 1H), 8.11 – 7.98 (m, 2H), 7.81 (d, 1H), 7.74 (d, 1H), 7.41 (t, 2H), 7.19 (d, 1H), 4.04 (s, 3H), 3.95 (s, 2H), 3.87 – 3.81 (m, 3H), 2.77 – 2.62 (m, 2H), 2.56 (s, 2H), 2.38 – 2.22 (m, 3H), 2.17 (s, 3H), 1.87 – 1.77 (m, 1H), 1.22 (s, 6H). Example 33: (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- hydroxyethyl)(methyl)amino)methyl)picolinamide (a) tert-Butyl (S)-((3'-chloro-2'-(3-(5-(((2- hydroxyethyl)(methyl)amino)methyl)picolinamido)-2-methylphen yl)-6-methoxy-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te A mixture of tert-butyl (S)-((3'-chloro-2'-(3-(5-formylpicolinamido)-2-methylphenyl) - 6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-y l)methyl)carbamate (Example 29, step (b)) (50 mg, 0.07 mmol), 2-(methylamino)ethanol (11 mg, 0.15 mmol) and acetic acid (4 µL, 4 mg, 0.07 mmol) in MeOH/THF (1:1) was stirred for 1 hour at room temperature. Sodium cyanoborohydride (9 mg, 0.15 mmol) was added and the mixture stirred for an additional 30 min, quenched with water, and directly purified by preparative HPLC to give tert-butyl (S)-((3'-chloro-2'-(3-(5-(((2- hydroxyethyl)(methyl)amino)methyl)picolinamido)-2-methylphen yl)-6-methoxy-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te. LCMS: m/z found 744.3 [M+H] ⁺ , retention time = 0.77 min (Method B). (b) (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((2- hydroxyethyl)(methyl)amino)methyl)picolinamide A solution of tert-butyl (S)-((3'-chloro-2'-(3-(5-(((2- hydroxyethyl)(methyl)amino)methyl)picolinamido)-2-methylphen yl)-6-methoxy-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te (45 mg, 0.06 mmol) in dichloromethane : trifluoroacetic acid (1:1) was stirred for 30 min, concentrated to dryness and converted to free base by neutralization and extraction to give (S)-N-(3-(3'-chloro-6- methoxy-5-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4 '-bipyridin]-2'-yl)-2- methylphenyl)-5-(((2-hydroxyethyl)(methyl)amino)methyl)picol inamide. LCMS: m/z found 644.3 [M+H] ⁺ , retention time = 2.22 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.69 (s, 1H), 8.62 (d, 1H), 8.20 (d, 1H), 8.04 (t, 2H), 7.81 (d, 1H), 7.74 (d, 1H), 7.41 (t, 2H), 7.19 (d, 1H), 4.04 (s, 3H), 3.90 – 3.77 (m, 3H), 3.76 – 3.65 (m, 4H), 2.75 – 2.63 (m, 2H), 2.60 (t, 2H), 2.40 – 2.21 (m, 6H), 2.17 (s, 3H), 1.88 – 1.75 (m, 1H). Example 34: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- methoxyethyl)amino)methyl)picolinamide (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-methoxyethyl) amino)methyl)picolinamide (yellow solid) was prepared in a similar fashion to Example 28, replacing (R)-pyrrolidin-3-ol with 2-methoxyethan-1-amine in step (a). LCMS: m/z found 644 [M+H] ⁺ , retention time = 2.13 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): 8.70 (d, 1H), 8.64 (d, 1H), 8.23 (d, 1H), 8.07 (d, 1H), 8.04 (dd, 1H), 7.83 (d, 1H), 7.76 (d, 1H), 7.45-7.41 (m, 2H), 7.21 (d, 1H), 4.06 (s, 3H), 3.96 (s, 2H), 3.87-3.83 (m, 3H), 3.55 (t, 2H), 3.38 (s, 3H), 2.82 (t, 2H), 2.77- 2.67 (m, 2H), 2.38-2.29 (m, 3H), 2.19 (s, 3H), 1.86-1.82 (m, 1H). Example 35: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-((3-hydroxyazetidin- 1-yl)methyl)picolinamide (a) tert-Butyl (S)-((3'-chloro-2'-(3-(5-((3-hydroxyazetidin-1-yl)methyl)pic olinamido)- 2-methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-o xopyrrolidin-2- yl)methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-2'-(3-(5-formylpicolinamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate (Example 27, step (d)) (0.3 g, 0.44 mmol) and azetidin-3-ol hydrochloride salt (0.09 g, 0.88 mmol) in THF/MeOH mixture (1:1 v/v, 5 mL) was added triethylamine (0.18 mL, 1.31 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 3 hours. Sodium triacetoxyborohydride (0.37 g, 1.75 mmol) was then added and the mixture was stirred at room temperature for 2 hours. The mixture was combined with another batch at 30 mg scale. Water (10 mL) was added, and the mixture extracted with dichloromethane (2 x 10 mL). The combined organic phases were washed with saturated aqueous brine solution (10 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-20% methanol / ethyl acetate) to afford tert-butyl (S)-((3'-chloro-2'-(3-(5-((3-hydroxyazetidin-1- yl)methyl)picolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipy ridin]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (250 mg, 70% yield) as a brown solid. LCMS: m/z found 742 [M+H] ⁺ . (b) (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidi n-1-yl)methyl)picolinamide To a mixture of tert-butyl (S)-((3'-chloro-2'-(3-(5-((3-hydroxyazetidin-1- yl)methyl)picolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipy ridin]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (0.24 g, 0.32 mmol) in 1,4-dioxane (1 mL) was added concentrated HCl solution (0.3 mL) in one portion under N ₂ and the mixture stirred at room temperature for 0.5 hours. The mixture was combined with another batch at 10 mg scale. The mixture was neutralized with sodium hydroxide and then purified by prep-HPLC to afford (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide (94.2 mg, 44% yield) as a white solid. LCMS: m/z found 642 [M+H] ⁺ , retention time = 2.13 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.65-8.63 (m, 2H), 8.22 (d, 1H), 8.06 (d, 1H), 7.98 (dd, 1H), 7.83 (d, 1H), 7.76 (d, 1H), 7.45-7.41 (m, 2H), 7.21 (dd, 1H), 4.42-4.39 (m, 1H), 4.06 (s, 3H), 3.87-3.86 (m, 3H), 3.81 (s, 2H), 3.70-3.66 (m, 2H), 3.07-3.03 (m, 2H), 2.73-2.70 (m, 2H), 2.38-2.27 (m, 3H), 2.19 (s, 3H), 1.86-1.83 (m, 1H). Example 36: N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((oxetan-2- ylmethyl)amino)methyl)picolinamide (a) tert-Butyl ((3'-chloro-6-methoxy-2'-(2-methyl-3-(5-(((oxetan-2- ylmethyl)amino)methyl)picolinamido)phenyl)-[2,4'-bipyridin]- 5-yl)methyl)(((S)-5- oxopyrrolidin-2-yl)methyl)carbamate A mixture of tert-butyl (S)-((3'-chloro-2'-(3-(5-formylpicolinamido)-2-methylphenyl) - 6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-y l)methyl)carbamate (Example 29, step (b)) (75 mg, 0.11 mmol), oxetan-2-ylmethanamine (19 mg, 0.22 mmol) and acetic acid (6 µL, 7 mg, 0.11 mmol) in MeOH/THF (1:1 v/v) was stirred for 1 hour at room temperature. Sodium cyanoborohydride (14 mg, 0.22 mmol) was added and the mixture stirred for an additional 30 minutes, quenched with water, and directly purified by preparative HPLC to give tert-butyl ((3'-chloro-6-methoxy-2'-(2-methyl-3-(5-(((oxetan-2- ylmethyl)amino)methyl)picolinamido)phenyl)-[2,4'-bipyridin]- 5-yl)methyl)(((S)-5- oxopyrrolidin-2-yl)methyl)carbamate. LCMS: m/z found 756.3 [M+H] ⁺ , retention time = 2.32 min (Method D). (b) N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((oxetan-2- ylmethyl)amino)methyl)picolinamide A solution of tert-butyl ((3'-chloro-6-methoxy-2'-(2-methyl-3-(5-(((oxetan-2- ylmethyl)amino)methyl)picolinamido)phenyl)-[2,4'-bipyridin]- 5-yl)methyl)(((S)-5- oxopyrrolidin-2-yl)methyl)carbamate (45 mg, 0.06 mmol) in dichloromethane : trifluoroacetic acid (1:1) was stirred for 30 min, concentrated to dryness and converted to free base by neutralization and extraction to give N-(3-(3'-chloro-6-methoxy-5-(((((S)-5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5- (((oxetan-2-ylmethyl)amino)methyl)picolinamide. LCMS: m/z found 656.3 [M+H] ⁺ , retention time = 2.22 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.74 – 8.67 (m, 1H), 8.62 (d, 1H), 8.21 (d, 1H), 8.10 – 7.98 (m, 2H), 7.81 (d, 1H), 7.74 (d, 1H), 7.42 (t, 2H), 7.23 – 7.13 (m, 1H), 5.03 – 4.93 (m, 1H), 4.69 (ddd, 1H), 4.55 (dt, 1H), 4.04 (s, 3H), 3.96 (s, 2H), 3.91 – 3.76 (m, 3H), 2.96 (dd, 1H), 2.81 (dd, 1H), 2.77 – 2.62 (m, 3H), 2.57 – 2.43 (m, 1H), 2.39 – 2.23 (m, 3H), 2.17 (s, 3H), 1.90 – 1.75 (m, 1H). Example 37: N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-((((1r,3r)-3-hydroxy- 3-methylcyclobutyl)amino)methyl)picolinamide (a) tert-Butyl ((3'-chloro-2'-(3-(5-((((1r,3r)-3-hydroxy-3- methylcyclobutyl)amino)methyl)picolinamido)-2-methylphenyl)- 6-methoxy-[2,4'- bipyridin]-5-yl)methyl)(((S)-5-oxopyrrolidin-2-yl)methyl)car bamate A mixture of tert-butyl (S)-((3'-chloro-2'-(3-(5-formylpicolinamido)-2-methylphenyl) - 6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-y l)methyl)carbamate (Example 29, step (b)) (75 mg, 0.11 mmol), 3-amino-1-methyl-cyclobutanol (22 mg, 0.22 mmol) and acetic acid (6 µL, 7 mg, 0.11 mmol) in MeOH/THF (1:1 v/v) was stirred for 1 hour at room temperature. Sodium cyanoborohydride (14 mg, 0.22 mmol) was added and the mixture was stirred for an additional 30 min, quenched with water, and directly purified by preparative HPLC to give tert-butyl ((3'-chloro-2'-(3-(5-((((1r,3r)-3-hydroxy-3- methylcyclobutyl)amino)methyl)picolinamido)-2-methylphenyl)- 6-methoxy-[2,4'-bipyridin]- 5-yl)methyl)(((S)-5-oxopyrrolidin-2-yl)methyl)carbamate. LCMS: m/z found 770.3 [M+H] ⁺ , retention time = 2.29 min (Method D). (b) N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((((1r,3r)-3-hydro xy-3- methylcyclobutyl)amino)methyl)picolinamide A solution of tert-butyl ((3'-chloro-2'-(3-(5-((((1r,3r)-3-hydroxy-3- methylcyclobutyl)amino)methyl)picolinamido)-2-methylphenyl)- 6-methoxy-[2,4'-bipyridin]- 5-yl)methyl)(((S)-5-oxopyrrolidin-2-yl)methyl)carbamate (45 mg, 0.06 mmol) in dichloromethane : trifluoroacetic acid (1:1) was stirred for 30 min, concentrated to dryness and converted to free base by neutralization and extraction to give N-(3-(3'-chloro-6- methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2- methylphenyl)-5-((((1r,3r)-3-hydroxy-3-methylcyclobutyl)amin o)methyl)picolinamide. LCMS: m/z found 670.3 [M+H] ⁺ , retention time = 2.15 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.67 (d, 1H), 8.62 (d, 1H), 8.20 (d, 1H), 8.05 (d, 1H), 8.01 (dd, 1H), 7.81 (d, 1H), 7.74 (d, 1H), 7.47 – 7.37 (m, 2H), 7.23 – 7.14 (m, 1H), 4.04 (s, 3H), 3.91 – 3.82 (m, 3H), 3.81 (s, 2H), 3.47 (m, 1H), 2.78 – 2.61 (m, 2H), 2.38 – 2.22 (m, 5H), 2.17 (s, 3H), 1.93 – 1.75 (m, 3H), 1.34 (s, 3H). Example 38: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-((3- (hydroxymethyl)azetidin-1-yl)methyl)picolinamide (a) tert-Butyl (S)-((3'-chloro-2'-(3-(5-((3-(hydroxymethyl)azetidin-1- yl)methyl)picolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipy ridin]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate A mixture of tert-butyl (S)-((3'-chloro-2'-(3-(5-formylpicolinamido)-2-methylphenyl) - 6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-y l)methyl)carbamate (Example 29, step (b)) (70 mg, 0.10 mmol), azetidin-3-ylmethanol (18 mg, 0.20 mmol) and acetic acid (6 µL, 6 mg, 0.10 mmol) in MeOH/THF (1:1 v/v) was stirred for 1 hour at room temperature. Sodium cyanoborohydride (13 mg, 0.20 mmol) was added and the mixture was stirred for an additional 30 min, quenched with water, and directly purified by preparative HPLC to give tert-butyl (S)-((3'-chloro-2'-(3-(5-((3-(hydroxymethyl)azetidin-1-yl)me thyl)picolinamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate. LCMS: m/z found 756.3 [M+H] ⁺ , retention time = 0.78 min (Method B). (b) (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-(hydroxymethyl )azetidin-1- yl)methyl)picolinamide A solution of tert-butyl (S)-((3'-chloro-2'-(3-(5-((3-(hydroxymethyl)azetidin-1- yl)methyl)picolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipy ridin]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (45 mg, 0.06 mmol) in dichloromethane : trifluoroacetic acid (1:1) was stirred for 30 min, concentrated to dryness and converted to free base by neutralization and extraction to give (S)-N-(3-(3'-chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-((3- (hydroxymethyl)azetidin-1-yl)methyl)picolinamide. LCMS: m/z found 656.3 [M+H] ⁺ , retention time = 2.11 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.63 (dd, 2H), 8.20 (d, 1H), 8.05 (d, 1H), 7.96 (dd, 1H), 7.81 (d, 1H), 7.74 (d, 1H), 7.47 – 7.37 (m, 2H), 7.19 (d, 1H), 4.04 (s, 3H), 3.90 – 3.80 (m, 3H), 3.77 (s, 2H), 3.67 (d, 2H), 3.44 (t, 2H), 3.13 (t, 2H), 2.77 – 2.62 (m, 3H), 2.38 – 2.22 (m, 3H), 2.17 (s, 3H), 1.90 – 1.76 (m, 1H). Example 39: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((3- hydroxypropyl)amino)methyl)picolinamide (a) tert-Butyl (S)-((3'-chloro-2'-(3-(5-(((3- hydroxypropyl)amino)methyl)picolinamido)-2-methylphenyl)-6-m ethoxy-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te A mixture of tert-butyl (S)-((3'-chloro-2'-(3-(5-formylpicolinamido)-2-methylphenyl) - 6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-y l)methyl)carbamate (Example 29, step (b)) (70 mg, 0.10 mmol), 3-aminopropan-1-ol (15 mg, 0.20 mmol) and acetic acid (6 µL, 6 mg, 0.10 mmol) in MeOH/THF (1:1 v/v) was stirred for 1 hour at room temperature. Sodium cyanoborohydride (13 mg, 0.20 mmol) was then added and the mixture stirred for an additional 30 minutes, quenched with water, and directly purified by preparative HPLC to give tert-butyl (S)-((3'-chloro-2'-(3-(5-(((3-hydroxypropyl)amino)methyl)pic olinamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate. LCMS: m/z found 744.3 [M+H] ⁺ , retention time = 0.77 min (Method B). (b) (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((3- hydroxypropyl)amino)methyl)picolinamide A solution of tert-butyl (S)-((3'-chloro-2'-(3-(5-(((3- hydroxypropyl)amino)methyl)picolinamido)-2-methylphenyl)-6-m ethoxy-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (45 mg, 0.06 mmol) in dichloromethane / trifluoroacetic acid (1:1) was stirred for 30 minutes, then concentrated to dryness and converted to free base by neutralization and extraction to give (S)-N-(3-(3'-chloro-6- methoxy-5-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4 '-bipyridin]-2'-yl)-2- methylphenyl)-5-(((3-hydroxypropyl)amino)methyl)picolinamide . LCMS: m/z found 644.3 [M+H] ⁺ , retention time = 2.10 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.69 (d, 1H), 8.62 (d, 1H), 8.21 (d, 1H), 8.06 (d, 1H), 8.02 (dd, 1H), 7.81 (d, 1H), 7.74 (d, 1H), 7.47 – 7.36 (m, 2H), 7.19 (d, 1H), 4.04 (s, 3H), 3.91 (s, 2H), 3.90 – 3.79 (m, 3H), 3.64 (t, 2H), 2.78 – 2.62 (m, 4H), 2.40 – 2.23 (m, 3H), 2.17 (s, 3H), 1.88 – 1.72 (m, 3H). Example 40: N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-((((S)-1-hydroxy-3- methylbutan-2-yl)amino)methyl)picolinamide (a) tert-Butyl ((3'-chloro-2'-(3-(5-((((S)-1-hydroxy-3-methylbutan-2- yl)amino)methyl)picolinamido)-2-methylphenyl)-6-methoxy-[2,4 '-bipyridin]-5- yl)methyl)(((S)-5-oxopyrrolidin-2-yl)methyl)carbamate A mixture of tert-butyl (S)-((3'-chloro-2'-(3-(5-formylpicolinamido)-2-methylphenyl) - 6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-y l)methyl)carbamate (Example 29, step (b)) (70 mg, 0.10 mmol), (S)-2-amino-3-methylbutan-1-ol (21 mg, 0.20 mmol) and acetic acid (6 µL, 6 mg, 0.10 mmol) in MeOH/THF (1:1 v/v) was stirred for 1 hour at room temperature. Sodium cyanoborohydride (13 mg, 0.20 mmol) was added and the mixture stirred for an additional 30 minutes, the reaction then quenched with water, and directly purified by preparative HPLC to give tert-butyl ((3'-chloro-2'-(3-(5-((((S)-1-hydroxy- 3-methylbutan-2-yl)amino)methyl)picolinamido)-2-methylphenyl )-6-methoxy-[2,4'- bipyridin]-5-yl)methyl)(((S)-5-oxopyrrolidin-2-yl)methyl)car bamate. LCMS: m/z found 772.4 [M+H] ⁺ , retention time = 0.81 min (Method B). (b) N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((((S)-1-hydroxy-3 -methylbutan-2- yl)amino)methyl)picolinamide A solution of tert-butyl ((3'-chloro-2'-(3-(5-((((S)-1-hydroxy-3-methylbutan-2- yl)amino)methyl)picolinamido)-2-methylphenyl)-6-methoxy-[2,4 '-bipyridin]-5- yl)methyl)(((S)-5-oxopyrrolidin-2-yl)methyl)carbamate (45 mg, 0.06 mmol) in dichloromethane / trifluoroacetic acid (1:1) was stirred for 30 minutes, concentrated to dryness and converted to free base by neutralization and extraction to give N-(3-(3'-chloro-6- methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2- methylphenyl)-5-((((S)-1-hydroxy-3-methylbutan-2-yl)amino)me thyl)picolinamide. LCMS: m/z found 672.3 [M+H] ⁺ , retention time = 2.35 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.71 (s, 1H), 8.62 (d, 1H), 8.20 (d, 1H), 8.06 (dd, 2H), 7.81 (d, 1H), 7.74 (d, 1H), 7.48 – 7.36 (m, 2H), 7.19 (d, 1H), 4.04 (s, 3H), 4.01 – 3.92 (m, 2H), 3.90 – 3.79 (m, 3H), 3.68 (dd, 1H), 3.52 (dd, 1H), 2.70 (qd, 2H), 2.43 (q, 1H), 2.38 – 2.24 (m, 3H), 2.17 (s, 3H), 1.95 – 1.77 (m, 2H), 1.03 – 0.83 (m, 6H). Example 41: N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((R)-3- methoxypyrrolidin-1-yl)methyl)picolinamide (a) tert-Butyl ((3'-chloro-6-methoxy-2'-(3-(5-(((R)-3-methoxypyrrolidin-1- yl)methyl)picolinamido)-2-methylphenyl)-[2,4'-bipyridin]-5-y l)methyl)(((S)-5- oxopyrrolidin-2-yl)methyl)carbamate A mixture of tert-butyl (S)-((3'-chloro-2'-(3-(5-formylpicolinamido)-2-methylphenyl) - 6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-y l)methyl)carbamate (Example 29, step (b)) (70 mg, 0.10 mmol), (R)-3-methoxypyrrolidine (21 mg, 0.20 mmol) and acetic acid (6 µL, 6 mg, 0.10 mmol) in MeOH/THF (1:1 v/v) was stirred for 1 hour at room temperature. Sodium cyanoborohydride (13 mg, 0.20 mmol) was added and the mixture stirred for an additional 30 minutes, then the reaction quenched with water, and directly purified by preparative HPLC to give tert-butyl ((3'-chloro-6-methoxy-2'-(3-(5-(((R)-3- methoxypyrrolidin-1-yl)methyl)picolinamido)-2-methylphenyl)- [2,4'-bipyridin]-5- yl)methyl)(((S)-5-oxopyrrolidin-2-yl)methyl)carbamate. LCMS: m/z found 770.3 [M+H] ⁺ , retention time = 0.80 min (Method B). (b) N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-methoxypyr rolidin-1- yl)methyl)picolinamide A solution of tert-butyl ((3'-chloro-6-methoxy-2'-(3-(5-(((R)-3-methoxypyrrolidin-1- yl)methyl)picolinamido)-2-methylphenyl)-[2,4'-bipyridin]-5-y l)methyl)(((S)-5-oxopyrrolidin- 2-yl)methyl)carbamate (45 mg, 0.06 mmol) in dichloromethane / trifluoroacetic acid (1:1) was stirred for 30 minutes, concentrated to dryness and converted to free base by neutralization and extraction to give N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((R)-3- methoxypyrrolidin-1-yl)methyl)picolinamide. LCMS: m/z found 670.3 [M+H] ⁺ , retention time = 2.35 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.71 (s, 1H), 8.62 (d, 1H), 8.20 (d, 1H), 8.06 (dd, 2H), 7.81 (d, 1H), 7.74 (d, 1H), 7.48 – 7.36 (m, 2H), 7.19 (d, 1H), 4.04 (s, 3H), 4.01 – 3.92 (m, 2H), 3.90 – 3.79 (m, 3H), 3.68 (dd, 1H), 3.52 (dd, 1H), 2.70 (qd, 2H), 2.43 (q, 1H), 2.38 – 2.24 (m, 3H), 2.17 (s, 3H), 1.95 – 1.77 (m, 2H), 1.03 – 0.83 (m, 6H). Example 42: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- hydroxyethyl)amino)methyl)-6-methoxypicolinamide (a) Methyl 5-formyl-6-methoxypicolinate To a mixture of 6-chloro-2-methoxynicotinaldehyde (5 g, 29.1 mmol) and sodium acetate (4.78 g, 58.3 mmol) in methanol/toluene mixture (7:2, 90 mL) was added palladium(II)acetate (0.13 g, 0.58 mmol) and 1,1’-bis(diphenylphosphino)ferrocene (0.48 g, 0.87 mmol) in one portion. The mixture was stirred at 50 °C for 20 hours under CO (30 psi). The mixture was then concentrated, water (150 mL) and saturated aqueous brine solution (50 mL) added to the residue, and the mixture extracted with ethyl acetate (200 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-10% ethyl acetate / petroleum ether) to afford methyl 5-formyl-6-methoxypicolinate (5 g, 87% yield) as a yellow solid. ¹ H NMR (400 MHz, Chloroform-d): δ 10.35 (s, 1H), 8.15 (d, 1H), 7.72 (d, 1H), 4.10 (s, 3H), 3.93 (s, 3H). (b) Methyl 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-6-methoxypicolina te To a mixture of methyl 5-formyl-6-methoxypicolinate (0.2 g, 1.02 mmol) in THF/MeOH mixture (3:1 v/v, 4 mL) was added 2-((tert-butyldimethylsilyl)oxy)ethan-1- amine (0.18 g, 1.02 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 2 hours. Sodium triacetoxyborohydride (0.65 g, 3.06 mmol) was then added and the mixture stirred at room temperature for 10 hours to give methyl 5-(((2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-6-methoxypicolina te (LCMS: m/z found 355 [M+H] ⁺ ).Triethylamine (0.14 mL, 1.02 mmol) and di-tert-butyl dicarbonate (0.33 g, 1.53 mmol) were the added in one portion under N ₂ and the mixture stirred at room temperature for 1 h. The mixture was concentrated, water (5 mL) and saturated aqueous brine solution (5 mL) added to the residue, and the mixture was extracted with an ethyl acetate/THF mixture (1:1 v/v, 10 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-30% ethyl acetate/petroleum ether) to afford methyl 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-6-methoxypicolina te (0.28 g, 60% yield) as a yellow gum. ¹ H NMR (400 MHz, Chloroform-d): δ 7.66 (d, 1H), 7.48-7.44 (m, 1H), 4.48- 4.45 (m, 2H), 4.00 (s, 3H), 3.92 (s, 3H), 3.75-3.66 (m, 2H), 3.38-3.28 (m, 2H), 1.44-1.31 (m, 9H), 0.80 (s, 9H), 0.00 (s, 6H). (c) Lithium 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-6-methoxypicolina te To a mixture of methyl 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-6-methoxypicolina te (0.23 g, 0.51 mmol) in THF/water mixture (20:1 v/v, 4.2 mL) was added lithium hydroxide monohydrate (0.08 g, 2.02 mmol) in one portion. The mixture was stirred at room temperature for 12 hours, then the mixture concentrated to afford crude lithium 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-6-methoxypicolina te (0.29 g, crude) as a yellow solid. LCMS: m/z found 441 [M+H] ⁺ . (d) tert-butyl (S)-((2'-(3-amino-2-methylphenyl)-3'-chloro-6-methoxy-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te To a mixture of tert-butyl (S)-((2',3'-dichloro-6-methoxy-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (Example 23, step (c)) (5 g, 10.4 mmol) and 2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anil ine (3.87 g, 16.6 mmol) in 1,4-dioxane/water mixture (10:1 v/v, 60.6 mL) was added potassium carbonate (4.31 g, 31.2 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (0.42 g, 0.52 mmol) in one portion under N ₂ and the mixture stirred at 105 °C for 6 hours. The mixture was concentrated, water (50 mL) and saturated aqueous brine solution (50 mL) added to the residue, and the mixture extracted with an ethyl acetate/THF mixture (1:1 v/v, 200 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0- 15% ethyl acetate/petroleum ether) to afford tert-butyl (S)-((2'-(3-amino-2-methylphenyl)-3'- chloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrroli din-2-yl)methyl)carbamate (2.98 g, 47% yield) as a yellow solid. LCMS: m/z found 552 [M+H] ⁺ . (e) tert-Butyl (S)-((2'-(3-(5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-6-methoxypicolina mido)-2-methylphenyl)- 3'-chloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrr olidin-2- yl)methyl)carbamate and tert-butyl (S)-((2'-(3-(5-(((tert-butoxycarbonyl)(2- hydroxyethyl)amino)methyl)-6-methoxypicolinamido)-2-methylph enyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl) methyl)carbamate To a mixture of lithium 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-6-methoxypicolina te (0.32 g, 0.72 mmol) in DMF (5 mL) was added 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5- b]pyridinium 3-oxide hexafluorophosphate (HATU) (0.47 g, 1.25 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 0.5 hours. tert-Butyl (S)-((2'-(3-amino-2- methylphenyl)-3'-chloro-6-methoxy-[2,4'-bipyridin]-5-yl)meth yl)((5-oxopyrrolidin-2- yl)methyl)carbamate (0.28 g, 0.5 mmol) was added and the mixture stirred at room temperature for 12 hours. Water (50 mL) and saturated aqueous brine solution (25 mL) were then added, and the mixture extracted with an ethyl acetate/THF mixture (10:1 v/v, 30 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether) to afford tert-butyl (S)-((2'-(3-(5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-6-methoxypicolina mido)-2-methylphenyl)-3'- chloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrroli din-2-yl)methyl)carbamate (270 mg, 20% yield) as a yellow gum (LCMS: m/z found 974 [M+H] ⁺ ) and tert-butyl (S)- ((2'-(3-(5-(((tert-butoxycarbonyl)(2-hydroxyethyl)amino)meth yl)-6-methoxypicolinamido)-2- methylphenyl)-3'-chloro-6-methoxy-[2,4'-bipyridin]-5-yl)meth yl)((5-oxopyrrolidin-2- yl)methyl)carbamate (120 mg, 8% yield) as a yellow solid (LCMS: m/z found 860 [M+H] ⁺ ). (f) (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl) amino)methyl)-6- methoxypicolinamide To a mixture of tert-butyl (S)-((2'-(3-(5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-6-methoxypicolina mido)-2-methylphenyl)-3'- chloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrroli din-2-yl)methyl)carbamate (0.26 g, 0.27 mmol) in 1,4-dioxane (1.5 mL) was added concentrated aqueous HCl solution (12 M, 0.29 mL) in one portion and the mixture stirred at room temperature for 2 h. The mixture was combined with another batch at 115 mg scale. The mixture was neutralized with saturated aqueous sodium carbonate solution, concentrated and the residue purified by reverse phase HPLC to afford (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- hydroxyethyl)amino)methyl)-6-methoxypicolinamide (51.8 mg, 50% yield) as a white solid. LCMS: m/z found 660 [M+H] ⁺ , retention time = 2.34 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.64 (d, 1H), 8.19 (d, 1H), 7.92 (d, 1H), 7.86-7.82 (m, 2H), 7.76 (d, 1H), 7.45-7.42 (m, 2H), 7.20 (dd, 1H), 4.14 (s, 3H), 4.06 (s, 3H), 3.89-3.81 (m, 5H), 3.70 (t, 2H), 2.83-2.69 (m, 4H), 2.38-2.27 (m, 3H), 2.23 (s, 3H), 1.86-1.81 (m, 1H). Example 43: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-4-(((2- hydroxyethyl)amino)methyl)thiazole-2-carboxamide (a) tert-Butyl (S)-((2'-(3-(4-bromothiazole-2-carboxamido)-2-methylphenyl)- 3'- chloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrroli din-2-yl)methyl)carbamate To a mixture of 4-bromothiazole-2-carboxylic acid (0.17 g, 0.82 mmol) in DMF (4 mL) was added 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyri dinium 3- oxide hexafluorophosphate (HATU) (0.62 g, 1.63 mmol) and N,N-diisopropylethylamine (0.28 mL, 1.63 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 0.5 hours. To the mixture was added tert-butyl (S)-((2'-(3-amino-2-methylphenyl)-3'- chloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrroli din-2-yl)methyl)carbamate (Example 42, step (d)) (0.3 g, 0.54 mmol) and the mixture stirred at room temperature for 11.5 hours. The mixture was combined with another batch at 50 mg scale. Water (50 mL) and saturated aqueous brine solution (50 mL) was added, and the mixture extracted with ethyl acetate (50 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (10-100% ethyl acetate/petroleum ether) to afford tert-butyl (S)-((2'-(3-(4-bromothiazole-2- carboxamido)-2-methylphenyl)-3'-chloro-6-methoxy-[2,4'-bipyr idin]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (270 mg, 65% yield). ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.61 (s, 1H), 8.71 (d, 1H), 8.26-8.25 (m, 1H), 7.79-7.76 (m, 1H), 7.71-7.69 (m, 1H), 7.49- 7.46 (m, 2H), 7.36 (t, 1H), 7.24 (d, 1H), 4.44-4.36 (m, 2H), 3.96 (s, 3H), 3.62-3.60 (m, 1H), 3.28-3.27 (m, 2H), 2.19-2.07 (m, 3H), 2.01 (s, 3H), 1.75-1.72 (m, 1H), 1.44-1.30 (m, 9H). (b) tert-Butyl (S)-((3'-chloro-6-methoxy-2'-(2-methyl-3-(4-vinylthiazole-2- carboxamido)phenyl)-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrr olidin-2- yl)methyl)carbamate To a mixture of tert-butyl (S)-((2'-(3-(4-bromothiazole-2-carboxamido)-2- methylphenyl)-3'-chloro-6-methoxy-[2,4'-bipyridin]-5-yl)meth yl)((5-oxopyrrolidin-2- yl)methyl)carbamate (0.24 g, 0.32 mmol) and 4,4,5,5-tetramethyl-2-vinyl-1,3,2- dioxaborolane (0.06 g, 0.42 mmol) in 1,4-dioxane/water mixture (6:1 v/v, 3.5 mL) was added potassium phosphate (0.21 g, 0.97 mmol) and chloro(2-dicyclohexylphosphino-2′,4′,6′- triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl) ]palladium(II) (0.01 g, 0.02 mmol) in one portion under N ₂ and the mixture stirred at 100 °C for 6 hours. The mixture was concentrated, water (50 mL) and saturated aqueous brine solution (15 mL) added to the residue, and the mixture extracted with an ethyl acetate/THF mixture (1:1 v/v, 50 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-15% MeOH/ethyl acetate) to afford tert-butyl (S)-((3'-chloro-6-methoxy-2'-(2-methyl-3-(4-vinylthiazole-2- carboxamido)phenyl)-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrr olidin-2-yl)methyl)carbamate (200 mg, 69% yield) as a white solid. LCMS: m/z found 689 [M+H] ⁺ . (c) tert-Butyl (S)-((3'-chloro-2'-(3-(4-formylthiazole-2-carboxamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-6-methoxy-2'-(2-methyl-3-(4-vinylthiazole- 2-carboxamido)phenyl)-[2,4'-bipyridin]-5-yl)methyl)((5-oxopy rrolidin-2- yl)methyl)carbamate (0.09 g, 0.13 mmol) in THF/water mixture (5:1 v/v, 2.4 mL) was added potassium osmate (VI) dihydrate (0.01 g, 0.02 mmol) in one portion at 0°C under N ₂ and the mixture was stirred at 0 °C for 0.2 hours. To the mixture was added sodium periodate (0.08 g, 0.39 mmol) and the mixture stirred at room temperature for 12 hours. The mixture was combined with another batch at 110 mg scale. The mixture was quenched with saturate aqueous sodium sulfite solution, water (50 mL) and saturated aqueous brine solution (15 mL) added, and the mixture extracted with ethyl acetate (50 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated to afford tert-butyl (S)-((3'-chloro- 2'-(3-(4-formylthiazole-2-carboxamido)-2-methylphenyl)-6-met hoxy-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (130 mg, 65% yield) as a yellow solid. LCMS: m/z found 691 [M+H] ⁺ . (d) tert-Butyl (S)-((3'-chloro-2'-(3-(4-(((2-hydroxyethyl)amino)methyl)thia zole-2- carboxamido)-2-methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl )methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate A mixture tert-butyl (S)-((3'-chloro-2'-(3-(4-formylthiazole-2-carboxamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate (0.12 g, 0.17 mmol) and 2-aminoethan-1-ol (0.01 g, 0.23 mmol) in methanol (1 mL) was stirred at room temperature under N ₂ for 11.5 hours. Sodium cyanoborohydride (0.03 g, 0.52 mmol) was then added and the mixture stirred at room temperature for 0.5 hours. The mixture was combined with another batch at 10 mg scale. The mixture was concentrated, water (25 mL) and saturated aqueous brine solution (5 mL) added to the residue, and the mixture extracted with an ethyl acetate/THF mixture (1:1 v/v, 20 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-30% methanol/ethyl acetate) to afford tert-butyl (S)-((3'-chloro-2'-(3-(4-(((2-hydroxyethyl)amino)methyl)thia zole-2- carboxamido)-2-methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl )methyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (60 mg, 40% yield) as a yellow oil. LCMS: m/z found 736 [M+H] ⁺ . (e) (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl) amino)methyl)thiazole-2- carboxamide To a mixture of tert-butyl (S)-((3'-chloro-2'-(3-(4-(((2- hydroxyethyl)amino)methyl)thiazole-2-carboxamido)-2-methylph enyl)-6-methoxy-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te (50 mg, 0.07 mmol) in 1,4- dioxane (1 mL) was added concentrated HCl solution (0.3 mL) in one portion under N ₂ , and the mixture stirred at room temperature for 0.5 hours. The mixture was combined with another batch at 10 mg scale. The mixture was neutralized with saturated aqueous sodium bicarbonate solution, concentrated and the residue purified by reverse phase HPLC to afford (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)thiazole-2-carboxamide (12.7 mg, 24% yield) as a white solid. LCMS: m/z found 636 [M+H] ⁺ , retention time = 2.34 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.64 (d, 1H), 7.83 (d, 1H), 7.80 (d, 1H), 7.76-7.75 (m, 2H), 7.44-7.41 (m, 2H), 7.26 (dd, 1H), 4.06 (s, 3H), 4.03 (s, 2H), 3.91- 3.83 (m, 3H), 3.72 (t, 2H), 2.81 (t, 2H), 2.76-2.67 (m, 2H), 2.38-2.25 (m, 3H), 2.17 (s, 3H), 1.86-1.82 (m, 1H). Example 44: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-4-(((2- hydroxyethyl)amino)methyl)-1-methyl-1H-imidazole-2-carboxami de (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl) amino)methyl)-1-methyl-1H- imidazole-2-carboxamide was prepared in a similar fashion to Example 43, replacing 4- bromothiazole-2-carboxylic acid with 4-bromo-1-methyl-1H-imidazole-2-carboxylic acid in step (a). LCMS: m/z found 633 [M +H] ⁺ , retention time = 2.08 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.51 (d, 1H), 7.76 (d, 1H), 7.71 (d, 1H), 7.63 (d, 1H), 7.32-7.27 (m, 2H), 7.14 (s, 1H), 7.09 (d, 1H), 3.95 (s, 3H), 3.94 (s, 3H), 3.79-3.70 (m, 5H), 3.60 (t, 2H), 2.72 (t, 2H), 2.64-2.55 (m, 2H), 2.26-2.15 (m, 3H), 2.04 (s, 3H), 1.76-1.68 (m, 1H). Example 45: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- hydroxyethyl)amino)methyl)pyrazine-2-carboxamide (a) Methyl 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)pyrazine-2-carboxy late A mixture of methyl 5-formylpyrazine-2-carboxylate (0.2 g, 1.2 mmol) and 2-((tert- butyldimethylsilyl)oxy)ethan-1-amine (0.22 g, 1.26 mmol) in THF/methanol mixture (1:1 v/v, 4 mL) was stirred at room temperature for 10 hours. Sodium cyanoborohydride (0.23 g, 3.61 mmol) was then added and the mixture stirred at room temperature for 2 hours to give methyl 5-(((2-((tert-butyldimethylsilyl)oxy)ethyl)amino)methyl)pyra zine-2-carboxylate (LCMS: m/z found 326 [M+H] ⁺ ). Di-tert-butyl dicarbonate (0.52 g, 2.4 mmol) and triethylamine (0.17 mL, 1.2 mmol) were then added in one portion and the mixture stirred at room temperature under N ₂ for 2 h. Water (10 mL) was added and the mixture extracted with ethyl acetate (2 x 10 mL). The combined organic phases were washed with saturated aqueous brine solution (10 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by reverse phase HPLC to afford methyl 5-(((tert- butoxycarbonyl)(2-((tert-butyldimethylsilyl)oxy)ethyl)amino) methyl)pyrazine-2-carboxylate (0.23 g, 40% yield) as a yellow oil. ¹ H NMR (400 MHz, Chloroform-d): δ 9.19-9.18 (m, 1H), 8.63-8.61 (m, 1H), 4.70 (d, 2H), 4.01 (d, 3H), 3.79-3.70 (m, 2H), 3.51-3.39 (m, 2H), 1.53- 1.45 (m, 9H), 0.84-0.83 (m, 9H), 0.00 (s, 6H). (b) Lithium 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)pyrazine-2-carboxy late To a mixture of methyl 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)pyrazine-2-carboxy late (0.2 g, 0.47 mmol) in THF/water mixture (10:1 v/v, 3.3 mL) was added lithium hydroxide monohydrate (0.06 g, 1.41 mmol) in one portion and the mixture stirred at room temperature for 3 hours. The mixture was concentrated to afford lithium 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)pyrazine-2-carboxy late (260 mg, crude) as a yellow solid. LCMS: m/z found 412 [M+H] ⁺ . (c) tert-Butyl (S)-((5-((3-(5-(((tert-butoxycarbonyl)((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-3'-chloro-6-methoxy-[2,4'-bipyridin] -2'-yl)-2- methylphenyl)carbamoyl)pyrazin-2-yl)methyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)carbamate To a mixture of 2-chloro-1-methylpyridinium iodide (0.18 g, 0.69 mmol) and lithium 5-(((tert-butoxycarbonyl)(2-((tert-butyldimethylsilyl)oxy)et hyl)amino)methyl)pyrazine-2- carboxylate (0.28 g, 0.67 mmol) in DMF (5 mL) was added N,N-diisopropylethylamine (0.09 g, 0.69 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 15 minutes. tert-Butyl (S)-((2'-(3-amino-2-methylphenyl)-3'-chloro-6-methoxy-[2,4'- bipyridin]- 5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (Example 42, step (d)) (0.19 g, 0.34 mmol) was then added and the mixture stirred at room temperature for 18 hours. Water (10 mL) and saturated aqueous brine solution (10 mL) were added, and the mixture extracted with an ethyl acetate/THF mixture (10:1 v/v, 30 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-15% ethyl acetate/petroleum ether) to afford tert-butyl (S)- ((5-((3-(5-(((tert-butoxycarbonyl)((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'-yl)-2-methylphenyl)carbamoyl)pyr azin-2-yl)methyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)carbamate (230 mg, 48% yield) as a yellow gum. LCMS: m/z found 945 [M+H] ⁺ . (d) (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl) amino)methyl)pyrazine-2- carboxamide To a mixture of tert-butyl (S)-((5-((3-(5-(((tert-butoxycarbonyl)((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-3'-chloro-6-methoxy-[2,4'-bipyridin] -2'-yl)-2- methylphenyl)carbamoyl)pyrazin-2-yl)methyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)carbamate (0.22 g,0.23 mmol) in 1,4-dioxane (1.3 mL) was added concentrated aqueous HCl solution (12 M, 0.26 mL) in one portion and the mixture stirred at room temperature for 0.5 hours. The mixture was combined with two additional batches at 60 mg and 10 mg scale. The mixture was neutralized with saturated aqueous sodium carbonate solution, concentrated and the residue purified by reverse phase HPLC to afford (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl) amino)methyl)pyrazine-2- carboxamide (42.3 mg, 30% yield) as a yellow solid. LCMS: m/z found 631 [M+H] ⁺ , retention time = 2.00 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 9.34 (d, 1H), 8.80 (d, 1H), 8.64 (d, 1H), 7.96 (d, 1H), 7.83 (d, 1H), 7.76 (d, 1H), 7.46-7.41 (m, 2H), 7.24 (dd, 1H), 4.13 (s, 2H), 4.06 (s, 3H), 3.89-3.83 (m, 3H), 3.73 (t, 2H), 2.85 (t, 2H), 2.72-2.68 (m, 2H), 2.38-2.29 (m, 3H), 2.17 (s, 3H), 1.86-1.78 (m, 1H). Example 46: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- hydroxyethyl)amino)methyl)thiazole-2-carboxamide (a) Ethyl 5-formylthiazole-2-carboxylate A mixture of ethyl 2-amino-2-thioxoacetate (4.41 g, 33.1 mmol) and 2- bromomalonaldehyde (5 g, 33.1 mmol) in 1,4-dioxane (200 mL) was degassed and purged with N ₂ and then the mixture stirred at 60 °C for 12 hours. Water (50 mL) was added and the mixture extracted with ethyl acetate (2 x 50 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 50 mL), dried with anhydrous sodium sulfate, filtered and concentrated to give ethyl 5-formylthiazole-2-carboxylate (5.4 g, crude) as a brown oil. LCMS: m/z found 186 [M+H] ⁺ . (b) Ethyl 5-(((tert-butoxycarbonyl)(2-hydroxyethyl)amino)methyl)thiazo le-2- carboxylate To a mixture of ethyl 5-formylthiazole-2-carboxylate (2 g, 10.8 mmol) and 2- aminoethan-1-ol (0.26 mL, 4.32 mmol) in THF/ethanol mixture (3:2, 10 mL) was added sodium acetate (1.77 g, 21.6 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 12 hours. Sodium cyanoborohydride (2.04 g, 32.4 mmol) was then added and the mixture stirred at room temperature for 1 hour to give ethyl 5-(((2- hydroxyethyl)amino)methyl)thiazole-2-carboxylate (LCMS: m/z found 231 [M+H] ⁺ ). Di-tert- butyl dicarbonate (2.48 mL, 10.8 mmol) and triethylamine (0.9 mL, 6.49 mmol) were then added, and the mixture stirred at room temperature for 12 hours under N ₂ . The mixture was combined with another batch at 435 mg scale. Water (30 mL) was added and the mixture extracted with ethyl acetate (2 x 30 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 30 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (25-100% ethyl acetate/petroleum ether) to afford ethyl 5-(((tert-butoxycarbonyl)(2- hydroxyethyl)amino)methyl)thiazole-2-carboxylate (0.9 g, 22% yield) as a yellow oil. LCMS: m/z found 331 [M+H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4): δ 7.82 (s, 1H), 4.64 (s, 2H), 4.34 (q, 2H), 3.60-3.52 (m, 2H), 3.31-3.22 (m, 2H), 1.39 (s, 9H), 1.30 (t, 3H). (c) Lithium 5-(((tert-butoxycarbonyl)(2-hydroxyethyl)amino)methyl)thiazo le-2- carboxylate To a mixture of ethyl 5-(((tert-butoxycarbonyl)(2- hydroxyethyl)amino)methyl)thiazole-2-carboxylate (0.5 g, 1.51 mmol) in THF/water mixture (10:1 v/v, 2.2 mL) was added lithium hydroxide monohydrate (0.07 g, 3.03 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 3 hours. The mixture was then concentrated to give lithium 5-(((tert-butoxycarbonyl)(2- hydroxyethyl)amino)methyl)thiazole-2-carboxylate (0.5 g, crude) as a yellow oil. LCMS: m/z found 303 [M+H] ⁺ . (d) tert-Butyl (S)-((2'-(3-(5-(((tert-butoxycarbonyl)(2- hydroxyethyl)amino)methyl)thiazole-2-carboxamido)-2-methylph enyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl) methyl)carbamate To a mixture of lithium 5-(((tert-butoxycarbonyl)(2- hydroxyethyl)amino)methyl)thiazole-2-carboxylate (0.28 g, 0.91 mmol) and tert-butyl (S)- ((2'-(3-amino-2-methylphenyl)-3'-chloro-6-methoxy-[2,4'-bipy ridin]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (Example 42, step (d)) in DMF (5 mL) was added N,N-diisopropylethylamine (0.08 mL, 0.45 mmol) and 2-chloro-1-methylpyridinium iodide (0.23 g, 0.91 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 12 hours. The mixture was combined with another batch at 56 mg scale. Water (20 mL) was added, and the mixture extracted with ethyl acetate (2 x 20 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 20 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-25% methanol/ethyl acetate) to afford tert-butyl (S)-((2'-(3-(5-(((tert- butoxycarbonyl)(2-hydroxyethyl)amino)methyl)thiazole-2-carbo xamido)-2-methylphenyl)- 3'-chloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrr olidin-2-yl)methyl)carbamate (0.4 g, 88% yield) as a yellow solid. LCMS: m/z found 836 [M+H] ⁺ . (e) (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl) amino)methyl)thiazole-2- carboxamide To a mixture of tert-butyl (S)-((2'-(3-(5-(((tert-butoxycarbonyl)(2- hydroxyethyl)amino)methyl)thiazole-2-carboxamido)-2-methylph enyl)-3'-chloro-6-methoxy- [2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)c arbamate (0.4 g, 0.48 mmol) in 1,4-dioxane (3 mL) was added concentrated HCl solution (1.17 mL) in one portion under N ₂ and the mixture stirred at room temperature for 1 hour. The mixture was combined with another batch at 10 mg scale. The mixture was neutralized with saturated aqueous sodium bicarbonate solution, concentrated and the residue purified by reverse phase HPLC to afford (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)thiazole-2-carboxamide (104.5 mg, 33% yield) as a white solid. LCMS: m/z found 636 [M+H] ⁺ , retention time = 2.06 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.64 (d, 1H), 7.91 (s, 1H), 7.83 (d, 2H), 7.75 (d, 1H), 7.44-7.40 (m, 2H), 7.24 (d, 1H), 4.14 (s, 2H), 4.06 (s, 3H), 3.87-3.83 (m, 3H), 3.69 (t, 2H), 2.80-2.67 (m, 4H), 2.38-2.27 (m, 3H), 2.15 (s, 3H), 1.88-1.80 (m, 1H). Example 47: (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-3-(2- ((3- fluoropropyl)(methyl)amino)ethyl)-1H-pyrazole-5-carboxamide (a) Ethyl 6-benzyl-4,5,6,7-tetrahydropyrazolo[1,5-c]pyrimidine-2-carbo xylate To a mixture of 21% sodium ethoxide solution in ethanol (47.1 g, 145 mmol) in ethanol (250 mL) was added diethyl oxalate (19.3 g, 132 mmol) at -10°C, then 1- benzylpiperidin-4-one (25 g, 132 mmol) added to the mixture at -10°C for 1 hour, and the mixture stirred at room temperature for 10 hours under N ₂ . Hydrazine hydrate (9.91 mL, 204 mmol) was then added, and the mixture stirred at room temperature for 10 min under N ₂ . Then pyridinium p-toluenesulfonate (66.4 g, 264 mmol) was added, and the mixture stirred at room temperature for 6 hours under N ₂ . Saturated aqueous sodium bicarbonate solution (400 mL) was then added and the mixture extracted with EtOAc (3 x 500 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-50 % ethyl acetate / petroleum ether) to afford ethyl 6-benzyl-4,5,6,7-tetrahydropyrazolo[1,5- c]pyrimidine-2-carboxylate (12 g, 16% yield) as a yellow oil. ¹ H NMR (400 MHz, DMSO- d ₆ ): δ 7.33-7.25 (m, 5H), 6.52 (s, 1H), 4.85 (s, 2H), 4.23-4.18 (m, 2H), 3.75 (s, 2H), 3.00 (t, 2H), 2.85 (t, 2H), 1.23 (t, 3H). (b) Ethyl 4,5,6,7-tetrahydropyrazolo[1,5-c]pyrimidine-2-carboxylate A mixture of ethyl 6-benzyl-4,5,6,7-tetrahydropyrazolo[1,5-c]pyrimidine-2- carboxylate (1 g, 3.50 mmol) and palladium on carbon (10 wt.30%, 200 mg) in isopropanol (30 mL) was stirred at room temperature for 24 hours under H ₂ at 15 psi. The mixture was combined with another several batches totalling approximately 11 g. The mixture was filtered and the filtrate concentrated to afford ethyl 4,5,6,7-tetrahydropyrazolo[1,5-c]pyrimidine-2- carboxylate (5.5 g, crude) as a colourless oil. LCMS: m/z found 196 [M+H] ⁺ . The crude product was used in the next step without further purification. (c) Ethyl 6-(3-fluoropropyl)-4,5,6,7-tetrahydropyrazolo[1,5-c]pyrimidi ne-2- carboxylate To a mixture of ethyl 4,5,6,7-tetrahydropyrazolo[1,5-c]pyrimidine-2-carboxylate (1 g, 5.12 mmol) and 1-bromo-3-fluoro-propane (2.17 g, 15.4 mmol) in acetonitrile (20 mL) was added potassium carbonate (2.12 g, 15.4 mmol) and potassium iodide (0.17 g, 1.02 mmol) then the mixture was stirred at 100 °C for 12 hours under N ₂ . Water (50 mL) was added and the mixture extracted with EtOAc (2 x 500 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure to afford ethyl 6-(3- fluoropropyl)-4,5,6,7-tetrahydropyrazolo[1,5-c]pyrimidine-2- carboxylate (1.2 g, crude) as a yellow oil. LCMS: m/z found 256 [M+H] ⁺ . The crude product was used in the next step without further purification. (d) N-(3-Bromo-2-chlorophenyl)-6-(3-fluoropropyl)-4,5,6,7-tetrah ydropyrazolo[1,5- c]pyrimidine-2-carboxamide To a mixture of 3-bromo-2-chloroaniline (0.81 g, 3.92 mmol) in THF (15 mL) was added 1.0 M lithium bis(trimethylsilyl)amide solution in THF (7.83 mL, 7.84 mmol) at 0°C, and the mixture stirred at 0 °C for 0.5 hours under N ₂ . Ethyl 6-(3-fluoropropyl)-4,5,6,7- tetrahydropyrazolo[1,5-c]pyrimidine-2-carboxylate (1 g, 3.92 mmol) in THF (15 mL) was then added and the mixture stirred at 0 °C for 0.5 hours under N ₂ . The mixture was combined with another batch at the 0.2 g scale. Water (50 mL) was added, and the mixture extracted with EtOAc (2 x 100 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-70 % ethyl acetate / Petroleum ether) to afford 440 mg of N-(3- bromo-2-chlorophenyl)-6-(3-fluoropropyl)-4,5,6,7-tetrahydrop yrazolo[1,5-c]pyrimidine-2- carboxamide. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 9.63 (s, 1H), 8.12 (d, 1H), 7.59 (d, 1H), 7.34 (t, 1H), 6.62 (s, 1H), 4.98 (s, 2H), 4.58 (t, 1H), 4.47 (t, 1H), 3.12-3.09 (m, 2H), 2.91-2.86 (m, 2H), 2.74-2.70 (m, 2H), 1.93-1.84 (m, 2H). (e) N-(2-Chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)p henyl)-6-(3- fluoropropyl)-4,5,6,7-tetrahydropyrazolo[1,5-c]pyrimidine-2- carboxamide To a mixture of N-(3-bromo-2-chlorophenyl)-6-(3-fluoropropyl)-4,5,6,7- tetrahydropyrazolo[1,5-c]pyrimidine-2-carboxamide (0.39 g, 0.94 mmol) and bis(pinacolato)diboron (1.43 g, 5.63 mmol) in 1,4-dioxane (10 mL) was added potassium acetate (0.28 g, 2.81 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (0.08 g, 0.09 mmol), and the mixture stirred at 130 °C for 2 hours under N ₂ . The mixture was combined with another batch at the 0.05 g scale. The mixture was concentrated and the residue purified by normal phase SiO ₂ chromatography (0-70 % ethyl acetate / petroleum ether) to afford N-(2-chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)p henyl)-6-(3- fluoropropyl)-4,5,6,7-tetrahydropyrazolo[1,5-c]pyrimidine-2- carboxamide (450 mg) as a yellow oil. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 9.47 (s, 1H), 8.19 (dd, 1H), 7.39-7.31 (m, 2H), 6.57 (s, 1H), 4.94 (s, 2H), 4.54 (t, 1H), 4.43 (t, 1H), 3.08-3.05 (m, 2H), 2.87-2.84 (m, 2H), 2.70-2.66 (m, 2H), 1.90-1.80 (m, 2H), 1.29 (s, 12H). (f) N-(2-Chloro-3-(3'-chloro-5-formyl-6-methoxy-[2,4'-bipyridin] -2'-yl)phenyl)-6-(3- fluoropropyl)-4,5,6,7-tetrahydropyrazolo[1,5-c]pyrimidine-2- carboxamide To a mixture of N-(2-chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)p henyl)- 6-(3-fluoropropyl)-4,5,6,7-tetrahydropyrazolo[1,5-c]pyrimidi ne-2-carboxamide (400 mg, 0.86 mmol) and 2',3'-dichloro-6-methoxy-[2,4'-bipyridine]-5-carbaldehyde (Example 23, step (a)) (294 mg, 1.04 mmol) in THF/water (5:1 v/v, 12 mL) was added potassium phosphate (550 mg, 2.59 mmol) and chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl- 1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II ) (68 mg, 0.09 mmol) and the mixture stirred at 80 °C for 1 hour under N ₂ . Water (10 mL) was added, and the mixture extracted with EtOAc (2 x 20 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-80 % EtOAc / Petroleum ether) to afford N-(2-chloro-3-(3'-chloro- 5-formyl-6-methoxy-[2,4'-bipyridin]-2'-yl)phenyl)-6-(3-fluor opropyl)-4,5,6,7- tetrahydropyrazolo[1,5-c]pyrimidine-2-carboxamide (240 mg, 47% yield) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.31 (s, 1H), 9.58 (s, 1H), 8.78 (d, 1H), 8.30-8.27 (m, 2H), 7.82 (d, 1H), 7.60 (d, 1H), 7.53 (t, 1H), 7.31 (dd, 1H), 6.64 (s, 1H), 4.98 (s, 2H), 4.58 (t, 1H), 4.46 (t, 1H), 4.09 (s, 3H), 3.12-3.09 (m, 2H), 2.92-2.89 (m, 2H), 2.73-2.70 (m, 2H), 1.97-1.84 (m, 2H). (g) (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-3-(2- ((3- fluoropropyl)(methyl)amino)ethyl)-1H-pyrazole-5-carboxamide To a mixture of N-(2-chloro-3-(3'-chloro-5-formyl-6-methoxy-[2,4'-bipyridin] -2'- yl)phenyl)-6-(3-fluoropropyl)-4,5,6,7-tetrahydropyrazolo[1,5 -c]pyrimidine-2-carboxamide (50 mg, 0.086 mmol) and (S)-5-(aminomethyl)pyrrolidin-2-one hydrochloride salt (25.8 mg, 0.171 mmol) in dichloromethane/methanol (1:1 v/v, 6 mL) was added sodium acetate (21.0 mg, 0.257 mmol) and the mixture stirred at room temperature for 1.5 hours under N ₂ . Sodium cyanoborohydride (16.1 mg, 0.257 mmol) was then added and the mixture stirred at room temperature for 0.5 hours under N ₂ . The mixture was concentrated and the residue purified by reverse phase HPLC to afford (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin - 2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-3-( 2-((3- fluoropropyl)(methyl)amino)ethyl)-1H-pyrazole-5-carboxamide (14.6 mg, 22% yield) as a white solid. LCMS: m/z found 683 [M+H] ⁺ , retention time =2.29 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.65 (d, 1H), 8.52 (d, 1H), 7.83 (d, 1H), 7.80 (d, 1H), 7.53 (t, 1H), 7.44 (d, 1H), 7.26 (d, 1H), 6.72 (s, 1H), 4.56 (t, 1H), 4.43 (t, 1H), 4.06 (s, 3H), 3.91-3.83 (m, 3H), 2.96-2.92 (m, 2H), 2.78-2.69 (m, 4H), 2.63-2.59 (m, 2H), 2.38-2.25 (m, 6H), 1.95- 1.84 (m, 3H). Example 48: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- hydroxyethyl)amino)methyl)-3-methoxypicolinamide (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl) amino)methyl)-3- methoxypicolinamide was prepared in a similar fashion to Example 43, replacing 4- bromothiazole-2-carboxylic acid with 5-bromo-3-methoxypicolinic acid in step (a) and potassium osmate (VI) dihydrate with osmium tetroxide in step (c). LCMS: m/z found 660 [M+H] ⁺ , retention time = 1.96 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.63 (d, 1H), 8.28 (d, 1H), 7.99 (d, 1H), 7.83 (d, 1H), 7.79 (s, 1H), 7.75 (d, 1H), 7.45-7.40 (m, 2H), 7.21 (d, 1H), 4.09-4.02 (m, 6H), 3.97 (s, 2H), 3.91-3.83 (m, 3H), 3.76-3.71 (m, 2H), 2.88- 2.79 (m, 3H), 2.76-2.69 (m, 1H), 2.48-2.25 (m, 3H), 2.18 (s, 3H), 1.98-1.79 (m, 1H). Example 49: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- hydroxyethyl)amino)methyl)-3-methylpicolinamide (a) Methyl 3-methyl-5-vinylpicolinate To a mixture of methyl 5-bromo-3-methylpicolinate (1.5 g, 6.52 mmol) and 4,4,5,5- tetramethyl-2-vinyl-1,3,2-dioxaborolane (1.22 mL, 7.17 mmol) in THF/water mixture (5:1 v/v, 12 mL) was added chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1 ,1′- biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (0.4 g, 0.51 mmol) and potassium phosphate (4.15 g, 19.6 mmol) in one portion under N ₂ and the mixture stirred at 80 °C for 6 hours. Water (40 mL) was added and the mixture extracted with ethyl acetate (2 x 40 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 40 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (9-11% ethyl acetate/petroleum ether) to afford methyl 3-methyl-5-vinylpicolinate (1.2 g, 95% yield) as a yellow oil. LCMS: m/z found 178 [M+H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d4): δ 8.48 (d, 1H), 7.55 (d, 1H), 6.68- 6.61 (m, 1H), 5.86 (d, 1H), 5.42 (d, 1H), 3.91 (s, 3H), 2.55 (s, 3H). (b) Methyl 5-formyl-3-methylpicolinate To a mixture of methyl 3-methyl-5-vinylpicolinate (0.3 g, 1.69 mmol) in THF/water mixture (10:1 v/v, 3.3 mL) was added potassium osmate(VI) dihydrate (0.12 g, 0.34 mmol) in one portion under N ₂ and the mixture stirred at 0 °C for 0.5 hours. To the mixture was added sodium periodate (1.09 g, 5.08 mmol) at 0 °C under N ₂ and the mixture was stirred at room temperature for 12 hours. To the mixture was was quenched by the addition of aqueous sodium sulfite solution (2 mL) and the mixture combined with another batch at 100 mg scale. Water (5 mL) was added, and the mixture was extracted with ethyl acetate (2 x 5 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 5 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (9-25% ethyl acetate/petroleum ether) to afford methyl 5- formyl-3-methylpicolinate (0.2 g, 49% yield) as a yellow oil. LCMS: m/z found 180 [M+H] ⁺ . (c) Methyl 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-3-methylpicolinat e A mixture of methyl 5-formyl-3-methylpicolinate (0.2 g, 1.12 mmol) and 2-((tert- butyldimethylsilyl)oxy)ethan-1-amine (0.2 g, 1.12 mmol) in THF/methanol mixture (1:1 v/v, 3 mL) was stirred at room temperature for 0.5 hours. Sodium cyanoborohydride (0.21 g, 3.35 mmol) was then added and the mixture stirred at room temperature for 2.5 hours to give methyl 5-(((2-((tert-butyldimethylsilyl)oxy)ethyl)amino)methyl)-3-m ethylpicolinate (LCMS: m/z found 339 [M+H] ⁺ ). Di-tert-butyl dicarbonate (0.3 mL, 1.3 mmol) and triethylamine (0.16 mL, 1.18 mmol) were then added in one portion under N ₂ and the mixture stirred at room temperature for 12 hours. Water (15 mL) was added, and the mixture extracted with ethyl acetate (2 x 15 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 15 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-25% ethyl acetate/petroleum ether) to afford methyl 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-3-methylpicolinat e (0.3 g, 47% yield) as a yellow oil. LCMS: m/z found 439 [M+H] ⁺ . (d) Lithium 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-3-methylpicolinat e To a mixture of methyl 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-3-methylpicolinat e (0.3 g, 0.68 mmol) in THF/water mixture (15:1 v/v, 3.2 mL) was added lithium hydroxide monohydrate (0.03 g, 1.37 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 12 hours. The mixture was then concentrated to afford lithium 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-3-methylpicolinat e (0.3 g, crude) as a white solid. LCMS: m/z found 425 [M+H] ⁺ . (e) tert-Butyl (S)-((2'-(3-(5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-3-methylpicolinam ido)-2-methylphenyl)-3'- chloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrroli din-2-yl)methyl)carbamate To a mixture of lithium 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-3-methylpicolinat e (0.25 g, 0.58 mmol) and tert- butyl (S)-((2'-(3-amino-2-methylphenyl)-3'-chloro-6-methoxy-[2,4'- bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (Example 42, step (d)) (0.22 g, 0.41 mmol) in DMF (7 mL) was added 2-chloro-1-methylpyridinium iodide (0.15 g, 0.58 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 5 hours. The mixture was combined with another batch at 50 mg scale. Water (15 mL) was added, and the mixture extracted with ethyl acetate (2 x 15 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 15 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (14-100% ethyl acetate/petroleum ether) to afford tert-butyl (S)-((2'-(3-(5-(((tert-butoxycarbonyl)(2- ((tert-butyldimethylsilyl)oxy)ethyl)amino)methyl)-3-methylpi colinamido)-2-methylphenyl)- 3'-chloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrr olidin-2-yl)methyl)carbamate (0.45 g, 75% yield) as a yellow solid. LCMS: m/z found 958 [M+H] ⁺ . (f) (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl) amino)methyl)-3- methylpicolinamide To a mixture of tert-butyl (S)-((2'-(3-(5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-3-methylpicolinam ido)-2-methylphenyl)-3'- chloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrroli din-2-yl)methyl)carbamate (0.25 g, 0.26 mmol) in 1,4-dioxane (3 mL) was added concentrated HCl solution (0.5 mL) in one portion under N ₂ and the mixture stirred at room temperature for 0.5 hours. The mixture was neutralized with saturated aqueous sodium bicarbonate solution, concentrated and the residue purified by reverse phase HPLC to afford (S)-N-(3-(3'-chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-(((2- hydroxyethyl)amino)methyl)-3-methylpicolinamide (26.3 mg, 15% yield) as a yellow solid. LCMS: m/z found 644 [M+H] ⁺ , retention time = 2.19 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.63 (d, 1H), 8.52 (d, 1H), 8.02 (d, 1H), 7.84-7.81 (m, 2H), 7.75 (d, 1H), 7.45-7.40 (m, 2H), 7.20 (d, 1H), 4.06 (s, 3H), 3.91 (s, 2H), 3.88-3.82 (m, 3H), 3.71 (t, 2H), 2.83-2.67 (m, 7H), 2.38-2.27 (m, 3H), 2.18 (s, 3H), 1.88-1.80 (m, 1H). Example 50: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-4-(((2- hydroxyethyl)amino)methyl)picolinamide (a) tert-Butyl (S)-((3'-chloro-2'-(3-(4-(hydroxymethyl)picolinamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate To a mixture of tert-butyl (S)-((2'-(3-amino-2-methylphenyl)-3'-chloro-6-methoxy- [2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)c arbamate (Example 42, step (d)) (0.8 g, 1.45 mmol) and 4-(hydroxymethyl)picolinic acid (0.4 g, 2.61 mmol) in DMF (10 mL) was added N,N-diisopropylethylamine (0.5 mL) and 2-chloro-1-methylpyridinium iodide (0.74 g, 2.90 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 12 hours. Water (50 mL) was added, and the mixture extracted with ethyl acetate (50 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (10-100% ethyl acetate/petroleum ether) to afford tert-butyl (S)-((3'-chloro-2'-(3-(4- (hydroxymethyl)picolinamido)-2-methylphenyl)-6-methoxy-[2,4' -bipyridin]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (550 mg, 41% yield) as a yellow oil. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.41 (s, 1H), 8.72 (d, 1H), 8.67 (d, 1H), 8.15 (s, 1H), 7.91 (d, 1H), 7.76 (s, 1H), 7.71 (d, 1H), 7.61 (d, 1H), 7.38 (t, 1H), 7.17 (d, 1H), 5.61 (t, 1H), 4.68 (d, 2H), 4.44- 4.36 (m, 2H), 3.97 (s, 3H), 3.79-3.77 (m, 1H), 3.29-3.27 (m, 2H), 2.10-2.06 (m, 5H), 1.76- 1.70 (m, 1H), 1.44-1.31 (m, 9H). (b) tert-Butyl (S)-((3'-chloro-2'-(3-(4-(((2- hydroxyethyl)amino)methyl)picolinamido)-2-methylphenyl)-6-me thoxy-[2,4'-bipyridin]- 5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-2'-(3-(4-(hydroxymethyl)picolinamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate (0.2 g, 0.29 mmol) in dichloromethane (3 mL) was added manganese dioxide (0.51 g, 5.82 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 12 hours. Additional manganese dioxide (0.25 g, 2.91 mmol) was added, and the mixture stirred at room temperature for 6 hours. The mixture was combined with another batch at the same scale. The mixture was filtered through Celite® to afford a solution of tert- butyl (S)-((3'-chloro-2'-(3-(4-formylpicolinamido)-2-methylphenyl) -6-methoxy-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te (LCMS: m/z found 685 [M+H] ⁺ ).2-Aminoethan-1-ol (0.06 g, 0.99 mmol) in THF/methanol mixture (1:1 v/v, 4 mL) and sodium acetate (0.16 g, 1.97 mmol) were added and the mixture was stirred at room temperature for 11.5 hours. Sodium cyanoborohydride (0.12 g, 1.97 mmol) was then added and the mixture stirred at room temperature for 0.5 hours. The mixture was combined with another batch at 100 mg scale. The mixture was concentrated, water (50 mL) and saturated aqueous brine solution (15 mL) added, and the mixture extracted with ethyl acetate (50 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (3-30% methanol/ethyl acetate) to afford tert-butyl (S)-((3'-chloro-2'-(3-(4-(((2-hydroxyethyl)amino)methyl)pico linamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate (180 mg, 30% yield) as a yellow gum. LCMS: m/z found 730 [M+H] ⁺ . (c) (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl) amino)methyl)picolinamide To a mixture of tert-butyl (S)-((3'-chloro-2'-(3-(4-(((2- hydroxyethyl)amino)methyl)picolinamido)-2-methylphenyl)-6-me thoxy-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (0.18 g, 0.24 mmol) 1,4-dioxane (1 mL) was added concentrated HCl solution (0.3 mL) in one portion under N ₂ and the mixture stirred at room temperature for 0.5 hours. The mixture was neutralized with saturated aqueous sodium bicarbonate solution and the mixture purified by reverse phase HPLC to afford the product as a formic salt (~50 mg). The product (~50 mg) was neutralized with saturated aqueous sodium bicarbonate solution, deionized water (15 mL) was added and the mixture extracted with dichloromethane (3 x 5 mL). The combined organic phase was concentrated and lyophilized to afford (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin- 2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylph enyl)-4-(((2- hydroxyethyl)amino)methyl)picolinamide (25.2 mg, 18% yield) as a white solid. LCMS: m/z found 630 [M+H] ⁺ , retention time = 2.10 min (Method A). ¹ H NMR (400 MHz, Methanol- d4): δ 8.67 (d, 1H), 8.64 (d, 1H), 8.27 (s, 1H), 8.09 (d, 1H), 7.83 (d, 1H), 7.76 (d, 1H), 7.64 (dd, 1H), 7.45-7.41 (m, 2H), 7.21 (dd, 1H), 4.06 (s, 3H), 3.98 (s, 2H), 3.87-3.84 (m, 3H), 3.72 (t, 2H), 2.78 (t, 2H), 2.73-2.66 (m, 2H), 2.38-2.27 (m, 3H).2.20 (s, 3H), 1.87-1.81 (m, 1H). Example 51: (S)-N-(3-(3-Chloro-2-(2-(2-hydroxypropyl)-8-methoxy-1,2,3,4- tetrahydroisoquinolin-6-yl)pyridin-4-yl)-2-methylphenyl)-5-( ((2- hydroxyethyl)amino)methyl)picolinamide (a) (S)-1-(6-bromo-8-methoxy-3,4-dihydroisoquinolin-2(1H)-yl)pro pan-2-ol To a mixture of 6-bromo-8-methoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride salt (0.25 g, 0.9 mmol) in ethanol (4 mL) was added N,N-diisopropylethylamine (0.94 mL, 5.38 mmol) and (S)-2-methyloxirane (0.38 mL, 5.38 mmol) in one portion under N ₂ atmosphere and the mixture stirred at room temperature for 12 hours. The mixture was then concentrated to afford (S)-1-(6-bromo-8-methoxy-3,4-dihydroisoquinolin-2(1H)-yl)pro pan-2-ol (0.35 g, crude) as a yellow gum. LCMS: m/z found 300 and 302 [M+H] ⁺ . (b) (S)-1-(8-Methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2 -yl)-3,4- dihydroisoquinolin-2(1H)-yl)propan-2-ol To a mixture of (S)-1-(6-bromo-8-methoxy-3,4-dihydroisoquinolin-2(1H)-yl)pro pan- 2-ol (0.3 g, 1 mmol) and bis(pinacolato)diboron (0.63 g, 2.5 mmol) in 1,4-dioxane (6 mL) was added potassium acetate (0.2 g, 2 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (0.04 g, 0.05 mmol) in one portion under N ₂ atmosphere and the mixture stirred at 115 °C for 3 h. The mixture was concentrated and the residue purified by normal phase SiO ₂ chromatography (0-15% ethyl acetate/petroleum ether to 20% MeOH/ethyl acetate) to afford (S)-1-(8- methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4- dihydroisoquinolin-2(1H)- yl)propan-2-ol (0.17 g, 45% yield) as a yellow gum. LCMS: m/z found 348 [M+H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 7.23 (s, 1H), 7.17 (s, 1H), 4.26-4.20 (m, 1H), 4.18-4.10 (m, 2H), 3.89 (s, 3H), 3.30-3.23 (m, 2H), 3.10-3.07 (m, 2H), 3.03-2.95 (m, 2H), 1.37 (s, 12H), 1.27-1.25 (m, 3H). (c) tert-Butyl (S)-((6-((3-(3-chloro-2-(2-(2-hydroxypropyl)-8-methoxy-1,2,3 ,4- tetrahydroisoquinolin-6-yl)pyridin-4-yl)-2-methylphenyl)carb amoyl)pyridin-3- yl)methyl)(2-hydroxyethyl)carbamate To a mixture of tert-butyl ((6-((3-(2,3-dichloropyridin-4-yl)-2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)c arbamate (Example 1, step (e)) (0.17 g, 0.32 mmol) and (S)-1-(8-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2 - yl)-3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol (0.22 g, 0.64 mmol) in 1,4-dioxane/water mixture (6:1 v/v, 7 mL) was added potassium carbonate (0.13 g, 0.96 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (0.03 g, 0.03 mmol) in one portion under N ₂ and the mixture stirred at 110 °C for 15 h. The mixture was concentrated, water (5 mL) and saturated aqueous brine solution (5 mL) added to the residue, and the mixture extracted with an ethyl acetate/THF mixture (10:1 v/v, 10 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether to 10% MeOH/ethyl acetate) to afford tert-butyl (S)-((6-((3-(3-chloro-2-(2-(2- hydroxypropyl)-8-methoxy-1,2,3,4-tetrahydroisoquinolin-6-yl) pyridin-4-yl)-2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)c arbamate (0.13 g, 15% yield) as a brown gum. LCMS: m/z found 716 [M+H] ⁺ . (d) (S)-N-(3-(3-Chloro-2-(2-(2-hydroxypropyl)-8-methoxy-1,2,3,4- tetrahydroisoquinolin-6-yl)pyridin-4-yl)-2-methylphenyl)-5-( ((2- hydroxyethyl)amino)methyl)picolinamide To a mixture of tert-butyl (S)-((6-((3-(3-chloro-2-(2-(2-hydroxypropyl)-8-methoxy- 1,2,3,4-tetrahydroisoquinolin-6-yl)pyridin-4-yl)-2-methylphe nyl)carbamoyl)pyridin-3- yl)methyl)(2-hydroxyethyl)carbamate (0.12 g, 0.17 mmol) in 1,4-dioxane (1.5 mL) was added concentrated HCl solution (12 M, 0.25 mL) in one portion and the mixture stirred at room temperature for 0.5 hours. The mixture was combined with another batch at 5 mg scale. The mixture was purified by reverse phase HPLC to afford (S)-N-(3-(3-chloro-2-(2-(2- hydroxypropyl)-8-methoxy-1,2,3,4-tetrahydroisoquinolin-6-yl) pyridin-4-yl)-2- methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)picolinamide (14.1 mg, 10% yield) as a yellow solid. LCMS: m/z found 616 [M+H] ⁺ , retention time = 2.46 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.71 (s, 1H), 8.60 (d, 1H), 8.22 (d, 1H), 8.06-8.00 (m, 2H), 7.44-7.38 (m, 2H), 7.12 (d, 1H), 7.07-7.05 (m, 2H), 4.12-4.06 (m, 1H), 3.96 (s, 2H), 3.90 (s, 3H), 3.78-3.66 (m, 4H), 3.00-2.98 (m, 2H), 2.87-2.84 (m, 2H), 2.78 (t, 2H), 2.61-2.53 (m, 2H), 2.19 (s, 3H), 1.22 (d, 3H). Example 52: (S)-N-(3-(3-Chloro-2-(8-methoxy-2-((5-oxopyrrolidin-2-yl)met hyl)-1,2,3,4- tetrahydroisoquinolin-6-yl)pyridin-4-yl)-2-methylphenyl)-5-( ((2- hydroxyethyl)amino)methyl)picolinamide (a) (S)-5-((6-Bromo-8-methoxy-3,4-dihydroisoquinolin-2(1H)-yl)me thyl)pyrrolidin- 2-one To a mixture of 6-bromo-8-methoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride salt (0.5 g, 2 mmol) and (S)-5-(bromomethyl)pyrrolidin-2-one (0.4 g, 1.44 mmol) in acetonitrile (10 mL) was added potassium carbonate (0.6 g, 4.31 mmol) in one portion under N ₂ atmosphere and the mixture stirred at 100 °C for 12 h. The mixture was filtered through SiO ₂ gel to afford (S)-5-((6-bromo-8-methoxy-3,4-dihydroisoquinolin-2(1H)-yl)me thyl)pyrrolidin- 2-one (0.46 g, crude) as a yellow solid. ¹ H NMR (400 MHz, Methanol-d4): δ 6.92-6.91 (m, 2H), 4.03-3.99 (m, 1H), 3.83 (s, 3H), 3.64-3.48 (m, 2H), 2.90-2.80 (m, 3H), 2.74-2.56 (m, 3H), 2.42-2.26 (m, 3H), 1.89-1.80 (m, 1H). (b) (S)-5-((8-Methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2-yl)-3,4- dihydroisoquinolin-2(1H)-yl)methyl)pyrrolidin-2-one To a mixture of (S)-5-((6-bromo-8-methoxy-3,4-dihydroisoquinolin-2(1H)- yl)methyl)pyrrolidin-2-one (0.4 g, 1.18 mmol) and bis(pinacolato)diboron (0.9 g, 3.54 mmol) in 1,4-dioxane (5 mL) was added potassium acetate (0.35 g, 3.54 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (0.05 g, 0.06 mmol) in one portion under N ₂ atmosphere and the mixture stirred at 105 °C for 3 h. The mixture was combined with another batch at 30 mg scale. The mixture was concentrated and the residue purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether to 10% methanol/ethyl acetate) to afford (S)-5-((8-methoxy-6- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroiso quinolin-2(1H)- yl)methyl)pyrrolidin-2-one (0.4 g, 70% yield) as a brown gum. LCMS: m/z found 387 [M+H] ⁺ . (c) tert-Butyl (S)-((6-((3-(3-chloro-2-(8-methoxy-2-((5-oxopyrrolidin-2-yl) methyl)- 1,2,3,4-tetrahydroisoquinolin-6-yl)pyridin-4-yl)-2-methylphe nyl)carbamoyl)pyridin-3- yl)methyl)(2-hydroxyethyl)carbamate To a mixture of tert-butyl ((6-((3-(2,3-dichloropyridin-4-yl)-2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)c arbamate (Example 1, step (e)) (0.23 g, 0.43 mmol) and (S)-5-((8-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2- yl)-3,4-dihydroisoquinolin-2(1H)-yl)methyl)pyrrolidin-2-one (0.2 g, 0.52 mmol) in 1,4- dioxane/water mixture (6:1 v/v, 5.8 mL) was added potassium phosphate (0.28 g, 1.3 mmol) and chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1 ,1′-biphenyl)[2-(2′-amino-1,1′- biphenyl)]palladium(II) (0.03 g, 0.04 mmol) in one portion under N ₂ and the mixture stirred at 110 °C for 3 h. The mixture was combined with another batch at 50 mg scale. The mixture was concentrated, water (5 mL) and saturated aqueous brine solution (5 mL) added to the residue, and the mixture was extracted with an ethyl acetate/THF mixture (10:1 v/v, 10 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether to 10% methanol/ethyl acetate) to afford tert-butyl (S)-((6-((3-(3-chloro-2-(8-methoxy- 2-((5-oxopyrrolidin-2-yl)methyl)-1,2,3,4-tetrahydroisoquinol in-6-yl)pyridin-4-yl)-2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)c arbamate (0.2 g, 50% yield) as a brown gum. LCMS: m/z found 755 [M+H] ⁺ . (d) (S)-N-(3-(3-Chloro-2-(8-methoxy-2-((5-oxopyrrolidin-2-yl)met hyl)-1,2,3,4- tetrahydroisoquinolin-6-yl)pyridin-4-yl)-2-methylphenyl)-5-( ((2- hydroxyethyl)amino)methyl)picolinamide To a mixture of tert-butyl (S)-((6-((3-(3-chloro-2-(8-methoxy-2-((5-oxopyrrolidin-2- yl)methyl)-1,2,3,4-tetrahydroisoquinolin-6-yl)pyridin-4-yl)- 2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(2-hydroxyethyl)c arbamate (0.19 g, 0.25 mmol) in 1,4-dioxane (1 mL) was added concentrated HCl solution (12 M, 0.3 mL) in one portion and the mixture stirred at room temperature for 0.5 hours. The mixture was combined with another batch at 10 mg scale. The mixture was neutralized with saturated aqueous sodium carbonate solution and the mixture purified by reverse phase HPLC to afford (S)-N- (3-(3-chloro-2-(8-methoxy-2-((5-oxopyrrolidin-2-yl)methyl)-1 ,2,3,4-tetrahydroisoquinolin-6- yl)pyridin-4-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)m ethyl)picolinamide (24.3 mg, 10% yield) as a yellow solid. LCMS: m/z found 655 [M+H] ⁺ , retention time = 2.27 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.71 (d, 1H), 8.60 (d, 1H), 8.22 (d, 1H), 8.06-8.00 (m, 2H), 7.44-7.39 (m, 2H), 7.18-7.06 (m, 3H), 4.07-3.98 (m, 1H), 3.96-3.90 (m, 5H), 3.80-3.63 (m, 4H), 3.02-2.99 (m, 2H), 2.92-2.87 (m, 1H), 2.80-2.64 (m, 5H), 2.41-2.19 (m, 3H), 2.19 (s, 3H), 1.88-1.83 (m, 1H). Example 53: (S)-N-(3-(3-Chloro-4-(6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)pyrazin-2-yl)pyridin-2-yl)-2-methylph enyl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide (a) 5-Bromo-3-methoxypyrazine-2-carbaldehyde To a mixture of 5-bromo-2-iodo-3-methoxypyrazine (22.5 g, 71.5 mmol) in THF (350 mL) was dropwise added 2.5 M n-Butyllithium solution in n-hexane (29 mL, 72.5 mmol) at - 80 °C under N ₂ and the mixture stirred at -80 °C for 1 hours. To the mixture was added DMF (14 mL, 178 mmol) and the mixture stirred at -80 °C for 0.5 hours. Water (100 mL) was added and the mixture combined with another batch at 5 g scale. The mixture was extracted with ethyl acetate (2 x 50 mL), the combined organic phases washed with saturated aqueous brine solution (2 x 500 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-15% ethyl acetate/petroleum ether) to afford 5-bromo-3-methoxypyrazine-2-carbaldehyde (8.8 g, 25% yield) as a yellow solid. ¹ H NMR (400 MHz, Chloroform-d): δ 10.15 (s, 1H), 8.38 (s, 1H), 4.08 (s, 3H). (b) 5-(2,3-Dichloropyridin-4-yl)-3-methoxypyrazine-2-carbaldehyd e To a mixture of 5-bromo-3-methoxypyrazine-2-carbaldehyde (1 g, 4.61 mmol) and 2,3-dichloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine (1.89 g, 6.91 mmol) in THF/water mixture (26:5, 31 mL) was added potassium carbonate (1.91 g, 13.8 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (0.23 g, 0.28 mmol) in one portion under N ₂ and the mixture stirred at 80 °C for 3 hours. The mixture was concentrated, water (5 mL) and saturated aqueous brine solution (5 mL) added, and the mixture extracted with an ethyl acetate/THF mixture (10:1 v/v, 50 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-20% ethyl acetate/petroleum ether) to afford 5-(2,3-dichloropyridin-4-yl)-3-methoxypyrazine-2-carbaldehyd e (0.9 g, 41% yield) as a yellow solid. ¹ H NMR (400 MHz, Chloroform-d): δ 10.26 (s, 1H), 8.68 (s, 1H), 8.40 (d, 1H), 7.44 (d, 1H), 4.10 (s, 3H). (c) tert-Butyl (S)-((5-(2,3-dichloropyridin-4-yl)-3-methoxypyrazin-2-yl)met hyl)((5- oxopyrrolidin-2-yl)methyl)carbamate To a mixture of 5-(2,3-dichloropyridin-4-yl)-3-methoxypyrazine-2-carbaldehyd e (0.6 g, 2.11 mmol) and (S)-5-(aminomethyl)pyrrolidin-2-one hydrochloride salt (0.35 g, 2.32 mmol) in THF/methanol mixture (3:1 v/v, 20 mL) was added sodium acetate (0.69 g, 8.45 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 2 hours. Sodium cyanoborohydride (0.4 g, 6.34 mmol) was then added and the mixture stirred at room temperature for 1 hour to give (S)-5-((((5-(2,3-dichloropyridin-4-yl)-3-methoxypyrazin-2- yl)methyl)amino)methyl)pyrrolidin-2-one (LCMS: m/z found 382 [M+H] ⁺ ). Triethylamine (0.35 mL, 2.51 mmol) and di-tert-butyl dicarbonate (0.86 mL, 3.77 mmol) were added in one portion under N ₂ and the mixture stirred at room temperature for 1 hour. The mixture was concentrated, water (5 mL) and saturated aqueous brine solution (5 mL) added, and the mixture extracted with an ethyl acetate/THF mixture (10:1 v/v, 50 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-15% ethyl acetate/petroleum ether) and further purified by reverse phase HPLC to afford tert-butyl (S)-((5-(2,3-dichloropyridin-4-yl)-3- methoxypyrazin-2-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)car bamate (0.34 g, 34% yield) as a yellow gum. ¹ H NMR (400 MHz, Methanol-d4): δ 8.55-8.52 (m, 1H), 8.46-8.45 (m, 1H), 7.68 (d, 1H), 4.74-4.60 (m, 2H), 4.09 (s, 3H), 4.08-3.95 (m, 1H), 3.59-3.51 (m, 2H), 2.50- 2.25 (m, 3H), 2.05-1.95 (m, 1H). (d) tert-Butyl (S)-((5-(2-(3-(5-(((tert-butoxycarbonyl)(2- hydroxyethyl)amino)methyl)picolinamido)-2-methylphenyl)-3-ch loropyridin-4-yl)-3- methoxypyrazin-2-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)car bamate To a mixture of tert-butyl (S)-((5-(2,3-dichloropyridin-4-yl)-3-methoxypyrazin-2- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (0.1 g, 0.21 mmol) and tert-butyl (2- hydroxyethyl)((6-((2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dio xaborolan-2- yl)phenyl)carbamoyl)pyridin-3-yl)methyl)carbamate (Example 20, step (a)) (0.14 g, 0.27 mmol) in 1,4-dioxane/water mixture (10:1 v/v, 3.3 mL) was added potassium phosphate (0.13 g, 0.62 mmol) and chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1 ,1′-biphenyl)[2-(2′- amino-1,1′-biphenyl)]palladium(II) (0.02 g, 0.02 mmol) in one portion under N ₂ and the mixture stirred at 105 °C for 1 hour. The mixture was combined with 3 batches at 20 mg scale. The mixture was concentrated, water (5 mL) and saturated aqueous brine solution (5 mL) added, and the mixture extracted with an ethyl acetate/THF mixture (10:1 v/v, 30 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-15% ethyl acetate/petroleum ether) to afford 100 mg of the product.170 mg of the product (70 mg from another batch) was purified by reverse phase HPLC. The eluent was neutralized with saturated aqueous sodium carbonate solution. The mixture was extracted with an ethyl acetate/THF mixture (10:1 v/v, 30 mL), the organic phase dried with anhydrous sodium sulfate, filtered and concentrated to afford tert-butyl (S)-((5-(2-(3-(5-(((tert-butoxycarbonyl)(2- hydroxyethyl)amino)methyl)picolinamido)-2-methylphenyl)-3-ch loropyridin-4-yl)-3- methoxypyrazin-2-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)car bamate (70 mg, 54% yield) as a yellow solid. LCMS: m/z found 831 [M+H] ⁺ . (e) (S)-N-(3-(3-Chloro-4-(6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)pyrazin-2-yl)pyridin-2-yl)-2-methylph enyl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide To a mixture of tert-butyl (S)-((5-(2-(3-(5-(((tert-butoxycarbonyl)(2- hydroxyethyl)amino)methyl)picolinamido)-2-methylphenyl)-3-ch loropyridin-4-yl)-3- methoxypyrazin-2-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)car bamate (0.06 g, 0.07 mmol) in 1,4-dioxane (1 mL) was added concentrated aqueous HCl solution (12 M, 0.2 mL) in one portion and the mixture stirred at room temperature for 0.5 hours. The mixture was combined with another batch at 10 mg scale. The mixture was neutralized with saturated aqueous sodium carbonate solution and purified by reverse phase HPLC to afford (S)-N-(3-(3-chloro- 4-(6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl) pyrazin-2-yl)pyridin-2-yl)-2- methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)picolinamide (20.3 mg, 10% yield) as a white solid. LCMS: m/z found 631 [M+H] ⁺ , retention time = 1.98 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.72-8.69 (m, 2H), 8.60 (s, 1H), 8.23 (d, 1H), 8.08-8.04 (m, 2H), 7.80 (d, 1H), 7.44 (t, 1H), 7.22 (d, 1H), 4.11 (s, 3H), 4.09-4.01 (m, 2H), 3.97 (s, 2H), 3.91- 3.85 (m, 1H), 3.71 (t, 2H), 2.84-2.76 (m, 4H), 2.39-2.29 (m, 3H), 2.19 (s, 3H), 1.88-1.82 (m, 1H). Example 54: (S)-(5-Oxopyrrolidin-2-yl)methyl ((3'-chloro-2'-(2-chloro-3-(5-(((2- hydroxyethyl)amino)methyl)picolinamido)phenyl)-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)carbamate (a) (S)-(5-Oxopyrrolidin-2-yl)methyl 1H-imidazole-1-carboxylate A flask was charged with (S)-5-(hydroxymethyl)pyrrolidin-2-one (0.15 g, 1.30 mmol, 1 eq) and 1,1’-carbonyl diimidazole (0.27 g, 1.69 mmol, 1.3 eq) and the system was purged with argon. Dry dichloromethane (3 mL) was added, and the resulting solution stirred for 30 minutes. The reaction was then diluted with ethyl acetate (50 mL) and washed successively with saturated sodium bicarbonate (10 mL), and saturated brine solution (10 mL). The organic layer was dried with sodium sulfate and concentrated under reduced pressure to give (S)-(5-oxopyrrolidin-2-yl)methyl 1H-imidazole-1-carboxylate 0.15 g (27 % yield). The product was used in the next step without further purification. LCMS: m/z found 210 [M+H] ⁺ . (b) (S)-(5-Oxopyrrolidin-2-yl)methyl ((6-bromo-2-methoxypyridin-3- yl)methyl)carbamate A vial was charged with (6-bromo-2-methoxypyridin-3-yl)methanamine (0.19 g, 0.86 mmol, 1.2 eq), 4-dimethylaminopyridine (0.02 g, 0.14 mmol, 0.2 eq), and (S)-(5- oxopyrrolidin-2-yl)methyl 1H-imidazole-1-carboxylate (0.15 g, 0.72 mmol, 1 eq). DMF (2 mL) followed by N,N-diisopropylethylamine (0.25 ml, 1.43 mmol, 2 eq) were then added and the reaction was stirred overnight at 65ºC. The mixture was diluted with ethyl acetate (50 mL), then washed with saturated aqueous brine solution (30 mL), the aqueous layer extracted with ethyl acetate (3 x 30 mL), then the combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography using a linear gradient (0-5 % methanol/dichloromethane) to afford (S)-(5-oxopyrrolidin-2-yl)methyl ((6-bromo-2-methoxypyridin-3-yl)methyl)carbamate (0.24 g, 92 % yield). LCMS: m/z found 358 [M+H] ⁺ . (c) (S)-(5-Oxopyrrolidin-2-yl)methyl ((2',3'-dichloro-6-methoxy-[2,4'-bipyridin]-5- yl)methyl) carbamate A microwave vial was charged with (S)-(5-oxopyrrolidin-2-yl)methyl ((6-bromo-2- methoxypyridin-3-yl)methyl)carbamate (0.10 g, 0.28 mmol, 1 eq), 2,3-dichloro-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.11 g, 0.42 mmol, 1.5), potassium carbonate (0.12 g, 0.84 mmol, 3 eq), and tetrakis(triphenylphosphine)palladium(0) (0.06 g, 0.06 mmol, 0.2 eq).1,4-Dioxane (2 mL) was added, and the reaction was sparged with nitrogen, then water (0.3 ml) was added and the mixture stirred at 110 °C for 20 minutes. The reaction was then diluted with ethyl acetate (50 mL), washed with saturated aqueous brine solution (30 mL), the aqueous layer extracted with ethyl acetate (3 x 30 mL), and the combined organic layers dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography using a linear gradient (0-5 % methanol / dichloromethane) to afford (S)-(5-oxopyrrolidin-2-yl)methyl ((2',3'-dichloro-6-methoxy-[2,4'- bipyridin]-5-yl)methyl) carbamate (0.074 g, 66 % yield). LCMS: m/z found 425 [M+H] ⁺ . (d) (S)-(5-Oxopyrrolidin-2-yl)methyl ((3'-chloro-2'-(2-chloro-3-(5- formylpicolinamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)m ethyl)carbamate A microwave vial was charged with (S)-(5-oxopyrrolidin-2-yl)methyl ((2',3'-dichloro- 6-methoxy-[2,4'-bipyridin]-5-yl)methyl) carbamate (0.07 g, 0.17 mmol, 1 eq), N-(2-chloro-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-5-formy lpicolinamide (0.07 g, 0.17 mmol, 1.5), potassium carbonate (0.07 g, 0.52 mmol, 3 eq), and tetrakis(triphenylphosphine)palladium(0) (0.04 g, 0.03 mmol, 0.2 eq).1,4-Dioxane (2 mL) was added, the reaction was sparged with nitrogen, then water (0.3 mL) was added, and the mixture stirred at 110 °C for 20 minutes. The reaction was diluted with ethyl acetate (50 mL), washed with saturated aqueous brine solution (30 mL), the aqueous layer extracted with ethyl acetate (3 x 30 mL), and the combined organic layers dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography using a linear gradient (0-10 % methanol / dichloromethane) to afford (S)- (5-oxopyrrolidin-2-yl)methyl ((3'-chloro-2'-(2-chloro-3-(5-formylpicolinamido)phenyl)-6- methoxy-[2,4'-bipyridin]-5-yl)methyl)carbamate (0.042 g, 37 % yield). LCMS: m/z found 649 [M+H] ⁺ . (e) (S)-(5-Oxopyrrolidin-2-yl)methyl ((3'-chloro-2'-(2-chloro-3-(5-(((2-hydroxyethyl) amino)methyl)picolinamido)phenyl)-6-methoxy-[2,4'-bipyridin] -5-yl)methyl)carbamate To a mixture (S)-(5-oxopyrrolidin-2-yl)methyl ((3'-chloro-2'-(2-chloro-3-(5- formylpicolinamido) phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)carbamate (0.04 g, 0.06 mmol, 1 eq), and 2-aminoethan-1-ol (0.01 g, 0.12 mmol, 2 eq), in 1:1 THF/methanol (8 mL) was added acetic acid (0.01 g, 0.12 mmol, 2 eq) and 4 A molecular sieves (1 g) and the mixture stirred at room temperature for 3 hours. Sodium cyanoborohydride (0.01 g, 0.15 mmol, 2.5 eq) was added and the mixture was stirred at room temperature for 1 hour. The reaction was then quenched by addition of water (1 mL), the mixture was diluted with ethyl acetate (50 mL), washed with saturated aqueous brine solution (30 mL), and the aqueous layer extracted with ethyl acetate (3 x 30 mL). The combined organic phases were then dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by reverse phase HPLC to give (S)-(5-oxopyrrolidin-2-yl)methyl ((3'-chloro-2'-(2-chloro-3-(5- (((2-hydroxyethyl) amino)methyl)picolinamido)phenyl)-6-methoxy-[2,4'-bipyridin] -5- yl)methyl)carbamate (4.1 mg, 10 % yield) as a white solid (TFA salt). LCMS: m/z found 694 [M+H] ⁺ , retention time = 1.94 min (Method D). ¹ H NMR (400 MHz, Methanol-d4) δ 8.79 (s, 1H), 8.68 – 8.57 (m, 2H), 8.37 – 8.29 (m, 1H), 8.20 – 8.13 (m, 1H), 7.75 (d, 1H), 7.69 (d, 1H), 7.52 (t, 1H), 7.38 (d, 1H), 7.24 (d, 1H), 4.39 (s, 2H), 4.28 (s, 2H), 4.08 (d, 2H), 4.00 – 3.83 (m, 5H), 3.82 – 3.77 (m, 2H), 3.19 (s, 1H), 2.31 (d, 3H), 1.90 (s, 1H). Example 55: (S)-5-(((2-Hydroxyethyl)amino)methyl)-N-(3-(4-(6-methoxy-5-( (((5- oxopyrrolidin-2-yl)methyl)amino)methyl)pyrazin-2-yl)-3-methy lpyridin-2-yl)-2- methylphenyl)picolinamide (a) 2-Chloro-3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2-yl)pyridine To a mixture of 2-chloro-4-iodo-3-methylpyridine (4 g, 15.78 mmol) and bis(pinacolato)diboron (12 g, 47.3 mmol) in 1,4-dioxane (80 mL) was added potassium acetate (4.65 g, 47.3 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1.29 g, 1.58 mmol) in one portion under N ₂ . The mixture was stirred at 110 °C for 12 h. The mixture was then concentrated and the residue purified by normal phase SiO ₂ chromatography (0-15% ethyl acetate/petroleum ether) and then further purified by reverse phase HPLC to afford 2-chloro-3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2- yl)pyridine (1.5 g, 37% yield) as an off-white gum. LCMS: m/z found 254 [M+H] ⁺ . (b) 5-(2-Chloro-3-methylpyridin-4-yl)-3-methoxypyrazine-2-carbal dehyde To a mixture of 2-chloro-3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2- yl)pyridine (0.4 g, 1.57 mmol) and 5-bromo-3-methoxypyrazine-2-carbaldehyde (0.31 g, 1.43 mmol) (Example 53, step (a)) in THF / water mixture (10:1 v/v, 11 mL) was added potassium carbonate (0.59 g, 4.29 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (0.06 g, 0.07 mmol) in one portion under N ₂ . The mixture was stirred at 80 °C for 1 h. The mixture was combined with another batch at 167 mg scale and concentrated. Water (20 mL) and saturated aqueous brine solution (20 mL) were added to the residue and the mixture extracted with ethyl acetate/THF mixture (10:1 v/v, 50 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-50% ethyl acetate/petroleum ether) to afford 5-(2-chloro-3- methylpyridin-4-yl)-3-methoxypyrazine-2-carbaldehyde (0.36 g, 41% yield) as a yellow solid. ¹ H NMR (400 MHz, Chloroform-d): δ 10.26 (s, 1H), 8.44 (s, 1H), 8.33 (d, 1H), 7.27 (d, 1H), 4.09 (s, 3H), 2.42 (s, 3H). (c) tert-Butyl (S)-((5-(2-chloro-3-methylpyridin-4-yl)-3-methoxypyrazin-2- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate To a mixture of 5-(2-chloro-3-methylpyridin-4-yl)-3-methoxypyrazine-2- carbaldehyde (0.33 g, 1.25 mmol) and (S)-5-(aminomethyl)-2-pyrrolidinone hydrochloride salt (0.2 g, 1.31 mmol) in THF / methanol mixture (2:1 v/v, 15 mL) was added sodium acetate (0.31 g, 3.75 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 1 h. Sodium cyanoborohydride (0.24 g, 3.75 mmol) was then added and the mixture stirred at room temperature for 0.5 hours. Triethylamine (0.18 mL, 1.29 mmol) and di-tert-butyl dicarbonate (0.38 mL, 1.67 mmol) were than added in one portion and the mixture stirred at room temperature for 1 hour. The mixture was combined with another batch at 40 mg scale. Water (5 mL) was added, and the mixture concentrated. Water (5 mL) and saturated aqueous brine solution (5 mL) were then added to the residue and the mixture extracted with ethyl acetate / THF mixture (10:1 v/v, 50 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-80% ethyl acetate/petroleum ether) to afford tert-butyl (S)- ((5-(2-chloro-3-methylpyridin-4-yl)-3-methoxypyrazin-2-yl)me thyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (0.45 g, 66% yield/2 steps) as a yellow gum. ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.31-8.25 (m, 2H), 7.43 (d, 1H), 4.65-4.52 (m, 2H), 4.00-3.94 (m, 4H), 3.55- 3.31 (m, 2H), 2.43 (s, 3H), 2.33-2.16 (m, 3H), 1.90-1.75 (m, 1H), 1.43-1.34 (m, 9H). (d) tert-Butyl (S)-((5-(2-(3-(5-(((tert-butoxycarbonyl)(2- hydroxyethyl)amino)methyl)picolinamido)-2-methylphenyl)-3-me thylpyridin-4-yl)-3- methoxypyrazin-2-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)car bamate To a mixture of tert-butyl (S)-((5-(2-chloro-3-methylpyridin-4-yl)-3-methoxypyrazin- 2-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (0.2 g, 0.43 mmol) and tert-butyl (2- hydroxyethyl)((6-((2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dio xaborolan-2- yl)phenyl)carbamoyl)pyridin-3-yl)methyl)carbamate (0.25 g, 0.5 mmol) (Example 20, step (a)) in 1,4-dioxane / water mixture (10:1 v/v, 11 mL) was added potassium phosphate (0.28 g, 1.3 mmol) and chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1 ,1′-biphenyl)[2-(2′- amino-1,1′-biphenyl)]palladium(II) (0.07 g, 0.09 mmol) in one portion under N ₂ and the mixture stirred at 110 °C for 5 h. The mixture was combined with another batch at 60 mg scale and concentrated. Water (10 mL) and saturated aqueous brine solution (10 mL) were added to the residue and the mixture was extracted with ethyl acetate/THF mixture (10:1 v/v, 20 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether) to afford tert-butyl (S)-((5-(2-(3-(5-(((tert-butoxycarbonyl)(2- hydroxyethyl)amino)methyl)picolinamido)-2-methylphenyl)-3-me thylpyridin-4-yl)-3- methoxypyrazin-2-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)car bamate (210 mg, 54% yield) as a yellow gum. LCMS: m/z found 811 [M+H] ⁺ . (e) (S)-5-(((2-Hydroxyethyl)amino)methyl)-N-(3-(4-(6-methoxy-5-( (((5- oxopyrrolidin-2-yl)methyl)amino)methyl)pyrazin-2-yl)-3-methy lpyridin-2-yl)-2- methylphenyl)picolinamide To a mixture of tert-butyl (S)-((5-(2-(3-(5-(((tert-butoxycarbonyl)(2- hydroxyethyl)amino)methyl)picolinamido)-2-methylphenyl)-3-me thylpyridin-4-yl)-3- methoxypyrazin-2-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)car bamate (0.2 g, 0.25 mmol) in 1,4-dioxane (1.3 mL) was added concentrated aqueous HCl solution (12 M, 0.3 mL) in one portion and the mixture stirred at room temperature for 1 hour. The mixture was combined with another batch at 10 mg scale. The mixture was neutralized with saturated aqueous sodium carbonate solution and purified by reverse phase HPLC to afford (S)-5-(((2- Hydroxyethyl)amino)methyl)-N-(3-(4-(6-methoxy-5-((((5-oxopyr rolidin-2- yl)methyl)amino)methyl)pyrazin-2-yl)-3-methylpyridin-2-yl)-2 -methylphenyl)picolinamide (25.6 mg, 16% yield) as a yellow solid. LCMS: m/z found 611 [M+H] ⁺ , retention time = 1.38 min (Method A).1H NMR (400 MHz, Methanol-d ₄ ): δ 8.71 (d, 1H), 8.57 (d, 1H), 8.42 (s, 1H), 8.22 (d, 1H), 8.06-8.04 (m, 2H), 7.61 (d, 1H), 7.43 (t, 1H), 7.17 (d, 1H), 4.08 (s, 3H), 4.04-4.00 (m, 2H), 3.96 (s, 2H), 3.92-3.85 (m, 1H), 3.71 (t, 2H), 2.84-2.74 (m, 4H), 2.39-2.28 (m, 3H), 2.24 (s, 3H), 2.14 (s, 3H), 1.88-1.82 (m, 1H). Example 56: (S)-N-(3-(3-Chloro-4-(6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)pyrazin-2-yl)pyridin-2-yl)-2-methylph enyl)-5-(((2- hydroxyethyl)amino)methyl)pyrazine-2-carboxamide (a) tert-Butyl ((5-((3-bromo-2-methylphenyl)carbamoyl)pyrazin-2-yl)methyl)( 2- ((tert-butyldimethylsilyl)oxy)ethyl)carbamate To a mixture of lithium 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)pyrazine-2-carboxy late (Example 45, step (b)) (0.44 g, 1.05 mmol) and 3-bromo-2-methylaniline (0.25 g, 1.37 mmol) in DMF (7 mL) was added 2-chloro-1-methylpyridinium iodide (0.27 g, 1.05 mmol) in one portion under N ₂ and the mixture was stirred at room temperature for 5 hours. Water (20 mL) was then added, and the mixture extracted with ethyl acetate (2 x 20 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 20 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (5-8% ethyl acetate/petroleum ether) to afford tert-butyl ((5-((3-bromo-2- methylphenyl)carbamoyl)pyrazin-2-yl)methyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)carbamate (0.24 g, 32% yield) as a yellow solid. LCMS: m/z found 579 and 581 [M+H] ⁺ . (b) tert-Butyl (2-((tert-butyldimethylsilyl)oxy)ethyl)((5-((2-methyl-3-(4,4 ,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamoyl)pyrazin -2-yl)methyl)carbamate To a mixture of tert-butyl ((5-((3-bromo-2-methylphenyl)carbamoyl)pyrazin-2- yl)methyl)(2-((tert-butyldimethylsilyl)oxy)ethyl)carbamate (0.12 g, 0.21 mmol) and bis(pinacolato)diboron (0.16 g, 0.62 mmol) in 1,4-dioxane (5 mL) was added [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (0.02 g, 0.02 mmol) and potassium acetate (0.06 g, 0.62 mmol) in one portion under N ₂ , and the mixture stirred at 110 °C for 3 hours. The mixture was concentrated and the residue purified by normal phase SiO ₂ chromatography (9-16% ethyl acetate/petroleum ether) to afford tert- butyl (2-((tert-butyldimethylsilyl)oxy)ethyl)((5-((2-methyl-3-(4,4 ,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)phenyl)carbamoyl)pyrazin-2-yl)methyl)carba mate (0.17 g, 39% yield) as a yellow solid. LCMS: m/z found 627 [M+H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d): δ 9.70 (s, 1H), 9.36 (s, 1H), 8.54 (d, 1H), 8.28-8.24 (m, 1H), 7.59 (d, 1H), 7.26-7.24 (m, 1H), 4.71 (s, 2H), 3.81-3.70 (m, 2H), 3.52-3.43 (m, 2H), 2.55 (s, 3H), 1.52 (s, 9H), 1.32 (s, 12H). (c) tert-Butyl (S)-((5-(2-(3-(5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)pyrazine-2-carboxa mido)-2-methylphenyl)- 3-chloropyridin-4-yl)-3-methoxypyrazin-2-yl)methyl)((5-oxopy rrolidin-2- yl)methyl)carbamate To a mixture of tert-butyl (S)-((5-(2,3-dichloropyridin-4-yl)-3-methoxypyrazin-2- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (0.05 g, 0.11 mmol) (Example 53, step (c)) and tert-butyl (2-((tert-butyldimethylsilyl)oxy)ethyl)((5-((2-methyl-3-(4,4 ,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamoyl)pyrazin -2-yl)methyl)carbamate (0.07 g, 0.12 mmol) in 1,4-dioxane / water mixture (5:1 v/v, 3.6 mL) was added potassium phosphate (0.07 g, 0.32 mmol) and chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1 ,1′- biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (0.02 g, 0.02 mmol) in one portion under N ₂ , and the mixture stirred at 120 °C for 3 hours. The mixture was combined with another batch at 25.5 mg scale. Water (15 mL) was added, and the mixture extracted with ethyl acetate (2 x 15 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 15 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (17-100% ethyl acetate/petroleum ether) to afford tert-butyl (S)-((5-(2-(3-(5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)pyrazine-2-carboxa mido)-2-methylphenyl)-3- chloropyridin-4-yl)-3-methoxypyrazin-2-yl)methyl)((5-oxopyrr olidin-2-yl)methyl)carbamate (0.11 g, 41% yield) as a yellow gum. LCMS: m/z found 946 [M+H] ⁺ . (d) (S)-N-(3-(3-Chloro-4-(6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)pyrazin-2-yl)pyridin-2-yl)-2-methylph enyl)-5-(((2- hydroxyethyl)amino)methyl)pyrazine-2-carboxamide To a mixture of tert-butyl (S)-((5-(2-(3-(5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)pyrazine-2-carboxa mido)-2-methylphenyl)-3- chloropyridin-4-yl)-3-methoxypyrazin-2-yl)methyl)((5-oxopyrr olidin-2-yl)methyl)carbamate (0.12 g, 0.13 mmol) in 1,4-dioxane (2 mL) was added concentrated HCl solution (0.3 mL) in one portion under N ₂ , and the mixture stirred at room temperature for 0.5 hours. The mixture was purified by reverse phase HPLC. The product was lyophilized and neutralized with saturated aqueous sodium bicarbonate solution. Water (3 mL) was added, and the mixture extracted with dichloromethane (2 x 3 mL). The combined organic phases were concentrated and lyophilized to afford (S)-N-(3-(3-chloro-4-(6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)pyrazin-2-yl)pyridin-2-yl)-2-methylph enyl)-5-(((2- hydroxyethyl)amino)methyl)pyrazine-2-carboxamide (19.4 mg, 22% yield) as a yellow solid. LCMS: m/z found 632 [M+H] ⁺ , retention time = 1.88 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 9.34 (d, 1H), 8.80 (d, 1H), 8.71-8.69 (m, 1H), 8.62-8.54 (m, 1H), 7.96 (d, 1H), 7.81-7.78 (m, 1H), 7.45 (t, 1H), 7.25 (d, 1H), 4.12-4.11 (m, 5H), 4.07-4.03 (m, 2H), 3.91-3.85 (m, 1H), 3.73 (t, 2H), 2.88-2.74 (m, 4H), 2.39-2.28 (m, 3H), 2.18 (s, 3H), 1.91-1.82 (m, 1H). Example 57: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- hydroxyethyl)amino)methyl)-6-methylpicolinamide (a) Methyl 6-methyl-5-vinylpicolinate To a mixture of methyl 5-bromo-6-methylpicolinate (1 g, 4.35 mmol) and 4,4,5,5- tetramethyl-2-vinyl-1,3,2-dioxaborolane (0.81 mL, 4.78 mmol) in THF / water mixture (5:1 v/v, 12 mL) was added chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1 ,1′- biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (0.34 g, 0.43 mmol) and potassium phosphate (2.77 g, 13.0 mmol) in one portion under N ₂ and the mixture stirred at 80 °C for 3 hours. Water (30 mL) was then added, and the mixture extracted with ethyl acetate (2 x 30 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 30 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-8% ethyl acetate/petroleum ether) to afford methyl 6-methyl-5-vinylpicolinate (0.9 g, 95% yield) as a yellow solid. LCMS: m/z found 178 [M+H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d): δ 7.90 (d, 1H), 7.78 (d, 1H), 6.89- 6.82 (m, 1H), 5.71 (d, 1H), 5.46 (d, 1H), 3.93 (s, 3H), 2.60 (s, 3H). (b) Methyl 5-formyl-6-methylpicolinate To a mixture of methyl 6-methyl-5-vinylpicolinate (0.6 g, 3.39 mmol) in THF / water mixture (10:1 v/v, 11 mL) was added potassium osmate(VI) dihydrate (0.25 g, 0.68 mmol) in one portion under N ₂ , and the mixture stirred at 0 °C for 0.5 hours. Sodium periodate (2.17 g, 10.2 mmol) was then added at 0 °C under N ₂ , and the mixture stirred at room temperature for 2 hours. The reaction mixture was then quenched by the addition of aqueous sodium sulfite solution. The mixture was combined with another batch at 300 mg scale, water (15 mL) added, and the mixture extracted with ethyl acetate (2 x 15 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 15 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (8-11% ethyl acetate/petroleum ether) to afford methyl 5-formyl-6- methylpicolinate (0.6 g, 66% yield) as a gray solid. LCMS: m/z found 180 [M+H] ⁺ . (c) Methyl 5-(((tert-butoxycarbonyl)(2-hydroxyethyl)amino)methyl)-6- methylpicolinate A mixture of methyl 5-formyl-6-methylpicolinate (0.2 g, 1.12 mmol) and 2- aminoethan-1-ol (0.06 mL, 1.06 mmol) in THF / methanol mixture (1:1 v/v, 5 mL) was stirred at room temperature for 2 hours under N ₂ . Sodium cyanoborohydride (0.21 g, 3.35 mmol) was then added and the mixture stirred at room temperature for 0.5 hours. Di-tert- butyl dicarbonate (0.56 mL, 2.45 mmol) and triethylamine (0.31 mL, 2.23 mmol) were then added in one portion under N ₂ and the mixture stirred at room temperature for 2 hours. Water (15 mL) was then added and the mixture extracted with ethyl acetate (2 x15 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 15 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (50-75% ethyl acetate/petroleum ether) to afford methyl 5-(((tert-butoxycarbonyl)(2-hydroxyethyl)amino)methyl)-6-met hylpicolinate (0.12 g, 33% yield/2 steps) as a white solid. LCMS: m/z found 325 [M+H] ⁺ . (d) Lithium 5-(((tert-butoxycarbonyl)(2-hydroxyethyl)amino)methyl)-6- methylpicolinate To a mixture of methyl 5-(((tert-butoxycarbonyl)(2-hydroxyethyl)amino)methyl)-6- methylpicolinate (0.24 g, 0.74 mmol) in THF / water mixture (10:1 v/v, 2.2 mL) was added lithium hydroxide monohydrate (0.06 g, 1.48 mmol) in one portion under N ₂ , and the mixture stirred at room temperature for 4 hours. The mixture was concentrated to give lithium 5- (((tert-butoxycarbonyl)(2-hydroxyethyl)amino)methyl)-6-methy lpicolinate (0.25 g, crude) as a white solid. LCMS: m/z found 311 [M+H] ⁺ (acid). (e) tert-Butyl (S)-((2'-(3-(5-(((tert-butoxycarbonyl)(2-hydroxyethyl)amino) methyl)- 6-methylpicolinamido)-2-methylphenyl)-3'-chloro-6-methoxy-[2 ,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate To a mixture of lithium 5-(((tert-butoxycarbonyl)(2-hydroxyethyl)amino)methyl)-6- methylpicolinate (0.25 g, 0.79 mmol) and tert-butyl (S)-((2'-(3-amino-2-methylphenyl)-3'- chloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrroli din-2-yl)methyl)carbamate (Example 42, step (d)) (0.29 g, 0.53 mmol) in DMF (6 mL) was added 2-chloro-1- methylpyridinium iodide (0.13 g, 0.53 mmol) in one portion under N ₂ , and the mixture stirred at room temperature for 12 hours. The mixture was combined with another batch at 30 mg scale. Water (15 mL) was added, and the mixture extracted with ethyl acetate (2 x 10 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 10 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (50-100% ethyl acetate/petroleum ether to 10% methanol/ethyl acetate) to afford tert-butyl (S)-((2'-(3-(5-(((tert-butoxycarbonyl)(2- hydroxyethyl)amino)methyl)-6-methylpicolinamido)-2-methylphe nyl)-3'-chloro-6-methoxy- [2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)c arbamate (0.2 g, 40% yield) as a yellow gum. LCMS: m/z found 844 [M+H] ⁺ . (f) (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- hydroxyethyl)amino)methyl)-6-methylpicolinamide To a mixture of tert-butyl (S)-((2'-(3-(5-(((tert-butoxycarbonyl)(2- hydroxyethyl)amino)methyl)-6-methylpicolinamido)-2-methylphe nyl)-3'-chloro-6-methoxy- [2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)c arbamate (0.2 g, 0.23 mmol) in 1,4-dioxane (1 mL) was added concentrated HCl solution (0.5 mL) in one portion under N ₂ , and the mixture stirred at room temperature for 1 hour. The mixture was combined with another batch at 5 mg scale. The mixture was purified by reverse phase HPLC. The fraction containing product was lyophilized and neutralized with saturated aqueous sodium bicarbonate solution. Water (3 mL) was added, and the mixture extracted with dichloromethane (2 x 3 mL). The combined organic phases were concentrated and lyophilized to afford (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- hydroxyethyl)amino)methyl)-6-methylpicolinamide (31.6 mg, 21% yield) as a white solid. LCMS: m/z found 644 [M+H] ⁺ , retention time = 2.20 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.64 (d, 1H), 8.13-8.06 (m, 2H), 7.99-7.97 (m, 1H), 7.83 (d, 1H), 7.76 (d, 1H), 7.45-7.41 (m, 2H), 7.20 (d, 1H), 4.06 (s, 3H), 3.94 (s, 2H), 3.91-3.83 (m, 3H), 3.73 (t, 2H), 2.83 (t, 2H), 2.75-2.69 (m, 5H), 2.38-2.25 (m, 3H), 2.20 (s, 3H), 1.88-1.80 (m, 1H). Example 58: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- hydroxyethyl)amino)methyl)-4-methylpicolinamide (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl) amino)methyl)-4- methylpicolinamide was prepared in a similar fashion to Example 57, replacing methyl 5- bromo-6-methylpicolinate with methyl 5-bromo-4-methylpicolinate in step (a). LCMS: m/z found 644 [M+H] ⁺ , retention time = 2.13 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ) δ = 8.61 (d, 1H), 8.50 (s, 1H), 8.00 (d, 1H), 7.81 - 7.79 (m, 2H), 7.73 (d, 1H), 7.45 - 7.36 (m, 2H), 7.17 (d, 1H), 4.03 (s, 3H), 3.89 (s, 2H), 3.87 - 3.79 (m, 3H), 3.69 (t, 2H), 2.77 - 2.64 (m, 7H), 2.34 - 2.26 (m, 3H), 2.16 (s, 3H), 1.83 - 1.76 (m, 1H). Example 59: (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 3- fluoropropyl)amino)methyl)thiazole-2-carboxamide (a) tert-Butyl (S)-((2'-(3-amino-2-chlorophenyl)-3'-chloro-6-methoxy-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te To a mixture of tert-butyl (S)-((2',3'-dichloro-6-methoxy-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (Example 23, step (c)) (2 g, 4.15 mmol), 2-chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anil ine (1.58 g, 6.23 mmol) in 1,4- dioxane / water (5:1 v/v, 24 mL) was added potassium carbonate (1.72 g, 12.5 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (0.34 g, 0.42 mmol), and the mixture stirred at 110 °C for 1 hour under N ₂ . Water (30 mL) was added, and the mixture extracted with ethyl acetate (2 x50 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-100 % ethyl acetate / petroleum ether) to afford tert-butyl (S)-((2'-(3-amino-2-chlorophenyl)-3'-chloro-6-methoxy- [2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)c arbamate (1.6 g, 67% yield) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 8.66 (d, 1H), 7.77 (s, 1H), 7.69 (d, 1H), 7.54-7.49 (m, 1H), 7.47-7.43 (m, 1H), 7.13 (t, 1H), 6.88 (dd, 1H), 6.58 (dd, 1H), 5.49 (s, 2H), 4.48-4.36 (m, 2H), 3.96 (s, 3H), 3.78-3.76 (m, 1H), 3.33-3.28 (m, 1H), 2.18-2.06 (m, 4H), 1.76-1.73 (m, 1H), 1.38-1.24 (m, 9H). (b) tert-Butyl (S)-((2'-(3-(5-bromothiazole-2-carboxamido)-2-chlorophenyl)- 3'- chloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrroli din-2-yl)methyl)carbamate To a mixture of 5-bromothiazole-2-carboxylic acid (220 mg, 1.06 mmol) and tert- butyl (S)-((2'-(3-amino-2-chlorophenyl)-3'-chloro-6-methoxy-[2,4'- bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (605 mg, 1.06 mmol) in DMF (5 mL) was added 2-chloro-1-methylpyridinium iodide (405 mg, 1.59 mmol) and N,N- diisopropylethylamine (273 mg, 2.12 mmol), and the mixture stirred at room temperature for 2 hours under N ₂ . Water (20 mL) was then added and the mixture filtered to afford tert-butyl (S)-((2'-(3-(5-bromothiazole-2-carboxamido)-2-chlorophenyl)- 3'-chloro-6-methoxy-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te (750 mg, crude) as a white solid. The crude product was used in the next step without further purification. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.36 (s, 1H), 8.72 (d, 1H), 8.26 (s, 1H), 8.01 (d, 1H), 7.77-7.76 (m, 2H), 7.56 (t, 1H), 7.50-7.38 (m, 3H), 4.49-4.40 (m, 1H), 3.97 (s, 3H), 3.77 (s, 1H), 3.32-3.28 (m, 2H), 2.18-2.06 (m, 3H), 1.44-1.36 (m, 9H). (c) tert-Butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-vinylthiazole-2-carboxamid o)phenyl)- 6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-y l)methyl)carbamate To a mixture of tert-butyl (S)-((2'-(3-(5-bromothiazole-2-carboxamido)-2- chlorophenyl)-3'-chloro-6-methoxy-[2,4'-bipyridin]-5-yl)meth yl)((5-oxopyrrolidin-2- yl)methyl)carbamate (700 mg, 0.92 mmol), 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (141 mg, 0.92 mmol) in THF / water (5:1 v/v, 12 mL) was added potassium phosphate (585 mg, 2.75 mmol) and [1,1′-bis(di-tert-butylphosphino)ferrocene]dichloropalladi um(II) (59.8 mg, 0.09 mmol), and the mixture stirred at 80 °C for 1 hour under N ₂ . Water (20 mL) was then added and the mixture extracted with ethyl acetate (2 x 40 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-100 % ethyl acetate / petroleum ether) to afford tert-butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-vinylthiazole-2- carboxamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)( (5-oxopyrrolidin-2- yl)methyl)carbamate (500 mg, 76% yield) as a yellow solid. LCMS: m/z found 709 [M+H] ⁺ . (d) tert-Butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-formylthiazole-2- carboxamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)( (5-oxopyrrolidin-2- yl)methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-vinylthiazole-2- carboxamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)( (5-oxopyrrolidin-2- yl)methyl)carbamate (400 mg, 0.56 mmol) in THF / water (10:1 v/v, 11 mL) was added osmium tetroxide (50 mg, 0.20 mmol), and the mixture stirred at 0°C for 0.5 hours under N ₂ . Sodium periodate (723 mg, 3.38 mmol) was then added, and the mixture stirred at room temperature for 4.5 hours under N ₂ . Saturated aqueous sodium sulfite solution (50 mL) was added to quench the reaction, the mixture diluted with water (100 mL) and extracted with ethyl acetate (2 x100 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure to afford tert-butyl (S)-((3'-chloro-2'-(2- chloro-3-(5-formylthiazole-2-carboxamido)phenyl)-6-methoxy-[ 2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (350 mg, crude) as a white solid. LCMS: m/z found 711 [M+H] ⁺ . The product was used in the next step without further purification. (e) tert-Butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-(((3- fluoropropyl)amino)methyl)thiazole-2-carboxamido)phenyl)-6-m ethoxy-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te To a mixture of tert-butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-formylthiazole-2- carboxamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)( (5-oxopyrrolidin-2- yl)methyl)carbamate (100 mg, 0.14 mmol) and 3-fluoropropan-1-amine hydrochloride salt (31.9 mg, 0.281 mmol) in dichloromethane / methanol (1:1 v/v, 2 mL) was added sodium acetate (34.5 mg, 0.42 mmol) and the mixture stirred at room temperature for 0.5 hours under N ₂ . Sodium cyanoborohydride (26.4 mg, 0.42 mmol) was then added and the mixture stirred at room temperature for 0.5 hours under N ₂ . Water (10 mL) was then added, and the mixture extracted with ethyl acetate (2 x 20 mL). The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford tert- butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-(((3-fluoropropyl)amino)me thyl)thiazole-2- carboxamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)( (5-oxopyrrolidin-2- yl)methyl)carbamate (0.11 g, crude) as a yellow oil. LCMS: m/z found 772 [M+H] ⁺ . (f) (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 3- fluoropropyl)amino)methyl)thiazole-2-carboxamide To a mixture of tert-butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-(((3- fluoropropyl)amino)methyl)thiazole-2-carboxamido)phenyl)-6-m ethoxy-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (100 mg, 0.13 mmol) in dichloromethane (10 mL) was added trifluoroacetic acid (8.0 mL, 108 mmol), and the mixture stirred at room temperature for 12 hours under N ₂ . The mixture was concentrated and the residue purified by reverse phase HPLC to afford (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin - 2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-( ((3- fluoropropyl)amino)methyl)thiazole-2-carboxamide (15.5 mg, 15% yield) as a white solid. LCMS: m/z found 672 [M+H] ⁺ , retention time = 2.45 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.54 (d, 1H), 8.38 (dd, 1H), 7.78 (s, 1H), 7.71 (d, 1H), 7.68 (d, 1H), 7.44 (t, 1H), 7.33 (d, 1H), 7.19 (dd, 1H), 4.49-4.46 (m, 1H), 4.36 (t, 1H), 3.99 (s, 2H), 3.94 (s, 3H), 3.79-3.71 (m, 3H), 2.68-2.58 (m, 4H), 2.26-2.17 (m, 3H), 1.86-1.73 (m, 3H). Example 60: N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( S)-3-hydroxypyrrolidin-1- yl)methyl)thiazole-2-carboxamide (a) tert-Butyl ((3'-chloro-2'-(2-chloro-3-(5-(((S)-3-hydroxypyrrolidin-1- yl)methyl)thiazole-2-carboxamido)phenyl)-6-methoxy-[2,4'-bip yridin]-5-yl)methyl)(((S)- 5-oxopyrrolidin-2-yl)methyl)carbamate To the mixture of tert-butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-formylthiazole-2- carboxamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)( (5-oxopyrrolidin-2- yl)methyl)carbamate (Example 59, step (d)) (100 mg, 0.14 mmol), (S)-pyrrolidin-3-ol (24.4 mg, 0.28 mmol) in dichloromethane / methanol (1:1 v/v, 10 mL) was added sodium acetate (34.5 mg, 0.42 mmol), and the mixture stirred at room temperature for 1.5 hours under N ₂ . Sodium cyanoborohydride (26.4 mg, 0.42 mmol) was then added and the mixture stirred at room temperature for 0.5 hours under N ₂ . Water (100 mL) was then added and the mixture extracted with ethyl acetate (2 x 100 mL). The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated to afford tert-butyl ((3'-chloro-2'-(2- chloro-3-(5-(((S)-3-hydroxypyrrolidin-1-yl)methyl)thiazole-2 -carboxamido)phenyl)-6- methoxy-[2,4'-bipyridin]-5-yl)methyl)(((S)-5-oxopyrrolidin-2 -yl)methyl)carbamate (110 mg, crude) as a yellow solid. LCMS: m/z found 782 [M+H] ⁺ . (b) N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( S)-3-hydroxypyrrolidin-1- yl)methyl)thiazole-2-carboxamide To the mixture of tert-butyl ((3'-chloro-2'-(2-chloro-3-(5-(((S)-3-hydroxypyrrolidin-1- yl)methyl)thiazole-2-carboxamido)phenyl)-6-methoxy-[2,4'-bip yridin]-5-yl)methyl)(((S)-5- oxopyrrolidin-2-yl)methyl)carbamate (110 mg, 0.14 mmol) in dichloromethane (10 mL) was added trifluoroacetic acid (5.5 mL, 74.2 mmol), and the mixture stirred at room temperature for 1 hour under N ₂ . The mixture was concentrated and the residue purified by prep-HPLC to afford N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( S)-3-hydroxypyrrolidin-1- yl)methyl)thiazole-2-carboxamide (24.9 mg, 25% yield) as a pink solid. LCMS: m/z found 682 [M+H] ⁺ , retention time = 2.33 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.67 (d, 1H), 8.48 (d, 1H), 7.96 (s, 1H), 7.89 (d, 1H), 7.80 (d, 1H), 7.57 (t, 1H), 7.49 (d, 1H), 7.32 (d, 1H), 4.45-4.42 (m, 1H), 4.22 (s, 2H), 4.10 (s, 3H), 4.07 (s, 2H), 3.98-3.91 (m, 1H), 3.05-2.94 (m, 4H), 2.79-2.77 (m, 2H), 2.41-2.34 (m, 3H), 2.24-2.19 (m, 1H), 1.91-1.84 (m, 2H). Example 61: (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 2- hydroxyethyl)amino)methyl)thiazole-2-carboxamide (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 2- hydroxyethyl)amino)methyl)thiazole-2-carboxamide was prepared in a similar fashion to Example 60, replacing (S)-pyrrolidin-3-ol with 2-aminoethanol in step (a). LCMS: m/z found 656 [M+H] ⁺ , retention time = 2.19 min (Method A). ¹ H NMR (400 MHz, Methanol- d4): δ 8.65 (d, 1H), 8.49 (dd, 1H), 7.91 (s, 1H), 7.83 (d, 1H), 7.80 (d, 1H), 7.56 (t, 1H), 7.45 (d, 1H), 7.30 (dd, 1H), 4.15 (s, 2H), 4.06 (s, 3H), 3.87-3.85 (m, 3H), 3.70 (t, 2H), 2.81-2.70 (m, 4H), 2.38-2.29 (m, 3H),1.87-1.80 (m, 1H). Example 62: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-3-hydroxy-5-(((2- hydroxyethyl)amino)methyl)picolinamide (a) Methyl 5-bromo-3-(methoxymethoxy)picolinate To a mixture of methyl 5-bromo-3-hydroxypicolinate (0.65 g, 2.8 mmol) and N,N- diisopropylethylamine (1.1 mL, 6.16 mmol) in dichloromethane (10 mL) was dropwise added chloro(methoxy)methane (0.65 mL, 8.57 mmol) at 0 °C under N ₂ and the mixture stirred at room temperature for 3 hours. Water (5 mL) and saturated aqueous brine solution (5 mL) were then added, and the mixture extracted with dichloromethane (10 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-15% ethyl acetate/petroleum ether) to afford methyl 5-bromo-3-(methoxymethoxy)picolinate (1.1 g, 71% yield) as a light yellow oil. ¹ H NMR (400 MHz, Chloroform-d): δ 8.41 (d, 1H), 7.83 (d, 1H), 5.31 (s, 2H), 4.00 (s, 3H), 3.55 (s, 3H). (b) Methyl 3-(methoxymethoxy)-5-vinylpicolinate To a mixture of methyl 5-bromo-3-(methoxymethoxy)picolinate (1.2 g, 4.35 mmol) and 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (1.25 mL, 7.39 mmol) in THF / water mixture (15:2 v/v, 17 mL) was added potassium phosphate (2.77 g, 13 mmol) and chloro(2- dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-bip henyl)[2-(2′-amino-1,1′- biphenyl)]palladium(II) (0.14 g, 0.17 mmol) and in one portion under N ₂ and the mixture stirred at 80 °C for 2 hours. The mixture was concentrated, water (5 mL) and saturated aqueous brine solution (5 mL) added to the residue, and the mixture extracted with ethyl acetate/THF mixture (10:1 v/v, 30 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-10% ethyl acetate/petroleum ether) to afford methyl 3- (methoxymethoxy)-5-vinylpicolinate (0.9 g, 80% yield) as a yellow gum. ¹ H NMR (400 MHz, Chloroform-d): δ 8.36 (s, 1H), 7.62 (s, 1H), 6.77-6.70 (m, 1H), 5.93 (d, 1H), 5.53 (d, 1H), 5.32 (s, 2H), 3.99 (s, 3H), 3.55 (s, 3H). (c) Methyl 5-formyl-3-(methoxymethoxy)picolinate To a mixture of methyl 3-(methoxymethoxy)-5-vinylpicolinate (0.8 g, 3.58 mmol) in THF / water mixture (10:1 v/v, 22 mL) was added potassium osmate(VI) dihydrate (0.26 g, 0.72 mmol) in one portion at 0 °C and the mixture stirred at 0 °C for 0.5 hours. Sodium periodate (2.3 g, 10.8 mmol) was then added, and the mixture stirred at room temperature for 12 hours. Aqueous Sodium sulfite solution (20 mL) was added and the mixture extracted with ethyl acetate (40 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated to afford methyl 5-formyl-3-(methoxymethoxy)picolinate (0.24 g, 21% yield) as a yellow gum. ¹ H NMR (400 MHz, Chloroform-d): δ 10.08 (s, 1H), 8.68 (d, 1H), 7.95 (d, 1H), 5.28 (s, 2H), 3.95 (s, 3H), 3.46 (s, 3H). (d) Methyl 5-(((tert-butoxycarbonyl)(2-hydroxyethyl)amino)methyl)-3- (methoxymethoxy)picolinate A mixture of methyl 5-formyl-3-(methoxymethoxy)picolinate (0.27 g, 1.2 mmol) and 2-aminoethanol (0.07 g, 1.2 mmol) in THF / methanol mixture (5:1 v/v, 6 mL) was stirred at room temperature for 1 hour under N ₂ . Sodium cyanoborohydride (0.22 g, 3.6 mmol) was then added, and the mixture stirred at room temperature for 1 hour. Di-tert-butyl dicarbonate (0.43 mL, 1.86 mmol) and triethylamine (0.17 mL, 1.24 mmol) were added in one portion and the mixture stirred at room temperature for 1 hour. Water (5 mL) was added and the mixture concentrated. Water (5 mL) and saturated aqueous brine solution (5 mL) were added to the residue and the mixture extracted with ethyl acetate/THF mixture (10:1 v/v, 10 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-80% ethyl acetate/petroleum ether) to afford methyl 5-(((tert-butoxycarbonyl)(2-hydroxyethyl)amino)methyl)-3- (methoxymethoxy)picolinate (0.23 g, 33% yield/2 steps) as a yellow gum. LCMS: m/z found 371 [M+H] ⁺ . (e) Lithium 5-(((tert-butoxycarbonyl)(2-hydroxyethyl)amino)methyl)-3- (methoxymethoxy)picolinate To a mixture of methyl 5-(((tert-butoxycarbonyl)(2-hydroxyethyl)amino)methyl)-3- (methoxymethoxy)picolinate (0.22 g, 0.58 mmol) in THF / water mixture (10:1 v/v, 3.3 mL) was added lithium hydroxide monohydrate (0.05 g, 1.16 mmol) in one portion under N ₂ , and the mixture stirred at room temperature for 4 hours. The mixture was concentrated to afford lithium 5-(((tert-butoxycarbonyl)(2-hydroxyethyl)amino)methyl)-3- (methoxymethoxy)picolinate (0.25 g, crude) as a yellow solid. LCMS: m/z found 357 [M+H] ⁺ (acid). (f) tert-Butyl (S)-((2'-(3-(5-(((tert-butoxycarbonyl)(2-hydroxyethyl)amino) methyl)- 3-hydroxypicolinamido)-2-methylphenyl)-3'-chloro-6-methoxy-[ 2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate To a mixture of lithium 5-(((tert-butoxycarbonyl)(2-hydroxyethyl)amino)methyl)-3- (methoxymethoxy)picolinate (0.25 g, 0.68 mmol) and tert-butyl (S)-((2'-(3-amino-2- methylphenyl)-3'-chloro-6-methoxy-[2,4'-bipyridin]-5-yl)meth yl)((5-oxopyrrolidin-2- yl)methyl)carbamate (Example 42, step (d)) (0.27 g, 0.49 mmol) in DMF (5 mL) was added 2-chloro-1-methylpyridinium iodide (0.25 g, 0.98 mmol) in one portion under N ₂ , and the mixture stirred at room temperature for 12 hours. Water (5 mL) and saturated aqueous brine solution (5 mL) were added, and the mixture extracted with ethyl acetate / THF mixture (10:1 v/v, 15 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether) to afford 290 mg of the product that was further purified by reverse phase HPLC. The fraction with product was neutralized with saturated aqueous sodium bicarbonate solution and concentrated. Water (5 mL) and saturated aqueous brine solution (5 mL) were added to the residue, and the mixture extracted with ethyl acetate / THF mixture (10:1 v/v, 10 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated to afford tert-butyl (S)-((2'-(3-(5-(((tert-butoxycarbonyl)(2- hydroxyethyl)amino)methyl)-3-hydroxypicolinamido)-2-methylph enyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl) methyl)carbamate (0.07 g, 40% yield) as a yellow solid. LCMS: m/z found 846 [M+H] ⁺ . (g) (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-3-hydroxy-5-(((2- hydroxyethyl)amino)methyl)picolinamide To a mixture of tert-butyl (S)-((2'-(3-(5-(((tert-butoxycarbonyl)(2- hydroxyethyl)amino)methyl)-3-hydroxypicolinamido)-2-methylph enyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl) methyl)carbamate (65 mg, 0.08 mmol) in 1,4-dioxane (1 mL) was added concentrated HCl solution (0.1 mL) in one portion and the mixture stirred at room temperature for 0.5 hours. The mixture was neutralized with saturated aqueous sodium bicarbonate solution and purified by reverse phase HPLC to afford (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-3-hydroxy-5-(((2- hydroxyethyl)amino)methyl)picolinamide (23.6 mg, 21% yield) as a white solid. LCMS: m/z found 646 [M+H] ⁺ , retention time = 2.34 min (Method A). ¹ H NMR (400 MHz, Methanol- d ₄ ): δ 8.64 (d, 1H), 8.17-8.11 (m, 2H), 7.83 (d, 1H), 7.76 (d, 1H), 7.45-7.41 (m, 3H), 7.20 (d, 1H), 4.06 (s, 3H), 3.92 (s, 2H), 3.89-3.83 (m, 3H), 3.72 (t, 2H), 2.82 (t, 2H), 2.75-2.70 (m, 2H), 2.38-2.27 (m, 3H), 2.19 (s, 3H), 1.87-1.81 (m, 1H). Example 63: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-4-(((2- hydroxyethyl)amino)methyl)-1H-imidazole-2-carboxamide (a) Ethyl 4-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2- carboxylate To a mixture of ethyl 4-bromo-1H-imidazole-2-carboxylate (1.2 g, 5.48 mmol) and triethylamine (1.39 g, 13.7 mmol) in THF (20 mL) was added (2- chloromethoxyethyl)trimethylsilane (1.37 g, 8.22 mmol), and the mixture stirred at 0°C for 0.5 hours, and then at room temperature for 11.5 hours under N ₂ . Water (500 mL) was added, and the mixture extracted with ethyl acetate (2 x 500 mL). The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-11% ethyl acetate / petroleum ether) to afford ethyl 4-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2- carboxylate (1.1 g, 57 % yield) as a yellow oil. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 7.90 (s, 1H), 5.72 (s, 2H), 4.36 (q, 2H), 3.59 (t, 2H), 1.36 (t, 3H), 0.89 (t, 2H), 0.00 (s, 9H). (b) Lithium 4-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2- carboxylate To the mixture of ethyl 4-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole- 2-carboxylate (900 mg, 2.58 mmol) in water / 1,4-dioxane (1:2 v/v, 30 mL) was added lithium hydroxide monohydrate (92.5 mg, 3.86 mmol), and the mixture stirred at room temperature for 12 hours under N ₂ . The mixture was concentrated to afford lithium 4-bromo- 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxyl ate (1 g, crude) as a white solid. LCMS: m/z found 321 and 323 [M+H] ⁺ (acid). (c) tert-Butyl (S)-((2'-(3-(4-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H - imidazole-2-carboxamido)-2-methylphenyl)-3'-chloro-6-methoxy -[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate To the mixture of lithium 4-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H- imidazole-2-carboxylate (0.6 g, 1.83 mmol) and tert-butyl (S)-((2'-(3-amino-2- methylphenyl)-3'-chloro-6-methoxy-[2,4'-bipyridin]-5-yl)meth yl)((5-oxopyrrolidin-2- yl)methyl)carbamate (Example 42, step (d)) (1 g, 1.83 mmol) in DMF (10 mL) was added 4- methylmorpholine (0.09 g, 0.92 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.7 g, 3.67 mmol) and 1-hydroxybenzotriazole (0.49 g, 3.67 mmol), and the mixture stirred at 50 °C for 12 hours under N ₂ . The mixture was combined with another batch at the 450 mg scale. Water (200 mL) was added, and the mixture extracted with ethyl acetate (2 x 200 mL). The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0- 93 % ethyl acetate / petroleum ether) to afford tert-butyl (S)-((2'-(3-(4-bromo-1-((2- (trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxamido)-2 -methylphenyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl) methyl)carbamate (1.9 g, 70 % yield) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.28 (s, 1H), 8.75 (d, 1H), 7.86- 7.81 (m, 3H), 7.76-7.75 (m, 2H), 7.39 (t, 1H), 7.25 (d, 1H), 5.86 (s, 2H), 4.54-4.41 (m, 2H), 4.09 (q, 1H), 4.02 (s, 3H), 3.63 (t, 2H), 2.26-2.22 (m, 2H), 2.21-2.10 (m, 2H), 2.05 (s, 3H), 1.39-1.46 (m, 9H), 1.23 (t, 2H), 0.91 (t, 2H), 0.00 (s, 9H). (d) tert-Butyl (S)-((3'-chloro-6-methoxy-2'-(2-methyl-3-(1-((2- (trimethylsilyl)ethoxy)methyl)-4-vinyl-1H-imidazole-2-carbox amido)phenyl)-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te To a mixture of tert-butyl (S)-((2'-(3-(4-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)- 1H-imidazole-2-carboxamido)-2-methylphenyl)-3'-chloro-6-meth oxy-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (400 mg, 0.47 mmol) and 4,4,5,5- tetramethyl-2-vinyl-1,3,2-dioxaborolane (79.2 mg, 0.51 mmol) in 1,4-dioxane / water (5:1 v/v, 18 mL) was added chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1 ,1′- biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (36.8 mg, 0.05 mmol) and potassium phosphate (297 mg, 1.40 mmol), and the mixture stirred at 110 °C for 1 hour under N ₂ . Water (200 mL) was added, and the mixture extracted with ethyl acetate (2 x 200 mL). The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-19 % methanol / ethyl acetate) to afford tert-butyl (S)-((3'-chloro-6-methoxy-2'-(2-methyl-3-(1-((2- (trimethylsilyl)ethoxy)methyl)-4-vinyl-1H-imidazole-2-carbox amido)phenyl)-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te (360 mg, 95 % yield) as a yellow solid. LCMS: m/z found 802 [M+H] ⁺ . (e) tert-Butyl (S)-((3'-chloro-2'-(3-(4-formyl-1-((2-(trimethylsilyl)ethoxy )methyl)- 1H-imidazole-2-carboxamido)-2-methylphenyl)-6-methoxy-[2,4'- bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-6-methoxy-2'-(2-methyl-3-(1-((2- (trimethylsilyl)ethoxy)methyl)-4-vinyl-1H-imidazole-2-carbox amido)phenyl)-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te (300 mg, 0.37 mmol) in THF / water (10:1 v/v, 11 mL) was added osmium tetroxide (20 mg, 0.08 mmol), and the mixture stirred at 0 °C for 0.5 hours under N ₂ . Sodium periodate (239 mg, 1.12 mmol) was then added, and the mixture stirred at room temperature for 1.5 hours under N ₂ . The reaction was quenched by the addition of aqueous sodium sulfate solution (50 mL), the mixture diluted with water (100 mL) and extracted with ethyl acetate (2 x 100 mL). The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-9 % methanol / ethyl acetate) to afford tert-butyl (S)-((3'-chloro-2'-(3-(4-formyl-1-((2-(trimethylsilyl)ethoxy )methyl)-1H- imidazole-2-carboxamido)-2-methylphenyl)-6-methoxy-[2,4'-bip yridin]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (240 mg, 79 % yield) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.49 (s, 1H), 9.94 (s, 1H), 8.77-8.75 (m, 1H), 8.51 (s, 1H), 7.82 (s, 1H), 7.77-7.76 (m, 1H), 7.56-7.51 (m, 2H), 7.41 (t, 1H), 7.28-7.24 (m, 1H), 5.92 (s, 2H), 4.50-4.45 (m, 2H), 4.02 (s, 3H), 3.83-3.82 (m, 1H), 3.65 (t, 2H), 2.76 (s, 1H), 2.29-2.21 (m, 2H), 2.18- 2.12 (m, 2H), 2.07 (s, 3H), 1.79-1.78 (m, 1H), 1.49-1.37 (m, 9H), 0.94-0.89 (m, 2H), 0.00 (s, 9H). (f) tert-Butyl (S)-((3'-chloro-2'-(3-(4-(((2-hydroxyethyl)amino)methyl)-1-( (2- (trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxamido)-2 -methylphenyl)-6- methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl) methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-2'-(3-(4-formyl-1-((2- (trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxamido)-2 -methylphenyl)-6-methoxy- [2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)c arbamate (210 mg, 0.261 mmol) and 2-aminoethanol (47.8 mg, 0.783 mmol) in dichloromethane / methanol (1:1 v/v, 6 mL) was added sodium acetate (64.2 mg, 0.78 mmol), and the mixture stirred at room temperature for 3.5 hours under N ₂ . Sodium cyanoborohydride (49.2 mg, 0.783 mmol), was then added and the mixture stirred at room temperature for 0.5 hours under N ₂ . Water (150 mL) was added and the mixture extracted with ethyl acetate (2 x 150 mL). The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by prep-HPLC to afford tert-butyl (S)-((3'-chloro-2'-(3-(4-(((2- hydroxyethyl)amino)methyl)-1-((2-(trimethylsilyl)ethoxy)meth yl)-1H-imidazole-2- carboxamido)-2-methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl )methyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (80 mg, 40 % yield) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.09 (s, 1H), 8.76 (d, 1H), 7.81 (s, 1H), 7.76 (d, 1H), 7.65-7.63 (m, 1H), 7.47 (s, 1H), 7.39 (t, 1H), 7.23 (d, 1H), 5.85 (s, 2H), 4.54-4.45 (m, 3H), 4.02 (s, 3H), 3.86-3.83 (m, 1H), 3.73 (s, 2H), 3.61 (t, 2H), 3.56-3.52 (m, 2H), 2.69 (t, 2H), 2.28-2.21 (m, 2H), 2.18-2.12 (m, 2H), 2.07 (s, 3H), 1.82-1.75 (m, 1H), 1.49-1.36 (m, 9H), 1.30 (s, 2H), 0.90 (t, 2H), 0.00 (s, 9H). (g) (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-4-(((2- hydroxyethyl)amino)methyl)-1H-imidazole-2-carboxamide To a mixture of tert-butyl (S)-((3'-chloro-2'-(3-(4-(((2-hydroxyethyl)amino)methyl)-1- ((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxamid o)-2-methylphenyl)-6- methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl) methyl)carbamate (50 mg, 0.06 mmol) in dichloromethane (2 mL) was added trifluoroacetic acid (0.8 mL, 10.8 mmol), and the mixture stirred at room temperature for 1 hour under N ₂ . The mixture was concentrated and the residue purified by prep-HPLC to afford (S)-N-(3-(3'-chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-4-(((2- hydroxyethyl)amino)methyl)-1H-imidazole-2-carboxamide (13 mg, 34 % yield) as a white solid. LCMS: m/z found 619 [M+H] ⁺ , retention time = 1.84 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.64 (d, 1H), 7.86-7.82 (m, 2H), 7.75 (d, 1H), 7.44-7.37 (m, 2H), 7.37 (s, 1H), 7.23 (d, 1H), 4.09 (s, 2H), 4.06 (s, 3H), 3.89-3.85 (m, 3H), 3.78 (t, 2H), 3.02 (m, 2H), 2.77-2.69 (m, 2H), 2.38-2.29 (m, 3H), 2.16 (s, 3H), 1.87-1.81 (m, 1H). Example 64: (S)-5-(((1-Acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3'-chloro-6- methoxy-5-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4 '-bipyridin]-2'- yl)phenyl)thiazole-2-carboxamide (S)-5-(((1-Acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3'-chloro-6-methoxy- 5-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyri din]-2'-yl)phenyl)thiazole-2- carboxamide was prepared in a similar fashion to Example 60, replacing (S)-pyrrolidin-3-ol with 1-(4-aminopiperidin-1-yl)ethan-1-one in step (a). LCMS: m/z found 737 [M+H] ⁺ , retention time = 2.32 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.68 (d, 1H), 8.47 (dd, 1H), 8.01 (m, 1H), 7.92 (d, 1H), 7.80 (d, 1H), 7.57 (t, 1H), 7.51 (d, 1H), 7.33 (dd, 1H), 4.54-4.51 (m, 2H), 4.37-4.36 (m, 2H), 4.19-4.14 (m, 2H), 4.12 (s, 3H), 4.01-3.98 (m, 2H), 3.23-3.19 (m, 1H), 3.09-3.04 (m, 2H), 2.79-2.72 (m, 1H), 2.43-2.36 (m, 3H), 2.13 (s, 3H), 2.11-2.05 (m, 2H), 1.91-1.89 (m, 1H), 1.42-1.41 (m, 2H). Example 65: N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( R)-3-hydroxypyrrolidin-1- yl)methyl)thiazole-2-carboxamide N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( R)-3-hydroxypyrrolidin-1- yl)methyl)thiazole-2-carboxamide was prepared in a similar fashion to Example 60, replacing (S)-pyrrolidin-3-ol with (R)-pyrrolidin-3-ol in step (a). LCMS: m/z found 682 [M+H] ⁺ , retention time = 2.35 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.66 (d, 1H), 8.50 (dd, 1H), 7.90 (s, 1H), 7.83 (d, 1H), 7.81 (d, 1H), 7.56 (t, 1H), 7.44 (d, 1H), 7.31 (dd, 1H), 4.41-4.36 (m, 1H), 4.06 (s, 3H), 4.01-4.00 (m, 2H), 3.89-3.83 (m, 3H), 2.90-2.82 (m, 2H), 2.74-2.70 (m, 2H), 2.62-2.58 (m, 2H), 2.38-2.29 (m, 3H), 2.21-2.16 (m, 1H), 1.86- 1.75 (m, 2H). Example 66: (S)-1-((2-((2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrro lidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)carbam oyl)thiazol-5- yl)methyl)piperidine-4-carboxylic acid (S)-1-((2-((2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrro lidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)carbam oyl)thiazol-5- yl)methyl)piperidine-4-carboxylic acid was prepared in a similar fashion to Example 60, replacing (S)-pyrrolidin-3-ol with piperidine-4-carboxylic acid in step (a). LCMS: m/z found 724 [M+H] ⁺ , retention time = 2.37 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₆ ): δ 8.67 (d, 1H), 8.50-8.48 (m, 1H), 7.90 (s, 1H), 7.86 (d, 1H), 7.80 (d, 1H), 7.56 (t, 1H), 7.47 (d, 1H), 7.31 (dd, 1H), 4.08 (s, 3H), 3.99-3.98 (m, 2H), 3.94-3.89 (m, 3H), 3.00-2.97 (m, 2H), 2.86-2.83 (m, 2H), 2.39-2.25 (m, 6H), 1.98-1.95 (m, 2H), 1.87-1.75 (m, 3H). Example 67: (S)-5-(((2-Hydroxyethyl)amino)methyl)-N-(3-(6-methoxy-3'-met hyl-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2- methylphenyl)picolinamide (a) 2'-Chloro-6-methoxy-3'-methyl-[2,4'-bipyridine]-5-carbaldehy de To a mixture of 2-chloro-3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2- yl)pyridine (1.52 g, 5.98 mmol) (Example 56, step (a)) and 6-chloro-2- methoxynicotinaldehyde (0.57 g, 3.32 mmol) in 1,4-dioxane / water mixture (10:1 v/v, 30 mL) was added [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (0.14 g, 0.17 mmol) and potassium carbonate (1.38 g, 9.97 mmol) in one portion under N ₂ and the mixture stirred at 80°C for 2 hours. The mixture was combined with another batch at 300 mg scale. The mixture was concentrated, water (10 mL) and saturated aqueous brine solution (10 mL) added, and the mixture extracted with ethyl acetate (2 x 10 mL). The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-15% ethyl acetate/petroleum ether) to afford 2'-chloro-6-methoxy-3'-methyl-[2,4'-bipyridine]-5- carbaldehyde (0.5 g, 57% yield) as a white solid. ¹ H NMR (400 MHz, Chloroform-d): δ 10.35 (s, 1H), 8.26 (d, 1H), 8.16 (d, 1H), 7.22-7.19 (m, 1H), 7.07 (d, 1H), 4.03 (s, 3H), 2.39 (s, 3H). (b) tert-Butyl (S)-((2'-chloro-6-methoxy-3'-methyl-[2,4'-bipyridin]-5-yl)me thyl)((5- oxopyrrolidin-2-yl)methyl)carbamate To a mixture of 2'-chloro-6-methoxy-3'-methyl-[2,4'-bipyridine]-5-carbaldehy de (0.5 g, 1.9 mmol) and (S)-5-(aminomethyl)pyrrolidin-2-one as a hydrochloride salt (0.38 g, 2.47 mmol) in THF / methanol mixture (1:1 v/v, 20 mL) was added sodium acetate (0.47 g, 5.71 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 2 hours. Sodium cyanoborohydride (0.36 g, 5.71 mmol) was then added and the mixture stirred at room temperature for 0.5 hours. Triethylamine (0.21 mL, 2.05 mmol) and di-tert-butyl dicarbonate (0.9 g, 4.1 mmol) were then added in one portion under N ₂ and the mixture stirred at room temperature for 1 hour. The mixture was concentrated, water (30 mL) and saturated aqueous brine solution (10 mL) added to the residue, and the mixture extracted with ethyl acetate (40 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether) to afford tert-butyl (S)-((2'-chloro-6-methoxy-3'-methyl-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te (0.75 g, 79% yield) as a colorless solid. ¹ H NMR (400 MHz, Chloroform-d): δ 8.22 (d, 1H), 7.45-7.40 (m, 1H), 7.23- 7.21 (m, 1H), 6.94 (d, 1H), 4.41 (s, 2H), 3.91 (s, 3H), 3.86-3.82 (m, 1H), 3.29-3.22 (m, 2H), 2.38 (s, 3H), 2.30-2.15 (m, 3H), 1.75-1.71 (m, 1H), 1.56-1.25 (m, 9H). (c) tert-Butyl (S)-((2'-(3-amino-2-methylphenyl)-6-methoxy-3'-methyl-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te To a mixture of tert-butyl (S)-((2'-chloro-6-methoxy-3'-methyl-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (0.2 g, 0.43 mmol) and 2-methyl-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (0.16 g, 0.69 mmol) in 1,4-dioxane / water mixture (10:1 v/v, 4.4 mL) was added chloro(2-dicyclohexylphosphino-2′,4′,6′- triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl) ]palladium(II) (0.03 g, 0.04 mmol) and potassium phosphate (0.28 g, 1.3 mmol) in one portion under N ₂ and the mixture stirred at 110 °C for 16 hours. The mixture was concentrated, water (30 mL) and saturated aqueous brine solution (30 mL) added to the residue, and the mixture extracted with ethyl acetate (40 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (50-100% ethyl acetate/petroleum ether) to afford tert-butyl (S)-((2'-(3-amino-2-methylphenyl)-6-methoxy-3'- methyl-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)m ethyl)carbamate (0.16 g, 69% yield) as a white solid. LCMS: m/z found 532 [M+H] ⁺ . (d) Methyl 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)picolinate A mixture of methyl 5-formylpicolinate (0.5 g, 3.03 mmol) and 2-((tert- butyldimethylsilyl)oxy)ethanamine (0.53 g, 3.03 mmol) in THF / methanol mixture (1:1 v/v, 6 mL) was stirred at room temperature for 6 hours under N ₂ . Sodium cyanoborohydride (0.57 g, 9.08 mmol) was then added and the mixture stirred at room temperature for 1 hour. Di-tert- butyl dicarbonate (1.39 mL, 6.04 mmol) and triethylamine (0.42 mL, 3.02 mmol) were then added in one portion under N ₂ and the mixture stirred at room temperature for 1 hour. The mixture was combined with another batch at 50 mg scale. Water (20 mL) was added, and the mixture extracted with ethyl acetate (2 x 20 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 20 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0- 15% ethyl acetate/petroleum ether) to afford methyl 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)picolinate (0.8 g, 56% yield) as a yellow oil. LCMS: m/z found 425 [M+H] ⁺ . (e) Lithium 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)picolinate To a mixture of methyl 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)picolinate (0.4 g, 0.94 mmol, 1 eq) in THF / methanol mixture (10:1 v/v, 4.4 mL) was added lithium hydroxide monohydrate (0.06 g, 1.41 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 1 hour. The mixture was concentrated to afford lithium 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)picolinate (470 mg, crude) as a yellow solid. LCMS: m/z found 411 [M+H] ⁺ (acid). (f) tert-Butyl (S)-((2'-(3-(5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)picolinamido)-2-me thylphenyl)-6-methoxy- 3'-methyl-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-y l)methyl)carbamate To a mixture of tert-butyl (S)-((2'-(3-amino-2-methylphenyl)-6-methoxy-3'-methyl- [2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)c arbamate (0.06 g, 0.11 mmol) and lithium 5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)picolinate (0.09 g, 0.23 mmol) in DMF (1.5 mL) was added N,N-diisopropylethylamine (0.03 g, 0.23 mmol) and 2-chloro-1-methylpyridinium iodide (0.06 g, 0.23 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 12 hours. The mixture was combined with another batch at 70 mg scale. Water (10 mL) was added, and the mixture extracted with ethyl acetate (2 x 10 mL). The combined organic phases were washed with saturated aqueous brine solution (2 x 10 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by prep-TLC (silica gel, methanol/ethyl acetate = 10:1 /v/v) to afford tert-butyl (S)-((2'-(3-(5- (((tert-butoxycarbonyl)(2-((tert-butyldimethylsilyl)oxy)ethy l)amino)methyl)picolinamido)-2- methylphenyl)-6-methoxy-3'-methyl-[2,4'-bipyridin]-5-yl)meth yl)((5-oxopyrrolidin-2- yl)methyl)carbamate (17 mg, 6% yield) as a colorless oil. LCMS: m/z found 924 [M+H] ⁺ . (g) (S)-5-(((2-Hydroxyethyl)amino)methyl)-N-(3-(6-methoxy-3'-met hyl-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2- methylphenyl)picolinamide To a mixture of tert-butyl (S)-((2'-(3-(5-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)picolinamido)-2-me thylphenyl)-6-methoxy-3'- methyl-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)m ethyl)carbamate (0.05 g, 0.05 mmol) in 1,4-dioxane (1 mL) was added concentrated HCl solution (0.1 mL) in one portion under N ₂ and the mixture stirred at room temperature for 1 hour. The mixture was combined with another batch at 17 mg scale. The mixture was purified by reverse phase HPLC to afford (S)-5-(((2-Hydroxyethyl)amino)methyl)-N-(3-(6-methoxy-3'-met hyl-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)picolinamide (10.4 mg, 25% yield) as a white solid. LCMS: m/z found 610 [M+H] ⁺ , retention time = 2.22 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.71 (d, 1H), 8.52 (d, 1H), 8.23 (d, 1H), 8.06-8.04 (m, 2H), 7.83 (d, 1H), 7.54 (d, 1H), 7.43 (t, 1H), 7.24 (d, 1H), 7.17 (d, 1H), 4.03 (s, 3H), 3.97 (s, 2H), 3.89-3.86 (m, 3H), 3.71 (t, 2H), 2.78 (t, 2H), 2.75-2.67 (m, 2H), 2.38-2.31 (m, 3H), 2.21 (s, 3H), 2.14 (s, 3H), 1.87-1.81 (m, 1H). Example 68: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-7-(2-hydroxyethyl)- 5,6,7,8-tetrahydro-2,7-naphthyridine-3-carboxamide (a) 2-(2-((tert-Butyldimethylsilyl)oxy)ethyl)-6-chloro-1,2,3,4-t etrahydro-2,7- naphthyridine To a mixture of 6-chloro-1,2,3,4-tetrahydro-2,7-naphthyridine hydrochloride salt (0.3 g, 1.46 mmol) and (2-bromoethoxy)(tert-butyl)dimethylsilane (1.05 g, 4.39 mmol) in DMF (4 mL) was added potassium carbonate (1.21 g, 8.78 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 12 hours. Water (50 mL) and saturated aqueous brine solution (50 mL) were added, and the mixture extracted with ethyl acetate (50 mL). The organic phase was dried with anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-10% ethyl acetate/petroleum ether) to afford 2-(2-((tert-butyldimethylsilyl)oxy)ethyl)-6-chloro-1,2,3,4-t etrahydro-2,7- naphthyridine (250 mg, 52% yield) as a white oil. LCMS: m/z: 327 found [M+H] ⁺ . (b) Ethyl 7-(2-((tert-butyldimethylsilyl)oxy)ethyl)-5,6,7,8-tetrahydro -2,7- naphthyridine-3-carboxylate To a mixture of 2-(2-((tert-butyldimethylsilyl)oxy)ethyl)-6-chloro-1,2,3,4-t etrahydro- 2,7-naphthyridine (0.4 g, 1.22 mmol) in ethanol (4 mL) was added triethylamine (0.85 mL, 6.12 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (0.02 g, 0.25 mmol) in one portion under CO (50 psi) and the mixture stirred at 80 °C for 18 hours. The mixture was concentrated, water (50 mL) and saturated aqueous brine solution (15 mL) added, and the mixture extracted with ethyl acetate (50 mL). The organic phase was dried with anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by normal phase SiO ₂ chromatography (10-40% ethyl acetate/petroleum ether) to afford ethyl 7-(2-((tert-butyldimethylsilyl)oxy)ethyl)-5,6,7,8-tetrahydro -2,7- naphthyridine-3-carboxylate (300 mg, 60% yield) as a yellow oil. ¹ H NMR (400 MHz, Chloroform-d): δ 8.32 (s, 1H), 7.81 (s, 1H), 4.39 (q, 2H), 3.80-3.77 (m, 2H), 3.74-3.62 (m, 2H), 2.88-2.87 (m, 2H), 2.82-2.81 (m, 2H), 2.69 (t, 2H), 1.36 (t, 3H), 0.83 (s, 3H), 0.00 (s, 6H). (c) Lithium 7-(2-((tert-butyldimethylsilyl)oxy)ethyl)-5,6,7,8-tetrahydro -2,7- naphthyridine-3-carboxylate To a mixture of ethyl 7-(2-((tert-butyldimethylsilyl)oxy)ethyl)-5,6,7,8-tetrahydro -2,7- naphthyridine-3-carboxylate (0.2 g, 0.55 mmol) in THF / water mixture (20:1 v/v, 2.1 mL) was added lithium hydroxide monohydrate (0.05 g, 1.10 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 12 hours. The mixture was concentrated to afford lithium 7-(2-((tert-butyldimethylsilyl)oxy)ethyl)-5,6,7,8-tetrahydro -2,7-naphthyridine- 3-carboxylate (230 mg, crude). LCMS: m/z found 337 [M+H] ⁺ (acid). (d) tert-Butyl (S)-((2'-(3-(7-(2-((tert-butyldimethylsilyl)oxy)ethyl)-5,6,7 ,8-tetrahydro- 2,7-naphthyridine-3-carboxamido)-2-methylphenyl)-3'-chloro-6 -methoxy-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te To a mixture of lithium 7-(2-((tert-butyldimethylsilyl)oxy)ethyl)-5,6,7,8-tetrahydro - 2,7-naphthyridine-3-carboxylate (0.19 g, 0.55 mmol) and tert-butyl (S)-((2'-(3-amino-2- methylphenyl)-3'-chloro-6-methoxy-[2,4'-bipyridin]-5-yl)meth yl)((5-oxopyrrolidin-2- yl)methyl)carbamate (0.2 g, 0.36 mmol) (Example 42, step (d)) in DMF (3 mL) was added 2-chloro-1-methylpyridinium iodide (0.19 g, 0.73 mmol) and N,N- diisopropylethylamine (0.16 mL, 0.91 mmol) in one portion under N ₂ , and the mixture stirred at room temperature for 12 hours. Water (50 mL) and saturated aqueous brine solution (50 mL) were added, and the mixture extracted with ethyl acetate (50 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (50-100% methanol / ethyl acetate) to afford of tert- butyl (S)-((2'-(3-(7-(2-((tert-butyldimethylsilyl)oxy)ethyl)-5,6,7 ,8-tetrahydro-2,7- naphthyridine-3-carboxamido)-2-methylphenyl)-3'-chloro-6-met hoxy-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (300 mg, 85% yield) as a yellow solid. LCMS: m/z found 870 [M+H] ⁺ . (e) (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-7-(2-hydroxyethyl)-5 ,6,7,8-tetrahydro-2,7- naphthyridine-3-carboxamide To a mixture of tert-butyl (S)-((2'-(3-(7-(2-((tert-butyldimethylsilyl)oxy)ethyl)- 5,6,7,8-tetrahydro-2,7-naphthyridine-3-carboxamido)-2-methyl phenyl)-3'-chloro-6-methoxy- [2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)c arbamate (0.29 g, 0.33 mmol) in 1,4-dioxane (1 mL) was added concentrated HCl solution (12 M, 0.3 mL) in one portion under N ₂ , and the mixture stirred at room temperature for 0.5 hours. The mixture was combined with another batch at 10 mg scale. The mixture was neutralized with saturated aqueous sodium bicarbonate solution and purified by reverse phase HPLC to afford (S)-N-(3- (3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl)amino )methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-7-(2-hydroxyethyl)-5,6,7,8-tetrahydro-2, 7-naphthyridine-3-carboxamide (36.5 mg, 17% yield) as a yellow solid. LCMS: m/z found 656 [M+H] ⁺ retention time = 2.12 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): 8.64 (d, 1H), 8.43 (s, 1H), 8.08 (d, 1H), 8.02 (s, 1H), 7.83 (d, 1H), 7.75 (d, 1H), 7.45-7.40 (m, 2H), 7.20 (dd, 1H), 4.06 (s, 3H), 3.87- 3.81 (m, 7H), 3.07 (t, 2H), 2.93 (t, 2H), 2.81-2.67 (m, 4H), 2.38-2.27 (m, 3H), 2.18 (s, 3H), 1.88-1.80 (m, 1H). Example 69: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino) methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydro xyethyl)amino)methyl)-1- methyl-1H-imidazole-2-carboxamide (a) Ethyl 5-bromo-1-methyl-1H-imidazole-2-carboxylate To the mixture of ethyl chloroformate (13 g, 124 mmol) and N,N- diisopropylethylamine (16 g, 124 mmol) in acetonitrile (250 mL) was slowly added a solution of 5-bromo-1-methyl-1H-imidazole (10 g, 62.1 mmol) in acetonitrile (100 mL) at 0 °C and the mixture stirred at room temperature for 12 hours. The mixture was concentrated, water (500 mL) added, and the mixture extracted with ethyl acetate (3 x 200 mL). The combined extracts were washed with saturated aqueous brine solution, dried with anhydrous sulfate, filtered, concentrated under reduced pressure. The mixture was combined with another batch at the 1 g scale. The residue was purified by normal phase SiO ₂ chromatography (0-12% ethyl acetate/petroleum ether) to afford ethyl 5-bromo-1-methyl-1H-imidazole-2-carboxylate (9.19 g, 45% yield) as a yellow oil. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ.7.25 (s, 1H), 4.30 (q, 2H), 3.89 (s, 3H), 1.30 (t, 3H) (b) 5-Bromo-1-methyl-1H-imidazole-2-carboxylic acid To a solution of ethyl 5-bromo-1-methyl-1H-imidazole-2-carboxylate (1 g, 4.29 mmol) in THF / water (5:1 v/v, 12 mL) was added lithium hydroxide monohydrate (0.27 g, 6.44 mmol) and the mixture stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to afford 5-bromo-1-methyl-1H-imidazole-2- carboxylic acid (1.02 g, crude) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ.7.02 (s, 1H), 3.95 (s, 3H). (c) tert-Butyl (S)-((2'-(3-(5-bromo-1-methyl-1H-imidazole-2-carboxamido)-2- methylphenyl)-3'-chloro-6-methoxy-[2,4'-bipyridin]-5-yl)meth yl)((5-oxopyrrolidin-2- yl)methyl)carbamate To a solution of 5-bromo-1-methyl-1H-imidazole-2-carboxylic acid (167 mg, 0.82 mmol) and tert-butyl (S)-((2'-(3-amino-2-methylphenyl)-3'-chloro-6-methoxy-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te (Example 42, step (d)) (300 mg, 0.54 mmol) in DMF (4 mL) was added N,N-diisopropylethylamine (211 mg, 1.63 mmol) and 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethy luronium hexafluorophosphate(V) (310 mg, 0.82 mmol), and the mixture stirred at room temperature for 12 hours. The mixture was combined with another batch at the 23.0 mg scale. Water (50 mL) was added, and the mixture extracted with ethyl acetate (2 x 60 mL). The combined organic layers were washed with saturated aqueous brine solution (10 mL), dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-87% ethyl acetate/petroleum ether) to afford tert-butyl (S)-((2'-(3-(5-bromo-1-methyl-1H-imidazole-2-carboxamido)-2- methylphenyl)-3'-chloro-6-methoxy-[2,4'-bipyridin]-5-yl)meth yl)((5-oxopyrrolidin-2- yl)methyl)carbamate (390 mg, 90% yield) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.03 (s, 1H), 8.69 (d, 1H), 7.75 (s, 1H), 7.70 (d, 1H), 7.63 (d, 1H), 7.54-7.43 (m, 2H), 7.34 (t, 1H), 7.29 (s, 1H), 7.18 (d, 1H), 4.48-4.35 (m, 2H), 3.98 (s, 3H), 3.96 (s, 3H), 3.80-3.76 (m, 1H), 3.28-3.25 (m, 1H), 2.27 - 2.05 (m, 5H), 2.01 (s, 3H), 1.43-1.30 (m, 9H). (d) tert-Butyl (S)-((3'-chloro-6-methoxy-2'-(2-methyl-3-(1-methyl-5-vinyl-1 H- imidazole-2-carboxamido)phenyl)-[2,4'-bipyridin]-5-yl)methyl )((5-oxopyrrolidin-2- yl)methyl)carbamate To a solution of tert-butyl (S)-((2'-(3-(5-bromo-1-methyl-1H-imidazole-2- carboxamido)-2-methylphenyl)-3'-chloro-6-methoxy-[2,4'-bipyr idin]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (310 mg, 0.42 mmol) and 4,4,5,5-tetramethyl-2-vinyl- 1,3,2-dioxaborolane (71 mg, 0.46 mmol) in 1,4-dioxane / water (5:1 v/v, 3.6 mL) was added potassium phosphate (267 mg, 1.26 mmol) and [1,1′-bis(di-tert- butylphosphino)ferrocene]dichloropalladium(II) (27.3 mg, 0.04 mmol) and the mixture stirred at 95 °C for 2 hours. Water (50 mL) was added, and the mixture extracted with ethyl acetate (2 x 100 mL). The combined organic layers were washed with saturated aqueous brine solution (30 mL) dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-90% ethyl acetate/petroleum ether) to afford tert-butyl (S)-((3'-chloro-6-methoxy-2'-(2-methyl-3-(1- methyl-5-vinyl-1H-imidazole-2-carboxamido)phenyl)-[2,4'-bipy ridin]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (220 mg, 41% yield) as a yellow solid. LCMS: m/z found 686 [M+H] ⁺ . (e) tert-Butyl (S)-((3'-chloro-2'-(3-(5-formyl-1-methyl-1H-imidazole-2- carboxamido)-2-methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl )methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-6-methoxy-2'-(2-methyl-3-(1-methyl-5- vinyl-1H-imidazole-2-carboxamido)phenyl)-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin- 2-yl)methyl)carbamate (200 mg, 0.29 mmol) in THF / water (10:1 v/v, 5.5 mL) was added potassium osmate(VI) dihydrate (21 mg, 0.06 mmol) at 0°C under N ₂ , and the mixture stirred at 0 °C for 0.5 hours. Sodium periodate (499 mg, 2.33 mmol) was then added, and the mixture stirred at room temperature for 12 hours. Aqueous sodium sulfite solution was added to quench the reaction, the mixture diluted with water (100 mL) and the mixture extracted with ethyl acetate (2 x 100 mL). The combined organic layers were washed with saturated aqueous brine solution (50 mL) dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by prep-TLC (SiO ₂ , ethyl acetate : methanol = 10:1 v/v) to afford tert-butyl (S)-((3'-chloro-2'-(3-(5-formyl-1-methyl-1H-imidazole-2- carboxamido)-2-methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl )methyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (80 mg, 29% yield) as a yellow solid. LCMS: m/z found 688 [M+H] ⁺ . (f) tert-Butyl (S)-((3'-chloro-2'-(3-(5-(((2-hydroxyethyl)amino)methyl)-1-m ethyl-1H- imidazole-2-carboxamido)-2-methylphenyl)-6-methoxy-[2,4'-bip yridin]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate To a solution of tert-butyl (S)-((3'-chloro-2'-(3-(5-formyl-1-methyl-1H-imidazole-2- carboxamido)-2-methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl )methyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (60 mg, 0.087 mmol) and 2-aminoethan-1-ol (10.6 mg, 0.17 µmol) in dichloromethane / methanol (1:1 v/v, 2 mL) was added sodium acetate (21.5 mg, 0.26 mmol) and sodium cyanoborohydride (32.9 mg, 0.52 mmol), and the mixture was stirred at room temperature for 2 hours. Water (20 mL) was added, and the mixture extracted with ethyl acetate (2 x 15 mL). The combined organic layers were washed with saturated aqueous brine solution (10 mL) dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by prep-TLC (SiO ₂ , Petroleum ether : ethyl acetate = 0:1) to afford tert-butyl (S)-((3'-chloro-2'-(3-(5-(((2-hydroxyethyl)amino)methyl)-1-m ethyl-1H- imidazole-2-carboxamido)-2-methylphenyl)-6-methoxy-[2,4'-bip yridin]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (25 mg, 32 % yield) as a white solid. LCMS: m/z found 733 [M+H] ⁺ . (g) (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl) amino)methyl)-1-methyl- 1H-imidazole-2-carboxamide To a solution of tert-butyl (S)-((3'-chloro-2'-(3-(5-(((2-hydroxyethyl)amino)methyl)- 1-methyl-1H-imidazole-2-carboxamido)-2-methylphenyl)-6-metho xy-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (20 mg, 0.03 mmol) in dichloromethane (2 mL) was added trifluoroacetic acid (1 mL, 13.5 mmol), and the mixture stirred at room temperature for 0.5 hours. The reaction mixture was concentrated under reduced pressure and the residue purified by reverse phase HPLC to afford (S)-N-(3-(3'-chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-(((2- hydroxyethyl)amino)methyl)-1-methyl-1H-imidazole-2-carboxami de (11.9 mg, 67% yield) as a white solid. LCMS: m/z found 633 [M+H] ⁺ retention time = 2.70 (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ.8.66 (d, 1H), 7.97 (d, 1H), 7.88 (dd, 1H), 7.73 (d, 1H), 7.51 (d, 1H), 7.40 (t, 1H), 7.35 (s, 1H), 7.20 (dd, 1H), 4.45 (s, 2H), 4.35 (d, 2H), 4.13 (s, 3H), 4.12 (s, 3H), 4.10-4.04 (m, 1H), 3.88-3.85 (m, 2H), 3.27-3.24 (m, 4H), 2.46-2.35 (m, 3H), 2.13 (s, 3H), 1.96-1.90 (m, 1H). Example 70: N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)thiazole-2- carboxamide (a) Ethyl 5-(dimethoxymethyl)thiazole-2-carboxylate To a mixture of ethyl 5-formylthiazole-2-carboxylate (3 g, 16.2 mmol) in methanol (20 mL) was added p-toluenesulfonic acid (279 mg, 1.62 mmol) and trimethoxymethane (1.95 mL, 17.8 mmol), and the mixture stirred at 60 °C for 1 hour under N ₂ . Saturated aqueous sodium bicarbonate solution (30 mL) was added and the mixture extracted with ethyl acetate (2 x 100 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure to afford ethyl 5- (dimethoxymethyl)thiazole-2-carboxylate (2.9 g, 77% yield) as a yellow solid. LCMS: m/z: found 232 [M+H] ⁺ . The crude product was used in the next step without further purification. (b) N-(3-Bromo-2-methylphenyl)-5-(dimethoxymethyl)thiazole-2-car boxamide To a mixture of 3-bromo-2-methyl-aniline (2.1 g, 11.3 mmol) in THF (30 mL) was added 1M lithium bis(trimethylsilyl)amide in THF (22.6 mL, 22.6 mmol) at 0°C, and the mixture stirred at 0 °C for 0.5 hours under N ₂ . Ethyl 5-(dimethoxymethyl)thiazole-2- carboxylate (2.61 g, 11.3 mmol) in THF (10 mL) was then added, and the mixture stirred at 0 °C for 0.5 hours under N ₂ . Water (50 mL) was added, and the mixture extracted with ethyl acetate (2 x 100 mL). The combined organic phases were dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-35 % ethyl acetate / petroleum ether) to afford N-(3-bromo-2- methylphenyl)-5-(dimethoxymethyl)thiazole-2-carboxamide (3.3 g, 78% yield) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.49 (s, 1H), 7.98 (s, 1H), 7.47 (d, 1H), 7.35 (d, 1H), 7.11 (t, 1H), 5.56 (s, 1H), 3.25 (s, 6H), 2.22 (s, 1H). (c) N-(3-Bromo-2-methylphenyl)-5-formylthiazole-2-carboxamide To a mixture of N-(3-bromo-2-methylphenyl)-5-(dimethoxymethyl)thiazole-2- carboxamide (3 g, 8.08 mmol) in THF (50 mL) was added 1 N aqueous HCl (10 mL) and then the mixture stirred at room temperature for 1 hour under N ₂ . The mixture was combined with another batch at the 0.3 g scale. The mixture was neutralized with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate (2 x 100 mL). The combined organic phases were dried over anhydrous sulfate, filtered, and concentrated under reduced pressure to afford N-(3-bromo-2-methylphenyl)-5-formylthiazole-2-carboxamide (2.7 g, crude) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.82 (s, 1H), 10.16 (s, 1H), 8.92 (s, 1H), 7.58 (d, 1H), 7.43 (d, 1H), 7.21 (t, 1H), 2.31(s, 3H). The crude product was used in the next step without further purification. (d) tert-Butyl ((2-((3-bromo-2-methylphenyl)carbamoyl)thiazol-5-yl)methyl)( 2- ((tert-butyldimethylsilyl)oxy)ethyl)carbamate To a mixture of N-(3-bromo-2-methylphenyl)-5-formylthiazole-2-carboxamide (2.5 g, 7.69 mmol) and 2-((tert-butyldimethylsilyl)oxy)ethan-1-amine (2.70 g, 15.4 mmol) in dichloromethane (25 mL) was added sodium acetate (1.89 g, 23.1 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 1.5 hours under N _2. Sodium cyanoborohydride (1.45 g, 23.1 mmol) was then added, and the mixture stirred at room temperature for 0.5 hours under N ₂ . Di-tert-butyl dicarbonate (4.20 g, 19.3 mmol) and triethylamine (3.21 mL, 23.1 mmol) were then added, and the mixture stirred at room temperature for 1 hour under N ₂ . The mixture was combined with another batch at the 0.2 g scale. Water (100 mL) was added, and the mixture extracted with ethyl acetate (2 x 200 mL). The combined organic phases were dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0- 40 % ethyl acetate / petroleum ether) to afford tert-butyl ((2-((3-bromo-2- methylphenyl)carbamoyl)thiazol-5-yl)methyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)carbamate (4.2 g, crude) as a yellow oil. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.45 (s, 1H), 7.97 (s, 1H), 7.50 (d, 1H), 7.38 (d, 1H), 7.15 (d, 1H), 6.69 (s, 1H), 4.62 (s, 2H), 3.64 (s, 2H), 3.27-3.26 (m, 2H), 2.36 (s, 3H), 1.43-1.40 (m, 9H), 0.82 (s, 9H), 0.01 (m, 6H). (e) tert-Butyl (2-((tert-butyldimethylsilyl)oxy)ethyl)((2-((2-methyl-3-(4,4 ,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamoyl)thiazol -5-yl)methyl)carbamate To a mixture of tert-butyl ((2-((3-bromo-2-methylphenyl)carbamoyl)thiazol-5- yl)methyl)(2-((tert-butyldimethylsilyl)oxy)ethyl)carbamate (3 g, 5.13 mmol) and bis(pinacolato)diboron (2.61 g, 10.3 mmol) in 1,4-dioxane (30 mL) was added potassium acetate (1.51 g, 15.4 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (0.42 g, 0.51 mmol), and the mixture stirred at 110 °C for 2 hours under N ₂ . The mixture was combined with another batch at the 1 g scale. The mixture was concentrated and the residue purified by normal phase SiO ₂ chromatography (0-40 % ethyl acetate / petroleum ether) to afford tert-butyl (2-((tert-butyldimethylsilyl)oxy)ethyl)((2-((2-methyl-3-(4,4 ,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)phenyl)carbamoyl)thiazol-5-yl)methyl )carbamate (2 g, 37% yield) as a yellow oil. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.16 (s, 1H), 7.96 (s, 1H), 7.52 (d, 1H), 7.48 (d, 1H), 7.20 (d, 1H), 4.62 (s, 2H), 3.64 (s, 2H), 3.28-3.26 (m, 2H), 2.37 (s, 3H), 1.41 (s, 9H), 1.29 (s, 9H), 0.83 (s, 9H), 0.00 (m, 6H). (f) tert-Butyl (2-((tert-butyldimethylsilyl)oxy)ethyl)((2-((3-(3'-chloro-5- formyl-6- methoxy-[2,4'-bipyridin]-2'-yl)-2-methylphenyl)carbamoyl)thi azol-5- yl)methyl)carbamate To a mixture of 2',3'-dichloro-6-methoxy-[2,4'-bipyridine]-5-carbaldehyde (Example 23, step (a)) (0.5 mg, 1.77 mmol) and tert-butyl (2-((tert-butyldimethylsilyl)oxy)ethyl)((2- ((2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ph enyl)carbamoyl)thiazol-5- yl)methyl)carbamate (1.45 g, 2.30 mmol) in THF / water (5:1 v/v, 12 mL) was added [1,1′- bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) (0.12 g, 0.18 mmol) and potassium phosphate (1.12 g, 5.30 mmol) and the mixture stirred at 80 °C for 2 hours under N ₂ . Water (100 mL) was added, and the mixture extracted with ethyl acetate (2 x 100 mL). The combined organic phases were dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0- 40 % ethyl acetate / petroleum ether) to afford tert-butyl (2-((tert- butyldimethylsilyl)oxy)ethyl)((2-((3-(3'-chloro-5-formyl-6-m ethoxy-[2,4'-bipyridin]-2'-yl)-2- methylphenyl)carbamoyl)thiazol-5-yl)methyl)carbamate (0.67 g, 50% yield) as a yellow oil. LCMS: m/z found 752 [M+H] ⁺ . (g) tert-Butyl ((2-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro -6- methoxy-[2,4'-bipyridin]-2'-yl)-2-methylphenyl)carbamoyl)thi azol-5-yl)methyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)carbamate To a mixture of tert-butyl (2-((tert-butyldimethylsilyl)oxy)ethyl)((2-((3-(3'-chloro-5- formyl-6-methoxy-[2,4'-bipyridin]-2'-yl)-2-methylphenyl)carb amoyl)thiazol-5- yl)methyl)carbamate (150 mg, 0.20 mmol) and 1-(4-aminopiperidin-1-yl)ethan-1-one (56.7 mg, 0.40 mmol) in dichloromethane / methanol (1:1 v/v, 6 mL) was added sodium acetate (49.1 mg, 0.60 mmol) and the mixture stirred at room temperature for 1.5 hours under N ₂ . Sodium cyanoborohydride (37.6 mg, 0.60 mmol) was added, and the mixture stirred at room temperature for 0.5 hours under N ₂ . Water (20 mL) was added, and the mixture extracted with dichloromethane (2 x 20 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure to afford tert-butyl ((2-((3-(5-(((1- acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6-methoxy-[2,4' -bipyridin]-2'-yl)-2- methylphenyl)carbamoyl)thiazol-5-yl)methyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)carbamate (120 mg, 68% yield) as a yellow oil. LCMS: m/z found 878 [M+H] ⁺ . The crude product was used in the next step without further purification. (h) N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)thiazole-2- carboxamide To a mixture of tert-butyl ((2-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'- chloro-6-methoxy-[2,4'-bipyridin]-2'-yl)-2-methylphenyl)carb amoyl)thiazol-5-yl)methyl)(2- ((tert-butyldimethylsilyl)oxy)ethyl)carbamate (100 mg, 0.11 mmol) in dichloromethane (5 mL) was added trifluoroacetic acid (20 mL, 270 mmol), and the mixture stirred at room temperature for 0.5 hours under N ₂ . The mixture was concentrated and the residue purified by reverse phase HPLC to afford N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydro xyethyl)amino)methyl)thiazole- 2-carboxamide (22.6 mg, 28% yield) as a white solid. LCMS: m/z found 664 [M+H] ⁺ , retention time = 2.82 (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.64 (d, 1H), 7.91 (s, 1H), 7.84 (t, 1H), 7.75 (d, 1H), 7.45-7.40 (m, 2H), 7.24 (dd, 1H), 4.52-4.48 (m, 2H), 4.15 (s, 2H), 4.10 (s, 3H), 3.97-3.93 (m, 3H), 3.70 (t, 2H), 3.18-3.14 (m, 1H), 2.86-2.71 (m, 4H), 2.15 (s, 3H), 2.14 (s, 3H), 2.10-2.01 (m, 2H), 1.46-1.31 (m, 2H). Example 71: 1-((3'-Chloro-2'-(3-(5-(((2-hydroxyethyl)amino)methyl)thiazo le-2- carboxamido)-2-methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl )methyl)piperidine-4- carboxylic acid 1-((3'-Chloro-2'-(3-(5-(((2-hydroxyethyl)amino)methyl)thiazo le-2-carboxamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)piperid ine-4-carboxylic acid was prepared in a similar fashion to Example 70, replacing 1-(4-aminopiperidin-1-yl)ethan-1-one with tert-butyl piperidine-4-carboxylate in step (g). White solid, LCMS: m/z found 651 [M+H] ⁺ retention time = 2.88 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.67 (d, 1H), 8.01 (s, 1H), 7.96 (d, 1H), 7.80 (d, 1H), 7.76 (d, 1H), 7.52 (d, 1H), 7.43 (t, 1H), 7.26 (dd, 1H), 4.37 (s, 2H), 4.16 (s, 2H), 4.10 (s, 3H), 3.77 (t, 2H), 3.37-3.34 (m, 2H), 3.00-2.91 (m, 4H), 2.46-2.44 (m, 1H), 2.15 (s, 3H), 2.11-2.06 (m, 2H), 1.97-1.91 (m, 2H). Example 72: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-((3-methoxyazetidin- 1-yl)methyl)picolinamide (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-methoxyazetidi n-1-yl)methyl)picolinamide was prepared in a similar fashion to Example 28, replacing (R)-pyrrolidin-3-ol with 3- methoxyazetidine and sodium acetate with acetic acid in step (a). LCMS: m/z found 656 [M+H] ⁺ , retention time = 2.33 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.65 – 8.63 (m, 1H), 8.62 (d, 1H), 8.20 (d, 1H), 8.05 (d, 1H), 7.96 (dd, 1H), 7.81 (d, 1H), 7.74 (d, 1H), 7.46 – 7.37 (m, 2H), 7.19 (d, 1H), 4.09 (q, 1H), 4.04 (s, 3H), 3.90 – 3.77 (m, 5H), 3.63 (m, 2H), 3.26 (s, 3H), 3.11 (dd, 2H), 2.77 – 2.61 (m, 2H), 2.38 – 2.24 (m, 3H), 2.17 (s, 3H), 1.88 – 1.76 (m, 1H). Example 73: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-((3- (methoxymethyl)azetidin-1-yl)methyl)picolinamide (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-(methoxymethyl )azetidin-1- yl)methyl)picolinamide was prepared in a similar fashion to Example 28, replacing (R)- pyrrolidin-3-ol with 3-(methoxymethyl)azetidine and sodium acetate with acetic acid in step (a). LCMS: m/z found 670 [M+H] ⁺ , retention time = 2.50 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.65 – 8.58 (m, 2H), 8.19 (d, 1H), 8.05 (d, 1H), 7.95 (dd, 1H), 7.81 (d, 1H), 7.74 (d, 1H), 7.47 – 7.37 (m, 2H), 7.19 (d, 1H), 4.04 (s, 3H), 3.91 – 3.79 (m, 3H), 3.77 (s, 2H), 3.51 (d, 2H), 3.45 (t, 2H), 3.35 (s, 3H), 3.13 (t, 2H), 2.82 – 2.63 (m, 3H), 2.38 – 2.22 (m, 3H), 2.17 (s, 3H), 1.89 – 1.74 (m, 1H). Example 74: (R)-N-(3-(3'-Chloro-5-((3-hydroxypyrrolidin-1-yl)methyl)-6-m ethoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)thiazole-2- carboxamide (R)-N-(3-(3'-Chloro-5-((3-hydroxypyrrolidin-1-yl)methyl)-6-m ethoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)thiazole-2-carboxamide was prepared in a similar fashion to Example 70, replacing 1-(4-aminopiperidin-1-yl)ethan- 1-one with (R)-pyrrolidin-3-ol in step (g). White solid, LCMS: m/z found 609 [M+H] ⁺ retention time = 2.07 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.51 (d, 1H), 7.79 (s, 1H), 7.75 (d, 1H), 7.71 (d, 1H), 7.64 (d, 1H), 7.33-7.30 (m, 2H), 7.12 (d, 1H), 4.28- 4.24 (m, 1H), 4.02 (s, 2H) , 3.92 (s, 3H), 3.69-3.64 (m, 2H), 3.58 (t, 2H), 2.80-2.74 (m, 2H), 2.67 (t, 2H), 2.54-2.48 (m, 2H), 2.12-2.07 (m, 1H), 2.03 (s, 3H), 1.68-1.60 (m, 1H). Example 75: (S)-N-(3-(3'-Chloro-5-((3-hydroxypyrrolidin-1-yl)methyl)-6-m ethoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)thiazole-2- carboxamide (S)-N-(3-(3'-Chloro-5-((3-hydroxypyrrolidin-1-yl)methyl)-6-m ethoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)thiazole-2-carboxamide was prepared in a similar fashion to Example 70, replacing 1-(4-aminopiperidin-1-yl)ethan- 1-one with (S)-pyrrolidin-3-ol in step (g). White solid, LCMS: m/z found 609 [M+H] ⁺ retention time = 2.07 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.63 (d, 1H), 7.90 (s, 1H), 7.87 (d, 1H), 7.83 (d, 1H), 7.76 (d, 1H), 7.45-7.40 (m, 2H), 7.24 (dd, 1H), 4.41- 4.36 (m, 1H), 4.13 (s, 2H), 4.04 (s, 3H), 3.80-3.75 (m, 2H), 3.70 (t, 2H), 2.91-2.82 (m, 2H), 2.79 (t, 2H), 2.62-2.58 (m, 2H), 2.22-2.18 (m, 1H), 2.16 (s, 3H), 1.79-1.72 (m, 1H). Example 76: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- hydroxyethyl)amino)methyl)-4-methoxypicolinamide (a) Lithium 5-bromo-4-methoxypicolinate To a solution of methyl 5-bromo-4-methoxypicolinate (0.9 g, 3.66 mmol) in THF / water mixture (18:1 v/v, 9.5 mL) was added lithium hydroxide monohydrate (0.31 g, 7.32 mmol) in one portion under N ₂ , and the mixture was stirred at room temperature for 3 hours. The mixture was concentrated to afford lithium 5-bromo-4-methoxypicolinate (1.1 g, crude) as a white solid. LCMS: m/z found 232 [M+H] ⁺ (acid). (b) tert-Butyl (S)-((2'-(3-(5-bromo-4-methoxypicolinamido)-2-methylphenyl)- 3'- chloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrroli din-2-yl)methyl)carbamate To a mixture of tert-butyl (S)-((2'-(3-amino-2-methylphenyl)-3'-chloro-6-methoxy- [2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)c arbamate (Example 42, step (d)) (0.3 g, 0.54 mmol) and lithium 5-bromo-4-methoxypicolinate (0.25 g, 1.06 mmol) in DMF (3 mL) was added N,N-diisopropylethylamine (0.24 mL) and 2-chloro-1- methylpyridinium iodide (0.28 g, 1.09 mmol) in one portion under N ₂ and the mixture stirred at room temperature for 12 hours. Water (50 mL) and saturated aqueous brine solution (15 mL) were then added, and the mixture was extracted with ethyl acetate (50 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (50-100% ethyl acetate/petroleum ether) to afford tert-butyl (S)-((2'-(3-(5-bromo-4-methoxypicolinamido)-2-methylphenyl)- 3'-chloro-6- methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl) methyl)carbamate (320 mg, 55% yield) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.40 (s, 1H), 8.76-8.71 (m, 2H), 7.83-7.77 (m, 3H), 7.73-7.71 (m, 1H), 7.55-7.46 (m, 2H), 7.38 (t, 1H), 7.19 (d, 1H), 4.45-4.36 (m, 2H), 4.09 (s, 3H), 3.97 (s, 3H), 3.78-3.76 (m, 1H), 3.31-3.29 (m, 2H), 2.21- 2.10 (m, 3H), 2.06 (s, 3H), 1.93-1.89 (m, 1H), 1.44-1.31 (m, 9H). (c) tert-Butyl (S)-((3'-chloro-6-methoxy-2'-(3-(4-methoxy-5-vinylpicolinami do)-2- methylphenyl)-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin -2-yl)methyl)carbamate To a mixture of tert-butyl (S)-((2'-(3-(5-bromo-4-methoxypicolinamido)-2- methylphenyl)-3'-chloro-6-methoxy-[2,4'-bipyridin]-5-yl)meth yl)((5-oxopyrrolidin-2- yl)methyl)carbamate (0.12 g, 0.16 mmol) and 4,4,5,5-tetramethyl-2-vinyl-1,3,2- dioxaborolane (0.04 g, 0.23 mmol) in 1,4-dioxane / water mixture (10:1 v/v, 2.2 mL) was added [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (0.01 g, 0.01 mmol) and potassium carbonate (0.06 g, 0.47 mmol) in one portion under N ₂ and the mixture stirred at 110 °C for 12 hours. The mixture was concentrated, water (30 mL) and saturated aqueous brine solution (15 mL) added to the residue, and the mixture extracted with ethyl acetate (50 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (50-100% ethyl acetate / petroleum ether) to afford tert-butyl (S)-((3'-chloro-6-methoxy-2'-(3-(4-methoxy-5-vinylpicolinami do)-2-methylphenyl)-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te (270 mg, 90% yield) as a yellow solid. LCMS: m/z found 713 [M+H] ⁺ . (d) tert-Butyl (S)-((3'-chloro-2'-(3-(5-formyl-4-methoxypicolinamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-6-methoxy-2'-(3-(4-methoxy-5- vinylpicolinamido)-2-methylphenyl)-[2,4'-bipyridin]-5-yl)met hyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (0.27 g, 0.38 mmol) in THF / water mixture (10:1 v/v, 3.3 mL) was added potassium osmate(VI) dihydrate (0.03 g, 0.08 mmol) in one portion at 0 °C under N ₂ , and the mixture stirred at 0 °C for 0.5 hours. Sodium periodate (0.24 g, 1.14 mmol) was then added, and the mixture stirred at room temperature for 11.5 hours. Aqueous sodium sulfite solution was added, and the mixture concentrated. Water (25 mL) and saturated aqueous brine solution (5 mL) were added to the residue, and the mixture was extracted with ethyl acetate / THF mixture (1:1 v/v, 20 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated to afford tert-butyl (S)-((3'-chloro-2'-(3-(5-formyl-4- methoxypicolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipyrid in]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (230 mg, crude) as a yellow solid. LCMS: m/z found 715 [M+H] ⁺ . (e) tert-Butyl (S)-((3'-chloro-2'-(3-(5-(((2-hydroxyethyl)amino)methyl)-4- methoxypicolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipyrid in]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-2'-(3-(5-formyl-4-methoxypicolinamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate (0.23 g, 0.32 mmol) and 2-aminoethan-1-ol (0.04 g, 0.64 mmol) in THF / methanol mixture (1:1 v/v, 4 mL) was added sodium acetate (0.08 g, 0.96 mmol) in one portion under N ₂ , and the mixture was at room temperature for 11.5 hours. Sodium cyanoborohydride (0.06 g, 0.96 mmol) was then added, and the mixture stirred at room temperature for 0.5 hours. The mixture was combined with another batch at 100 mg scale. The mixture was concentrated, water (50 mL) and saturated aqueous brine solution (15 mL) added to the residue, and the mixture extracted with ethyl acetate (50 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-15% methanol / ethyl acetate) to afford tert-butyl (S)-((3'-chloro-2'-(3-(5-(((2-hydroxyethyl)amino)methyl)-4-m ethoxypicolinamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate (130 mg, 37% yield) as a yellow solid. LCMS: m/z found 760 [M+H] ⁺ . (f) (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- hydroxyethyl)amino)methyl)-4-methoxypicolinamide To a mixture of tert-butyl (S)-((3'-chloro-2'-(3-(5-(((2-hydroxyethyl)amino)methyl)-4- methoxypicolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipyrid in]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (0.13 g, 0.16 mmol) in 1,4-dioxane (1 mL) was added concentrated HCl solution (0.3 mL) in one portion under N ₂ , and the mixture was stirred at room temperature for 1 hour. The mixture was purified by reverse phase HPLC to afford the product as a formic salt (~20 mg). The product was neutralized with saturated aqueous sodium bicarbonate solution, deionized water (15 mL) added, and the mixture extracted with dichloromethane (3 x 5 mL). The combined organic phases were concentrated and lyophilized to afford (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((2- hydroxyethyl)amino)methyl)-4-methoxypicolinamide (16.6 mg, 13% yield) as a yellow solid. LCMS: m/z found 660 [M+H] ⁺ , retention time = 2.18 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): 8.64 (d, 1H), 8.49 (s, 1H), 8.09 (d, 1H), 7.89 (s, 1H), 7.83 (d, 1H), 7.76 (d, 1H), 7.45-7.41 (m, 2H), 7.21 (d, 1H), 4.08 (s, 3H), 4.06 (s, 3H), 3.96-3.79 (m, 5H), 3.70 (t, 2H), 2.77-2.67 (m, 4H), 2.41-2.27 (m, 3H), 2.18 (s, 3H), 1.87-1.82 (m, 1H). Example 77: (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino) methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydro xyethyl)amino)methyl)-5- methoxypicolinamide (a) Lithium 4-bromo-5-methoxypicolinate To a mixture of methyl 4-bromo-5-methoxypicolinate (0.15 g, 0.61 mmol) in THF / water mixture (10:1 v/v, 2.2 mL) was added lithium hydroxide monohydrate (0.05 g, 1.22 mmol) in one portion under N ₂ , and the mixture stirred at room temperature for 12 hours. The mixture was concentrated to afford lithium 4-bromo-5-methoxypicolinate (180 mg, crude). LCMS: m/z found 232 and 234 [M+H] ⁺ (acid). (b) tert-Butyl (S)-((2'-(3-(4-bromo-5-methoxypicolinamido)-2-methylphenyl)- 3'- chloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrroli din-2-yl)methyl)carbamate To a mixture of lithium 4-bromo-5-methoxypicolinate (0.18 g, 0.75 mmol) in DMF (3 mL) was added N,N-diisopropylethylamine (0.12 mL, 0.68 mmol) and 2-(3H- [1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethyluroni um hexafluorophosphate(V) (0.34 g, 0.91 mmol) in one portion under N ₂ , and the mixture was stirred at room temperature for 0.5 hours. To the mixture was added tert-butyl (S)-((2'-(3-amino-2-methylphenyl)-3'- chloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrroli din-2-yl)methyl)carbamate (Example 42, step (d)) (0.25 g, 0.45 mmol) and the mixture stirred at room temperature for 11.5 hours. The mixture was combined with another batch at 80 mg scale. Water (50 mL) and saturated aqueous brine solution (50 mL) were added, and the mixture extracted with ethyl acetate (50 mL). The organic phase was dried with anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by normal phase SiO ₂ chromatography (50-100% ethyl acetate/petroleum ether) to afford tert-butyl (S)-((2'-(3-(4-bromo-5- methoxypicolinamido)-2-methylphenyl)-3'-chloro-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (400 mg, 80% yield) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.12 (s, 1H), 8.58 (d, 1H), 8.40 (s, 1H), 8.18 (s, 1H), 7.71 (d, 1H), 7.64 (s, 1H), 7.58 (d, 1H), 7.44-7.33 (m, 2H), 7.24 (t, 1H), 7.05 (d, 1H), 4.32-4.23 (m, 2H), 3.98 (s, 3H), 3.84 (s, 3H), 3.68-3.64 (m, 1H), 3.18-3.15 (m, 2H), 2.06-1.96 (m, 3H), 1.93 (s, 3H), 1.61-1.57 (m, 1H), 1.31-1.18 (m, 9H). (c) tert-Butyl (S)-((3'-chloro-6-methoxy-2'-(3-(5-methoxy-4-vinylpicolinami do)-2- methylphenyl)-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin -2-yl)methyl)carbamate To a mixture of tert-butyl (S)-((2'-(3-(4-bromo-5-methoxypicolinamido)-2- methylphenyl)-3'-chloro-6-methoxy-[2,4'-bipyridin]-5-yl)meth yl)((5-oxopyrrolidin-2- yl)methyl)carbamate (0.15 g, 0.19 mmol) and 4,4,5,5-tetramethyl-2-vinyl-1,3,2- dioxaborolane (0.04 g, 0.28 mmol) in 1,4-dioxane / water mixture (10:1 v/v, 2.2 mL) was added potassium carbonate (0.08 g, 0.57 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (0.02 g, 0.02 mmol) in one portion under N ₂ , and the mixture stirred at 105 °C for 12 hours. The mixture was combined with another batch at 110 mg scale. The mixture was concentrated, water (50 mL) and saturated aqueous brine solution (15 mL) added to the residue, and the mixture extracted with ethyl acetate / THF mixture (1:1 v/v, 50 mL). The organic phase was dried with anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by normal phase SiO ₂ chromatography (5-100% ethyl acetate/petroleum ether) to afford tert- butyl (S)-((3'-chloro-6-methoxy-2'-(3-(5-methoxy-4-vinylpicolinami do)-2-methylphenyl)- [2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)c arbamate (265 mg, 57% yield) as a yellow oil. LCMS: m/z found 713 [M+H] ⁺ . (d) tert-Butyl (S)-((3'-chloro-2'-(3-(4-formyl-5-methoxypicolinamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-6-methoxy-2'-(3-(5-methoxy-4- vinylpicolinamido)-2-methylphenyl)-[2,4'-bipyridin]-5-yl)met hyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (0.15 g, 0.21 mmol) in THF / H ₂ O mixture (10:1 v/v, 2.2 mL) was added potassium osmate(VI) dihydrate (0.02 g, 0.04 mmol) in one portion at 0°C under N ₂ , and the mixture stirred at 0 °C for 0.5 hours. Sodium periodate (0.27 g, 1.26 mmol) was then added, and the mixture stirred at room temperature for 11.5 hours. To the mixture was added sodium sulfite aqueous solution. The mixture was concentrated, water (25 mL) and saturated aqueous brine solution (5 mL) added to the residue, and the mixture was extracted with ethyl acetate / THF mixture (1:1 v/v, 20 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated to afford tert-butyl (S)-((3'-chloro-2'-(3-(4-formyl-5- methoxypicolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipyrid in]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (150 mg, crude) as a yellow solid. LCMS: m/z found 715 [M+H] ⁺ . (e) tert-Butyl (S)-((3'-chloro-2'-(3-(4-(((2-hydroxyethyl)amino)methyl)-5- methoxypicolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipyrid in]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-2'-(3-(4-formyl-5-methoxypicolinamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate (0.15 g, 0.21 mmol) and 2-aminoethan-1-ol (0.02 g, 0.34 mmol) in THF / methanol mixture (1:1 v/v, 2 mL) was added sodium acetate (0.05 g, 0.63 mmol) in one portion under N ₂ , and the mixture stirred at room temperature for 3 hours. Sodium cyanoborohydride (0.04 g, 0.63 mmol) was then added, and the mixture stirred at room temperature for 0.5 hours. The mixture was combined with another batch at 85 mg scale. The mixture was concentrated, water (30 mL) and saturated aqueous brine solution (15 mL) added to the residue, and the mixture extracted with ethyl acetate (30 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated to afford tert-butyl (S)-((3'- chloro-2'-(3-(4-(((2-hydroxyethyl)amino)methyl)-5-methoxypic olinamido)-2-methylphenyl)- 6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-y l)methyl)carbamate (250 mg, crude) as a yellow solid. LCMS: m/z found 760 [M+H] ⁺ . (f) (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl) amino)methyl)-5- methoxypicolinamide To a mixture of tert-butyl (S)-((3'-chloro-2'-(3-(4-(((2-hydroxyethyl)amino)methyl)-5- methoxypicolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipyrid in]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (0.24 g, 0.32 mmol) in 1,4-dioxane (1 mL) was added concentrated HCl solution (0.3 mL) in one portion under N ₂ , and the mixture stirred at room temperature for 1 hour. The mixture was combined with another batch at 10 mg scale. The mixture was purified by reverse phase HPLC to afford (S)-N-(3-(3'-chloro-6- methoxy-5-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4 '-bipyridin]-2'-yl)-2- methylphenyl)-4-(((2-hydroxyethyl)amino)methyl)-5-methoxypic olinamide (35.5 mg, 16% yield) as a yellow solid. LCMS: m/z found 660 [M+H] ⁺ retention time = 2.44 min. ¹ H NMR (400 MHz, Methanol-d4): 8.64 (d, 1H), 8.44 (s, 1H), 8.23 (s, 1H), 8.06 (d, 1H), 7.83 (d, 1H), 7.75 (d, 1H), 7.45-7.40 (m, 2H), 7.20 (d, 1H), 4.10 (s, 3H), 4.06 (s, 3H), 3.94-3.83 (m, 5H), 3.72 (t, 2H), 2.79-2.67 (m, 4H), 2.38-2.27 (m, 3H), 2.18 (s, 3H), 1.87-1.82 (m, 1H). Example 78: N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((R)-3- hydroxypyrrolidin-1-yl)methyl)-1-methyl-1H-imidazole-2-carbo xamide N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-hydroxypyr rolidin-1-yl)methyl)-1-methyl- 1H-imidazole-2-carboxamide was prepared in a similar fashion to Example 69, replacing 2- aminoethan-1-ol with (R)-pyrrolidin-3-ol in step (f). White solid, LCMS: m/z found 659 [M+H] ⁺ retention time = 2.31 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.61 (d, 1H), 7.90 (d, 1H), 7.81 (d, 1H), 7.73 (d, 1H), 7.43-7.37 (m, 2H), 7.18 (dd, 1H), 7.03 (s, 1H), 4.36-4.33 (m, 1H), 4.10 (s, 3H), 4.04 (s, 3H), 3.85-3.83 (m, 3H), 3.72-3.67 (m, 2H), 2.80- 2.65 (m, 4H), 2.55-2.49 (m, 2H), 2.36-2.27 (m, 3H), 2.14 (s, 3H), 1.84-1.68 (m, 3H). Example 79: (S)-5-(((1-Acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chlor o-6-methoxy- 5-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyri din]-2'-yl)-2- methylphenyl)-1-methyl-1H-imidazole-2-carboxamide (S)-5-(((1-Acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chlor o-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-1-methyl- 1H-imidazole-2-carboxamide was prepared in a similar fashion to Example 69, replacing 2- aminoethan-1-ol with 1-(4-aminopiperidin-1-yl)ethan-1-one in step (f). White solid, LCMS: m/z found 714 [M+H] ⁺ retention time = 2.34 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.61 (d, 1H), 7.91 (d, 1H), 7.81 (d, 1H), 7.73 (d, 1H), 7.43-7.37 (m, 2H), 7.17 (d, 1H), 7.07 (s, 1H), 4.43-4.38 (m, 1H), 4.08 (s, 3H), 4.04 (s, 3H), 3.93-3.81 (m, 6H), 3.21-3.13 (m, 1H), 2.81-2.65 (m, 4H), 2.35-2.23 (m, 3H), 2.13 (s, 3H), 2.10 (s, 3H), 2.04- 1.95 (m, 2H), 1.87-1.77 (m, 1H), 1.39-1.33 (m, 2H). Example 80: N-(3-(3-Chloro-2-(3-methoxy-4-(((((S)-1-methyl-5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((R)-3- hydroxypyrrolidin-1-yl)methyl)picolinamide N-(3-(3-chloro-2-(3-methoxy-4-(((((S)-1-methyl-5-oxopyrrolid in-2- yl)methyl)amino)methyl) phenyl)pyridin-4-yl)-2-methylphenyl)-5-(((R)-3- hydroxypyrrolidin-1-yl)methyl)picolinamide was prepared in a similar fashion to Example 6, replacing (S)-5-(aminomethyl)pyrrolidin-2-one hydrochloride salt with (S)-5-(aminomethyl)- 1-methylpyrrolidin-2-one in step (h). White solid, LCMS: m/z found 669 [M+H] ⁺ retention time = 2.45 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.71 (s, 1H), 8.62 (d, 1H), 8.22 (d, 1H), 8.05-7.99 (m, 2H), 7.43-7.38 (m, 3H), 7.30-7.26 (m, 2H), 7.13 (d, 1H), 4.41- 4.36 (m, 1H), 3.95-3.90 (m, 4H), 3.88-3.76 (m, 3H), 3.75-3.70 (m, 1H), 2.87-2.70 (m, 7H), 2.59-2.55 (m, 2H), 2.51-2.42 (m, 1H), 2.37-2.28 (m, 1H), 2.25-2.17 (m, 5H), 1.98-1.91 (m, 1H), 1.79-1.72 (m, 1H). Example 81: 3-(((3'-Chloro-2'-(3-(5-(((2-hydroxyethyl)amino)methyl)thiaz ole-2- carboxamido)-2-methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl )methyl)amino)-2,2- dimethylpropanoic acid 3-(((3'-Chloro-2'-(3-(5-(((2-hydroxyethyl)amino)methyl)thiaz ole-2-carboxamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)amino)- 2,2-dimethylpropanoic acid was prepared in a similar fashion to Example 70, replacing 1-(4-aminopiperidin-1-yl)ethan- 1-one with 3-amino-2,2-dimethylpropanoic acid in step (g). White solid, LCMS: m/z found 639 [M+H] ⁺ retention time = 2.30 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.66 (d, 1H), 7.93 (d, 1H), 7.91 (s, 1H), 7.82 (d, 1H), 7.76 (d, 1H), 7.50 (d, 1H), 7.43 (t, 1H), 7.20 (d, 1H), 4.24 (s, 2H), 4.14 (s, 3H), 3.70 (t, 2H), 3.33-3.32 (m, 2H), 3.02 (s, 2H), 2.79 (t, 2H), 2.15 (s, 3H), 1.24 (s, 6H). Example 82: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-2-(2-hydroxyethyl)- 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-6-carboxamide (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-2-(2-hydroxyethyl)-2 ,3-dihydro-1H-pyrrolo[3,4- c]pyridine-6-carboxamide was prepared in a similar fashion to Example 68, replacing 6- chloro-1,2,3,4-tetrahydro-2,7-naphthyridine with 6-chloro-2,3-dihydro-1H-pyrrolo[3,4- c]pyridine in step (a). Yellow solid, LCMS: m/z found 642 [M+H] ⁺ retention time = 2.19 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): 8.64 (d, 1H), 8.60 (s, 1H), 8.17 (s, 1H), 8.08 (d, 1H), 7.83 (d, 1H), 7.76 (d, 1H), 7.45-7.41 (m, 2H), 7.20 (d, 1H), 4.22-4.13 (m, 4H), 4.06 (s, 3H), 3.91-3.85 (m, 3H), 3.80 (t, 2H), 2.98 (t, 2H), 2.73-2.67 (m, 2H), 2.38-2.21 (m, 3H), 2.19 (s, 3H), 1.87-1.82 (m, 1H). Example 83: N-(3-(3'-Chloro-6-methoxy-5-((7-oxo-2,6-diazaspiro[3.4]octan -2- yl)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hyd roxyazetidin-1- yl)methyl)picolinamide (a) N-(3-Bromo-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl )picolinamide To a mixture of N-(3-bromo-2-methylphenyl)-5-formylpicolinamide (Example 1, step (c)) (278 mg, 871.06 μmol) and azetidin-3-ol (127.34 mg, 1.74 mmol) in dichloromethane (26 mL) and methanol (13 mL) was added sodium cyanoborohydride (164.22 mg, 2.61 mmol) and the mixture stirred at room temperature for 12 hours under N ₂ . The mixture was extracted with ethyl acetate (2 x 50 mL) and the combined organic phases dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0~100% methanol / ethyl acetate) to afford N-(3-bromo- 2-methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picolinami de (146 mg, 82% yield) as a red solid. LCMS: m/z found 376 [M+H] ⁺ . (b) 5-((3-Hydroxyazetidin-1-yl)methyl)-N-(2-methyl-3-(4,4,5,5-te tramethyl-1,3,2- dioxaborolan-2-yl)phenyl)picolinamide To a mixture of N-(3-bromo-2-methylphenyl)-5-((3-hydroxyazetidin-1- yl)methyl)picolinamide (116 mg, 0.31 mmol) and bis(pinacolato)diboron (392 mg, 1.54 mmol) in 1,4-dioxane (3 mL) was added potassium acetate (90.8 mg, 0.925 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (75.5 mg, 0.092 mmol), and the mixture stirred at 130 °C for 3 hours under N ₂ . Water (50 mL) was added, and the mixture extracted with ethyl acetate (2 x 50 mL). The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0~100% methanol / ethyl acetate) to afford 5-((3-hydroxyazetidin-1-yl)methyl)-N-(2-methyl-3-(4,4,5,5-te tramethyl-1,3,2-dioxaborolan- 2-yl)phenyl)picolinamide (96.3 mg, 73% yield) as a black solid. LCMS: m/z found 424 [M+H] ⁺ . (c) N-(3-(3'-chloro-5-formyl-6-methoxy-[2,4'-bipyridin]-2'-yl)-2 -methylphenyl)-5- ((3-hydroxyazetidin-1-yl)methyl)picolinamide To a mixture of 5-((3-hydroxyazetidin-1-yl)methyl)-N-(2-methyl-3-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)picolinamide (225 mg, 0.532 mmol) and 2',3'- dichloro-6-methoxy-[2,4'-bipyridine]-5-carbaldehyde (Example 23, step (a)) (150.5 mg, 0.532 mmol) in THF (10 mL) and water (2 mL) was added chloro(2-dicyclohexylphosphino- 2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1 ,1′-biphenyl)]palladium(II) (41.8 mg, 0.053 mmol) and potassium phosphate (338.5 mg, 1.59 mmol), and the mixture stirred at 80 °C for 2 h under N ₂ . Water (50 mL) was added, and the mixture extracted with ethyl acetate (2 x 50 mL). The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0~100% methanol / ethyl acetate) to afford N-(3-(3'-chloro-5-formyl-6-methoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picoli namide (205.1 mg, 70% yield) as a green solid. LCMS: m/z found 544 [M+H] ⁺ . (d) N-(3-(3'-chloro-6-methoxy-5-((7-oxo-2,6-diazaspiro[3.4]octan -2-yl)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide To a mixture of N-(3-(3'-chloro-5-formyl-6-methoxy-[2,4'-bipyridin]-2'-yl)-2 - methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picolinamide (195 mg, 0.358 mmol) and 2,6-diazaspiro[3.4]octan-7-one (67.8 mg, 0.538 mmol) in methanol (5 mL) and dichloromethane (5 mL) was added sodium acetate (88.2 mg, 1.08 mmol), and the mixture stirred at room temperature for 11.5 hours under N ₂ . Sodium cyanoborohydride (67.6 mg, 1.08 mmol) was then added, and the mixture stirred at room temperature for 0.5 hours. The mixture was filtered, and the filtrate concentrated. The residue was purified by reverse phase HPLC to afford N-(3-(3'-chloro-6-methoxy-5-((7-oxo-2,6-diazaspiro[3.4]octan -2-yl)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidi n-1-yl)methyl)picolinamide (38.7 mg, 16% yield) as a white solid. LCMS: m/z found 654 [M+H] ⁺ , retention time = 2.23 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.65-8.63 (m, 2H), 8.22 (d, 1H), 8.06 (d, 1H), 7.98 (dd, 1H), 7.76 (d, 1H), 7.74 (d, 1H), 7.44 - 7.42 (m, 2H), 7.21 (d, 1H), 4.42 - 4.39 (m, 1H), 4.04 (s, 3H), 3.81 (s, 2H), 3.75 (s, 2H), 3.67 (m, 2H), 3.61 (s, 2H), 3.44 (m, 4H), 3.06 - 3.05 (m, 2H), 2.60 (s, 2H), 2.18 (s, 3H). Example 84: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-6-(2-hydroxyethyl)- 5,6,7,8-tetrahydro-2,6-naphthyridine-3-carboxamide (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-6-(2-hydroxyethyl)-5 ,6,7,8-tetrahydro-2,6- naphthyridine-3-carboxamide was prepared in a similar fashion to Example 68, replacing 6- chloro-1,2,3,4-tetrahydro-2,7-naphthyridine hydrochloride salt with 7-chloro-1,2,3,4- tetrahydro-2,6-naphthyridine hydrochloride salt in step (a). LCMS: m/z found 656 [M+H] ⁺ retention time = 2.76 (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): 8.64 (d, 1H), 8.48 (s, 1H), 8.08 (d, 1H), 7.96 (s, 1H), 7.83 (d, 1H), 7.75 (d, 1H), 7.45-7.40 (m, 2H), 7.20 (d, 1H), 4.06 (s, 3H), 3.91-3.80 (m, 7H), 3.04 (t, 2H), 2.95-2.94 (m, 2H), 2.78 (t, 2H), 2.73-2.70 (m, 4H), 2.38-2.27 (m, 3H), 2.18 (s, 3H), 1.86-1.81 (m, 1H). Example 85: (S)-4-(((2-Hydroxyethyl)amino)methyl)-N-(3-(6-methoxy-3'-met hyl-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl) picolinamide (a) tert-Butyl (S)-((2'-(3-(4-(hydroxymethyl)picolinamido)-2-methylphenyl)- 6- methoxy-3'-methyl-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrol idin-2- yl)methyl)carbamate To a mixture of tert-butyl (S)-((2'-(3-amino-2-methylphenyl)-6-methoxy-3'-methyl- [2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)c arbamate (Example 67, step (c)) (0.55 g, 1.03 mmol) and 4-(hydroxymethyl)picolinic acid (0.24 g, 1.55 mmol) in DMF (7 mL) was added 2-chloro-1-methylpyridinium iodide (0.53 g, 2.07 mmol) and N,N- diisopropylethylamine (0.45 mL, 2.59 mmol) in one portion under N ₂ , and the mixture stirred at room temperature for 12 hours. Water (50 mL) and saturated aqueous brine solution (50 mL) were added, and the mixture extracted with ethyl acetate (100 mL). The organic phase was dried with anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by normal phase SiO ₂ chromatography (50-80% ethyl acetate/petroleum ether) to afford tert- butyl (S)-((2'-(3-(4-(hydroxymethyl)picolinamido)-2-methylphenyl)- 6-methoxy-3'-methyl- [2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)c arbamate (800 mg, 42% yield) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.40 (s, 1H), 8.67 (d, 1H), 8.57 (d, 1H), 8.17 (s, 1H), 7.90 (d, 1H), 7.76 (s, 1H), 7.61 (d, 1H), 7.53-7.47 (m, 2H), 7.38-7.30 (m, 2H), 7.10 (dd, 1H), 5.61 (t, 1H), 4.68 (d, 2H), 4.48-4.36 (m, 2H), 3.94 (s, 3H), 3.78-3.76 (m, 1H), 3.29-3.27 (m, 2H), 2.20-2.03 (m, 9H), 1.72-1.68 (m, 1H), 1.45-1.31 (m, 9H). (b) tert-Butyl (S)-((2'-(3-(4-(((2-hydroxyethyl)amino)methyl)picolinamido)- 2- methylphenyl)-6-methoxy-3'-methyl-[2,4'-bipyridin]-5-yl)meth yl)((5-oxopyrrolidin-2- yl)methyl)carbamate To a mixture of tert-butyl (S)-((2'-(3-(4-(hydroxymethyl)picolinamido)-2- methylphenyl)-6-methoxy-3'-methyl-[2,4'-bipyridin]-5-yl)meth yl)((5-oxopyrrolidin-2- yl)methyl)carbamate (0.2 g, 0.3 mmol) in dichloromethane (4 mL) was added manganese dioxide (0.52 g, 6 mmol) in one portion under N ₂ , and the mixture stirred at room temperature for 12 hours. The mixture was filtered through Celite to afford a solution of tert- butyl (S)-((2'-(3-(4-formylpicolinamido)-2-methylphenyl)-6-methoxy -3'-methyl-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te.2-Aminoethan-1-ol (0.04 g, 0.72 mmol) and sodium acetate (0.15 g, 1.81 mmol) in THF / methanol mixture (1:1 v/v, 4 mL) were in one portion under N ₂ , and the mixture stirred at room temperature for 2 hours. Sodium cyanoborohydride (0.11 g, 1.81 mmol) was then added, and the mixture stirred at room temperature for 0.5 hours. The mixture was combined with another batch at 100 mg scale. The mixture was purified by reverse phase HPLC to afford tert-butyl (S)-((2'-(3-(4- (((2-hydroxyethyl)amino)methyl)picolinamido)-2-methylphenyl) -6-methoxy-3'-methyl-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te (40 mg, 6% yield) as a yellow solid. LCMS: m/z found 710 [M+H] ⁺ . (c) (S)-4-(((2-Hydroxyethyl)amino)methyl)-N-(3-(6-methoxy-3'-met hyl-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2- methylphenyl)picolinamide To a mixture of tert-butyl (S)-((2'-(3-(4-(((2- hydroxyethyl)amino)methyl)picolinamido)-2-methylphenyl)-6-me thoxy-3'-methyl-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te (0.04 g, 0.06 mmol) in 1,4- dioxane (1 mL) was added concentrated HCl solution (0.01 mL) in one portion under N ₂ , and the mixture was stirred at room temperature for 30 min. The mixture was combined with another batch at 5 mg scale. The mixture was neutralized with saturated aqueous sodium bicarbonate solution and the mixture purified by reverse phase HPLC to afford product (~15 mg) as a formic salt. The product was neutralized with saturated aqueous sodium bicarbonate solution, the mixture was extracted with dichloromethane (3 x 5 mL), and the combined organic phases were concentrated and lyophilized to afford (S)-4-(((2- hydroxyethyl)amino)methyl)-N-(3-(6-methoxy-3'-methyl-5-((((5 -oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)picolinamide (12.3 mg, 30% yield) as a yellow solid. LCMS: m/z found 610 [M+H] ⁺ retention time = 1.48 min. ¹ H NMR (400 MHz, Methanol-d4): 8.54 (d, 1H), 8.40 (d, 1H), 8.15 (s, 1H), 7.94 (d, 1H), 7.71 (d, 1H), 7.52 (dd, 1H), 7.42 (d, 1H), 7.31 (t, 1H), 7.12 (d, 1H), 7.05 (d, 1H), 3.91 (s, 3H), 3.86 (s, 2H), 3.76-3.73 (m, 3H), 3.60 (t, 2H), 2.67-2.55 (m, 4H), 2.26-2.15 (m, 3H), 2.09 (s, 3H), 2.09 (s, 3H), 1.76-1.69 (m, 1H). Example 86: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino) methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydro xyethyl)amino)methyl)-6,7- dihydro-5H-cyclopenta[c]pyridine-1-carboxamide (a) Methyl 2-(((trifluoromethyl)sulfonyl)oxy)cyclopent-1-ene-1-carboxyl ate To a solution of methyl 2-oxocyclopentane-1-carboxylate (25 g, 176 mmol) in dichloromethane (300 mL) at -78 °C under N ₂ , was added N,N- diisopropylethylamine (34.1 g, 264 mmol) followed by trifluoromethanesulfonic anhydride (34.8 mL, 211 mmol) and the mixture stirred at -78 °C to room temperature for 1 hour. The mixture was combined with another batch at the same scale. The mixture was concentrated and the residue purified by normal phase SiO ₂ chromatography (0-10% ethyl acetate/petroleum ether) to afford methyl 2-(((trifluoromethyl)sulfonyl)oxy)cyclopent-1-ene- 1-carboxylate (80 g, 82% yield) as an yellow oil. ¹ H NMR (400 MHz, Chloroform-d): δ.3.72 (s, 3H), 2.69-2.63 (m, 4H), 1.99-1.93 (m, 2H). (b) Methyl 2-((trimethylsilyl)ethynyl)cyclopent-1-ene-1-carboxylate To a mixture of methyl 2-(((trifluoromethyl)sulfonyl)oxy)cyclopent-1-ene-1- carboxylate (35 g, 128 mmol) in THF (300 mL) was added bis(triphenylphosphine)dichloropalladium (1.79 g, 2.55 mmol), copper(I)iodide (1.70 g, 8.93 mmol), and triethylamine (53.3 mL, 383 mmol) then ethynyl(trimethyl)silane (26.5 mL, 191 mmol) was added and the mixture stirred at room temperature for 1 hour under N ₂ . The mixture was combined with another two batches at the same scale and 10 g scale. Saturated aqueous ammonium chloride solution (500 mL) was added, and the mixture extracted with ethyl acetate (2 x 1 L). The combined organic phases were dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-10% ethyl acetate/petroleum ether) to afford methyl 2-((trimethylsilyl)ethynyl)cyclopent-1-ene-1-carboxylate (44 g, 68% yield) as a brown oil. ¹ H NMR (400 MHz, Chloroform-d): δ.3.58 (s, 3H), 2.52-2.45 (m, 4H), 1.76-1.70 (m, 2H), 0.05 (s, 9H). (c) 2-Ethynylcyclopent-1-ene-1-carboxylic acid To mixture of methyl 2-((trimethylsilyl)ethynyl)cyclopent-1-ene-1-carboxylate (20 g, 89.9 mmol) in THF / methanol (1:1 v/v, 100 mL) was added lithium hydroxide monohydrate (7.55 g, 180 mmol), and the mixture stirred at 50 °C for 2 hours under N ₂ . The mixture was combined with another two batches at the same scale and 10 g scale. The mixture was concentrated, water (1 L) added to the residue, and the mixture washed with ethyl acetate (1L). The aqueous layer was acidified with 2 N aqueous hydrochloric acid and extracted with ethyl acetate (2 x 1L). The combined organic phases were dried over anhydrous sulfate, filtered, and concentrated under reduced pressure to afford 2-ethynylcyclopent-1-ene-1- carboxylic acid (19 g, crude) as a red solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ.12.5 (s, 1H), 4.55 (s, 1H), 2.60-2.56 (m, 4H), 1.87-1.79 (m, 2H). The product was used in the next step without further purification. (d) 2-Ethynylcyclopent-1-ene-1-carboxamide To a mixture of 2-ethynylcyclopent-1-ene-1-carboxylic acid (9 g, 66.1 mmol) in dichloromethane (150 mL) was added ammonium chloride (17.7 g, 331 mmol), O- (7-azabenzotriazol-1-yl)-N,N,N’,N’-tetramethyluronium hexafluorophosphate (37.7 g, 99.2 mmol) and N,N-diisopropylethylamine (25.6 g, 198 mmol), and the mixture stirred at room temperature for 12 hours under N ₂ . The mixture was combined with another two batches at the same scale and 1 g scale. Water (500 mL) was added, and the mixture extracted with dichloromethane (2 x 500 mL). The combined organic phases were dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-80%, ethyl acetate/petroleum ether) to afford 2- ethynylcyclopent-1-ene-1-carboxamide (13 g, 69% yield) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ.7.34 (s, 1H), 7.09 (s, 1H), 4.59 (s, 1H), 2.62-2.55 (m, 4H), 1.88-1.82 (m, 2H). (e) 6,7-Dihydro-5H-cyclopenta[c]pyridin-1-ol To a mixture of 2-ethynylcyclopent-1-ene-1-carboxamide (6 g, 44.4 mmol) in methanol (40 mL) was added 2 M dimethylamine in THF (222 mL, 444 mol) and the mixture stirred at 80°C for 12 hours under N ₂ . The mixture was then concentrated, 1,4- dioxane (100 mL) added to the residue and the mixture stirred at 110 °C for 2 hours under N ₂ . The mixture was combined with another two batches at the same scale and 1.0 g scale. The mixture was concentrated, and the residue triturated with ethyl acetate (80 mL) at room temperature for 0.5 hour. The mixture was filtered to afford 6,7-dihydro-5H- cyclopenta[c]pyridin-1-ol 6,7-dihydro-5H-cyclopenta[c]pyridin-1-ol (11 g, 84% yield) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ.11.30 (s, 1H), 7.19 (d, 1H), 7.16 (d, 1H), 2.78 (t, 2H), 2.61 (t, 2H), 1.97-1.92 (m, 2H). (f) 4-Bromo-6,7-dihydro-5H-cyclopenta[c]pyridin-1-ol To a mixture of 6,7-dihydro-5H-cyclopenta[c]pyridin-1-ol (5 g, 37.0 mmol) in acetic acid (50 mL) was added bromine (2.29 mL, 44.4 mmol), and the mixture stirred at room temperature for 1 hour under N ₂ . The mixture was combined with another batch at the same scale. The mixture was concentrated and the residue purified by normal phase SiO ₂ chromatography (0-10%, methanol / dichloromethane) to afford 4-bromo-6,7-dihydro-5H- cyclopenta[c]pyridin-1-ol (18 g, crude) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ. 10.01 (s, 1H), 7.55 (s, 1H), 2.82 (t, 2H), 2.74 (t, 2H), 2.02-1.95 (m, 2H). (g) 4-Bromo-1-chloro-6,7-dihydro-5H-cyclopenta[c]pyridine A mixture of 4-bromo-6,7-dihydro-5H-cyclopenta[c]pyridin-1-ol (3 g, 14.0 mmol) in thionyl chloride (30.00 mL, 413 mmol) and DMF (5 mL, 65.0 mmol) was stirred at 70 °C for 12 hours under N ₂ . The mixture was combined with another batch at the 1 g scale. The mixture was concentrated and water (100 mL) added to the residue. The mixture was neutralized with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate (2 x100 mL). The combined organic phases were dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-5%, ethyl acetate/petroleum ether) to afford 4-bromo-1-chloro-6,7- dihydro-5H-cyclopenta[c]pyridine (2.5 g, 76% yield) as a brown oil. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ.8.35 (s, 1H), 3.05-2.98 (m, 4H), 2.16-2.08 (m, 2H). (h) 1-Chloro-4-vinyl-6,7-dihydro-5H-cyclopenta[c]pyridine To a mixture of 4-bromo-1-chloro-6,7-dihydro-5H-cyclopenta[c]pyridine (2.3 g, 9.89 mmol), 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (1.83 g, 11.9 mmol) in 1,4-dioxane / water (5:1 v/v, 36 mL) was added potassium phosphate (6.30 g, 29.7 mmol), [1,1′-bis(di-tert- butylphosphino)ferrocene]dichloropalladium(II) (0.64 g, 0.99 mmol), and the mixture stirred at 110 °C for 2 hours under N ₂ . The mixture was combined with another batch at the 0.2 g scale. water (100 mL) was added, and the mixture extracted with ethyl acetate (2 x 100 mL). The combined organic phases were dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0- 15%, ethyl acetate/petroleum ether) to afford 1-chloro-4-vinyl-6,7-dihydro-5H- cyclopenta[c]pyridine (1.3 g, 73% yield) as a brown solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ.8.35 (s, 1H), 6.80-6.72 (m, 1H), 5.89 (d, 1H), 5.47 (d, 1H), 3.05 (t, 2H), 2.92 (t, 2H), 2.13- 2.05 (m, 2H). (i) 1-Chloro-6,7-dihydro-5H-cyclopenta[c]pyridine-4-carbaldehyde To a mixture of 1-chloro-4-vinyl-6,7-dihydro-5H-cyclopenta[c]pyridine (1.1 g, 6.12 mmol) in THF/ water (10:1 v/v, 55 mL) was added potassium osmate(VI) dihydrate (0.45 g, 1.22 mmol) and the mixture stirred at 0°C for 0.5 hours under N ₂ . Sodium periodate (3.93 g, 18.4 mmol) was then added, and the mixture stirred at room temperature for 1.5 hours under N ₂ . The mixture was combined with another batch at the 0.2 g scale. water (50 mL) was added, and the mixture extracted with ethyl acetate (2 x 100 mL). The combined organic phases were dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-20%, ethyl acetate/petroleum ether) to afford 1-chloro-6,7-dihydro-5H-cyclopenta[c]pyridine-4- carbaldehyde (900 mg, 81% yield) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ.10.16 (s, 1H), 8.72 (s, 1H), 3.31 (t, 2H), 2.95 (t, 2H), 2.18-2.10 (m, 2H). (j) tert-Butyl (2-((tert-butyldimethylsilyl)oxy)ethyl)((1-chloro-6,7-dihydr o-5H- cyclopenta[c]pyridin-4-yl)methyl)carbamate To a mixture of 1-chloro-6,7-dihydro-5H-cyclopenta[c]pyridine-4-carbaldehyde (300 mg, 1.65 mmol), 2-((tert-butyldimethylsilyl)oxy)ethan-1-amine (434 mg, 2.48 mmol) in dichloromethane (15 mL), was added sodium acetate (406 mg, 4.96 mmol), and the mixture was stirred at room temperature for 1.5 hours under N ₂ . Sodium cyanoborohydride (311 mg, 4.96 mmol) was then added, and the mixture stirred at room temperature for 0.5 hours under N ₂ to afford 2-[tert-butyl(dimethyl)silyl]oxy-N-[(1-chloro-6,7-dihydro-5H - cyclopenta[c]pyridin-4-yl)methyl]ethanamine. Di-tert-butyl dicarbonate (0.75 mL, 3.28 mmol) and triethylamine (0.69 mL, 4.93 mmol) were then added, and the mixture stirred at room temperature for 1 hour under N ₂ . Water (20 mL) was added, and the mixture extracted with dichloromethane (2 x 50 mL). The combined organic phases were dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-30%, ethyl acetate/petroleum ether) to afford tert-butyl(2-((tert-butyldimethylsilyl)oxy)ethyl)((1-chloro- 6,7-dihydro-5H- cyclopenta[c]pyridin-4-yl)methyl)carbamate (400 mg, two step 55% yield) as a yellow oil. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ.7.96 (s, 1H), 4.43 (s, 2H), 3.61-3.57 (m, 2H), 3.25-3.18 (m, 2H), 2.91-2.88 (m, 4H), 2.10-2.03 (m, 2H), 1.41-1.31 (m, 9H), 0.83 (s, 9H), 0.00 (s, 6H). (k) Methyl 4-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-6,7-dihydro-5H-cy clopenta[c]pyridine-1- carboxylate To a mixture of tert-butyl(2-((tert-butyldimethylsilyl)oxy)ethyl)((1-chloro- 6,7- dihydro-5H-cyclopenta[c]pyridin-4-yl)methyl)carbamate (350 mg, 0.79 mmol) in methanol (10 mL) was added [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (130 mg, 159 μmol) and triethylamine (0.55 mL, 3.97 mmol), and the mixture stirred at 80 °C for 12 hours under CO at 50 psi. The mixture was concentrated, water (30 mL) added to the residue, and the mixture extracted with ethyl acetate (2 x 50 mL). The combined organic phases were dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0- 30%, ethyl acetate/petroleum ether) to afford methyl4-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-6,7-dihydro-5H-cy clopenta[c]pyridine-1- carboxylate (330 mg, 89% yield) as a yellow oil. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ.8.21 (s, 1H), 4.43 (s, 2H), 3.83 (s, 3H), 3.21-3.15 (m, 4H), 2.86-2.82 (m, 2H), 2.05-2.02 (m, 2H), 1.42-1.27 (m, 9H), 0.83 (s, 9H), 0.00 (s, 6H). (l) lithium 4-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-6,7-dihydro-5H-cy clopenta[c]pyridine-1- carboxylate To a mixture of methyl4-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino) methyl)-6,7-dihydro-5H-cyclopenta[c]pyridine-1- carboxylate (300 mg, 0.65 mmol) in THF / water (2:1 v/v, 6 mL) was added lithium hydroxide monohydrate (54.2 mg, 1.29 mmol), and the mixture stirred at room temperature for 2 hours under N ₂ . The mixture was concentrated to afford lithium 4-(((tert- butoxycarbonyl)(2-((tert-butyldimethylsilyl)oxy)ethyl)amino) methyl)-6,7-dihydro-5H- cyclopenta[c]pyridine-1-carboxylate (300 mg, crude) as a white solid. LCMS: m/z found 451 [M+H] ⁺ (acid). (m) tert-Butyl (S)-((2'-(3-(4-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-6,7-dihydro-5H-cy clopenta[c]pyridine-1- carboxamido)-2-methylphenyl)-3'-chloro-6-methoxy-[2,4'-bipyr idin]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate To a mixture of lithium 4-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino) methyl)-6,7-dihydro-5H-cyclopenta[c]pyridine-1- carboxylate (280 mg, 0.61 mmol) and tert-butyl (S)-((2'-(3-amino-2-methylphenyl)-3'-chloro- 6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-y l)methyl)carbamate (Example 42, step (d)) (339 mg, 0.61 mmol) in dichloromethane (10 mL) was added 2-chloro-1- methylpyridinium iodide (313 mg, 1.23 mmol), and the mixture stirred at room temperature for 1 hour under N ₂ . Water (50 mL) was added, and the mixture extracted with dichloromethane (2 x 100 mL). The combined organic phase was dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-100%, ethyl acetate/petroleum ether) to afford tert- butyl (S)-((2'-(3-(4-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy)ethyl)amino)methyl)-6,7-dihydro-5H-cy clopenta[c]pyridine-1- carboxamido)-2-methylphenyl)-3'-chloro-6-methoxy-[2,4'-bipyr idin]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (450 mg, 74% yield) as a yellow solid. LCMS: m/z found 984 [M+H] ⁺ . (n) (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl) amino)methyl)-6,7-dihydro- 5H-cyclopenta[c]pyridine-1-carboxamide To a mixture of tert-butyl (S)-((2'-(3-(4-(((tert-butoxycarbonyl)(2-((tert- butyldimethylsilyl)oxy) ethyl)amino)methyl)-6,7-dihydro-5H-cyclopenta[c]pyridine-1- carboxamido)-2-methylphenyl)-3'-chloro-6-methoxy-[2,4'-bipyr idin]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (420 mg, 0.43 mmol) in dichloromethane (10 mL) was added trifluoroacetic acid (4.2 mL, 56.54 mmol), and the mixture stirred at room temperature for 0.5 hours under N ₂ . The mixture was concentrated and the residue purified by reverse phase HPLC to afford (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-4-(((2- hydroxyethyl)amino)methyl)-6,7-dihydro-5H-cyclopenta[c]pyrid ine-1-carboxamide (103.3 mg, 35% yield) as a white solid. LCMS: m/z found 670 [M+H] ⁺ , retention time = 2.58 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.64 (d, 1H), 8.53 (s, 1H), 8.09 (d, 1H), 7.83 (d, 1H), 7.76 (d, 1H), 7.45-7.40 (m, 2H), 7.19 (d, 1H), 4.11 (s, 2H), 4.06 (s, 3H), 3.93- 3.87 (m, 3H), 3.78 (t, 2H), 3.50 (t, 2H), 3.10 (t, 2H), 2.99-2.97 (m, 2H), 2.76-2.72 (m, 2H), 2.38-2.21 (m, 5H), 2.18 (s, 3H),1.86-1.82 (m, 1H). Example 87: N-(3-(3'-Chloro-5-((3-hydroxyazetidin-1-yl)methyl)-6-methoxy -[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide N-(3-(3'-Chloro-5-((3-hydroxyazetidin-1-yl)methyl)-6-methoxy -[2,4'-bipyridin]-2'-yl)-2- methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picolinamide To a solution of N-(3-(3'-chloro-5-formyl-6-methoxy-[2,4'-bipyridin]-2'-yl)-2 - methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picolinamide (Example 83, step (c)) (130 mg, 0.24 mmol) and azetidin-3-ol (34.9 mg, 0.48 mmol) in methanol / dichloromethane (1:1 v/v, 2 mL) was added sodium acetate (58.8 mg, 0.72 mmol), and the mixture stirred at room temperature for 11.5 hours. Sodium cyanoborohydride (75.1 mg, 1.19 mmol) was then added, and the mixture stirred at room temperature for 0.5 hours. The mixture was combined with another batch at the 20 mg scale. The mixture was concentrated under reduced pressure and the residue purified by reverse phase HPLC to afford N-(3-(3'-chloro-5-((3-hydroxyazetidin- 1-yl)methyl)-6-methoxy-[2,4'-bipyridin]-2'-yl)-2-methylpheny l)-5-((3-hydroxyazetidin-1- yl)methyl)picolinamide (48.5 mg) as a white solid. LCMS: m/z found 601 [M+H] ⁺ , retention time = 2.12 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ.8.64-8.61 (m, 2H), 8.20 (d, 1H), 8.04 (d, 1H), 7.96 (dd, 1H), 7.74-7.73 (m, 2H), 7.42-7.39 (m, 2H), 7.19 (d, 1H), 4.41-4.35 (m, 2H), 4.02 (s, 3H), 3.79 (s, 2H), 3.74 (s, 2H), 3.72-3.64 (m, 4H), 3.12-3.02 (m, 4H), 2.17 (s, 3H). Example 88: (S)-N-(3-(5-(((1-Acetylpyrrolidin-3-yl)amino)methyl)-3'-chlo ro-6-methoxy- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidi n-1-yl)methyl)picolinamide (S)-N-(3-(5-(((1-Acetylpyrrolidin-3-yl)amino)methyl)-3'-chlo ro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide was prepared in a similar fashion to Example 87, replacing azetidin-3-ol with (S)-1-(3- aminopyrrolidin-1-yl)ethan-1-one hydrochloride salt in step (a). LCMS: m/z found 656 [M+H] ⁺ , retention time = 2.36 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.65- 8.63 (m, 2H), 8.22 (d, 1H), 8.06 (d, 1H), 7.98 (dd, 1H), 7.86-7.83 (m, 1H), 7.76 (d, 1H), 7.45- 7.41 (m, 2H), 7.21 (d, 1H), 4.42-4.38 (m, 1H), 4.06 (s, 3H), 3.88-3.86 (m, 2H), 3.81 (s, 2H), 3.77-3.66 (m, 3H), 3.63-3.37 (m, 4H), 3.07-3.03 (m, 2H), 2.24-2.14 (m, 4H), 2.07-2.05 (m, 3H), 2.02-1.84 (m, 1H). Example 89: N-(3-(5-((((1-Acetylpiperidin-4-yl)methyl)amino)methyl)-3'-c hloro-6- methoxy-[2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydrox yazetidin-1- yl)methyl)picolinamide N-(3-(5-((((1-acetylpiperidin-4-yl)methyl)amino)methyl)-3'-c hloro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide was prepared in a similar fashion to Example 87, replacing azetidin-3-ol with 1-(4- (aminomethyl)piperidin-1-yl)ethan-1-one hydrochloride salt in step (a). LCMS: m/z found 684 [M+H] ⁺ , retention time = 2.57 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.65-8.63 (m, 2H), 8.22 (d, 1H), 8.06 (d, 1H), 7.98 (dd, 1H), 7.82 (d, 1H), 7.76 (d, 1H), 7.45- 7.41 (m, 2H), 7.21 (d, 1H), 4.56-4.53 (m, 1H), 4.43-4.39 (m, 1H), 4.06 (s, 3H), 3.96-3.93 (m, 1H), 3.85-3.81 (m, 4H), 3.69-3.66 (m, 2H), 3.15-3.10 (m, 1H), 3.07-3.04 (m, 2H), 2.68-2.61 (m, 1H), 2.56 (d, 2H), 2.19 (s, 3H), 2.11 (s, 3H), 1.89-1.82 (m, 3H), 1.25-1.09 (m, 2H). Example 90: (S)-N-(3-(3'-Chloro-6-methoxy-5-(((oxetan-2-ylmethyl)amino)m ethyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidi n-1-yl)methyl)picolinamide (S)-N-(3-(3'-Chloro-6-methoxy-5-(((oxetan-2-ylmethyl)amino)m ethyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide was prepared in a similar fashion to Example 87, replacing azetidin-3-ol with (S)-oxetan-2- ylmethanamine in step (a). LCMS: m/z found 615 [M+H] ⁺ , retention time = 2.53 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.65-8.64 (m, 2H), 8.22 (d, 1H), 8.06 (d, 1H), 7.98 (dd, 1H), 7.83 (d, 1H), 7.76 (d, 1H), 7.45-7.41 (m, 2H), 7.21 (d, 1H), 5.05-4.99 (m, 1H), 4.74-4.69 (m, 1H), 4.60-4.55 (m, 1H), 4.42-4.37 (m, 1H), 4.06 (s, 3H), 3.92 (s, 2H), 3.82 (s, 2H), 3.70-3.66 (m, 2H), 3.08-3.01 (m, 3H) 2.88-2.84 (m, 1H), 2.78-2.70 (m, 1H), 2.55- 2.47 (m, 1H), 2.19 (s, 3H). Example 91: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((1-methyl-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-((3-hydroxyazetidin- 1-yl)methyl)picolinamide (S)-N-(3-(3'-Chloro-6-methoxy-5-((((1-methyl-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-((3-hydroxyazetidin-1- yl)methyl)picolinamide was prepared in a similar fashion to Example 87, replacing azetidin- 3-ol with (S)-5-(aminomethyl)-1-methylpyrrolidin-2-one in step (a). LCMS: m/z found 656 [M+H] ⁺ , retention time = 2.39 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.65- 8.63 (m, 2H), 8.22 (d, 1H), 8.06 (d, 1H), 7.98 (dd, 1H), 7.83 (d, 1H), 7.76 (d, 1H), 7.45-7.41 (m, 2H), 7.21 (d, 1H), 4.40 (m, 1H), 4.06 (s, 3H), 3.88-3.86 (m, 2H), 3.81 (s, 2H), 3.76-3.72 (m, 1H), 3.70-3.66 (m, 2H), 3.07-3.04 (m, 2H), 2.89-2.77 (m, 5H), 2.53-2.44 (m, 1H), 2.38- 2.29 (m, 1H), 2.27-2.21 (m, 1H), 2.19 (s, 3H), 2.00-1.92 (m, 1H). Example 92: N-(3-(3'-Chloro-6-methoxy-5-((6-oxo-2,5-diazaspiro[3.4]octan -2- yl)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hyd roxyazetidin-1- yl)methyl)picolinamide N-(3-(3'-Chloro-6-methoxy-5-((6-oxo-2,5-diazaspiro[3.4]octan -2-yl)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide was prepared in a similar fashion to Example 87, replacing azetidin-3-ol with 2,5- diazaspiro[3.4]octan-6-one hydrochloride salt in step (a). LCMS: m/z found 654 [M+H] ⁺ , retention time = 2.38 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.63 (d, 1H), 8.62 (d, 1H), 8.20 (d, 1H), 8.04 (d, 1H), 7.96 (dd, 1H), 7.76 (d, 1H), 7.73 (d, 1H), 7.43-7.39 (m, 2H), 7.19 (d, 1H), 4.41-4.35 (m, 1H), 4.02 (s, 3H), 3.79 (s, 2H), 3.73 (s, 2H), 3.68-3.64 (m, 2H), 3.57 (d, 2H), 3.37 (d, 2H), 3.05-3.02 (m, 2H), 2.45-2.33 (m, 4H), 2.16 (s, 3H). Example 93: (S)-5-(((1-Acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chlor o-6-methoxy- 5-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyri din]-2'-yl)-2- methylphenyl)-4-methoxypicolinamide (a) tert-Butyl (S)-((2'-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-4- methoxypicolinamido)-2-methylphenyl)-3'-chloro-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-2'-(3-(5-formyl-4-methoxypicolinamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate (Example 76, step (d)) (60 mg, 0.084 mmol) and 1-(4-aminopiperidin- 1-yl)ethan-1-one hydrochloride salt (23 mg, 0.17 mmol) in dichloromethane / methanol (1:1 v/v, 6 mL) was added sodium acetate (20.6 mg, 0.25 mmol), and the mixture stirred at room temperature for 0.5 hours under N ₂ . Sodium cyanoborohydride (15.8 mg, 0.25 mmol) was then added, and the mixture stirred at room temperature for 0.5 hours under N ₂ . Water (10 mL) was added, and the mixture extracted with dichloromethane (2 x 20 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure to afford tert-butyl (S)-((2'-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-4- methoxypicolinamido)-2-methylphenyl)-3'-chloro-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (80 mg, crude) as a yellow solid. LCMS: m/z found 841 [M+H] ⁺ . (b) (S)-5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chlor o-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-4- methoxypicolinamide To a mixture of tert-butyl (S)-((2'-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-4- methoxypicolinamido)-2-methylphenyl)-3'-chloro-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (70 mg, 0.08 mmol) in dichloromethane (5 mL) was added trifluoroacetic acid (2 mL, 26.9 mmol), and the mixture stirred at room temperature for 0.5 hours under N ₂ . The mixture was concentrated and the residue purified by reverse phase HPLC to afford (S)-5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chlor o- 6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2 ,4'-bipyridin]-2'-yl)-2- methylphenyl)-4-methoxypicolinamide (15.8 mg, 24% yield) as a white solid. LCMS: m/z found 741 [M+H] ⁺ , retention time = 2.56 min (Method A). ¹ H NMR (400 MHz, Methanol- d4): δ 8.53 (d, 1H), 8.40 (s, 1H), 7.98 (d, 1H), 7.77 (s, 1H), 7.71 (d, 1H), 7.64 (d, 1H), 7.34- 7.30 (m, 2H), 7.09 (d, 1H), 4.37-4.34 (m, 1H), 3.96 (s, 3H), 3.95 (s, 3H), 3.84-3.73 (m, 6H), 3.06-3.03 (m, 1H), 2.67-2.58 (m, 4H), 2.27-2.19 (m, 3H), 2.07 (s, 3H), 2.00 (s, 3H), 1.91- 1.88 (m, 2H), 1.75-1.74 (m, 1H), 1.30-1.17 (m, 2H). Example 94: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((3- fluoropropyl)amino)methyl)-4-methoxypicolinamide (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((3-fluoropropyl) amino)methyl)-4- methoxypicolinamide was prepared in a similar fashion to Example 93, replacing 1-(4- aminopiperidin-1-yl)ethan-1-one hydrochloride salt with 3-fluoropropan-1-amine hydrochloride salt in step (a). LCMS: m/z found 676 [M+H] ⁺ , retention time = 2.42 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.64 (d, 1H), 8.50 (s, 1H), 8.09 (d, 1H), 7.89 (s, 1H), 7.83 (d, 1H), 7.76 (d, 1H), 7.45-7.41 (m, 2H), 7.21 (d, 1H), 4.59 (t, 1H), 4.47 (t, 1H), 4.07 (s, 3H), 4.06 (s, 3H), 3.91-3.83 (m, 5H), 2.79-2.69 (m, 4H), 2.38-2.29 (m, 3H), 2.18 (s, 3H), 1.99-1.83 (m, 3H). Example 95: N-(3-(5-(((1-Acetylpiperidin-4-yl)(methyl)amino)methyl)-3'-c hloro-6- methoxy-[2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydrox yazetidin-1- yl)methyl)picolinamide (a) N-(3-(5-(((1-Acetylpiperidin-4-yl)(methyl)amino)methyl)-3'-c hloro-6-methoxy- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidi n-1-yl)methyl)picolinamide A mixture of N-(3-(3'-chloro-5-formyl-6-methoxy-[2,4'-bipyridin]-2'-yl)-2 - methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picolinamide (Example 83, step (c)) (0.06 g, 0.11 mmol) and 1-(4-(methylamino)piperidin-1-yl)ethan-1-one (0.03 g, 0.22 mmol) in THF / methanol mixture (2:1 v/v, 3 mL) was stirred at 60 °C for 12 hours. Sodium triacetoxyborohydride (0.07 g, 0.33 mmol) was then added, and the mixture stirred at 60 °C for 12 hours. The mixture was purified by reverse phase HPLC to afford N-(3-(5-(((1- acetylpiperidin-4-yl)(methyl)amino)methyl)-3'-chloro-6-metho xy-[2,4'-bipyridin]-2'-yl)-2- methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picolinamide (9.6 mg, 10% yield) as a white solid. LCMS: m/z found 684 [M+H] ⁺ , retention time = 2.25 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.65-8.63 (m, 2H), 8.22 (d, 1H), 8.06 (d, 1H), 7.98 (dd, 1H), 7.86 (d, 1H), 7.76 (d, 1H), 7.45-7.41 (m, 2H), 7.21 (d, 1H), 4.64-4.59 (m, 1H), 4.43-4.37 (m, 1H), 4.04-4.00 (m, 4H), 3.81 (s, 2H), 3.70-3.66 (m, 4H), 3.17-3.12 (m, 1H), 3.07-3.04 (m, 2H), 2.80-2.76 (m, 1H), 2.70-2.63 (m, 1H), 2.32 (s, 3H), 2.19 (s, 3H), 2.13 (s, 3H), 2.02-1.95 (m, 2H), 1.67-1.50 (m, 2H). Example 96: N-(3-(3-chloro-2-(3-methoxy-4-((methyl(((S)-5-oxopyrrolidin- 2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((R)-3- hydroxypyrrolidin-1-yl)methyl)picolinamide (a) N-(3-(3-chloro-2-(3-methoxy-4-((methyl(((S)-5-oxopyrrolidin- 2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((R)-3- hydroxypyrrolidin-1-yl)methyl)picolinamide A mixture of (R)-N-(3-(3-chloro-2-(4-formyl-3-methoxyphenyl)pyridin-4-yl) -2- methylphenyl)-5-((3-hydroxypyrrolidin-1-yl)methyl)picolinami de (0.07 g, 0.13 mmol) (Example 6, step (g)) and (S)-5-((methylamino)methyl)pyrrolidin-2-one (0.03 g, 0.25 mmol) in THF / methanol mixture (3:2 v/v, 5 mL) was stirred at 60 °C for 12 hours under N ₂ . Sodium cyanoborohydride (0.02 g, 0.38 mmol) was then added, and the mixture stirred at 60 °C for 20 hours. The mixture was purified by reverse phase HPLC twice to afford N-(3-(3- chloro-2-(3-methoxy-4-((methyl(((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((R)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide (16.8 mg, 20% yield) as a white solid. LCMS: m/z found 669 [M+H] ⁺ , retention time = 2.39 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.59 (s, 1H), 8.50 (d, 1H), 8.10 (d, 1H), 7.92 (dd, 1H), 7.89 (d, 1H), 7.35 (d, 1H), 7.32-7.28 (m, 2H), 7.18-7.15 (m, 2H), 7.01 (d, 1H), 4.29-4.25 (m, 1H), 3.87-3.84 (m, 1H), 3.81 (s, 3H), 3.74- 3.61 (m, 3H), 3.48-3.45 (m, 1H), 2.72-2.68 (m, 2H), 2.46-2.37 (m, 4H), 2.22-2.03 (m, 10H), 1.68-1.63 (m, 2H). Example 97: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-4-methoxy-5-((3- (methoxymethyl)azetidin-1-yl)methyl)picolinamide (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-((3-(met hoxymethyl)azetidin-1- yl)methyl)picolinamide was prepared in a similar fashion to Example 93, replacing 1-(4- aminopiperidin-1-yl)ethan-1-one hydrochloride salt with 3-(methoxymethyl)azetidine in step (a). LCMS: m/z found 700 [M+H] ⁺ , retention time = 3.64 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.62 (d, 1H), 8.41 (s, 1H), 8.07 (d, 1H), 7.85 (s, 1H), 7.81 (d, 1H), 7.74 (d, 1H), 7.43-7.39 (m, 2H), 7.19 (d, 1H), 4.04 (s, 3H), 4.03 (s, 3H), 3.89-3.81 (m, 3H), 3.74 (s, 2H), 3.51-3.47 (m, 4H), 3.35 (s, 3H), 3.16 (t, 2 H), 2.77-2.68 (m, 3H), 2.36-2.27 (m, 3H), 2.16 (s, 3H), 1.85-1.80 (m, 1H). Example 98: N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((S)-3- hydroxypyrrolidin-1-yl)methyl)-4-methoxypicolinamide N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-hydroxypyr rolidin-1-yl)methyl)-4- methoxypicolinamide was prepared in a similar fashion to Example 93, replacing 1-(4- aminopiperidin-1-yl)ethan-1-one hydrochloride salt with (S)-pyrrolidin-3-ol in step (a). LCMS: m/z found 686 [M+H] ⁺ , retention time = 3.46 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.64 (d, 1H), 8.57 (s, 1H), 8.08 (d, 1H), 7.92 (s, 1H), 7.84 (d, 1H), 7.76 (d, 1H ), 7.45-7.43 (m, 2H), 7.21 (d, 1H), 4.49-4.41 (m, 1H), 4.12-4.01 (m, 8H), 3.94-3.84 (m, 4H), 3.15-2.73 (m, 5H), 2.38-2.21 (m, 4H), 2.18 (s, 3H), 1.88-1.82 (m, 2H). Example 99: N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-4-methoxy-5-(((((S)-5- oxopyrrolidin-2-yl)methyl)amino)methyl)picolinamide N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-(((((S)- 5-oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamide was prepared in a similar fashion to Example 93, replacing 1-(4-aminopiperidin-1-yl)ethan-1-one hydrochloride salt with (S)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt in step (a). LCMS: m/z found 713 [M+H] ⁺ , retention time = 3.41 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.52 (d, 1H), 8.39 (s, 1H), 7.97 (d, 1H), 7.77 (s, 1H), 7.71 (d, 1H), 7.64 (d, 1H), 7.33-7.29 (m, 2H), 7.09 (d, 1H), 3.96 (s, 3H), 3.95 (s, 3H), 3.80-3.71 (m, 6H), 2.62-2.58 (m, 4H), 2.25-2.17 (m, 6H), 2.06 (s, 3H), 1.75-1.70 (m, 2H). Example 100: N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-(((R)-3- hydroxypyrrolidin-1-yl)methyl)-4-methoxypicolinamide N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-hydroxypyr rolidin-1-yl)methyl)-4- methoxypicolinamide was prepared in a similar fashion to Example 93, replacing 1-(4- aminopiperidin-1-yl)ethan-1-one hydrochloride salt with (R)-pyrrolidin-3-ol in step (a). LCMS: m/z found 686 [M+H] ⁺ , retention time = 3.44 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.64 (d, 1H), 8.55 (s, 1H), 8.09 (d, 1H), 7.90 (s, 1H), 7.83 (d, 1H), 7.76 (t, 1H), 7.45-7.41 (m, 2H), 7.21 (d, 1H), 4.43-4.39 (m, 1H), 4.07-4.00 (m, 6H), 3.94-3.84 (m, 5H), 2.96-2.90 (m, 2H), 2.76-2.68 (m, 4H), 2.38-2.30 (m, 4H), 2.20 (s, 3H), 1.85-1.80 (m, 2H). Example 101: (S)-N-(3-(3'-Chloro-6-methoxy-5-((methyl((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-((3-hydroxyazetidin- 1-yl)methyl)picolinamide (a) N-(3-Bromo-2-methylphenyl)-5-(dimethoxymethyl)picolinamide To a solution of 3-bromo-2-methylaniline (18.1 g, 97.3 mmol) in THF (85 mL) was added 1 M Lithium bis(trimethylsilyl)amide in THF (162 mL, 162 mmol) at 0 °C, and the mixture was stirred at 0 °C for 0.5 hours under N ₂ . Methyl 5-(dimethoxymethyl)picolinate ((Example 6, step (a)) (17.1 g, 81 mmol) in THF (85 mL) was then added, and the mixture stirred at 0 °C for 0.5 hours under N ₂ . The mixture was combined with another batch at the 24.9 g scale. Water (800 mL) was added and the mixture extracted with ethyl acetate (2 x 2000 mL). The combined organic layers were dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-30% ethyl acetate/petroleum ether) to give 150 g of the crude product. The crude product was triturated with petroleum ether / ethyl acetate / THF (30:10:1 v/v, 430 mL) at room temperature for 10 min to afford N-(3-bromo-2-methylphenyl)-5- (dimethoxymethyl)picolinamide (56.6 g, 78% yield) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.54 (s, 1H), 8.72 (d, 1H), 8.18 (d, 1H), 8.04 (dd, 1H), 7.63 (d, 1H), 7.50 (d, 1H), 7.19 (t, 1H), 5.62 (s, 1H), 3.31 (s, 6H), 2.33 (s, 3H). (b) 5-(Dimethoxymethyl)-N-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2 -dioxaborolan-2- yl)phenyl)picolinamide To a solution of N-(3-bromo-2-methylphenyl)-5-(dimethoxymethyl)picolinamide (10 g, 27.4 mmol) and bis(pinacolato)diboron (34.8 g, 137 mmol) in 1,4-dioxane (100 mL) was added potassium acetate (8.06 g, 82.1 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (2.24 g, 2.74 mmol), and the mixture stirred at 130 °C for 5 hours. The mixture was combined with another batch at the 5 g scale. water (300 mL) was added, and the mixture extracted with ethyl acetate (2 x 300 mL). The combined organic layers were washed with saturated aqueous brine solution (50 mL) dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-10% ethyl acetate/petroleum ether) to give 43 g of crude product. The crude product was triturated with petroleum ether (150 mL) at room temperature for 10 min to afford 5-(dimethoxymethyl)-N- (2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phe nyl)picolinamide (20.5 g) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.33 (s, 1H), 8.72 (d, 1H), 8.18 (d, 1H), 8.04 (dd, 1H), 7.78 (d, 1H), 7.52 (dd, 1H), 7.23 (t, 1H), 5.62 (s, 1H), 3.32 (s, 6H), 2.45 (s, 3H), 1.32 (s, 12H). (c) (2',3'-Dichloro-6-methoxy-[2,4'-bipyridin]-5-yl)methanol To a solution of 2',3'-dichloro-6-methoxy-[2,4'-bipyridine]-5-carbaldehyde (Example 23, step (a)) (5 g, 17.6 mmol) in THF / methanol (1:1 v/v, 50 mL) was added sodium borohydride (1 g, 26.5 mmol) at 0°C and the mixture stirred at room temperature for 3 hours. Water (300 mL) was added at 0°C, and the mixture extracted with ethyl acetate (2 x 300 mL). The combined organic phase was dried with anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-30% ethyl acetate/petroleum ether) to afford (2',3'-dichloro-6-methoxy-[2,4'-bipyridin]-5-yl)methanol (3.92 g, 61% yield) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ.8.47 (d, 1H), 7.88 (d, 1H), 7.69 (d, 1H), 7.41 (d, 1H), 5.35 (t, 1H), 4.53 (d, 2H), 3.91 (s, 3H). (d) N-(3-(3'-Chloro-5-(hydroxymethyl)-6-methoxy-[2,4'-bipyridin] -2'-yl)-2- methylphenyl)-5-(dimethoxymethyl)picolinamide To a solution of 5-(dimethoxymethyl)-N-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2 - dioxaborolan-2-yl)phenyl)picolinamide (7.05 g, 17.1 mmol) and (2',3'-dichloro-6-methoxy- [2,4'-bipyridin]-5-yl)methanol (3.25 g, 11.4 mmol) in THF / water (5:1 v/v, 36 mL) was added potassium phosphate (7.26 g, 34.2 mmol) and chloro(2-dicyclohexylphosphino-2′,4′,6′- triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl) ]palladium(II) (0.90 g, 1.14 mmol), and the mixture stirred at 80 °C for 12 hours. The mixture was combined with another batch at the 1 g scale. Water (150 mL) was added, and the mixture extracted with ethyl acetate (2 x 200 mL). The combined organic layers were washed with saturated aqueous brine solution (50 mL) dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-80% ethyl acetate/petroleum ether) to afford N-(3-(3'-chloro-5-(hydroxymethyl)-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(dimethoxymethyl)picolin amide (2.4 g, 39% yield) as a yellow solid. LCMS: m/z found 535 [M+H] ⁺ . (e) N-(3-(3'-Chloro-5-(hydroxymethyl)-6-methoxy-[2,4'-bipyridin] -2'-yl)-2- methylphenyl)-5-formylpicolinamide To a solution of N-(3-(3'-chloro-5-(hydroxymethyl)-6-methoxy-[2,4'-bipyridin] -2'-yl)- 2-methylphenyl)-5-(dimethoxymethyl)picolinamide (2.3 g, 4.30 mmol) in THF (23 mL) was added 6 N aqueous hydrochloride solution (4.60 mL, 27.6 mmol), and the mixture stirred at room temperature for 1 hour. The reaction mixture was neutralized with saturated aqueous sodium bicarbonate solution. Water (100 mL) was added, and the mixture extracted with ethyl acetate (2 x 125 mL). The combined organic layers were washed with saturated aqueous brine solution (50 mL), dried over anhydrous sulfate, filtered, and concentrated under reduced pressure to afford N-(3-(3'-chloro-5-(hydroxymethyl)-6-methoxy-[2,4'-bipyridin] -2'- yl)-2-methylphenyl)-5-formylpicolinamide (1.92 g, crude) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ.10.57 (s, 1H), 10.23 (s, 1H), 9.22 (s, 1H), 8.70 (d, 1H), 8.51 (dd, 1H), 8.36 (d, 1H), 7.89-7.85 (m, 1H), 7.79-7.76 (m, 1H), 7.71 (d, 1H), 7.45 (d, 1H), 7.40-7.33 (m, 1H), 7.20 (d, 1H), 5.33-5.29 (m, 1H), 4.53 (d, 2H), 3.94 (s, 3H), 2.07 (s, 3H). (f) N-(3-(3'-Chloro-5-(hydroxymethyl)-6-methoxy-[2,4'-bipyridin] -2'-yl)-2- methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picolinamide To a solution of N-(3-(3'-chloro-5-(hydroxymethyl)-6-methoxy-[2,4'-bipyridin] -2'-yl)- 2-methylphenyl)-5-formylpicolinamide (1.98 g, 4.05 mmol) and azetidin-3-ol (0.59 g, 8.10 mmol) in methanol / dichloromethane (1:1 v/v, 20 mL) was added sodium acetate (1.00 g, 12.2 mmol), and the mixture stirred at room temperature for 12 hours. Sodium cyanoborohydride (1.27 g, 20.3 mmol) was then added, and the mixture stirred at 50 °C for 6 hours. Water (100 mL) was added, and the mixture extracted with dichloromethane (2 x 125 mL). The combined organic phases were dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-20% methanol/ethyl acetate) to afford N-(3-(3'-chloro-5- (hydroxymethyl)-6-methoxy-[2,4'-bipyridin]-2'-yl)-2-methylph enyl)-5-((3-hydroxyazetidin- 1-yl)methyl)picolinamide (1.27 g, 52% yield) as a yellow solid. LCMS: m/z found 546 [M+H] ⁺ . (g) N-(3-(3'-Chloro-5-formyl-6-methoxy-[2,4'-bipyridin]-2'-yl)-2 -methylphenyl)-5- ((3-hydroxyazetidin-1-yl)methyl)picolinamide To a solution of N-(3-(3'-chloro-5-(hydroxymethyl)-6-methoxy-[2,4'-bipyridin] -2'-yl)- 2-methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picolinami de (0.5 g, 0.92 mmol) in dichloromethane (6 mL) was added Dess-Martin periodinane (0.58 g, 1.37 mmol), and the mixture stirred at room temperature for 0.5 hours. The mixture was concentrated and the residue purified by normal phase SiO ₂ chromatography (0-15% ethyl acetate/petroleum ether) to afford N-(3-(3'-chloro-5-formyl-6-methoxy-[2,4'-bipyridin]-2'-yl)-2 -methylphenyl)-5-((3- hydroxyazetidin-1-yl)methyl)picolinamide (0.45 g, 68% yield) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ.10.39 (s, 1H), 10.31 (s, 1H), 8.76 (d, 1H), 8.60 (s, 1H), 8.27 (d, 1H), 8.12 (d, 1H), 7.93 (dd, 1H), 7.86 (d, 1H), 7.76 (d, 1H), 7.60 (d, 1H), 7.37 (t, 1H), 7.18 (d, 1H), 5.35 (s, 1H), 4.22-4.18 (m, 1H), 4.08 (s, 3H), 3.69 (s, 2H), 3.53-3.50 (m, 2H), 2.84- 2.80 (m, 2H), 2.07 (s, 3H). (h) (S)-N-(3-(3'-Chloro-6-methoxy-5-((methyl((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-((3-hydroxyazetidin- 1-yl)methyl)picolinamide To a mixture of N-(3-(3'-chloro-5-formyl-6-methoxy-[2,4'-bipyridin]-2'-yl)-2 - methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picolinamide (0.06 g, 0.11 mmol) and (S)- 5-((methylamino)methyl)pyrrolidin-2-one (0.02 g, 0.14 mmol) in THF / methanol mixture (1:1 v/v, 2 mL) was added acetic acid (0.1 mL) in one portion under N ₂ , and the mixture stirred at 80 °C for 12 hours. Sodium cyanoborohydride (0.02 g, 0.33 mmol) was then added, and the mixture stirred at 80 °C for 12 hours. The residue was purified by reverse phase HPLC to afford (S)-N-(3-(3'-chloro-6-methoxy-5-((methyl((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-((3-hydroxyazetidin-1- yl)methyl)picolinamide (15.5 mg, 19% yield) as a yellow solid. LCMS: m/z found 656 [M+H] ⁺ , retention time = 2.13 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.66- 8.63 (m, 2H), 8.22 (d, 1H), 8.07 (d, 1H), 7.98 (dd, 1H), 7.89 (d, 1H), 7.77 (d, 1H), 7.46-7.41 (m, 2H), 7.21 (d, 1H), 4.40 (t, 1H), 4.05 (s, 3H), 3.99-3.96 (m, 1H), 3.82 (s, 2H), 3.73-3.67 (m, 3H), 3.59-3.56 (m, 1H), 3.08-3.01 (m, 2H), 2.61-2.48 (m, 2H), 2.37-2.26 (m, 6H), 2.19 (s, 3H), 1.84-1.75 (m, 1H). Example 102: (S)-4-(((1-Acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chlor o-6-methoxy- 5-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyri din]-2'-yl)-2- methylphenyl)-5-methoxypicolinamide (a) 2-Chloro-5-methoxyisonicotinaldehyde To a mixture of 2-chloro-5-methoxy-pyridine (5 g, 34.83 mmol) in THF (50 mL) was added lithium diisopropylamide solution (2 M in THF, 34.8 mL, 69.6 mmol) at -78°C, and the mixture was stirred at -78 °C for 0.5 hours under N ₂ . DMF (5.36 mL, 69.6 mmol) was then added at -78 °C, and the mixture stirred at -78 °C for 1 hour under N ₂ . Saturated aqueous ammonium chloride solution (50 mL) was then added, and the mixture extracted with ethyl acetate (2 x 100 mL). The combined organic phases were dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-25% ethyl acetate/petroleum ether) to afford 2-chloro-5-methoxy- pyridine-4-carbaldehyde (3.6 g, 60% yield) as a white solid. ¹ H NMR (400 MHz, Chloroform-d): δ 10.36 (s, 1H), 8.22 (s, 1H), 7.55 (s, 1H), 3.99 (s, 3H). (b) Methyl 4-formyl-5-methoxypicolinate To a mixture of 2-chloro-5-methoxy-pyridine-4-carbaldehyde (3.5 g, 20.4 mmol) in methanol (50 mL) was added [1,1′- bis(diphenylphosphino)ferrocene] dichloropalladium(II) complex with dichloromethane (0.83 g, 1.02 mmol) and triethylamine (8.52 mL, 61.2 mmol), and the mixture stirred at 80 °C for 12 hours under CO at 50 psi. The mixture was concentrated, water (50 mL) added to the residue, and the mixture extracted with ethyl acetate (2 x 50 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-85%, ethyl acetate/petroleum ether) to afford methyl 4-formyl-5-methoxy-pyridine-2-carboxylate (3.2 g, 80% yield) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.37 (s, 1H), 8.85 (s, 1H), 8.18 (s, 1H), 4.17 (s, 3H), 3.90 (s, 3H). (c) Methyl 4-(dimethoxymethyl)-5-methoxypicolinate To a mixture of methyl 4-formyl-5-methoxy-pyridine-2-carboxylate (1 g, 5.12 mmol) in methanol (5 mL) was added 4-methylbenzenesulfonic acid (0.09 g, 0.51 mmol) and trimethoxymethane (0.60 g, 5.64 mmol), and the mixture stirred at 60 °C for 1 hour under N ₂ . Saturated aqueous sodium bicarbonate solution (30 mL) was added, and the mixture extracted with ethyl acetate (2 x 50 mL). The combined organic phases were dried over anhydrous sulfate, filtered, and concentrated under reduced pressure to afford methyl 4- (dimethoxymethyl)-5-methoxypicolinate (1.2 g, crude) as a white solid. LCMS: m/z found 242 [M+H] ⁺ . The crude product was used to next step without further purification. (d) Lithium 4-(dimethoxymethyl)-5-methoxypicolinate To a mixture of methyl 4-(dimethoxymethyl)-5-methoxypicolinate (1.2 g, 4.97 mmol) in THF / water (5:1 v/v, 12 mL) was added lithium hydroxide monohydrate (0.42 g, 9.95 mmol), and the mixture stirred at room temperature for 1 hour under N ₂ . The mixture was concentrated to afford lithium 4-(dimethoxymethyl)-5-methoxypicolinate (1.5 g, crude) as a white solid. LCMS: m/z found 228 [M+H] ⁺ (acid). The crude product was used to next step without further purification. (e) 4-Formyl-5-methoxypicolinic acid To a mixture of lithium 4-(dimethoxymethyl)-5-methoxypicolinate (1.4 g, 6.00 mmol) in THF (10 mL) was added 4 N aqueous hydrochloric acid (5 mL), and the mixture stirred at room temperature for 1 hour under N ₂ . The mixture was concentrated to afford 4- formyl-5-methoxypicolinic acid (2 g, crude) as a white solid. LCMS: m/z found 182 [M+H] ⁺ . The crude product was used to next step without further purification. (f) tert-Butyl (S)-((3'-chloro-2'-(3-(4-formyl-5-methoxypicolinamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate To mixture of tert-butyl (S)-((2'-(3-amino-2-methylphenyl)-3'-chloro-6-methoxy- [2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)c arbamate (Example 42, step (d)) (2.5 g, 4.53 mmol) and 4-formyl-5-methoxypicolinic acid (1.64 g, 9.06 mmol) in DMF (10 mL) was added 2-chloro-1-methylpyridinium iodide (2.31 g, 9.06 mmol) and N,N- diisopropylethylamine (3.94 mL, 22.6 mmol), and the mixture stirred at room temperature for 1 hour under N ₂ . Water (50 mL) was added, and the mixture extracted with ethyl acetate (2 x 100 mL). The combined organic phases were dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-20% methanol / ethyl acetate) to afford tert-butyl (S)-((3'-chloro-2'- (3-(4-formyl-5-methoxypicolinamido)-2-methylphenyl)-6-methox y-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (1.1 g, 34% yield) as a yellow solid. LCMS: m/z found 715 [M+H] ⁺ . (g) tert-Butyl (S)-((2'-(3-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-5- methoxypicolinamido)-2-methylphenyl)-3'-chloro-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-2'-(3-(4-formyl-5-methoxypicolinamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate (150 mg, 0.21 mmol) and 1-(4-aminopiperidin-1-yl)ethan-1-one hydrochloride salt (74.9 mg, 0.42 mmol) in dichloromethane / methanol (1:1 v/v, 6 mL) was added sodium acetate (51.6 mg, 0.63 mmol) and the mixture stirred at room temperature for 0.5 hours under N ₂ . Sodium cyanoborohydride (39.5 mg, 0.63 mmol) was then added, and the mixture stirred at room temperature for 0.5 hours under N ₂ . The mixture was concentrated, and the residue purified by prep-TLC (SiO ₂ , ethyl acetate: methanol = 2:1 v/v) to afford tert- butyl (S)-((2'-(3-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-5-met hoxypicolinamido)-2- methylphenyl)-3'-chloro-6-methoxy-[2,4'-bipyridin]-5-yl)meth yl)((5-oxopyrrolidin-2- yl)methyl)carbamate (140 mg, 79% yield) as a white solid. LCMS: m/z found 841 [M+H] ⁺ . (h) (S)-4-(((1-Acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chlor o-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5- methoxypicolinamide To a mixture of tert-butyl (S)-((2'-(3-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-5- methoxypicolinamido)-2-methylphenyl)-3'-chloro-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (130 mg, 0.16 mmol) in dichloromethane (5 mL) was added trifluoroacetic acid (2 mL, 26.9 mmol), and the mixture stirred at room temperature. for 0.5 hour under N ₂ . The mixture was concentrated and the residue purified by reverse phase HPLC to afford (S)-4-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chlor o- 6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2 ,4'-bipyridin]-2'-yl)-2- methylphenyl)-5-methoxypicolinamide (32.4 mg, 27% yield) as a white solid. LCMS: m/z found 741 [M+H] ⁺ retention time = 2.27 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.64 (d, 1H), 8.43 (s, 1H), 8.27 (s, 1H), 8.06 (d, 1H), 7.83 (d, 1H), 7.76 (d, 1H), 7.45-7.40 (m, 2H), 7.19 (d, 1H), 4.48-4.45 (m, 1H), 4.12 (s, 3H), 4.09 (s, 3H), 3.95-3.83 (m, 6H), 3.19- 3.14 (m, 1H), 2.79-2.70 (m, 4H), 2.38-2.31 (m, 3H), 2.18 (s, 3H), 2.12 (s, 3H), 2.07-1.99 (m, 2H), 1.86-1.85 (m, 1H), 1.43-1.31 (m, 2H). Example 103: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino) methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphenyl)-4-(((3-fluor opropyl)amino)methyl)-5- methoxypicolinamide (a) tert-Butyl (S)-((3'-chloro-2'-(3-(4-(((3-fluoropropyl)amino)methyl)-5- methoxypicolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipyrid in]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-2'-(3-(4-formyl-5-methoxypicolinamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate (Example 102, step (f)) (150 mg, 0.21 mmol) and 3-fluoropropan-1- amine hydrochloride salt (47.6 mg, 0.42 mmol) in dichloromethane / methanol (1:1 v/v, 6 mL) was added sodium acetate (51.6 mg, 0.63 mmol) and the mixture stirred at room temperature for 0.5 hour under N ₂ . Sodium cyanoborohydride (39.5 mg, 0.63 mmol) was then added, and the mixture stirred at room temperature for 0.5 hours under N ₂ . The mixture was concentrated an the residue purified by prep-TLC (SiO ₂ , ethyl acetate : methanol = 1:1 v/v) to afford tert-butyl (S)-((3'-chloro-2'-(3-(4-(((3-fluoropropyl)amino)methyl)-5- methoxypicolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipyrid in]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (110 mg, 67% yield) as a white solid. LCMS: m/z found 776 [M+H] ⁺ . (b) (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-4-(((3-fluoropropyl) amino)methyl)-5- methoxypicolinamide To a mixture of tert-butyl (S)-((3'-chloro-2'-(3-(4-(((3-fluoropropyl)amino)methyl)-5- methoxypicolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipyrid in]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (100 mg, 0.13 mmol) in dichloromethane (5 mL) was added trifluoroacetic acid (2 mL, 26.9 mmol), and the mixture stirred at room temperature for 0.5 hours under N ₂ . The mixture was concentrated and the residue was purified by reverse phase HPLC to afford (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-4-(((3- fluoropropyl)amino)methyl)-5-methoxypicolinamide (35.5 mg, 40% yield) as a white solid. LCMS: m/z found 676 [M+H] ⁺ retention time = 2.39 min. ¹ H NMR (400 MHz, Methanol- d4): δ 8.64 (d, 1H), 8.44 (s, 1H), 8.23 (s, 1H), 8.06 (d, 1H), 7.83 (d, 1H), 7.76 (d, 1H), 7.45- 7.40 (m, 2H), 7.19 (d, 1H), 4.46 (t, 1H), 4.48 (t, 1H), 4.10 (s, 3H), 4.06 (s, 3H), 3.92-3.83 (m, 5H), 2.81-2.70 (m, 4H), 2.38-2.29 (m, 3H), 2.18 (s, 3H), 2.01-1.85 (m, 3H). Example 104: N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl) amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphenyl)-4-(((S )-3-hydroxypyrrolidin-1- yl)methyl)-5-methoxypicolinamide N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-4-(((S)-3-hydroxypyr rolidin-1-yl)methyl)-5- methoxypicolinamide was prepared in a similar fashion to Example 103, replacing 3- fluoropropan-1-amine hydrochloride salt with (3S)-pyrrolidin-3-ol in step (a). White solid, LCMS: m/z found 686 [M+H] ⁺ retention time = 2.25 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.64 (d, 1H), 8.43 (s, 1H), 8.29 (s, 1H), 8.07 (d, 1H), 7.83 (d, 1H), 7.76 (d, 1H), 7.45-7.40 (m, 2H ), 7.21 (d, 1H), 4.41-4.38 (m, 1H), 4.08 (s, 3H), 4.06 (s, 3H), 3.89-3.81 (m, 5H), 2.94-2.82 (m, 2H), 2.74-2.61 (m, 4H), 2.38-2.27 (m, 3H), 2.24-2.14 (m, 4H), 1.85- 1.78 (m, 2H). Example 105: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino) methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-methoxy-4- ((3- (methoxymethyl)azetidin-1-yl)methyl)picolinamide (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-methoxy-4-((3-(met hoxymethyl)azetidin-1- yl)methyl)picolinamide was prepared in a similar fashion to Example 103, replacing 3- fluoropropan-1-amine hydrochloride salt with 3-(methoxymethyl)azetidine in step (a). White solid, LCMS: m/z found 700 [M+H] ⁺ , retention time = 2.51 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ.8.62 (d, 1H), 8.39 (s, 1H), 8.14 (s, 1H), 8.05 (d, 1H), 7.81 (d, 1H), 7.73 (d, 1H), 7.43-7.38 (m, 2H), 7.17 (d, 1H), 4.05 (s, 3H), 4.04 (s, 3H), 3.89-3.81 (m, 3H), 3.74 (s, 2H), 3.54-3.50 (m, 4H), 3.36 (s, 3H), 3.18 (t, 2H), 2.84-2.66 (m, 3H), 2.36-2.27 (m, 3H), 2.16 (s, 3H), 1.85-1.79 (m, 1H). Example 106: N-(3-(3'-Chloro-6-methoxy-5-(((((S)-oxetan-2-yl)methyl)amino )methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((((S)-oxetan-2- yl)methyl)amino)methyl)picolinamide (a) tert-Butyl (S)-((6-((3-(3'-chloro-5-(hydroxymethyl)-6-methoxy-[2,4'-bip yridin]- 2'-yl)-2-methylphenyl)carbamoyl)pyridin-3-yl)methyl)(oxetan- 2-ylmethyl)carbamate To a solution of N-(3-(3'-chloro-5-(hydroxymethyl)-6-methoxy-[2,4'-bipyridin] -2'-yl)- 2-methylphenyl)-5-formylpicolinamide (Example 101, step (e)) (6 g, 1.23 mmol) and (S)- oxetan-2-ylmethanamine (0.21 g, 2.45 mmol) in dichloromethane / methanol (1:1 v/v, 4 mL) was added sodium acetate (0.3 g, 3.68 mmol), and the mixture stirred at room temperature for 1 hour. Sodium cyanoborohydride (0.23 g, 3.68 mmol) was then added, and the mixture stirred at room temperature for 0.5 hours. Triethylamine (0.48 mL, 3.48 mmol) and di-tert- butyl dicarbonate (0.53 mL, 2.32 mmol) were then added, and the mixture stirred at room temperature for 1 hour. Water (100 mL) was added, and the mixture extracted with ethyl acetate (2 x 300 mL). The combined organic phases were dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-100 % ethyl acetate/petroleum ether) to afford tert-butyl (S)-((6-((3- (3'-chloro-5-(hydroxymethyl)-6-methoxy-[2,4'-bipyridin]-2'-y l)-2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(oxetan-2-ylmethy l)carbamate (0.33 g, 37% yield) as a white solid. LCMS: m/z found 660 [M+H] ⁺ . (b) tert-Butyl (S)-((6-((3-(3'-chloro-5-formyl-6-methoxy-[2,4'-bipyridin]-2 '-yl)-2- methylphenyl)carbamoyl)pyridin-3-yl)methyl)(oxetan-2-ylmethy l)carbamate To a solution of tert-butyl (S)-((6-((3-(3'-chloro-5-(hydroxymethyl)-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)carbamoyl)pyridin-3-yl)meth yl)(oxetan-2- ylmethyl)carbamate (0.33 g, 0.5 mmol) in dichloromethane (5 mL) was added Dess-Martin periodinane (0.32 g, 0.75 mmol), and the mixture stirred at room temperature for 0.5 hours. The mixture was purified by normal phase SiO ₂ chromatography (0-100 % ethyl acetate/petroleum ether) to afford tert-butyl (S)-((6-((3-(3'-chloro-5-formyl-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)carbamoyl)pyridin-3-yl)meth yl)(oxetan-2- ylmethyl)carbamate (0.28 g, 80% yield) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): 10.45 (s, 1H), 10.37 (s, 1H), 8.83 (d, 1H), 8.57 (s, 1H), 8.33 (d, 1H), 8.22 (d, 1H), 7.96 (dd, 1H), 7.92 (d, 1H), 7.82 (d, 1H), 7.65 (d, 1H), 7.44 (t, 1H), 7.24 (d, 1H), 4.92 (s, 1H), 4.73- 4.62 (m, 2H), 4.45 (s, 1H), 4.14 (s, 3H), 3.6-3.54 (m, 2H), 2.68-2.62 (m, 1H), 2.46-2.38 (m, 1H), 2.32-2.24 (m, 1H), 2.13 (s, 3H), 1.50-1.38 (m, 9H). (c) tert-butyl ((6-((3-(3'-chloro-6-methoxy-5-(((((S)-oxetan-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)carbamoyl)pyridin-3- yl)methyl)(((S)-oxetan-2-yl)methyl)carbamate To a solution of tert-butyl (S)-((6-((3-(3'-chloro-5-formyl-6-methoxy-[2,4'-bipyridin]- 2'-yl)-2-methylphenyl)carbamoyl)pyridin-3-yl)methyl)(oxetan- 2-ylmethyl)carbamate (140 mg, 0.21 mmol) and (S)-oxetan-2-ylmethanamine (37 mg, 0.43 mmol) in dichloromethane / methanol (1:1 v/v, 4 mL) was added sodium acetate (52.4 mg, 0.64 mmol), and the mixture stirred at room temperature for 1 hour. Sodium cyanoborohydride (40.1 mg, 0.64 mmol) was then added, and the mixture stirred at room temperature for 0.5 hours. Water (60 mL) was added, and the mixture extracted with ethyl acetate (2 x 200 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-50% methanol /ethyl acetate) to afford tert-butyl ((6-((3-(3'-chloro-6-methoxy-5-(((((S)-oxetan-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)carbamoyl)pyridin-3- yl)methyl)(((S)-oxetan-2-yl)methyl)carbamate (85 mg, 55 % yield) as a yellow oil. LCMS: m/z found 729 [M+H] ⁺ . (d) N-(3-(3'-Chloro-6-methoxy-5-(((((S)-oxetan-2-yl)methyl)amino )methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((((S)-oxetan-2- yl)methyl)amino)methyl)picolinamide To a solution of tert-butyl ((6-((3-(3'-chloro-6-methoxy-5-(((((S)-oxetan-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)carbamoyl)pyridin-3- yl)methyl)(((S)-oxetan-2-yl)methyl)carbamate (15 mg, 0.021 mmol) in 1,4-dioxane (0.9 mL) was added 12 N aqueous HCl (0.1 mL), and the mixture stirred at room temperature for 1hour. The mixture was combined with another batch at 70 mg scale. The mixture was neutralized with saturated aqueous sodium bicarbonate solution and concentrated under reduced pressure. The residue was purified by reverse phase HPLC to afford N-(3-(3'-chloro- 6-methoxy-5-(((((S)-oxetan-2-yl)methyl)amino)methyl)-[2,4'-b ipyridin]-2'-yl)-2- methylphenyl)-5-(((((S)-oxetan-2-yl)methyl)amino)methyl)pico linamide (9.1 mg, 12 % yield) as a white solid. LCMS: m/z found 629 [M+H] ⁺ , retention time = 2.23 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.58 (s, 1H), 8.51 (d, 1H), 8.45 (s, 1H), 8.10 (d, 1H), 7.96-7.91 (m, 2H), 7.75 (d, 1H), 7.64 (d, 1H), 7.33-7.29 (m, 2H), 7.09 (d, 1H), 4.29-4.25 (m, 2H), 3.92 (s, 3H), 3.73-3.58 (m, 4H), 2.77-2.68 (m, 4H), 2.54-2.42 (m, 4H), 2.11-2.03 (m, 5H), 1.67-1.61 (m, 2H). Example 107: N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5-methoxy-4-(((((S)-5- oxopyrrolidin-2-yl)methyl)amino)methyl)picolinamide N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-methoxy-4-(((((S)- 5-oxopyrrolidin-2-yl)methyl) amino)methyl)picolinamide was prepared in a similar fashion to Example 103, replacing 3- fluoropropan-1-amine hydrochloride salt with (S)-5-(aminomethyl)pyrrolidin-2-one hydrochloride salt in step (a). White solid, LCMS: m/z found 713 [M+H] ⁺ retention time = 2.22 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.64 (d, 1H), 8.42 (s, 1H), 8.26 (s, 1H), 8.06 (d, 1H), 7.83 (d, 1H), 7.75 (d, 1H), 7.45-7.40 (m, 2H), 7.19 (d, 1H), 4.09 (s, 3H), 4.06 (s, 3H), 3.93-3.83 (m, 6H), 2.76-2.66 (m, 4H), 2.37-2.27 (m, 6H), 2.18 (s, 3H), 1.87- 1.82 (m, 2H). Example 108: N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino) methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphenyl)-4-(((R)-3-hy droxypyrrolidin-1- yl)methyl)-5-methoxypicolinamide N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-4-(((R)-3-hydroxypyr rolidin-1-yl)methyl)-5- methoxypicolinamide was prepared in a similar fashion to Example 103, replacing 3- fluoropropan-1-amine hydrochloride salt with (R)-pyrrolidin-3-ol in step (a). White solid, LCMS: m/z found 686 [M+H] ⁺ retention time = 2.25 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.64 (d, 1H), 8.44 (s, 1H), 8.29 (s, 1H), 8.06 (d, 1H), 7.83 (d, 1H), 7.76 (d, 1H), 7.45-7.40 (m, 2H), 7.20 (d, 1H), 4.40-4.39 (m, 1H), 4.08 (s, 3H), 4.06 (s, 3H), 3.92-3.82 (m, 5H), 2.97-2.68 (m, 6H), 2.38-2.27 (m, 4H), 2.18 (s, 3H), 1.85-1.78 (m, 2H). Example 109: (S)-N-(3-(5-(((1-Acetylpiperidin-3-yl)amino)methyl)-3'-chlor o-6-methoxy- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidi n-1-yl)methyl)picolinamide (S)-N-(3-(5-(((1-acetylpiperidin-3-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide was prepared in a similar fashion to Example 101, by replacing (S)-5- ((methylamino)methyl)pyrrolidin-2-one with (S)-1-(3-aminopiperidin-1-yl)ethan-1-one in step (h). White solid, LCMS: m/z found 670 [M+H] ⁺ retention time = 2.69 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): 8.65-8.63 (m, 2H), 8.22 (d, 1H), 8.06 (d, 1H), 7.98 (d, 1H), 7.87-7.83 (m, 1H), 7.76 (d, 1H), 7.46-7.41 (m, 2H), 7.21 (d, 1H), 4.42-4.39 (m, 1H), 4.19-4.01 (m, 4H), 3.96-3.66 (m, 7H), 3.22-3.15 (m, 1H), 3.08-3.04 (m, 2H), 2.87-2.81 (m, 1H), 2.72-2.60 (m, 1H), 2.18 (s, 3H), 2.12-2.04 (m, 4H), 1.89-1.75 (m, 1H), 1.56-1.47 (m, 2H). Example 110: (S)-N-(3-(3'-Chloro-5-((3-hydroxyazetidin-1-yl)methyl)-6-met hoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((oxetan-2-ylmethyl)ami no)methyl)picolinamide (S)-N-(3-(3'-Chloro-5-((3-hydroxyazetidin-1-yl)methyl)-6-met hoxy-[2,4'-bipyridin]- 2'-yl)-2-methylphenyl)-5-(((oxetan-2-ylmethyl)amino)methyl)p icolinamide was prepared in a similar fashion to Example 106, by replacing (S)-oxetan-2-ylmethanamine with azetidin-3-ol in step (c). White solid, LCMS: m/z found 615 [M+H] ⁺ retention time = 2.59 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.58 (d, 1H), 8.52 (d, 1H), 8.10 (d, 1H), 7.96-7.91 (m, 2H), 7.64-7.62 (m, 2H), 7.33-7.29 (m, 2H), 7.09 (dd, 1H), 4.29-4.25 (m, 2H), 3.92 (s, 3H), 3.73-3.59 (m, 6H), 2.98-2.94 (m, 2H), 2.72-7.68 (m, 2H), 2.48-2.42 (m, 2H), 2.10-2.05 (m, 4H), 1.67-1.61 (m, 1H). Example 111: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-7-(3-fluoropropyl)- 5,6,7,8-tetrahydro-2,7-naphthyridine-3-carboxamide (a) tert-Butyl (S)-((3'-chloro-2'-(3-(7-(3-fluoropropyl)-5,6,7,8-tetrahydro -2,7- naphthyridine-3-carboxamido)-2-methylphenyl)-6-methoxy-[2,4' -bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate tert-Butyl (S)-((3'-chloro-2'-(3-(7-(3-fluoropropyl)-5,6,7,8-tetrahydro -2,7- naphthyridine-3-carboxamido)-2-methylphenyl)-6-methoxy-[2,4' -bipyridin]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate was prepared in a similar fashion to Example 68 (steps (a) through (d)), by replacing (2-bromoethoxy)(tert-butyl)dimethylsilane with 1-bromo-3- fluoropropane in step (a). (b) (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-7-(3-fluoropropyl)-5 ,6,7,8-tetrahydro-2,7- naphthyridine-3-carboxamide To a mixture of tert-butyl (S)-((3'-chloro-2'-(3-(7-(3-fluoropropyl)-5,6,7,8-tetrahydro - 2,7-naphthyridine-3-carboxamido)-2-methylphenyl)-6-methoxy-[ 2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (130 mg, 0.2 mmol) in dichloromethane (2 mL) was added trifluoroacetic acid (0.8 mL, 10.8 mmol) and the mixture stirred at room temperature for 0.5 hours under N ₂ . The mixture was concentrated and the residue purified by reverse phase HPLC to afford (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-7-(3-fluoropropyl)-5,6,7,8- tetrahydro-2,7-naphthyridine-3-carboxamide (25.2 mg, 21% yield) as a white solid. LCMS: m/z found 672 [M+H] ⁺ , retention time = 2.29 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.64 (d, 1H), 8.45 (s, 1H), 8.08 (d, 1H), 8.03 (s, 1H), 7.83 (d, 1H), 7.75 (d, 1H), 7.45-7.41 (m, 2H), 7.20 (d, 1H), 4.62 (t, 1H), 4.50 (t, 1H), 4.06 (s, 3H), 3.88-3.81 (m, 5H), 3.07 (t, 2H), 2.88 (t, 2H), 2.78-2.67 (m, 4H), 2.38-2.27 (m, 3H), 2.18 (s, 3H), 2.09-1.98 (m, 2H), 1.88-1.80 (m, 1H). Example 112: (S)-3-(2-((2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrol idin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)carbam oyl)thiazol-5- yl)propanoic acid (a) Ethyl (S,E)-3-(2-((3-(5-(((tert-butoxycarbonyl)((5-oxopyrrolidin-2 - yl)methyl)amino)methyl)-3'-chloro-6-methoxy-[2,4'-bipyridin] -2'-yl)-2- chlorophenyl)carbamoyl)thiazol-5-yl)acrylate To a mixture of tert-butyl (S)-((2'-(3-(5-bromothiazole-2-carboxamido)-2- chlorophenyl)-3'-chloro-6-methoxy-[2,4'-bipyridin]-5-yl)meth yl)((5-oxopyrrolidin-2- yl)methyl)carbamate (Example 59, step (b)) (1.6 g, 2.10 mmol) in 1,4-dioxane / water (5/1 v/v, 30 mL) was added ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (712 mg, 3.15 mmol) , [1,1′-bis(di-tert-butylphosphino)ferrocene]dichloropalladi um(II) (137 mg, 0.21 mmol) and potassium carbonate (1.34 g, 6.30 mmol) and the reaction heated to 110 °C for 2 hours under N ₂ . After cooling, the combined mixture with another batch at 1 g and 0.1 g scale. Water (30 ml) was added, and the mixture extracted with ethyl acetate (3 x 30 ml). The combined organic phases were washed with brine (2 x 50 ml), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether) to afford ethyl (S,E)-3- (2-((3-(5-(((tert-butoxycarbonyl)((5-oxopyrrolidin-2-yl)meth yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)thi azol-5-yl)acrylate (3.2 g in total, 90% yield) as a yellow solid. LCMS: m/z found 781 [M+H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.64 (d, 1 H), 8.46 (dd, 1 H), 8.21 (s, 1 H), 7.89 (d, 1 H), 7.79 (d, 1 H), 7.59 (d, 1 H), 7.54 (t, 1 H), 7.44 (d, 1 H), 7.32 (dd, 1 H), 7.52 (d, 1 H). (b) Ethyl (S)-3-(2-((3-(5-(((tert-butoxycarbonyl)((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-3'-chloro-6-methoxy-[2,4'-bipyridin] -2'-yl)-2- chlorophenyl)carbamoyl)thiazol-5-yl)propanoate To a mixture of ethyl (S,E)-3-(2-((3-(5-(((tert-butoxycarbonyl)((5-oxopyrrolidin-2 - yl)methyl)amino)methyl)-3'-chloro-6-methoxy-[2,4'-bipyridin] -2'-yl)-2- chlorophenyl)carbamoyl)thiazol-5-yl)acrylate (1.5 g, 1.92 mmol) and copper(I) chloride (38.0 mg, 0.38 mmol) in methanol (40 mL) was added sodium borohydride (363 mg, 9.59 mmol) at 0 °C under N ₂ , and the reaction was warmed to room temperature and stirred for 12 hours. The mixture was combined with another batch at 200 mg scale, quenched with H ₂ O (10 mL), then filtered and washed with methanol (50 mL). The filtrate was concentrated, water (20 mL) added to the residue, and the mixture extracted with ethyl acetate (3 x 40 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0- 100% ethyl acetate/ petroleum ether) to afford ethyl (S)-3-(2-((3-(5-(((tert- butoxycarbonyl)((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-3 '-chloro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)thiazol-5-yl)prop anoate (1.5 g, 30% yield) as a white solid. LCMS: m/z found 783 [M+H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.65 (d, 1 H), 8.49 (dd, 1 H), 7.81-7.80 (m, 2 H), 7.61 (d, 1 H), 7.55 (t, 1 H), 7.45 (d, 1 H), 7.30 (dd, 1 H), 4.56 (s, 2 H), 4.20-4.11 (m, 2 H), 4.05 (s, 3 H), 4.00-4.97 (m, 1 H), 3.45 (s, 2 H), 3.28 (t, 3 H), 2.78 (t, 2 H), 2.40-2.23 (m, 3 H), 1.88 (s, 1 H), 1.47 (d, 9 H), 1.26 (t, 3 H). (c) Lithium (S)-3-(2-((3-(5-(((tert-butoxycarbonyl)((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-3'-chloro-6-methoxy-[2,4'-bipyridin] -2'-yl)-2- chlorophenyl)carbamoyl)thiazol-5-yl)propanoate To a mixture of ethyl (S)-3-(2-((3-(5-(((tert-butoxycarbonyl)((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-3'-chloro-6-methoxy-[2,4'-bipyridin] -2'-yl)-2- chlorophenyl)carbamoyl)thiazol-5-yl)propanoate (500 mg, 0.64 mmol) in THF / water (5/1 v/v, 4.8 mL) was added lithium hydroxide monohydrate (53.5 mg, 1.28 mmol) and the mixture stirred for 2 hours at room temperature The mixture was concentrated directly to afford lithium (S)-3-(2-((3-(5-(((tert-butoxycarbonyl)((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-3'-chloro-6-methoxy-[2,4'-bipyridin] -2'-yl)-2- chlorophenyl)carbamoyl)thiazol-5-yl)propanoate (500 mg, crude) as a yellow solid. LCMS: m/z found 755 [M+H] ⁺ , which was used in the next step without further purification. (d) (S)-3-(2-((2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrol idin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)carbam oyl)thiazol-5- yl)propanoic acid To a mixture of lithium (S)-3-(2-((3-(5-(((tert-butoxycarbonyl)((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-3'-chloro-6-methoxy-[2,4'-bipyridin] -2'-yl)-2- chlorophenyl)carbamoyl)thiazol-5-yl)propanoate (200 mg, 0.26 mmol) in dichloromethane (3 mL) was added trifluoroacetic acid (1 mL, 13.5 mmol) and the reaction stirred for 1 hour at room temperature. The mixture was concentrated directly and then aqueous ammonium hydroxide (28%) added to pH 7. The residue was purified by reverse phase HPLC to afford (S)-3-(2-((2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrol idin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)carbam oyl)thiazol-5-yl)propanoic acid (76.4 mg, 43% yield) as a white solid. LCMS: m/z: 655 [M+H] ⁺ , retention time = 3.19 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): 8.64 (d, 1H), 8.47 (dd, 1H), 7.84 (d, 1H), 7.78-7.77 (m, 2H), 7.53 (t, 1H), 7.45 (d, 1H), 7.28 (dd, 1H), 4.06 (s, 3H), 3.96 (d, 2H), 3.90- 3.87 (m, 1H), 3.24 (t, 2H), 2.84-2.81 (m, 2H), 2.70 (t, 2H), 2.38-2.30 (m, 3H), 1.87-1.82 (m, 1H). Example 113: (S)-5-(2-Aminoethyl)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-(( ((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)thiazole-2- carboxamide (a) tert-Butyl (S)-((2'-(3-(5-(2-aminoethyl)thiazole-2-carboxamido)-2-chlor ophenyl)- 3'-chloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrr olidin-2- yl)methyl)carbamate To the mixture of lithium (S)-3-(2-((3-(5-(((tert-butoxycarbonyl)((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-3'-chloro-6-methoxy-[2,4'-bipyridin] -2'-yl)-2- chlorophenyl)carbamoyl)thiazol-5-yl)propanoate (Example 112, step (c)), (200 mg, 0.26 mmol) in 1,4-dioxane (2 mL) was added diphenylphosphoryl azide (217 mg, 0.79 mmol) and triethylamine (79.6 mg, 0.79 mmol) and the reaction was stirred for 3 hours at 60 °C. After cooling, the mixture was concentrated, sodium trimethylsilanolate (294 mg, 2.62 mmol) added, and the mixture was stirred for another 1 hour at room temperature. The mixture combined with another batch at 50 mg scale and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether to 0-22% methanol/ethyl acetate) to afford tert-butyl (S)-((2'-(3-(5-(2- aminoethyl)thiazole-2-carboxamido)-2-chlorophenyl)-3'-chloro -6-methoxy-[2,4'-bipyridin]- 5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (450 mg, 99% yield) as a yellow oil. LCMS: m/z found 726 [M+H] ⁺ . (b) (S)-5-(2-aminoethyl)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-(( ((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)thiazo le-2-carboxamide To the mixture of tert-butyl (S)-((2'-(3-(5-(2-aminoethyl)thiazole-2-carboxamido)-2- chlorophenyl)-3'-chloro-6-methoxy-[2,4'-bipyridin]-5-yl)meth yl)((5-oxopyrrolidin-2- yl)methyl)carbamate (120 mg, 0.17 mmol) in dichloromethane (1 mL) was added trifluoroacetic acid (0.3 mL, 4.04 mmol) and the reaction stirred for 1 hour at room temperature. The mixture combined with another batch at 10 mg scale, aqueous ammonium hydroxide (28%) added to pH 7 and the mixture concentrated. The residue was purified by reverse phase HPLC to afford (S)-5-(2-aminoethyl)-N-(2-chloro-3-(3'-chloro-6-methoxy-5- ((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridi n]-2'-yl)phenyl)thiazole-2- carboxamide (12.4 mg, 11% yield) as a light yellow solid. LCMS: m/z found 626 [M+H] ⁺ , retention time = 2.44 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): 8.66 (d, 1H), 8.50 (dd, 1H), 7.84-7.82 (m, 2H), 7.80 (d, 1H), 7.56 (t, 1H), 7.44 (d, 1H), 7.31 (dd, 1H), 4.06 (s, 3 H), 3.91-3.83 (m, 3 H), 3.16 (t, 2H), 3.04 (t, 2 H), 2.76-2.66 (m, 2H), 2.38-2.27 (m, 3H), 1.86-1.81 (m, 1H). Example 114: N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-7-(((S)-5- oxopyrrolidin-2-yl)methyl)-5,6,7,8-tetrahydro-2,7-naphthyrid ine-3-carboxamide N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-7-(((S)-5-oxopyrroli din-2-yl)methyl)-5,6,7,8- tetrahydro-2,7-naphthyridine-3-carboxamide was prepared in a similar fashion to Example 111, by replacing 1-bromo-3-fluoropropane with (S)-5-(bromomethyl)pyrrolidin-2-one in step (a). White solid, LCMS: m/z found 709 [M+H] ⁺ , retention time = 2.17 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): 8.64 (d, 1H), 8.43 (s, 1H), 8.08 (d, 1H), 8.02 (s, 1H), 7.83 (d, 1H), 7.75 (d, 1H), 7.45-7.41 (m, 2H), 7.20 (d, 1H), 4.06-4.02 (m, 4H), 3.92-3.77 (m, 5H), 3.07 (t, 2H), 2.98-2.92 (m, 1H), 2.87-2.73 (m, 1H), 2.75-2.60 (m, 4H), 2.40-2.25 (m, 6H), 2.18 (s, 3H), 1.88-1.80 (m, 1H). Example 115: (S)-4-(((1-Acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3'-chloro-6- methoxy-5-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4 '-bipyridin]-2'- yl)phenyl)-5-methoxypicolinamide (a) tert-Butyl (S)-((3'-chloro-2'-(2-chloro-3-(4-formyl-5- methoxypicolinamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl) methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate To a mixture of tert-butyl (S)-((2'-(3-amino-2-chlorophenyl)-3'-chloro-6-methoxy- [2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)c arbamate (Example 59, step (a)) (500 mg, 0.873 mmol) and 4-formyl-5-methoxy-pyridine-2-carboxylic acid (Example 102, step (e)) (316 mg, 1.75 mmol) in DMF (10 mL) was added 2-chloro-1-methylpyridinium iodide (446 mg, 1.75 mmol) and N,N-diisopropylethylamine (0.76 mL, 4.37 mmol), and the mixture stirred at room temperature for 2 hours under N ₂ . Water (30 mL) was added, and the mixture extracted with dichloromethane (2 x 30 mL). The combined organic phases were dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-15% methanol / ethyl acetate) to afford tert-butyl (S)-((3'-chloro-2'-(2-chloro-3-(4-formyl-5-methoxypicolinami do)phenyl)-6- methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl) methyl)carbamate (300 mg, 46% yield) as a yellow solid. LCMS: m/z found 735 [M+H] ⁺ . (b) tert-Butyl (S)-((2'-(3-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-5- methoxypicolinamido)-2-chlorophenyl)-3'-chloro-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate To a solution of tert-butyl (S)-((3’-chloro-2’-(2-chloro-3-(4-formyl-5- methoxypicolinamido)phenyl)-6-methoxy-[2,4’-bipyridin]-5-y l)methyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (130 mg, 0.177 mmol) and 1-(4-aminopiperidin-1-yl)ethan-1-one hydrochloride salt (63.2 mg, 0.35 mmol) in methanol / dichloromethane (1:1 v/v, 3 mL) was added sodium acetate (43.5 mg, 0.53 mmol), and mixture stirred at room temperature for 1 hour. Sodium cyanoborohydride (33.3 mg, 0.53 mmol) was then added, and the mixture stirred at room temperature for 0.5 hours. Water (15 mL) was added, and the mixture extracted with dichloromethane (2 x 15 mL). The combined organic layers were dried over anhydrous sulfate, filtered, and concentrated under reduced pressure. The residue was purified by prep-TLC (SiO ₂ , ethyl acetate : methanol = 1:1 v/v) to afford tert-butyl (S)-((2’- (3-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-5-methoxypicol inamido)-2-chlorophenyl)-3’- chloro-6-methoxy-[2,4’-bipyridin]-5-yl)methyl)((5-oxopyrro lidin-2-yl)methyl)carbamate (80 mg, 47% yield) as a white solid. LCMS: m/z found 861 [M+H] ⁺ . (c) (S)-4-(((1-Acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3'-chloro-6- methoxy-5-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4 '-bipyridin]-2'- yl)phenyl)-5-methoxypicolinamide To a solution of tert-butyl (S)-((2'-(3-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-5- methoxypicolinamido)-2-chlorophenyl)-3'-chloro-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (70 mg, 0.08 mmol) in dichloromethane (1.5 mL) was added trifluoroacetic acid (0.5 mL, 6.73 mmol), and the mixture stirred at room temperature for 0.5 hours. The reaction mixture was neutralized with sodium bicarbonate. The reaction mixture was concentrated under reduced pressure and the residue purified by reverse phase HPLC to afford (S)-4-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl)amino )methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-5-methoxypicolinamide (25.9 mg, 40% yield) as a white solid. LCMS: m/z found 761 [M+H] ⁺ , retention time = 2.54 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ). δ: 8.67 (dd, 1H), 8.64 (d, 1H), 8.42 (s, 1H), 8.29 (s, 1H), 7.81 (d, 1H), 7.79 (d, 1H), 7.53 (t, 1H), 7.43 (d, 1H), 7.24 (dd, 1H), 4.47-4.44 (m, 1H), 4.08 (s, 3H), 4.05 (s, 3H), 3.94-3.89 (m, 3H), 3.87-3.81 (m, 3H), 3.19-3.12 (m, 1H), 2.77-2.65 (m, 4H), 2.36-2.25 (m, 3H), 2.11 (s, 3H), 2.06-1.98 (m, 2H), 1.87-1.78 (m, 1H), 1.41-1.29 (m, 2H). Example 116: N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-met hoxy-4-(((((S)-5- oxopyrrolidin-2-yl)methyl)amino)methyl)picolinamide N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-met hoxy-4-(((((S)-5-oxopyrrolidin- 2-yl)methyl)amino)methyl) picolinamide was prepared in a similar fashion to Example 115, replacing 1-(4-aminopiperidin-1-yl)ethan-1-one hydrochloride salt with (S)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt in step (b). White solid, LCMS: m/z found 733 [M+H] ⁺ , retention time = 2.56 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ. 8.67 (dd, 1H), 8.64 (d, 1H), 8.41 (s, 1H), 8.28 (s, 1H), 7.81 (d, 1H), 7.79 (d, 1H), 7.54 (t, 1H), 7.44 (d, 1H), 7.24 (dd, 1H), 4.07 (s, 3H), 4.05 (s, 3H), 3.95-3.91 (m, 2H), 3.89-3.81 (m, 4H), 2.75-2.68 (m, 4H), 2.36-2.27 (m, 6H), 1.87-1.78 (m, 2H). Example 117: N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-((( R)-3-hydroxypyrrolidin-1- yl)methyl)-5-methoxypicolinamide N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-((( R)-3-hydroxypyrrolidin-1- yl)methyl)-5-methoxypicolinamide was prepared in a similar fashion to Example 115, replacing 1-(4-aminopiperidin-1-yl)ethan-1-one hydrochloride salt with (R)-pyrrolidin-3-ol in step (b). Yellow solid, LCMS: m/z found 706 [M+H] ⁺ , retention time = 2.46 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ.8.68 (d, 1H), 8.64 (d, 1H), 8.42 (s, 1H), 8.31 (s, 1H), 7.81 (d, 1H), 7.79 (d, 1H), 7.53 (t, 1H), 7.44 (d, 1H), 7.24 (dd, 1H), 4.41-4.36 (m, 1H), 4.06 (s, 3H), 4.05 (s, 3H), 3.89-3.81 (m, 3H), 3.79 (s, 2H), 2.91-2.82 (m, 2H), 2.72-2.56 (m, 4H), 2.36-2.18 (m, 4H), 1.84-1.74 (m, 2H). Example 118: (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-((( 2-hydroxyethyl) (methyl)amino)methyl)-5-methoxypicolinamide (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-((( 2-hydroxyethyl) (methyl)amino)methyl)-5-methoxypicolinamide was prepared in a similar fashion to Example 115, replacing 1-(4-aminopiperidin-1-yl)ethan-1-one hydrochloride salt with 2- (methylamino)ethan-1-ol in step (b). White solid, LCMS: m/z found 694 [M+H] ⁺ , retention time = 2.39 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.69 (d, 1H), 8.66 (d, 1H), 8.43 (s, 1H), 8.36 (s, 1H), 7.83 (d, 1H), 7.81 (d, 1H), 7.55 (t, 1H), 7.45 (d, 1H), 7.26 (dd, 1H), 4.08 (s, 3H), 4.07 (s, 3H), 3.91-3.82 (m, 3H), 3.76-373 (m, 4H), 2.73-2.65 (m, 3H), 2.38-2.31 (m, 7H), 1.89-1.80 (m, 1H). Example 119: N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-((( S)-3-hydroxypyrrolidin-1- yl)methyl)-5-methoxypicolinamide N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-((( S)-3-hydroxypyrrolidin-1- yl)methyl)-5-methoxypicolinamide was prepared in a similar fashion to Example 115, replacing 1-(4-aminopiperidin-1-yl)ethan-1-one hydrochloride with (S)-pyrrolidin-3-ol in step (b). White solid, LCMS: m/z found 706 [M+H] ⁺ , retention time = 2.52 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.58 (dd, 1H), 8.55 (d, 1H), 8.34 (s, 1H), 8.22 (s, 1H), 7.73 (d, 1H), 7.69 (d, 1H), 7.44 (t, 1H), 7.34 (d, 1H), 7.15 (dd, 1H), 4.33-4.28 (m, 1H), 3.98 (s, 3H), 3.96 (s, 3H), 3.81-3.74 (m, 5H), 2.89-3.86 (m, 2H), 3.66-2.57 (m, 4H), 2.27-2.10 (m, 4H), 1.76-1.69 (m, 2H). Example 120: (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-((( 2- hydroxyethyl)amino)methyl)-5-methoxypicolinamide (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-((( 2-hydroxyethyl)amino)methyl)- 5-methoxypicolinamide was prepared in a similar fashion to Example 115, replacing 1-(4- aminopiperidin-1-yl)ethan-1-one hydrochloride with 2-aminoethanol in step (b). White solid, LCMS: m/z found 680 [M+H] ⁺ , retention time = 2.44 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.69 (dd, 1H), 8.66 (d, 1H), 8.45 (s, 1H), 8.27 (s, 1H), 7.83 (d, 1H), 7.81 (d, 1H), 7.55 (t, 1H), 7.45 (d, 1H), 7.26 (dd, 1H), 4.12 (s, 3H), 4.10 (s, 3H), 3.94 (s, 2H), 3.91- 3.83 (m, 3H), 3.72 (t, 2H), 2.79-2.70 (m, 4H), 2.38-2.29 (m, 3H), 1.86-1.81 (m, 1H). Example 121: (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl) amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-methoxy-4-((3 - (methoxymethyl)azetidin-1-yl)methyl)picolinamide (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl) amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-methoxy-4-((3 -(methoxymethyl)azetidin-1- yl)methyl)picolinamide was prepared in a similar fashion to Example 115, replacing 1-(4- aminopiperidin-1-yl)ethan-1-one hydrochloride with 3-(methoxymethyl)azetidine as a hydrochloride salt in step (b). White solid, LCMS: m/z found 720 [M+H] ⁺ , retention time = 2.73 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.68 (dd, 1H), 8.66 (d, 1H), 8.42 (s, 1H), 8.20 (s, 1H), 7.83 (d, 1H), 7.81 (d, 1H), 7.55 (t, 1H), 7.45 (d, 1H), 7.26 (dd, 1H), 4.08 (s, 3H), 4.07 (s, 3H), 3.91-3.83 (m, 3H), 3.78 (s, 2H), 3.58-3.54 (m, 4H), 3.39 (s, 3H), 3.23 (t, 2H), 2.84-2.70 (m, 3H), 2.38-2.29 (m, 3H), 1.87-1.82 (m, 1H). Example 122: (S)-5-(((1-Acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3'-chloro-6- methoxy-5-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4 '-bipyridin]-2'- yl)phenyl)-4-methoxypicolinamide (a) Methyl 4-methoxy-5-vinylpicolinate To a mixture of methyl 5-bromo-4-methoxypicolinate (2 g, 8.13 mmol) and 4,4,5,5- tetramethyl-2-vinyl-1,3,2-dioxaborolane (2.50 g, 16.2 mmol) in 1,4-dioxane / water (5:1 v/v, 12 mL) was added [1,1′-bis(di-tert-butylphosphino)ferrocene]dichloropalladi um(II) (529 mg, 0.81 mmol) and potassium phosphate (5.18 g, 24.3 mmol), and the mixture stirred at 110 °C for 1 hour under N ₂ . Water (200 mL) was added and the mixture extracted with ethyl acetate (2 x 200 mL). The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0- 29 % ethyl aceate / petroleum ether) to afford methyl 4-methoxy-5-vinylpicolinate (810 mg, 25% yield) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 8.69 (s, 1H), 7.66 (s, 1H), 6.93-6.85 (m, 1H), 6.12 (dd, 1H), 5.54 (dd, 1H), 3.99 (s, 3H), 3.90 (s, 3H). (b) Lithium 4-methoxy-5-vinylpicolinate To a solution of methyl 4-methoxy-5-vinylpicolinate (810 mg, 4.19 mmol) in THF / water (2:1 v/v, 6 mL) was added lithium hydroxide (150 mg, 6.29 mmol), and the mixture stirred at room temperature for 1 hour under N ₂ . The mixture was concentrated to afford lithium 4-methoxy-5-vinylpicolinate (820 mg, crude) as a white solid. LCMS: m/z found 180 [M+H] ⁺ (acid). (c) tert-Butyl (S)-((3'-chloro-2'-(2-chloro-3-(4-methoxy-5- vinylpicolinamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)me thyl)((5-oxopyrrolidin-2- yl)methyl)carbamate To the mixture of lithium 4-methoxy-5-vinylpicolinate (0.80 g, 4.32 mmol) and tert- butyl (S)-((2'-(3-amino-2-chlorophenyl)-3'-chloro-6-methoxy-[2,4'- bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (Example 59, step (a)) (1.24 g, 2.16 mmol) in DMF (5 mL) was added 2-chloro-1-methylpyridinium iodide (1.10 g, 4.32 mmol) and N,N-diisopropylethylamine (837 mg, 6.48 mmol), and the mixture stirred at room temperature for 12 hours under N ₂ . Water (100 mL) was added and the mixture extracted with ethyl acetate (2 x 100 mL). The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-100 % ethyl acetate / petroleum ether) to afford tert-butyl (S)-((3'-chloro- 2'-(2-chloro-3-(4-methoxy-5-vinylpicolinamido)phenyl)-6-meth oxy-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (1.5 g, 66% yield) as a brown solid. LCMS: m/z found 733 [M+H] ⁺ . (d) tert-Butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-formyl-4- methoxypicolinamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl) methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-2'-(2-chloro-3-(4-methoxy-5- vinylpicolinamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)me thyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (600 mg, 0.82 mmol) in THF / water (10:1 v/v, 4.4 mL) was added potassium osmate(VI) dihydrate (60.2 mg, 0.16 mmol), and the mixture stirred at 0 °C for 0.5 hours under N ₂ . Sodium periodate (1.05 g, 4.91 mmol) was then added, and the mixture stirred at 0 °C for 0.5 hours and then at room temperature for 11 hours under N ₂ . Water (100 mL) was added and the mixture extracted with ethyl acetate (2 x 100 mL). The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-30 % methanol / ethyl acetate) to afford tert-butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-formyl-4-methoxypicolinami do)phenyl)- 6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-y l)methyl)carbamate (450 mg, 74% yield) as a brown solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.81 (s, 1H), 10.41 (s, 1H), 8.88 (s, 1H), 8.75 (d, 1H), 8.45 (dd, 1H), 8.01 (s, 1H), 7.80-7.77 (m, 2H), 7.70-7.68 (m, 1H), 7.63-7.59 (m, 1H), 7.52-7.46 (m, 1H), 7.42-7.36 (m, 1H), 4.50-4.37 (m, 2H), 4.05 (s, 3H), 3.98 (s, 3H), 3.80-3.76 (m, 1H), 3.31-3.28 (m, 2H), 2.19-2.07 (m, 3H), 1.75-1.71 (m, 1H), 1.45-1.31 (m, 9H). (e) tert-Butyl (S)-((2'-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-4- methoxypicolinamido)-2-chlorophenyl)-3'-chloro-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-formyl-4- methoxypicolinamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl) methyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (90 mg, 0.12 mmol) and 1-(4-aminopiperidin-1-yl)ethan-1-one hydrochloride salt (32.8 mg, 0.18 mmol) in dichloromethane / methanol (1:1 v/v, 6 mL) was added sodium acetate (30.1 mg, 0.37 mmol) and the mixture stirred at room temperature for 1.5 hours under N ₂ . Sodium cyanoborohydride (23.1 mg, 0.37 mmol) was then added and the mixture stirred at room temperature for 0.5 hours under N ₂ . Water (10 mL) was added, and the mixture extracted with dichloromethane (2 x 20 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure. The residue was purified by prep-TLC (SiO ₂ , ethyl acetate : methanol = 1:1 v/v) to afford tert-butyl (S)- ((2'-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-4-methoxy picolinamido)-2-chlorophenyl)- 3'-chloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrr olidin-2-yl)methyl)carbamate (65 mg, 61% yield) as a white solid. LCMS: m/z found 861 [M+H] ⁺ . (f) (S)-5-(((1-Acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3'-chloro-6- methoxy-5-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4 '-bipyridin]-2'- yl)phenyl)-4-methoxypicolinamide To a mixture of tert-butyl (S)-((2'-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-4- methoxypicolinamido)-2-chlorophenyl)-3'-chloro-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (60 mg, 0.07 mmol) in dichloromethane (5 mL) was added trifluoroacetic acid (2 mL, 26.9 mmol), and the mixture stirred at room temperature for 0.5 hours under N ₂ . The mixture was concentrated and the residue purified by reverse phase HPLC to afford (S)-5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl)amino )methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-4-methoxypicolinamide (17.8 mg, 32% yield). as a white solid. LCMS: m/z found 761 [M+H] ⁺ , retention time = 2.62 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.71 (dd, 1H), 8.66 (d, 1H), 8.52 (s, 1H), 7.92 (s, 1H), 7.83 (d, 1H), 7.81 (d, 1H), 7.56 (t, 1H), 7.45 (d, 1H), 7.28 (dd, 1H), 4.49-4.45 (m, 1H), 4.12 (s, 3H), 4.09 (s, 3H), 3.94-3.83 (m, 6H), 3.16-3.15 (m, 1H), 2.78-2.70 (m, 4H), 2.38-2.31 (m, 3H), 2.11 (s, 3H), 2.06-2.02 (m, 2H), 1.86-1.85 (m, 1H), 1.41-1.29 (m, 2H). Example 123: (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 2- hydroxyethyl)amino)methyl)-4-methoxypicolinamide (a) tert-Butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-(((2-hydroxyethyl)amino)me thyl)-4- methoxypicolinamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl) methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-formyl-4- methoxypicolinamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl) methyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (90 mg, 0.12 mmol), 2-aminoethanol (14.9 mg, 0.24 mmol) in dichloromethane / methanol (1:1 v/v, 2 mL) was added sodium acetate (30.1 mg, 0.37 mmol), and the mixture stirred at room temperature for 1 hour under N ₂ . Sodium cyanoborohydride (23.1 mg, 0.37 mmol) was then added, and the mixture stirred at room temperature for 1 hour under N ₂ . Water (50 mL) was added, and the mixture extracted with dichloromethane (2 x 50 mL). The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by prep-TLC (SiO ₂ , ethyl acetate : methanol = 2:1 v/v) to afford tert-butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-(((2-hydroxyethyl)amino)me thyl)-4- methoxypicolinamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl) methyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (40 mg, 41% yield) as a white solid. LCMS: m/z found 780 [M+H] ⁺ . (b) (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 2- hydroxyethyl)amino)methyl)-4-methoxypicolinamide To a mixture of tert-butyl (S)-((3'-chloro-2'-(2-chloro-3-(5-(((2- hydroxyethyl)amino)methyl)-4-methoxypicolinamido)phenyl)-6-m ethoxy-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (30 mg, 0.03 mmol) in dichloromethane (1 mL) was added trifluoroacetic acid (0.2 mL, 2.69 mmol), and the mixture stirred at room temperature for 1 hour under N ₂ . The mixture was concentrated and the residue purified by prep-HPLC to afford (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 2-hydroxyethyl)amino)methyl)- 4-methoxypicolinamide (11.9 mg, 45% yield) as a white solid. LCMS: m/z found 680 [M+H] ⁺ , retention time = 2.52 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.71 (d, 1H), 8.66 (d, 1H), 8.50 (s, 1H), 7.93 (s, 1H), 7.84 (d, 1H), 7.81 (d, 1H), 7.56 (t, 1H), 7.45 (d, 1H), 7.28 (d, 1H), 4.09 (s, 3H), 4.07 (s, 3H), 3.93 (s, 2H), 3.87-3.86 (m, 3H), 3.70 (t, 2H), 2.79-2.69 (m, 4H), 2.36-2.34 (m, 3H), 1.88-1.80 (m, 1H). Example 124: (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-((( 3- fluoropropyl)amino)methyl)-5-methoxypicolinamide (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-((( 3-fluoropropyl)amino)methyl)-5- methoxypicolinamide was prepared in a similar fashion to Example 115, replacing 1-(4- aminopiperidin-1-yl)ethan-1-one hydrochloride with 3-fluoropropan-1-amine hydrochloride salt in step (b). White solid, LCMS: m/z found 696 [M+H] ⁺ , retention time = 2.25 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.68 (dd, 1H), 8.65 (d, 1H), 8.41 (s, 1H), 8.25 (s, 1H), 7.82 (d, 2H), 7.79 (d, 1H), 7.54 (t, 1H), 7.43 (d, 1H), 7.25 (dd, 1H), 4.60 (t, 1H), 4.49 (t, 1H), 4.08 (s, 3H), 4.06 (s, 3H), 3.89-3.85 (m, 5H), 2.79-2.69 (m, 4H), 3.78-3.28 (m, 3H), 2.01-1.82 (m, 3H). Example 125: N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( S)-3-hydroxypyrrolidin-1- yl)methyl)-4-methoxypicolinamide N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( S)-3-hydroxypyrrolidin-1- yl)methyl)-4-methoxypicolinamide was prepared in a similar fashion to Example 123, replacing 2-aminoethanol with (S)-pyrrolidin-3-ol in step (a). LCMS: m/z found 706 [M+H] ⁺ , retention time = 2.63 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ.8.68 (d, 1H), 8.64 (d, 1H), 8.51 (s, 1H), 7.88 (s, 1H), 7.81 (d, 1H), 7.78 (d, 1H), 7.54 (t, 1H), 7.43 (d, 1H), 7.25 (d, 1H), 4.37-4.32 (m, 1H), 4.05 (s, 6H), 3.89-3.82 (m, 3H), 3.78-3.74 (m, 2H), 2.86- 2.82 (m, 2H), 2.71-2.54 (m, 4H), 2.35-2.23 (m, 3H), 2.20-2.11 (m, 1H), 1.84-1.81 (m, 1H), 1.74-1.70 (m, 1H). Example 126: N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-(((((S)-5- oxopyrrolidin-2-yl)methyl)amino)methyl)picolinamide N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-(((((S)-5-oxopyrrolidin- 2-yl)methyl)amino)methyl)picolinamide was prepared in a similar fashion to Example 123, replacing 2-aminoethanol with (S)-5-(aminomethyl)pyrrolidin-2-one in step (a). LCMS: m/z found 733 [M+H] ⁺ , retention time = 2.46 min (Method A). ¹ H NMR (400 MHz, Methanol- d4): δ 8.71 (d, 1H), 8.66 (d, 1H), 8.51 (s, 1H), 7.92 (s, 1H), 7.84 (d, 1H), 7.81 (d, 1H), 7.56 (t, 1H), 7.45 (d, 1H), 7.28 (dd, 1H), 4.09 (s, 3H), 4.07 (s, 3H), 3.91 (d, 2H), 3.87-3.83 (m, 4H), 2.77-2.67 (m, 4H), 2.37-2.29 (m, 6H), 1.89-1.80 (m, 2H). Example 127: N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( R)-3-hydroxypyrrolidin-1- yl)methyl)-4-methoxypicolinamide N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( R)-3-hydroxypyrrolidin-1- yl)methyl)-4-methoxypicolinamide was prepared in a similar fashion to Example 123, replacing 2-aminoethanol with (R)-pyrrolidin-3-ol in step (a). LCMS: m/z found 706 [M+H] ⁺ , retention time = 2.61 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.71 (dd, 1H), 8.66 (d, 1H), 8.54 (s, 1H), 7.91 (s, 1H), 7.83 (d, 1H), 7.81 (d, 1H), 7.56 (t, 1H), 7.45 (d, 1H), 7.28 (dd, 1H), 4.39-4.34 (m, 1H), 4.07 (s, 6H), 3.91-3.86 (m, 3H), 3.84-3.76 (m, 2H), 2.91-2.82 (m, 2H), 2.73-2.56 (m, 4H), 2.36-2.34 (m, 3H), 2.20-2.15 (m, 1H), 1.86-1.71 (m, 2H). Example 128: (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-((3- (methoxymethyl)azetidin-1-yl)methyl)picolinamide (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-((3- (methoxymethyl)azetidin-1-yl)methyl)picolinamide was prepared in a similar fashion to Example 123, replacing 2-aminoethanol with 3-(methoxymethyl)azetidine hydrochloride salt in step (a). LCMS: m/z found 720 [M+H] ⁺ , retention time = 2.78 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.69 (dd, 1H), 8.66 (d, 1H), 8.43 (s, 1H), 7.90 (s, 1H), 7.83 (d, 1H), 7.81 (d, 1H), 7.56 (t, 1H), 7.45 (d, 1H), 7.28 (dd, 1H), 4.07 (s, 6H), 3.88-3.87 (m, 3H), 3.77 (s, 2H), 3.54-3.50 (m, 4H), 3.33 (s, 3H), 3.19-3.15 (m, 2H), 2.80-2.70 (m, 3H), 2.38- 2.27 (m, 3H), 1.89-1.82 (m, 1H). Example 129: (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 2- hydroxyethyl)(methyl)amino)methyl)-4-methoxypicolinamide (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 2- hydroxyethyl)(methyl)amino)methyl)-4-methoxypicolinamide was prepared in a similar fashion to Example 123, replacing 2-aminoethanol with 2-(methylamino)ethan-1-ol in step (a). LCMS: m/z found 694 [M+H] ⁺ , retention time = 2.55 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.71 (dd, 1H), 8.66 (d, 1H), 8.55 (s, 1H), 7.90 (s, 1H), 7.84-7.80 (m, 2H), 7.56 (t, 1H), 7.45 (d, 1H), 7.28 (dd, 1H), 4.07 (s, 3H), 4.06 (s, 3H), 3.87-3.84 (m, 3H), 3.74-3.71 (m, 4H), 2.73-2.63 (m, 4H), 2.38-2.31 (m, 6H), 1.86-1.81 (m, 1H). Example 130: (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 3- fluoropropyl)amino)methyl)-4-methoxypicolinamide ((S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidi n-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 3-fluoropropyl)amino)methyl)-4- methoxypicolinamide was prepared in a similar fashion to Example 123, replacing 2- aminoethanol with 3-fluoropropan-1-amine hydrochloride salt in step (a). LCMS: m/z found 696 [M+H] ⁺ , retention time = 2.76 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.60 (dd, 1H), 8.56 (d, 1H), 8.39 (s, 1H), 7.81 (s, 1H), 7.73 (d, 1H), 7.70 (d, 1H), 7.46 (t, 1H), 7.35 (d, 1H), 7.17 (dd, 1H), 4.48 (t, 1H), 4.36 (t, 1H), 3.98 (s, 3H), 3.96 (s, 3H), 3.81-3.73 (m, 5H), 2.68-2.59 (m, 4H), 2.28-2.19 (m, 3H), 1.89-1.75 (m, 3H). Example 131: N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino) methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphenyl)-7-(((R)-5-ox opyrrolidin-2-yl)methyl)- 5,6,7,8-tetrahydro-2,7-naphthyridine-3-carboxamide N-(3-(3'-Chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-7-(((S)-5-oxopyrroli din-2-yl)methyl)-5,6,7,8- tetrahydro-2,7-naphthyridine-3-carboxamide was prepared in a similar fashion to Example 111, by replacing 1-bromo-3-fluoropropane with (R)-5-(bromomethyl)pyrrolidin-2-one in step (a). Pale red solid, LCMS: m/z found 709 [M+H] ⁺ retention time = 2.10 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): 8.64 (d, 1H), 8.43 (s, 1H), 8.08 (d, 1H), 8.02 (s, 1H), 7.83 (d, 1H), 7.76 (d, 1H), 7.45-7.41 (m, 2H), 7.20 (dd, 1H), 4.06-4.02 (m, 4H), 3.92-3.77 (m, 5H), 3.07 (t, 2H), 2.98-2.94 (m, 1H), 2.87-2.81 (m, 1H), 2.75-2.61 (m, 4H), 2.40-2.26 (m, 6H), 2.18 (s, 3H), 1.87-1.80 (m, 1H). Example 132: (S)-7-(1-Acetylpiperidin-4-yl)-N-(3-(3'-chloro-6-methoxy-5-( (((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)- 5,6,7,8-tetrahydro-2,7-naphthyridine-3-carboxamide (a) 1-(4-(6-Chloro-3,4-dihydro-2,7-naphthyridin-2(1H)-yl)piperid in-1-yl)ethan-1-one A mixture of 6-chloro-1,2,3,4-tetrahydro-2,7-naphthyridine hydrochloride salt (500 mg, 2.44 mmol), 1-acetylpiperidin-4-one (413 mg, 2.93 mmol) and titanium tetraisopropoxide (1.04 g, 3.66 mmol) in dichloromethane (10 mL) was stirred for 2 hours. Sodium triacetoxyborohydride (1.55 g, 7.31 mmol) was then added, and the mixture stirred for another 10 hours at room temperature. The reaction was quenched with water (1 mL) and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether to 0-15% methanol / ethyl acetate) to afford 1-(4-(6-chloro-3,4-dihydro-2,7-naphthyridin-2(1H)-yl)piperid in-1-yl)ethan-1-one (500 mg, 41% yield) as a brown oil. LCMS: m/z found 294 [M +H] ⁺ . (b) Ethyl 7-(1-acetylpiperidin-4-yl)-5,6,7,8-tetrahydro-2,7-naphthyrid ine-3- carboxylate To a mixture of 1-(4-(6-chloro-3,4-dihydro-2,7-naphthyridin-2(1H)-yl)piperid in-1- yl)ethan-1-one (450 mg, 1.53 mmol) in ethanol (10 mL) was added triethylamine (1.07 mL, 7.66 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (250 mg, 0.31 mmol), and the mixture stirred for 12 hours at 80 °C under CO (50 psi) atmosphere. The reaction was combined with another batch at 50 mg scale, filtered and washed with ethanol (50 mL). The filtrate was concentrated, water (15 mL) added, and the mixture extracted with dichloromethane (3 x 15 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether to 0-15% methanol / ethyl acetate) to afford ethyl 7-(1- acetylpiperidin-4-yl)-5,6,7,8-tetrahydro-2,7-naphthyridine-3 -carboxylate (0.2 g, 30% yield) as a dark orange oil. LCMS: m/z found 332 [M +H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 8.42 (s, 1 H), 7.96 (s, 1 H), 4.65-4.61 (m, 1 H), 4.44 (q, 2 H), 4.06-4.02 (m, 1 H), 3.95 (s, 2 H), 3.22-3.15 (m, 1 H), 3.02-2.94 (m, 4 H), 2.89-2.84 (m, 1 H), 2.73-2.67 (m, 1 H), 2.14 (s, 3 H), 2.07-2.00 (m, 2 H), 1.65-1.61 (m, 1 H), 1.55-1.51 (m, 1 H), 1.43 (t, 3 H). (c) Lithium 7-(1-acetylpiperidin-4-yl)-5,6,7,8-tetrahydro-2,7-naphthyrid ine-3- carboxylate To a mixture of ethyl 7-(1-acetyl-4-piperidyl)-6,8-dihydro-5H-2,7-naphthyridine-3- carboxylate (62.5 mg, 0.19 mmol) in THF / water (2/1 v/v, 3 mL) was added lithium hydroxide monohydrate (39.6 mg, 0.94 mmol) and the reaction mixture was stirred for 2 hours at room temperature. The reaction mixture was concentrated directly to afford the crude product lithium 7-(1-acetylpiperidin-4-yl)-5,6,7,8-tetrahydro-2,7-naphthyrid ine-3-carboxylate (120 mg, crude) as a yellow solid, which was used into the next step without further purification. (d) tert-Butyl (S)-((2'-(3-(7-(1-acetylpiperidin-4-yl)-5,6,7,8-tetrahydro-2 ,7- naphthyridine-3-carboxamido)-2-methylphenyl)-3'-chloro-6-met hoxy-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate To a mixture of lithium 7-(1-acetylpiperidin-4-yl)-5,6,7,8-tetrahydro-2,7- naphthyridine-3-carboxylate (60 mg, 0.19 mmol) in DMF (3 mL) was added 2-chloro-1- methylpyridinium iodide (74.3 mg, 0.29 mmol), N,N-diisopropylethylamine (0.1 mL, 0.58 mmol) and tert-butyl (S)-((2'-(3-amino-2-methylphenyl)-3'-chloro-6-methoxy-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te (Example 42, step (d)) (107 mg, 0.19 mmol) and the mixture stirred for 12 hours at room temperature. Additional 2- chloro-1-methylpyridinium iodide (1.5 eq) and N,N-diisopropylethylamine (1.5 eq) were added and the mixture stirred for another 5 hours at room temperature. Water (20 mL) was added, and the mixture extracted with ethyl acetate (3 x 20 ml). The organic layer was washed with brine (2 x 20 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated. The residue combined with another batch at 47 mg scale was purified by normal phase SiO ₂ chromatography (0-15% ethyl acetate/petroleum ether) to afford tert-butyl (S)-((2'-(3-(7-(1-acetylpiperidin-4-yl)-5,6,7,8-tetrahydro-2 ,7-naphthyridine-3-carboxamido)- 2-methylphenyl)-3'-chloro-6-methoxy-[2,4'-bipyridin]-5-yl)me thyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (185 mg, 35% yield) as a brown solid. LCMS: m/z found 837 [M +H] ⁺ . (e) (S)-7-(1-Acetylpiperidin-4-yl)-N-(3-(3'-chloro-6-methoxy-5-( (((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5,6,7,8-tetrahydro-2,7- naphthyridine-3-carboxamide To a mixture of tert-butyl (S)-((2'-(3-(7-(1-acetylpiperidin-4-yl)-5,6,7,8-tetrahydro- 2,7-naphthyridine-3-carboxamido)-2-methylphenyl)-3'-chloro-6 -methoxy-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (180 mg, 0.21 mmol) in dichloromethane (4 mL) was added trifluoroacetic acid (1 mL, 13.5 mmol) and the reaction stirred for 1 hour at room temperature. The reaction was concentrated directly under reduced pressure and the residue purified by reverse phase HPLC to afford (S)-7-(1-acetylpiperidin-4-yl)-N-(3-(3'- chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl)amino)met hyl)-[2,4'-bipyridin]-2'-yl)-2- methylphenyl)-5,6,7,8-tetrahydro-2,7-naphthyridine-3-carboxa mide (48.4 mg, 29% yield) as a brown solid. LCMS: m/z found 737 [M+H] ⁺ , retention time = 2.18 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.64 (d, 1 H), 8.45 (m, 1 H), 8.08 (d, 1 H), 8.02 (s, 1 H), 7.83 (d, 1 H), 7.75 (d, 1 H), 7.45-7.40 (m, 2 H), 7.20 (d, 1 H), 4.63 (d, 1 H), 4.06-4.02 (m, 4 H), 3.96 (s, 2 H), 3.91-3.83 (m, 3 H), 3.22-3.16 (m, 1 h), 3.06-3.04 (m, 2 H), 2.99-2.96 (m, 2 H), 2.88-2.82 (m, 1 H), 2.77-2.67 (m, 3 H), 2.38-2.29 (m, 3 H), 2.18 (s, 3 H), 2.14 (s, 3 H), 2.05 (t, 2 H), 1.67-1.63 (m, 1 H), 1.56-1.52 (m, 1 H). Example 133: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-7-(oxetan-3-ylmethyl)- 5,6,7,8-tetrahydro-2,7-naphthyridine-3-carboxamide (a) 6-Chloro-2-(oxetan-3-ylmethyl)-1,2,3,4-tetrahydro-2,7-naphth yridine A mixture of 6-chloro-1,2,3,4-tetrahydro-2,7-naphthyridine hydrochloride salt (300 mg, 1.46 mmol), oxetane-3-carbaldehyde (189 mg, 2.19 mmol) and sodium acetate (360 mg, 4.39 mmol) in methanol (4 mL) was stirred at room temperature for 2 hours. Sodium triacetoxyborohydride (276 mg, 4.39 mmol) was then added, and the mixture stirred for another 10 hours at room temperature. The reaction was quenched with water (1 mL) and then concentrated under reduced pressure. The residue combined with another batch at 200 mg scale was purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether to 0-10% methanol/ethyl acetate) to afford a light-yellow oil (400 mg). The oil was further purified by reverse phase HPLC to afford 6-chloro-2-(oxetan-3- ylmethyl)-1,2,3,4-tetrahydro-2,7-naphthyridine (180 mg, 47% yield) as a light yellow solid. ¹ H NMR (400 MHz, Methanol-d4): δ 8.10 (s, 1 H), 7.29 (s, 1 H), 4.86-4.84 (m, 2 H), 4.48 (t, 2 H), 3.63 (s, 2 H), 3.46-3.39 (m, 1 H), 2.95-2.92 (m, 4 H), 2.76 (t, 1 H). (b) Ethyl 7-(oxetan-3-ylmethyl)-5,6,7,8-tetrahydro-2,7-naphthyridine-3 -carboxylate To a mixture of 6-chloro-2-(oxetan-3-ylmethyl)-1,2,3,4-tetrahydro-2,7-naphth yridine (0.16 g, 0.67 mmol) in ethanol (15 mL) was added triethyl amine (0.47 mL, 3.35 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (109 mg, 0.13 mmol) and the reaction mixture stirred for 12 hours at 80 °C under CO (50 psi) atmosphere. Additional [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (100 mg) was added and the mixture stirred for another 12 hours at 80 °C under CO (50 psi). The reaction combined with another batch at 20 mg scale was filtered and washed with ethanol (100 mL). The filtrate was concentrated under reduced pressure and the residue purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether to 0-20% methanol / ethyl acetate) to afford ethyl 7-(oxetan-3-ylmethyl)-5,6,7,8-tetrahydro-2,7- naphthyridine-3-carboxylate (300 mg, 90% yield) as a black solid. LCMS: m/z found 277 [M +H] ⁺ . (c) Lithium 7-(oxetan-3-ylmethyl)-5,6,7,8-tetrahydro-2,7-naphthyridine-3 - carboxylate To a mixture of ethyl 7-(oxetan-3-ylmethyl)-5,6,7,8-tetrahydro-2,7-naphthyridine-3 - carboxylate (220 mg, 0.796 mmol) in THF / water (4/1 v/v, 5 mL) was added lithium hydroxide monohydrate (167 mg, 3.98 mmol) and the reaction mixture stirred for 12 hours at room temperature. The reaction was concentrated under reduced pressure to afford lithium 7- (oxetan-3-ylmethyl)-5,6,7,8-tetrahydro-2,7-naphthyridine-3-c arboxylate (197 mg, crude) as a brown solid, which was used into the next step without further purification. (d) tert-Butyl (S)-((3'-chloro-6-methoxy-2'-(2-methyl-3-(7-(oxetan-3-ylmeth yl)- 5,6,7,8-tetrahydro-2,7-naphthyridine-3-carboxamido)phenyl)-[ 2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate To a mixture of lithium 7-(oxetan-3-ylmethyl)-5,6,7,8-tetrahydro-2,7-naphthyridine- 3-carboxylate (197 mg, 0.77 mmol) in DMF (3 mL) was added 2-chloro-1-methylpyridinium iodide (297 mg, 1.16 mmol), N,N-diisopropylethylamine (300 mg, 2.32 mmol) and tert-butyl (S)-((2'-(3-amino-2-methylphenyl)-3'-chloro-6-methoxy-[2,4'- bipyridin]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (Example 42, step (d)) (214 mg, 0.39 mmol) and the reaction was stirred for 12 hours at room temperature. Water (10 mL) was added, and the mixture extracted with dichloromethane (3 x 10 mL). The combined organic layers were washed with brine (2 x 20 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate/petroleum ether to 0-25% methanol /ethyl acetate) to afford tert-butyl (S)-((3'- chloro-6-methoxy-2'-(2-methyl-3-(7-(oxetan-3-ylmethyl)-5,6,7 ,8-tetrahydro-2,7- naphthyridine-3-carboxamido)phenyl)-[2,4'-bipyridin]-5-yl)me thyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (120 mg, 16% yield) as a dark orange oil. LCMS: m/z found 782 [M +H] ⁺ . (e) (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-7-(oxetan-3-ylmethyl )-5,6,7,8-tetrahydro-2,7- naphthyridine-3-carboxamide To a mixture of tert-butyl (S)-((3'-chloro-6-methoxy-2'-(2-methyl-3-(7-(oxetan-3- ylmethyl)-5,6,7,8-tetrahydro-2,7-naphthyridine-3-carboxamido )phenyl)-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (75 mg, 0.10 mmol) in dichloromethane (5 mL) was added 2,6-dimethylpyridine (102.7 mg, 0.96 mmol) and trimethylsilyl trifluoromethanesulfonate (107 mg, 0.48 mmol) and the reaction was stirred for 12 hours at room temperature. Additional 2,6-dimethylpyridine (20 eq) and trimethylsilyl trifluoromethanesulfonate (20 eq) were added, and the mixture stirred for another 12 hours. Additional 2,6-dimethylpyridine (15 eq) and trimethylsilyl trifluoromethanesulfonate (15 eq) were added and stirred for another 24 hours at room temperature. The reaction mixture was concentrated directly and the residue purified by reverse phase HPLC to afford (S)-N-(3-(3'- chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl)amino)met hyl)-[2,4'-bipyridin]-2'-yl)-2- methylphenyl)-7-(oxetan-3-ylmethyl)-5,6,7,8-tetrahydro-2,7-n aphthyridine-3-carboxamide (4.9 mg, 6% yield) as a light brown solid (formic acid salt). LCMS: m/z found 682 [M +H] ⁺ , retention time = 2.18 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.68 (d, 1 H), 8.06-8.03 (m, 1 H), 7.97 (d, 1 H), 7.76-7.74 (m, 1 H), 7.55-7.52 (m, 1 H), 7.51-7.48 (m, 1 H), 7.45-7.40 (m, 1 H), 7.38 (d, 1 H), 7.36 (d, 1 H), 7.24-7.20 (m, 1 H), 5.01-4.91 (m, 4 H), 4.54- 4.47 (m, 2 H), 4.38-4.31 (m, 2 H), 4.14 (s, 3 H), 4.06-3.93 (m, 2 H), 3.72-3.70 (m, 1 H), 3.51- 3.40 (m, 2 H), 3.25-3.20 (m, 2 H), 3.16-3.09 (m, 2 H), 3.00-2.97 (m, 1 H), 2.47-2.37 (m, 3 H), 2.17 (s, 3 H), 1.97-1.89 (m, 1 H). Example 134: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-fluorophen yl)-5-(((2- hydroxyethyl)amino)methyl)-4-methoxypicolinamide (a) tert-Butyl (S)-((2'-(3-amino-2-fluorophenyl)-3'-chloro-6-methoxy-[2,4'- bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbama te To a mixture of 2-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anil ine (2 g, 8.44 mmol) and tert-butyl (S)-((2',3'-dichloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl) ((5- oxopyrrolidin-2-yl)methyl)carbamate (Example 23, step (c)) (2.03 g, 4.22 mmol) in 1,4- dioxane / water (5:1 v/v, 18 mL) was added tetrakis(triphenylphosphine)palladium(0) (243 mg, 0.21 mmol) and potassium carbonate (1.75 g, 12.6 mmol), and then the mixture stirred at 95 °C for 1 hour under N ₂ . The mixture was combined with another batch at the 100 mg scale. Water (200 mL) was added and the mixture extracted with ethyl acetate (2 x 200 mL). The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-84 % ethyl acetate / petroleum ether) to afford tert-butyl (S)-((2'-(3-amino-2-fluorophenyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl) methyl)carbamate (2.2 g) as a black solid. LCMS: m/z found 556 [M+H] ⁺ . (b) tert-Butyl (S)-((3'-chloro-2'-(2-fluoro-3-(4-methoxy-5- vinylpicolinamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)me thyl)((5-oxopyrrolidin-2- yl)methyl)carbamate To a mixture of tert-butyl (S)-((2'-(3-amino-2-fluorophenyl)-3'-chloro-6-methoxy- [2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)c arbamate (500 mg, 0.89 mmol) and lithium 4-methoxy-5-vinylpicolinate (Example 122, step (b)) (499 mg, 2.70 mmol) in DMF (5 mL) was added 2-chloro-1-methylpyridinium iodide (459 mg, 1.80 mmol) and N,N- diisopropylethylamine (348 mg, 2.70 mmol), and the mixture stirred at room temperature for 1 hour under N ₂ . Water (30 mL) was added and the suspension filtered to give the solid product tat was dried under vacuum to afford tert-butyl (S)-((3'-chloro-2'-(2-fluoro-3-(4- methoxy-5-vinylpicolinamido)phenyl)-6-methoxy-[2,4'-bipyridi n]-5-yl)methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate (720 mg, crude) as a black solid. LCMS: m/z found 717 [M+H] ⁺ . (c) tert-Butyl (S)-((3'-chloro-2'-(2-fluoro-3-(5-formyl-4- methoxypicolinamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl) methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-2'-(2-fluoro-3-(4-methoxy-5- vinylpicolinamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)me thyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (620 mg, 0.86 mmol) in THF / water (5:1 v/v, 6 mL) was added potassium osmate(VI) dihydrate (63.7 mg, 0.17 mmol), and the mixture stirred at 0 °C for 0.5 hours under N ₂ . Sodium periodate (924 mg, 4.32 mmol) was then added, and the mixture stirred at 0 °C for 0.5 hours and then at room temperature for 11 hours under N ₂ . The mixture was combined with another batch at the 100 mg scale. Water (100 mL) was added, and the mixture extracted with ethyl acetate (2 x 100 mL). The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-23 % methanol / ethyl acetate) to afford tert-butyl (S)-((3'- chloro-2'-(2-fluoro-3-(5-formyl-4-methoxypicolinamido)phenyl )-6-methoxy-[2,4'-bipyridin]- 5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (350 mg) as a black solid. LCMS: m/z found 719 [M+H] ⁺ . (d) tert-Butyl (S)-((3'-chloro-2'-(2-fluoro-3-(5-(((2-hydroxyethyl)amino)me thyl)-4- methoxypicolinamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl) methyl)((5- oxopyrrolidin-2-yl)methyl)carbamate To a mixture of tert-butyl (S)-((3'-chloro-2'-(2-fluoro-3-(5-formyl-4- methoxypicolinamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl) methyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (300 mg, 0.41 mmol) and 2-aminoethanol (50.9 mg, 0.83 mmol) in dichloromethane / methanol (1:1 v/v, 4 mL) was added sodium acetate (102 mg, 1.25 mmol), and the mixture stirred at room temperature for 1 hour under N ₂ . Sodium cyanoborohydride (78.6 mg, 1.25 mmol) was then added, and the mixture stirred at room temperature for 1 hour under N ₂ . The mixture was combined with another batch at the 50 mg scale. Water (50 mL) was added and the mixture extracted with dichloromethane (2 x 50 mL). The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by prep-TLC (SiO ₂ , ethyl acetate : methanol = 2:1 v/v) to afford tert- butyl (S)-((3'-chloro-2'-(2-fluoro-3-(5-(((2-hydroxyethyl)amino)me thyl)-4- methoxypicolinamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl) methyl)((5-oxopyrrolidin-2- yl)methyl)carbamate (120 mg) as a brown solid. LCMS: m/z found 764 [M+H] ⁺ . (e) (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-fluorophen yl)-5-(((2- hydroxyethyl)amino)methyl)-4-methoxypicolinamide To a mixture of tert-butyl (S)-((3'-chloro-2'-(2-fluoro-3-(5-(((2- hydroxyethyl)amino)methyl)-4-methoxypicolinamido)phenyl)-6-m ethoxy-[2,4'-bipyridin]-5- yl)methyl)((5-oxopyrrolidin-2-yl)methyl)carbamate (110 mg, 0.14 mmol) in dichloromethane (5 mL) was added trifluoroacetic acid (1 mL, 13.4 mmol), and the mixture stirred at room temperature for 0.5 hours under N ₂ . The mixture was concentrated and the residue purified by prep-HPLC to afford (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-fluorophen yl)-5-(((2- hydroxyethyl)amino)methyl)-4-methoxypicolinamide (34.9 mg) a white solid. LCMS: m/z found 664 [M+H] ⁺ , retention time = 2.38 min (Method A). ¹ H NMR (400 MHz, Methanol- d ₄ ): δ 8.67 (d, 1H), 8.57-8.53 (m, 1H), 8.49 (s, 1H), 7.90 (s, 1H), 7.83 (d, 1H), 7.77 (d, 1H), 7.44-7.38 (m, 2H), 7.32-7.28 (m, 1H), 4.08 (s, 3H), 4.06 (s, 3H), 3.91 (s, 2H), 3.87-3.83 (m, 3H), 3.69 (t, 2H), 2.77-2.70 (m, 4H), 2.38-2.27 (m, 3H), 1.87-1.82 (m, 1H). Example 135: N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl) amino)methyl)-4- methoxypicolinamide (a) tert-Butyl (1-acetylpiperidin-4-yl)((2',3'-dichloro-6-methoxy-[2,4'-bip yridin]-5- yl)methyl)carbamate To a mixture of 2',3'-dichloro-6-methoxy-[2,4'-bipyridine]-5-carbaldehyde (Example 23, step (a)) (1 g, 3.53 mmol) and 1-(4-aminopiperidin-1-yl)ethan-1-one hydrochloride salt (0.95 g, 5.30 mmol) in methanol / dichloromethane (1:1 v/v, 20 mL) was added sodium acetate (0.58 g, 7.06 mmol), and the mixture stirred at room temperature for 0.5 hours under N ₂ . Sodium cyanoborohydride (0.44 g, 7.06 mmol) was then added, and the mixture stirred at room temperature for 0.5 hours under N ₂ . Di-tert-butyl dicarbonate (1.55 g, 7.09 mmol) and triethylamine (0.99 mL, 7.09 mmol) were then added, and the mixture stirred at room temperature for 1 hour under N ₂ . Water (50 mL) was added, and the mixture extracted with dichloromethane (2 x 50 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-100%, ethyl acetate / petroleum ether) to afford tert-butyl (1- acetylpiperidin-4-yl)((2',3'-dichloro-6-methoxy-[2,4'-bipyri din]-5-yl)methyl)carbamate (900 mg, 49% yield) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 8.48 (d, 1H), 7.70 (d, 1H), 7.59-7.58 (m, 1H), 7.41 (d, 1H), 4.46-4.42 (m, 1H), 4.30-7.28 (m, 2H), 3.94 (s, 3H), 3.85-3.82 (m, 1H), 3.08-3.02 (m, 1H), 2.60-2.58 (m, 1H), 1.97 (s, 3H), 1.76-1.65 (m, 4H), 1.47-1.29 (m, 13H). (b) tert-Butyl (1-acetylpiperidin-4-yl)((2'-(3-amino-2-methylphenyl)-3'-chl oro-6- methoxy-[2,4'-bipyridin]-5-yl)methyl)carbamate To a mixture of tert-butyl (1-acetylpiperidin-4-yl)((2',3'-dichloro-6-methoxy-[2,4'- bipyridin]-5-yl)methyl)carbamate (850 mg, 1.67 mmol) and 2-methyl-3-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)aniline (467 mg, 2.00 mmol) in 1,4-dioxane / water (5:1 v/v, 12 mL) was added potassium carbonate (692 mg, 5.01 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (136 mg, 0.17 mmol), and the mixture stirred at 110 °C for 2 hours under N ₂ . water (30 mL) was added, and the mixture extracted with ethyl acetate (2 x50 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-100%, ethyl acetate / petroleum ether) to afford tert-butyl (1-acetylpiperidin-4-yl)((2'-(3-amino-2-methylphenyl)- 3'-chloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)carbamate (600 mg, 61% yield) as a yellow solid. LCMS: m/z found 580 [M+H] ⁺ . (c) tert-Butyl (1-acetylpiperidin-4-yl)((3'-chloro-6-methoxy-2'-(3-(4-metho xy-5- vinylpicolinamido)-2-methylphenyl)-[2,4'-bipyridin]-5-yl)met hyl)carbamate To a mixture of tert-butyl (1-acetylpiperidin-4-yl)((2'-(3-amino-2-methylphenyl)-3'- chloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)carbamate (550 mg, 0.95 mmol) and lithium 4-methoxy-5-vinylpicolinate (Example 122, step (b)) (351 mg, 1.90 mmol) in DMF (5 mL) was added N,N-diisopropylethylamine (245 mg, 1.90 mmol) and 2-chloro-1- methylpyridinium iodide (484 mg, 1.90 mmol), and the mixture stirred at room temperature for 2 hours under N ₂ . Water (50 mL) was added and the mixture filtered to afford tert-butyl (1-acetylpiperidin-4-yl)((3'-chloro-6-methoxy-2'-(3-(4-metho xy-5-vinylpicolinamido)-2- methylphenyl)-[2,4'-bipyridin]-5-yl)methyl)carbamate (630 mg, crude) as a brown solid. LCMS: m/z found 741 [M+H] ⁺ . (d) tert-Butyl (1-acetylpiperidin-4-yl)((3'-chloro-2'-(3-(5-formyl-4- methoxypicolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipyrid in]-5- yl)methyl)carbamate To a mixture of tert-butyl (1-acetylpiperidin-4-yl)((3'-chloro-6-methoxy-2'-(3-(4- methoxy-5-vinylpicolinamido)-2-methylphenyl)-[2,4'-bipyridin ]-5-yl)methyl)carbamate (600 mg, 0.81 mmol) in THF / water (20:2 v/v, 22 mL) was added potassium osmate(VI) dihydrate (59.6 mg, 0.16 mmol) at 0°C, and the mixture stirred at 0°C for 0.5 hour. under N ₂ . Sodium periodate (519 mg, 2.43 mmol) was then added, and the mixture stirred at room temperature for 2.5 hours under N ₂ . Water (50 mL) was added, and the mixture extracted with ethyl acetate (2 x 50 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-15%, methanol / ethyl acetate) to afford tert-butyl (1-acetylpiperidin-4- yl)((3'-chloro-2'-(3-(5-formyl-4-methoxypicolinamido)-2-meth ylphenyl)-6-methoxy-[2,4'- bipyridin]-5-yl)methyl)carbamate (240 mg, 39% yield) as a yellow solid. LCMS: m/z found 743 [M+H] ⁺ . (e) tert-Butyl (1-acetylpiperidin-4-yl)((3'-chloro-2'-(3-(5-(((2- hydroxyethyl)amino)methyl)-4-methoxypicolinamido)-2-methylph enyl)-6-methoxy- [2,4'-bipyridin]-5-yl)methyl)carbamate To a mixture of tert-butyl (1-acetylpiperidin-4-yl)((3'-chloro-2'-(3-(5-formyl-4- methoxypicolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipyrid in]-5-yl)methyl)carbamate (110 mg, 0.148 mmol), 2-aminoethanol (18.1 mg, 0.296 mmol) in dichloromethane / methanol (1:1 v/v, 6 mL) was added sodium acetate (36.4 mg, 0.444 mmol), and the mixture stirred at room temperature for 0.5 hours under N ₂ . Sodium cyanoborohydride (27.9 mg, 0.444 mmol) was then added, and the mixture stirred at room temperature for 0.5 hours under N ₂ . The mixture was concentrated and the residue purified by prep-TLC (SiO ₂ , ethyl acetate : methanol = 3:2 v/v) to afford tert-butyl (1-acetylpiperidin-4-yl)((3'-chloro-2'-(3-(5-(((2- hydroxyethyl)amino)methyl)-4-methoxypicolinamido)-2-methylph enyl)-6-methoxy-[2,4'- bipyridin]-5-yl)methyl)carbamate (65 mg, 55% yield) as a white solid. LCMS: m/z found 788 [M+H] ⁺ . (f) N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-4- methoxypicolinamide To mixture of tert-butyl (1-acetylpiperidin-4-yl)((3'-chloro-2'-(3-(5-(((2- hydroxyethyl)amino)methyl)-4-methoxypicolinamido)-2-methylph enyl)-6-methoxy-[2,4'- bipyridin]-5-yl)methyl)carbamate (60 mg, 0.08 mmol) in dichloromethane (5 mL) was added trifluoroacetic acid (2 mL, 26.9 mmol) , and the mixture stirred at room temperature for 0.5 hours under N ₂ . The mixture was concentrated and the residue purified by reverse phase HPLC to afford N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-4- methoxypicolinamide (11.8 mg, 21% yield) as a white solid. LCMS: m/z found 688 [M+H] ⁺ , retention time = 2.35 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.64 (d, 1H), 8.50 (s, 1H), 8.09 (d, 1H), 7.90 (s, 1H), 7.84 (d, 1H), 7.76 (d, 1H), 7.45-7.41 (m, 2H), 7.21 (d, 1H), 4.50-4.47 (m, 1H), 4.12 (s, 3H), 4.08 (s, 3H), 3.97-3.90 (m, 5H), 3.71 (t, 2H), 3.17-3.15 (m, 1H), 2.82-2.71 (m, 4H), 2.18 (s, 3H), 2.12 (s, 3H), 2.08-2.00 (m, 2H), 1.43-1.30 (m, 2H). Example 136: (S)-N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-((((5-ox opyrrolidin-2- yl)methyl)amino)methyl)picolinamide (a) tert-Butyl (S)-(1-acetylpiperidin-4-yl)((3'-chloro-6-methoxy-2'-(3-(4-m ethoxy-5- ((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)picolinamido)-2 -methylphenyl)-[2,4'- bipyridin]-5-yl)methyl)carbamate To a mixture of tert-butyl (1-acetylpiperidin-4-yl)((3'-chloro-2'-(3-(5-formyl-4- methoxypicolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipyrid in]-5-yl)methyl)carbamate (Example 135, step (d)) (110 mg, 0.148 mmol) and (S)-5-(aminomethyl)pyrrolidin-2-one hydrochloride salt (44.6 mg, 0.296 mmol) in dichloromethane / methanol (1:1 v/v, 6 mL) was added sodium acetate (36.4 mg, 444 μmol), and the mixture was stirred at room temperature for 0.5 hours under N ₂ . Sodium cyanoborohydride (27.9 mg, 0.444 mmol) was then added, and the mixture stirred at room temperature for 0.5 hours under N ₂ . The mixture was concentrated and the residue was purified by prep-TLC (SiO ₂ , ethyl acetate : methanol = 3:2 v/v) to afford tert-butyl (S)-(1-acetylpiperidin-4-yl)((3'-chloro-6-methoxy-2'-(3-(4-m ethoxy- 5-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)picolinamido) -2-methylphenyl)-[2,4'- bipyridin]-5-yl)methyl)carbamate (55 mg, 44% yield) as a white solid. LCMS: m/z found 841 [M+H] ⁺ . (b) (S)-N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-((((5-oxopyrro lidin-2- yl)methyl)amino)methyl)picolinamide To a mixture of tert-butyl (S)-(1-acetylpiperidin-4-yl)((3'-chloro-6-methoxy-2'-(3-(4- methoxy-5-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)picol inamido)-2-methylphenyl)- [2,4'-bipyridin]-5-yl)methyl)carbamate (50 mg, 0.06 mmol) in dichloromethane (5 mL) was added trifluoroacetic acid (2 mL, 26.9 mmol), and the mixture stirred at room temperature for 0.5 hours under N ₂ . The mixture was concentrated and the residue was purified by reverse phase HPLC to afford (S)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6- methoxy-[2,4'-bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5- ((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamide (13.7 mg, 29% yield) as a white solid. LCMS: m/z found 741 [M+H] ⁺ , retention time = 2.35 min (Method A). ¹ H NMR (400 MHz, Methanol- d4): δ 8.64 (d, 1H), 8.50 (s, 1H), 8.09 (dd, 1H), 7.88 (s, 1H), 7.84 (d, 1H), 7.76 (d, 1H), 7.45- 7.41 (m, 2H), 7.21 (dd, 1H), 4.51-4.47 (m, 1H), 4.08 (s, 3H), 4.07 (s, 3H), 3.95-3.83 (m, 6H), 3.18-3.17 (m, 1H), 2.75-2.68 (m, 4H), 2.37-2.29 (m, 3H), 2.18 (s, 3H), 2.12 (s, 3H), 2.05- 2.04 (m, 2H), 1.86-1.84 (m, 1H), 1.36-1.28 (m, 2H). Example 137: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-fluorophen yl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide (a) tert-Butyl (S)-((3'-chloro-2'-(3-(5-(dimethoxymethyl)picolinamido)-2- fluorophenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate To a mixture of tert-butyl (S)-((2'-(3-amino-2-fluorophenyl)-3'-chloro-6-methoxy- [2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-yl)methyl)c arbamate (Example 134, step (a)) (300 mg, 0.53 mmol) and lithium 5-(dimethoxymethyl)picolinate (Example 6, step (b)) (328 mg, 1.62 mmol) in DMF (5 mL) was added 2-chloro-1-methylpyridinium iodide (275 mg, 1.08 mmol) and N,N-diisopropylethylamine (209 mg, 1.62 mmol), and the mixture stirred at room temperature for 1 hour under N ₂ . Water (80 mL) was then added, and the resulting suspension filtered to give the solid product. The product was dried under vacuum to afford tert-butyl (S)-((3'-chloro-2'-(3-(5-(dimethoxymethyl)picolinamido)-2-fl uorophenyl)- 6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxopyrrolidin-2-y l)methyl)carbamate (450 mg, crude) as a brown solid. LCMS: m/z found 735 [M+H] ⁺ . (b) (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-fluorophenyl)-5-formylpicolinamide To a solution of tert-butyl (S)-((3'-chloro-2'-(3-(5-(dimethoxymethyl)picolinamido)-2- fluorophenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)((5-oxo pyrrolidin-2- yl)methyl)carbamate (350 mg, 0.47 mmol) in dichloromethane (6 mL) was added trifluoroacetic acid (3 mL, 40.3 mmol), and the mixture stirred at room temperature for 12 hours under N ₂ . The mixture was combined with another batch at the 100 mg scale. Water (50 mL) was added, and the mixture extracted with dichloromethane (2 x 50 mL). The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by normal phase SiO ₂ chromatography (0-48 % methanol / ethyl acetate) to afford (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-fluorophen yl)-5-formylpicolinamide (140 mg) as a brown oil. LCMS: m/z found 589 [M+H] ⁺ . (c) (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-fluorophen yl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide To a mixture of (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-fluorophen yl)-5-formylpicolinamide (100 mg, 0.17 mmol) and 2-aminoethanol (20.7 mg, 0.34 mmol) in dichloromethane / methanol (1:1 v/v, 4 mL) was added sodium acetate (41.7 mg, 0.51 mmol), and the mixture was stirred at room temperature for 0.5 hours under N ₂ . Sodium cyanoborohydride (32.0 mg, 0.51 mmol) was then added, and the mixture stirred at room temperature for 1.5 hours under N ₂ . The mixture was combined with another batch at the 40 mg scale. The mixture was concentrated and the residue purified by prep-HPLC to afford (S)-N-(3-(3'-chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-fluorophenyl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide (59.8 mg) as a white solid. LCMS: m/z found 634 [M+H] ⁺ , retention time = 2.27 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.71 (d, 1H), 8.67 (d, 1H), 8.56-8.52 (m, 1H), 8.24 (d, 1H), 8.06 (dd, 1H), 7.83 (d, 1H), 7.77 (d, 1H), 7.45-7.39 (m, 2H), 7.33-7.29 (m, 1H), 4.07 (s, 3H), 3.96 (s, 2H), 3.91-3.83 (m, 3H), 3.71 (t, 2H), 2.79-2.67 (m, 4H), 2.38-2.29 (m, 3H), 1.86-1.82 (m, 1H). Example 138: (R)-N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxypropyl )amino)methyl)-4- methoxypicolinamide (R)-N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxypropyl)amino )methyl)-4- methoxypicolinamide was prepared in a similar fashion to Example 136, replacing (S)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt with (R)-1-aminopropan-2-ol in step (a). LCMS: m/z found 702 [M+H] ⁺ , retention time = 2.40 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.64 (d, 1H), 8.49 (s, 1H), 8.09 (dd, 1H), 7.89 (s, 1H), 7.84 (d, 1H), 7.76 (d, 1H), 7.45-7.41 (m, 2H), 7.21 (dd, 1H), 4.50-4.46 (m, 1H), 4.08 (s, 3H), 4.06 (s, 3H), 3.96- 3.85 (m, 6H), 3.17-3.15 (m, 1H), 2.80-2.74 (m, 2H), 2.62-2.61 (m, 1H), 2.57-2.54 (m, 1H), 2.18 (s, 3H), 2.12 (s, 3H), 2.07-2.00 (m, 2H), 1.42-1.29 (m, 2H), 1.17 (d, 3H). Example 139: (S)-N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxypyrroli din-1-yl)methyl)-4- methoxypicolinamide (S)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxypyrrolidin-1- yl)methyl)-4- methoxypicolinamide was prepared in a similar fashion to Example 136, replacing (S)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt with (S)-pyrrolidin-3-ol in step (a). LCMS: m/z found 714 [M+H] ⁺ , retention time = 2.42 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.53 (d, 1H), 8.42 (s, 1H), 7.98 (d, 1H), 7.76 (s, 1H), 7.72 (d, 1H), 7.64 (d, 1H), 7.34-7.30 (m, 2H), 7.09 (d, 1H), 4.38-4.35 (m, 1H), 4.27-4.24 (m, 1H), 3.95 (s, 3H), 3.94 (s, 3H), 3.85-3.81 (m, 1H), 3.78 (s, 2H), 3.68 (m, 2H), 3.09-3.02 (m, 1H), 2.79-2.66 (m, 4H), 2.52-2.44 (m, 2H), 2.09-2.05 (m, 4H), 2.01 (s, 3H), 1.96-1.88 (m, 2H), 1.65-1.61 (m, 1H), 1.31-1.18 (m, 2H). Example 140: N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-(hydroxymethyl )azetidin-1-yl)methyl)-4- methoxypicolinamide N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-(hydroxymethyl)azeti din-1-yl)methyl)-4- methoxypicolinamide was prepared in a similar fashion to Example 136, replacing (S)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt with azetidin-3-ylmethanol in step (a). LCMS: m/z found 714 [M+H] ⁺ , retention time = 2.40 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.64 (d, 1H), 8.44 (s, 1H), 8.09 (dd, 1H), 7.87 (s, 1H), 7.83 (d, 1H), 7.76 (d, 1H), 7.45-7.41 (m, 2H), 7.21 (dd, 1H), 4.50-4.46 (m, 1H), 4.06 (s, 3H), 4.05 (s, 3H), 3.97- 3.93 (m, 1H), 3.89 (s, 2H), 3.76 (s, 2H), 3.67 (d, 2H), 3.50 (t, 2H), 3.20-3.16 (m, 3H), 2.80- 2.70 (m, 3H), 2.18 (s, 3H), 2.12 (s, 3H), 2.07-2.04 (m, 2H), 1.44-1.29 (m, 2H). Example 141: N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy- [2,4'-bipyridin]-2'-yl)-2-chlorophenyl)-5-(((2-hydroxyethyl) amino)methyl)-4- methoxypicolinamide (a) tert-Butyl (1-acetylpiperidin-4-yl)((2'-(3-amino-2-chlorophenyl)-3'-chl oro-6- methoxy-[2,4'-bipyridin]-5-yl)methyl)carbamate A mixture of tert-butyl (1-acetylpiperidin-4-yl)((2',3'-dichloro-6-methoxy-[2,4'- bipyridin]-5-yl)methyl)carbamate (Example 135, step (a)) (8 g, 15.70 mmol), 2-chloro-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (5.97 g, 23.6 mmol), [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1.28 g, 1.57 mmol) and potassium carbonate (6.51 g, 47.11 mmol) in water / 1,4-dioxane (1:5 v/v, 180 mL) was stirred at 110 °C for 2 hours under N ₂ . The mixture was combined with another batch at 0.3 g scale. Water (100 mL) was added, and the mixture extracted with ethyl acetate (2 x 300 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-100% ethyl acetate / petroleum ether) to afford tert-butyl (1- acetylpiperidin-4-yl)((2'-(3-amino-2-chlorophenyl)-3'-chloro -6-methoxy-[2,4'-bipyridin]-5- yl)methyl)carbamate (7 g) as a yellow solid. LCMS: m/z found 600 [M+H] ⁺ . (b) tert-Butyl (1-acetylpiperidin-4-yl)((3'-chloro-2'-(2-chloro-3-(4-methox y-5- vinylpicolinamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)me thyl)carbamate A mixture of tert-butyl (1-acetylpiperidin-4-yl)((2'-(3-amino-2-chlorophenyl)-3'- chloro-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)carbamate (5 g, 8.33 mmol) and lithium 4- methoxy-5-vinylpicolinate (Example 122, step (b)) (3.85 g, 20.8 mmol), 2-chloro-1- methylpyridinium iodide (4.25 g, 16.7 mmol) and N,N-diisopropylethylamine (2.9 mL, 16.7mmol) in DMF (30 mL) was stirred at room temperature for 1 hour under N ₂ . The mixture was combined with another batch at 2.55 g scale. Water (200 mL) was added, and the resulting suspension filtered. The filter cake was dried under vacuum to afford tert-butyl (1-acetylpiperidin-4-yl)((3'-chloro-2'-(2-chloro-3-(4-methox y-5-vinylpicolinamido)phenyl)- 6-methoxy-[2,4'-bipyridin]-5-yl)methyl)carbamate (9 g, crude) as a black solid. LCMS: m/z found 761 [M+H] ⁺ . (c) tert-Butyl (1-acetylpiperidin-4-yl)((3'-chloro-2'-(2-chloro-3-(5-formyl -4- methoxypicolinamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-yl) methyl)carbamate To a solution of tert-butyl (1-acetylpiperidin-4-yl)((3'-chloro-2'-(2-chloro-3-(4- methoxy-5-vinylpicolinamido)phenyl)-6-methoxy-[2,4'-bipyridi n]-5-yl)methyl)carbamate (9 g, 11.8 mmol) in water / THF (1:9 v/v, 100 mL) was added potassium osmate(VI) dihydrate (0.87 g, 2.36 mmol) at 0 °C, and the mixture stirred at 0 °C for 0.5 hours. Sodium periodate (17.7 g, 82.7 mmol) was added, and the mixture stirred at room temperature for 12 hours. The mixture was concentrated, water (150 mL) added to the residue and the mixture extracted with ethyl acetate (2 x 400 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-10% methanol / ethyl acetate) to afford tert-butyl (1- acetylpiperidin-4-yl)((3'-chloro-2'-(2-chloro-3-(5-formyl-4- methoxypicolinamido)phenyl)-6- methoxy-[2,4'-bipyridin]-5-yl)methyl)carbamate (2 g) as a brown solid. LCMS: m/z found 763 [M+H] ⁺ . (d) tert-Butyl (1-acetylpiperidin-4-yl)((3'-chloro-2'-(2-chloro-3-(5-(((2- hydroxyethyl)amino)methyl)-4-methoxypicolinamido)phenyl)-6-m ethoxy-[2,4'- bipyridin]-5-yl)methyl)carbamate To a solution of tert-butyl (1-acetylpiperidin-4-yl)((3'-chloro-2'-(2-chloro-3-(5- formyl-4-methoxypicolinamido)phenyl)-6-methoxy-[2,4'-bipyrid in]-5-yl)methyl)carbamate (170 mg, 0.22 mmol) and 2-aminoethan-1-ol (27.2 mg, 0.45 mmol) in dichloromethane / methanol (1:1 v/v, 4 mL) was added sodium acetate (54.8 mg, 0.67 mmol), and the mixture stirred at room temperature for 1 hour. Sodium cyanoborohydride (42.0 mg, 0.67 mmol) was then added, and the mixture stirred at room temperature for 0.5 hours. Water (20 mL) was added, and the mixture extracted with dichloromethane (2 x 30 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure. The residue was purified by prep-TLC (SiO ₂ , methanol : ethyl acetate = 1:1 v/v) to afford tert-butyl (1-acetylpiperidin-4-yl)((3'-chloro-2'-(2-chloro-3-(5-(((2- hydroxyethyl)amino)methyl)-4-methoxypicolinamido)phenyl)-6-m ethoxy-[2,4'-bipyridin]-5- yl)methyl)carbamate (60 mg, 31% yield) as a yellow solid. LCMS: m/z found 808 [M+H] ⁺ . (e) N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)-5-(((2-hydroxyethyl)amino) methyl)-4- methoxypicolinamide To a solution of tert-butyl (1-acetylpiperidin-4-yl)((3'-chloro-2'-(2-chloro-3-(5-(((2- hydroxyethyl)amino)methyl)-4-methoxypicolinamido)phenyl)-6-m ethoxy-[2,4'-bipyridin]-5- yl)methyl)carbamate (50 mg, 0.06 mmol) in dichloromethane (1 mL) was added trifluoroacetic acid (0.5 mL, 6.73 mmol), and the mixture stirred at room temperature for 1 hour. The residue was purified by reverse phase HPLC to afford N-(3-(5-(((1-acetylpiperidin- 4-yl)amino)methyl)-3'-chloro-6-methoxy-[2,4'-bipyridin]-2'-y l)-2-chlorophenyl)-5-(((2- hydroxyethyl)amino)methyl)-4-methoxypicolinamide (13.8 mg, 34 % yield) as a white solid. LCMS: m/z found 708 [M+H] ⁺ , retention time = 2.61 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.59 (dd, 1H), 8.54 (d, 1H), 8.38 (s, 1H), 7.80 (s, 1H), 7.72 (d, 1H), 7.69 (d, 1H), 7.44 (t, 1H), 7.33 (d, 1H), 7.16 (dd, 1H), 4.38-4.34 (m, 1H), 3.97 (s, 3H), 3.95 (s, 3H), 3.85-3.78 (m, 5H), 3.58 (t, 2H), 3.08-3.02 (m, 1H), 2.70-2.59 (m, 4H), 2.00 (s, 3H), 1.94-1.91 (m, 2H), 1.30-1.17 (m, 2H). Example 142: (S)-N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxypropyl )amino)methyl)-4- methoxypicolinamide (S)-N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxypropyl)amino )methyl)-4- methoxypicolinamide was prepared in a similar fashion to Example 136, replacing (S)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt with (S)-1-aminopropan-2-ol in step (a). LCMS: m/z found 702 [M+H] ⁺ , retention time = 2.38 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.64 (d, 1H), 8.49 (s, 1H), 8.09 (d, 1H), 7.89 (s, 1H), 7.84 (d, 1H), 7.76 (d, 1H), 7.45-7.41 (m, 2H), 7.21 (d, 1H), 4.50-4.47 (m, 1H), 4.08 (s, 3H), 4.06 (s, 3H), 3.97-3.87 (m, 6H), 3.20-3.15 (m, 1H), 2.83-2.55 (m, 4H), 2.19 (s, 3H), 2.12 (s, 3H), 2.07-2.00 (m, 2H), 1.42-1.31 (m, 2H), 1.18 (d, 3H). Example 143: (R)-N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxypyrroli din-1-yl)methyl)-4- methoxypicolinamide (R)-N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxypyrrolidin-1- yl)methyl)-4- methoxypicolinamide was prepared in a similar fashion to Example 136, replacing (S)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt with (R)-pyrrolidin-3-ol in step (a). LCMS: m/z found 714 [M+H] ⁺ , retention time = 2.36 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.64 (d, 1H), 8.53 (s, 1H), 8.09 (dd, 1H), 7.88 (s, 1H), 7.84 (d, 1H), 7.76 (d, 1H), 7.45-7.41 (m, 2H), 7.21 (dd, 1H), 4.50-4.47 (m, 1H), 4.39-4.34 (m, 1H), 4.06 (s, 3H), 4.05 (s, 3H), 3.97-3.93 (m, 1H), 3.89 (s, 2H), 3.80 (d, 2H), 3.20-3.14 (m, 1H), 2.91-2.70 (m, 4H), 2.63-2.56 (m, 2H), 2.20-2.15 (m, 4H), 2.12 (s, 3H), 2.06-2.00 (m, 2H), 1.76-1.72 (m, 1H), 1.42-1.29 (m, 2H). Example 144: N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-((3-(met hoxymethyl)azetidin-1- yl)methyl)picolinamide N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-((3-(methoxyme thyl)azetidin-1- yl)methyl)picolinamide was prepared in a similar fashion to Example 136, replacing (S)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt with 3-(methoxymethyl)azetidine in step (a). LCMS: m/z found 728 [M+H] ⁺ , retention time = 2.56 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.53 (d, 1H), 8.31 (s, 1H), 7.97 (d, 1H ), 7.75 (s, 1H), 7.72 (d, 1H), 7.64 (d, 1H), 7.34-7.30 (m, 2H), 7.09 (d, 1H), 4.39-4.35 (m, 1H), 3.95 (s, 3H), 3.94 (s, 3H), 3.85-3.81 (m, 1H), 3.78 (s, 2H), 3.64 (s, 2H), 3.42-3.39 (m, 4H), 3.25 (s, 3H), 3.08-3.05 (m, 3H), 2.70-2.63 (m, 3H), 2.07 (s, 3H), 2.01 (s, 3H), 1.96-1.89 (m, 2H), 1.33-1.18 (m, 2H). Example 145: (S)-N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy- [2,4'-bipyridin]-2'-yl)-2-chlorophenyl)-4-methoxy-5-((((5-ox opyrrolidin-2- yl)methyl)amino)methyl)picolinamide (a) tert-Butyl (S)-(1-acetylpiperidin-4-yl)((3'-chloro-2'-(2-chloro-3-(4-me thoxy-5- ((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)picolinamido)ph enyl)-6-methoxy-[2,4'- bipyridin]-5-yl)methyl)carbamate To a solution of tert-butyl (1-acetylpiperidin-4-yl)((3'-chloro-2'-(2-chloro-3-(5- formyl-4-methoxypicolinamido)phenyl)-6-methoxy-[2,4'-bipyrid in]-5-yl)methyl)carbamate (Example 141, step (c)) (200 mg, 0.26 mmol) and (S)-5-(aminomethyl)pyrrolidin-2-one hydrochloride salt (78.9 mg, 0.52 mmol) in dichloromethane / methanol (1:1 v/v, 4 mL) was added sodium acetate (64.5 mg, 0.79 mmol), and the mixture stirred at room temperature for 1 hour. Sodium cyanoborohydride (49.4 mg, 0.79 mmol) was then added, and the mixture stirred at room temperature for 0.5 hours. Water (20 mL) was added, and the mixture extracted with dichloromethane (2 x 30 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure. The residue was purified by prep-TLC (SiO ₂ , methanol : ethyl acetate = 1:1 v/v) to afford tert-butyl (S)-(1- acetylpiperidin-4-yl)((3'-chloro-2'-(2-chloro-3-(4-methoxy-5 -((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamido)phenyl)-6-methoxy-[2,4'- bipyridin]-5- yl)methyl)carbamate (100 mg, 39% yield) as a yellow solid. LCMS: m/z found 861 [M+H] ⁺ . (b) (S)-N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)-4-methoxy-5-((((5-oxopyrro lidin-2- yl)methyl)amino)methyl)picolinamide To a solution of tert-butyl (S)-(1-acetylpiperidin-4-yl)((3'-chloro-2'-(2-chloro-3-(4- methoxy-5-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)picol inamido)phenyl)-6-methoxy- [2,4'-bipyridin]-5-yl)methyl)carbamate (90 mg, 0.09 mmol) in dichloromethane (1 mL) was added trifluoroacetic acid (0.5 mL, 6.73 mmol), and the mixture stirred at room temperature for 1 hour. The mixture was concentrated and the residue purified by reverse phase HPLC to afford (S)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)-4-methoxy-5-((((5-oxopyrro lidin-2- yl)methyl)amino)methyl)picolinamide (14.9 mg, 20 % yield) as a white solid. LCMS: m/z found 761 [M+H] ⁺ , retention time = 2.61 min (Method A). ¹ H NMR (400 MHz, Methanol- d4): δ 8.71 (d, 1H), 8.67 (d, 1H), 8.51 (s, 1H), 7.92 (s, 1H), 7.85 (d, 1H), 7.82 (d, 1H), 7.57 (t, 1H), 7.46 (d, 1H), 7.29 (d, 1H), 4.51-4.47 (m, 1H), 4.09 (s, 3H), 4.08 (s, 3H), 3.97-3.84 (m, 6H), 3.21-3.15 (m, 1H), 2.82-2.68 (m, 4H), 2.38-2.28 (m, 3H), 2.13 (s, 3H), 2.07-2.01 (m, 2H), 1.85-1.83 (m, 1H), 1.43-1.30 (m, 2H). Example 146: (S)-N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy- [2,4'-bipyridin]-2'-yl)-2-chlorophenyl)-5-((3-hydroxypyrroli din-1-yl)methyl)-4- methoxypicolinamide (S)-N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)-5-((3-hydroxypyrrolidin-1- yl)methyl)-4- methoxypicolinamide was prepared in a similar fashion to Example 145, replacing (S)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt with (S)-pyrrolidin-3-ol in step (a). LCMS: m/z found 734 [M+H] ⁺ , retention time = 2.66 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.69 (d, 1H), 8.64 (d, 1H), 8.52 (s, 1H), 7.88 (s, 1H), 7.82 (d, 1H), 7.79 (d, 1H), 7.54 (t, 1H), 7.43 (d, 1H), 7.26 (d, 1H), 4.48-4.44 (m, 1H), 4.37-4.33 (m, 1H), 4.05 (s, 6H), 3.94-3.91 (m, 1H), 3.88 (s, 2H), 3.82-3.74 (m, 2H), 3.18-3.12 (m, 1H), 2.87-2.73 (m, 4H), 2.58-2.54 (m, 2H), 2.18-2.13 (m, 1H), 2.10 (s, 3H), 2.06-1.98 (m, 2H), 1.74-1.70 (m, 1H), 1.40-1.29 (m, 2H). Example 147: N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy- [2,4'-bipyridin]-2'-yl)-2-chlorophenyl)-5-((3-(hydroxymethyl )azetidin-1-yl)methyl)-4- methoxypicolinamide N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)-5-((3-(hydroxymethyl)azeti din-1-yl)methyl)-4- methoxypicolinamide was prepared in a similar fashion to Example 145, replacing (S)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt with azetidin-3-ylmethanol in step (a). LCMS: m/z found 734 [M+H] ⁺ , retention time = 2.65 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.70 (dd, 1H), 8.66 (d, 1H), 8.43 (s, 1H), 7.89 (s, 1H), 7.84 (d, 1H), 7.80 (d, 1H), 7.56 (t, 1H), 7.45 (d, 1H), 7.27 (dd, 1H), 4.50-4.46 (m, 1H), 4.07 (s, 3H), 4.06 (s, 3H), 3.93-3.90 (m, 1H), 3.89 (s, 2H), 3.76 (s, 2H), 3.67 (d, 2H), 3.50 (t, 2H), 3.20-3.16 (m, 3H), 2.83-2.68 (m, 3H), 2.12 (s, 3H), 2.08-2.00 (m, 2H), 1.44-1.29 (m, 2H). Example 148: 1-((6-((3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chlo ro-6-methoxy- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)carbamoyl)-4-methoxyp yridin-3- yl)methyl)piperidine-4-carboxylic acid (a) tert-butyl 1-((6-((3-(5-(((1-acetylpiperidin-4-yl)(tert- butoxycarbonyl)amino)methyl)-3'-chloro-6-methoxy-[2,4'-bipyr idin]-2'-yl)-2- methylphenyl)carbamoyl)-4-methoxypyridin-3-yl)methyl)piperid ine-4-carboxylate To a mixture of tert-butyl (1-acetylpiperidin-4-yl)((3'-chloro-2'-(3-(5-formyl-4- methoxypicolinamido)-2-methylphenyl)-6-methoxy-[2,4'-bipyrid in]-5-yl)methyl)carbamate (Example 135, step (d)) (200 mg, 0.27 mmol) and tert-butyl piperidine-4-carboxylate (179 mg, 0.81 mmol) in methanol / THF (1:1 v/v, 5 mL) was added sodium acetate (66.2 mg, 0.81 mmol), and the mixture stirred at 60 °C for 1 hour under N ₂ . Sodium cyanoborohydride (50.7 mg, 0.81 mmol) was then added, and the mixture stirred at room temperature for 1 hour under N ₂ . The mixture was combined with another batch at the 30 mg scale. Water (50 mL) was added, and the mixture extracted with dichloromethane (2 x 50 mL). The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by prep-TLC (SiO ₂ , dichloromethane / methanol = 10:1 v/v) to afford tert-butyl 1- ((6-((3-(5-(((1-acetylpiperidin-4-yl)(tert-butoxycarbonyl)am ino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'-yl)-2-methylphenyl)carbamoyl)-4- methoxypyridin-3- yl)methyl)piperidine-4-carboxylate (50 mg) as a white solid. LCMS: m/z found 912 [M+H] ⁺ . (b) 1-((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlo ro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)carbamoyl)-4-methoxypyridin -3-yl)methyl)piperidine- 4-carboxylic acid To a solution of tert-butyl 1-((6-((3-(5-(((1-acetylpiperidin-4-yl)(tert- butoxycarbonyl)amino)methyl)-3'-chloro-6-methoxy-[2,4'-bipyr idin]-2'-yl)-2- methylphenyl)carbamoyl)-4-methoxypyridin-3-yl)methyl)piperid ine-4-carboxylate (40 mg, 0.04 mmol) in dichloromethane (3 mL) was added trifluoroacetic acid (0.3 mL, 4.04 mmol), and the mixture stirred at room temperature for 1 hour under N ₂ . The mixture was combined with another batch at the 10 mg scale. The mixture was concentrated and the residue purified by prep-HPLC to afford 1-((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlo ro-6- methoxy-[2,4'-bipyridin]-2'-yl)-2-methylphenyl)carbamoyl)-4- methoxypyridin-3- yl)methyl)piperidine-4-carboxylic acid (23.4 mg) as a white solid. LCMS: m/z found 756 [M+H] ⁺ , retention time = 2.47 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.65 (d, 1H), 8.57 (s, 1H), 8.08 (d, 1H), 7.92 (s, 1H), 7.86 (d, 1H), 7.75 (d, 1H), 7.47-7.41 (m, 2H), 7.21 (d, 1H), 4.55-4.50 (m, 1H), 4.09 (s, 3H), 4.08 (s, 3H), 3.98 (m, 5H), 3.18-3.15 (m, 3H), 2.93-2.88 (m, 1H), 2.77-2.71 (m, 1H), 2.59-2.58 (m, 1H), 2.36-2.27 (m, 1H), 2.18 (s, 3H), 2.13 (s, 3H), 2.08-1.98 (m, 4H), 1.86-1.83 (m, 2H), 1.47-1.31 (m, 3H). Example 149: N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy- [2,4'-bipyridin]-2'-yl)-2-chlorophenyl)-4-methoxy-5-((3-(met hoxymethyl)azetidin-1- yl)methyl)picolinamide N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)-4-methoxy-5-((3-(methoxyme thyl)azetidin-1- yl)methyl)picolinamide was prepared in a similar fashion to Example 145, replacing (S)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt with 3-(methoxymethyl)azetidine hydrochloride salt in step (a). LCMS: m/z found 748 [M+H] ⁺ , retention time = 2.82 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.58 (dd, 1H), 8.54 (d, 1H), 8.31 (s, 1H), 7.77 (s, 1H), 7.72 (d, 1H), 7.69 (d, 1H), 7.44 (t, 1H), 7.33 (d, 1H), 7.15 (dd, 1H), 4.38-4.34 (m, 1H), 3.95 (s, 3H), 3.94 (s, 3H), 3.84-3.81 (m, 1H), 3.78 (s, 2H), 3.64 (s, 2H), 3.41-3.37 (m, 4H), 3.24 (s, 3H), 3.06 (t, 3H), 2.71-2.59 (m, 3H), 2.00 (s, 3H), 1.95-1.88 (m, 2H), 1.21- 1.20 (m, 2H). Example 150: (R)-N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy- [2,4'-bipyridin]-2'-yl)-2-chlorophenyl)-5-((3-hydroxypyrroli din-1-yl)methyl)-4- methoxypicolinamide (R)-N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)-5-((3-hydroxypyrrolidin-1- yl)methyl)-4- methoxypicolinamide was prepared in a similar fashion to Example 145, replacing (S)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt with (R)-pyrrolidin-3-ol in step (a). LCMS: m/z found 734 [M+H] ⁺ , retention time = 2.79 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.71 (dd, 1H), 8.66 (d, 1H), 8.54 (s, 1H), 7.91 (s, 1H), 7.84 (d, 1H), 7.81 (d, 1H), 7.56 (t, 1H), 7.45 (d, 1H), 7.28 (dd, 1H), 4.50-4.46 (m, 1H), 4.38-4.35 (m, 1H), 4.07 (s, 3H), 4.06 (s, 3H), 3.97-3.93 (m, 1H), 3.89 (s, 2H), 3.84-3.76 (m, 2H), 3.20-3.14 (m, 1H), 2.90-2.77 (m, 4H), 2.59-2.56 (m, 2H), 2.20-2.15 (m, 1H), 2.12 (s, 3H), 2.07-2.00 (m, 2H), 1.75-1.74 (m, 1H), 1.42-1.29 (m, 2H). Example 151: (S)-N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy- [2,4'-bipyridin]-2'-yl)-2-chlorophenyl)-5-(((2-hydroxypropyl )amino)methyl)-4- methoxypicolinamide (S)-N-(3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)-5-(((2-hydroxypropyl)amino )methyl)-4- methoxypicolinamide was prepared in a similar fashion to Example 145, replacing (S)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt with (S)-1-aminopropan-2-ol in step (a). LCMS: m/z found 722 [M+H] ⁺ , retention time = 2.83 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.59 (dd, 1H), 8.54 (d, 1H), 8.37 (s, 1H), 7.80 (s, 1H), 7.72 (d, 1H), 7.69 (d, 1H), 7.45 (t, 1H), 7.34 (d, 1H), 7.16 (dd, 1H), 4.38-3.35 (m, 1H), 3.97 (s, 3H), 3.96 (s, 3H), 3.84-3.73 (m, 6H), 3.09-3.02 (m, 1H), 2.70-2.60 (m, 2H), 2.53-2.40 (m, 2H), 2.01 (s, 3H), 1.96-1.88 (m, 2H), 1.33-1.18 (m, 2H), 1.06 (d, 3H). Example 152: (R)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy- [2,4'-bipyridin]-2'-yl)-2-chlorophenyl)-5-(((2-hydroxypropyl )amino)methyl)-4- methoxypicolinamide (R)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)-5-(((2-hydroxypropyl)amino )methyl)-4- methoxypicolinamide was prepared in a similar fashion to Example 145, replacing (R)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt with (S)-1-aminopropan-2-ol in step (a). LCMS: m/z found 722 [M+H] ⁺ , retention time = 2.83 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.70 (dd, 1H), 8.66 (d, 1H), 8.48 (s, 1H), 7.91 (s, 1H), 7.83 (d, 1H), 7.80 (d, 1H), 7.56 (t, 1H), 7.44 (d, 1H), 7.27 (dd, 1H), 4.49-4.46 (m, 1H), 4.08 (s, 3H), 4.06 (s, 3H), 3.96-3.84 (m, 6H), 3.20-3.13 (m, 1H), 2.81-2.74 (m, 2H), 2.64-2.53 (m, 2H), 2.12 (s, 3H), 2.03-1.99 (m, 2H), 1.44-1.29 (m, 2H), 1.17 (d, 3H). Example 153: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methoxyphe nyl)-5-(((2- hydroxyethyl)amino)methyl)-4-methoxypicolinamide (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methoxyphenyl)-5-(((2-hydroxyethyl )amino)methyl)-4- methoxypicolinamide was prepared in a similar fashion to Example 134, replacing 2-fluoro- 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline with 2-methoxy-3-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)aniline in step (a). LCMS: m/z found 676 [M+H] ⁺ , retention time = 2.51 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.66 (d, 1H), 8.63 (dd, 1H), 8.49 (s, 1H), 7.91 (s, 1H), 7.83 (d, 1H), 7.77 (d, 1H), 7.45 (d, 1H), 7.33 (t, 1H), 7.17 (dd, 1H), 4.09 (s, 3H), 4.07 (s, 3H), 3.90 (s, 2H), 3.87-3.86 (m, 3H), 3.69 (t, 2H), 3.63 (s, 3H), 2.76-2.70 (m, 4H), 2.36-2.34 (m, 3H), 1.89-1.82 (m, 1H). Example 154: 1-((6-((3-(5-(((1-a\Acetylpiperidin-4-yl)amino)methyl)-3'-ch loro-6- methoxy-[2,4'-bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4- methoxypyridin-3- yl)methyl)piperidine-4-carboxylic acid 1-((6-((3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chlo ro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3-yl)methyl)piperidine-4- carboxylic acid was prepared in a similar fashion to Example 145, replacing (S)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt with tert-butyl piperidine-4-carboxylate in step (a). White solid, LCMS: m/z found 776 [M+H] ⁺ , retention time = 2.79 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.70 (dd, 1H), 8.67 (d, 1H), 8.57 (s, 1H), 7.95 (s, 1H), 7.87 (d, 1H), 7.80 (d, 1H), 7.57 (t, 1H), 7.47 (d, 1H), 7.28 (dd, 1H), 4.55-4.51 (m, 1H), 4.10 (s, 3H), 4.08 (s, 3H), 3.99-3.97 (m, 5H), 3.20-3.15 (m, 3H), 2.99-2.94 (m, 1H), 2.77-2.70 (m, 1H), 2.61-2.54 (m, 2H), 2.33-2.27 (m, 1H), 2.13 (s, 3H), 2.09-1.97 (m, 4H), 1.85-1.83 (m, 2H), 1.47-1.34 (m, 2H). Example 155: (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methoxyphe nyl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide (S)-N-(3-(3'-Chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methoxyphenyl)-5-(((2-hydroxyethyl )amino)methyl)picolinamide was prepared in a similar fashion to Example 67, replacing 2-chloro-3-methyl-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine with 2,3-dichloro-4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)pyridine in step (a) and 2-methyl-3-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)aniline with 2-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)aniline in step (c). White solid, LCMS: m/z found 646 [M+H] ⁺ , retention time = 2.36 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.71 (s, 1H), 8.66-8.62 (m, 2H), 8.25 (d, 1H), 8.06 (d, 1H), 7.83 (d, 1H), 7.78 (d, 1H), 7.45 (d, 1H), 7.33 (t, 1H), 7.17 (dd, 1H), 4.07 (s, 3H), 3.96 (s, 2H), 3.87-3.86 (m, 3H), 3.70 (t, 2H), 3.63 (s, 3H), 2.79-2.70 (m, 4H), 2.38-2.29 (m, 3H), 1.91-1.82 (m, 1H). Example 156: 3-(((6-((3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chl oro-6- methoxy-[2,4'-bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4- methoxypyridin-3- yl)methyl)amino)-2,2-dimethylpropanoic acid 3-(((6-((3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chl oro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3-yl)methyl)amino)-2,2- dimethylpropanoic acid was prepared in a similar fashion to Example 145, replacing (S)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt with 3-amino-2,2-dimethylpropanoic acid in step (a). LCMS: m/z found 764 [M+H] ⁺ , retention time = 2.86 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.70 (dd, 1H), 8.66 (d, 1H), 8.57 (s, 1H), 8.01 (s, 1H), 7.85 (d, 1H), 7.81 (d, 1H), 7.57 (t, 1H), 7.45 (d, 1H), 7.29 (dd, 1H), 4.51-4.48 (m, 1H), 4.28 (s, 2H), 4.18 (s, 3H), 4.07 (s, 3H), 3.98-3.93 (m, 3H), 3.17-3.14 (m, 1H), 3.01 (s, 2H), 2.85-2.74 (m, 2H), 2.12 (s, 3H), 2.09-2.01 (m, 2H), 1.35-1.31 (m, 2H), 1.22 (s, 6H). Example 157: (1r,4r)-4-(((6-((3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl )-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4- methoxypyridin-3- yl)methyl)amino)cyclohexane-1-carboxylic acid (1r,4r)-4-(((6-((3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl )-3'-chloro-6-methoxy- [2,4'-bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxyp yridin-3- yl)methyl)amino)cyclohexane-1-carboxylic acid was prepared in a similar fashion to Example 145, replacing (S)-5-(aminomethyl)pyrrolidin-2-one hydrochloride salt with (1r,4r)-4-aminocyclohexane-1-carboxylic acid in step (a). LCMS: m/z found 790 [M+H] ⁺ , retention time = 2.92 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.70 (dd, 1H), 8.66 (d, 1H), 8.57 (s, 1H), 7.99 (s, 1H), 7.85 (d, 1H), 7.81 (d, 1H), 7.57 (t, 1H), 7.45 (d, 1H), 7.29 (dd, 1H), 4.51-4.48 (m, 1H), 4.22 (s, 2H), 4.14 (s, 3H), 4.07 (s, 3H), 3.97-3.93 (m, 3H), 3.21-3.14 (m, 1H), 3.01-2.99 (m, 1H), 2.87-2.85 (m, 1H), 2.74-2.71 (m, 1H), 2.12-2.02 (m, 10H), 1.54-1.35 (m, 6H). Example 158: (1s,4s)-4-(((6-((3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl )-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4- methoxypyridin-3- yl)methyl)amino)cyclohexane-1-carboxylic acid (1s,4s)-4-(((6-((3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl )-3'-chloro-6-methoxy- [2,4'-bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxyp yridin-3- yl)methyl)amino)cyclohexane-1-carboxylic acid was prepared in a similar fashion to Example 145, replacing (S)-5-(aminomethyl)pyrrolidin-2-one hydrochloride salt with (1s,4s)-4-aminocyclohexane-1-carboxylic acid in step (a). LCMS: m/z found 790 [M+H] ⁺ , retention time = 2.97 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.70 (dd, 1H), 8.66 (d, 1H), 8.59 (s, 1H), 7.99 (s, 1H), 7.85 (d, 1H), 7.80 (d, 1H), 7.57 (t, 1H), 7.45 (d, 1H), 7.29 (dd, 1H), 4.51-4.48 (m, 1H), 4.25 (s, 2H), 4.14 (s, 3H), 4.07 (s, 3H), 3.98-3.93 (m, 3H), 3.17-3.14 (m, 2H), 2.87-2.85 (m, 1H), 2.75-2.74 (m, 1H), 2.48-2.46 (m, 1H), 2.21-2.19 (m, 2H), 2.18 (s, 3H), 2.17-1.93 (m, 4H), 1.78-1.75 (m, 2H), 1.64-1.60 (m, 2H), 1.35-1.31 (m, 2H). Example 159: N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (R)-2- hydroxypropyl)amino)methyl)-4-methoxypicolinamide N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (R)-2- hydroxypropyl)amino)methyl)-4-methoxypicolinamide was prepared in a similar fashion to Example 123, replacing 2-aminoethanol with (R)-1-aminopropan-2-ol in step (a). LCMS: m/z found 694 [M+H] ⁺ , retention time = 1.63 min (Method D). ¹ H NMR (400 MHz, Methanol-d4) δ 8.70 – 8.61 (m, 2H), 8.44 (s, 1H), 7.90 – 7.73 (m, 3H), 7.52 (t, 1H), 7.41 (d, 1H), 7.23 (dd, 1H), 4.03 (d, 6H), 3.94 – 3.75 (m, 4H), 3.32 (d, 2H), 2.74 – 2.43 (m, 3H), 2.38 – 2.18 (m, 3H), 1.89 – 1.72 (m, 1H), 1.26 (s, 1H), 1.20 – 1.09 (m, 3H). Example 160: N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (S)-2- hydroxypropyl)amino)methyl)-4-methoxypicolinamide N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (S)-2- hydroxypropyl)amino)methyl)-4-methoxypicolinamide was prepared in a similar fashion to Example 123, replacing 2-aminoethanol with (S)-1-aminopropan-2-ol in step (a). LCMS: m/z found 694 [M+H] ⁺ , retention time = 1.63 min (Method D). ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.71 – 8.58 (m, 2H), 8.44 (s, 1H), 7.87 (s, 1H), 7.83 – 7.73 (m, 2H), 7.52 (t, 1H), 7.41 (d, 1H), 7.23 (dd, 1H), 4.03 (d, 6H), 3.91 – 3.75 (m, 4H), 3.32 (d, 2H), 2.75 – 2.43 (m, 3H), 2.38 – 2.18 (m, 3H), 1.89 – 1.72 (m, 1H), 1.26 (s, 1H), 1.13 (d, 3H). Example 161: (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 3- hydroxypropyl)amino)methyl)-4-methoxypicolinamide (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( 3- hydroxypropyl)amino)methyl)-4-methoxypicolinamide was prepared in a similar fashion to Example 123, replacing 2-aminoethanol with 3-aminopropan-1-ol in step (a). LCMS: m/z found 694 [M+H] ⁺ , retention time = 1.60 min (Method D). ¹ H NMR (400 MHz, Methanol-d4) δ 8.70 – 8.56 (m, 2H), 8.44 (s, 1H), 7.87 (s, 1H), 7.83 – 7.72 (m, 2H), 7.51 (t, 1H), 7.40 (d, 1H), 7.23 (dd, 1H), 4.02 (d, 6H), 3.91 – 3.75 (m, 5H), 3.60 (t, 2H), 3.32 (s, 1H), 2.76 – 2.59 (m, 4H), 2.38 – 2.17 (m, 3H), 1.89 – 1.68 (m, 2H). Example 162: (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (1- hydroxycyclopropyl)methyl)amino)methyl)-4-methoxypicolinamid e (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (1- hydroxycyclopropyl)methyl)amino)methyl)-4-methoxypicolinamid e was prepared in a similar fashion to Example 123, replacing 2-aminoethanol with 1- (aminomethyl)cyclopropan-1-ol in step (a). LCMS: m/z found 706 [M+H] ⁺ , retention time = 1.67 min (Method D). ¹ H NMR (400 MHz, Methanol-d4) δ 8.71 – 8.59 (m, 2H), 8.46 (s, 1H), 7.88 (s, 1H), 7.84 – 7.74 (m, 2H), 7.52 (t, 1H), 7.41 (d, 1H), 7.24 (dd, 1H), 4.03 (d, 5H), 3.91 (s, 2H), 3.82 (d, 3H), 3.32 (s, 2H), 2.75 – 2.59 (m, 4H), 2.36 – 2.23 (m, 1H), 1.89 – 1.73 (m, 1H), 1.26 (s, 1H), 0.69 (t, 2H), 0.52 (t, 2H). Example 163: 3-(((6-((3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chl oro-6- methoxy-[2,4'-bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4- methoxypyridin-3- yl)methyl)amino)propanoic acid 3-(((6-((3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chl oro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3-yl)methyl)amino)propanoic acid was prepared in a similar fashion to Example 145, replacing (S)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt with 3-aminopropanoic acid in step (a). LCMS: m/z found 736 [M+H] ⁺ , retention time = 2.63 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.60-8.57 (m, 2H), 8.47 (s, 1H), 7.90 (s, 1H), 7.84 (d, 1H), 7.68 (d, 1H), 7.46 (t, 1H), 7.40 (d, 1H), 7.18 (dd, 1H), 4.55-4.52 (m, 1H), 4.22 (s, 2H), 4.14 (s, 2H), 4.06 (s, 3H), 4.01 (s, 3H), 3.98-3.94 (m, 1H), 3.14-3.22 (m, 1H), 3.14-3.08 (m, 3H), 2.65-2.58 (m, 1H), 2.44 (t, 2H), 2.14-2.07 (m, 2H), 2.03 (s, 3H), 1.52-1.37 (m, 2H). Example 164: ((6-((3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chloro -6-methoxy- [2,4'-bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxyp yridin-3- yl)methyl)glycine ((6-((3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chloro -6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3-yl)methyl)glycine was prepared in a similar fashion to Example 145, replacing (S)-5-(aminomethyl)pyrrolidin-2- one hydrochloride salt with glycine in step (a). LCMS: m/z found 722 [M+H] ⁺ , retention time = 2.61 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.70 (dd, 1H), 8.66 (d, 1H), 8.57 (s, 1H), 7.99 (s, 1H), 7.85 (d, 1H), 7.80 (d, 1H), 7.57 (t, 1H), 7.45 (d, 1H), 7.29 (dd, 1H), 4.51-4.48 (m, 1H), 4.29 (s, 2H), 4.15 (s, 3H), 4.07 (s, 3H), 3.98-3.93 (m, 3H), 3.51 (s, 2H), 3.21-3.14 (m, 1H), 2.87-2.71 (m, 2H), 2.12 (s, 3H), 2.09-2.01 (m, 2H), 1.44-1.31 (m, 2H). Example 165: 4-(((6-((3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chl oro-6- methoxy-[2,4'-bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4- methoxypyridin-3- yl)methyl)amino)butanoic acid 4-(((6-((3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chl oro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3-yl)methyl)amino)butanoic acid was prepared in a similar fashion to Example 145, replacing (S)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt with 4-aminobutanoic acid in step (a). LCMS: m/z found 750 [M+H] ⁺ , retention time = 2.68 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ 8.70 (dd, 1H), 8.66 (d, 1H), 8.57 (s, 1H), 7.98 (s, 1H), 7.84 (d, 1H), 7.80 (d, 1H), 7.57 (t, 1H), 7.45 (d, 1H), 7.28 (dd, 1H), 4.50-4.48 (m, 1H), 4.21 (s, 2H), 4.15 (s, 3H), 4.07 (s, 3H), 3.97-3.90 (m, 3H), 3.20-3.14 (m, 1H), 3.06 (t, 2H), 2.82-2.71 (m, 2H), 2.40 (t, 2H), 2.12 (s, 3H), 2.08-2.02 (m, 2H), 1.94-1.89 (m, 2H), 1.43-1.30 (m, 2H). Example 166: (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (1- (hydroxymethyl)cyclopropyl)methyl)amino)methyl)-4-methoxypic olinamide (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (1- (hydroxymethyl)cyclopropyl)methyl)amino)methyl)-4-methoxypic olinamide was prepared in a similar fashion to Example 123, replacing 2-aminoethanol with (1- (aminomethyl)cyclopropyl)methanol in step (a). LCMS: m/z found 720 [M+H] ⁺ , retention time = 1.81 min (Method D). ¹ H NMR (400 MHz, Methanol-d4) δ 8.67 (dd, 1H), 8.62 (d, 1H), 8.45 (s, 1H), 7.87 (s, 1H), 7.84 – 7.74 (m, 2H), 7.52 (t, 1H), 7.41 (d, 1H), 7.24 (dd, 1H), 4.03 (d, 5H), 3.93 – 3.76 (m, 4H), 3.46 (s, 2H), 3.32 (s, 2H), 2.75 – 2.60 (m, 4H), 2.35 – 2.18 (m, 2H), 2.02 (s, 1H), 1.87 (s, 1H), 1.85 – 1.73 (m, 1H), 0.44 (d, 3H). Example 167: (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((3 -hydroxyazetidin-1- yl)methyl)-4-methoxypicolinamide (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((3 -hydroxyazetidin-1-yl)methyl)- 4-methoxypicolinamide was prepared in a similar fashion to Example 123, replacing 2- aminoethanol with azetidin-3-ol in step (a). LCMS: m/z found 692 [M+H] ⁺ , retention time = 1.67 min (Method D). ¹ H NMR (400 MHz, Methanol-d4) δ 8.70 – 8.58 (m, 2H), 8.39 (s, 1H), 7.85 (s, 1H), 7.83 – 7.73 (m, 2H), 7.51 (t, J = 8.0 Hz, 1H), 7.40 (d, 1H), 7.23 (dd, 1H), 4.38 – 4.26 (m, 1H), 4.01 (s, 5H), 3.82 (d, 3H), 3.73 (s, 2H), 3.64 (t, 2H), 3.32 (s, 1H), 3.03 (t, 2H), 2.74 – 2.59 (m, 2H), 2.38 – 2.18 (m, 3H), 1.89 – 1.72 (m, 1H). Example 168: (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((3 -(hydroxymethyl)azetidin- 1-yl)methyl)-4-methoxypicolinamide (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((3 -(hydroxymethyl)azetidin-1- yl)methyl)-4-methoxypicolinamide was prepared in a similar fashion to Example 123, replacing 2-aminoethanol with azetidin-3-ylmethanol in step (a). LCMS: m/z found 706 [M+H] ⁺ , retention time = 1.75 min (Method D). ¹ H NMR (400 MHz, Methanol-d4) δ 8.70 – 8.58 (m, 2H), 8.39 (s, 1H), 7.85 (s, 1H), 7.83 – 7.73 (m, 2H), 7.51 (t, 1H), 7.40 (d, 1H), 7.23 (dd, 1H), 4.01 (s, 6H), 3.81 (d, 3H), 3.74 (s, 2H), 3.62 (t, 2H), 3.22 (s, 3H), 3.09 (t, 2H), 2.74 – 2.59 (m, 2H), 2.38 – 2.18 (m, 3H), 1.89 – 1.72 (m, 1H). Example 169: (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((4 -hydroxypiperidin-1- yl)methyl)-4-methoxypicolinamide (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((4 -hydroxypiperidin-1-yl)methyl)- 4-methoxypicolinamide was prepared in a similar fashion to Example 123, replacing 2- aminoethanol with piperidin-4-ol in step (a). LCMS: m/z found 720 [M+H] ⁺ , retention time = 1.67 min (Method D). ¹ H NMR (400 MHz, Methanol-d4) δ 8.70 – 8.57 (m, 2H), 8.47 (s, 1H), 7.86 (s, 1H), 7.84 – 7.73 (m, 2H), 7.52 (t, 1H), 7.41 (d, 1H), 7.24 (d, 1H), 4.01 (s, 6H), 3.82 (d, 3H), 3.62 (s, 2H), 3.32 (s, 1H), 2.85 – 2.77 (m, 2H), 2.75 – 2.59 (m, 2H), 2.35 – 2.19 (m, 5H), 1.90 – 1.73 (m, 4H), 1.61 – 1.49 (m, 1H). Example 170: (S)-1-((6-((3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'- chloro-6- methoxy-[2,4'-bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4- methoxypyridin-3- yl)methyl)pyrrolidine-3-carboxylic acid (S)-1-((6-((3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'- chloro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3-yl)methyl)pyrrolidine-3- carboxylic acid was prepared in a similar fashion to Example 145, replacing (S)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt with (S)-pyrrolidine-3-carboxylic acid in step (a). LCMS: m/z found 762 [M+H] ⁺ , retention time = 2.68 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.70 (dd, 1H), 8.66 (d, 1H), 8.60 (s, 1H), 7.98 (s, 1H), 7.86 (d, 1H), 7.80 (d, 1H), 7.56 (t, 1H), 7.46 (d, 1H), 7.29 (dd, 1H), 4.51 (d, 1H), 4.29 (s, 2H), 4.13 (s, 3H), 4.08 (s, 3H), 3.97 (m, 3H), 3.37-3.35 (m, 1H), 3.29-3.27 (m, 1H), 3.22-3.18 (m, 3H), 3.15-3.04 (m, 1H), 2.95-2.89 (m, 1H), 2.78-2.71 (m, 1H), 2.32-2.19 (m, 2H), 2.13 (s, 3H), 2.10-2.04 (m, 2H), 1.49-1.34 (m, 2H). Example 171: 4-((((6-((3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-ch loro-6- methoxy-[2,4'-bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4- methoxypyridin-3- yl)methyl)amino)methyl)bicyclo[2.2.1]heptane-1-carboxylic acid (a) Methyl 4-formylbicyclo[2.2.1]heptane-1-carboxylate To a mixture of methyl 4-(hydroxymethyl)bicyclo[2.2.1]heptane-1-carboxylate (5 g, 27.1 mmol) in dichloromethane (120 mL) was added Dess-Martin periodinane (13.8 g, 32.6 mmol), and the mixture stirred at room temperature for 2 hours under N ₂ . The mixture was concentrated, water (200 mL) added to the residue, and the mixture extracted with dichloromethane (2 x 300 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-30% ethyl acetate / petroleum ether) to afford methyl 4- formylbicyclo[2.2.1]heptane-1-carboxylate (3.8 g, 65% yield) as a colourless oil. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 9.76 (s, 1H), 3.62 (s, 3H), 1.99-1.91 (m, 6H), 1.68-1.64 (m, 2H), 1.48-1.43 (m, 2H). (b) Methyl 4-((benzylamino)methyl)bicyclo[2.2.1]heptane-1-carboxylate To a mixture of methyl 4-formylbicyclo[2.2.1]heptane-1-carboxylate (1 g, 5.49 mmol) and benzylamine (0.59 g, 5.49 mmol) in dichloromethane / methanol (1:1 v/v, 20 mL) was added sodium acetate (1.35 g, 16.5 mmol), and the mixture stirred at room temperature for 1.5 hours under N ₂ . Sodium cyanoborohydride (0.52 g, 8.23 mmol) was then added, and the mixture stirred at room temperature for 0.5 hours under N ₂ . The mixture was combined with another batch at the 200 mg scale. The mixture was concentrated, water (80 mL) was added to the residue and the mixture extracted with dichloromethane (2 x 100 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase SiO ₂ chromatography (0-60% ethyl acetate / petroleum ether) to afford methyl 4- ((benzylamino)methyl)bicyclo[2.2.1]heptane-1-carboxylate (0.85 g) as a colorless oil. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 7.34-7.20 (m, 5H), 3.71 (s, 2H), 3.59 (s, 3H), 2.55 (s, 2H), 1.87-1.83 (m, 2H), 1.64-1.54 (m, 4H), 1.46 (s, 2H), 1.34-1.32 (m, 2H). (c) Methyl 4-(aminomethyl)bicyclo[2.2.1]heptane-1-carboxylate To a mixture of methyl 4-((benzylamino)methyl)bicyclo[2.2.1]heptane-1-carboxylate (0.75 g, 2.74 mmol) in methanol (15 mL) was added 10% palladium on carbon (1.46 g, 1.37 mmol), and the mixture stirred at 60 °C for 12 hours under H ₂ at 50 psi. The mixture was filtered and the filtrate concentrated to afford methyl 4-(aminomethyl)bicyclo[2.2.1]heptane- 1-carboxylate (0.37 g, crude) as a colorless oil. ¹ H NMR (400 MHz, Chloroform-d): δ 3.61 (s, 3H), 2.76 (s, 2H), 1.96-1.90 (m, 2H), 1.65-1.51 (m, 4H), 1.45 (s, 2H), 1.36-1.33 (m, 2H). (d) Methyl 4-((((6-((3-(5-(((1-acetylpiperidin-4-yl)(tert- butoxycarbonyl)amino)methyl)-3'-chloro-6-methoxy-[2,4'-bipyr idin]-2'-yl)-2- chlorophenyl)carbamoyl)-4-methoxypyridin-3- yl)methyl)amino)methyl)bicyclo[2.2.1]heptane-1-carboxylate To a mixture of tert-butyl (1-acetylpiperidin-4-yl)((3'-chloro-2'-(2-chloro-3-(5-formyl - 4-methoxypicolinamido)phenyl)-6-methoxy-[2,4'-bipyridin]-5-y l)methyl)carbamate (Example 141, step (c)) (100 mg, 0.13 mmol) and methyl 4- (aminomethyl)bicyclo[2.2.1]heptane-1-carboxylate (48.0 mg, 0.26 mmol) in dichloromethane / methanol (1:1 v/v, 4 mL) was added sodium acetate (32.2 mg, 0.39 mmol), and the mixture stirred at room temperature for 1.5 hours under N ₂ . Sodium cyanoborohydride (24.7 mg, 0.393 mmol) was then added, and the mixture stirred at room temperature for 0.5 hours under N ₂ . The mixture was concentrated, water (40 mL) added to the residue, and the mixture extracted with dichloromethane (2 x 50 mL). The combined organic phases were dried over anhydrous sulfate, filtered and concentrated under reduced pressure. The residue was purified by prep-TLC (SiO ₂ , dichloromethane : methanol = 10:1 v/v) to afford methyl 4-((((6-((3-(5- (((1-acetylpiperidin-4-yl)(tert-butoxycarbonyl)amino)methyl) -3'-chloro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3- yl)methyl)amino)methyl)bicyclo[2.2.1]heptane-1-carboxylate (110 mg) as a yellow oil. LCMS: m/z found 930 [M+H] ⁺ . (e) Methyl 4-((((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-ch loro-6- methoxy-[2,4'-bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4- methoxypyridin-3- yl)methyl)amino)methyl)bicyclo[2.2.1]heptane-1-carboxylate To a mixture of methyl 4-((((6-((3-(5-(((1-acetylpiperidin-4-yl)(tert- butoxycarbonyl)amino)methyl)-3'-chloro-6-methoxy-[2,4'-bipyr idin]-2'-yl)-2- chlorophenyl)carbamoyl)-4-methoxypyridin-3- yl)methyl)amino)methyl)bicyclo[2.2.1]heptane-1-carboxylate (100 mg, 0.11 mmol) in dichloromethane (4 mL) was added trifluoroacetic acid (1.5 mL, 20.2 mmol), and the mixture stirred at room temperature for 0.5 hours under N ₂ . The mixture was combined with another batch at the 10 mg scale. The mixture was concentrated to afford methyl 4-((((6-((3-(5-(((1- acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6-methoxy-[2,4' -bipyridin]-2'-yl)-2- chlorophenyl)carbamoyl)-4-methoxypyridin-3- yl)methyl)amino)methyl)bicyclo[2.2.1]heptane-1-carboxylate (100 mg, crude) as a yellow oil. LCMS: m/z found 830 [M+H] ⁺ . The product was used in the next step without further purification. (f) 4-((((6-((3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-ch loro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3- yl)methyl)amino)methyl)bicyclo[2.2.1]heptane-1-carboxylic acid To a mixture of methyl 4-((((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'- chloro-6-methoxy-[2,4'-bipyridin]-2'-yl)-2-chlorophenyl)carb amoyl)-4-methoxypyridin-3- yl)methyl)amino)methyl)bicyclo[2.2.1]heptane-1-carboxylate (90 mg, 0.11 mmol) in THF / water (2:1 v/v, 3 mL) was added lithium hydroxide (13.0 mg, 0.54 mmol), and the mixture stirred at room temperature for 1 hour under N ₂ . The mixture was concentrated and the residue purified by reverse phase HPLC to afford 4-((((6-((3-(5-(((1-acetylpiperidin-4- yl)amino)methyl)-3'-chloro-6-methoxy-[2,4'-bipyridin]-2'-yl) -2-chlorophenyl)carbamoyl)-4- methoxypyridin-3-yl)methyl)amino)methyl)bicyclo[2.2.1]heptan e-1-carboxylic acid (24.3 mg) as a white solid. LCMS: m/z found 816 [M+H] ⁺ , retention time = 3.03 min (Method A). ¹ H NMR (400 MHz, Methanol-d4): δ.8.70 (dd, 1H), 8.66 (d, 1H), 8.55 (s, 1H), 7.97 (s, 1H), 7.85 (d, 1H), 7.81 (d, 1H), 7.57 (t, 1H), 7.46 (d, 1H), 7.28 (dd, 1H), 4.53-4.48 (m, 1H), 4.13 (s, 3H), 4.07 (s, 3H), 3.98-3.94 (m, 3H), 3.22-3.14 (m, 2H), 2.96 (s, 2H), 2.87-2.86 (m, 1H), 2.78-2.71 (m, 1H), 2.12 (s, 3H), 2.06-1.97 (m, 4H), 1.68-1.66 (m, 4H), 1.56 (s, 2H), 1.51- 1.31 (m, 5H). Example 172: 1-((6-((3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chlo ro-6-methoxy- [2,4'-bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxyp yridin-3- yl)methyl)azetidine-3-carboxylic acid 1-((6-((3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'-chlo ro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3-yl)methyl)azetidine-3- carboxylic acid was prepared in a similar fashion to Example 145, replacing (S)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt with azetidine-3-carboxylic acid in step (a). LCMS: m/z found 748 [M+H] ⁺ , retention time = 2.67 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.70-8.66 (m, 2H), 8.55 (s, 1H), 7.97 (s, 1H), 7.87 (d, 1H), 7.80 (d, 1H), 7.57 (t, 1H), 7.47 (d, 1H), 7.28 (d, 1H), 4.53-4.51 (m, 1H), 4.27 (s, 2H), 4.12 (s, 3H), 4.09-3.97 (m, 10H), 3.40-3.38 (m, 1H), 3.21-3.15 (m, 1H), 3.02-2.95 (m, 1H), 2.77-2.71 (m, 1H), 2.13 (s, 3H), 2.10-2.06 (m, 2H), 1.49-1.31 (m, 2H). Example 173: (R)-1-((6-((3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'- chloro-6- methoxy-[2,4'-bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4- methoxypyridin-3- yl)methyl)pyrrolidine-3-carboxylic acid (R)-1-((6-((3-(5-(((1-Acetylpiperidin-4-yl)amino)methyl)-3'- chloro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3-yl)methyl)pyrrolidine-3- carboxylic acid was prepared in a similar fashion to Example 145, replacing (S)-5- (aminomethyl)pyrrolidin-2-one hydrochloride salt with (R)-pyrrolidine-3-carboxylic acid in step (a). LCMS: m/z found 762 [M+H] ⁺ , retention time = 2.67 min (Method A). ¹ H NMR (400 MHz, Methanol-d ₄ ): δ 8.71-8.66 (m, 2H), 8.61 (s, 1H), 7.99 (s, 1H), 7.86 (d, 1H), 7.80 (d, 1H), 7.57 (t, 1H), 7.46 (d, 1H), 7.29 (d, 1H), 4.54-4.51 (m, 1H), 4.32 (s, 2H), 4.16 (s, 3H), 4.08 (s, 3H), 4.00-3.97 (m, 3H), 3.25-3.18 (m, 5H), 3.15-3.08 (m, 1H), 2.93-2.91 (m, 1H), 2.77-2.71 (m, 1H), 2.30-2.21 (m, 2H), 2.12 (s, 3H), 2.11-2.03 (m, 2H), 1.46-1.31 (m, 2H). Example 174: (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-((3- methoxyazetidin-1-yl)methyl)picolinamide (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-((3-methoxyazetidin-1- yl)methyl)picolinamide was prepared in a similar fashion to Example 123, replacing 2- aminoethanol with 3-methoxyazetidine in step (a). LCMS: m/z found 706 [M+H] ⁺ , retention time = 1.70 min (Method D). ¹ H NMR (400 MHz, Methanol-d4) δ 8.70 – 8.58 (m, 2H), 8.39 (s, 1H), 7.85 (s, 1H), 7.83 – 7.74 (m, 2H), 7.52 (t, 1H), 7.41 (d, 1H), 7.24 (dd, 1H), 4.02 (s, 6H), 3.90 – 3.78 (m, 3H), 3.74 (s, 2H), 3.66 – 3.58 (m, 2H), 3.34 (d, 2H), 3.23 (s, 3H), 3.14 – 3.05 (m, 2H), 2.74 – 2.59 (m, 2H), 2.36 – 2.18 (m, 2H), 1.89 – 1.73 (m, 1H). Example 175: (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-(((2- methoxyethyl)amino)methyl)picolinamide (S)-N-(2-Chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-(((2- methoxyethyl)amino)methyl)picolinamide was prepared in a similar fashion to Example 123, replacing 2-aminoethanol with 2-methoxyethan-1-amine in step (a). LCMS: m/z found 694 [M+H] ⁺ , retention time = 1.69 min (Method D). ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.70 – 8.58 (m, 2H), 8.43 (s, 1H), 7.86 (s, 1H), 7.82 – 7.73 (m, 2H), 7.51 (t, 1H), 7.40 (d, 1H), 7.22 (dd, 1H), 4.02 (d, 6H), 3.89 – 3.75 (m, 5H), 3.48 (t, 2H), 3.31 (d, 4H), 2.77 – 2.58 (m, 4H), 2.36 – 2.17 (m, 2H), 1.88 – 1.72 (m, 1H). Example 176: (S)-5-(((2-Amino-2-oxoethyl)amino)methyl)-N-(2-chloro-3-(3'- chloro-6- methoxy-5-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4 '-bipyridin]-2'- yl)phenyl)-4-methoxypicolinamide (S)-5-(((2-Amino-2-oxoethyl)amino)methyl)-N-(2-chloro-3-(3'- chloro-6-methoxy-5- ((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridi n]-2'-yl)phenyl)-4- methoxypicolinamide was prepared in a similar fashion to Example 123, replacing 2- aminoethanol with 2-aminoacetamide in step (a). LCMS: m/z found 693 [M+H] ⁺ , retention time = 1.57 min (Method D). ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.69 – 8.56 (m, 2H), 8.44 (s, 1H), 7.85 (s, 1H), 7.83 – 7.72 (m, 2H), 7.51 (t, 1H), 7.40 (d, 1H), 7.23 (dd, 1H), 4.02 (d, 6H), 3.81 (d, 4H), 3.31 (s, 1H), 3.23 (s, 2H), 2.73 – 2.58 (m, 2H), 2.39 – 2.17 (m, 3H), 1.88 – 1.72 (m, 1H). Example 177: N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-(((R)-3- methoxypyrrolidin-1-yl)methyl)picolinamide N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-4-met hoxy-5-(((R)-3- methoxypyrrolidin-1-yl)methyl)picolinamide was prepared in a similar fashion to Example 123, replacing 2-aminoethanol with (R)-3-methoxypyrrolidine in step (a). LCMS: m/z found 720 [M+H] ⁺ , retention time = 1.74 min (Method D). ¹ H NMR (400 MHz, Methanol-d4) δ 8.67 (dd, 1H), 8.61 (d, 1H), 8.47 (s, 1H), 7.86 (s, 1H), 7.83 – 7.73 (m, 2H), 7.52 (t, 1H), 7.41 (d, 1H), 7.23 (dd, 1H), 4.02 (s, 5H), 3.97 – 3.88 (m, 1H), 3.82 (d, 3H), 3.74 (d, 2H), 3.32 (s, 2H), 3.23 (s, 2H), 2.82 – 2.59 (m, 5H), 2.59 – 2.48 (m, 1H), 2.38 – 2.18 (m, 3H), 2.14 – 2.00 (m, 1H), 1.89 – 1.71 (m, 2H). Example 178: N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( R)-3- (hydroxymethyl)pyrrolidin-1-yl)methyl)-4-methoxypicolinamide N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( R)-3-(hydroxymethyl)pyrrolidin- 1-yl)methyl)-4-methoxypicolinamide was prepared in a similar fashion to Example 123, replacing 2-aminoethanol with (R)-pyrrolidin-3-ylmethanol in step (a). LCMS: m/z found 720 [M+H] ⁺ , retention time = 1.72 min (Method D). ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.65 – 8.57 (m, 2H), 8.47 (s, 1H), 7.86 (s, 1H), 7.82 – 7.73 (m, 2H), 7.55 – 7.48 (m, 1H), 7.41 (d, 1H), 7.24 (dd, 1H), 4.02 (d, 6H), 3.82 (d, 3H), 3.73 (d, 2H), 3.52 – 3.38 (m, 2H), 3.32 (d, 2H), 2.82 – 2.74 (m, 1H), 2.71 – 2.58 (m, 2H), 2.43 – 2.24 (m, 4H), 2.02 (s, 1H), 1.97 – 1.90 (m, 1H), 1.87 (s, 2H), 1.83 – 1.73 (m, 1H), 1.56 – 1.43 (m, 1H). Example 179: N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (1r,3r)-3- hydroxycyclobutyl)amino)methyl)-4-methoxypicolinamide N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (1r,3r)-3- hydroxycyclobutyl)amino)methyl)-4-methoxypicolinamide was prepared in a similar fashion to Example 123, replacing 2-aminoethanol with (1r,3r)-3-aminocyclobutan-1-ol in step (a). LCMS: m/z found 706 [M+H] ⁺ , retention time = 1.69 min (Method D). ¹ H NMR (400 MHz, Methanol-d4) δ 8.70 – 8.58 (m, 2H), 8.41 (s, 1H), 7.85 (s, 1H), 7.83 – 7.73 (m, 2H), 7.51 (t, 1H), 7.41 (d, 1H), 7.23 (d, 1H), 4.42 – 4.31 (m, 1H), 4.02 (d, 6H), 3.82 (d, 3H), 3.73 (s, 2H), 3.46 – 3.36 (m, 1H), 3.32 (d, 1H), 2.74 – 2.59 (m, 2H), 2.38 – 2.25 (m, 2H), 2.15 – 2.00 (m, 4H), 1.89 – 1.72 (m, 1H). Example 180: N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (1s,3s)-3- hydroxycyclobutyl)amino)methyl)-4-methoxypicolinamide N-(2-Chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)-5-((( (1s,3s)-3- hydroxycyclobutyl)amino)methyl)-4-methoxypicolinamide was prepared in a similar fashion to Example 123, replacing 2-aminoethanol with (1s,3s)-3-aminocyclobutan-1-ol in step (a). LCMS: m/z found 706 [M+H] ⁺ , retention time = 1.71 min (Method D). ¹ H NMR (400 MHz, Methanol-d4) δ 8.69 – 8.56 (m, 2H), 8.41 (d, 1H), 7.84 (s, 1H), 7.82 – 7.72 (m, 2H), 7.51 (t, 1H), 7.40 (d, 1H), 7.22 (dd, 1H), 4.02 (d, 6H), 3.93 – 3.71 (m, 6H), 3.31 (d, 1H), 2.84 – 2.58 (m, 3H), 2.57 – 2.46 (m, 2H), 2.37 – 2.24 (m, 2H), 1.87 – 1.72 (m, 1H), 1.68 – 1.56 (m, 2H). Example 181: (S)-5-((4-Acetamidopiperidin-1-yl)methyl)-N-(2-chloro-3-(3'- chloro-6- methoxy-5-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4 '-bipyridin]-2'- yl)phenyl)-4-methoxypicolinamide (S)-5-((4-Acetamidopiperidin-1-yl)methyl)-N-(2-chloro-3-(3'- chloro-6-methoxy-5- ((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridi n]-2'-yl)phenyl)-4- methoxypicolinamide was prepared in a similar fashion to Example 123, replacing 2- aminoethanol with N-(piperidin-4-yl)acetamide in step (a). LCMS: m/z found 761 [M+H] ⁺ , retention time = 1.73 min (Method D). ¹ H NMR (400 MHz, Methanol-d4) δ 8.72 – 8.59 (m, 2H), 8.48 (s, 1H), 7.87 (s, 1H), 7.84 – 7.74 (m, 2H), 7.53 (t, 1H), 7.42 (d, 1H), 7.24 (dd, 1H), 4.02 (s, 5H), 3.83 (d, 3H), 3.64 (s, 2H), 3.36 – 3.30 (m, 1H), 2.90 (d, 2H), 2.75 – 2.60 (m, 2H), 2.36 – 2.15 (m, 3H), 2.03 (d, 1H), 1.93 – 1.73 (m, 8H), 1.58 – 1.44 (m, 2H). Table 1. Cmpd Compound No.

Example 182: In vitro activity in a T cell activation luciferase reporter cell culture system (T Cell Activation Assay) PD-1/PD-L1 binding has the net effect of inhibiting T cell receptor signaling. A test compound that is capable of binding to and inhibiting PD-L1 will disrupt PD-1/PD-L1 binding and thus cause an increase in T cell receptor signaling. Disruption and/or inhibition of the PD-1/PD-L1 interaction represents a validated target for the treatment of many advanced cancers. Compounds capable of disrupting and/or inhibiting the PD-1/PD-L1 interaction, either directly or indirectly, can be considered effective for the treatment of diseases which can be characterized by immunodeficiency and/or overexpression of PD-L1, including but not limited to cancer and hepatitis B and/or hepatitis D. In one aspect, this assay measures the ability of a test compound to bind to and/or inhibit activity of PD-L1 (i.e., PD-L1/PD-1 binding). The ability of compounds to mediate T cell activation in a T cell activation luciferase reporter cell culture system was assessed as described previously (Park et al., Nat Commun 12, 1222 (2021)). CHO-K1 cells stably expressing human PD-L1 and a cell surface protein designed to activate cognate T cell receptor in an antigen-independent manner (PD-L1 aAPC/CHO-K1, Promega) were incubated with PD-1 effector Jurkat T cells stably expressing human PD-1 and NFAT- transcription factor-induced luciferase in the absence or presence of small molecules or anti- PD-L1 blocking antibody at indicated concentration range according to the manufacturer’s instruction (Promega). Bio-Glo™ Reagent was added and luminescence quantified as a signal for Jurkat T cell activation. In the absence of PD-L1 inhibition, the PD-1/PD-L1 interaction in this co-culture system results in inhibition of T cell receptor signaling and inhibition of NFAT-mediated luciferase activity. Disruption of PD-1/PD-L1 interaction with compound or antibody treatment results in luciferase activity. Table 2. T Cell Activation EC ₅₀ Values in Luciferase Reporter Assay As described elsewhere herein, PD-1/PD-L1 binding has the net effect of inhibiting T cell receptor signaling, and accordingly, disruption and/or inhibition of the PD-1/PD-L1 interaction represents a validated target for the treatment of many advanced cancers. Compounds capable of disrupting and/or inhibiting the PD-1/PD-L1 interaction, either directly or indirectly, can be considered effective for the treatment of diseases which can be characterized by immunodeficiency and/or overexpression of PD-L1, including but not limited to cancer and hepatitis B and/or hepatitis D. As described in the literature (Park et al., Nat Commun 12, 1222 (2021)), disruption of the PD-L1/PD-1 interaction may comprise small-molecule induced PD-L1 dimerization and internalization. Thus, in one aspect, internalization of PD-L1 induced by a compound can be a measure of PD-L1/PD-1 disruption. This assay measures the PD-L1 protein levels on the surface of Chinese hamster ovary cells overexpressing PD-L1 (CHO-K1-PD-L1). Internalization of PD-L1 can be measured by comparing the mean fluorescence intensity levels of PD-L1 in cells incubated with and without PD-L1 small molecule inhibitors. PD-L1 small molecule inhibitors were serially diluted using DMEM/Ham’s F12, 50/50 media and added to a 96-well V-bottom polystyrene plate. Designated control wells had media only. Chinese hamster ovary cells (CHO-K1) overexpressing PD-L1 were then added to the plate at 80,000-100,000 cells per well. The plates were then incubated at 37 °C/5% CO ₂ for 40 minutes. After incubation, the plates were centrifuged at 1,500 rpm for 5 minutes and the supernatant discarded. After vortexing the plates briefly, antibody staining cocktail containing LIVE/DEAD fixable dead cell stain and anti-PD-L1 PE antibody in phosphate buffered saline + 2% fetal bovine serum were added to the wells. Mouse IgG1 kappa isotype PE was used as staining control. The plates were then incubated in the dark at room temperature while gently shaking (35 rpm) for 20 minutes. The wells were subsequently washed with FACS buffer, centrifuged at 1,500 rpm for 5 minutes and the supernatant was discarded. The plates were vortexed briefly and the cells were fixed by addition of 2% paraformaldehyde in PBS. Plates were read using a BD LSRFortessa and the data analyzed using GraphPad Prism 8 software. Table 3. Internalization IC ₅₀ Values in PD-L1 Internalization Assay MC38 tumor mouse model In one aspect, this assay measures the ability of a PD-L1 inhibitor to reduce the size of MC38 (a murine colon adenocarcinoma cell line) tumors in mice, as an indication of the PD-L1 inhibitor’s ability to help treat, ameliorate, and/or prevent cancer in the subject. In vivo anti-tumor efficacy of compounds was evaluated in mice expressing humanized PD-1 and PD-L1, in which the extracellular domains of murine PD-1 and PD-L1 were genetically replaced with the human extracellular domain counterparts (Huang et al., Scientific Reports, 2017;7:42687). Humanized PD-1/PD-L1 (hPD-1/hPD-L1) mice were subcutaneously implanted with the colorectal cancer cell line MC38 expressing human PD- L1 and compound treatment initiated when tumor volumes reached approximately 150 mm ³ . Compound was administered via oral gavage once daily at 10 and 30 mg/kg for 28 days. The anti-PD-L1 monoclonal antibody atezolizumab was included as a positive reference control and administered via intraperitoneal injection at 5 mg/kg thrice weekly between study days 0 and 16 for 8 total doses. Tumor lengths and widths were measured by digital caliper and tumor volumes were calculated by the formula: Volume = ½ (Length × Width) ² . Table 4. Tumor volumes (group mean, mm ³ ) of MC38-tumor-bearing hPD-1/hPD-L1 mice treated with a compound of the present disclosure. Enumerated Embodiments The following enumerated embodiments are provided, the numbering of which is not to be construed as designating levels of importance. Embodiment 1 provides a compound of formula (I), or a salt, solvate, geometric isomer, isotopologue, stereoisomer, or tautomer thereof: (I), wherein: X ¹ is selected from the group consisting of CR ^2a and N; X ² is selected from the group consisting of CR ^2b and N; X ³ is selected from the group consisting of CR ^2c and N; X ⁴ is selected from the group consisting of CR ^2d and N; X ⁵ is selected from the group consisting of CR ^2e and N; X ⁶ is selected from the group consisting of CR ^2f and N; wherein one to four selected from the group consisting of X ¹ , X ² , X ³ , X ⁴ , X ⁵ , and X ⁶ are N; R ^1a and R ^1b are each independently selected from the group consisting of H, halogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₁ -C ₆ alkoxy, CN, NO ₂ , optionally substituted C ₁ -C ₆ haloalkyl, and optionally substituted C ₁ -C ₆ haloalkoxy; R ^1c is selected from the group consisting of and ; R ^1d is selected from the group consisting of , ,

R ^2a , R ^2b , R ^2c , R ^2d , R ^2e , and R ^2f , if present, are each independently selected from the group consisting of H, halogen, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₁ -C ₆ alkoxy, CN, NO ₂ , optionally substituted C ₁ -C ₆ haloalkyl, and optionally substituted C ₁ -C ₆ haloalkoxy; R ^3a , if present, is selected from the group consisting of H, -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₁ -C ₆ alkyl), -(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocylyl), -(CH ₂ ) _{1- 3} N(R ⁸ )(optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _1-3 N(R ⁸ )(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _1-3 N(R ⁸ )C(=O)O(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₃ -C ₈ cycloalkyl), optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ alkoxy, optionally substituted C ₁ -C ₆ hydroxyalkyl, optionally substituted C ₂ -C ₉ heterocyclyl, C(=O)R ^I , C(=O)OR ^I , C(=O)N(R ^I )(R ^II ), N(R ^I )C(=O)R ^II , and S(=O) ₂ R ^I ; R ^3b , if present, is selected from the group consisting of H, -(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocylyl), C(=O)O(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _{1- 3} N(R ⁸ )(optionally substituted C ₁ -C ₆ alkyl), optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ hydroxyalkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₂ -C ₉ heterocyclyl, C(=O)R ^I , C(=O)OR ^I , C(=O)N(R ^I )(R ^II ), and S(=O) ₂ R ^I ; R ^3c , if present, is selected from the group consisting of -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₁ -C ₆ alkyl), -(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _{1- 3} N(R ⁸ )(optionally substituted C ₃ -C ₈ cycloalkyl), -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₂ -C ₉ heterocyclyl), and -(CH ₂ ) _1-3 N(R ⁸ )(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl); R ^3d , if present, is selected from the group consisting of H, -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₁ -C ₆ alkyl), -(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocylyl), -(CH ₂ ) _{1- 3} N(R ⁸ )(optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _1-3 N(R ⁸ )(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _1-3 N(R ⁸ )C(=O)O(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₃ -C ₈ cycloalkyl), optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ alkoxy, optionally substituted C ₁ -C ₆ hydroxyalkyl, optionally substituted C ₂ -C ₉ heterocyclyl, C(=O)R ^I , C(=O)OR ^I , C(=O)N(R ^I )(R ^II ), N(R ^I )C(=O)R ^II , and S(=O) ₂ R ^I ; R ^3e , if present, is selected from the group consisting of H, -(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocylyl), C(=O)O(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _{1- 3} N(R ⁸ )(optionally substituted C ₁ -C ₆ alkyl), optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ hydroxyalkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₂ -C ₉ heterocyclyl, C(=O)R ^I , C(=O)OR ^I , C(=O)N(R ^I )(R ^II ), and S(=O) ₂ R ^I ; R ^4a , R ^4b , R ^4c , R ^4d , and R ^4e , if present, are each independently selected from the group consisting of H, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₁ -C ₆ alkoxy, cyano, halogen, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ haloalkoxy, C(=O)R ^I , C(=O)OR ^I , C(=O)N(R ^I )(R ^II ), N(R ^I )C(=O)R ^II , and S(=O) ₂ R ^I ; R ^5a , R ^5b , R ^5c , R ^5d , R ^5e , R ^5f , R ^5g , R ^5h , R ⁵ⁱ , R ^5j , R ^5k , and R ^5l , if present, are each independently selected from the group consisting of H, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₁ -C ₆ alkoxy, CN, NO ₂ , halogen, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ haloalkoxy, C(=O)R ^I , C(=O)OR ^I , C(=O)N(R ^I )(R ^II ), N(R ^I )C(=O)R ^II , and S(=O) ₂ R ^I ; R ^6a , R ^6b , R ^6c , R ^6d , and R ^6e , if present, are each independently selected from the group consisting of H, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₁ -C ₆ alkoxy, CN, NO ₂ , halogen, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₁ -C ₆ haloalkoxy, C(=O)R ^I , C(=O)OR ^I , C(=O)N(R ^I )(R ^II ), N(R ^I )C(=O)R ^II , and S(=O) ₂ R ^I , wherein two vicinal substituents selected from the group consisting of R ^6a , R ^6b , R ^6c , R ^6d , and R ^6e can combine with the atoms to which they are bound to form an optionally substituted C ₄ -C ₈ cycloalkyl; each occurrence of R ^7a and R ^7b , if present, is each independently selected from the group consisting of H, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₂ -C ₈ heterocycloalkyl, optionally substituted C ₇ -C ₁₂ aralkyl, optionally substituted C ₆ -C10 aryl, and optionally substituted C ₂ -C ₁₂ heteroaryl; each occurrence of R ⁸ is independently selected from the group consisting of H, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₂ -C ₈ heterocycloalkyl, optionally substituted C ₇ -C ₁₂ aralkyl, optionally substituted C ₆ -C10 aryl, and optionally substituted C ₂ -C ₁₂ heteroaryl; each occurrence of R ^I and R ^II , if present, is independently selected from the group consisting of H, optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₂ -C ₈ heterocycloalkyl, optionally substituted C7-C ₁₂ aralkyl, optionally substituted C ₆ -C ₁₀ aryl, and optionally substituted C ₂ -C ₁₂ heteroaryl; each occurrence of CH ₂ in R ^3a , R ^3b , R ^3c , and R ^3d , if present, is independently optionally substituted with at least one substituent selected from the group consisting of C ₁ -C ₃ alkyl, C ₃ - C ₈ cycloalkyl, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkyl, C ₁ -C ₃ haloalkoxy, and halogen; each occurrence of Y is independently selected from the group consisting of O, S, and NR ^7b ; Z ¹ , if present, is selected from the group consisting of CR ^4d and N; Z ² , if present, is selected from the group consisting of CR ^4e and N; Z ³ , if present, is selected from the group consisting of CR ^6d and N; and Z ⁴ , if present, is selected from the group consisting of CR ^6e and N; wherein the compound of Formula (I) is not a compound selected from the group consisting of: N-(3-(3-chloro-2-(4-(((2-hydroxyethyl)amino)methyl)-3-methox yphenyl)pyridin-4-yl)-2- methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)picolinamide; N-(2-chloro-3-(3-chloro-2-(4-(((2-hydroxyethyl)amino)methyl) -3- methoxyphenyl)pyridin-4-yl)phenyl)-5-(((2-hydroxyethyl)amino )methyl)picolinamide; N-(3-(2-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-3-methoxy phenyl)-3-chloropyridin-4- yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)picolin amide; N-(3-(3-chloro-2-(3-methoxy-4-(((tetrahydro-2H-pyran-4- yl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(2-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-3-methoxy phenyl)-3-chloropyridin-4- yl)-2-chlorophenyl)-5-(((2-hydroxyethyl)amino)methyl)picolin amide; (S)-N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((7-oxo-2,6-diazaspiro[3.4]oct an-2- yl)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(2-chloro-3-(3-chloro-2-(3-methoxy-4-((7-oxo-2,6-diazaspir o[3.4]octan-2- yl)methyl)phenyl)pyridin-4-yl)phenyl)-5-(((2-hydroxyethyl)am ino)methyl)picolinamide; N-(3-(2-(4-((6-acetyl-2,6-diazaspiro[3.3]heptan-2-yl)methyl) -3-methoxyphenyl)-3- chloropyridin-4-yl)-2-chlorophenyl)-5-(((2-hydroxyethyl)amin o)methyl)picolinamide; N-(3-(3-chloro-2-(3-fluoro-4-(((2-hydroxyethyl)amino)methyl) -5- methoxyphenyl)pyridin-4-yl)-2-methylphenyl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((tetrahydro-2H-pyran-4-yl)amin o)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)picolinamide; N-(2-chloro-3-(3-chloro-2-(3-methoxy-4-(((tetrahydro-2H-pyra n-4- yl)amino)methyl)phenyl)pyridin-4-yl)phenyl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)picolin amide; (S)-N-(3-(3-chloro-2-(3-(difluoromethoxy)-4-((((5-oxopyrroli din-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((7-oxo-2,6-diazaspiro[3.4]oct an-2- yl)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)-5-((7-oxo-2,6 -diazaspiro[3.4]octan-2- yl)methyl)picolinamide; 5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(2-(4-(((1-ac etylpiperidin-4- yl)amino)methyl)-3-methoxyphenyl)-3-chloropyridin-4-yl)-2-me thylphenyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-(((tetrahydro-2H-pyran-4- yl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)-5-(((te trahydro-2H-pyran-4- yl)amino)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamide; 5-((6-acetyl-2,6-diazaspiro[3.3]heptan-2-yl)methyl)-N-(3-(2- (4-((6-acetyl-2,6- diazaspiro[3.3]heptan-2-yl)methyl)-3-methoxyphenyl)-3-chloro pyridin-4-yl)-2- methylphenyl)picolinamide; N-(3-(3-chloro-2-(4-((((S)-2-hydroxypropyl)amino)methyl)-3-m ethoxyphenyl)pyridin-4- yl)-2-methylphenyl)-5-((((S)-2-hydroxypropyl)amino)methyl)pi colinamide; N-(2-chloro-3-(3-chloro-2-(3-methoxy-4-((7-oxo-2,6-diazaspir o[3.4]octan-2- yl)methyl)phenyl)pyridin-4-yl)phenyl)-5-((7-oxo-2,6-diazaspi ro[3.4]octan-2- yl)methyl)picolinamide; 5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(2-(4-(((1-ac etylpiperidin-4- yl)amino)methyl)-3-methoxyphenyl)-3-chloropyridin-4-yl)-2-ch lorophenyl)picolinamide; N-(2-chloro-3-(3-chloro-2-(3-methoxy-4-(((tetrahydro-2H-pyra n-4- yl)amino)methyl)phenyl)pyridin-4-yl)phenyl)-5-(((tetrahydro- 2H-pyran-4- yl)amino)methyl)picolinamide; N-(2-chloro-3-(3-chloro-2-(3-methoxy-4-(((((S)-5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)phenyl)-5-(((((S) -5-oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamide; 5-((6-acetyl-2,6-diazaspiro[3.3]heptan-2-yl)methyl)-N-(3-(2- (4-((6-acetyl-2,6- diazaspiro[3.3]heptan-2-yl)methyl)-3-methoxyphenyl)-3-chloro pyridin-4-yl)-2- chlorophenyl)picolinamide; N-(2-chloro-3-(3-chloro-2-(4-((((S)-2-hydroxypropyl)amino)me thyl)-3- methoxyphenyl)pyridin-4-yl)phenyl)-5-((((S)-2-hydroxypropyl) amino)methyl)picolinamide; N-(2-chloro-3-(3-chloro-2-(3-methoxy-4-((methylamino)methyl) phenyl)pyridin-4- yl)phenyl)-5-((methylamino)methyl)picolinamide; 5-(((2-oxaspiro[3.3]heptan-6-yl)amino)methyl)-N-(3-(2-(4-((( 2-oxaspiro[3.3]heptan-6- yl)amino)methyl)-3-methoxyphenyl)-3-chloropyridin-4-yl)-2-ch lorophenyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((methylamino)methyl)phenyl)py ridin-4-yl)-2- methylphenyl)-5-((methylamino)methyl)picolinamide; 5-((2-oxa-6-azaspiro[3.3]heptan-6-yl)methyl)-N-(3-(2-(4-((2- oxa-6-azaspiro[3.3]heptan- 6-yl)methyl)-3-methoxyphenyl)-3-chloropyridin-4-yl)-2-chloro phenyl)picolinamide; N-(2-chloro-3-(3-chloro-2-(4-(((3-fluoropropyl)amino)methyl) -3-methoxyphenyl)pyridin- 4-yl)phenyl)-5-(((3-fluoropropyl)amino)methyl)picolinamide; 5-(((2-acetyl-2-azaspiro[3.3]heptan-6-yl)amino)methyl)-N-(3- (2-(4-(((2-acetyl-2- azaspiro[3.3]heptan-6-yl)amino)methyl)-3-methoxyphenyl)-3-ch loropyridin-4-yl)-2- chlorophenyl)picolinamide; N-(3-(3-chloro-2-(3-(difluoromethoxy)-4-(((((S)-5-oxopyrroli din-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(3-chloro-2-(3-fluoro-5-methoxy-4-(((((S)-5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamide; (S)-N-(3-(2-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-3-met hoxyphenyl)-3- chloropyridin-4-yl)-2-methylphenyl)-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamide; (S)-N-(3-(3-chloro-2-(3-methoxy-4-(((tetrahydro-2H-pyran-4- yl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)-5-((((5 -oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamide; (S)-N-(3-(3-chloro-2-(4-(((3-fluoropropyl)amino)methyl)-3-me thoxyphenyl)pyridin-4- yl)-2-methylphenyl)-5-((((5-oxopyrrolidin-2-yl)methyl)amino) methyl)picolinamide; (S)-N-(2-chloro-3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)phenyl)-5-((methy lamino)methyl)picolinamide; (S)-N-(2-chloro-3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)phenyl)-5-(((2- hydroxyethyl)amino)methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)picolinamide; (S)-N-(3-(3-chloro-2-(4-(((2-hydroxyethyl)amino)methyl)-3-me thoxyphenyl)pyridin-4- yl)-2-methylphenyl)-5-((((5-oxopyrrolidin-2-yl)methyl)amino) methyl)picolinamide; and (S)-N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5- ((methylamino)methyl)picolinamide. Embodiment 2 provides the compound of Embodiment 1, which is selected from the group consisting of:

Embodiment 3 provides the compound of Embodiment 2, wherein one of the following applies: (a) each of R ^2b , R ^2c , R ^2d , R ^2e , and R ^2f is independently H; (b) each of R ^2a , R ^2c , R ^2d , R ^2e , and R ^2f is independently H; (c) each of R ^2a , R ^2b , R ^2d , R ^2e , and R ^2f is independently H; (d) each of R ^2a , R ^2b , R ^2c , R ^2e , and R ^2f is independently H; (e) each of R ^2a , R ^2b , R ^2c , R ^2d , and R ^2f is independently H; (f) each of R ^2a , R ^2b , R ^2c , R ^2d , and R ^2e is independently H; (g) each of R ^2b , R ^2c , R ^2e , and R ^2f is independently H; (h) each of R ^2b , R ^2c , R ^2d , and R ^2f is independently H; (i) each of R ^2b , R ^2c , R ^2d , and R ^2e is independently H; (j) each of R ^2a , R ^2c , R ^2e , and R ^2f is independently H; (k) each of R ^2a , R ^2c , R ^2d , and R ^2f is independently H; (l) each of R ^2a , R ^2c , R ^2d , and R ^2e is independently H; (m) each of R ^2a , R ^2b , R ^2e , and R ^2f is independently H; (n) each of R ^2a , R ^2b , R ^2d , and R ^2f is independently H; and (o) each of R ^2a , R ^2b , R ^2d , and R ^2e is independently H. Embodiment 4 provides the compound of any one of Embodiments 1-3, wherein R ^1a and R ^1b are each independently selected from the group consisting of Me, Cl, F, and OMe. Embodiment 5 provides the compound of any one of Embodiments 1-4, wherein R ^1a and R ^1b are identical. Embodiment 6 provides the compound of any one of Embodiments 1-5, wherein Z ¹ , Z ² , and Z ³ are each independently selected from the group consisting of N and CH. Embodiment 7 provides the compound of any one of Embodiments 1-6, wherein R ^4a , R ^4b , R ^4c , R ^4d , and R ^4e , if present, are each independently selected from the group consisting of H, F, Me, Et, OMe, and OCHF ₂ . Embodiment 8 provides the compound of any one of Embodiments 1-7, wherein R ^3a is selected from the group consisting of -(CH ₂ ) _1-3 NH(CH ₂ ) _1-3 (optionally substituted 5- oxopyrrolidin-2-yl), -(CH ₂ ) _1-3 N(CH ₃ )(CH ₂ ) _1-3 (optionally substituted 5-oxopyrrolidin-2-yl), - (CH ₂ ) _1-3 NH(CH ₂ ) _1-3 (optionally substituted oxetanyl), -(CH ₂ ) _1-3 NH(CH ₂ ) _1-3 (optionally substituted piperidinyl), -(CH ₂ )NH(optionally substituted C ₁ -C ₆ haloalkyl), -(CH ₂ ) _{1- 3} NH(CH ₂ )0-2C(CH ₃ ) ₂ (CH ₂ )0-2C(=O)OH, -(CH ₂ ) _1-3 (optionally substituted azetidinyl), -(CH ₂ ) _{1- 3} (optionally substituted 2,6-diazaspiro[3.4]octan-2-yl), -(CH ₂ ) _1-3 (optionally substituted 2,5- diazaspiro[3.4]octan-2-yl), -(CH ₂ ) _1-3 (optionally substituted 7-oxa-2-azaspiro[3.5]nonan-2-yl), -(CH ₂ ) _1-3 (optionally substituted pyrrolidinyl), -(CH ₂ ) _1-3 (optionally substituted piperidinyl), - (CH ₂ ) _1-3 NH(optionally substituted 2-azaspiro[3.3]heptan-6-yl), -(CH ₂ ) _1-3 NH(optionally substituted pyrrolidinyl), -(CH ₂ ) _1-3 NH(optionally substituted piperidin-4-yl), -(CH ₂ ) _{1- 3} N(CH ₃ )(optionally substituted piperidin-4-yl), -(CH ₂ ) _1-3 NH(optionally substituted piperidin- 3-yl), and -(CH ₂ ) _1-3 NHC(=O)O(CH ₂ ) _1-3 (optionally substituted 5-oxopyrrolidin-2-yl). Embodiment 9 provides the compound of any one of Embodiments 1-8, wherein R ^3a is selected from the group consisting of , ,

Embodiment 10 provides the compound of any one of Embodiments 1-5 and 7, wherein at least one of the following applies: (a) at least one of R ^5a , R ^5b , R ^5c , R ^5d , R ^5e , and R ^5f is H; (b) at least two of R ^5a , R ^5b , R ^5c , R ^5d , R ^5e , and R ^5f are H; (c) at least three of R ^5a , R ^5b , R ^5c , R ^5d , R ^5e , and R ^5f are H; (d) at least four of R ^5a , R ^5b , R ^5c , R ^5d , R ^5e , and R ^5f are H; (e) at least five of R ^5a , R ^5b , R ^5c , R ^5d , R ^5e , and R ^5f are H; and (f) each of R ^5a , R ^5b , R ^5c , R ^5d , R ^5e , and R ^5f are H. Embodiment 11 provides the compound of any one of Embodiments 1-5, 7, and 10, wherein R ^3b is selected from the group consisting of -(CH ₂ ) _1-3 CH(CH ₃ )(OH) and -(CH ₂ ) _1- 3(optionally substituted 5-oxopyrrolidin-2-yl). Embodiment 12 provides the compound of any one of Embodiments 1-5, 7, and 10- 11, wherein R ^3b is selected from the group consisting of Embodiment 13 provides the compound of any one of Embodiments 1-9, wherein R ^1c is , R ^1d is , and at least one of the following applies: (a) R ^1a and R ^1b are identical, R ^3a and R ^3c are not identical, and R ^3c is -(CH ₂ ) _{1- 3} N(R ⁸ )(C ₁ -C ₆ haloalkyl); (b) R ^3a and R ^3c are not identical, and R ^3c is selected from the group consisting of - (CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₃ -C ₈ cycloalkyl), and -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₂ -C ₉ heterocyclyl); (c) R ^3a and R ^3c are not identical, R ^3c is -(CH ₂ ) _1-3 N(R ⁸ )(C ₁ -C ₆ alkyl), and R ^3a is selected from the group consisting of H, -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₁ -C ₆ alkyl), -(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocylyl), -(CH ₂ ) _{1- 3} N(R ⁸ )C(=O)O(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _{1- 3} N(R ⁸ )(optionally substituted C ₃ -C ₈ cycloalkyl), optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ alkoxy, optionally substituted C ₁ -C ₆ hydroxyalkyl, optionally substituted C ₂ -C ₉ heterocyclyl, C(=O)R ^I , C(=O)OR ^I , C(=O)N(R ^I )(R ^II ), N(R ^I )C(=O)R ^II , and S(=O) ₂ R ^I ; (d) R ^3a and R ^3c are not identical, and at least one of R ^4a , R ^4b , R ^4d , and R ^4e is selected from the group consisting of C ₁ -C ₆ alkyl and halogen; (e) R ^3a and R ^3c are not identical, R ^1a and R ^1b are identical, and R ^3c is optionally substituted 2-azaspiro[3.3]heptanyl; (f) R ^3a is optionally substituted 7-oxa-2-azaspiro[3.5]nonanyl; (g) R ^3c is -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₁ -C ₆ alkyl), wherein R ⁸ is selected from the group consisting of optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₃ -C ₈ cycloalkyl, optionally substituted C ₂ -C ₈ heterocycloalkyl, optionally substituted C7-C ₁₂ aralkyl, optionally substituted C ₆ -C ₁₀ aryl, and optionally substituted C ₂ -C ₁₂ heteroaryl; (h) R ^3c is -(CH ₂ ) _1-3 N(R ⁸ )(C ₁ -C ₆ alkoxy); (i) R ^3c is -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₃ -C ₆ hydroxyalkyl); (j) at least one of R ^3a and R ^3c is -(CH ₂ ) _1-3 (optionally substituted pyrrolidin-1-yl); (k) X ³ is N and at least one of R ^4a , R ^4b , R ^4d , and R ^4e is C ₁ -C ₆ haloalkoxy; (l) X ³ is N, and R ^1a and R ^1b are identical; (m) X ³ is N, and R ^3c is -(CH ₂ ) _1-3 N(R ⁸ )(C ₁ -C ₆ hydroxyalkyl), wherein the hydroxyalkyl in R ^3c is substituted at any position with at least one C ₁ -C ₆ alkyl; (n) X ³ is N and R ^3c is -(CH ₂ ) _1-3 N(R ⁸ )(C ₁ -C ₆ haloalkyl); (o) X ³ is N and R ^3c is -(CH ₂ ) _1-3 N(R ⁸ )(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl); (p) X ³ is N and R ^3c is -(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl); (q) X ³ is N and R ^3a is selected from the group consisting of H, -(CH ₂ ) _{1- 3} N(R ⁸ )(optionally substituted C ₁ -C ₆ alkyl), -(CH ₂ ) _1-3 (optionally substituted C ₂ - C ₉ heterocylyl), -(CH ₂ ) _1-3 N(R ⁸ )C(=O)O(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl), -(CH ₂ ) _1-3 N(R ⁸ )(optionally substituted C ₃ -C ₈ cycloalkyl), optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ alkoxy, optionally substituted C ₁ -C ₆ hydroxyalkyl, optionally substituted C ₂ -C ₉ heterocyclyl, C(=O)R ^I , C(=O)OR ^I , C(=O)N(R ^I )(R ^II ), N(R ^I )C(=O)R ^II , and S(=O) ₂ R ^I ; (r) Z ² is N; (s) Z ³ is CR ^6d ; (t) Z ³ is N and at least one of R ^6a , R ^6c , and R ^6e is selected from the group consisting of C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, hydroxy, and halogen; (u) Z ⁴ is N; (v) R ^3a is -(CH ₂ ) _1-3 N(R ⁸ )(CH ₂ ) _1-3 (1-methyl-5-oxopyrrolidinyl) or R ^3c is -(CH ₂ ) _1- 3(optionally substituted pyrrolidinyl); (w) Z ¹ is N and R ^3c is -(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl); (x) Z ¹ is N and R ^3a and R ^3c are identical; (y) Z ¹ is N, R ^3a is –(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl), and R ^3c is -(CH ₂ ) _1-3 N(R ⁸ )(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₀ heterocyclyl); and (z) at least one of R ^1a and R ^1b is F or OMe. Embodiment 14 provides the compound of any one of Embodiments 1-9 and 13, wherein R ^1c is , R ^1d is , and at least one of the following applies: (a) R ^1a and R ^1b are Cl, and R ^3c is CH ₂ N(R ⁸ )(C ₁ -C ₆ haloalkyl); and (b) R ^3a and R ^3c are not identical, and at least one of R ^4a , R ^4b , R ^4d , and R ^4e is selected from the group consisting of Me, Et, F, and Cl; (c) R ^3c is CH ₂ N(R ⁸ )(methoxyethyl); (d) R ^3c is CH ₂ N(CH ₃ )(C ₁ -C ₆ hydroxyalkyl); (e) R ^3c is CH ₂ N(R ⁸ )(optionally substituted hydroxypropyl). (f) X ³ is N and at least one of R ^4a , R ^4b , R ^4d , and R ^4e is OCHF ₂ ; (g) X ³ is N, and R ^1a and R ^1b are Cl; (h) X ³ is N and R ^3c is CH ₂ N(R ⁸ )(C ₁ -C ₆ hydroxyalkyl), wherein the hydroxyalkyl in R ^3c is substituted at any position with at least one selected from the group consisting of methyl and isopropyl; (i) X ³ is N and R ^3c is CH ₂ N(R ⁸ )(C ₁ -C ₆ fluoroalkyl); (j) X ³ is N and R ^3c is CH ₂ N(R ⁸ )CH ₂ (optionally substituted C ₂ -C ₉ heterocyclyl); (k) X ³ is N and R ^3a is -(CH ₂ ) _1-3 N(R ⁸ )C(=O)O(CH ₂ ) _1-3 (optionally substituted C ₂ -C ₉ heterocyclyl); (l) Z ³ is N and at least one of R ^6a , R ^6c , and R ^6e is selected from the group consisting of Me, OMe, and F; and (m) Z ³ is CF. Embodiment 15 provides the compound of any one of Embodiments 1-14, wherein R ^3c is selected from the group consisting of -(CH ₂ ) _1-3 NH(C ₁ -C ₆ alkyl), -(CH ₂ ) _{1- 3} NH(optionally substituted C ₁ -C ₆ haloalkyl), -(CH ₂ ) _1-3 NH(optionally substituted C ₁ -C ₆ hydroxyalkyl), -(CH ₂ ) _1-3 N(C ₁ -C ₆ alkyl)(optionally substituted C ₁ -C ₆ hydroxyalkyl), -(CH ₂ ) _{1- 3} NH(optionally substituted C ₁ -C ₆ alkoxy), -(CH ₂ ) _1-3 NHCH ₂ C(CH ₃ )(OH), -(CH ₂ ) _{1- 3} NHCH ₂ C(CH ₃ ) ₂ (OH), -(CH ₂ ) _1-3 NHCH(CH(CH ₃ ) ₂ )CH ₂ OH, -(CH ₂ ) _1-3 NH(CH ₂ ) _1-3 (optionally substituted cyclopropylenyl)(CH ₂ ) _1-3 OH, -(CH ₂ ) _1-3 NH(CH ₂ ) _1-3 (C(CH ₃ ) ₂ )0-1(CH ₂ ) _1-3 C(=O)OH, -(CH ₂ ) _1-3 C(=O)NH ₂ , -(CH ₂ ) _1-3 (optionally substituted azetidin-1-yl), -(CH ₂ ) _1-3 (optionally substituted pyrrolidin-1-yl), -(CH ₂ ) _1-3 (optionally substituted piperidinyl), -(CH ₂ ) _{1- 3} NH(optionally substituted cyclopropyl), -(CH ₂ ) _1-3 NH(optionally substituted cyclobutyl), - (CH ₂ ) _1-3 NH(optionally substituted 2-azaspiro[3.3]heptan-2-yl), -(CH ₂ ) _1-3 N(optionally substituted piperidin-4-yl), -(CH ₂ ) _1-3 NH(optionally substituted cyclohexyl), -(CH ₂ ) _{1- 3} NH(CH ₂ ) _1-3 (optionally substituted oxetan-2-yl), -(CH ₂ ) _1-3 NH(CH ₂ ) _1-3 (optionally substituted 5-oxopyrrolidin-2-yl), and -(CH ₂ ) _1-3 NH(CH ₂ ) _1-3 (optionally substituted bicyclo[2.2.1]heptanyl). Embodiment 16 provides the compound of any one of Embodiments 1-15, wherein R ^3c is selected from the group consisting of , , ,

Embodiment 17 provides the compound of any one of Embodiments 1-12, wherein R ^3d is selected from the group consisting of -(CH ₂ ) _1-3 NH(C ₁ -C ₆ hydroxyalkyl) and -(CH ₂ ) _{1- 3} N(C ₁ -C ₆ alkyl)(C ₁ -C ₆ haloalkyl). Embodiment 18 provides the compound of any one of Embodiments 1-12 and 17, wherein R ^3d is selected from the group consisting of Embodiment 19 provides the compound of any one of Embodiments 1-12, wherein at least one of the following applies: (a) at least one of R ^5g , R ^5h , R ⁵ⁱ , R ^5j , R ^5k , and R ^5l is H; (b) at least two of R ^5g , R ^5h , R ⁵ⁱ , R ^5j , R ^5k , and R ^5l are H; (c) at least three of R ^5g , R ^5h , R ⁵ⁱ , R ^5j , R ^5k , and R ^5l are H; (d) at least four of R ^5g , R ^5h , R ⁵ⁱ , R ^5j , R ^5k , and R ^5l are H; (e) at least five of R ^5g , R ^5h , R ⁵ⁱ , R ^5j , R ^5k , and R ^5l are H; and (f) each of R ^5g , R ^5h , R ⁵ⁱ , R ^5j , R ^5k , and R ^5l are H. Embodiment 20 provides the compound of any one of Embodiments 1-12 and 19, wherein R ^3e is selected from the group consisting of -(CH ₂ ) _1-3 OH, -(CH ₂ ) _1-3 F, -(CH ₂ ) _{1- 3} (optionally substituted oxetanyl), -(CH ₂ ) _1-3 (optionally substituted 5-oxopyrrolidin-2-yl), and -(CH ₂ ) _1-3 (optionally substituted piperidinyl). Embodiment 21 provides the compound of any one of Embodiments 1-13 and 19-20, wherein R ^3e is selected from the group consisting of , , , , , and . Embodiment 22 provides the compound of any one of Embodiments 1-21, wherein R ^1c is selected from the group consisting of

wherein: R ^9a and R ^9b , if present, are each independently selected from the group consisting of C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₁ -C ₆ haloalkoxy, and halogen; and R ^10a and R ^10b , if present, are each independently selected from the group consisting of H, C ₁ -C ₆ alkyl, and C(=O)(C ₁ -C ₆ alkyl). Embodiment 23 provides the compound of Embodiment 22, wherein R ^9a and R ^9b are each independently selected from the group consisting of methyl, ethyl, methoxy, fluoro, chloro, and difluoromethoxy. Embodiment 24 provides the compound of Embodiment 22 or 23, wherein R ^10a and R ^10b are each independently selected from the group consisting of H, CH ₃ , and C(=O)CH ₃ . Embodiment 25 provides the compound of any one of Embodiments 1-24, wherein R ^1c is selected from the group consisting of

Embodiment 26 provides the compound of any one of Embodiments 1-25, wherein R ^1d is selected from the group consisting of

wherein: each occurrence of R ^11a , R ^11b , and R ^11c , if present, is independently selected from the group consisting of H, C ₁ -C ₆ alkyl, and C(=O)(C ₁ -C ₆ alkyl); and each occurrence of R ¹² , if present, is independently selected from the group consisting of C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, hydroxy, and halogen. Embodiment 27 provides the compound of Embodiment 26, wherein R ^11a , R ^11b , and R ^11c are each independently selected from the group consisting of H, CH ₃ , and C(=O)CH ₃ . Embodiment 28 provides the compound of Embodiment 26 or 27, wherein R ¹² is selected from the group consisting of CH ₃ , OH, OCH ₃ , and F. Embodiment 29 provides the compound of any one of Embodiments 1-28, wherein R ^7a is H. Embodiment 30 provides the compound of any one of Embodiments 1-29, wherein R ^1d is selected from the group consisting of , Embodiment 31 provides the compound of any one of Embodiments 1-30, wherein each occurrence of optionally substituted alkyl, optionally substituted alkoxy, optionally substituted haloalkyl, optionally substituted haloalkoxy, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl is independently optionally substituted with at least one substituent selected from the group consisting of C ₁ -C ₆ alkyl, C ₃ -C ₈ cycloalkyl, C ₂ -C ₁₂ heterocycloalkyl, C ₁ -C ₆ hydroxyalkyl, halogen, CN, NO ₂ OR’, N(R’)(R”), C ₁ -C ₆ haloalkoxy, C ₃ -C ₈ halocycloalkoxy, aryl, heteroaryl, (C ₁ -C ₆ alkylenyl)C(=O)N(R’)(R”), (C ₁ -C ₆ alkylenyl)C(=O)OR’, O(C ₁ -C ₃ alkylenyl)C(=O)OR’, O(C ₁ -C ₃ alkylenyl)C(=O)N(R’)(R’), C(=O)R’, C(=O)OR’, OC(=O)R’, OC(=O)OR’, SR’, S(=O)R’, S(=O) ₂ R’, S(=O) ₂ N(R’)(R”), S(=O) ₂ NR’C(=O)NHR”, N(R’)S(=O) ₂ R”, N(R’)C(=O)R”, and C(=O)NR’R”, wherein R’ and R” are each independently selected from the group consisting of H, -C(=O)(C ₁ -C ₆ alkyl), C ₁ -C ₆ alkyl, C ₁ - C ₆ haloalkyl, C ₁ -C ₆ heteroalkyl, C ₃ -C ₈ cycloalkyl, C ₂ -C ₁₂ heterocycloalkyl, C7-C ₁₂ aralkyl, aryl, and heteroaryl. Embodiment 32 provides the compound of any one of Embodiments 1-31, which is selected from the group consisting of: N-(3-(3-chloro-2-(3-fluoro-5-methoxy-4-((((5-oxopyrrolidin-2 - yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; (S)-N-(3-(3-chloro-2-(3-fluoro-5-methoxy-4-((((5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; (R)-N-(3-(3-chloro-2-(3-fluoro-5-methoxy-4-((((5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(2-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-3-methoxy phenyl)-3-chloropyridin-4-yl)- 2-methylphenyl)-5-((methylamino)methyl)picolinamide; N-(3-(3-chloro-2-(4-(((3-fluoropropyl)amino)methyl)-3-methox yphenyl)pyridin-4-yl)-2- methylphenyl)-5-((methylamino)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- methoxyethyl)amino)methyl)picolinamide; (S)-N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- methoxyethyl)amino)methyl)picolinamide; (R)-N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- methoxyethyl)amino)methyl)picolinamide; N-(3-(2-(4-((7-oxa-2-azaspiro[3.5]nonan-2-yl)methyl)-3-metho xyphenyl)-3-chloropyridin-4- yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)picolin amide; N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-((3-hydroxypyrrolidin-1- yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((S)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-(((((S)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((R)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-(((((R)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((S)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-(((((R)-5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((R)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(2-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-3-methoxy phenyl)-3-chloropyridin-4-yl)- 2-methylphenyl)-5-((3-hydroxypyrrolidin-1-yl)methyl)picolina mide; (S)-N-(3-(2-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-3-met hoxyphenyl)-3-chloropyridin- 4-yl)-2-methylphenyl)-5-((3-hydroxypyrrolidin-1-yl)methyl)pi colinamide; (R)-N-(3-(2-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-3-met hoxyphenyl)-3-chloropyridin- 4-yl)-2-methylphenyl)-5-((3-hydroxypyrrolidin-1-yl)methyl)pi colinamide; N-(3-(3-chloro-2-(4-((3-hydroxypyrrolidin-1-yl)methyl)-3-met hoxyphenyl)pyridin-4-yl)-2- methylphenyl)-5-((3-hydroxypyrrolidin-1-yl)methyl)picolinami de; N-(3-(3-chloro-2-(4-(((S)-3-hydroxypyrrolidin-1-yl)methyl)-3 -methoxyphenyl)pyridin-4-yl)- 2-methylphenyl)-5-(((S)-3-hydroxypyrrolidin-1-yl)methyl)pico linamide; N-(3-(3-chloro-2-(4-(((S)-3-hydroxypyrrolidin-1-yl)methyl)-3 -methoxyphenyl)pyridin-4-yl)- 2-methylphenyl)-5-(((R)-3-hydroxypyrrolidin-1-yl)methyl)pico linamide; N-(3-(3-chloro-2-(4-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-3 -methoxyphenyl)pyridin-4-yl)- 2-methylphenyl)-5-(((S)-3-hydroxypyrrolidin-1-yl)methyl)pico linamide; N-(3-(3-chloro-2-(4-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-3 -methoxyphenyl)pyridin-4-yl)- 2-methylphenyl)-5-(((R)-3-hydroxypyrrolidin-1-yl)methyl)pico linamide; N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)(methyl)amino)methyl)picolinamide; (S)-N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)(methyl)amino)methyl)picolinamide; (R)-N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)(methyl)amino)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((7-oxo-2,6-diazaspiro[3.4]oct an-2- yl)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)-5-((3-hydroxy pyrrolidin-1- yl)methyl)picolinamide; (S)-N-(3-(3-chloro-2-(3-methoxy-4-((7-oxo-2,6-diazaspiro[3.4 ]octan-2- yl)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)-5-((3-hydroxy pyrrolidin-1- yl)methyl)picolinamide; (R)-N-(3-(3-chloro-2-(3-methoxy-4-((7-oxo-2,6-diazaspiro[3.4 ]octan-2- yl)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)-5-((3-hydroxy pyrrolidin-1- yl)methyl)picolinamide; N-(3-(2-(4-(((1-acetylpiperidin-4-yl)amino)methyl)-3-methoxy phenyl)-3-chloropyridin-4-yl)- 2-methylphenyl)-5-(((2-hydroxyethyl)(methyl)amino)methyl)pic olinamide; N-(3-(2-(4-(((2-acetyl-2-azaspiro[3.3]heptan-6-yl)amino)meth yl)-3-methoxyphenyl)-3- chloropyridin-4-yl)-2-chlorophenyl)-5-(((2-hydroxyethyl)amin o)methyl)picolinamide; 5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3-(3-c hloro-2-(3-methoxy-4-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)phenyl)pyridin-4-yl)p henyl)picolinamide; (S)-5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3-chloro-2-(3-methoxy-4-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)phenyl)pyridin-4-yl)p henyl)picolinamide; 5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3-(3-c hloro-2-(3-methoxy-4-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)phenyl)pyridin-4-yl)p henyl)picolinamide; N-(2-chloro-3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2 - yl)methyl)amino)methyl)phenyl)pyridin-4-yl)phenyl)-5-(((3- fluoropropyl)amino)methyl)picolinamide; (S)-N-(2-chloro-3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)phenyl)-5-(((3- fluoropropyl)amino)methyl)picolinamide; (R)-N-(2-chloro-3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)phenyl)-5-(((3- fluoropropyl)amino)methyl)picolinamide; 5-(((2-acetyl-2-azaspiro[3.3]heptan-6-yl)amino)methyl)-N-(2- chloro-3-(3-chloro-2-(3- methoxy-4-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)pheny l)pyridin-4- yl)phenyl)picolinamide; (S)-5-(((2-acetyl-2-azaspiro[3.3]heptan-6-yl)amino)methyl)-N -(2-chloro-3-(3-chloro-2-(3- methoxy-4-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)pheny l)pyridin-4- yl)phenyl)picolinamide; (R)-5-(((2-acetyl-2-azaspiro[3.3]heptan-6-yl)amino)methyl)-N -(2-chloro-3-(3-chloro-2-(3- methoxy-4-((((5-oxopyrrolidin-2-yl)methyl)amino)methyl)pheny l)pyridin-4- yl)phenyl)picolinamide; N-(3-(3-chloro-2-(3-methyl-4-((((5-oxopyrrolidin-2-yl)methyl )amino)methyl)phenyl)pyridin- 4-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)picol inamide; (S)-N-(3-(3-chloro-2-(3-methyl-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; (R)-N-(3-(3-chloro-2-(3-methyl-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(3-chloro-2-(3-ethyl-4-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)phenyl)pyridin-4- yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)picolin amide; (S)-N-(3-(3-chloro-2-(3-ethyl-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; (R)-N-(3-(3-chloro-2-(3-ethyl-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(3-chloro-2-(3-fluoro-4-((((5-oxopyrrolidin-2-yl)methyl )amino)methyl)phenyl)pyridin- 4-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)picol inamide; (S)-N-(3-(3-chloro-2-(3-fluoro-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; (R)-N-(3-(3-chloro-2-(3-fluoro-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(3-chloro-2-(3-chloro-4-((((5-oxopyrrolidin-2-yl)methyl )amino)methyl)phenyl)pyridin- 4-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)picol inamide; (S)-N-(3-(3-chloro-2-(3-chloro-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; (R)-N-(3-(3-chloro-2-(3-chloro-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(3'-chloro-4-fluoro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)picolinamide; (S)-N-(3-(3'-chloro-4-fluoro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl) amino)methyl)picolinamide; (R)-N-(3-(3'-chloro-4-fluoro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl) amino)methyl)picolinamide; N-(3-(3'-chloro-6-(difluoromethoxy)-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)picolinamide; (S)-N-(3-(3'-chloro-6-(difluoromethoxy)-5-((((5-oxopyrrolidi n-2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl) amino)methyl)picolinamide; (R)-N-(3-(3'-chloro-6-(difluoromethoxy)-5-((((5-oxopyrrolidi n-2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl) amino)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 2-fluoro-4-(((2- hydroxyethyl)amino)methyl)benzamide; (S)-N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 2-fluoro-4-(((2- hydroxyethyl)amino)methyl)benzamide; (R)-N-(3-(3-chloro-2-(3-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 2-fluoro-4-(((2- hydroxyethyl)amino)methyl)benzamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-(((2-hydroxyethyl)amino)methyl)pi colinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((2-hydroxyethyl)amino)met hyl)picolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((2-hydroxyethyl)amino)met hyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-(((S)-3-hydroxypyrrolidin-1-yl)me thyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((S)-3-hydroxypyrrolidin-1 -yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((R)-3-hydroxypyrrolidin-1 -yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((S)-3-hydroxypyrrolidin-1 -yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((R)-3-hydroxypyrrolidin-1 -yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-(((2-methoxyethyl)amino)methyl)pi colinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((2-methoxyethyl)amino)met hyl)picolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((2-methoxyethyl)amino)met hyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-(((3-fluoropropyl)amino)methyl)pi colinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((3-fluoropropyl)amino)met hyl)picolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((3-fluoropropyl)amino)met hyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxypyrrolidin-1- yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-hydroxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-hydroxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-hydroxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-hydroxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxypyrrolidin-1- yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-hydroxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-hydroxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-hydroxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-hydroxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxypropyl)amino )methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((S)-2-hydroxypropyl)a mino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((R)-2-hydroxypropyl)a mino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((S)-2-hydroxypropyl)a mino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((R)-2-hydroxypropyl)a mino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((3-fluoropropyl)amino) methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((3-fluoropropyl)amino) methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((3-fluoropropyl)amino) methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxypropyl)amino )methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((S)-2-hydroxypropyl)a mino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((R)-2-hydroxypropyl)a mino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((S)-2-hydroxypropyl)a mino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((R)-2-hydroxypropyl)a mino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxy-2- methylpropyl)amino)methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxy-2- methylpropyl)amino)methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxy-2- methylpropyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)(methy l)amino)methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)(methy l)amino)methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)(methy l)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-methoxyethyl)amino) methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-methoxyethyl)amino) methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-methoxyethyl)amino) methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((oxetan-2-ylmethyl)ami no)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((oxetan-2-ylmethyl)ami no)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((oxetan-2-ylmethyl)ami no)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((3-hydroxy-3- methylcyclobutyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((1r,3s)-3-hydroxy-3- methylcyclobutyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((1r,3s)-3-hydroxy-3- methylcyclobutyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((1r,3r)-3-hydroxy-3- methylcyclobutyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((1r,3r)-3-hydroxy-3- methylcyclobutyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-(hydroxymethyl)azeti din-1-yl)methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-(hydroxymethyl)azeti din-1-yl)methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-(hydroxymethyl)azeti din-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((3-hydroxypropyl)amino )methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((3-hydroxypropyl)amino )methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((3-hydroxypropyl)amino )methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((1-hydroxy-3-methylbut an-2- yl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((S)-1-hydroxy-3-methy lbutan-2- yl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((R)-1-hydroxy-3-methy lbutan-2- yl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((S)-1-hydroxy-3-methy lbutan-2- yl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((((R)-1-hydroxy-3-methy lbutan-2- yl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-methoxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-methoxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-methoxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-methoxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-methoxypyrrolidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-6- methoxypicolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-6- methoxypicolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-6- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)thiazole-2- carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)thiazole-2- carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)thiazole-2- carboxamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-1-methyl-1H- imidazole-2-carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-1-methyl-1H- imidazole-2-carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-1-methyl-1H- imidazole-2-carboxamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)pyrazine-2- carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)pyrazine-2- carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)pyrazine-2- carboxamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)thiazole-2- carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)thiazole-2- carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)thiazole-2- carboxamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-3-(2-((3-fluoropropyl)(methyl)amino )ethyl)-1H-pyrazole-5- carboxamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-3-(2-((3-fluoropropyl)(methyl )amino)ethyl)-1H-pyrazole-5- carboxamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-3-(2-((3-fluoropropyl)(methyl )amino)ethyl)-1H-pyrazole-5- carboxamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-3- methoxypicolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-3- methoxypicolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-3- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-3-methylpicolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-3-methylpicolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-3-methylpicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)picolinamide; N-(3-(3-chloro-2-(2-(2-hydroxypropyl)-8-methoxy-1,2,3,4-tetr ahydroisoquinolin-6- yl)pyridin-4-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)m ethyl)picolinamide; (S)-N-(3-(3-chloro-2-(2-(2-hydroxypropyl)-8-methoxy-1,2,3,4- tetrahydroisoquinolin-6- yl)pyridin-4-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)m ethyl)picolinamide; (R)-N-(3-(3-chloro-2-(2-(2-hydroxypropyl)-8-methoxy-1,2,3,4- tetrahydroisoquinolin-6- yl)pyridin-4-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)m ethyl)picolinamide; N-(3-(3-chloro-2-(8-methoxy-2-((5-oxopyrrolidin-2-yl)methyl) -1,2,3,4- tetrahydroisoquinolin-6-yl)pyridin-4-yl)-2-methylphenyl)-5-( ((2- hydroxyethyl)amino)methyl)picolinamide; (S)-N-(3-(3-chloro-2-(8-methoxy-2-((5-oxopyrrolidin-2-yl)met hyl)-1,2,3,4- tetrahydroisoquinolin-6-yl)pyridin-4-yl)-2-methylphenyl)-5-( ((2- hydroxyethyl)amino)methyl)picolinamide; (R)-N-(3-(3-chloro-2-(8-methoxy-2-((5-oxopyrrolidin-2-yl)met hyl)-1,2,3,4- tetrahydroisoquinolin-6-yl)pyridin-4-yl)-2-methylphenyl)-5-( ((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(3-chloro-4-(6-methoxy-5-((((5-oxopyrrolidin-2-yl)methy l)amino)methyl)pyrazin-2- yl)pyridin-2-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)m ethyl)picolinamide; (S)-N-(3-(3-chloro-4-(6-methoxy-5-((((5-oxopyrrolidin-2-yl)m ethyl)amino)methyl)pyrazin- 2-yl)pyridin-2-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino )methyl)picolinamide; and (R)-N-(3-(3-chloro-4-(6-methoxy-5-((((5-oxopyrrolidin-2-yl)m ethyl)amino)methyl)pyrazin- 2-yl)pyridin-2-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino )methyl)picolinamide. (5-oxopyrrolidin-2-yl)methyl ((3'-chloro-2'-(2-chloro-3-(5-(((2- hydroxyethyl)amino)methyl)picolinamido)phenyl)-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)carbamate; (S)-(5-oxopyrrolidin-2-yl)methyl ((3'-chloro-2'-(2-chloro-3-(5-(((2- hydroxyethyl)amino)methyl)picolinamido)phenyl)-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)carbamate; (R)-(5-oxopyrrolidin-2-yl)methyl ((3'-chloro-2'-(2-chloro-3-(5-(((2- hydroxyethyl)amino)methyl)picolinamido)phenyl)-6-methoxy-[2, 4'-bipyridin]-5- yl)methyl)carbamate; 5-(((2-hydroxyethyl)amino)methyl)-N-(3-(4-(6-methoxy-5-((((5 -oxopyrrolidin-2- yl)methyl)amino)methyl)pyrazin-2-yl)-3-methylpyridin-2-yl)-2 -methylphenyl)picolinamide; (S)-5-(((2-hydroxyethyl)amino)methyl)-N-(3-(4-(6-methoxy-5-( (((5-oxopyrrolidin-2- yl)methyl)amino)methyl)pyrazin-2-yl)-3-methylpyridin-2-yl)-2 -methylphenyl)picolinamide; (R)-5-(((2-hydroxyethyl)amino)methyl)-N-(3-(4-(6-methoxy-5-( (((5-oxopyrrolidin-2- yl)methyl)amino)methyl)pyrazin-2-yl)-3-methylpyridin-2-yl)-2 -methylphenyl)picolinamide; N-(3-(3-chloro-4-(6-methoxy-5-((((5-oxopyrrolidin-2-yl)methy l)amino)methyl)pyrazin-2- yl)pyridin-2-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino)m ethyl)pyrazine-2- carboxamide; (S)-N-(3-(3-chloro-4-(6-methoxy-5-((((5-oxopyrrolidin-2-yl)m ethyl)amino)methyl)pyrazin- 2-yl)pyridin-2-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino )methyl)pyrazine-2- carboxamide; (R)-N-(3-(3-chloro-4-(6-methoxy-5-((((5-oxopyrrolidin-2-yl)m ethyl)amino)methyl)pyrazin- 2-yl)pyridin-2-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino )methyl)pyrazine-2- carboxamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-6-methylpicolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-6-methylpicolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-6-methylpicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-4-methylpicolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-4-methylpicolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-4-methylpicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-(((3-fluoropropyl)amino)methyl)th iazole-2-carboxamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((3-fluoropropyl)amino)met hyl)thiazole-2-carboxamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((3-fluoropropyl)amino)met hyl)thiazole-2-carboxamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-((3-hydroxypyrrolidin-1-yl)methyl )thiazole-2-carboxamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((S)-3-hydroxypyrrolidin-1 -yl)methyl)thiazole-2- carboxamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((R)-3-hydroxypyrrolidin-1 -yl)methyl)thiazole-2- carboxamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((S)-3-hydroxypyrrolidin-1 -yl)methyl)thiazole-2- carboxamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((R)-3-hydroxypyrrolidin-1 -yl)methyl)thiazole-2- carboxamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-(((2-hydroxyethyl)amino)methyl)th iazole-2-carboxamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((2-hydroxyethyl)amino)met hyl)thiazole-2-carboxamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((2-hydroxyethyl)amino)met hyl)thiazole-2-carboxamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-3-hydroxy-5-(((2- hydroxyethyl)amino)methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-3-hydroxy-5-(((2- hydroxyethyl)amino)methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-3-hydroxy-5-(((2- hydroxyethyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-1H-imidazole-2- carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-1H-imidazole-2- carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-1H-imidazole-2- carboxamide; 5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3-(3'- chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)thiazole-2- carboxamide; (S)-5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3'-chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)thiazole-2- carboxamide; (R)-5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3'-chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)thiazole-2- carboxamide; 1-((2-((2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidi n-2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)carbamoyl)thiazol-5-yl)methyl) piperidine-4-carboxylic acid; (S)-1-((2-((2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrro lidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)carbam oyl)thiazol-5- yl)methyl)piperidine-4-carboxylic acid; (R)-1-((2-((2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrro lidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)carbam oyl)thiazol-5- yl)methyl)piperidine-4-carboxylic acid; 5-(((2-hydroxyethyl)amino)methyl)-N-(3-(6-methoxy-3'-methyl- 5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)picolinamide; (S)-5-(((2-hydroxyethyl)amino)methyl)-N-(3-(6-methoxy-3'-met hyl-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)picolinamide; (R)-5-(((2-hydroxyethyl)amino)methyl)-N-(3-(6-methoxy-3'-met hyl-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(2-hydroxyethyl)-5,6,7,8 -tetrahydro-2,7-naphthyridine- 3-carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(2-hydroxyethyl)-5,6,7,8 -tetrahydro-2,7-naphthyridine- 3-carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(2-hydroxyethyl)-5,6,7,8 -tetrahydro-2,7-naphthyridine- 3-carboxamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-1-methyl-1H- imidazole-2-carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-1-methyl-1H- imidazole-2-carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-1-methyl-1H- imidazole-2-carboxamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'-yl)- 2-methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)thiazole-2- carboxamide; 1-((3'-chloro-2'-(3-(5-(((2-hydroxyethyl)amino)methyl)thiazo le-2-carboxamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)piperid ine-4-carboxylic acid; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-methoxyazetidin-1-yl )methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-methoxyazetidin-1-yl )methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-methoxyazetidin-1-yl )methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-(methoxymethyl)azeti din-1-yl)methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-(methoxymethyl)azeti din-1-yl)methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-(methoxymethyl)azeti din-1-yl)methyl)picolinamide; N-(3-(3'-chloro-5-((3-hydroxypyrrolidin-1-yl)methyl)-6-metho xy-[2,4'-bipyridin]-2'-yl)-2- methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)thiazole-2-ca rboxamide; (S)-N-(3-(3'-chloro-5-((3-hydroxypyrrolidin-1-yl)methyl)-6-m ethoxy-[2,4'-bipyridin]-2'-yl)- 2-methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)thiazole-2- carboxamide; (R)-N-(3-(3'-chloro-5-((3-hydroxypyrrolidin-1-yl)methyl)-6-m ethoxy-[2,4'-bipyridin]-2'-yl)- 2-methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)thiazole-2- carboxamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-4- methoxypicolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-4- methoxypicolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((2-hydroxyethyl)amino) methyl)-4- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-5- methoxypicolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-5- methoxypicolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-5- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxypyrrolidin-1- yl)methyl)-1-methyl-1H- imidazole-2-carboxamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-hydroxypyrrolidi n-1-yl)methyl)-1-methyl-1H- imidazole-2-carboxamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-hydroxypyrrolidi n-1-yl)methyl)-1-methyl-1H- imidazole-2-carboxamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-hydroxypyrrolidi n-1-yl)methyl)-1-methyl-1H- imidazole-2-carboxamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-hydroxypyrrolidi n-1-yl)methyl)-1-methyl-1H- imidazole-2-carboxamide; 5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chloro-6- methoxy-5-((((5-oxopyrrolidin- 2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylph enyl)-1-methyl-1H-imidazole- 2-carboxamide; (S)-5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chlor o-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-1-methyl- 1H-imidazole-2-carboxamide; (R)-5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chlor o-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-1-methyl- 1H-imidazole-2-carboxamide; N-(3-(3-chloro-2-(3-methoxy-4-((((1-methyl-5-oxopyrrolidin-2 - yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-((3-hydroxypyrrolidin-1- yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-(((((S)-1-methyl-5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((S)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-(((((S)-1-methyl-5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((R)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-(((((R)-1-methyl-5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((S)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-(((((R)-1-methyl-5-oxopyrrolid in-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((R)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; 3-(((3'-chloro-2'-(3-(5-(((2-hydroxyethyl)amino)methyl)thiaz ole-2-carboxamido)-2- methylphenyl)-6-methoxy-[2,4'-bipyridin]-5-yl)methyl)amino)- 2,2-dimethylpropanoic acid; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-2-(2-hydroxyethyl)-2,3-dih ydro-1H-pyrrolo[3,4- c]pyridine-6-carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-2-(2-hydroxyethyl)-2,3-dih ydro-1H-pyrrolo[3,4- c]pyridine-6-carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-2-(2-hydroxyethyl)-2,3-dih ydro-1H-pyrrolo[3,4- c]pyridine-6-carboxamide; N-(3-(3'-chloro-6-methoxy-5-((7-oxo-2,6-diazaspiro[3.4]octan -2-yl)methyl)-[2,4'-bipyridin]- 2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)pic olinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-6-(2-hydroxyethyl)-5,6,7,8 -tetrahydro-2,6-naphthyridine- 3-carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-6-(2-hydroxyethyl)-5,6,7,8 -tetrahydro-2,6-naphthyridine- 3-carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-6-(2-hydroxyethyl)-5,6,7,8 -tetrahydro-2,6-naphthyridine- 3-carboxamide; 4-(((2-hydroxyethyl)amino)methyl)-N-(3-(6-methoxy-3'-methyl- 5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)picolinamide; (S)-4-(((2-hydroxyethyl)amino)methyl)-N-(3-(6-methoxy-3'-met hyl-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)picolinamide; (R)-4-(((2-hydroxyethyl)amino)methyl)-N-(3-(6-methoxy-3'-met hyl-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-6,7-dihydro-5H- cyclopenta[c]pyridine-1-carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-6,7-dihydro-5H- cyclopenta[c]pyridine-1-carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((2-hydroxyethyl)amino) methyl)-6,7-dihydro-5H- cyclopenta[c]pyridine-1-carboxamide; N-(3-(3'-chloro-5-((3-hydroxyazetidin-1-yl)methyl)-6-methoxy -[2,4'-bipyridin]-2'-yl)-2- methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picolinamide ; N-(3-(5-(((1-acetylpyrrolidin-3-yl)amino)methyl)-3'-chloro-6 -methoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picoli namide; (S)-N-(3-(5-(((1-acetylpyrrolidin-3-yl)amino)methyl)-3'-chlo ro-6-methoxy-[2,4'-bipyridin]- 2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)pic olinamide; (R)-N-(3-(5-(((1-acetylpyrrolidin-3-yl)amino)methyl)-3'-chlo ro-6-methoxy-[2,4'-bipyridin]- 2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)pic olinamide; N-(3-(5-((((1-acetylpiperidin-4-yl)methyl)amino)methyl)-3'-c hloro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((oxetan-2-ylmethyl)amino)methy l)-[2,4'-bipyridin]-2'-yl)-2- methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picolinamide ; (S)-N-(3-(3'-chloro-6-methoxy-5-(((oxetan-2-ylmethyl)amino)m ethyl)-[2,4'-bipyridin]-2'-yl)- 2-methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picolinami de; (R)-N-(3-(3'-chloro-6-methoxy-5-(((oxetan-2-ylmethyl)amino)m ethyl)-[2,4'-bipyridin]-2'-yl)- 2-methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picolinami de; N-(3-(3'-chloro-6-methoxy-5-((((1-methyl-5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((1-methyl-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidi n-1-yl)methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((1-methyl-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidi n-1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((6-oxo-2,5-diazaspiro[3.4]octan -2-yl)methyl)-[2,4'-bipyridin]- 2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)pic olinamide; 5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chloro-6- methoxy-5-((((5-oxopyrrolidin- 2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylph enyl)-4-methoxypicolinamide; (S)-5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chlor o-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-4- methoxypicolinamide; (R)-5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chlor o-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-4- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((3-fluoropropyl)amino) methyl)-4- methoxypicolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((3-fluoropropyl)amino) methyl)-4- methoxypicolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((3-fluoropropyl)amino) methyl)-4- methoxypicolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)(methyl)amino)methyl)-3'-c hloro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((methyl((5-oxopyrrolidin-2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-((3-hydroxypyrrolidin-1- yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((methyl(((S)-5-oxopyrrolidin- 2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((S)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((methyl(((S)-5-oxopyrrolidin- 2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((R)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((methyl(((R)-5-oxopyrrolidin- 2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((S)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(3-chloro-2-(3-methoxy-4-((methyl(((R)-5-oxopyrrolidin- 2- yl)methyl)amino)methyl)phenyl)pyridin-4-yl)-2-methylphenyl)- 5-(((R)-3-hydroxypyrrolidin- 1-yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-((3-(methoxyme thyl)azetidin-1- yl)methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-((3-(methoxyme thyl)azetidin-1- yl)methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-((3-(methoxyme thyl)azetidin-1- yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxypyrrolidin-1- yl)methyl)-4- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-hydroxypyrrolidi n-1-yl)methyl)-4- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-hydroxypyrrolidi n-1-yl)methyl)-4- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((S)-3-hydroxypyrrolidi n-1-yl)methyl)-4- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-(((R)-3-hydroxypyrrolidi n-1-yl)methyl)-4- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-((((5-oxopyrro lidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-(((((S)-5-oxop yrrolidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-(((((R)-5-oxop yrrolidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-(((((S)-5-oxop yrrolidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-methoxy-5-(((((R)-5-oxop yrrolidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((methyl((5-oxopyrrolidin-2-yl)m ethyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl )methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((methyl((5-oxopyrrolidin-2- yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidi n-1-yl)methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((methyl((5-oxopyrrolidin-2- yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)-2-methylphenyl)-5-((3-hydroxyazetidi n-1-yl)methyl)picolinamide; 4-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chloro-6- methoxy-5-((((5-oxopyrrolidin- 2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylph enyl)-5-methoxypicolinamide; (S)-4-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chlor o-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5- methoxypicolinamide; (R)-4-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(3-(3'-chlor o-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((3-fluoropropyl)amino) methyl)-5- methoxypicolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((3-fluoropropyl)amino) methyl)-5- methoxypicolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((3-fluoropropyl)amino) methyl)-5- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-((3-hydroxypyrrolidin-1- yl)methyl)-5- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((S)-3-hydroxypyrrolidi n-1-yl)methyl)-5- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((R)-3-hydroxypyrrolidi n-1-yl)methyl)-5- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((S)-3-hydroxypyrrolidi n-1-yl)methyl)-5- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-4-(((R)-3-hydroxypyrrolidi n-1-yl)methyl)-5- methoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-methoxy-4-((3-(methoxyme thyl)azetidin-1- yl)methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-methoxy-4-((3-(methoxyme thyl)azetidin-1- yl)methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-methoxy-4-((3-(methoxyme thyl)azetidin-1- yl)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((oxetan-2-yl)methyl)amino)met hyl)-[2,4'-bipyridin]-2'-yl)-2- methylphenyl)-5-((((oxetan-2-yl)methyl)amino)methyl)picolina mide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-oxetan-2-yl)methyl)amino )methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-(((((S)-oxetan-2-yl)methyl)amino)methy l)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-oxetan-2-yl)methyl)amino )methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-(((((R)-oxetan-2-yl)methyl)amino)methy l)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-oxetan-2-yl)methyl)amino )methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-(((((S)-oxetan-2-yl)methyl)amino)methy l)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-oxetan-2-yl)methyl)amino )methyl)-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-(((((R)-oxetan-2-yl)methyl)amino)methy l)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-methoxy-4-((((5-oxopyrro lidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-methoxy-4-(((((S)-5-oxop yrrolidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-methoxy-4-(((((R)-5-oxop yrrolidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-methoxy-4-(((((S)-5-oxop yrrolidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-5-methoxy-4-(((((R)-5-oxop yrrolidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(5-(((1-acetylpiperidin-3-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'-yl)- 2-methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picolinami de; (S)-N-(3-(5-(((1-acetylpiperidin-3-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picoli namide; (R)-N-(3-(5-(((1-acetylpiperidin-3-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-((3-hydroxyazetidin-1-yl)methyl)picoli namide; N-(3-(3'-chloro-5-((3-hydroxyazetidin-1-yl)methyl)-6-methoxy -[2,4'-bipyridin]-2'-yl)-2- methylphenyl)-5-(((oxetan-2-ylmethyl)amino)methyl)picolinami de; (S)-N-(3-(3'-chloro-5-((3-hydroxyazetidin-1-yl)methyl)-6-met hoxy-[2,4'-bipyridin]-2'-yl)-2- methylphenyl)-5-(((oxetan-2-ylmethyl)amino)methyl)picolinami de; (R)-N-(3-(3'-chloro-5-((3-hydroxyazetidin-1-yl)methyl)-6-met hoxy-[2,4'-bipyridin]-2'-yl)-2- methylphenyl)-5-(((oxetan-2-ylmethyl)amino)methyl)picolinami de; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(3-fluoropropyl)-5,6,7,8 -tetrahydro-2,7-naphthyridine-3- carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(3-fluoropropyl)-5,6,7,8 -tetrahydro-2,7-naphthyridine-3- carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(3-fluoropropyl)-5,6,7,8 -tetrahydro-2,7-naphthyridine-3- carboxamide; 3-(2-((2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)carbamoyl)thiazol-5-yl)propano ic acid; (S)-3-(2-((2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrol idin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)carbam oyl)thiazol-5-yl)propanoic acid; (R)-3-(2-((2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrol idin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)carbam oyl)thiazol-5-yl)propanoic acid; 5-(2-aminoethyl)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5- oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)thiazo le-2-carboxamide; (S)-5-(2-aminoethyl)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-(( ((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)thiazo le-2-carboxamide; (R)-5-(2-aminoethyl)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-(( ((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)phenyl)thiazo le-2-carboxamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-((5-oxopyrrolidin-2-yl)m ethyl)-5,6,7,8-tetrahydro-2,7- naphthyridine-3-carboxamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(((S)-5-oxopyrrolidin-2- yl)methyl)-5,6,7,8-tetrahydro- 2,7-naphthyridine-3-carboxamide; N-(3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(((R)-5-oxopyrrolidin-2- yl)methyl)-5,6,7,8-tetrahydro- 2,7-naphthyridine-3-carboxamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(((S)-5-oxopyrrolidin-2- yl)methyl)-5,6,7,8-tetrahydro- 2,7-naphthyridine-3-carboxamide; N-(3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(((R)-5-oxopyrrolidin-2- yl)methyl)-5,6,7,8-tetrahydro- 2,7-naphthyridine-3-carboxamide; 4-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3-(3'- chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-5- methoxypicolinamide; (S)-4-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3'-chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-5- methoxypicolinamide; (R)-4-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3'-chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-5- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-methoxy-4-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-methoxy-4-(((((S)-5-oxopyrr olidin-2- yl)methyl)amino)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-methoxy-4-(((((R)-5-oxopyrr olidin-2- yl)methyl)amino)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-methoxy-4-(((((S)-5-oxopyrr olidin-2- yl)methyl)amino)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-methoxy-4-(((((R)-5-oxopyrr olidin-2- yl)methyl)amino)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-4-((3-hydroxypyrrolidin-1-yl)methyl )-5-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-(((S)-3-hydroxypyrrolidin-1 -yl)methyl)-5- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-(((R)-3-hydroxypyrrolidin-1 -yl)methyl)-5- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-(((S)-3-hydroxypyrrolidin-1 -yl)methyl)-5- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-(((R)-3-hydroxypyrrolidin-1 -yl)methyl)-5- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-4-(((2-hydroxyethyl)(methyl)amino)m ethyl)-5- methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-(((2-hydroxyethyl)(methyl)a mino)methyl)-5- methoxypicolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-(((2-hydroxyethyl)(methyl)a mino)methyl)-5- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-4-(((2-hydroxyethyl)amino)methyl)-5 -methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-(((2-hydroxyethyl)amino)met hyl)-5-methoxypicolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-(((2-hydroxyethyl)amino)met hyl)-5-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-methoxy-4-((3-(methoxymethyl)azet idin-1- yl)methyl)picolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-methoxy-4-((3-(methoxymethy l)azetidin-1- yl)methyl)picolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-methoxy-4-((3-(methoxymethy l)azetidin-1- yl)methyl)picolinamide; 5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3-(3'- chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-4- methoxypicolinamide; (S)-5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3'-chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-4- methoxypicolinamide; (R)-5-(((1-acetylpiperidin-4-yl)amino)methyl)-N-(2-chloro-3- (3'-chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-(((2-hydroxyethyl)amino)methyl)-4 -methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((2-hydroxyethyl)amino)met hyl)-4-methoxypicolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((2-hydroxyethyl)amino)met hyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-4-(((3-fluoropropyl)amino)methyl)-5 -methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-(((3-fluoropropyl)amino)met hyl)-5-methoxypicolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-(((3-fluoropropyl)amino)met hyl)-5-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-((3-hydroxypyrrolidin-1-yl)methyl )-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((S)-3-hydroxypyrrolidin-1 -yl)methyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((R)-3-hydroxypyrrolidin-1 -yl)methyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((S)-3-hydroxypyrrolidin-1 -yl)methyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((R)-3-hydroxypyrrolidin-1 -yl)methyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-4-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-methoxy-5-(((((S)-5-oxopyrr olidin-2- yl)methyl)amino)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-methoxy-5-(((((R)-5-oxopyrr olidin-2- yl)methyl)amino)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-methoxy-5-(((((S)-5-oxopyrr olidin-2- yl)methyl)amino)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-methoxy-5-(((((R)-5-oxopyrr olidin-2- yl)methyl)amino)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-4-methoxy-5-((3-(methoxymethyl)azet idin-1- yl)methyl)picolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-methoxy-5-((3-(methoxymethy l)azetidin-1- yl)methyl)picolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-methoxy-5-((3-(methoxymethy l)azetidin-1- yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-(((2-hydroxyethyl)(methyl)amino)m ethyl)-4- methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((2-hydroxyethyl)(methyl)a mino)methyl)-4- methoxypicolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((2-hydroxyethyl)(methyl)a mino)methyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-(((3-fluoropropyl)amino)methyl)-4 -methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((3-fluoropropyl)amino)met hyl)-4-methoxypicolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((3-fluoropropyl)amino)met hyl)-4-methoxypicolinamide; 7-(1-acetylpiperidin-4-yl)-N-(3-(3'-chloro-6-methoxy-5-((((5 -oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5,6,7,8-tetrahydro-2,7- naphthyridine-3-carboxamide; (S)-7-(1-acetylpiperidin-4-yl)-N-(3-(3'-chloro-6-methoxy-5-( (((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5,6,7,8-tetrahydro-2,7- naphthyridine-3-carboxamide; (R)-7-(1-acetylpiperidin-4-yl)-N-(3-(3'-chloro-6-methoxy-5-( (((5-oxopyrrolidin-2- yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'-yl)-2-methylphen yl)-5,6,7,8-tetrahydro-2,7- naphthyridine-3-carboxamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(oxetan-3-ylmethyl)-5,6, 7,8-tetrahydro-2,7- naphthyridine-3-carboxamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(oxetan-3-ylmethyl)-5,6, 7,8-tetrahydro-2,7- naphthyridine-3-carboxamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methylphenyl)-7-(oxetan-3-ylmethyl)-5,6, 7,8-tetrahydro-2,7- naphthyridine-3-carboxamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-fluorophenyl)-5-(((2-hydroxyethyl)amino) methyl)-4- methoxypicolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-fluorophenyl)-5-(((2-hydroxyethyl)amino) methyl)-4- methoxypicolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-fluorophenyl)-5-(((2-hydroxyethyl)amino) methyl)-4- methoxypicolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'-yl)- 2-methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)-4-methoxyp icolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'-yl)- 2-methylphenyl)-4-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)picolinamide; (S)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-4-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamide; (R)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-4-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-fluorophenyl)-5-(((2-hydroxyethyl)amino) methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-fluorophenyl)-5-(((2-hydroxyethyl)amino) methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-fluorophenyl)-5-(((2-hydroxyethyl)amino) methyl)picolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'-yl)- 2-methylphenyl)-5-(((2-hydroxypropyl)amino)methyl)-4-methoxy picolinamide; (S)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-(((2-hydroxypropyl)amino)methyl)-4-met hoxypicolinamide; (R)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-(((2-hydroxypropyl)amino)methyl)-4-met hoxypicolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'-yl)- 2-methylphenyl)-5-((3-hydroxypyrrolidin-1-yl)methyl)-4-metho xypicolinamide; (S)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-((3-hydroxypyrrolidin-1-yl)methyl)-4-m ethoxypicolinamide; (R)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)-5-((3-hydroxypyrrolidin-1-yl)methyl)-4-m ethoxypicolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'-yl)- 2-methylphenyl)-5-((3-(hydroxymethyl)azetidin-1-yl)methyl)-4 -methoxypicolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'-yl)- 2-chlorophenyl)-5-(((2-hydroxyethyl)amino)methyl)-4-methoxyp icolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'-yl)- 2-methylphenyl)-4-methoxy-5-((3-(methoxymethyl)azetidin-1-yl )methyl)picolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'-yl)- 2-chlorophenyl)-4-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)picolinamide; (S)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'-bipyridin]-2'- yl)-2-chlorophenyl)-4-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamide; (R)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'-bipyridin]-2'- yl)-2-chlorophenyl)-4-methoxy-5-((((5-oxopyrrolidin-2- yl)methyl)amino)methyl)picolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'-yl)- 2-chlorophenyl)-5-((3-hydroxypyrrolidin-1-yl)methyl)-4-metho xypicolinamide; (S)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'-bipyridin]-2'- yl)-2-chlorophenyl)-5-((3-hydroxypyrrolidin-1-yl)methyl)-4-m ethoxypicolinamide; (R)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'-bipyridin]-2'- yl)-2-chlorophenyl)-5-((3-hydroxypyrrolidin-1-yl)methyl)-4-m ethoxypicolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'-yl)- 2-chlorophenyl)-5-((3-(hydroxymethyl)azetidin-1-yl)methyl)-4 -methoxypicolinamide; 1-((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlo ro-6-methoxy-[2,4'-bipyridin]-2'- yl)-2-methylphenyl)carbamoyl)-4-methoxypyridin-3-yl)methyl)p iperidine-4-carboxylic acid; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'-yl)- 2-chlorophenyl)-4-methoxy-5-((3-(methoxymethyl)azetidin-1-yl )methyl)picolinamide; N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro-6- methoxy-[2,4'-bipyridin]-2'-yl)- 2-chlorophenyl)-5-(((2-hydroxypropyl)amino)methyl)-4-methoxy picolinamide; (S)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'-bipyridin]-2'- yl)-2-chlorophenyl)-5-(((2-hydroxypropyl)amino)methyl)-4-met hoxypicolinamide; (R)-N-(3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlor o-6-methoxy-[2,4'-bipyridin]-2'- yl)-2-chlorophenyl)-5-(((2-hydroxypropyl)amino)methyl)-4-met hoxypicolinamide; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methoxyphenyl)-5-(((2-hydroxyethyl)amino )methyl)-4- methoxypicolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methoxyphenyl)-5-(((2-hydroxyethyl)amino )methyl)-4- methoxypicolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methoxyphenyl)-5-(((2-hydroxyethyl)amino )methyl)-4- methoxypicolinamide; 1-((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlo ro-6-methoxy-[2,4'-bipyridin]-2'- yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin-3-yl)methyl)p iperidine-4-carboxylic acid; N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)methyl) amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methoxyphenyl)-5-(((2-hydroxyethyl)amino )methyl)picolinamide; (S)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methoxyphenyl)-5-(((2-hydroxyethyl)amino )methyl)picolinamide; (R)-N-(3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-yl)met hyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)-2-methoxyphenyl)-5-(((2-hydroxyethyl)amino )methyl)picolinamide; 3-(((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chl oro-6-methoxy-[2,4'-bipyridin]- 2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin-3-yl)methy l)amino)-2,2- dimethylpropanoic acid; 4-(((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chl oro-6-methoxy-[2,4'-bipyridin]- 2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin-3-yl)methy l)amino)cyclohexane-1- carboxylic acid; (1s,4s)-4-(((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl )-3'-chloro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3- yl)methyl)amino)cyclohexane-1-carboxylic acid; (1r,4r)-4-(((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl )-3'-chloro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3- yl)methyl)amino)cyclohexane-1-carboxylic acid; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-(((2-hydroxypropyl)amino)methyl)- 4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((((S)-2-hydroxypropyl)amin o)methyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((((R)-2-hydroxypropyl)amin o)methyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((((S)-2-hydroxypropyl)amin o)methyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((((R)-2-hydroxypropyl)amin o)methyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-(((3-hydroxypropyl)amino)methyl)- 4-methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((3-hydroxypropyl)amino)me thyl)-4-methoxypicolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((3-hydroxypropyl)amino)me thyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-((((1-hydroxycyclopropyl)methyl)a mino)methyl)-4- methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((((1-hydroxycyclopropyl)me thyl)amino)methyl)-4- methoxypicolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((((1-hydroxycyclopropyl)me thyl)amino)methyl)-4- methoxypicolinamide; 3-(((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chl oro-6-methoxy-[2,4'-bipyridin]- 2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin-3-yl)methy l)amino)propanoic acid; ((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chloro -6-methoxy-[2,4'-bipyridin]-2'- yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin-3-yl)methyl)g lycine; 4-(((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chl oro-6-methoxy-[2,4'-bipyridin]- 2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin-3-yl)methy l)amino)butanoic acid; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-((((1-(hydroxymethyl)cyclopropyl) methyl)amino)methyl)-4- methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((((1-(hydroxymethyl)cyclop ropyl)methyl)amino)methyl)-4- methoxypicolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((((1-(hydroxymethyl)cyclop ropyl)methyl)amino)methyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-((3-hydroxyazetidin-1-yl)methyl)- 4-methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((3-hydroxyazetidin-1-yl)me thyl)-4-methoxypicolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((3-hydroxyazetidin-1-yl)me thyl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-((3-(hydroxymethyl)azetidin-1-yl) methyl)-4- methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((3-(hydroxymethyl)azetidin -1-yl)methyl)-4- methoxypicolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((3-(hydroxymethyl)azetidin -1-yl)methyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-((4-hydroxypiperidin-1-yl)methyl) -4-methoxypicolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((4-hydroxypiperidin-1-yl)m ethyl)-4-methoxypicolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((4-hydroxypiperidin-1-yl)m ethyl)-4-methoxypicolinamide; 1-((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlo ro-6-methoxy-[2,4'-bipyridin]-2'- yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin-3-yl)methyl)p yrrolidine-3-carboxylic acid; (S)-1-((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'- chloro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3-yl)methyl)pyrrolidine-3- carboxylic acid; (R)-1-((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'- chloro-6-methoxy-[2,4'- bipyridin]-2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin -3-yl)methyl)pyrrolidine-3- carboxylic acid; 4-((((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-ch loro-6-methoxy-[2,4'-bipyridin]- 2'-yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin-3- yl)methyl)amino)methyl)bicyclo[2.2.1]heptane-1-carboxylic acid; 1-((6-((3-(5-(((1-acetylpiperidin-4-yl)amino)methyl)-3'-chlo ro-6-methoxy-[2,4'-bipyridin]-2'- yl)-2-chlorophenyl)carbamoyl)-4-methoxypyridin-3-yl)methyl)a zetidine-3-carboxylic acid; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-4-methoxy-5-((3-methoxyazetidin-1-y l)methyl)picolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-methoxy-5-((3-methoxyazetid in-1-yl)methyl)picolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-methoxy-5-((3-methoxyazetid in-1-yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-4-methoxy-5-(((2-methoxyethyl)amino )methyl)picolinamide; (S)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-methoxy-5-(((2-methoxyethyl )amino)methyl)picolinamide; (R)-N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-methoxy-5-(((2-methoxyethyl )amino)methyl)picolinamide; 5-(((2-amino-2-oxoethyl)amino)methyl)-N-(2-chloro-3-(3'-chlo ro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-4- methoxypicolinamide; (S)-5-(((2-amino-2-oxoethyl)amino)methyl)-N-(2-chloro-3-(3'- chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-4- methoxypicolinamide; (R)-5-(((2-amino-2-oxoethyl)amino)methyl)-N-(2-chloro-3-(3'- chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-4-methoxy-5-((3-methoxypyrrolidin-1 -yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-methoxy-5-(((S)-3-methoxypy rrolidin-1- yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-methoxy-5-(((R)-3-methoxypy rrolidin-1- yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-methoxy-5-(((S)-3-methoxypy rrolidin-1- yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-4-methoxy-5-(((R)-3-methoxypy rrolidin-1- yl)methyl)picolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-((3-(hydroxymethyl)pyrrolidin-1-y l)methyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((S)-3-(hydroxymethyl)pyrr olidin-1-yl)methyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((R)-3-(hydroxymethyl)pyrr olidin-1-yl)methyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((S)-3-(hydroxymethyl)pyrr olidin-1-yl)methyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-(((R)-3-(hydroxymethyl)pyrr olidin-1-yl)methyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-((((5-oxopyrrolidin-2-y l)methyl)amino)methyl)-[2,4'- bipyridin]-2'-yl)phenyl)-5-(((3-hydroxycyclobutyl)amino)meth yl)-4-methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((((1s,3s)-3-hydroxycyclobu tyl)amino)methyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((S)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((((1r,3r)-3-hydroxycyclobu tyl)amino)methyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((((1s,3s)-3-hydroxycyclobu tyl)amino)methyl)-4- methoxypicolinamide; N-(2-chloro-3-(3'-chloro-6-methoxy-5-(((((R)-5-oxopyrrolidin -2-yl)methyl)amino)methyl)- [2,4'-bipyridin]-2'-yl)phenyl)-5-((((1r,3r)-3-hydroxycyclobu tyl)amino)methyl)-4- methoxypicolinamide; 5-((4-acetamidopiperidin-1-yl)methyl)-N-(2-chloro-3-(3'-chlo ro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-4- methoxypicolinamide; (S)-5-((4-acetamidopiperidin-1-yl)methyl)-N-(2-chloro-3-(3'- chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-4- methoxypicolinamide; and (R)-5-((4-acetamidopiperidin-1-yl)methyl)-N-(2-chloro-3-(3'- chloro-6-methoxy-5-((((5- oxopyrrolidin-2-yl)methyl)amino)methyl)-[2,4'-bipyridin]-2'- yl)phenyl)-4- methoxypicolinamide. Embodiment 33 provides a pharmaceutical composition comprising at least one compound of any one of Embodiments 1-32 and at least one pharmaceutically acceptable carrier. Embodiment 34 provides the pharmaceutical composition of Embodiment 33, further comprising at least one additional agent that treats, ameliorates, and/or prevents hepatitis virus infection. Embodiment 35 provides the pharmaceutical composition of Embodiment 34, wherein the at least one additional agent comprises at least one selected from the group consisting of reverse transcriptase inhibitor; capsid inhibitor; cccDNA formation inhibitor; RNA destabilizer; oligomeric nucleotide targeted against the HBV genome; immunostimulator; GalNAc-siRNA conjugate targeted against an HBV gene transcript; and therapeutic vaccine. Embodiment 36 provides the pharmaceutical composition of Embodiment 35, wherein the immunostimulator is a checkpoint inhibitor. Embodiment 37 provides the pharmaceutical composition of Embodiment 36, wherein the checkpoint inhibitor is a PD-L1 inhibitor. Embodiment 38 provides the pharmaceutical composition of any one of Embodiments 33-37, wherein the hepatitis virus is at least one selected from the group consisting of hepatitis B virus (HBV) and hepatitis D virus (HDV). Embodiment 39 provides a method of treating, ameliorating, and/or preventing hepatitis virus infection in a subject, the method comprising administering to the subject in need thereof a therapeutically effective amount of the compound of any one of Embodiments 1-32 and/or the pharmaceutical composition of any one of Embodiments 33-38, or a salt, solvate, prodrug, stereoisomer, tautomer, or any mixtures thereof. Embodiment 40 provides the method of Embodiment 39, wherein the subject is infected with hepatitis B virus (HBV). Embodiment 41 provides the method of Embodiment 39 or 40, wherein the subject is further infected with hepatitis D virus (HDV). Embodiment 42 provides the method of any one of Embodiments 39-41, wherein the subject is infected with HBV and HDV. Embodiment 43 provides the method of any one of Embodiments 39-42, wherein the subject is further administered at least one additional agent useful for treating the hepatitis virus infection. Embodiment 44 provides the method of Embodiment 43, wherein the at least one additional agent comprises at least one selected from the group consisting of reverse transcriptase inhibitor; capsid inhibitor; cccDNA formation inhibitor; RNA destabilizer; oligomeric nucleotide targeted against the HBV genome; immunostimulator; GalNAc-siRNA conjugate targeted against an HBV gene transcript; and therapeutic vaccine. Embodiment 45 provides the method of Embodiment 44, wherein the immunostimulator is a checkpoint inhibitor. Embodiment 46 provides the method of Embodiment 45, wherein the checkpoint inhibitor is a PD-L1 inhibitor. Embodiment 47 provides the method of any one of Embodiments 43-46, wherein the subject is co-administered the at least one compound and the at least one additional agent. Embodiment 48 provides the method of any one of Embodiments 43-47, wherein the at least one compound and the at least one additional agent are coformulated. Embodiment 49 provides the method of any one of Embodiments 39-48, wherein the subject is a mammal. Embodiment 50 provides the method of Embodiment 49, wherein the mammal is a human. Embodiment 51 provides a method of treating, ameliorating, and/or preventing cancer in a subject, the method comprising administering to the subject in need thereof a therapeutically effective amount of the compound of any one of Embodiments 1-32 and/or the pharmaceutical composition of any one of Embodiments 33-38, or a salt, solvate, prodrug, stereoisomer, tautomer, or any mixtures thereof. Embodiment 52 provides the method of Embodiment 51, wherein the compound or composition is the only anticancer agent administered to the subject. Embodiment 53 provides the method of Embodiment 51 or 52, wherein the compound is administered to the subject in a pharmaceutically acceptable composition. Embodiment 54 provides the method of Embodiment 51 or 53, wherein the subject is further administered at least one additional agent or therapy useful for treating, ameliorating, and/or preventing the cancer. Embodiment 55 provides the method of Embodiment 54, wherein the additional anticancer agent or therapy comprises nivolumab, pembrolizumab, atezolizumab, ipilimumab, chemotherapy, radiation therapy, and/or resection therapy. Embodiment 56 provides the method of Embodiment 54, wherein the additional anticancer agent or therapy comprises rituximab, doxorubicin, gemcitabine, nivolumab, pembrolizumab, and/or ipilimumab. Embodiment 57 provides the method of any one of Embodiments 51 and 53-56, wherein the compound or composition is coformulated and/or co-administered with the at least one additional agent. Embodiment 58 provides the method of any one of Embodiments 51-57, wherein the cancer is amenable to treatment by inhibiting PD-1, PD-L1, or the PD-1/PD-L1 interaction. Embodiment 59 provides the method of any one of Embodiments 51-58, wherein the cancer is at least one of pancreatic cancer, bladder cancer, colorectal cancer, breast cancer, prostate cancer, renal cancer, hepatocellular cancer, lung cancer, ovarian cancer, cervical cancer, gastric cancer, esophageal cancer, head and neck cancer, melanoma, neuroendocrine cancer, CNS cancer, brain cancer, bone cancer, soft tissue sarcoma, non-small cell lung cancer, small-cell lung cancer, or colon cancer. Embodiment 60 provides the method of any one of Embodiments 51-58, wherein the cancer is at least one of acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), myelodysplastic syndrome (MDS), myeloproliferative disease (MPD), chronic myeloid leukemia (CML), multiple myeloma (MM), non-Hodgkin's lymphoma (NHL), mantle cell lymphoma (MCL), follicular lymphoma, Waldestrom's macroglobulinemia (WM), T-cell lymphoma, B-cell lymphoma and diffuse large B-cell lymphoma (DLBCL). Embodiment 61 provides the method of any one of Embodiments 51-60, wherein the subject is a mammal. Embodiment 62 provides the method of Embodiment 61, wherein the mammal is a human. The disclosures of each and every patent, patent application, and publication cited herein are hereby incorporated herein by reference in their entirety. While this disclosure has been disclosed with reference to specific embodiments, it is apparent that other embodiments and variations of this disclosure may be devised by others skilled in the art without departing from the true spirit and scope of the disclosure. The appended claims are intended to be construed to include all such embodiments and equivalent variations.