Pyrazolo[3,4-b]pyridine derivative or salt thereof, and pharmaceutical composition comprising same

Abstract

The present invention provides a novel pyrazolo[3,4-b]pyridine derivative or a pharmaceutically acceptable salt thereof, a preparation method therefor, a pharmaceutical composition comprising same, and use thereof. The pyrazolo[3,4-b]pyridine derivative or the pharmaceutically acceptable salt thereof can be effectively applied in the treatment and prevention of various blood cancers or solid cancers through excellent inhibitory activity against hematopoietic progenitor kinase 1 (HPK1).

Description

Pyrazolo[3,4-B]pyridine derivative or salt thereof and pharmaceutical composition containing same

[0001] The present invention relates to a pyrazolo[3,4-b]pyridine derivative or a pharmaceutically acceptable salt thereof having excellent inhibitory activity against hematopoietic progenitor kinase 1 (HPK1), a method for preparing the same, a pharmaceutical composition comprising the same, and a use thereof.

[0002] Antibody-based immunotherapy drugs demonstrate sustained antitumor effects in a significant proportion of cancer patients, making the development of immunotherapy an effective platform for future cancer treatment. While antibody-based immunotherapy has demonstrated improved survival compared to conventional standard therapies, response rates to these treatments vary significantly across tumor types, ranging from 15% for head and neck cancer to 87% for leukemia (Science 2018; 23;359(6382):1350-1355). These characteristics hinder the widespread use of immunotherapy as a broad-spectrum anticancer treatment and necessitate the development of biomarkers that can predict response (Nature 2017;18;541(7637):321-330; Nat. Rev. Cancer 2019; Mar;19(3):133-150). Therefore, alternative approaches that modulate immune cell responses beyond current immunotherapy approaches are urgently needed.

[0003] Recently, approaches targeting intracellular pathways that modulate immune responses with small molecules have been re-evaluated. To enhance the effectiveness of immunotherapies based on this approach, it is essential to modulate immune suppression in the microtumor environment and to control peripheral tolerance to tumor antigens. Furthermore, because most immunotherapies are antibody-based and target receptors on the cell membrane, developing antibody-based drugs that target intracellular targets within tumor cells or immune cells is challenging.

[0004] Hematopoietic progenitor kinase 1 (HPK1) is a member of the MAP4K family and a serine / threonine kinase. It is mainly expressed only in hematopoietic cell lineages (T cells, B cells, DC cells, monocytes, NK cells, etc.). HPK1 has a mechanism of action that regulates the function of immune cells by participating in various signal transduction pathways such as JNK, AP-1, and NK-κB (Genes Devel. 1996; 10:2251-2264, . EMBO J. 1996; 15:7013-7025, . Proc Nat Acad Sci USA. 2009; 106(34):14508-14513). For example, HPK1 suppresses excessive T cell activity by phosphorylating and activating the T cell receptor adapter protein SLP-76 when the T cell receptor binds to its ligand and becomes active (J. Exp. Med. 2007; 204:681). In addition, in B cells, HPK1 inhibits B cell activity by interfering with the signal transduction of the B cell receptor through the phosphorylation of a protein called BLNK (J. Biol. Chem. 2012; 287:11037). Therefore, when examining HPK1 KO / KD mice in which the function of HPK1 is suppressed, it can be confirmed that T cell proliferation and inflammatory cytokines are increased, and in a tumor model using HPK1 KO / KD mice, the tumor growth rate is reduced and the effect of immunotherapy is increased when administered (Cell Rep. 2018; 25(1):80-94). In addition, the activity of COX-2 and PGE2 / adenosine in a microtumor environment has been reported to be an important factor in reducing the effectiveness of immunotherapy, and it was confirmed that the tumor growth rate induced by the immune response was reduced in HPK1 KD mice even in the presence of high levels of PGE2 (Cancer Immunol Immunother. 2010; 59(3):419-429).These mechanisms suggest that inhibition of HPK1 may increase immune cell activity and improve immunosuppression in the microtumor environment in most cancer patients. Therefore, substances that inhibit HPK1 may be useful for the prevention and treatment of all types of cancer, including various hematological malignancies and solid tumors.

[0005] The present inventors have conducted various studies to develop a substance with excellent inhibitory activity against HPK1, and as a result, discovered that a pyrazolo[3,4-b]pyridine derivative or a pharmaceutically acceptable salt thereof has excellent inhibitory activity against HPK1. Therefore, the pyrazolo[3,4-b]pyridine derivative or a salt thereof can be usefully used in the treatment and prevention of various hematological malignancies and solid cancers by inhibiting HPK1, thereby activating immune cells and improving the micro-tumor environment in which the immune system is suppressed.

[0006] Accordingly, the present invention aims to provide the pyrazolo[3,4-b]pyridine derivative or a pharmaceutically acceptable salt thereof, a method for preparing the same, a pharmaceutical composition comprising the same, and a use thereof.

[0007] According to one aspect of the present invention, a pyrazolo[3,4-b]pyridine derivative or a pharmaceutically acceptable salt thereof is provided.

[0008] According to another aspect of the present invention, a method for preparing the pyrazolo[3,4-b]pyridine derivative is provided.

[0009] According to another aspect of the present invention, a pharmaceutical composition comprising the pyrazolo[3,4-b]pyridine derivative as an active ingredient is provided.

[0010] According to another aspect of the present invention, a therapeutic method comprising administering the pyrazolo[3,4-b]pyridine derivative is provided.

[0011] According to another aspect of the present invention, there is provided the use of the pyrazolo[3,4-b]pyridine derivative or a pharmaceutically acceptable salt thereof for use in the manufacture of a medicament for inhibition of hematopoietic progenitor kinase 1.

[0012] The present invention has revealed that the above pyrazolo[3,4-b]pyridine derivative or a pharmaceutically acceptable salt thereof has excellent inhibitory activity against HPK1. Therefore, the compound according to the present invention or a pharmaceutically acceptable salt thereof can be usefully applied to the treatment and prevention of various hematological cancers or solid cancers through inhibition of HPK1 activity.

[0013] As used herein, the term 'alkyl' refers to an aliphatic hydrocarbon radical, and includes both straight-chain and branched hydrocarbon radicals. For example, C1∼C6 alkyl is an aliphatic hydrocarbon having 1 to 6 carbon atoms, and includes methyl, ethyl, propyl, n-butyl, n-pentyl, n-hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, neopentyl, isopentyl, etc.

[0014] Also, the term 'hydroxy' is defined as -OH, and the term 'alkoxy', unless otherwise defined, means a radical in which the hydrogen atom of the hydroxy group is replaced by an alkyl. For example, C1∼C6 alkoxy includes methoxy, ethoxy, propoxy, n-butoxy, n-pentyloxy, isopropoxy, sec-butoxy, tert-butoxy, neopentyloxy, isopentyloxy, etc.

[0015] Additionally, the term 'halogen' refers to fluorine, bromine, chlorine, and iodine.

[0016] Additionally, the term 'amino' is defined as -NH2, and the term 'alkylamino' means an amino substituted with a mono- or di-alkyl. For example, C1∼C6 alkylamino includes an amino substituted with a mono- or di-C1∼C6 alkyl.

[0017] Additionally, the term 'cyano' is defined as -CN.

[0018] Additionally, the term 'cycloalkyl' means a cyclic alkyl, wherein alkyl is as defined above. Examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0019] Additionally, the term 'heterocycloalkyl' means a 3 to 12 membered cycloalkyl or spirocycloalkyl containing 1 to 3 heteroatoms selected from N, O or S. Examples include, but are not limited to, azetidine, pyrrolidinyl, piperidinyl, N-methylpiperidinyl, pyrazolidinyl, morpholinyl, piperazinyl, tetrahydropyranyl, tetrahydrofuranyl, oxazolidin-2-onyl, 2,8-diazaspiro[4.5]decanyl, and the like.

[0020] Additionally, the term 'aryl' refers to an aromatic ring of 3 to 12 members, which may be single or multi-ring. Examples include, but are not limited to, phenyl, naphthyl, biphenyl, etc.

[0021] Additionally, the term 'heteroaryl' means a 3 to 12 membered aromatic ring containing 1 to 3 heteroatoms selected from N, O or S, which may be monocyclic or polycyclic. Examples thereof include, but are not limited to, thiophenyl, furyl, pyrrolyl, pyrazolyl, thiazolyl, oxazolyl, pyridinyl, pyrimidyl, quinolinyl, quinazolinyl, quinoxalinyl, [1,2,4]triazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, imidazo[1,2-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridin-6-yl, and the like.

[0022] Additionally, the term 'substituted' means substituted at one or more substitutable positions. For example, 'C1-C6 alkyl substituted with a halogen' includes C1-C6 alkyl substituted with one or more halogens, for example, 1, 2, or 3 halogens.

[0023] The present invention provides a pyrazolo[3,4-b]pyridine derivative having excellent inhibitory activity against HPK1 or a pharmaceutically acceptable salt thereof, i.e., a compound of the following chemical formula 1 or a pharmaceutically acceptable salt thereof:

[0024] <Chemical Formula 1>

[0025]

[0026] During the meal,

[0027] A is

[0028] (1) a 6 to 12 membered aryl group optionally substituted with 1 to 3 groups selected from the group consisting of hydroxy; halogen; amino; C1 to C6 alkyl; C1 to C6 alkyl substituted with 1 to 3 groups selected from the group consisting of hydroxy, halogen, C1 to C3 alkoxy, C3 to C6 cycloalkyl, and 4 to 7 membered heterocycloalkyl; mono- or di-C1 to C6 alkylamino; C1 to C6 alkoxy; C3 to C6 cycloalkyl; 4 to 7 membered heterocycloalkyl; and 4 to 7 membered heterocycloalkyloxy, wherein the cycloalkyl, heterocycloalkyl, or heterocycloalkyloxy is optionally substituted with halogen, C1 to C6 alkyl, or C1 to C6 alkyl substituted with halogen;

[0029] (2) C1∼C6 alkyl substituted with 1 to 3 groups selected from the group consisting of hydroxy; halogen; amino; C1∼C6 alkyl; hydroxy, halogen, C1∼C3 alkoxy, C3∼C6 cycloalkyl, and 4 to 7 membered heterocycloalkyl; mono- or di-C1∼C6 alkylamino; C1∼C6 alkoxy; C3∼C6 cycloalkyl; 4 to 7 membered heterocycloalkyl; 4 to 7 membered heterocycloalkyloxy; and a 5 to 12 membered heteroaryl group optionally substituted with 1 to 3 groups selected from the group consisting of 4 to 7 membered heterocycloalkylcarbonyl (wherein the cycloalkyl, heterocycloalkyl, heterocycloalkyloxy, or heterocycloalkylcarbonyl is optionally substituted with halogen, C1 to C6 alkyl, or C1 to C6 alkyl substituted with halogen).

[0030] (3) -C≡C-R1 group, wherein R1 is C1∼C6 alkyl optionally substituted with hydroxy; 4 to 7 membered heterocycloalkyl optionally substituted with halogen, C1∼C6 alkyl, or C1∼C6 alkyl substituted with 1 to 3 halogens; or 5 or 6 membered heteroaryl optionally substituted with halogen, C1∼C6 alkyl, or C1∼C6 alkyl substituted with 1 to 3 halogens,

[0031] (4) -C(O)-R2 group, wherein R2 is 4 to 7 membered heterocycloalkyl optionally substituted with 1 to 2 groups selected from the group consisting of hydroxy; halogen; C1∼C6 alkyl; and C1∼C6 alkyl substituted with 1 to 3 groups selected from the group consisting of hydroxy and halogen, or

[0032] (5) -C(O)NH-R3 group, wherein R3 is a 4 to 7 membered heterocycloalkyl group or C3 to C6 cycloalkyl group optionally substituted with 1 to 2 groups selected from the group consisting of hydroxy; halogen; C1 to C6 alkyl; and C1 to C6 alkyl substituted with 1 to 3 groups selected from the group consisting of hydroxy and halogen,

[0033] B is

[0034] (1) a 3 to 12 membered heterocycloalkyl group optionally substituted with 1 or 2 groups selected from the group consisting of halogen; C1∼C6 alkyl; C1∼C6 alkyl substituted with halogen, amino or hydroxy; hydroxy; amino; mono or di-C1∼C3 alkylamino; and C1∼C6 alkoxy;

[0035] (2) a C3∼C6 cycloalkylamino group optionally substituted with one or two groups selected from the group consisting of halogen; C1∼C6 alkyl; C1∼C6 alkyl substituted with halogen, amino or hydroxy; hydroxy; amino; mono or di-C1∼C3 alkylamino; and C1∼C6 alkoxy;

[0036] (3) a 3 to 12 membered heterocycloalkylamino group optionally substituted with 1 or 2 groups selected from the group consisting of halogen; C1∼C6 alkyl; C1∼C6 alkyl substituted with halogen, amino or hydroxy; hydroxy; amino; mono or di-C1∼C3 alkylamino; and C1∼C6 alkoxy, or

[0037] (4) -O-(CH2)n-R4 group, wherein R4 is a 3 to 12-membered heterocycloalkyl or C3∼C6 cycloalkyl, wherein the heterocycloalkyl or cycloalkyl is optionally substituted with 1 or 2 groups selected from the group consisting of hydroxy; amino; mono or di-C1∼C3 alkylamino; and C1∼C3 alkyl optionally substituted with hydroxy or amino, and n is 0, 1, or 2,

[0038] C is hydrogen; a C1∼C6 alkyl group; a C1∼C6 alkyl group substituted with 1 to 3 groups selected from the group consisting of halogen, hydroxy, C3∼C6 cycloalkyl, and hydroxycarbonyl; a C3∼C6 cycloalkyl group; a 6 to 12 membered aryl group; or a 4 to 7 membered heterocycloalkyl group,

[0039] D is hydrogen; a cyano group; an amino group; a C1∼C6 alkyl group; a C1∼C6 alkyl group substituted with halogen or hydroxy; a hydroxycarbonyl group; or a 4 to 7 membered heterocycloalkyl group optionally substituted with halogen, C1∼C6 alkyl, or C1∼C6 alkyl substituted with halogen or hydroxy.

[0040] In one embodiment of the present invention, A may be a 6 to 12 membered aryl group substituted with a 4 to 7 membered heterocycloalkyl, for example, a phenyl group substituted with morpholinyl.

[0041] In another embodiment of the present invention, A may be a 5 or 6 membered heteroaryl group optionally substituted with 1 to 3 groups selected from the group consisting of C1-C6 alkyl; C1-C6 alkyl substituted with 1 to 3 groups selected from the group consisting of halogen, C1-C3 alkoxy, C3-C6 cycloalkyl, and 4 to 7 membered heterocycloalkyl; mono- or di-C1-C6 alkylamino; C3-C6 cycloalkyl; 4 to 7 membered heterocycloalkyl; 4 to 7 membered heterocycloalkyloxy; and 4 to 7 membered heterocycloalkylcarbonyl. The cycloalkyl, heterocycloalkyl, heterocycloalkyloxy, or heterocycloalkylcarbonyl may be optionally substituted with, for example, halogen or C1-C6 alkyl. In addition, the heterocycloalkyl may be, for example, tetrahydropyranyl, piperazinyl, piperidinyl, or morpholinyl, and the heterocycloalkyloxy may be, for example, piperidinyloxy. In addition, the heterocycloalkylcarbonyl may be, for example, piperazinylcarbonyl or morpholinylcarbonyl. In addition, the heteroaryl group may be, for example, a pyrazolyl group or a pyridinyl group.

[0042] In another embodiment of the present invention, A may be a -C≡C-R1 group. For example, R1 may be tetrahydropyranyl; or pyrazolyl substituted with C1-C6 alkyl substituted with 1 to 3 halogens.

[0043] In one embodiment of the present invention, B may be a 3 to 12 membered heterocycloalkyl group substituted with one or two groups selected from the group consisting of halogen; C1 to C6 alkyl; hydroxy; and amino. The heterocycloalkyl group may be, for example, piperidinyl, pyrrolidinyl, or 2,8-diazaspiro[4.5]decanyl.

[0044] In another embodiment of the present invention, B may be a C3-C6 cycloalkylamino group substituted with amino or a C1-C6 alkyl group substituted with amino.

[0045] In another embodiment of the present invention, B may be an azetidinylamino group or a pyrrolidinylamino group.

[0046] In one embodiment of the present invention, C may be a C1-C6 alkyl group; a C1-C6 alkyl group substituted with one to three groups selected from the group consisting of halogen, hydroxy, C3-C6 cycloalkyl, and hydroxycarbonyl; a phenyl group; or a tetrahydrofuranyl group.

[0047] In one embodiment of the present invention, D may be hydrogen; a cyano group; an amino group; a C1-C6 alkyl group; a hydroxycarbonyl group; or an azetidinyl group substituted with a C1-C6 alkyl group substituted with a halogen or hydroxy.

[0048] In the compound of the above chemical formula 1 or a pharmaceutically acceptable salt thereof, a preferred compound may be a compound selected from the group consisting of the following compounds or a pharmaceutically acceptable salt thereof:

[0049] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0050] (S)-1-(2-((1-Isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0051] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0052] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0053] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0054] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0055] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(4-morpholinophenyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0056] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0057] N-(4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0058] N-(4-((3S,5S)-3-amino-5-methylpiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0059] (S)-N-(4-(3-amino-3-methylpiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0060] (3R,4R)-3-amino-1-(2-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-ol;

[0061] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0062] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0063] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0064] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0065] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(2-fluoroethyl)-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0066] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(2-fluoroethyl)-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0067] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(2,2-difluoroethyl)-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0068] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(2,2-difluoroethyl)-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0069] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isobutyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0070] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0071] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopentyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0072] N4'-((1S,4S)-4-aminocyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(morpholinomethyl)-[2,3'-bipyridine]-4',6'-diamine;

[0073] N-(4-((3S,5S)-3-amino-5-methylpiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0074] (S)-N-(4-(3-amino-3-methylpiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0075] (3R,4R)-3-amino-1-(2-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-ol;

[0076] N-(4-((S)-3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0077] (S)-6-((4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile;

[0078] N4-((1S,3R)-3-aminocyclopentyl)-N2-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridine-2,4-diamine;

[0079] N4-((1R,3R)-3-aminocyclopentyl)-N2-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridine-2,4-diamine;

[0080] N-(4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0081] N-(4-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0082] N4-(azetidin-3-yl)-N2-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridine-2,4-diamine;

[0083] (R)-N-(4-(3-aminopyrrolidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0084] (S)-N-(4-(3-aminopyrrolidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0085] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-phenyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0086] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-neopentyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0087] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-ethyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0088] N-(4-((S)-3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(sec-butyl)-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0089] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(3-fluoropropyl)-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0090] (S)-2-(1-(6-((4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-3-yl)azetidin-3-yl)propan-2-ol;

[0091] N4'-((1R,4R)-4-aminocyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(morpholinomethyl)-[2,3'-bipyridine]-4',6'-diamine;

[0092] N4'-((1S,4S)-4-(aminomethyl)cyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(morpholinomethyl)-[2,3'-bipyridine]-4',6'-diamine;

[0093] 1-Isopropyl-N-(4-(2-methyl-2,8-diazaspiro[4.5]decan-8-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0094] N-(4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0095] (S)-N-(4-(3-amino-3-methylpiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0096] N-(4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0097] N-(4-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0098] (3R,4R)-3-amino-1-(2-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-4-yl)piperidin-4-ol;

[0099] (S)-3-(6-((4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1H-pyrazolo[3,4-b]pyridin-1-yl)propan-1-ol;

[0100] (S)-2-(6-((4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetic acid;

[0101] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-ethyl-3-methyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0102] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-3-methyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0103] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(cyclopropylmethyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0104] (S)-N2-(1-Isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-N4-(pyrrolidin-3-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridine-2,4-diamine;

[0105] (S)-6-((4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-ethyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile;

[0106] (R)-N2-(1-Isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-N4-(pyrrolidin-3-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridine-2,4-diamine;

[0107] (S)-6-((4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile;

[0108] (S)-6-((4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxylic acid;

[0109] (S)-6-((4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-(2,2-difluoroethyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile;

[0110] (S)-6-((4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-(2-fluoroethyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile;

[0111] (S)-6-((4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-(3-fluoropropyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile;

[0112] (S)-6-((4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-(3,3,3-trifluoropropyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile;

[0113] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-ethyl-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0114] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0115] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0116] (S)-6-((4-(3-aminopiperidin-1-yl)-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile;

[0117] (S)-6-((4-(3-aminopiperidin-1-yl)-5-(1-ethyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile;

[0118] (S)-6-((4-(3-aminopiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile;

[0119] (S)-6-((4-(3-aminopiperidin-1-yl)-5-(1-cyclopropyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile;

[0120] N-(4-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0121] (S)-4-(3-Aminopiperidin-1-yl)-N6-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-N6',N6'-dimethyl-[3,3'-bipyridine]-6,6'-diamine;

[0122] (S)-N-(4-(3-aminopiperidin-1-yl)-6'-morpholino-[3,3'-bipyridin]-6-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0123] (S)-N-(4-(3-aminopiperidin-1-yl)-6'-((4-methylpiperazin-1-yl)methyl)-[3,3'-bipyridin]-6-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0124] (S)-N-(4-(3-aminopiperidin-1-yl)-6'-((4-fluoropiperidin-1-yl)methyl)-[3,3'-bipyridin]-6-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0125] (S)-N-(4-(3-aminopiperidin-1-yl)-6'-(piperazin-1-yl)-[3,3'-bipyridin]-6-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0126] N-(4-((3S,5S)-3-amino-5-fluoropiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0127] (3S)-1-(2-((1-(sec-butyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0128] (S)-1-(2-((1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0129] (S)-1-(2-((1-Isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0130] (S)-1-(2-((1-(3-fluoropropyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0131] (S)-1-(5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-2-((1-(3,3,3-trifluoropropyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)pyridin-4-yl)piperidin-3-ol;

[0132] (3S)-1-(2-((1-(sec-butyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0133] (S)-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((1-(3-fluoropropyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)pyridin-4-yl)piperidin-3-ol;

[0134] (S)-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)pyridin-4-yl)piperidin-3-ol;

[0135] (S)-1-(2-((1-ethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0136] (3S)-1-(2-((1-(sec-butyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0137] (S)-1-(2-((1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0138] (S)-1-(2-((1-(3-fluoropropyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0139] (S)-1-(5-(1-Isopropyl-1H-pyrazol-4-yl)-2-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)pyridin-4-yl)piperidin-3-ol;

[0140] N4'-((1R,4R)-4-aminocyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-((1-methylpiperidin-4-yl)oxy)-[2,3'-bipyridine]-4',6'-diamine;

[0141] N4'-((1S,4S)-4-(aminomethyl)cyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-((1-methylpiperidin-4-yl)oxy)-[2,3'-bipyridine]-4',6'-diamine;

[0142] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-3-(3-(difluoromethyl)azetidin-1-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0143] N4'-((1s,4s)-4-aminocyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(trifluoromethyl)-[2,3'-bipyridine]-4',6'-diamine;

[0144] N4'-((1s,4s)-4-aminocyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-N5,N5-dimethyl-[2,3'-bipyridine]-4',5,6'-triamine;

[0145] N4'-((1s,4s)-4-aminohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(tetrahydro-2H-pyran-4-yl)-[2,3'-bipyridine]-4',6'-diamine;

[0146] N4'-((1s,4s)-4-aminocyclohexyl)-N6'-(1-isopropyl-3-methyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(morpholinomethyl)-[2,3'-bipyridine]-4',6'-diamine;

[0147] (4'-(((1s,4s)-4-aminocyclohexyl)amino)-6'-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-[2,3'-bipyridin]-5-yl)(4-methylpiperazin-1-yl)methanone;

[0148] (4'-(((1s,4s)-4-aminocyclohexyl)amino)-6'-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-[2,3'-bipyridin]-5-yl)(morpholino)methanone;

[0149] N4'-((1s,4s)-4-aminocyclohexyl)-5-((4,4-difluoropiperidin-1-yl)methyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-[2,3'-bipyridine]-4',6'-diamine;

[0150] N4-((1s,4s)-4-aminocyclohexyl)-5-(1-isopropyl-1H-pyrazol-3-yl)-N2-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)pyridine-2,4-diamine;

[0151] N4-((1s,4s)-4-aminocyclohexyl)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-3-yl)-N2-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)pyridine-2,4-diamine;

[0152] N-[4-[(3R,4R)-3-amino-4-fluoro-1-piperidyl]-5-(1-isopropylpyrazol-4-yl)-2-pyridyl]-1-isopropyl-pyrazolo[5,4-b]pyridin-6-amine;

[0153] N6-[4-[(3S)-3-amino-1-piperidyl]-5-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-2-pyridyl]-1-isopropyl-pyrazolo[3,4-b]pyridine-3,6-diamine;

[0154] N-(4-((3S,5R)-3-amino-5-fluoropiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; and

[0155] N-(4-((3S,5S)-3-amino-5-fluoropiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine.

[0156] Among the compounds of the above chemical formula 1 or pharmaceutically acceptable salts thereof, a more preferred compound may be a compound selected from the group consisting of the following compounds or a pharmaceutically acceptable salt thereof:

[0157] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0158] (S)-1-(2-((1-Isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0159] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0160] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0161] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0162] N-(4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0163] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0164] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0165] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0166] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isobutyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0167] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0168] N4'-((1S,4S)-4-aminocyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(morpholinomethyl)-[2,3'-bipyridine]-4',6'-diamine;

[0169] (3R,4R)-3-amino-1-(2-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-ol;

[0170] N-(4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0171] N-(4-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0172] N4-(azetidin-3-yl)-N2-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridine-2,4-diamine;

[0173] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-ethyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0174] N-(4-((S)-3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(sec-butyl)-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0175] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(3-fluoropropyl)-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0176] N4'-((1R,4R)-4-aminocyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(morpholinomethyl)-[2,3'-bipyridine]-4',6'-diamine;

[0177] N-(4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0178] (S)-N-(4-(3-amino-3-methylpiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0179] N-(4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0180] (3R,4R)-3-amino-1-(2-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-4-yl)piperidin-4-ol;

[0181] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0182] N-(4-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0183] N-(4-((3S,5S)-3-amino-5-fluoropiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0184] N4'-((1s,4s)-4-aminocyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-N5,N5-dimethyl-[2,3'-bipyridine]-4',5,6'-triamine;

[0185] N4-((1s,4s)-4-aminocyclohexyl)-5-(1-isopropyl-1H-pyrazol-3-yl)-N2-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)pyridine-2,4-diamine;

[0186] N6-[4-[(3S)-3-amino-1-piperidyl]-5-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-2-pyridyl]-1-isopropyl-pyrazolo[3,4-b]pyridine-3,6-diamine;

[0187] N-(4-((3S,5R)-3-amino-5-fluoropiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; and

[0188] N-(4-((3S,5S)-3-amino-5-fluoropiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine.

[0189] Among the compounds of the above chemical formula 1 or pharmaceutically acceptable salts thereof, a more preferable compound may be a compound selected from the group consisting of the following compounds or a pharmaceutically acceptable salt thereof:

[0190] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0191] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0192] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0193] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0194] N4'-((1S,4S)-4-aminocyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(morpholinomethyl)-[2,3'-bipyridine]-4',6'-diamine;

[0195] N-(4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0196] N-(4-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine;

[0197] N4-(azetidin-3-yl)-N2-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridine-2,4-diamine;

[0198] N4'-((1s,4s)-4-aminocyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-N5,N5-dimethyl-[2,3'-bipyridine]-4',5,6'-triamine; and

[0199] N6-[4-[(3S)-3-Amino-1-piperidyl]-5-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-2-pyridyl]-1-isopropyl-pyrazolo[3,4-b]pyridine-3,6-diamine.

[0200] The compound of formula 1 or a pharmaceutically acceptable salt thereof may exist as structural isomers such as tautomers, stereoisomers such as R or S isomers having an asymmetric carbon center, geometric isomers (trans, cis), and optical isomers (enantiomers). Therefore, unless otherwise specified, the compound of formula 1 or a pharmaceutically acceptable salt thereof includes all optical isomers such as cis or trans, (R), (S), and the like, and a racemic form (RS).

[0201] The compound of formula 1 of the present invention may be in the form of a pharmaceutically acceptable salt. The salts include common acid addition salts, for example, salts derived from inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, perchloric acid, and hydrobromic acid, and salts derived from organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, succinic acid, benzoic acid, citric acid, maleic acid, malonic acid, malic acid, tartaric acid, gluconic acid, lactic acid, gentisic acid, fumaric acid, lactobionic acid, salicylic acid, phthalic acid, embonic acid, aspartic acid, glutamic acid, and acetylsalicylic acid. In addition, the salts include salts derived from amino acids such as glycine, alanine, valine, isoleucine, serine, cysteine, cystine, aspartic acid, glutamine, lysine, arginine, tyrosine, and proline. Additionally, the salt includes salts of sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, and toluenesulfonic acid.

[0202] The present invention includes a method for preparing a compound of the above chemical formula 1 or a pharmaceutically acceptable salt thereof.

[0203] For example, the compound of formula 1 or a pharmaceutically acceptable salt thereof according to the present invention can be prepared by a preparation method including a step of preparing a compound of formula II from a compound of formula I through synthesis method 1, as shown in the following reaction scheme 1 or 2; and a step of preparing a compound of formula 1 from a compound of formula II through synthesis method 2.

[0204] <Reaction Scheme 1>

[0205]

[0206] <Reaction Formula 2>

[0207]

[0208] In the above reaction formulas 1 and 2, Xa or Xb is a halogen; M is -B(OH)2 or pinacolborane (-BPin); and A, B, C, and D are as defined above.

[0209] The compounds of the above formulas Ia and Ib are commercially available.

[0210] The reaction of introducing a B group at the Xa position of the compound of formula Ia or Ib can be carried out by reacting the compound of formula Ia or Ib with B. When B is an amine substituent, the reaction can be carried out in an organic solvent such as dimethylformamide, acetonitrile, dichloromethane, or dimethyl sulfoxide, and using a base such as cesium carbonate (Cs2CO3), potassium carbonate (K2CO3), triethylamine (TEA), or diisopropylethylamine (DIPEA). In addition, the reaction can be carried out at room temperature or under heated (60°C to 110°C) conditions, but is not limited thereto. When B is an alcohol substituent, the reaction can be carried out in an organic solvent such as 1,4-dioxane, tetrahydrofuran, or acetonitrile, and using a base such as sodium hydride (NaH). Additionally, the above reaction can be performed at room temperature or low temperature (0°C), but is not limited thereto.

[0211] When A is a substituted aryl group or a substituted heteroaryl group, the reaction of introducing an A group into the Xb position of the compound of formula Ia or Ib can be carried out by reacting the compound of formula Ia or Ib having Xb with AB(OH)2 or A-pinacolborane through a Suzuki reaction. In addition, the reaction of introducing an A group into the M position of the compound of formula Ia or Ib can be carried out by reacting the compound of formula Ia or Ib having M with an A-halide through a Suzuki reaction. The Suzuki reaction can be carried out using a palladium catalyst. The above palladium catalyst includes palladium diacetate (Pd(OAc)2), tetrakis(triphenylphosphine)palladium (Pd(PPh3)4), palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride (PdCl2(dppf)2), dichlorobis(triphenylphosphine)palladium(II) (PdCl2(PPh3)2), etc. In addition, the above reaction can be performed at 80°C to 110°C using an organic solvent such as 1,4-dioxane, tetrahydrofuran, acetonitrile, 1,2-dimethoxyethane, or dimethylformamide and water in the presence of a base such as cesium carbonate (Cs2CO3), potassium carbonate (K2CO3), but is not limited thereto.

[0212] When A is a -C≡C-R1 group, the reaction of introducing the A group at the Xb position of the compound of formula Ia or Ib can be carried out by reacting the compound of formula Ia or Ib having Xb with A through a Sonogashira reaction. The Sonogashira reaction can be carried out using a palladium and copper catalyst. The palladium and copper catalysts include tetrakis(triphenylphosphine)palladium (Pd(PPh3)4), dichlorobis(triphenylphosphine)palladium(II) (PdCl2(PPh3)2), cuprous iodide (CuI), etc. In addition, the reaction can be carried out at 60 to 110°C using an organic solvent such as dimethylformamide or tetrahydrofuran in the presence of a base such as triethylamine (TEA) or diisopropylethylamine (DIPEA), but is not limited thereto.

[0213] The reaction of the compound of formula II-a with the compound of formula IV or the reaction of the compound of formula II-b with the compound of formula V (synthetic method 2) can be carried out via the Buchwald-hartwig reaction using a palladium catalyst.

[0214] The above palladium catalyst includes palladium diacetate (Pd(OAc)2), tris(dibenzylideneacetone)dipalladium (Pd2(dba)3), tetrakis(triphenylphosphine)palladium (Pd(PPh3)4), or palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride (PdCl2(dppf)2). In addition to the palladium catalyst, the reaction can be performed by adding a ligand and a base. The ligands include 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (XPhos), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos), (S)-2,2-bis(diphenylphosphino)-1,1-binaphthyl (BINAP), 1,1'-bis(diphenylphosphino)ferrocene (dppf), etc. The bases include cesium carbonate (Cs2CO3), potassium carbonate (K2CO3), potassium fluoride (KF), potassium phosphate (K3PO). 4) , sodium tert-butoxide (NaOtBu), etc. The reaction may be performed at 60°C to 110°C in an organic solvent such as benzene, toluene, 1,4-dioxane, tetrahydrofuran, acetonitrile, 1,2-dimethoxyethane, dimethylformamide, etc., but is not limited thereto.

[0215] The compounds of chemical formula IV and chemical formula V used as intermediates in the above reaction schemes 1 and 2 can be prepared according to the following reaction scheme 3.

[0216] <Reaction Formula 3>

[0217]

[0218] In the above reaction formula 3, C and D are as defined above.

[0219] A compound of formula III can be reacted with a C-halide to produce a compound of formula IV. The reaction can be carried out in an organic solvent such as dimethylformamide, acetonitrile, dichloromethane, dimethyl sulfoxide, 1,4-dioxane, or tetrahydrofuran, and using a base such as cesium carbonate (Cs2CO3), potassium carbonate (K2CO3), triethylamine (TEA), diisopropylethylamine (DIPEA), or sodium hydride (NaH). In addition, the reaction can be carried out under low temperature (0°C), room temperature, or heated (60°C to 110°C) conditions, but is not limited thereto.

[0220] A compound of formula V can be prepared by performing an amination reaction on a compound of formula IV. The reaction can be performed using a palladium catalyst. Palladium catalysts include palladium diacetate (Pd(OAc)2), tris(dibenzylideneacetone)dipalladium (Pd2(dba)3), tetrakis(triphenylphosphine)palladium (Pd(PPh3)4), or palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride (PdCl2(dppf)2). In addition to a palladium catalyst, the reaction can be performed by adding benzophenone imine, a ligand, and a base. The ligands include 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (XPhos), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos), (S)-2,2-bis(diphenylphosphino)-1,1-binaphthyl (BINAP), 1,1'-bis(diphenylphosphino)ferrocene (dppf), etc. The bases include cesium carbonate (Cs2CO3), potassium carbonate (K2CO3), potassium fluoride (KF), potassium phosphate (K3PO). 4), sodium tert-butoxide (NaOtBu), etc. The above reaction can be carried out at 60°C to 110°C in an organic solvent such as benzene, toluene, 1,4-dioxane, tetrahydrofuran, acetonitrile, 1,2-dimethoxyethane, dimethylformamide, etc., but is not limited thereto. In the case of an imine, the imine can be aminized using an acid such as 1N hydrochloric acid (HCl) in an organic solvent such as 1,4-dioxane, tetrahydrofuran, etc.

[0221] The pyrazolo[3,4-b]pyridine derivative according to the present invention or a pharmaceutically acceptable salt thereof, i.e., the compound of the following chemical formula 1 or a pharmaceutically acceptable salt thereof, has excellent inhibitory activity against hematopoietic progenitor kinase 1 (HPK1), and thus can be usefully used for the treatment and prevention of various diseases mediated by HPK1.

[0222] Accordingly, the present invention includes a pharmaceutical composition for inhibiting hematopoietic progenitor kinase 1, comprising a therapeutically effective amount of a compound of formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient. In one embodiment, the present invention provides a pharmaceutical composition for preventing or treating a disease associated with HPK1, such as cancer, including hematological cancer or solid cancer, for example, melanoma, blastoma, sarcoma, lymphoma, leukemia, bladder cancer, brain tumor, breast cancer, cervical cancer, colorectal cancer, esophageal cancer, endometrioma, liver cancer, laryngeal cancer, lung cancer, osteosarcoma, ovarian cancer, pancreatic cancer, prostate cancer, kidney cancer, thyroid cancer, ependymoma, glioblastoma, medulloblastoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma, renal cell carcinoma, etc., comprising a therapeutically effective amount of a compound of formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0223] The pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier such as a commonly used excipient, disintegrant, sweetener, lubricant or flavoring agent, and may be formulated into oral preparations such as tablets, capsules, powders, granules and suspensions, emulsions or syrups according to a conventional method; or parenteral preparations such as external solutions, external suspensions, external emulsions, gels (ointments, etc.), inhalants, sprays and injections. The preparations may be formulated into various forms, for example, single-dose or multiple-dose dosage forms.

[0224] The pharmaceutical composition of the present invention may include excipients such as lactose and corn starch, lubricants such as magnesium stearate, emulsifiers, suspending agents, stabilizers, and isotonic agents. If necessary, a sweetener and / or flavoring agent may be added.

[0225] The composition of the present invention may be administered orally or parenterally, including by inhalation, intravenous, intraperitoneal, subcutaneous, rectal, and topical administration. Accordingly, the composition of the present invention may be formulated in various forms, such as tablets, capsules, aqueous solutions, or suspensions. For oral tablets, carriers such as lactose and corn starch and lubricants such as magnesium stearate may typically be added. For oral capsules, lactose and / or dried corn starch may be used as diluents. If an oral aqueous suspension is required, the active ingredient may be combined with an emulsifying agent and / or a suspending agent. If desired, certain sweetening and / or flavoring agents may be added. For intramuscular, intraperitoneal, subcutaneous, and intravenous administration, a sterile solution of the active ingredient is typically prepared, and the pH of the solution should be suitably adjusted and buffered. For intravenous administration, the total concentration of the solute should be adjusted to impart isotonicity to the formulation. The composition according to the present invention may be in the form of an aqueous solution containing a pharmaceutically acceptable carrier, such as saline having a pH of 7.4. The solution may be introduced into the intramuscular bloodstream of a patient by local bolus injection.

[0226] The compound of the above chemical formula 1 or a pharmaceutically acceptable salt thereof may be administered to a patient in an effective dose of about 1 to 1000 mg / kg per day, and may be administered once or multiple times. Of course, the dosage may be changed depending on the patient's age, weight, sensitivity, symptoms, or the efficacy of the compound.

[0227] The present invention also encompasses a method of inhibiting hematopoietic pro-kinase 1 in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound of formula 1 or a pharmaceutically acceptable salt thereof. In one embodiment, the present invention provides a method of treating a disease associated with HPK1, such as a cancer, including a hematological cancer or a solid cancer, for example, melanoma, blastoma, sarcoma, lymphoma, leukemia, bladder cancer, brain tumor, breast cancer, cervical cancer, colorectal cancer, esophageal cancer, endometrioma, liver cancer, laryngeal cancer, lung cancer, osteosarcoma, ovarian cancer, pancreatic cancer, prostate cancer, kidney cancer, thyroid cancer, ependymoma, glioblastoma, medulloblastoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma, renal cell carcinoma, and the like, comprising administering to the mammal a therapeutically effective amount of a compound of formula 1 or a pharmaceutically acceptable salt thereof.

[0228] The present invention also provides the use of a compound of formula 1 or a pharmaceutically acceptable salt thereof for use in the manufacture of a medicament that inhibits hematopoietic progenitor kinase 1 in a mammal. In one embodiment, the present invention provides the use of a compound of formula 1 or a pharmaceutically acceptable salt thereof for use in the manufacture of a medicament for the prevention or treatment of a disease associated with HPK1, such as a cancer including a hematological cancer or a solid cancer, for example, a melanoma, a blastoma, a sarcoma, a lymphoma, a leukemia, a bladder cancer, a brain tumor, a breast cancer, a cervical cancer, a colorectal cancer, an esophageal cancer, an endometrioma, a liver cancer, a laryngeal cancer, a lung cancer, an osteosarcoma, an ovarian cancer, a pancreatic cancer, a prostate cancer, a kidney cancer, a thyroid cancer, an ependymoma, a glioblastoma, a medulloblastoma, a neuroblastoma, an osteosarcoma, a rhabdomyosarcoma, a renal cell carcinoma, and the like.

[0229] Hereinafter, the present invention will be described in more detail through examples and test examples. However, these examples and test examples are intended to illustrate the present invention and are not intended to limit the present invention to them.

[0230] The analyses of the compounds prepared below were performed as follows: Nuclear magnetic resonance (NMR) spectral analysis was performed on a Bruker 400 MHz spectrometer, and chemical shifts were analyzed in ppm. In addition, the molecular weight was measured using an Agilent 1260 Infinity series liquid chromatography / mass selective detector (MSD) (Single Quadrupole) equipped with an electrostatic spray interface, which indicates the m / z value in ESI+ (ESI-MS (cation) and indicates the [M+H]+ peak). In addition, the purification of the synthesized compounds below was performed using preparative medium pressure liquid chromatography (MPLC): CombiFlash NextGen 300+ from TELEEDYNE ISCO was used for the MPLC. In addition, the starting materials of each example were known compounds, synthesized according to the literature, or purchased from commercially available vendors.

[0231] The following reference examples illustrate methods for synthesizing intermediates for preparing compounds of the present invention or salts thereof (i.e., compounds of the examples).

[0232] Reference Example A-1: ​​tert-Butyl (S)-(1-(2-amino-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0233] Step 1: tert-Butyl (S)-(1-(2-amino-5-bromopyridin-4-yl)piperidin-3-yl)carbamate

[0234] 5-Bromo-4-fluoro-pyridin-2-amine (5.0 g, 26.17 mmol) was dissolved in anhydrous dimethyl sulfoxide (80.0 mL), and (S)-3-(tert-butoxycarbonylamino)piperidine (6.29 g, 31.41 mmol) and diisopropylethylamine (13.7 mL, 78.53 mmol) were added dropwise. The reaction mixture was refluxed overnight at 120°C. After completion of the reaction, the reaction mixture was cooled to room temperature, water was added, and the aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography to prepare the title compound (2.3 g). (Yield: 23.7%) 1H NMR (CDCl3, 400MHz) δ 8.10 (s, 1H), 6.13 (s, 1H), 5.24-5.04 (m, 1H), 4.49 (s, 2H), 4.00-3.87 (m, 1H), 3.24-2.91 (m, 4H), 1.97-1.84 (m, 1H), 1.82-1.65 (m, 3H), 1.56 (s, 9H)

[0235] Step 2: tert-Butyl (S)-(1-(2-amino-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0236] Tert-Butyl (S)-(1-(2-amino-5-bromopyridin-4-yl)piperidin-3-yl)carbamate (1.5 g, 4.04 mmol) was dissolved in anhydrous 1,4-dioxane (20.2 mL), and then 1-(tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (2.25 g, 8.08 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethane complex (489.9 mg, 0.60 mmol) and 2.0 M aqueous sodium carbonate solution (6.06 mL, 12.1 mmol) were added dropwise. The reaction mixture was stirred at 100°C for 4 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, water was added, and the aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography to produce the title compound (798.5 g). (Yield: 44.7%) 1H NMR (CDCl3, 400MHz) δ 7.75 (s, 1H), 7.66 (s, 2H), 6.12 (s, 1H), 5.02 (s, 2H), 4.55-4.45 (m, 1H), 4.40-4.39 (m, 1H), 4.15-4.12 (m, 2H), 3.73-3.70 (m, 1H), 3.66-3.60 (m, 2H), 3.46-3.43 (m, 1H), 3.03-2.99 (m, 1H), 2.60-2.55 (m, 2H), 2.32-2.11 (m, 5H), 1.95-1.75 (m, 2H), 1.45 (s, 9H)

[0237] Reference Example A-2: (S)-1-(2-amino-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0238] The title compound was prepared in the same manner as in Reference Example A-1 using (S)-piperidin-3-ol instead of (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 7.93 (s, 1H), 7.76 (d, 2H), 6.14 (s, 1H), 4.49 (s, 2H), 4.44-4.36 (m, 1H), 4.20-4.09 (m, 2H), 3.90-3.80 (m, 1H), 3.65-3.54 (m, 2H), 3.23-3.15 (m, 1H), 2.97-2.89 (m, 1H), 2.78-2.64 (m, 2H), 2.23-2.06 (m, 4H), 1.95-1.85 (m, 1H), 1.85-1.74 (m, 1H), 1.57-1.48 (m, 2H)

[0239] Reference Example A-3: tert-Butyl (S)-(1-(2-amino-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0240] The title compound was prepared in the same manner as in Reference Example A-1, using 1-(difluoromethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole instead of 1-(tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.02 (s, 1H), 7.88 (s, 2H), 7.36 (t, 1H), 6.09 (s, 1H), 4.55-4.53 (m, 1H), 4.43 (s, 2H), 3.74-3.52 (m, 1H), 3.36-3.34 (m, 1H), 2.95-2.92 (m, 1H), 2.57-2.51 (m, 2H), 1.88-1.87 (m, 1H), 1.71-1.70 (m, 1H), 1.66-1.61 (m, 1H), 1.53-1.50 (m, 1H), 1.45 (s, 9H), 1.31-1.28 (m, 1H)

[0241] Reference Example A-4: tert-Butyl (S)-(1-(2-amino-5-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0242] The title compound was prepared in the same manner as in Reference Example A-1 using 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole instead of 1-(tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 7.86 (s, 1H), 7.68 (s, 1H), 7.59 (s, 1H), 6.08 (s, 1H), 4.58 (br, 1H), 4.51 (s, 2H), 3.97 (s, 3H), 3.77 (br, 1H), 3.33-3.31 (m, 1H), 2.98-2.96 (m, 1H), 2.64-2.55 (m, 2H), 1.89-1.88 (m, 1H), 1.64 (br, 1H), 1.58-1.53 ​​(m, 1H), 1.47 (s, 9H)

[0243] Reference Example A-5: tert-Butyl (S)-(1-(2-amino-5-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0244] The title compound was prepared in the same manner as in Reference Example A-1 using 1-(2-methoxyethyl)-1H-pyrazole-4-boronic acid pinacol ester instead of 1-(tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 7.93 (s, 1H), 7.77-7.66 (m, 2H), 6.11 (s, 1H), 4.73-4.61 (m, 1H), 4.40-4.23 (m, 4H), 3.90-3.70 (m, 3H), 3.41 (s, 3H), 3.33-3.25 (m, 1H), 2.96-2.85 (m, 1H), 2.70-2.57 (m, 2H), 1.92-1.81 (m, 1H), 1.59-1.51 (m, 1H), 1.51 (s, 9H)

[0245] Reference Example A-6: tert-Butyl ((3S,4R)-1-(2-amino-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)-4-methylpiperidin-3-yl)carbamate

[0246] The title compound was prepared in the same manner as in Reference Example A-1 using tert-butyl N-[(3S,4R)-4-methylpiperidin-3-yl]carbamate instead of (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CD3OD, 400MHz) δ 7.97 (s, 1H), 7.76 (s, 2H), 6.26 (s, 1H), 4.53-4.41 (m, 1H), 4.14-4.04 (m, 2H), 3.70-3.54 (m, 2H), 3.44-3.38 (m, 1H), 3.31-3.19 (m, 3H), 2.53-2.42 (m, 1H), 2.38-2.27 (m, 1H), 2.19-1.99 (m, 5H), 1.72-1.62 (m, 1H), 1.52 (s, 9H), 1.09 (d, 3H)

[0247] Reference Example A-7: tert-Butyl (S)-(1-(2-amino-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl) carbamate

[0248] The title compound was prepared in the same manner as in Reference Example A-1, using 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazole instead of 1-(tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 7.89 (s, 1H), 7.78-7.77 (m, 2H), 6.09 (s, 1H), 4.79 (m, 2H), 4.54 (s, 2H), 3.73 (br, 1H), 3.37-3.35 (m, 1H), 3.04-2.97 (m, 1H), 2.60-2.49 (m, 2H), 1.89 (br, 1H), 1.68-1.53 ​​(m, 3H), 1.46 (s, 9H)

[0249] Reference Example A-8: tert-Butyl (S)-(1-(2-amino-5-(1-ethyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0250] The title compound was prepared in the same manner as in Reference Example A-1 using 1-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole instead of 1-(tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 7.86 (s, 1H), 7.69 (s, 1H), 7.64 (s, 1H), 6.08 (s, 1H), 4.60 (s, 2H), 4.23 (q, 2H), 3.78 (s, 1H), 3.35-3.32 (m, 1H), 2.98-2.95 (m, 1H), 2.63-2.56 (m, 2H), 1.68-1.63 (m, 1H), 1.57-1.53 ​​(m, 4H), 1.47 (s, 9H)

[0251] Reference Example A-9: tert-Butyl (S)-(1-(2-amino-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0252] The title compound was prepared in the same manner as in Reference Example A-1 using (1-isopropyl-1H-pyrazol-4-yl)boronic acid instead of 1-(tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 7.88 (s, 1H), 7.69 (s, 2H), 6.08 (s, 1H), 4.63 (br, 1H), 4.59-4.52 (m, 3H), 3.79 (br, 1H), 3.34-3.31 (m, 1H), 2.94-2.91 (m, 1H), 2.63-2.58 (m, 2H), 1.90-1.88 (m, 1H), 1.71-1.62 (m, 1H), 1.58 (d, 6H), 1.47 (s, 9H)

[0253] Reference Example A-10: tert-Butyl (S)-(1-(2-amino-5-(1-cyclopropyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0254] The title compound was prepared in the same manner as in Reference Example A-1 using 1-cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole instead of 1-(tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 7.85 (s, 1H), 7.67 (d, 1H), 6.07 (s, 1H), 4.60-4.55 (m, 3H), 3.77 (br, 1H), 3.68-3.64 (m, 1H), 3.35-3.33 (m, 1H), 2.97-2.94 (m, 1H), 2.59-2.54 (m, 2H), 1.90 (br, 1H), 1.47 (s, 9H), 1.30-1.27 (m, 2H), 1.21-1.87 (m, 2H), 1.07-1.05 (m, 2H)

[0255] Reference Example A-11: tert-Butyl ((3R,4S)-1-(2-amino-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)-4-fluoropiperidin-3-yl)carbamate

[0256] The title compound was prepared in the same manner as in Reference Example A-1, using tert-butyl ((3R,4S)-4-fluoropiperidin-3-yl)carbamate and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazole instead of (S)-3-(tert-butoxycarbonylamino)piperidine and 1-(tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, respectively. 1H NMR (CD3OD, 400MHz) δ 8.05 (s, 1H), 7.81 (s, 1H), 7.74 (s, 1H), 6.27 (s, 1H), 5.05-4.95 (m, 2H), 3.86-3.79 (m, 1H), 3.17 (d, 1H), 3.08 (d, 1H), 2.78 (q, 2H), 1.99-1.86 (m, 2H), 1.46 (s, 9H), 1.31-1.22 (m, 2H)

[0257] Reference Example A-12: tert-Butyl (S)-(1-(6-amino-6'-(dimethylamino)-[3,3'-bipyridin]-4-yl)piperidin-3-yl)carbamate

[0258] The title compound was prepared in the same manner as in Reference Example A-1 using (6-(dimethylamino)pyridin-3-yl)boronic acid instead of 1-(tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.22 (s, 1H), 7.73 (s, 1H), 7.64 (d, 1H), 6.58 (d, 1H), 6.08 (s, 1H), 4.63 (s, 2H), 3.74 (br, 1H), 3.31-3.28 (m, 1H), 3.14 (s, 6H), 2.92 (br, 1H), 2.68-2.63 (m, 2H), 1.57 (br, 1H), 1.47 (s, 9H), 1.44-1.33 (m, 2H)

[0259] Reference Example A-13: tert-Butyl (S)-(1-(6-amino-6'-morpholino-[3,3'-bipyridin]-4-yl)piperidin-3-yl)carbamate

[0260] The title compound was prepared in the same manner as in Reference Example A-1, using 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)morpholine instead of 1-(tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.27 (s, 1H), 7.74-7.70 (m, 2H), 6.70 (d, 1H), 6.09 (s, 1H), 4.59 (s, 2H), 3.88-3.86 (m, 4H), 3.72 (br, 1H), 3.57-3.51 (m, 4H), 3.33-3.30 (m, 1H), 2.96-2.93 (m, 1H), 2.61 (br, 2H), 1.86 (br, 1H), 1.54 (br, 1H), 1.47 (s, 9H) 1.37-1.33 (m, 2H)

[0261] Reference Example A-14: (S)-1-(2-amino-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0262] The title compound was prepared in the same manner as in Reference Example A-1 using 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazole and (S)-piperidin-3-ol instead of 1-(tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and (S)-3-(tert-butoxycarbonylamino)piperidine, respectively. 1H NMR (CDCl3, 400MHz) δ 8.03 (s, 1H), 7.85 (s, 1H), 7.74 (s, 1H), 6.24 (s, 1H), 4.98 (q, 2H), 3.78-3.73 (m, 1H), 3.30 (s, 1H), 3.06 (d, 1H), 2.54 (t, 1H), 2.46 (t, 1H), 2.01-1.96 (m, 1H), 1.76-1.74 (m, 1H), 1.74-1.70 (m, 1H), 1.58-1.55 (m, 1H)

[0263] Reference Example A-15: (S)-1-(2-amino-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0264] The title compound was prepared in the same manner as in Reference Example A-1 using 1-(tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and (S)-3-(tert-butoxycarbonylamino)piperidine instead of 1-(difluoromethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and (S)-piperidin-3-ol, respectively. 1H NMR (CDCl3, 400MHz) δ 8.29 (s, 1H), 8.01 (s, 1H), 7.78 (s, 1H), 7.65-7.35 (m, 1H), 6.24 (s, 1H), 3.78-3.71 (m, 1H), 3.30-3.26 (m, 1H), 3.03 (d, 1H), 2.56 (t, 1H), 2.45 (t, 1H), 2.01-1.96 (m, 1H), 1.77-1.73 (m, 1H), 1.61-1.57 (m, 1H), 1.55-1.51 (m, 1H)

[0265] Reference Example A-16: (S)-1-(2-amino-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0266] The title compound was prepared in the same manner as in Reference Example A-1 using 1-isopropylpyrazole-4-boronic acid and (S)-piperidin-3-ol instead of 1-(tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and (S)-3-(tert-butoxycarbonylamino)piperidine, respectively. 1H NMR (CDCl3, 400MHz) δ 7.94 (s, 1H), 7.72 (s, 2H), 6.22 (s, 1H), 4.60-4.53 (m, 1H), 3.77-3.71 (m, 1H), 3.33-3.30 (m, 1H), 3.06 (d, 1H), 2.55 (t, 1H), 2.43 (t, 1H), 2.01-1.96 (m, 1H), 1.77-1.74 (m, 1H), 1.56 (d, 6H), 1.40-1.29 (m, 1H)

[0267] Reference Example B-1: tert-Butyl (S)-(1-(2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl) carbamate

[0268] Step 1: tert-Butyl (S)-(1-(2-chloro-5-iodopyridin-4-yl)piperidin-3-yl)carbamate

[0269] 2-Chloro-4-fluoro-5-iodopyridine (5.0 g, 19.42 mmol) was dissolved in anhydrous dimethylformamide (90.6 mL), and (S)-3-(tert-butoxycarbonylamino)piperidine (4.28 g, 21.36 mmol) and diisopropylethylamine (7.9 mL, 58.26 mmol) were added dropwise. The reaction mixture was stirred at 50°C for 4 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, water was added, and the aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography to prepare the title compound (5.9 g). (Yield: 69.9%) 1H NMR (CDCl3, 400MHz) δ 8.57 (s, 1H), 6.85 (s, 1H), 4.92 (brs, 1H), 3.95-3.94 (m, 1H), 3.34 (d, 1H), 3.08-3.04 (m, 2H), 2.90-2.85 (m, 1H), 2.06-1.94 (m, 3H), 1.46 (s, 9H)

[0270] Step 2: tert-Butyl (S)-(1-(2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl) carbamate

[0271] Tert-Butyl (S)-(1-(2-chloro-5-iodopyridin-4-yl)piperidin-3-yl)carbamate (2.0 g, 4.57 mmol) was dissolved in anhydrous 1,4-dioxane (45.7 mL), and then 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole (1.51 g, 5.48 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethane complex (373.1 mg, 0.45 mmol) and 2.0 M aqueous sodium carbonate solution (11.4 mL, 22.8 mmol) were added dropwise. The reaction mixture was stirred at 100°C for 4 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, water was added, and the aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography to produce the title compound (1.6 g). (Yield: 76.1%) 1H NMR (CDCl3, 400MHz) δ 8.15 (s, 1H), 7.88 (s, 1H), 7.82 (s, 1H), 6.88 (s, 1H), 4.83-4.78 (m, 2H), 4.50-4.42 (m, 1H), 3.73-3.69 (m, 1H), 3.44-3.41 (m, 1H), 3.11-3.09 (m, 1H), 2.63-2.58 (m, 1H), 2.45-2.43 (m, 1H), 2.00-1.94 (m, 1H), 1.73-1.70 (m, 1H), 1.44 (s, 9H), 1.35-1.28 (m, 1H)

[0272] Reference Example B-2: tert-Butyl (S)-(1-(2-chloro-5-(4-morpholinophenyl)pyridin-4-yl)piperidin-3-yl)carbamate

[0273] The title compound was prepared in the same manner as in Reference Example B-1, using 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole instead of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]morpholine. 1H NMR (CDCl3, 400MHz) δ 8.06 (d, 2H), 6.71 (s, 2H), 6.67 (d, 2H), 4.66-4.53 (m, 1H), 3.79-3.66 (m, 4H), 3.51-3.42 (m, 2H), 3.25-3.16 (m, 2H), 3.14-3.06 (m, 1H), 2.04-1.97 (m, 1H), 1.87-1.74 (m, 2H), 1.73-1.66 (m, 2H), 1.64-1.58 (m, 3H), 1.53 (s, 9H)

[0274] Reference Example B-3: tert-Butyl (S)-(1-(2-chloro-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0275] The title compound was prepared in the same manner as in Reference Example B-1, using 1-(2,2-difluoroethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole instead of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.14 (s, 1H), 7.83 (s, 1H), 7.82 (s, 1H), 6.88 (s, 1H), 6.34-6.19 (m, 1H), 4.60-4.53 (m, 2H), 3.82-3.70 (m, 1H), 3.46-3.43 (m, 1H), 3.12-3.09 (m, 1H), 2.64-2.61 (m, 1H), 2.53-2.42 (m, 1H), 1.98-1.92 (m, 1H), 1.83-1.74 (m, 1H), 1.72-1.62 (m, 1H), 1.57 (s, 9H), 1.45-1.43 (m, 1H)

[0276] Reference Example B-4: tert-Butyl ((3S,5S)-1-(2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)-5-methylpiperidin-3-yl)carbamate

[0277] The title compound was prepared in the same manner as in Reference Example B-1 using tert-butyl N-[(3S,5S)-5-methylpiperidin-3-yl]carbamate instead of (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 8.17 (s, 1H), 7.85 (s, 1H), 7.80 (s, 1H), 6.93 (s, 1H), 4.90-4.78 (m, 2H), 4.78-4.67 (m, 1H), 4.05-3.89 (m, 1H), 3.20-3.07 (m, 2H), 3.04-2.88 (m, 1H), 2.27-2.12 (m, 1H), 1.91-1.74 (m, 2H), 1.49 (s, 9H), 0.85 (d, 3H)

[0278] Reference Example B-5: tert-Butyl (S)-(1-(2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)-3-methylpiperidin-3-yl)carbamate

[0279] The title compound was prepared in the same manner as in Reference Example B-1 using tert-butyl N-[(3S)-3-methylpiperidin-3-yl]carbamate instead of (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 8.17 (s, 1H), 7.92 (s, 2H), 6.92 (s, 1H), 4.87 (q, 2H), 4.62 (s, 1H), 3.47-3.34 (m, 1H), 3.19-3.09 (m, 1H), 2.75-2.67 (m, 1H), 2.60-2.46 (m, 1H), 2.21-2.10 (m, 1H), 1.49-1.40 (m, 10H), 1.40 (s, 3H)

[0280] Reference Example B-6: tert-Butyl ((3R,4R)-1-(2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)-4-hydroxypiperidin-3-yl)carbamate

[0281] The title compound was prepared in the same manner as in Reference Example B-1 using tert-butyl N-[(3R,4R)-4-hydroxy-3-piperidyl]carbamate instead of (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 8.20 (s, 1H), 7.93 (s, 1H), 7.86 (s, 1H), 6.93 (s, 1H), 4.91 (q, 2H), 4.60-4.48 (m, 1H), 3.63-3.47 (m, 3H), 3.33-3.23 (m, 1H), 2.76-2.64 (m, 1H), 2.64-2.54 (m, 1H), 2.54-2.39 (m, 1H), 2.09-1.99 (m, 1H), 1.72-1.60 (m, 1H), 1.53 (s, 9H)

[0282] Reference Example B-7: tert-Butyl ((3S,5S)-1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)-5-methylpiperidin-3-yl)carbamate

[0283] The title compound was prepared in the same manner as in Reference Example B-1 using 1-(tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole and (S)-3-(tert-butoxycarbonylamino)piperidine instead of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and tert-butyl N-[(3S,5S)-5-methylpiperidin-3-yl]carbamate, respectively. 1H NMR (CDCl3, 400MHz) δ 8.15 (s, 1H), 7.79 (s, 1H), 7.72 (s, 1H), 6.88 (s, 1H), 4.85-4.72 (m, 1H), 4.51-4.39 (m, 1H), 4.20-4.10 (m, 2H), 4.02-3.90 (m, 1H), 3.67-3.53 (m, 2H), 3.22-3.08 (m, 2H), 3.03-2.88 (m, 1H), 2.27-2.05 (m, 5H), 1.94-1.75 (m, 2H), 1.53 (s, 9H), 0.85 (d, 3H)

[0284] Reference Example B-8: tert-Butyl (S)-(1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)-3-methylpiperidin-3-yl)carbamate

[0285] The title compound was prepared in the same manner as in Reference Example B-1 using 1-(tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole and (S)-3-(tert-butoxycarbonylamino)piperidine instead of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and tert-butyl N-[(3S)-3-methylpiperidin-3-yl]carbamate, respectively. 1H NMR (CDCl3, 400MHz) δ 8.17 (s, 1H), 7.84 (s, 1H), 7.78 (s, 1H), 6.89 (s, 1H), 4.69 (s, 1H), 4.49-4.38 (m, 1H), 4.22-4.09 (m, 2H), 3.67-3.54 (m, 2H), 3.40-3.33 (m, 1H), 3.22-3.11 (m, 1H), 2.78-2.68 (m, 1H), 2.53-2.42 (m, 1H), 2.26-2.04 (m, 5H), 1.70-1.59 (m, 1H), 1.53 (s, 9H), 1.43 (s, 3H), 1.38-1.31 (m, 1H)

[0286] Reference Example B-9: tert-Butyl((3R,4R)-1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)-4-hydroxypiperidin-3-yl)carbamate

[0287] The title compound was prepared in the same manner as in Reference Example B-1 using 1-(tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole and (S)-3-(tert-butoxycarbonylamino)piperidine instead of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and tert-butyl N-[(3R,4R)-4-hydroxy-3-piperidyl]carbamate, respectively. 1H NMR (CDCl3, 400MHz) δ 8.19 (s, 1H), 7.84 (s, 1H), 7.80 (s, 1H), 6.92 (s, 1H), 4.65-4.51 (m, 1H), 4.49-4.35 (m, 1H), 4.22-4.08 (m, 2H), 3.71-3.46 (m, 5H), 3.32-3.20 (m, 1H), 2.82-2.70 (m, 1H), 2.70-2.60 (m, 1H), 2.57-2.39 (m, 1H), 2.26-2.08 (m, 4H), 2.08-1.96 (m, 1H), 1.54 (s, 9H)

[0288] Reference Example B-10: tert-Butyl ((1R,3S)-3-((2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridin-4-yl)amino)cyclopentyl)carbamate

[0289] The title compound was prepared in the same manner as in Reference Example B-1, using 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole and (S)-3-(tert-butoxycarbonylamino)piperidine instead of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole and (1S,3R)-S-(Boc-amino)cyclopentan-1-amine, respectively. 1H NMR (CDCl3, 400MHz) δ 8.38 (s, 1H), 8.22 (s, 1H), 7.61 (s, 1H), 6.79 (s, 1H), 6.61 (s, 1H), 4.91 (q, 2H), 4.73-4.58 (m, 1H), 4.22-4.02 (m, 1H), 3.97-3.85 (m, 1H), 2.69-2.51 (m, 1H), 2.23-2.00 (m, 2H), 1.91-1.74 (m, 1H), 1.74-1.62 (m, 1H), 1.54 (s, 9H)

[0290] Reference Example B-11: tert-Butyl ((1R,3R)-3-((2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridin-4-yl)amino)cyclopentyl)carbamate

[0291] The title compound was prepared in the same manner as in Reference Example B-1, using 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole and tert-butyl N-[(1R,3R)-3-aminocyclopentyl]carbamate instead of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole and (S)-3-(tert-butoxycarbonylamino)piperidine, respectively. 1H NMR (CDCl3, 400MHz) δ 8.37 (s, 1H), 8.32 (s, 1H), 7.61 (s, 1H), 6.77 (s, 1H), 6.57 (s, 1H), 4.88 (q, 2H), 4.61-4.47 (m, 1H), 4.30-4.13 (m, 1H), 4.06-3.92 (m, 1H), 2.37-2.15 (m, 2H), 2.15-1.99 (m, 1H), 1.99-1.87 (m, 1H), 1.74-1.62 (m, 1H), 1.56-1.49 (m, 1H), 1.49 (s, 9H)

[0292] Reference Example B-12: tert-Butyl((3R,4R)-1-(2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)-4-fluoropiperidin-3-yl)carbamate

[0293] The title compound was prepared in the same manner as in Reference Example B-1 using tert-butyl N-[(3R,4R)-4-fluoropiperidin-3-yl]carbamate instead of (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 8.21 (s, 1H), 7.89-7.77 (m, 2H), 6.96 (s, 1H), 4.91-4.77 (m, 2H), 4.75-4.63 (m, 1H), 4.62-4.55 (m, 1H), 4.50-4.42 (m, 1H), 3.96-3.78 (m, 1H), 3.61-3.44 (m, 1H), 3.21-3.06 (m, 1H), 2.91-2.76 (m, 1H), 2.74-2.59 (m, 1H), 2.15-1.97 (m, 1H), 1.89-1.77 (m, 1H), 1.52 (s, 9H)

[0294] Reference Example B-13: tert-Butyl ((3R,4S)-1-(2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)-4-fluoropiperidin-3-yl)carbamate

[0295] The title compound was prepared in the same manner as in Reference Example B-1 using tert-butyl N-[(3R,4S)-4-fluoropiperidin-3-yl]carbamate instead of (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 8.21 (s, 1H), 7.92 (s, 1H), 7.86 (s, 1H), 6.96 (s, 1H), 4.99-4.88 (m, 1H), 4.88-4.77 (m, 2H), 4.00-3.78 (m, 1H), 3.35-3.25 (m, 1H), 3.18-3.04 (m, 1H), 2.94-2.81 (m, 1H), 2.81-2.66 (m, 1H), 2.16-1.99 (m, 1H), 1.93-1.84 (m, 1H), 1.84-1.72 (m, 1H), 1.53 (s, 9H)

[0296] Reference Example B-14: tert-Butyl 3-((2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridin-4-yl)amino)azetidine-1-carboxylate

[0297] The title compound was prepared in the same manner as in Reference Example B-1, using 3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole and (S)-3-(tert-butoxycarbonylamino)piperidine instead of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole and (S)-3-(tert-butoxycarbonylamino)piperidine, respectively. 1H NMR (CDCl3, 400MHz) δ 7.99 (s, 1H), 7.77 (s, 1H), 7.71 (s, 1H), 6.34 (s, 1H), 4.88 (q, 2H), 4.42-4.30 (m, 2H), 4.28-4.15 (m, 1H), 3.79-3.67 (m, 2H), 1.49 (s, 9H)

[0298] Reference Example B-15: tert-Butyl (R)-(1-(2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)pyrrolidin-3-yl) carbamate

[0299] The title compound was prepared in the same manner as in Reference Example B-1 using (R)-3-(tert-butoxycarbonylamino)pyrrolidine instead of (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 7.92 (s, 1H), 7.65 (s, 1H), 7.57 (s, 1H), 6.62 (s, 1H), 4.83 (q, 2H), 4.60-4.45 (m, 1H), 4.26-4.14 (m, 1H), 3.40-3.32 (m, 1H), 3.28-3.11 (m, 2H), 2.97-2.87 (m, 1H), 2.21-2.08 (m, 1H), 1.88-1.77 (m, 1H), 1.48 (s, 9H)

[0300] Reference Example B-16: tert-Butyl (S)-(1-(2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)pyrrolidin-3-yl) carbamate

[0301] The title compound was prepared in the same manner as in Reference Example B-1 using (S)-3-(tert-butoxycarbonylamino)pyrrolidine instead of (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 7.93 (s, 1H), 7.64 (s, 1H), 7.58 (s, 1H), 6.61 (s, 1H), 4.83 (q, 2H), 4.60-4.42 (m, 1H), 4.27-4.09 (m, 1H), 3.41-3.31 (m, 1H), 3.27-3.11 (m, 2H), 2.97-2.87 (m, 1H), 2.22-2.09 (m, 1H), 1.89-1.76 (m, 1H), 1.50 (s, 9H)

[0302] Reference Example B-17: 8-(2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)-2-methyl-2,8-diazaspiro[4.5]decane

[0303] The title compound was prepared in the same manner as in Reference Example B-1 using 2-methyl-2,8-diazaspiro[4.5]decane instead of (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 8.15 (s, 1H), 7.94 (s, 1H), 7.89 (s, 1H), 6.91 (s, 1H), 4.85 (q, 2H), 2.97-2.82 (m, 4H), 2.63-2.52 (m, 2H), 2.43-2.37 (m, 2H), 2.37 (s, 3H), 1.73-1.52 (m, 6H)

[0304] Reference Example B-18: tert-Butyl (S)-3-((2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridin-4-yl)amino)pyrrolidine-1-carboxylate

[0305] The title compound was prepared in the same manner as in Reference Example B-1, using 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole and (S)-3-(tert-butoxycarbonylamino)piperidine instead of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole and (3S)-(+)-1-(tert-butoxycarbonyl)-3-aminopyrrolidine, respectively. 1H NMR (CDCl3, 400MHz) δ 8.38-8.25 (m, 2H), 7.58 (s, 1H), 6.78 (s, 1H), 6.61 (s, 1H), 4.78 (q, 2H), 4.19-4.05 (m, 1H), 3.82-3.65 (m, 1H), 3.62-3.46 (m, 2H), 3.46-3.25 (m, 1H), 2.37-2.16 (m, 1H), 2.03-1.97 (m, 1H), 1.53 (s, 9H)

[0306] Reference Example B-19: tert-Butyl (R)-3-((2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridin-4-yl)amino)pyrrolidine-1-carboxylate

[0307] The title compound was prepared in the same manner as in Reference Example B-1, using 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole and (S)-3-(tert-butoxycarbonylamino)piperidine instead of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole and (3R)-(+)-1-(tert-butoxycarbonyl)-3-aminopyrrolidine, respectively. 1H NMR (CDCl3, 400MHz) δ 8.42-8.23 (m, 2H), 7.60 (s, 1H), 6.78 (s, 1H), 6.63 (s, 1H), 4.78 (q, 2H), 4.22-4.08 (m, 1H), 3.84-3.68 (m, 1H), 3.64-3.48 (m, 2H), 3.48-3.28 (m, 1H), 2.36-2.18 (m, 1H), 2.01-1.94 (m, 1H), 1.65-1.60 (m, 1H), 1.29 (s, 9H)

[0308] Reference Example B-20: tert-Butyl (S)-(1-(2-chloro-5-(1-ethyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0309] The title compound was prepared in the same manner as in Reference Example B-1 using 1-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole instead of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.19 (s, 1H), 7.81-7.68 (m, 2H), 6.91 (s, 1H), 4.67-4.42 (m, 1H), 4.37 (q, 2H), 3.87-3.64 (m, 1H), 3.52-3.26 (m, 1H), 3.15-2.99 (m, 1H), 2.75-2.45 (m, 2H), 2.05-1.89 (m, 1H), 1.78-1.65 (m, 1H), 1.62 (t, 3H), 1.53 (s, 9H), 1.41-1.32 (m, 1H)

[0310] Reference Example B-21: tert-Butyl (S)-(1-(2-chloro-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0311] The title compound was prepared in the same manner as in Reference Example B-1 using 1-isopropylpyrazole-4-boronic acid instead of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.23 ​​(s, 1H), 7.84-7.67 (m, 2H), 6.91 (s, 1H), 4.65-4.46 (m, 1H), 3.86-3.62 (m, 1H), 3.48-3.32 (m, 1H), 3.14-2.99 (m, 1H), 2.71-2.47 (m, 2H), 2.02-1.88 (m, 1H), 1.74-1.65 (m, 1H), 1.61 (s, 6H), 1.51 (s, 9H), 1.41-1.34 (m, 1H)

[0312] Reference Example B-22: tert-Butyl (S)-(1-(2-chloro-5-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0313] The title compound was prepared in the same manner as in Reference Example B-1 using 1-cyclopropylmethyl-1H-pyrazole-4-boronic acid pinacol ester instead of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.19 (s, 1H), 7.91 (s, 1H), 7.79 (s, 1H), 6.89 (s, 1H), 4.66 (s, 1H), 4.10 (d, 2H), 3.85-3.68 (m, 1H), 3.46-3.31 (m, 1H), 3.11-2.99 (m, 1H), 2.72-2.50 (m, 2H), 1.98-1.89 (m, 1H), 1.78-1.64 (m, 1H), 1.64-1.50 (m, 1H), 1.42-1.33 (m, 2H), 1.33 (s, 9H), 0.76-0.66 (m, 2H), 0.50-0.35 (m, 2H)

[0314] Reference Example B-23: tert-Butyl (S)-(1-(6-chloro-6'-((4-methylpiperazin-1-yl)methyl)-[3,3'-bipyridin]-4-yl)piperidin-3-yl)carbamate

[0315] Step 1: 6-chloro-4-fluoro-6'-((4-methylpiperazin-1-yl)methyl)-3,3'-bipyridine

[0316] 1-((5-Bromopyridin-2-yl)methyl)4-methylpiperazine (300 mg, 1.11 mmol) was dissolved in anhydrous 1,4-dioxane (3 mL), and 2-chloro-4-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (314.52 mg, 1.22 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethane complex (90.68 mg, 0.11 mmol) and 3.0 M aqueous potassium carbonate solution (0.93 mL, 2.78 mmol) were added dropwise. The reaction mixture was stirred at 80°C for 3 h. After the reaction was completed, the reaction mixture was cooled to room temperature, water was added, and the aqueous layer was extracted with dichloromethane. The extracted organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography to prepare the title compound (125 mg). (Yield: 35.1%) 1H NMR (CDCl3, 400MHz) δ 8.73 (s, 1H), 8.50 (d, 1H), 7.83 (d, 1H), 7.57 (d, 1H), 7.26 (d, 1H), 3.76 (s, 2H), 2.98-2.91 (m, 8H), 2.32 (s, 3H)

[0317] Step 2: tert-Butyl (S)-(1-(6-chloro-6'-((4-methylpiperazin-1-yl)methyl)-[3,3'-bipyridin]-4-yl)piperidin-3-yl)carbamate

[0318] 6-Chloro-4-fluoro-6'-((4-methylpiperazin-1-yl)methyl)-3,3'-bipyridine (190 mg, 0.59 mmol) was dissolved in anhydrous dimethylacetamide (2 mL), and (S)-3-(tert-butoxycarbonylamino)piperidine (142.35 g, 0.71 mmol) and diisopropylethylamine (165.56 mL, 1.19 mmol) were added dropwise. The reaction mixture was stirred at 80°C for 3 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, water was added, and the aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography to prepare the title compound (203 mg). (Yield: 68.4%) 1H NMR (CDCl3, 400MHz) δ 8.68 (d, 1H), 8.04 (s, 1H), 7.82 (d, 1H), 7.51 (d, 1H), 6.91 (s, 1H), 4.87 (br, 1H), 4.49 (br, 1H), 3.75 (s, 2H), 3.64 (br, 2H), 3.37 (dd, 1H), 3.09 (dd, 1H), 2.98-2.95 (m, 1H), 2.87-2.84 (m, 2H), 2.71-2.57 (m, 8H), 2.34 (s, 3H), 1.47 (s, 9H)

[0319] Reference Example B-24: tert-Butyl (S)-(1-(6-chloro-6'-((4-fluoropiperidin-1-yl)methyl)-[3,3'-bipyridin]-4-yl)piperidin-3-yl)carbamate

[0320] The title compound was prepared in the same manner as in Reference Example B-23 using 5-bromo-2-((4-fluoropiperidin-1-yl)methyl)pyridine instead of 1-((5-bromopyridin-2-yl)methyl)4-methylpiperazine. 1H NMR (CDCl3, 400MHz) δ 8.69 (s, 1H), 8.05 (s, 1H), 7.83 (d, 1H), 7.52 (d, 1H), 6.91 (s, 1H), 4.74 (d, 1H), 4.47 (br, 1H), 3.75 (s, 2H), 3.65 (br, 1H), 3.37 (d, 1H), 2.71 (br, 2H), 2.65-2.61 (br, 2H), 2.51 (br, 2H), 1.94-1.86 (m, 5H), 1.45 (s, 9H), 1.35-1.30 (m, 2H)

[0321] Reference Example B-25: tert-Butyl (S)-4-(4'-(3-((tert-butoxycarbonyl)amino)piperidin-1-yl)-6'-chloro-[3,3'-bipyridin]-6-yl)piperazine-1-carboxylate

[0322] The title compound was prepared in the same manner as in Reference Example B-23 using tert-butyl 4-(5-bromopyridin-2-yl)piperazine-1-carboxylate instead of 1-((5-bromopyridin-2-yl)methyl)4-methylpiperazine. 1H NMR (CD3OD, 400MHz) δ 8.25 (s, 1H), 7.93 (s, 1H), 7.77 (d, 1H), 7.03 (s, 1H), 6.97 (d, 1H), 3.61-3.59 (m, 8H), 3.50-3.40 (m, 1H), 3.33 (s, 9H), 3.27-3.24 (m, 1H), 2.69 (t, 1H), 2.47 (t, 1H), 1.92-1.90 (m, 1H), 1.70-1.67 (m, 1H), 1.56 (br, 1H), 1.51 (s, 9H), 1.47-1.46 (m, 1H), 1.32 (br, 1H)

[0323] Reference Example B-26: tert-Butyl ((3S,5S)-1-(2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)-5-fluoropiperidin-3-yl)carbamate

[0324] The title compound was prepared in the same manner as in Reference Example B-1 using tert-butyl N-[(3S,5S)-5-fluoro-3-piperidyl]carbamate instead of (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 8.24 (s, 1H), 8.03 (s, 1H), 7.84 (s, 1H), 6.97 (s, 1H), 4.91-4.70 (m, 4H), 4.47-4.32 (m, 1H), 4.13-3.98 (m, 1H), 3.61-3.40 (m, 2H), 2.88-2.69 (m, 1H), 2.51-2.29 (m, 2H), 1.51 (s, 9H)

[0325] Reference Example B-27: tert-Butyl ((1R,4R)-4-((6'-chloro-5-((1-methylpiperidin-4-yl)oxy)-[2,3'-bipyridin]-4'-yl)amino)cyclohexyl)carbamate

[0326] The title compound was prepared in the same manner as in Reference Example B-23 using 2-bromo-5-((1-methylpiperidin-4-yl)oxy)pyridine and tert-butyl ((1R,4R)-4-aminocyclohexyl)carbamate instead of 1-((5-bromopyridin-2-yl)methyl)4-methylpiperazine and (S)-3-(tert-butoxycarbonylamino)piperidine, respectively. 1H NMR (CDCl3, 400MHz) δ 9.02 (d, 1H), 8.32-8.27 (m, 2H), 7.65 (d, 1H), 7.34 (dd, 1H), 6.55 (s, 1H), 4.44 (br, 1H), 3.52 (br, 1H), 3.33-3.31 (m, 1H), 2.75 (br, 2H), 2.41-2.34 (m, 5H), 2.19-2.07 (m, 6H), 1.96-1.91 (m, 2H), 1.48 (s, 9H), 1.43-1.29 (m, 5H)

[0327] Reference Example B-28: tert-Butyl(((1S,4S)-4-((6'-chloro-5-((1-methylpiperidin-4-yl)oxy)-[2,3'-bipyridin]-4'-yl)amino)cyclohexyl)methyl)carbamate

[0328] The title compound was prepared in the same manner as in Reference Example B-23 using 2-bromo-5-((1-methylpiperidin-4-yl)oxy)pyridine and tert-butyl (((1S,4S)-4-aminocyclohexyl)methyl)carbamate instead of 1-((5-bromopyridin-2-yl)methyl)4-methylpiperazine and (S)-3-(tert-butoxycarbonylamino)piperidine, respectively. 1H NMR (CDCl3, 400MHz) δ 9.53 (d, 1H), 8.35-8.32 (m, 2H), 7.69 (d, 1H), 7.36 (dd, 1H), 6.56 (s, 1H), 4.61 (br, 1H), 4.48 (br, 1H), 3.76 (br, 1H), 3.09 (t, 2H), 2.75 (br, 2H), 2.40-2.38 (m, 2H), 2.34 (s, 3H), 2.10-2.07 (m, 3H), 1.92-1.89 (m, 5H), 1.70-1.67 (m, 2H), 1.47 (s, 9H), 1.35-1.28 (m, 3H)

[0329] Reference Example B-29: tert-Butyl ((1S,4S)-4-((6'-chloro-5-(morpholinomethyl)-[2,3'-bipyridin]-4'-yl)amino)cyclohexyl)carbamate

[0330] The title compound was prepared in the same manner as in Reference Example B-23 using 4-((6-bromopyridin-3-yl)methyl)morpholine and tert-butyl ((1S,4S)-4-aminocyclohexyl)carbamate instead of 1-((5-bromopyridin-2-yl)methyl)4-methylpiperazine and (S)-3-(tert-butoxycarbonylamino)piperidine, respectively. 1H NMR (CDCl3, 400MHz) δ 9.81 (d, 1H), 8.55 (s, 1H), 8.46 (s, 1H), 7.83 (d, 1H), 7.76 (d, 1H), 6.58 (s, 1H), 4.56 (br, 1H), 3.78-3.76 (m, 4H), 3.66 (br, 2H), 3.59 (s, 2H), 3.52 (s, 4H), 1.85-1.83 (m, 7H), 1.49 (s, 9H)

[0331] Reference Example B-30: tert-Butyl ((1R,4R)-4-((6'-chloro-5-(morpholinomethyl)-[2,3'-bipyridin]-4'-yl)amino)cyclohexyl)carbamate

[0332] The title compound was prepared in the same manner as in Reference Example B-23 using 4-((6-bromopyridin-3-yl)methyl)morpholine and tert-butyl ((1R,4R)-4-aminocyclohexyl)carbamate instead of 1-((5-bromopyridin-2-yl)methyl)4-methylpiperazine and (S)-3-(tert-butoxycarbonylamino)piperidine, respectively. 1H NMR (CDCl3, 400MHz) δ 9.41 (d, 1H), 8.53 (s, 1H), 8.42 (s, 1H), 7.81 (d, 1H), 7.72 (d, 1H), 6.57 (s, 1H), 4.46 (br, 1H), 3.76-3.74 (m, 4H), 3.57 (s, 2H), 3.52 (br, 1H), 3.35-3.32 (m, 1H), 2.51 (s, 4H), 2.20-2.11 (m, 3H), 1.48 (s, 9H), 1.44-1.28 (m, 4H)

[0333] Reference Example B-31: tert-Butyl (((1S,4S)-4-((6'-chloro-5-(morpholinomethyl)-[2,3'-bipyridin]-4'-yl)amino)cyclohexyl)methyl)carbamate

[0334] The title compound was prepared in the same manner as in Reference Example B-23 using 4-((6-bromopyridin-3-yl)methyl)morpholine and tert-butyl (((1S,4S)-4-aminocyclohexyl)methyl)carbamate instead of 1-((5-bromopyridin-2-yl)methyl)4-methylpiperazine and (S)-3-(tert-butoxycarbonylamino)piperidine, respectively. 1H NMR (CDCl3, 400MHz) δ 9.89 (d, 1H), 8.54 (s, 1H), 8.45 (s, 1H), 7.83 (d, 1H), 7.76 (d, 1H), 6.58 (s, 1H), 4.62 (br, 1H), 3.73 (s, 4H), 3.58 (s, 2H), 3.08 (t, 2H), 2.52 (s, 4H), 1.92-1.89 (m, 2H), 1.72-1.69 (m, 3H), 1.47 (s, 9H), 1.38-1.28 (m, 4H)

[0335] Reference Example B-32: tert-Butyl ((1s,4s)-4-((6'-chloro-5-(trifluoromethyl)-[2,3'-bipyridin]-4'-yl)amino)cyclohexyl)carbamate

[0336] The title compound was prepared in the same manner as in the B-23 synthesis method, using 2-bromo-5-(trifluoromethyl)pyridine reagent and tert-butyl ((1s,4s)-4-aminocyclohexyl)carbamate reagent instead of 1-((5-bromopyridin-2-yl)methyl)4-methylpiperazine reagent and (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 9.64 (d, 1H), 8.90 (s, 1H), 8.52 (s, 1H), 8.06 (dd, 1H), 7.93 (d, 1H), 6.63 (s, 1H), 4.56 (br, 1H), 3.68-3.64 (m, 2H), 1.92-1.84 (m, 6H), 1.48 (s, 9H), 0.86 (br, 1H)

[0337] Reference Example B-33: tert-Butyl ((1s,4s)-4-((6'-chloro-5-(dimethylamino)-[2,3'-bipyridin]-4'-yl)amino)cyclohexyl)carbamate

[0338] The title compound was prepared in the same manner as in the B-23 synthesis method, using 6-bromo-N,N-dimethylpyridin-3-amine reagent and tert-butyl ((1s,4s)-4-aminocyclohexyl)carbamate reagent instead of 1-((5-bromopyridin-2-yl)methyl)4-methylpiperazine reagent and (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 9.59 (d, 1H), 8.33 (s, 1H), 8.09 (d, 1H), 7.62 (d, 1H), 7.15 (dd, 1H), 6.53 (s, 1H), 4.55 (br, 1H), 3.64 (br, 2H), 3.08 (s, 6H), 1.87-1.51 (m, 6H), 1.48 (s, 9H), 0.85 (br, 1H)

[0339] Reference Example B-34: tert-Butyl ((1s,4s)-4-((6'-chloro-5-(tetrahydro-2H-pyran-4-yl)-[2,3'-bipyridin]-4'-yl)amino)cyclohexyl)carbamate

[0340] The title compound was prepared in the same manner as in the B-23 synthesis method, using 2-bromo-5-(tetrahydro-2H-pyran-4-yl)pyridine reagent and tert-butyl ((1s,4s)-4-aminocyclohexyl)carbamate reagent instead of 1-((5-bromopyridin-2-yl)methyl)4-methylpiperazine reagent and (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 9.76 (d, 1H), 8.49 (s, 1H), 8.44 (s, 1H), 7.75 (d, 1H), 7.69 (dd, 1H), 6.58 (s, 1H), 4.55 (br, 1H), 4.16 (d, 1H), 3.66-3.56 (m, 4H), 2.93-2.85 (m, 1H), 1.92-1.83 (m, 10H), 1.49 (s, 9H), 0.90-0.83 (br, 1H)

[0341] Reference Example B-35: tert-Butyl ((1s,4s)-4-((6'-chloro-5-(morpholinomethyl)-[2,3'-bipyridin]-4'-yl)amino)cyclohexyl)carbamate

[0342] The title compound was prepared in the same manner as in the B-23 synthesis method, using 4-((6-bromopyridin-3-yl)methyl)morpholine reagent and tert-butyl ((1s,4s)-4-aminocyclohexyl)carbamate reagent instead of 1-((5-bromopyridin-2-yl)methyl)4-methylpiperazine reagent and (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 9.83 (d, 1H), 8.55 (s, 1H), 8.46 (s, 1H), 7.82 (d, 1H), 7.76 (d, 1H), 6.58 (s, 1H), 4.54 (br, 1H), 3.76 (t, 4H), 3.67 (br, 1H), 3.61 (s, 2H), 2.52 (t, 4H), 1.90-1.83 (m, 6H), 1.49 (s, 9H), 0.90 (br, 1H)

[0343] Reference Example B-36: tert-Butyl ((1s,4s)-4-((6'-chloro-5-(4-methylpiperazine-1-carbonyl)-[2,3'-bipyridin]-4'-yl)amino)cyclohexyl)carbamate

[0344] The title compound was prepared in the same manner as in the B-23 synthesis method, using ((6-bromopyridin-3-yl)(4-methylpiperazin-1-yl)methanone reagent and tert-butyl ((1s,4s)-4-aminocyclohexyl)carbamate reagent instead of 1-((5-bromopyridin-2-yl)methyl)4-methylpiperazine reagent and (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 9.66 (d, 1H), 8.71 (s, 1H), 8.48 (s, 1H), 7.88-7.82 (m, 2H), 6.60 (s, 1H), 4.54 (br, 1H), 3.87 (br, 2H), 3.68-3.56 (m, 4H), 2.54-2.46 (m, 4H), 2.38 (s, 3H), 1.90-1.83 (m, 6H), 1.54-1.51 (m, 1H), 1.48 (s, 9H)

[0345] Reference Example B-37: tert-Butyl ((1s,4s)-4-((6'-chloro-5-(morpholine-4-carbonyl)-[2,3'-bipyridin]-4'-yl)amino)cyclohexyl)carbamate

[0346] The title compound was prepared in the same manner as in the B-23 synthesis method, using (6-bromopyridin-3-yl)(morpholine)methanone reagent and tert-butyl ((1s,4s)-4-aminocyclohexyl)carbamate reagent instead of 1-((5-bromopyridin-2-yl)methyl)4-methylpiperazine reagent and (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 9.65 (d, 1H), 8.72 (s, 1H), 8.48 (s, 1H), 7.89-7.83 (m, 2H), 6.61 (s, 1H), 4.53 (br, 1H), 3.78-3.64 (m, 10H), 1.91-1.83 (m, 6H), 1.57-1.52 (m, 1H), 1.48 (s, 9H)

[0347] Reference Example B-38: tert-Butyl ((1s,4s)-4-((6'-chloro-5-((4,4-difluoropiperidin-1-yl)methyl)-[2,3'-bipyridin]-4'-yl)amino)cyclohexyl)carbamate

[0348] The title compound was prepared in the same manner as in the B-23 synthesis method using 2-bromo-5-((4,4-difluoropiperidin-1-yl)methyl)pyridine reagent and tert-butyl ((1s,4s)-4-aminocyclohexyl)carbamate reagent instead of 1-((5-bromopyridin-2-yl)methyl)4-methylpiperazine reagent and (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 9.80 (d, 1H), 8.54 (s, 1H), 8.47 (s, 1H), 7.82-7.76 (m, 2H), 6.59 (s, 1H), 4.54 (br, 1H), 3.67-3.63 (m, 4H), 2.63-2.61 (m, 4H), 2.10-2.00 (m, 5H), 1.90-1.83 (m, 6H), 1.49 (s, 9H)

[0349] Reference Example B-39: tert-Butyl ((1s,4s)-4-((2-chloro-5-(1-isopropyl-1H-pyrazol-3-yl)pyridin-4-yl)amino)cyclohexyl)carbamate

[0350] The title compound was prepared in the same manner as in B-1 synthesis, using tert-butyl ((1s,4s)-4-aminocyclohexyl)carbamate reagent and 1-isopropyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole reagent instead of (S)-3-(tert-butoxycarbonylamino)piperidine reagent and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole reagent. 1H NMR (CDCl3, 400MHz) δ 8.53 (d, 1H), 8.36 (s, 1H), 7.50 (s, 1H), 6.63 (s, 1H), 6.55 (s, 1H), 4.58-4.53 (m, 1H), 4.51 (br, 1H), 3.68 (br, 2H), 1.93-1.85 (m, 7H), 1.59 (d, 6H), 1.27 (s, 9H)

[0351] Reference Example B-40: tert-Butyl ((1s,4s)-4-((2-chloro-5-(1-(2,2-difluoroethyl)-1H-pyrazol-3-yl)pyridin-4-yl)amino)cyclohexyl)carbamate

[0352] The title compound was prepared in the same manner as in B-1 synthesis, using tert-butyl ((1s,4s)-4-aminocyclohexyl)carbamate reagent and 1-(2,2-difluoroethyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole reagent instead of (S)-3-(tert-butoxycarbonylamino)piperidine reagent and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole reagent. 1H NMR (CDCl3, 400MHz) δ 8.36 (s, 1H), 8.29 (d, 1H), 7.56 (s, 1H), 6.73 (s, 1H), 6.57 (s, 1H), 6.12 (tt, 1H), 4.60-4.49 (m, 2H), 3.69 (br, 1H), 3.61 (br, 1H), 1.90-1.83 (m, 6H), 1.63 (br, 2H), 1.29 (s, 9H)

[0353] Reference Example B-41: tert-Butyl N-[(3R,4R)-1-[2-chloro-5-(1-isopropylpyrazol-4-yl)-4-pyridyl]-4-fluoro-3-piperidyl]carbamate

[0354] The title compound was prepared in the same manner as in Reference Example B-1, using 1-isopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole and tert-butyl N-[(3S,4R)-4-fluoro-3-piperidyl]carbamate instead of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole and (S)-3-(tert-butoxycarbonylamino)piperidine, respectively. 1H NMR (CDCl3, 400MHz) δ 8.12 (d, 2H), 7.84 (s, 1H), 7.08 (s, 1H), 4.65-4.60 (m, 1H), 4.52-4.50 (m, 1H), 4.39-4.38 (m, 1H), 3.78-3.74 (m, 1H), 2.78 (t, 1H), 2.76 (t, 1H), 2.10 (brs, 1H), 1.79 (t 1H), 1.58-1.53 ​​(m, 6H), 1.45 (s, 9H)

[0355] Reference Example B-42: tert-Butyl N-[(3S,5R)-1-[2-chloro-5-(1-isopropylpyrazol-4-yl)-4-pyridyl]-5-fluoro-3-piperidyl]carbamate

[0356] The title compound was prepared in the same manner as in Reference Example B-1, using 1-isopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole and tert-butyl N-[(3S,5R)-5-fluoro-3-piperidyl]carbamate instead of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole and (S)-3-(tert-butoxycarbonylamino)piperidine, respectively. 1H NMR (CDCl3, 400MHz) δ 8.25 (s, 1H), 7.83 (s, 1H), 7.75 (s, 1H), 6.98 (s, 1H), 5.14-4.99 (m, 1H), 4.81-4.72 (m, 0.5H), 4.69-4.63 (m, 0.5H), 4.63-4.51 (m, 1H), 4.05-3.92 (m, 1H), 3.33-3.23 (m, 1H), 3.23-3.14 (m, 1H), 3.14-3.05 (m, 1H), 3.01-2.80 (m, 1H), 2.19-2.06 (m, 0.5H), 2.06-1.89 (m, 1.5H), 1.60 (d, 6H), 1.51 (s, 9H)

[0357] Reference Example B-43: tert-Butyl N-[(3S,5S)-1-[2-chloro-5-(1-isopropylpyrazol-4-yl)-4-pyridyl]-5-fluoro-3-piperidyl]carbamate

[0358] The title compound was prepared in the same manner as in Reference Example B-1, using 1-isopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole and tert-butyl N-[(3S,5S)-5-fluoro-3-piperidyl]carbamate instead of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole and (S)-3-(tert-butoxycarbonylamino)piperidine, respectively. 1H NMR (CDCl3, 400MHz) δ 8.23 ​​(s, 1H), 7.94 (s, 1H), 7.74 (s, 1H), 6.94 (s, 1H), 4.90-4.81 (m, 1H), 4.77-4.70 (m, 1H), 4.64-4.58 (m, 1H), 4.58-4.47 (m, 1H), 4.15-4.01 (m, 1H), 3.58-3.39 (m, 2H), 2.79-2.59 (m, 1H), 2.59-2.48 (m, 1H), 2.39-2.26 (m, 1H), 1.57 (d, 6H), 1.48 (s, 9H)

[0359] Reference Example C-1: tert-Butyl (S)-(1-(2-chloro-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-4-yl)piperidin-3-yl)carbamate

[0360] Tert-Butyl (S)-(1-(2-chloro-5-iodopyridin-4-yl)piperidin-3-yl)carbamate (300.0 mg, 0.68 mmol) prepared in step 1 of Reference Example B-1 was dissolved in anhydrous 1,4-dioxane (8.0 mL), and then 4-ethanyl-tetrahydro-2H-pyran (150.9 mg, 1.37 mmol), bis(triphenylphosphine)palladium(II) dichloride (22.9 mg, 0.033 mmol), cuprous iodide (7.8 mg, 0.041 mmol), and triethylamine (0.19 mL, 1.37 mmol) were added dropwise. The reaction mixture was stirred at 80°C for 4 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, water was added, and the aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography to produce the title compound (120.4 mg). (Yield: 41.8%) 1H NMR (CDCl3, 400MHz) δ 8.19 (s, 1H), 7.27 (s, 1H), 4.89-4.88 (m, 1H), 3.97-3.95 (m, 2H), 3.93-3.91 (m, 1H), 3.57-3.52 (m, 3H), 3.39-3.37 (m, 1H), 3.20-3.19 (m, 2H), 2.96-2.92 (m, 1H), 1.94-1.92 (m, 2H), 1.86-1.63 (m, 6H), 1.43 (s, 9H)

[0361] Reference Example C-2: tert-Butyl (S)-(1-(2-chloro-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethanyl)pyridin-4-yl)piperidin-3-yl)carbamate

[0362] The title compound was prepared in the same manner as in Reference Example C-1 using 1-(difluoromethyl)-4-ethanyl-1H-pyrazole instead of 4-ethanyl-tetrahydro-2H-pyran. 1H NMR (CDCl3, 400MHz) δ 8.28 (s, 1H), 8.19 (s, 1H), 7.82 (s, 1H), 7.33-7.03 (m, 1H), 6.77 (s, 1H), 4.80-4.78 (m, 1H), 3.88 (brs, 1H), 3.80-3.77 (m, 1H), 3.41-3.38 (m, 1H), 3.12-3.11 (m, 2H), 1.92-1.88 (m, 2H), 1.76-1.75 (m, 1H), 1.74-1.73 (m, 1H), 1.42 (s, 9H)

[0363] Reference Example C-3: tert-Butyl (S)-(1-(2-chloro-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethanyl)pyridin-4-yl)piperidin-3-yl)carbamate

[0364] The title compound was prepared in the same manner as in Reference Example C-1 using 1-(2,2-difluoroethyl)-4-ethanyl-1H-pyrazole instead of 4-ethanyl-tetrahydro-2H-pyran. 1H NMR (CDCl3, 400MHz) δ 8.26 (s, 1H), 7.81 (s, 1H), 7.74 (s, 1H), 6.76 (s, 1H), 6.25-5.95 (m, 1H), 4.82-4.80 (m, 1H), 4.50-4.42 (m, 2H), 3.87-3.86 (m, 1H), 3.72-3.69 (m, 1H), 3.43-3.40 (m, 1H), 3.17-3.15 (m, 2H), 1.92-1.88 (m, 2H), 1.75-1.74 (m, 1H), 1.73-1.71 (m, 1H), 1.43 (s, 9H)

[0365] Reference Example C-4: tert-Butyl (S)-(1-(2-chloro-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethanyl)pyridin-4-yl)piperidin-3-yl)carbamate

[0366] The title compound was prepared in the same manner as in Reference Example C-1 using 4-ethanyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole instead of 4-ethanyl-tetrahydro-2H-pyran. 1H NMR (CDCl3, 400MHz) δ 8.27 (s, 1H), 7.86 (s, 1H), 7.76 (s, 1H), 6.76 (s, 1H), 4.80-4.78 (m, 1H), 4.73-4.67 (q, 2H), 3.87-3.86 (m, 1H), 3.75-3.72 (m, 1H), 3.44-3.41 (m, 1H), 3.16-3.11 (m, 2H), 1.92-1.88 (m, 2H), 1.76-1.74 (m, 1H), 1.72-1.70 (m, 1H), 1.42 (s, 9H)

[0367] Reference Example C-5: tert-Butyl ((3S,4R)-1-(2-chloro-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-4-yl)-4-methylpiperidin-3-yl)carbamate

[0368] The title compound was prepared in the same manner as in Reference Example C-1 using tert-butyl N-[(3S,4R)-4-methylpiperidin-3-yl]carbamate instead of (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 8.22 (s, 1H), 6.77 (s, 1H), 4.54-4.43 (m, 1H), 4.16-4.03 (m, 1H), 4.01-3.91 (m, 2H), 3.90-3.81 (m, 1H), 3.61-3.51 (m, 2H), 3.51-3.42 (m, 1H), 3.01-2.92 (m, 1H), 2.89-2.78 (m, 1H), 2.63-2.53 (m, 1H), 2.00-1.90 (m, 2H), 1.90-1.84 (m, 1H), 1.84-1.74 (m, 2H), 1.56 (s, 9H), 1.15 (d, 3H)

[0369] Reference Example C-6: tert-Butyl (S)-(1-(2-chloro-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-4-yl)-3-methylpiperidin-3-yl)carbamate

[0370] The title compound was prepared in the same manner as in Reference Example C-1 using tert-butyl (S)-(3-methylpiperidin-3-yl)carbamate instead of (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 8.26 (s, 1H), 6.81 (s, 1H), 5.41 (s, 1H), 4.03-3.96 (m, 2H), 3.95-3.88 (m, 2H), 3.60-3.45 (m, 4H), 3.02-2.92 (m, 1H), 2.90-2.79 (m, 1H), 2.78-2.68 (m, 1H), 2.60-2.50 (m, 1H), 2.03-1.92 (m, 2H), 1.92-1.78 (m, 1H), 1.77-1.68 (m, 2H), 1.50 (s, 9H), 1.43-1.36 (m, 3H)

[0371] Reference Example C-7: tert-Butyl ((3R,4R)-1-(2-chloro-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-4-yl)-4-fluoropiperidin-3-yl)carbamate

[0372] The title compound was prepared in the same manner as in Reference Example C-1 using tert-butyl ((3R,4R)-4-fluoropiperidin-3-yl)carbamate instead of (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 8.31 (s, 1H), 6.84 (s, 1H), 5.28-5.14 (m, 1H), 4.89-4.81 (m, 1H), 4.76-4.68 (m, 1H), 4.03-3.89 (m, 3H), 3.70-3.47 (m, 4H), 3.40-3.26 (m, 2H), 3.02-2.92 (m, 1H), 2.27-2.11 (m, 1H), 2.10-2.01 (m, 1H), 1.99-1.88 (m, 2H), 1.88-1.72 (m, 3H), 1.55 (s, 9H)

[0373] Reference Example C-8: tert-Butyl ((3R,4S)-1-(2-chloro-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-4-yl)-4-fluoropiperidin-3-yl)carbamate

[0374] The title compound was prepared in the same manner as in Reference Example C-1 using tert-butyl ((3R,4S)-4-fluoropiperidin-3-yl)carbamate instead of (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 8.24 (s, 1H), 6.80 (s, 1H), 5.04-4.82 (m, 2H), 4.11-3.90 (m, 4H), 3.79-3.67 (m, 1H), 3.60-3.45 (m, 2H), 3.17-3.04 (m, 1H), 3.01-2.83 (m, 2H), 2.27-2.02 (m, 2H), 2.00-1.90 (m, 3H), 1.84-1.72 (m, 2H), 1.53 (s, 9H)

[0375] Reference Example C-9: tert-Butyl ((3R,4R)-1-(2-chloro-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-4-yl)-4-hydroxypiperidin-3-yl)carbamate

[0376] The title compound was prepared in the same manner as in Reference Example C-1 using tert-butyl ((3R,4R)-4-hydroxypiperidin-3-yl)carbamate instead of (S)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 8.25 (s, 1H), 6.79 (s, 1H), 5.02-4.89 (m, 1H), 4.01-3.93 (m, 2H), 3.93-3.85 (m, 1H), 3.82-3.74 (m, 1H), 3.74-3.64 (m, 2H), 3.61-3.50 (m, 2H), 3.15-3.00 (m, 2H), 2.98-2.91 (m, 1H), 2.65-2.53 (m, 1H), 2.18-2.09 (m, 1H), 2.01-1.90 (m, 2H), 1.86-1.72 (m, 3H), 1.53 (s, 9H)

[0377] Reference Example D-1: 6-Chloro-1-isopropyl-1H-pyrazolo[3,4-b]pyridine

[0378] 6-Chloro-1H-pyrazolo[3,4-b]pyridine (1.0 g, 6.51 mmol) was dissolved in anhydrous dimethylformamide (30.0 mL), and 60% sodium hydride (520.9 mg, 13.02 mmol) and 2-iodopropane (1.3 mL, 13.02 mmol) were added dropwise at 0°C. The reaction mixture was stirred for 2 hours. After completion of the reaction, water was added to the reaction mixture, and the aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography to prepare the title compound (0.94 g). (Yield: 74.1%) 1H NMR (CDCl3, 400MHz) δ 8.02-7.98 (m, 2H), 7.14 (d, 1H), 5.32-5.25 (m, 1H), 1.60 (d, 6H)

[0379] Reference Example D-2: 6-Chloro-1-(2-fluoroethyl)-1H-pyrazolo[3,4-b]pyridine

[0380] The title compound was prepared in the same manner as in Reference Example D-1 using 1-fluoro-2-iodoethane instead of 2-iodopropane. 1H NMR (CDCl3, 400MHz) δ 8.11 (s, 1H), 8.05 (d, 1H), 7.24 (d, 1H), 5.04-4.92 (m, 1H), 4.92-4.82 (m, 2H), 4.82-4.74 (m, 1H)

[0381] Reference Example D-3: 6-Chloro-1-(2,2-difluoroethyl)-1H-pyrazolo[3,4-b]pyridine

[0382] The title compound was prepared in the same manner as in Reference Example D-1 using 1,1-difluoro-2-iodoethane instead of 2-iodopropane. 1H NMR (CDCl3, 400 MHz) δ 8.13 (s, 1H), 8.08 (d, 1H), 7.26 (d, 1H), 6.48 (tt, 1H), 4.95 (td, 2H)

[0383] Reference Example D-4: 6-Chloro-1-(tetrahydrofuran-3-yl)-1H-pyrazolo[3,4-b]pyridine

[0384] The title compound was prepared in the same manner as in Reference Example D-1 using 3-iodotetrahydrofuran instead of 2-iodopropane. 1H NMR (CDCl3, 400MHz) δ 8.05(s, 1H), 8.01(d, 1H), 7.17(d, 1H), 5.72-5.66 (m, 1H), 4.32-4.21 (m, 2H), 4.13-4.02 (m, 2H), 2.54-2.49 (m, 2H)

[0385] Reference Example D-5: 6-Chloro-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile

[0386] The title compound was prepared in the same manner as in Reference Example D-1 using 6-chloro-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile instead of 6-chloro-1H-pyrazolo[3,4-b]pyridine. 1H NMR (CDCl3, 400 MHz) δ 8.14 (d, 1H), 7.36 (d, 1H), 5.40-5.33 (m, 1H), 1.63 (d, 6H)

[0387] Reference Example D-6: 6-Chloro-1-phenyl-1H-pyrazolo[3,4-b]pyridine

[0388] 6-Chloro-1H-pyrazolo[3,4-b]pyridine (200 mg, 1.30 mmol) was dissolved in a mixed solvent of anhydrous dichloromethane (0.6 mL) and methanol (0.6 mL), and then phenylboronic acid (238.2 mg, 1.95 mmol), copper(II) acetate (354.8 mg, 1.95 mmol), and pyridine (0.21 mL, 2.61 mmol) were added dropwise at room temperature. The reaction mixture was stirred for 17 hours. After completion of the reaction, water was added to the reaction mixture, and the aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and filtered. The obtained filtrate was concentrated and purified by silica gel column chromatography to prepare the title compound (0.28 g). 1H NMR (CDCl3, 400MHz) δ 8.22 (d, 2H), 8.17 (s, 1H), 8.04 (d, 1H), 7.53 (t, 2H), 7.33 (t, 1H), 7.25-7.20 (m, 1H)

[0389] Reference Example D-7: 6-Chloro-1-neopentyl-1H-pyrazolo[3,4-b]pyridine

[0390] The title compound was prepared in the same manner as in Reference Example D-1 using neopentyl iodide instead of 2-iodopropane. 1H NMR (CD3OD, 400MHz) δ 7.98 (t, 2H), 7.10 (d, 1H), 4.30 (s, 2H), 1.02 (s, 9H)

[0391] Reference Example D-8: 6-Chloro-1-ethyl-1H-pyrazolo[3,4-b]pyridine

[0392] The title compound was prepared in the same manner as in Reference Example D-1 using iodoethane instead of 2-iodopropane. 1H NMR (CDCl3, 400MHz) δ 8.02-8.00 (m, 2H), 7.14 (d, 1H), 4.57 (q, 2H), 4.55 (t, 3H)

[0393] Reference Example D-9: 1-(sec-butyl)-6-chloro-1H-pyrazolo[3,4-b]pyridine

[0394] The title compound was prepared in the same manner as in Reference Example D-1 using 2-iodobutane instead of 2-iodopropane. 1H NMR (CDCl3, 400MHz) δ 8.03 (s, 2H), 8.02-8.01 (m, 2H), 7.13 (d, 1H), 5.05-5.00 (m, 1H), 2.13-2.04 (m, 1H), 1.96-1.89 (m, 1H), 1.57 (d, 3H), 0.79 (t, 2H)

[0395] Reference Example D-10: 6-Chloro-1-(3-fluoropropyl)-1H-pyrazolo[3,4-b]pyridine

[0396] The title compound was prepared in the same manner as in Reference Example D-1 using 1-fluoro-3-iodopropane instead of 2-iodopropane. 1H NMR (CDCl3, 400MHz) δ 8.03-8.00 (m, 2H), 7.16 (d, 1H), 4.65 (q, 2H), 4.58 (t, 1H), 4.47 (t, 1H), 2.44-2.32 (m, 2H)

[0397] Reference Example D-11: 2-(1-(6-chloro-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-3-yl)azetidin-3-yl)propan-2-ol

[0398] Step 1: 6-Chloro-3-iodo-1-isopropyl-1H-pyrazolo[3,4-b]pyridine

[0399] 6-Chloro-3-iodo-1H-pyrazolo[3,4-b]pyridine (500 mg, 1.789 mmol) was dissolved in anhydrous dimethylformamide (5 mL), and 60% sodium hydride (143.13 mg, 3.578 mmol) and 2-iodopropane (357.8 μL, 3.578 mmol) were added dropwise at 0°C. The reaction mixture was stirred for 1 h. After completion of the reaction, water was added to the reaction mixture, and the aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography to prepare the title compound (453 mg). (Yield: 78.7%) 1H NMR (CDCl3, 400MHz) δ 7.74 (d, 1H), 7.17 (d, 1H), 5.28-5.21 (m, 1H), 1.61 (s, 6H)

[0400] Step 2: 2-(1-(6-chloro-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-3-yl)azetidin-3-yl)propan-2-ol

[0401] 6-Chloro-3-iodo-1-isopropyl-1H-pyrazolo[3,4-b]pyridine (70 mg, 0.22 mmol) was dissolved in anhydrous 1,4-dioxane (4.0 mL), and 2-(azetidin-3-yl)propan-2-ol hydrochloride (33.0 mg, 0.22 mmol) and tris(dibenzylideneacetone)dipalladium(0) (40.3 mg, 0.044 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (41.9 mg, 0.088 mol), and cesium carbonate (212.8 mg, 0.66 mmol) were added dropwise. The reaction mixture was stirred at 90°C for one and a half hours. After the reaction was completed, the reaction mixture was cooled to room temperature, water was added, and the aqueous layer was extracted with dichloromethane. The extracted organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography to prepare the title compound (33.0 mg). (Yield: 49.1%) 1H NMR (CDCl3, 400MHz) δ 7.78 (d, 1H), 6.89 (d, 1H), 5.11-5.05 (m, 1H), 4.20 (t, 2H), 4.10 (t, 2H), 2.93-2.86 (m, 1H), 1.50 (d, 6H), 1.27 (s, 6H)

[0402] Reference Example D-12: 6-Chloro-3-(3-(difluoromethyl)azetidin-1-yl)-1-isopropyl-1H-pyrazolo[3,4b]pyridine

[0403] The title compound was prepared in the same manner as in Reference Example D-11 using 3-(difluoromethyl)azetidine hydrochloride instead of 2-(azetidin-3-yl)propan-2-ol hydrochloride. 1H NMR (CDCl3, 400MHz) δ 7.32 (d, 1H), 6.91 (d, 1H), 6.11 (td, 1H), 5.11-5.04 (m, 1H), 4.26 (t, 2H), 4.14 (t, 2H), 3.25-3.15 (m, 1H), 1.48 (d, 6H)

[0404] Reference Example D-13: 6-Chloro-1-(3-tetrahydropyran-2-yloxypropyl)pyrazolo[5,4-b]pyridine

[0405] The title compound was prepared in the same manner as in Reference Example D-1 using 2-(3-chloropropoxy)tetrahydro2H-pyran instead of 2-iodopropane. 1H NMR (CD3OD, 400MHz) δ 8.02-7.99 (m, 2H), 7.14 (d, 1H), 4.67-4.62 (m, 2H), 4.56 (d, 1H), 3.84-3.77 (m, 2H), 3.48-3.45 (m, 1H), 3.38-3.35 (m, 1H), 2.29-2.24 (m, 2H), 1.84-1.80 (m, 1H), 1.75-1.69 (m, 1H), 1.61-1.50 (m, 4H)

[0406] Reference Example D-14: 2-(6-chloro-1H-pyrazolo[3,4-b]pyridin-1-yl)acetonitrile

[0407] The title compound was prepared in the same manner as in Reference Example D-1 using chloroacetonitrile instead of 2-iodopropane. 1H NMR (CD3OD, 400MHz) δ 8.14 (s, 1H), 8.08 (d, 1H), 7.27 (d, 1H), 5.43 (s, 2H)

[0408] Reference Example D-15: 6-Chloro-1-ethyl-3-methyl-1H-pyrazolo[3,4-b]pyridine

[0409] The title compound was prepared in the same manner as in Reference Example D-1, using 6-chloro-3-methyl-1H-pyrazolo[3,4-b]pyridine and iodoethane instead of 6-chloro-1H-pyrazolo[3,4-b]pyridine and 2-iodopropane, respectively. 1H NMR (CDCl3, 400 MHz) δ 7.92 (d, 1H), 7.09 (d, 1H), 4.49 (q, 2H), 2.58 (s, 3H), 1.52 (t, 3H)

[0410] Reference Example D-16: 6-Chloro-1-isopropyl-3-methyl-1H-pyrazolo[3,4-b]pyridine

[0411] The title compound was prepared in the same manner as in Reference Example D-1, using 6-chloro-3-methyl-1H-pyrazolo[3,4-b]pyridine instead of 6-chloro-1H-pyrazolo[3,4-b]pyridine. 1H NMR (CDCl3, 400 MHz) δ 7.91 (d, 1H), 7.08 (d, 1H), 5.24-5.17 (m, 1H), 2.58 (s, 3H), 1.57 (d, 6H)

[0412] Reference Example D-17: 6-Chloro-1-(cyclopropylmethyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine

[0413] The title compound was prepared in the same manner as in Reference Example D-1, using 6-chloro-3-methyl-1H-pyrazolo[3,4-b]pyridine and (iodomethyl)cyclopropane instead of 6-chloro-1H-pyrazolo[3,4-b]pyridine and 2-iodopropane, respectively. 1H NMR (CDCl3, 400 MHz) δ 7.92 (d, 1H), 7.08 (d, 1H), 4.29 (d, 2H), 2.59 (s, 3H), 1.45-1.38 (m, 1H), 0.58 (q, 2H), 0.48 (q, 2H)

[0414] Reference Example D-18: 6-Chloro-1-ethyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile

[0415] The title compound was prepared in the same manner as in Reference Example D-1, using 6-chloro-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile and iodoethane instead of 6-chloro-1H-pyrazolo[3,4-b]pyridine and 2-iodopropane, respectively. 1H NMR (CDCl3, 400 MHz) δ 8.15 (d, 1H), 7.37 (d, 1H), 4.65 (q, 2H), 1.61 (t, 3H)

[0416] Reference Example D-19: 6-Chloro-1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile

[0417] The title compound was prepared in the same manner as in Reference Example D-1, using 6-chloro-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile and (iodomethyl)cyclopropane instead of 6-chloro-1H-pyrazolo[3,4-b]pyridine and 2-iodopropane, respectively. 1H NMR (CDCl3, 400 MHz) δ 8.15 (d, 1H), 7.36 (d, 1H), 4.44 (d, 2H), 1.48-1.44 (m, 1H), 0.66-0.62 (m, 2H), 0.61-0.58 (m, 2H)

[0418] Reference Example D-20: 6-Chloro-1-(2,2-difluoroethyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile

[0419] The title compound was prepared in the same manner as in Reference Example D-1, using 6-chloro-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile and 1,1-difluoro-2-iodoethane instead of 6-chloro-1H-pyrazolo[3,4-b]pyridine and 2-iodopropane, respectively. 1H NMR (CDCl3, 400 MHz) δ 8.19 (d, 1H), 7.44 (d, 1H), 6.31 (tt, 1H), 4.95 (td, 2H)

[0420] Reference Example D-21: 6-Chloro-1-(2-fluoroethyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile

[0421] The title compound was prepared in the same manner as in Reference Example D-1, using 6-chloro-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile and 1-fluoro-2-iodoethane instead of 6-chloro-1H-pyrazolo[3,4-b]pyridine and 2-iodopropane, respectively. 1H NMR (CDCl3, 400 MHz) δ 8.18 (d, 1H), 7.40 (d, 1H), 5.02 (t, 1H), 4.94-4.85 (m, 3H)

[0422] Reference Example D-22: 6-Chloro-1-(3-fluoropropyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile

[0423] The title compound was prepared in the same manner as in Reference Example D-1, using 6-chloro-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile and 1-fluoro-3-iodopropane instead of 6-chloro-1H-pyrazolo[3,4-b]pyridine and 2-iodopropane, respectively. 1H NMR (CDCl3, 400 MHz) δ 8.16 (d, 1H), 7.38 (d, 1H), 4.75 (t, 2H), 4.62 (t, 1H), 4.50 (t, 1H), 2.49-2.36 (m, 2H)

[0424] Reference Example D-23: 6-Chloro-1-(3,3,3-trifluoropropyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile

[0425] The title compound was prepared in the same manner as in Reference Example D-1, using 6-chloro-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile and 1,1,1-trifluoro-3-iodopropane instead of 6-chloro-1H-pyrazolo[3,4-b]pyridine and 2-iodopropane, respectively. 1H NMR (CDCl3, 400 MHz) δ 8.17 (d, 1H), 7.41 (d, 1H), 4.85 (t, 2H), 2.96-2.85 (m, 2H)

[0426] Reference Example D-24: 6-Chloro-1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridine

[0427] The title compound was prepared in the same manner as in Reference Example D-1 using (iodomethyl)cyclopropane instead of 2-iodopropane. 1H NMR (CD3OD, 400MHz) δ 8.03-8.00 (m, 2H), 7.14 (d, 1H), 4.38 (d, 2H), 1.47-1.41 (m, 1H), 0.59 (q, 2H), 0.55 (q, 2H)

[0428] Reference Example D-25: 6-Chloro-1-(3,3,3-trifluoropropyl)-1H-pyrazolo[3,4-b]pyridine

[0429] The title compound was prepared in the same manner as in Reference Example D-1 using 1,1,1-trifluoro-3-iodopropane instead of 2-iodopropane. 1H NMR (CD3OD, 400MHz) δ 8.21 (d, 1H), 8.14 (s, 1H), 7.26 (d, 1H), 4.75 (t, 2H), 2.96-2.84 (m, 2H)

[0430] Reference Example D-26: 6-Chloro-1-isopropyl-3-nitro-1H-pyrazolo[2,3-b]pyridine

[0431] The title compound was prepared in the same manner as in Reference Example D-1, using 6-chloro-3-nitro-1H-pyrazolo[5,4-b]pyridine instead of 6-chloro-1H-pyrazolo[3,4-b]pyridine. 1H NMR (CD3OD, 400MHz) δ 8.59 (d, 1H), 7.59 (d, 1H), 5.43-5.35 (m, 1H), 1.65 (d, 6H)

[0432] Reference Example E-1: 1-Isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0433] Step 1: N-(1-Isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-1,1-diphenylmethanimine

[0434] 6-Chloro-1-isopropyl-1H-pyrazolo[3,4-b]pyridine (500 mg, 2.56 mmol, Reference Example D-1) was dissolved in anhydrous 1,4-dioxane (10.0 mL), and then tris(dibenzylideneacetone)dipalladium(0) (117 mg, 0.13 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthenate (148 mg, 0.26 mmol), cesium carbonate (1.67 g, 5.11 mmol), and benzophenonimine (0.43 ml, 2.56 mmol) were added dropwise. The reaction mixture was stirred at 90°C for 4 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, water was added, and the aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography to prepare the title compound (851 mg). (Yield: 97.8%) 1H NMR (CDCl3, 400MHz) δ 7.86-7.85 (m, 3H), 7.78 (d, 1H), 7.53-7.43 (m, 4H), 7.25-7.22 (m, 4H), 6.46 (d, 1H), 5.20-5.13 (m, 1H), 1.49 (d, 6H)

[0435] Step 2: 1-Isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0436] N-(1-Isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-1,1-diphenylmethanimine (851 mg, 2.50 mmol) was dissolved in anhydrous tetrahydrofuran (10.0 ml), and a 4.0 M hydrochloric acid solution (3.12 ml, 12.5 mmol) in 1,4-dioxane was added dropwise. The reaction mixture was stirred at room temperature for 2 hours. After completion of the reaction, the reaction mixture was neutralized by adding 1 N NaOH aqueous solution, and the aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography to prepare the title compound (364.7 mg). (Yield: 82.8%) 1H NMR (CDCl3, 400MHz) δ 7.80 (s, 1H), 7.75 (d, 1H), 6.37 (d, 1H), 5.12-5.05 (m, 1H), 4.66 (br s, 2H), 1.56 (d, 6H)

[0437] Reference Example E-2: 1-Isobutyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0438] The title compound was prepared in the same manner as in Reference Example E-1, using 6-chloro-1-isobutyl-1H-pyrazolo[3,4-b]pyridine instead of 6-chloro-1-isopropyl-1H-pyrazolo[3,4-b]pyridine. 1H NMR (CDCl3, 400 MHz) δ 7.81-7.72 (m, 2H), 6.40 (d, 1H), 4.81 (s, 2H), 4.24 (d, 2H), 2.51-2.28 (m, 1H), 1.05 (d, 6H)

[0439] Reference Example E-3: 1-(Cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridin-6-amine

[0440] The title compound was prepared in the same manner as in Reference Example E-1, using 6-chloro-1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridine (Reference Example D-24) instead of 6-chloro-1-isopropyl-1H-pyrazolo[3,4-b]pyridine. 1H NMR (CDCl3, 400 MHz) δ 7.86-7.70 (m, 2H), 6.40 (d, 1H), 4.78 (s, 2H), 4.28 (d, 2H), 1.47-1.34 (m, 1H), 0.63-0.53 (m, 2H), 0.51-0.43 (m, 2H)

[0441] Reference Example E-4: 1-Isopentyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0442] The title compound was prepared in the same manner as in Reference Example E-1, using 6-chloro-1-isopentyl-1H-pyrazolo[3,4-b]pyridine instead of 6-chloro-1-isopropyl-1H-pyrazolo[3,4-b]pyridine. 1H NMR (CDCl3, 400 MHz) δ 7.81-7.71 (m, 2H), 6.39 (d, 1H), 4.72 (s, 2H), 4.42 (dd, 2H), 1.88-1.78 (m, 2H), 1.68-1.60 (m, 1H), 1.05 (d, 6H)

[0443] Reference Example E-5: 1-Isopropyl-3-methyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0444] Step 1. N-(1-Isopropyl-3-methyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-1,1-diphenylmethanimine

[0445] 6-Chloro-1-isopropyl-3-methyl-1H-pyrazolo[3,4-b]pyridine (399.14 mg, Reference Example D-16) was dissolved in anhydrous 1,4-dioxane (5.0 mL), and then tris(dibenzylideneacetone)dipalladium(0) (87.16 mg, 0.095 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthenate (90.75 mg, 0.19 mmol), cesium carbonate (1.24 g, 3.81 mmol), and benzophenonimine (0.32 mL, 1.90 mmol) were added dropwise. The mixed solution was stirred at 90°C for 20 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, water was added, and the aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography to prepare the title compound (261.2 mg, yield: 38.7%). 1H NMR (CDCl3, 400 MHz) δ 7.86-7.84 (m, 2H), 7.70 (d, 1H), 7.69-7.43 (m, 4H), 7.26-7.22 (m, 4H), 6.40 (d, 1H), 5.13-5.06 (m, 1H), 2.50 (s, 3H), 1.47 (d, 6H)

[0446] Step 2. 1-Isopropyl-3-methyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0447] N-(1-Isopropyl-3-methyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-1,1-diphenylmethanimine (260 mg, 0.73 mmol) was dissolved in anhydrous tetrahydrofuran (2.0 mL), and trifluoroacetic acid (0.3 mL, 3.97 mmol) was added dropwise. The mixture was stirred at room temperature for 2 hours. After completion of the reaction, the reaction mixture was concentrated and purified by silica gel column chromatography to prepare the title compound (107.3 mg, yield: 79.8%). 1H NMR (CDCl3, 400MHz) δ 7.93 (d, 1H), 6.50 (d, 1H), 4.90-4.87 (m, 1H), 2.43 (s, 3H), 1.49 (d, 6H)

[0448] Example 1: (S)-N-(4-(3-Aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0449] Step 1: tert-Butyl (S)-(1-(2-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0450] tert-Butyl (S)-(1-(2-amino-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate (Reference Example A-1, 100 mg, 0.22 mmol) was dissolved in anhydrous 1,4-dioxane (4.0 mL), and then 6-chloro-1-isopropyl-1H-pyrazolo[3,4-b]pyridine (Reference Example D-1, 66.3 mg, 0.34 mmol) and tris(dibenzylideneacetone)dipalladium(0) (40.3 mg, 0.044 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (41.9 mg, 0.088 mol), cesium carbonate (143.4 mg, 0.44 mmol) was added dropwise. The reaction mixture was refluxed overnight at 100°C. After completion of the reaction, the reaction mixture was cooled to room temperature, water was added, and the aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography to prepare the title compound (72.5 mg). (Yield: 54.7%) 1H NMR (CDCl3, 400MHz) δ 8.31 (s, 1H), 8.14 (s, 1H), 7.90-7.83 (m, 3H), 7.83 (s, 1H), 7.56 (d, 1H), 6.72-6.65 (m, 1H), 5.28-5.18 (m, 1H), 4.63-4.50 (m, 1H), 4.50-4.37 (m, 1H), 4.21-4.12 (m, 2H), 3.92-3.80 (m, 1H), 3.67-3.56 (mm, 3H), 3.22-3.11 (m, 1H), 2.76-2.61 (m, 2H), 2.29-2.09 (m, 4H), 2.05-1.96 (m, 1H), 1.78-1.68 (m, 1H), 1.69 (d, 6H), 1.49 (s, 9H)

[0451] Step 2: (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0452] tert-Butyl (S)-(1-(2-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate (72.5 mg, 0.12 mmol) was dissolved in dichloromethane (6.0 ml), and a 4.0 M hydrochloric acid solution (0.2 ml) in 1,4-dioxane was added dropwise. The reaction mixture was stirred at room temperature for 4 hours. After completion of the reaction, the reaction mixture was concentrated, and the resulting solid was filtered and dried to prepare the title compound (56.1 mg). (Yield: 81.4%) 1H NMR (CD3OD, 400MHz) δ 8.34-8.24 (m, 2H), 8.22 (s, 1H), 8.12 (s, 1H), 7.92 (s, 1H), 7.06 (d, 1H), 6.99 (s, 1H), 5.48-5.38 (m, 1H), 4.63-4.51 (m, 1H), 4.19-4.07 (m, 2H), 3.93-3.82 (m, 1H), 3.70-3.54 (m, 2H), 3.54-3.41 (m, 1H), 3.06-2.95 (m, 1H), 2.95-2.85 (m, 1H), 2.27-2.18 (m, 1H), 2.18-2.10 (m, 5H), 1.93-1.82 (m, 1H), 1.82-1.70 (m, 1H), 1.64 (d, 6H), 1.56-1.51 (m, 1H) MS m / z= 502.3 (M+H)+

[0453] Example 2: (S)-1-(2-((1-Isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0454] The title compound (10.4 mg) was prepared in the same manner as in step 1 of Example 1, using Reference Example A-2 instead of Reference Example A-1. (Yield: 50.0%) 1H NMR (CDCl3, 400MHz) δ 8.41 (s, 1H), 8.14 (s, 1H), 7.92-7.85 (m, 2H), 7.85 (s, 2H), 6.76 (d, 1H), 5.31-5.20 (m, 1H), 4.50-4.38 (m, 1H), 4.22-4.13 (m, 2H), 3.97-3.88 (m, 1H), 3.66-3.55 (m, 2H), 3.45-3.36 (m, 1H), 3.20-3.10 (m, 1H), 2.90-2.80 (mm, 2H), 2.25-2.12 (m, 4H), 2.03-1.93 (m, 1H), 1.90-1.73 (m, 3H), 1.69 (d, 6H) MS m / z= 503.3 (M+H)+

[0455] Example 3: (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0456] The title compound (3.7 mg) was prepared in the same manner as in Example 1 using Reference Example A-3 instead of Reference Example A-1. (Yield: 45.2%) 1H NMR (CD3OD, 400MHz) δ 8.65 (s, 1H), 8.45-8.20 (m, 2H), 8.20 (d, 2H), 7.85 (t, 1H), 7.12-6.87 (m, 2H), 5.46-5.35 (m, 1H), 3.93-3.69 (m, 1H), 3.69-3.38 (m, 2H), 3.09-2.82 (m, 2H), 2.36-2.11 (m, 1H), 2.01-1.71 (m, 1H), 1.71-1.48 (m, 1H), 1.44 (d, 6H) MS m / z=468.2 (M+H)+

[0457] Example 4: (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0458] The title compound (3.7 mg) was prepared in the same manner as in Example 1 using Reference Example A-4 instead of Reference Example A-1. (Yield: 50.6%) 1H NMR (CD3OD, 400MHz) δ 8.29-8.27 (m, 2H), 8.09 (s, 1H), 8.06 (s, 1H), 7.85 (s, 1H), 7.01-6.93 (m, 2H), 5.46-5.39 (m, 1H), 4.03 (s, 3H), 3.86-3.83 (m, 1H), 3.62-3.59 (m, 1H), 3.50-3.43 (m, 1H), 2.96-2.91 (m, 2H), 2.24-2.22 (m, 1H), 1.89-1.75 (m, 2H), 1.68-1.59 (m, 7H) MS m / z= 432.3 (M+H)+

[0459] Example 5: (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0460] The title compound (4.8 mg) was prepared in the same manner as in Example 1 using Reference Example A-5 instead of Reference Example A-1. (Yield: 30.2%) 1H NMR (CD3OD, 400MHz) δ 8.30-8.27 (m, 2H), 8.10 (d, 2H), 7.88 (s, 1H), 7.00-6.97 (m, 1H), 6.92-6.91 (m, 1H), 5.46-5.39 (m, 1H), 4.44 (t, 2H), 3.86-3.82 (m, 3H), 3.62-3.58 (m, 1H), 3.50-3.35 (m, 4H), 2.96-2.86 (m, 2H), 2.24-2.22 (m, 1H), 1.89-1.82 (m, 2H), 1.69-1.59 (m, 7H) MS m / z= 476.3 (M+H)+

[0461] Example 6: (S)-N-(4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0462] Step 1: tert-Butyl (S)-(1-(2-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0463] tert-Butyl (S)-(1-(2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl) carbamate (Reference Example B-1, 195.7 mg, 0.42 mmol) was dissolved in anhydrous 1,4-dioxane (4.0 mL), and then 1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine (Reference Example E-1, 50.0 mg, 0.28 mmol) and tris(dibenzylideneacetone)dipalladium(0) (77.9 mg, 0.08 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (81.1 mg, 0.17 mol), cesium Carbonate (277.3 mg, 0.85 mmol) was added dropwise. The reaction mixture was refluxed overnight at 100°C. After completion of the reaction, the reaction mixture was cooled to room temperature, water was added, and the aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography to produce the title compound (65.7 mg). (Yield: 38.6%) 1H NMR (CD3OD, 400MHz) δ 8.46 (s, 1H), 8.22 (s, 1H), 8.12 (s, 1H), 8.00-7.92 (m, 2H), 7.91 (s, 1H), 6.97 (d, 1H), 5.32-5.19 (m, 1H), 5.14-4.92 (m, 2H), 3.82-3.66 (m, 1H), 3.62-3.47 (m, 1H), 3.31-3.25 (m, 1H), 2.66-2.46 (m, 2H), 2.05-1.93 (m, 1H), 1.77-1.68 (m, 2H), 1.63 (d, 3H), 1.51 (s, 9H)

[0464] Step 2: (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0465] tert-Butyl (S)-(1-(2-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate (65.7 mg, 0.12 mmol) was dissolved in dichloromethane (6.0 ml), and a 4.0 M hydrochloric acid solution (0.2 ml) dissolved in 1,4-dioxane was added dropwise. The mixture was stirred at room temperature for 4 hours. After completion of the reaction, the reaction mixture was concentrated, and the resulting solid was filtered and dried to prepare the title compound (30.2 mg). (Yield: 48.1%) 1H NMR (CD3OD, 400MHz) δ 8.31-8.24 (m, 3H), 8.09 (s, 1H), 7.98 (s, 1H), 7.02-6.93 (m, 2H), 5.45-5.38 (m, 1H), 5.11 (q, 2H), 3.85-3.83 (m, 1H), 3.59-3.56 (m, 1H), 3.50-3.43 (m, 1H), 3.00-2.88 (m, 2H), 2.24-2.21 (m, 1H), 1.85-1.76 (m, 2H), 1.67-1.53 ​​(m, 7H) MS m / z= 500 (M+H)+

[0466] Example 7: (S)-N-(4-(3-aminopiperidin-1-yl)-5-(4-morpholinophenyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0467] The title compound (7.0 mg) was prepared in the same manner as in Example 6 using Reference Example B-2 instead of Reference Example B-1. (Yield: 41.5%) 1H NMR (CD3OD, 400MHz) δ 8.28 (d, 1H), 8.17 (s, 1H), 8.08 (s, 1H), 7.60 (d, 2H), 7.35 (d, 2H), 6.04 (d, 1H), 6.92 (s, 1H), 5.45-5.39 (m, 1H), 3.97-3.94 (m, 4H), 3.84-3.81 (m, 1H), 3.57-3.54 (m, 1H), 3.41-3.39 (m, 4H), 2.98-2.87 (m, 2H), 2.19-2.16 (m, 1H), 1.81-1.63 (m, 2H), 1.62-1.50 (m, 7H) MS m / z= 513.3 (M+H)+

[0468] Example 8: (S)-N-(4-(3-Aminopiperidin-1-yl)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0469] The title compound (4.2 mg) was prepared in the same manner as in Example 6 using Reference Example B-3 instead of Reference Example B-1. (Yield: 45.2%) 1H NMR (CD3OD, 400MHz) δ 8.30-8.27 (m, 2H), 8.18 (s, 1H), 8.09 (s, 1H), 7.94 (s, 1H), 6.99 (d, 1H), 6.94 (s, 1H), 6.31 (tt, 1H), 5.45-5.38 (m, 1H), 4.72 (dt, 2H), 3.84 (d, 1H), 3.59 (d, 1H), 3.50-3.41 (m, 1H), 2.92 (t, 2H), 2.24-2.21 (m, 1H), 1.91-1.79 (m, 2H), 1.67-1.53 ​​(m, 7H) MS m / z= 482.3 (M+H)+

[0470] Example 9: N-(4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0471] The title compound (4.0 mg) was prepared in the same manner as in Example 1 using Reference Example A-6 instead of Reference Example A-1. (Yield: 45.2%) 1H NMR (CD3OD, 400MHz) δ 8.29-8.27 (m, 3H), 8.16 (s, 1H), 8.09 (s, 1H), 7.88 (s, 1H), 7.00 (d, 1H), 6.95 (s, 1H), 5.43-5.39 (m, 1H), 4.56-4.55 (m, 1H), 4.13 (d, 2H), 3.92-3.89 (m, 1H), 3.67-3.61 (m, 3H), 3.10-3.07 (m, 1H), 2.95-2.88 (m, 2H), 2.18-2.12 (m, 4H), 1.87-1.77 (m, 2H), 1.60 (d, 6H), 1.52 (d, 1H), 1.19 (d, 3H) MS m / z= 516.3 (M+H)+

[0472] Example 10: N-(4-((3S,5S)-3-amino-5-methylpiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0473] The title compound (10.7 mg) was prepared in the same manner as in Example 6 using Reference Example B-4 instead of Reference Example B-1. (Yield: 45.2%) 1H NMR (CD3OD, 400MHz) δ 8.29-8.27 (m, 3H), 8.09 (s, 1H), 8.00 (s, 1H), 7.02 (d, 1H), 6.96 (s, 1H), 5.45-5.39 (m, 1H), 5.13 (q, 2H), 3.79-3.73 (m, 1H), 3.55-3.48 (m, 3H), 2.65-2.59 (m, 1H), 2.06-1.97 (m, 2H), 1.76-1.73 (m, 1H), 1.60 (d, 6H), 0.88 (d, 3H) MS m / z= 514.3 (M+H)+

[0474] Example 11: (S)-N-(4-(3-amino-3-methylpiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0475] The title compound (10.5 mg) was prepared in the same manner as in Example 6 using Reference Example B-5 instead of Reference Example B-1. (Yield: 44.7%) 1H NMR (CD3OD, 400MHz) δ 8.29-8.27 (m, 2H), 8.23 ​​(s, 1H), 8.09 (s, 1H), 7.94 (s, 1H), 7.04-7.01 (m, 2H), 5.45-5.39 (m, 1H), 5.12 (q, 2H), 3.52-3.49 (m, 1H), 3.39-3.28 (m, 2H), 3.16-3.10 (m, 1H), 1.95-1.84 (m, 2H), 1.76-1.74 (m, 2H), 2.92 (d, 6H), 1.46 (s, 3H) MS m / z= 514.3 (M+H)+

[0476] Example 12: (3R,4R)-3-amino-1-(2-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-ol

[0477] The title compound (13.4 mg) was prepared in the same manner as in Example 6 using Reference Example B-6 instead of Reference Example B-1. (Yield: 56.3%) 1H NMR (CD3OD, 400MHz) δ 8.31-8.25 (m, 3H), 8.09 (s, 1H), 7.98 (s, 1H), 7.04-7.00 (m, 2H), 5.51-5.39 (m, 1H), 5.11 (q, 2H), 3.90 (d, 1H), 3.74-3.65 (m, 2H), 3.24-3.17 (m, 1H), 3.04-2.95 (m, 2H), 2.05-2.03 (m, 1H), 1.76-1.68 (m, 1H), 2.92 (d, 6H) MS m / z= 516.3 (M+H)+

[0478] Example 13: (S)-N-(4-(3-aminopiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0479] The title compound (10.6 mg) was prepared in the same manner as in Example 6 using Reference Example C-1 instead of Reference Example B-1. (Yield: 15.9%) 1H NMR (CD3OD, 400MHz) δ 8.42 (s, 1H), 8.26 (d, 1H), 8.07 (s, 1H), 6.98 (d, 1H), 6.81 (br s, 1H), 5.40-5.37 (m, 1H), 4.33-4.24 (m, 2H), 3.99-3.94 (m, 2H), 3.62-3.50 (m, 3H), 3.05-3.01 (m, 1H), 2.29-2.26 (m, 1H), 2.05-1.88 (m, 5H), 1.84-1.74 (m, 3H), 1.60 (d, 6H) MS m / z= 460.3 (M+H)+

[0480] Example 14: (S)-N-(4-(3-Aminopiperidin-1-yl)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0481] The title compound (11.0 mg) was prepared in the same manner as in Example 6 using Reference Example C-2 instead of Reference Example B-1. (Yield: 30.1%) 1H NMR (CD3OD, 400MHz) δ 8.54 (s, 1H), 8.49 (s, 1H), 8.29 (d, 1H), 8.09 (s, 1H), 7.98 (s, 1H), 7.58 (t, 1H), 7.00 (d, 1H), 6.85 (s, 1H), 5.45-5.38 (m, 1H), 4.39 (dd, 1H), 4.23 (d, 1H), 3.58-3.53 (m, 1H), 3.46-3.37 (m, 2H), 2.31-2.27 (m, 1H), 2.11-2.07 (m, 1H), 1.95-1.89 (m, 1H), 1.84-1.76 (m, 1H), 1.61 (d, 6H) MS m / z= 492.2 (M+H)+

[0482] Example 15: (S)-N-(4-(3-Aminopiperidin-1-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0483] The title compound (10.0 mg) was prepared in the same manner as in Example 6 using Reference Example C-3 instead of Reference Example B-1. (Yield: 45.2%) 1H NMR (CD3OD, 400MHz) δ 8.50 (s, 1H), 8.27 (d, 1H), 8.09 (d, 1H), 7.82 (s, 1H), 7.00 (d, 1H), 6.86 (br s, 1H), 6.25 (tt, 1H), 5.43-5.39 (m, 1H), 4.65 (dt, 2H), 4.37 (d, 1H), 4.24 (d, 1H), 3.56-3.52 (m, 1H), 3.45-3.40 (m, 2H), 2.31-2.27 (m, 1H), 2.08-2.03 (m, 1H), 1.95-1.93 (m, 1H), 1.81-1.77 (m, 1H), 1.61 (d, 6H) MS m / z= 506.3 (M+H)+

[0484] Example 16: (S)-N-(4-(3-Aminopiperidin-1-yl)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0485] The title compound (6.7 mg) was prepared in the same manner as in Example 6 using Reference Example C-4 instead of Reference Example B-1. (Yield: 18.9%) 1H NMR (CD3OD, 400MHz) δ 8.52 (s, 1H), 8.27 (d, 1H), 8.18 (s, 1H), 8.08 (s, 1H), 7.85 (s, 1H), 7.01 (d, 1H), 6.85 (s, 1H), 5.43-5.40 (m, 1H), 5.05 (q, 2H), 4.37 (d, 1H), 4.27 (d, 1H), 3.57-3.52 (m, 1H), 3.46-3.35 (m, 2H), 2.31-2.27 (m, 1H), 2.11-2.07 (m, 1H), 1.95-1.92 (m, 1H), 1.81-1.78 (m, 1H), 1.61 (d, 6H) MS m / z= 524.2 (M+H)+

[0486] Example 17: (S)-N-(4-(3-Aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(2-fluoroethyl)-1H-pyrazolo[3,4-b]pyridin-6-amine

[0487] The title compound (3.7 mg) was prepared in the same manner as in Example 1, using Reference Examples A-3 and D-2 instead of Reference Examples A-1 and D-1, respectively. (Yield: 45.2%) 1H NMR (CD3OD, 400MHz) δ 8.59 (s, 1H), 8.34 (d, 1H), 8.28 (s, 1H), 8.15 (d, 2H), 7.81 (t, 1H), 7.08 (d, 1H), 7.02 (s, 1H), 5.03 (s, 2H), 4.94-4.89 (m, 2H), 3.87-3.79 (m, 1H), 3.60-3.52 (m, 1H), 3.49-3.40 (m, 1H), 3.04-2.90 (m, 2H), 2.29-2.18 (m, 1H), 1.93-1.83 (m, 1H), 1.83-1.72 (m, 1H), 1.69-1.59 (m, 1H) MS m / z= 472.0(M+H)+

[0488] Example 18: (S)-N-(4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(2-fluoroethyl)-1H-pyrazolo[3,4-b]pyridin-6-amine

[0489] The title compound (4.8 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-2 instead of Reference Examples A-1 and D-1, respectively. (Yield: 43.2%) 1H NMR (CD3OD, 400MHz) δ 8.35 (d, 1H), 8.28 (s, 1H), 8.23 ​​(s, 1H), 8.15 (s, 1H), 8.01 (s, 1H), 7.09 (d, 1H), 7.01 (s, 1H), 5.17 (q, 2H), 5.02 (s, 2H), 4.93-4.89 (m, 2H), 3.91-3.81 (m, 1H), 3.81-3.74 (m, 1H), 3.73-3.65 (m, 1H), 3.63-3.52 (m, 1H), 3.52-3.42 (m, 1H), 3.02-2.85 (m, 2H), 2.28-2.17 (m, 1H), 1.90-1.82 (m, 1H), 1.82-1.70 (m, 1H), 1.70-1.58 (m, 1H) MS m / z= 504.0 (M+H)+

[0490] Example 19: (S)-N-(4-(3-Aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(2,2-difluoroethyl)-1H-pyrazolo[3,4-b]pyridin-6-amine

[0491] The title compound (4.0 mg) was prepared in the same manner as in Example 1, using Reference Examples A-3 and D-3 instead of Reference Examples A-1 and D-1, respectively. (Yield: 62.4%) 1H NMR (CD3OD, 400MHz) δ 8.59 (s, 1H), 8.36 (d, 1H), 8.28 (s, 1H), 8.19 (s, 1H), 8.15 (s, 1H), 7.82 (t, 1H), 7.11 (d, 1H), 7.04 (s, 1H), 6.52 (tt, 1H), 5.16 (td, 2H), 3.89-3.78 (m, 1H), 3.64-3.54 (m, 1H), 3.49-3.40 (m, 1H), 3.05-2.90 (m, 2H), 2.27-2.20 (m, 1H), 1.94-1.85 (m, 1H), 1.85-1.71 (m, 1H), 1.71-1.56 (m, 1H) MS m / z= 489.9 (M+H)+

[0492] Example 20: (S)-N-(4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(2,2-difluoroethyl)-1H-pyrazolo[3,4-b]pyridin-6-amine

[0493] The title compound (8.2 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-3 instead of Reference Examples A-1 and D-1, respectively. (Yield: 60.1%) 1H NMR (CD3OD, 400MHz) δ 8.36 (d, 1H), 8.28-8.19 (m, 2H), 8.19 (s, 1H), 8.01 (s, 1H), 7.12 (d, 1H), 7.03 (s, 1H), 6.53 (tt, 1H), 5.18-5.05 (m, 4H), 3.91-3.83 (m, 1H), 3.60-3.56 (m, 1H), 3.49-3.42 (m, 1H), 3.05-2.88 (m, 2H), 2.29-2.17 (m, 1H), 1.91-1.82 (m, 1H), 1.82-1.68 (m, 1H), 1.68-1.58 (m, 1H) MS m / z= 521.9 (M+H)+

[0494] Example 21: (S)-N-(4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isobutyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0495] The title compound (4.2 mg) was prepared in the same manner as in Example 6 using Reference Example E-2 instead of Reference Example E-1. (Yield: 45.2%) 1H NMR (CD3OD, 400MHz) δ 8.30 (d, 1H), 8.25 (s, 2H), 8.10 (s, 1H), 7.99 (s, 1H), 7.02-6.96 (m, 2H), 5.10 (q, 2H), 4.44 (d, 2H), 3.86-3.78 (m, 1H), 3.58 (d, 1H), 3.50-3.43 (m, 1H), 2.99-2.89 (m, 2H), 2.41-2.35 (m, 1H), 2.24-2.21 (m, 1H), 1.86-1.77 (m, 2H), 1.63-1.61 (m, 1H), 0.98 (d, 6H) MS m / z= 514.3 (M+H)+

[0496] Example 22: (S)-N-(4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridin-6-amine

[0497] The title compound (8.7 mg) was prepared in the same manner as in Example 6 using Reference Example E-3 instead of Reference Example E-1. (Yield: 48.8%) 1H NMR (CD3OD, 400MHz) δ 8.30 (d, 1H), 8.25 (s, 2H), 8.09 (s, 1H), 7.98 (s, 1H), 7.03-6.96 (m, 2H), 5.10 (q, 2H), 4.51 (d, 2H), 3.84 (d, 1H), 3.58 (d, 1H), 3.50-3.42 (m, 1H), 2.99-2.89 (m, 2H), 2.24-2.21 (m, 1H), 1.88-1.75 (m, 2H), 1.66-1.60 (m, 1H), 1.42-1.37 (m, 1H), 0.60-0.57 (m, 2H), 0.51-0.48 (m, 2H) MS m / z= 512.3 (M+H)+

[0498] Example 23: (S)-N-(4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopentyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0499] The title compound (7.7 mg) was prepared in the same manner as in Example 6, using Reference Example E-4 instead of Reference Example E-1. (Yield: 40.4%) 1H NMR (CD3OD, 400MHz) δ 8.29 (d, 1H), 8.25 (s, 1H), 8.19 (s, 1H), 8.08 (s, 1H), 7.97 (s, 1H), 7.04-6.99 (m, 2H), 5.11 (q, 2H), 4.65 (t, 2H), 3.86-3.84 (m, 1H), 3.57 (d, 1H), 3.50-3.43 (m, 1H), 2.99-2.88 (m, 2H), 2.23-2.21 (m, 1H), 1.89-1.75 (m, 4H), 1.64-1.52 (m, 2H), 0.98 (d, 6H) MS m / z= 528.3 (M+H)+

[0500] Example 24: N4'-((1S,4S)-4-aminocyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(morpholinomethyl)-[2,3'-bipyridine]-4',6'-diamine

[0501] The title compound (15.8 mg) was prepared in the same manner as in Example 6 using Reference Example B-29 instead of Reference Example B-1. (Yield: 70.7%) 1H NMR (CDCl3, 400MHz) δ 10.01 (d, 1H), 8.53 (s, 1H), 8.44 (s, 1H), 7.99 (s, 1H), 7.88-7.86 (m, 2H), 7.77 (s, 2H), 6.72 (d, 1H), 5.27-5.21 (m, 1H), 3.97 (br, 1H), 3.77-3.75 (m, 4H), 3.56 (s, 2H), 2.94-2.89 (m, 1H), 2.52 (s, 4H), 2.15-2.11 (m, 2H), 1.82-1.73 (m, 6H), 1.64 (s, 6H), 0.87-0.83 (m, 2H) MS m / z= 542.3 (M+H)+

[0502] Example 25: N-(4-((3S,5S)-3-amino-5-methylpiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0503] The title compound (11.1 mg) was prepared in the same manner as in Example 6 using Reference Example B-7 instead of Reference Example B-1. (Yield: 38.7%) 1H NMR (CD3OD, 400MHz) δ 8.29-8.21 (m, 3H), 8.09 (s, 1H), 7.89 (s, 1H), 7.02 (d, 1H), 6.95 (s, 1H), 5.44-5.40 (m, 1H), 4.61-4.58 (m, 1H), 4.15-4.09 (m, 2H), 3.82-3.72 (m, 1H), 3.68-3.62 (m, 2H), 3.59-3.49 (m, 3H), 2.65-2.59 (m, 1H), 2.20-2.14 (m, 4H), 2.06-1.98 (m, 2H), 1.77-1.73 (m, 1H), 1.60 (d, 6H), 0.88 (d, 3H) MS m / z= 516.3 (M+H)+

[0504] Example 26: (S)-N-(4-(3-amino-3-methylpiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0505] The title compound (16.3 mg) was prepared in the same manner as in Example 6 using Reference Example B-8 instead of Reference Example B-1. (Yield: 60.1%) 1H NMR (CD3OD, 400MHz) δ 8.29-8.25 (m, 2H), 8.15 (d, 1H), 8.09 (s, 1H), 7.85 (s, 1H), 7.04-6.96 (m, 2H), 5.44-5.41 (m, 1H), 4.59-4.57 (m, 1H), 4.14-4.11 (m, 2H), 3.67-3.61 (m, 2H), 3.53-3.50 (m, 1H), 3.45-3.24 (m, 2H), 3.16-3.13 (m, 1H), 2.18-2.15 (m, 4H), 1.96-1.84 (m, 2H), 1.80-1.72 (m, 2H), 1.60 (d, 6H), 1.45 (s, 3H) MS m / z= 516.3 (M+H)+

[0506] Example 27: (3R,4R)-3-Amino-1-(2-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-ol

[0507] The title compound (13.8 mg) was prepared in the same manner as in Example 6 using Reference Example B-9 instead of Reference Example B-1. (Yield: 50.7%) 1H NMR (CD3OD, 400MHz) δ 8.29-8.27 (m, 2H), 8.20 (s, 1H), 8.09 (s, 1H), 7.89 (s, 1H), 7.05-6.98 (m, 2H), 5.44-5.43 (m, 1H), 4.62-4.53 (m, 1H), 4.14-4.11 (m, 2H), 3.93-3.91 (m, 1H), 3.70-3.61 (m, 4H), 3.23-2.13 (m, 1H), 3.05-2.94 (m, 2H), 2.19-2.16 (m, 4H), 2.08-2.00 (m, 1H), 1.75-1.67 (m, 1H), 1.60 (d, 6H) MS m / z= 518.3 (M+H)+

[0508] Example 28: N-(4-((S)-3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo[3,4-b]pyridin-6-amine

[0509] The title compound (4.6 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-4 instead of Reference Examples A-1 and D-1, respectively. (Yield: 30.3%) 1H NMR (CD3OD, 400MHz) δ 8.29-8.25 (m, 2H), 8.04-7.97 (m, 3H), 7.03 (d, 1H), 6.95 (s, 1H), 5.67-5,58 (m, 1H), 5.09 (q, 2H), 4.69 (d, 1H), 4.40-4.31 (m, 1H), 4.21 (t, 1H), 3.97 (d, 1H), 3.83 (d, 1H), 3.57-3.45 (m, 2H), 3.02-2.89 (m, 2H), 2.71-2.68 (m, 1H), 2.23-2.21 (m, 2H), 1.83-1.74 (m, 2H), 1.63-1.61 (m, 1H) MS m / z= 528.2 (M+H)+

[0510] Example 29: (S)-6-((4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile

[0511] The title compound (7.5 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-5 instead of Reference Examples A-1 and D-1, respectively. (Yield: 46.1%) 1H NMR (CD3OD, 400MHz) δ 8.37 (d, 1H), 8.30 (s, 1H), 8.25 (s, 1H), 7.98 (s, 1H), 7.24 (d, 1H), 7.05 (s, 1H), 5.59-5.51 (m, 1H), 5.11 (q, 2H), 3.87 (d, 1H), 3.60 (d, 1H), 3.50-3.43 (m, 1H), 3.03-2.91 (m, 2H), 2.24-2.21 (m, 1H), 1.88-1.74 (m, 2H), 1.67-1.62 (m, 7H) MS m / z= 525.3 (M+H)+

[0512] Example 30: N4-((1S,3R)-3-aminocyclopentyl)-N2-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridine-2,4-diamine

[0513] The title compound (12.4 mg) was prepared in the same manner as in Example 6 using Reference Example B-10 instead of Reference Example B-1. (Yield: 48.8%) 1H NMR (CD3OD, 400MHz) δ 8.71 (s, 1H), 8.24 (d, 1H), 8.07 (s, 1H), 7.99 (d, 1H), 6.99-6.95 (m, 2H), 6.56 (s, 1H), 5.45-5.38 (m, 1H), 5.16 (q, 2H), 4.24-4.21 (m, 1H), 3.82-3.78 (m, 1H), 2.96-2.89 (m, 1H), 2.46-2.29 (m, 2H), 2.03-1.93 (m, 2H), 1.77-1.71 (m, 1H), 1.62 (d, 6H) MS m / z= 500.3 (M+H)+

[0514] Example 31: N4-((1R,3R)-3-aminocyclopentyl)-N2-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridine-2,4-diamine

[0515] The title compound (14.5 mg) was prepared in the same manner as in Example 6 using Reference Example B-11 instead of Reference Example B-1. (Yield: 57.1%) 1H NMR (CD3OD, 400MHz) δ 8.71 (s, 1H), 8.24 (d, 1H), 8.06 (s, 1H), 7.99 (d, 1H), 6.98 (dd, 2H), 6.60 (s, 1H), 5.45-5.38 (m, 1H), 5.16 (q, 2H), 4.43-4.40 (m, 1H), 3.91-3.87 (m, 1H), 2.58-2.50 (m, 1H), 2.44-2.37 (m, 1H), 2.35-2.27 (m, 2H), 1.96-1.88 (m, 2H), 1.62 (d, 6H) MS m / z= 500.2 (M+H)+

[0516] Example 32: N-(4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0517] The title compound (16.0 mg) was prepared in the same manner as in Example 6 using Reference Example B-12 instead of Reference Example B-1. (Yield: 53.2%) 1H NMR (CD3OD, 400MHz) δ 8.34 (s, 1H), 8.30-8.28 (m, 2H), 8.09 (s, 1H), 8.00 (s, 1H), 7.04-7.01 (m, 2H), 5.45-5.39 (m, 1H), 5.12 (q, 2H), 4.85-4.65 (m, 1H), 3.96-3.93 (m, 1H), 3.73-3.70 (m, 1H), 3.63-3.56 (m, 1H), 3.10-3.00 (m, 2H), 2.29-2.26 (m, 1H), 1.97 (t, 1H), 1.60 (d, 6H) MS m / z= 518.3 (M+H)+

[0518] Example 33: N-(4-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0519] The title compound (8.9 mg) was prepared in the same manner as in Example 6 using Reference Example B-13 instead of Reference Example B-1. (Yield: 29.6%) 1H NMR (CD3OD, 400MHz) δ 8.34 (s, 1H), 8.30-8.28 (m, 2H), 8.09 (s, 1H), 8.00 (s, 1H), 7.04-7.02 (m, 2H), 5.46-5.39 (m, 1H), 5.23-5.08 (m, 3H), 3.83-3.76 (m, 2H), 3.52-3.49 (m, 1H), 3.30-3.27 (m, 1H), 3.19-3.12 (m, 1H), 2.19-2.05 (m, 2H), 1.60 (d, 6H) MS m / z= 518 (M+H)+

[0520] Example 34: N4-(azetidin-3-yl)-N2-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridine-2,4-diamine

[0521] The title compound (12.3 mg) was prepared in the same manner as in Example 6 using Reference Example B-14 instead of Reference Example B-1. (Yield: 50.3%) 1H NMR (CD3OD, 400MHz) δ 8.78 (s, 1H), 8.26 (d, 1H), 8.08 (s, 1H), 8.01 (s, 1H), 7.01-6.99 (m, 2H), 6.42 (s, 1H), 5.44-5.41 (m, 1H), 5.23 (q, 2H), 4.99-4.91 (m, 1H), 4.68-4.63 (m, 2H), 4.30-4.25 (m, 2H), 1.62 (d, 6H) MS m / z= 472.2 (M+H)+

[0522] Example 35: (R)-N-(4-(3-Aminopyrrolidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0523] The title compound (12.7 mg) was prepared in the same manner as in Example 6 using Reference Example B-15 instead of Reference Example B-1. (Yield: 88.5%) 1H NMR (CD3OD, 400MHz) δ 8.24 (d, 1H), 8.07-8.06 (m, 3H), 7.80 (s, 1H), 6.95 (d, 1H), 6.57 (s, 1H), 5.41-5.34 (m, 1H), 5.09 (q, 2H), 4.02-3.97 (m, 1H), 3.76-3.71 (m, 1H), 3.66-3.62 (m, 1H), 3.55-3.54 (m, 1H), 3.44 (d, 1H), 2.46-2.38 (m, 1H), 2.19-2.16 (m, 1H), 1.58 (d, 6H) MS m / z= 486.2 (M+H)+

[0524] Example 36: (S)-N-(4-(3-Aminopyrrolidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0525] The title compound (9.1 mg) was prepared in the same manner as in Example 6 using Reference Example B-16 instead of Reference Example B-1. (Yield: 63.6%) 1H NMR (CD3OD, 400MHz) δ 8.24 (d, 1H), 8.08-8.06 (m, 3H), 7.79 (s, 1H), 6.94 (d, 1H), 6.55 (s, 1H), 5.40-5.34 (m, 1H), 5.09 (q, 2H), 4.00-3.98 (m, 1H), 3.75-3.71 (m, 1H), 3.68-3.61 (m, 1H), 3.58-3.52 (m, 1H), 3.42 (dd, 1H), 2.47-2.38 (m, 1H), 2.20-2.14 (m, 1H), 1.58 (d, 6H) MS m / z= 486.2 (M+H)+

[0526] Example 37: (S)-N-(4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-phenyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0527] The title compound (33.5 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-6 instead of Reference Examples A-1 and D-1, respectively. (Yield: 38.8%) 1H NMR (CD3OD, 400MHz) δ 8.33 (d, 1H), 8.23 ​​(d, 2H), 8.20-7.91 (m, 3H), 7.76 (s, 1H), 7.64 (t, 2H), 7.46 (t, 1H), 7.08 (d, 1H), 6.99 (s, 1H), 5.10-5.04 (m, 2H), 3.82 (d, 1H), 3.81-3.39 (m, 2H), 2.97 (t, 1H), 2.84 (t, 1H), 2.19-2.15 (m, 1H), 1.79-1.57 (m, 3H) MS m / z= 534.2 (M+H)+

[0528] Example 38: (S)-N-(4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-neopentyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0529] The title compound (48.3 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-7 instead of Reference Examples A-1 and D-1, respectively. (Yield: 56.5%) 1H NMR (CD3OD, 400MHz) δ 8.32-8.27 (m, 2H), 8.23 ​​(s, 1H), 8.09 (s, 1H), 7.99 (s, 1H), 7.04 (d, 1H), 6.99 (s, 1H), 5.11 (q, 2H), 4.46 (s, 2H), 3.86 (d, 1H), 3.57 (d, 1H), 3.49-3.43 (m, 1H), 3.00 (t, 1H), 2.91 (t, 1H), 2.24-2.21 (m, 1H), 1.86-1.58 (m, 3H), 1.06 (s, 9H) MS m / z= 528.3 (M+H)+

[0530] Example 39: (S)-N-(4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-ethyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0531] The title compound (5.3 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-8 instead of Reference Examples A-1 and D-1, respectively. (Yield: 58.1%) 1H NMR (CDCl3, 400MHz) δ 8.32 (s, 1H), 8.06 (s, 1H), 7.90-7.85 (m, 4H), 7.59 (s, 1H), 6.69 (d, 1H), 4.77 (q, 2H), 4.54 (q, 2H), 3.40 (d, 1H), 3.30 (d, 1H), 2.94 (br, 1H), 2.70-2.67 (m, 1H), 2.43-2.40 (m, 1H), 2.01-1.99 (m, 1H), 1.79-1.76 (m, 1H), 1.44-1.32 (m, 2H), 1.28-1.19 (m, 2H), 0.88-0.86 (m, 2H) MS m / z= 486.2 (M+H)+

[0532] Example 40: N-(4-((S)-3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(sec-butyl)-1H-pyrazolo[3,4-b]pyridin-6-amine

[0533] The title compound (26.5 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-9 instead of Reference Examples A-1 and D-1, respectively. (Yield: 73.6%) 1H NMR (CDCl3, 400MHz) δ 8.28 (d, 1H), 8.07 (s, 1H), 7.90-7.85 (m, 4H), 7.58 (s, 1H), 6.68 (d, 1H), 4.99-4.98 (m, 1H), 4.77 (q, 2H), 3.38 (d, 1H), 3.30 (d, 1H), 2.94-2.91 (m, 1H), 2.71-2.66 (m, 1H), 2.41-2.36 (m, 1H), 2.15-2.14 (m, 1H), 2.01-1.92 (m, 2H), 1.80-1.76 (m, 1H), 1.68-1.65 (m, 1H), 1.60 (d, 4H), 1.33-1.30 (m, 1H), 1.25-1.18 (m, 1H), 0.84 (t, 3H) MS m / z= 514.2 (M+H)+

[0534] Example 41: (S)-N-(4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(3-fluoropropyl)-1H-pyrazolo[3,4-b]pyridin-6-amine

[0535] The title compound (35 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-10 instead of Reference Examples A-1 and D-1, respectively. (Yield: 64.3%) 1H NMR (CDCl3, 400MHz) δ 8.30 (s, 1H), 8.07 (s, 1H), 7.90-7.85 (m, 4H), 7.57 (s, 1H), 6.68 (d, 1H), 4.77 (q, 2H), 4.64 (t, 2H), 4.58 (t, 1H), 4.46 (t, 1H), 3.39 (d, 1H), 3.27 (d, 1H), 2.93 (br, 1H), 2.66-2.65 (m, 1H), 2.45-2.35 (m, 3H), 2.00-1.97 (m, 1H), 1.75-1.64 (m, 1H), 1.60-1.57 (m, 2H), 1.30-1.25 (m, 1H), 1.22-1.18 (m, 1H) MS m / z= 518.2 (M+H)+

[0536] Example 42: (S)-2-(1-(6-((4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-3-yl)azetidin-3-yl)propan-2-ol

[0537] The title compound (14 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-11 instead of Reference Examples A-1 and D-1, respectively. (Yield: 54.3%) 1H NMR (CD3OD, 400MHz) δ 8.28 (s, 1H), 8.14 (s, 1H), 8.07 (s, 1H), 7.96 (s, 1H), 7.83 (d, 1H), 6.75 (d, 1H), 5.12-5.00 (m, 2H), 4.62 (br, 2H), 4.17-4.09 (m, 4H), 3.43 (d, 1H), 2.97-2.93 (m, 2H), 2.73 (t, 1H), 2.45 (t, 1H), 2.03 (br, 1H), 1.78-1.73 (m, 2H), 1.54 (d, 6H), 1.23 (s, 6H) MS m / z= 613.3 (M+H)+

[0538] Example 43: N4'-((1R,4R)-4-aminocyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(morpholinomethyl)-[2,3'-bipyridine]-4',6'-diamine

[0539] The title compound (17.9 mg) was prepared in the same manner as in Example 6 using Reference Example B-30 instead of Reference Example B-1. (Yield: 75.0%) 1H NMR (CDCl3, 400MHz) δ 9.49 (d, 1H), 8.50 (s, 1H), 8.41 (s, 1H), 7.89-7.86 (m, 2H), 7.78-7.71 (m, 3H), 7.64 (br, 1H), 6.79 (d, 1H), 5.32-5.22 (m, 1H), 3.77-3.74 (m, 4H), 3.61-3.58 (m, 1H), 3.55 (s, 2H), 2.87-2.82 (m, 1H), 2.51 (s, 4H), 2.31 (d, 2H), 2.04 (d, 2H), 1.66 (d, 6H), 1.52-1.45 (m, 2H), 1.32-1.30 (m, 2H), 0.88-0.83 (m, 2H) MS m / z= 542.3 (M+H)+

[0540] Example 44: N4'-((1S,4S)-4-(aminomethyl)cyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(morpholinomethyl)-[2,3'-bipyridine]-4',6'-diamine

[0541] The title compound (12.3 mg) was prepared in the same manner as in Example 6 using Reference Example B-31 instead of Reference Example B-1. (Yield: 69.0%) 1H NMR (CDCl3, 400MHz) δ 10.05 (d, 1H), 8.49-8.46 (m, 2H), 8.03 (s, 1H), 7.88-7.86 (m, 2H), 7.78 (s, 2H), 7.68 (br, 1H), 6.70 (d, 1H), 5.28-5.22 (m, 1H), 4.08 (br, 1H), 3.77-3.75 (m, 4H), 3.56 (s, 2H), 2.67 (d, 2H), 2.51 (s, 4H), 2.14 (d, 2H), 1.78-1.71 (m, 4H), 1.67 (d, 6H), 1.44-1.38 (m, 3H), 0.87-0.82 (m, 2H) MS m / z= 556.4 (M+H)+

[0542] Example 45: 1-Isopropyl-N-(4-(2-methyl-2,8-diazaspiro[4.5]decan-8-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-6-amine

[0543] The title compound (8.1 mg) was prepared in the same manner as in Example 6 using Reference Example B-17 instead of Reference Example B-1. (Yield: 26.0%) 1H NMR (CD3OD, 400MHz) δ 8.17 (s, 1H), 8.12 (s, 1H), 7.98-7.95 (m, 2H), 7.88 (s, 1H), 7.53 (d, 1H), 5.04 (q, 2H), 3.09-2.94 (m, 4H), 2.66 (t, 2H), 2.57-2.49 (m, 2H), 2.38 (s, 3H), 1.78-1.70 (m, 12H) MS m / z= 556.3 (M+H)+

[0544] Example 46: N-(4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0545] The title compound (7.2 mg) was prepared in the same manner as in Example 6 using Reference Example C-5 instead of Reference Example B-1. (Yield: 35.2%) 1H NMR (CD3OD, 400MHz) δ 8.43 (s, 1H), 8.27 (d, 1H), 8.08 (s, 1H), 7.00 (d, 1H), 6.81 (s, 1H), 5.43-5.37 (m, 1H), 4.51-4.46 (m, 2H), 3.98-3.95 (m, 2H), 3.59 (t, 2H), 3.24-3.11 (m, 3H), 3.06-3.01 (m, 1H), 2.06-1.92 (m, 4H), 1.83-1.77 (m, 2H), 1.69-1.53 ​​(m, 7H), 1.22 (d, 3H) MS m / z= 474.3 (M+H)+

[0546] Example 47: (S)-N-(4-(3-amino-3-methylpiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0547] The title compound (6.2 mg) was prepared in the same manner as in Example 6, using Reference Example C-6 instead of Reference Example B-1. (Yield: 41.3%) 1H NMR (CD3OD, 400MHz) δ 8.45 (s, 1H), 8.27 (d, 1H), 8.08 (s, 1H), 6.99 (d, 1H), 6.82 (s, 1H), 5.44-5.37 (m, 1H), 3.98-3.94 (m, 2H), 3.90-3.85 (m, 3H), 3.68-3.57 (m, 3H), 3.07-3.03 (m, 1H), 2.08-1.98 (m, 6H), 1.84-1.76 (m, 2H), 1.60 (d, 6H), 1.51 (s, 3H) MS m / z= 474.3 (M+H)+

[0548] Example 48: N-(4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0549] The title compound (7.8 mg) was prepared in the same manner as in Example 6 using Reference Example C-7 instead of Reference Example B-1. (Yield: 33.2%) 1H NMR (CD3OD, 400MHz) δ 8.47 (s, 1H), 8.28 (d, 1H), 8.09 (s, 1H), 7.01 (d, 1H), 6.85 (s, 1H), 5.42-5.39 (m, 1H), 5.00-4.90 (m, 1H), 4.58-4.50 (m, 2H), 3.98-3.94 (m, 2H), 3.64-3.56 (m, 3H), 3.28-3.22 (m, 1H), 3.06-3.03 (m, 1H), 2.47-2.46 (m, 1H), 2.15-1.97 (m, 4H), 1.84-1.75 (m, 2H), 1.60 (d, 6H) MS m / z= 478.2 (M+H)+

[0550] Example 49: N-(4-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0551] The title compound (6.2 mg) was prepared in the same manner as in Example 6, using Reference Example C-8 instead of Reference Example B-1. (Yield 44.7%) 1H NMR (CD3OD, 400MHz) δ 8.46 (s, 1H), 8.27 (d, 1H), 8.08 (s, 1H), 7.02 (d, 1H), 6.86 (s, 1H), 5.43-5.39 (m, 1H), 5.24 (d, 1H), 4.39-4.30 (m, 2H), 3.98-3.95 (m, 2H), 3.77-3.75 (m, 1H), 3.62-3.54 (m, 3H), 3.50-3.47 (m, 1H), 3.07-3.03 (m, 1H), 2.40-2.12 (m, 2H), 2.03-1.98 (m, 2H), 1.84-1.75 (m, 2H), 1.60 (d, 6H) MS m / z= 478.2 (M+H)+

[0552] Example 50: (3R,4R)-3-Amino-1-(2-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-4-yl)piperidin-4-ol

[0553] The title compound (8.0 mg) was prepared in the same manner as in Example 6 using Reference Example C-9 instead of Reference Example B-1. (Yield: 66.2%) 1H NMR (CD3OD, 400MHz) δ 8.44 (s, 1H), 8.27 (d, 1H), 8.08 (s, 1H), 7.00 (d, 1H), 6.82 (s, 1H), 5.44-5.37 (m, 1H), 4.55-4.45 (m, 2H), 3.98-3.95 (m, 2H), 3.82-3.79 (m, 1H), 3.62-3.56 (m, 2H), 3.28-3.21 (m, 3H), 3.07-3.02 (m, 1H), 2.25-2.22 (m, 1H), 2.01-1.98 (m, 2H), 1.84-1.79 (m, 3H), 1.60 (d, 6H) MS m / z= 476.2 (M+H)+

[0554] Example 51: (S)-3-(6-((4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1H-pyrazolo[3,4-b]pyridin-1-yl)propan-1-ol

[0555] The title compound (19.8 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-13 instead of Reference Examples A-1 and D-1, respectively. (Yield: 37.1%) 1H NMR (CD3OD, 400MHz) δ 8.28 (d, 2H), 8.10 (s, 1H), 8.05 (s, 1H), 7.97 (s, 1H), 7.05 (d, 1H), 6.99 (s, 1H), 5.12 (q, MS m / z= 516.2 (M+H)+

[0556] Example 52: (S)-2-(6-((4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetic acid

[0557] The title compound (9.2 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-14 instead of Reference Examples A-1 and D-1, respectively. (Yield: 17.2%) 1H NMR (CD3OD, 400MHz) δ 8.28 (d, 2H), 8.12 (s, 1H), 8.08 (s, 1H), 7.97 (s, 1H), 7.03 (d, 1H), 6.97 (s, 1H), 5.12 (q, 2H), 3.85 (d, 1H), 3.56-3.45 (m, 2H), 3.01 (t, 1H), 2.89 (t, 1H), 2.22 (d, 1H), 1.86-1.62 (m, 3H) MS m / z= 515.2 (M+H)+

[0558] Example 53: (S)-N-(4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-ethyl-3-methyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0559] The title compound (13.7 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-15 instead of Reference Examples A-1 and D-1, respectively. (Yield: 65.1%) 1H NMR (CD3OD, 400MHz) δ 8.27-8.24 (m, 3H), 7.98 (s, 1H), 6.96 (d, 2H), 5.11 (q, 2H), 4.57 (q, 2H), 3.83 (d, 1H), 3.57 (d, 1H), 3.59-3.45 (m, 1H), 2.98-2.88 (m, 2H), 2.56 (s, 3H), 2.22 (d, 1H), 1.87-1.82 (m, 2H), 1.79-1.72 (m, 1H), 1.66 (t, 3H) MS m / z=500.2 (M+H)+

[0560] Example 54: (S)-N-(4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-3-methyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0561] The title compound (19 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-16 instead of Reference Examples A-1 and D-1, respectively. (Yield: 88.1%) 1H NMR (CD3OD, 400MHz) δ 8.30 (s, 1H), 8.26-8.24 (d, 2H), 7.98 (s, 1H), 6.96-6.93 (m, 2H), 5.37-5.31 (m, 1H), 5.11 (q, 2H), 3.83 (d, 1H), 3.57 (d, 1H), 3.50-3.42 (m, 2H), 2.98-2.88 (m, 2H), 2.56 (s, 3H), 1.22 (d, 1H), 1.85-1.79 (m, 2H), 1.66-1.58 (m, 7H) MS m / z= 514.3 (M+H)+

[0562] Example 55: (S)-N-(4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(cyclopropylmethyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0563] The title compound (12.4 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-17 instead of Reference Examples A-1 and D-1, respectively. (Yield: 56.4%) 1H NMR (CD3OD, 400MHz) δ 8.28-8.24 (m, 3H), 7.98 (s, 1H), 6.98-6.96 (m, 2H), 5.13-5.07 (m, 2H), 4.43 (d, 2H), 3.84 (d, 1H), 3.57 (d, 1H), 3.50-3.42 (m, 2H), 2.99-2.88 (m, 2H), 2.57 (s, 3H), 2.22 (d, 1H), 1.88-1.75 (m, 2H), 1.64-1.60 (m, 1H), 1.37-1.31 (m, 1H), 0.57 (q, 2H), 0.47 (q, 2H) MS m / z= 526.3 (M+H)+

[0564] Example 56: (S)-N2-(1-Isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-N4-(pyrrolidin-3-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridine-2,4-diamine

[0565] The title compound (9.1 mg) was prepared in the same manner as in Example 6 using Reference Example B-18 instead of Reference Example B-1. (Yield: 60.2%) 1H NMR (CD3OD, 400MHz) δ 8.78 (s, 1H), 8.26 (d, 1H), 8.08 (s, 1H), 8.00 (s, 1H), 7.01-6.99 (m, 2H), 6.62 (s, 1H), 5.45-5.42 (m, 1H), 5.21 (q, 2H), 4.69-4.64 (m, 1H), 3.89-3.84 (m, 1H), 3.60 (t, 2H), 3.48 (dd, 1H), 2.71-2.64 (m, 1H), 2.35-2.29 (m, 1H), 1.63 (d, 6H) MS m / z= 487.2 (M+H)+

[0566] Example 57: (S)-6-((4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-ethyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile

[0567] The title compound (17.2 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-18 instead of Reference Examples A-1 and D-1, respectively. (Yield: 67.0%) 1H NMR (CD3OD, 400MHz) δ 8.30 (s, 1H), 8.17 (s, 1H), 8.13 (s, 1H), 8.04 (d, 1H), 7.98 (s, 1H), 7.22 (d, 1H), 5.04 (q, 2H), 4.62 (q, 2H), 3.46 (d, 1H), 2.99 (br, 1H), 2.69 (t, 1H), 2.50 (t, 1H), 2.06 (br, 1H), 1.77-1.75 (m, 2H), 1.60 (t, 3H), 1.35-1.31 (m, 2H) MS m / z= 511.2 (M+H)+

[0568] Example 58: (R)-N2-(1-Isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-N4-(pyrrolidin-3-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridine-2,4-diamine

[0569] The title compound (8.6 mg) was prepared in the same manner as in Example 6 using Reference Example B-19 instead of Reference Example B-1. (Yield: 54.8%) 1H NMR (CD3OD, 400MHz) δ 8.78 (s, 1H), 8.26 (d, 1H), 8.08 (s, 1H), 8.00 (d, 1H), 7.01-6.99 (m, 2H), 6.62 (s, 1H), 5.45-5.42 (m, 1H), 5.21 (q, 2H), 4.68-4.63 (m, 1H), 3.88-3.84 (m, 1H), 3.62-3.58 (m, 2H), 3.48 (dd, 1H), 2.71-2.66 (m, 1H), 2.33-2.29 (m, 1H), 1.62 (d, 6H) MS m / z= 487.2 (M+H)+

[0570] Example 59: (S)-6-((4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile

[0571] The title compound (3.9 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-19 instead of Reference Examples A-1 and D-1, respectively. (Yield: 14.5%) 1H NMR (CD3OD, 400MHz) δ 8.29 (s, 1H), 8.17 (s, 1H), 8.12 (s, 1H), 8.03 (d, 1H), 7.97 (s, 1H), 7.21 (d, 1H), 5.11-5.01 (m, 2H), 4.43 (d, 2H), 3.42 (d, 1H), 3.28-3.27 (m, 1H), 2.97-2.93 (m, 1H), 2.80-2.74 (m, 1H), 2.44 (t, 1H), 2.04 (d, 1H), 1.82-1.74 (m, 2H), 1.53-1.48 (m, 1H), 1.35-1.24 (m, 1H), 0.63 (d, 2H), 0.54 (d, 2H) MS m / z= 537.3 (M+H)+

[0572] Example 60: (S)-6-((4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxylic acid

[0573] The title compound (9 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-19 instead of Reference Examples A-1 and D-1, respectively. (Yield: 32.2%) 1H NMR (CD3OD, 400MHz) δ 8.38 (s, 1H), 8.32 (d, 1H), 8.17 (s, 1H), 8.11 (s, 1H), 7.98 (s, 1H), 7.09 (d, 1H), 5.15-5.01 (m, 2H), 4.65-4.61 (m, 1H), 4.43 (d, 1H), 3.43 (d, 1H), 2.97 (br, 1H), 2.82-2.79 (m, 1H), 2.48-2.43 (m, 1H), 2.06-2.03 (m, 1H), 1.84-1.75 (m, 2H), 1.54-1.51 (m, 1H), 1.35-1.31 (m, 1H), 0.62 (d, 2H), 0.55 (d, 2H) MS m / z= 556.3 (M+H)+

[0574] Example 61: (S)-6-((4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-(2,2-difluoroethyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile

[0575] The title compound (8.3 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-20 instead of Reference Examples A-1 and D-1, respectively. (Yield: 98.2%) 1H NMR (CDCl3, 400MHz) δ 8.17 (s, 1H), 8.11 (s, 1H), 8.00 (d, 1H), 7.92 (s, 1H), 7.89 (s, 1H), 6.99 (d, 1H), 6.33 (tt, 1H), 4.90 (td, 2H), 4.80 (q, 2H), 3.42 (d, 1H), 3.30 (d, 1H), 2.99-2.94 (m, 1H), 2.66 (t, 1H), 2.44 (t, 1H), 2.05-2.01 (m, 1H), 1.81-1.78 (m, 1H), 1.24-1.19 (m, 2H) MS m / z= 547.2 (M+H)+

[0576] Example 62: (S)-6-((4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-(2-fluoroethyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile

[0577] The title compound (8 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-21 instead of Reference Examples A-1 and D-1, respectively. (Yield: 63.4%) 1H NMR (CDCl3, 400MHz) δ 8.15 (s, 1H), 8.11 (s, 1H), 7.99 (d, 1H), 7.92 (s, 1H), 7.87 (s, 1H), 7.83 (br, 1H), 6.99 (d, 1H), 5.05-5.02 (m, 1H), 4.93-4.77 (m, 5H), 3.52 (s, 2H), 3.44 (d, 1H), 3.31 (d, 1H), 2.99-2.96 (m, 1H), 2.61-2.58 (m, 1H), 2.48-2.43 (m, 1H), 2.04-2.01 (m, 1H), 1.78-1.75 (m, 1H), 1.28-1.20 (m, 2H) MS m / z= 529.2 (M+H)+

[0578] Example 63: (S)-6-((4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-(3-fluoropropyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile

[0579] The title compound (2 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-22 instead of Reference Examples A-1 and D-1, respectively. (Yield: 15.5%) 1H NMR (CDCl3, 400MHz) δ 8.22 (s, 1H), 8.05 (s, 1H), 7.99 (d, 1H), 7.90 (s, 1H), 7.87 (s, 1H), 7.00 (d, 1H), 4.80 (q, 2H), 4.71 (t, 2H), 4.61 (t, 1H), 4.50 (t, 1H), 3.44 (d, 1H), 3.29 (d, 1H), 2.99 (br, 1H), 2.71 (t, 1H), 2.68-2.43 (m, 4H), 2.39 (t, 1H), 2.04-2.02 (m, 2H) MS m / z= 543.2 (M+H)+

[0580] Example 64: (S)-6-((4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-(3,3,3-trifluoropropyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile

[0581] The title compound (8 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-23 instead of Reference Examples A-1 and D-1, respectively. (Yield: 58.0%) 1H NMR (CD3OD, 400MHz) δ 8.17-8.14 (m, 3H), 8.06 (d, 1H), 7.98 (s, 1H), 7.30 (d, 1H), 5.04 (q, 2H), 4.88-4.78 (m, 2H), 4.60 (br, 2H), 3.42 (d, 1H), 3.33-3.27 (m, 1H), 3.05-2.97 (m, 2H), 2.73 (t, 1H), 2.46 (t, 1H), 2.06-2.02 (m, 1H), 1.79-1.71 (m, 2H) MS m / z= 579.2 (M+H)+

[0582] Example 65: (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-ethyl-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0583] The title compound (6.2 mg) was prepared in the same manner as in Example 6 using Reference Example B-20 instead of Reference Example B-1. (Yield: 36.72%) 1H NMR (CD3OD, 400MHz) δ 8.31 (s, 1H), 8.10 (s, 1H), 8.03 (s, 1H), 7.97 (d, 1H), 7.89 (d, 2H), 6.98 (d, 1H), 5.29-5.23 (m, 1H), 4.28 (q, 2H), 3.51 (d, 1H), 3.16-3.12 (m, 1H), 2.82 (t, 1H), 2.53 (t, 1H), 2.13-2.03 (m, 2H), 1.86-1.79 (m, 2H), 1.64-1.61 (m, 6H), 1.54 (t, 3H), 1.48-1.39 (m, 1H) MS m / z= 446.2 (M+H)+

[0584] Example 66: (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0585] The title compound (11.4 mg) was prepared in the same manner as in Example 6 using Reference Example B-21 instead of Reference Example B-1. (Yield: 65.3%) 1H NMR (CD3OD, 400MHz) δ 8.28-8.26 (m, 2H), 8.13 (s, 1H), 8.08 (s, 1H), 7.86 (s, 1H), 7.02-6.98 (m, 2H), 5.44-5.38 (m, 1H), 4.70-4.64 (m, 1H), 3.86 (d, 1H), 3.59 (d, 1H), 3.50-3.44 (m, 1H), 3.01-2.87 (m, 2H), 2.24-2.21 (m, 1H), 1.88-1.72 (m, 2H), 1.69-1.49 (m, 13H) MS m / z= 460.3 (M+H)+

[0586] Example 67: (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0587] The title compound (10.4 mg) was prepared in the same manner as in Example 6 using Reference Example B-22 instead of Reference Example B-1. (Yield: 58.1%) 1H NMR (CD3OD, 400MHz) δ 8.23 ​​(s, 1H), 8.19-8.14 (m, 2H), 8.01 (s, 1H), 7.88 (s, 1H), 7.01 (d, 1H), 5.37-5.33 (m, 1H), 4.12 (d, 2H), 3.77-3.75 (m, 1H), 3.54-3.50 (m, 1H), 3.46-3.41 (m, 1H), 2.95-2.85 (m, 2H), 2.24-2.21 (m, 1H), 1.84-1.78 (m, 2H), 1.68-1.52 (m, 7H), 1.42-1.36 (m, 1H), 0.72-0.67 (m, 2H), 0.51-0.47 (m, 2H) MS m / z= 472.3 (M+H)+

[0588] Example 68: (S)-6-((4-(3-aminopiperidin-1-yl)-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile

[0589] The title compound (24 mg) was prepared in the same manner as in Example 1, using Reference Examples A-4 and D-5 instead of Reference Examples A-1 and D-1, respectively. (Yield: 77.9%) 1H NMR (CDCl3, 400MHz) δ 8.12-8.10 (m, 2H), 7.97 (d, 1H), 7.84 (s, 1H), 7.70 (s, 2H), 6.96 (d, 1H), 5.28 (q, 1H), 4.00 (s, 3H), 3.45 (d, 1H), 3.34 (d, 1H), 3.02-2.97 (m, 1H), 2.66 (t, 1H), 2.43 (t, 1H), 2.03 (d, 1H), 1.80-1.74 (m, 2H), 1.67 (d, 6H), 1.25-1.22 (m, 1H) MS m / z= 457.3 (M+H)+

[0590] Example 69: (S)-6-((4-(3-Aminopiperidin-1-yl)-5-(1-ethyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile

[0591] The title compound (13.7 mg) was prepared in the same manner as in Example 1, using Reference Examples A-8 and D-5 instead of Reference Examples A-1 and D-1, respectively. (Yield: 74.4%) 1H NMR (CDCl3, 400MHz) δ 8.13-8.11 (m, 2H), 7.97 (d, 1H), 7.83 (s, 1H), 7.75 (s, 1H), 6.96 (d, 1H), 5.33-5.26 (m, 1H), 4.27 (q, 2H), 4.45 (d, 1H), 3.34 (d, 1H), 3.01-2.94 (m, 1H), 2.66 (t, 1H), 2.43 (t, 1H), 2.08-2.01 (m, 1H), 1.81-1.77 (m, 1H), 1.67 (d, 6H), 1.58 (t, 3H), 1.25-1.18 (m, 2H) MS m / z= 471.3 (M+H)+

[0592] Example 70: (S)-6-((4-(3-Aminopiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile

[0593] The title compound (16.5 mg) was prepared in the same manner as in Example 1, using Reference Examples A-9 and D-5 instead of Reference Examples A-1 and D-1, respectively. (Yield: 79.0%) 1H NMR (CDCl3, 400MHz) δ 8.13-8.12 (m, 2H), 7.96 (d, 1H), 7.82-7.79 (m, 2H), 6.96 (d, 1H), 5.31-5.28 (m, 1H), 4.61-4.57 (m, 1H), 3.44 (d, 1H), 3.33 (d, 1H), 2.99-2.96 (m, 1H), 2.66 (t, 1H), 2.42 (t, 1H), 2.07-2.02 (m, 1H), 1.80-1.77 (m, 1H), 1.67 (d, 6H), 1.58 (s, 6H), 1.272-1.18 (m, 1H) MS m / z= 485.3 (M+H)+

[0594] Example 71: (S)-6-((4-(3-Aminopiperidin-1-yl)-5-(1-cyclopropyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile

[0595] The title compound (9 mg) was prepared in the same manner as in Example 1, using Reference Examples A-10 and D-5 instead of Reference Examples A-1 and D-1, respectively. (Yield: 73.1%) 1H NMR (CDCl3, 400MHz) δ 8.15 (s, 1H), 8.08 (s, 1H), 7.97 (d, 1H), 7.79 (d, 1H), 6.97 (d, 1H), 5.32-5.27 (m, 1H), 3.70-3.66 (m, 1H), 3.44 (d, 1H), 3.33 (d, 1H), 3.00-2.97 (m, 1H), 2.66 (t, 1H), 2.44 (t, 1H), 2.07-2.02 (m, 1H), 1.77 (br, 1H), 1.67 (d, 6H), 1.30 (br, 2H), 1.27-1.20 (m, 2H), 1.11-1.07 (m, 2H) MS m / z= 483.3 (M+H)+

[0596] Example 72: N-(4-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridin-6-amine

[0597] The title compound (12.5 mg) was prepared in the same manner as in Example 1, using Reference Examples A-11 and D-24 instead of Reference Examples A-1 and D-1, respectively. (Yield: 65.3%) 1H NMR (CD3OD, 400MHz) δ 8.32-8.28 (m, 3H), 8.09 (s, 1H), 8.01 (s, 1H), 7.03-7.01 (m, 2H), 5.14-5.08 (m, 3H), 4.51 (d, 2H), 3.77-3.71 (m, 2H), 3.51 (d, 1H), 3.17-3.15 (m, 1H), 2.20-2.16 (m, 1H), 2.03 (br, 1H), 1.40-1.31 (m, 2H), 0.60-0.58 (m, 2H), 0.50-0.49 (m, 2H) MS m / z= 530.3 (M+H)+

[0598] Example 73: (S)-4-(3-Aminopiperidin-1-yl)-N6-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-N6',N6'-dimethyl-[3,3'-bipyridine]-6,6'-diamine

[0599] The title compound (4.6 mg) was prepared in the same manner as in Example 1 using Reference Example A-12 instead of Reference Example A-1. (Yield: 69.0%) 1H NMR (CD3OD, 400MHz) δ 8.37 (s, 1H), 8.31-8.23 (m, 3H), 8.10 (s, 1H), 7.44 (d, 1H), 7.06-7.02 (m, 2H), 5.45-5.42 (m, 1H), 3.90 (d, 1H), 3.60 (d, 1H), 3.33 (s, 6H), 3.00 (q, 2H), 2.22 (d, 1H), 1.93-1.90 (m, 1H), 1.79-1.73 (m, 1H), 1.67-1.65 (m, 2H), 1.59 (s, 6H) MS m / z= 472.3 (M+H)+

[0600] Example 74: (S)-N-(4-(3-Aminopiperidin-1-yl)-6'-morpholino-[3,3'-bipyridin]-6-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0601] The title compound (2.9 mg) was prepared in the same manner as in Example 1 using Reference Example A-13 instead of Reference Example A-1. (Yield: 86.7%) 1H NMR (CD3OD, 400MHz) δ 8.37 (s, 1H), 8.31-8.29 (m, 3H), 8.10 (s, 1H), 7.56 (d, 1H), 7.06-7.02 (m, 2H), 5.45-5.42 (m, 1H), 3.94-3.89 (m, 5H), 3.82 (br, 4H), 3.59 (d, 1H), 3.41 (br, 1H), 3.01-2.96 (m, 2H), 2.22-2.20 (m, 1H), 1.93-1.90 (m, 1H), 1.78-1.76 (m, 1H), 1.68-1.64 (m, 1H), 1.60 (d, 6H) MS m / z= 514.3 (M+H)+

[0602] Example 75: (S)-N-(4-(3-aminopiperidin-1-yl)-6'-((4-methylpiperazin-1-yl)methyl)-[3,3'-bipyridin]-6-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0603] The title compound (46 mg) was prepared in the same manner as in Example 6 using Reference Example B-23 instead of Reference Example B-1. (Yield: 84.3%) 1H NMR (CD3OD, 400MHz) δ 9.06 (s, 1H), 8.55 (d, 1H), 8.43 (s, 1H), 8.31 (d, 1H), 8.11 (s, 1H), 8.03 (d, 1H), 7.06-7.04 (m, 2H), 5.47-5.40 (m, 1H), 4.43 (s, 2H), 3.82 (d, 1H), 3.58-3.51 (m, 8H), 3.41-3.37 (m, 2H), 3.27-3.16 (m, 1H), 3.02 (s, 3H), 2.99-2.96 (m, 2H), 2.23-2.19 (m, 1H), 1.89-1.85 (m, 1H), 1.78-1.71 (m, 1H), 1.68-1.62 (m, 7H) MS m / z= 541.3 (M+H)+

[0604] Example 76: (S)-N-(4-(3-aminopiperidin-1-yl)-6'-((4-fluoropiperidin-1-yl)methyl)-[3,3'-bipyridin]-6-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0605] The title compound (27 mg) was prepared in the same manner as in Example 6 using Reference Example B-24 instead of Reference Example B-1. (Yield: 78.6%) 1H NMR (CD3OD, 400MHz) δ 8.97 (s, 1H), 8.33-8.29 (m, 2H), 8.21 (d, 1H), 8.10 (s, 1H), 7.75 (d, 1H), 7.05-7.01 (m, 2H), 5.46-5.41 (m, 1H), 5.03 (d, 1H), 4.66 (s, 2H), 3.84 (d, 1H), 3.68 (br, 4H), 3.56-3.39 (m, 3H), 3.04-2.91 (m, 2H), 2.25-2.18 (m, 5H), 1.81-1.77 (m, 1H), 1.65 (d, 6H), 0.91-0.86 (m, 1H) MS m / z= 544.3 (M+H)+

[0606] Example 77: (S)-N-(4-(3-Aminopiperidin-1-yl)-6'-(piperazin-1-yl)-[3,3'-bipyridin]-6-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0607] The title compound (16 mg) was prepared in the same manner as in Example 6 using Reference Example B-25 instead of Reference Example B-1. (Yield: 74.9%) 1H NMR (CD3OD, 400MHz) δ 8.40 (s, 1H), 8.39-8.28 (m, 2H), 8.16 (d, 1H), 8.09 (s, 1H), 7.40 (d, 1H), 7.03 (d, 1H), 6.99 (s, 1H), 5.44-5.41 (m, 1H), 4.13-4.11 (m, 4H), 3.90-3.87 (m, 1H), 3.60-3.57 (m, 1H), 3.51-3.49 (m, 4H), 3.46-3.40 (m, 2H), 2.96-2.93 (m, 2H), 2.23-2.19 (m, 1H), 1.89-1.86 (m, 1H), 1.76-1.73 (m, 1H), 1.59 (d, 6H) MS m / z= 513.3 (M+H)+

[0608] Example 78: N-(4-((3S,5S)-3-amino-5-fluoropiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0609] The title compound (6.2 mg) was prepared in the same manner as in Example 6 using Reference Example B-26 instead of Reference Example B-1. (Yield: 45.3%) 1H NMR ((CDCl3, 400MHz) δ 8.34 (s, 1H), 8.22 (s, 1H), 8.05 (s, 1H), 7.94-7.85 (m, 3H), 7.66 (s, 1H), 6.78 (d, 1H), 5.30-5.17 (m, 1H), 5.04-4.97 (m, 1H), 4.92-4.86 (m, 1H), 4.86-4.68 (m, 2H), 3.71-3.57 (m, 1H), 3.52-3.41 (m, 1H), 3.41-3.29 (m, 1H), 2.98-2.77 (m, 1H), 2.51-2.41 (m, 1H), 2.41-2.29 (m, 1H), 1.72 (d, 6H), MS m / z= 518.2 (M+H)+

[0610] Example 79: (3S)-1-(2-((1-(sec-butyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0611] The title compound (1.3 mg) was prepared in the same manner as in step 1 of Example 1, using reference examples A-14 and D-9 instead of reference examples A-1 and D-1, respectively. (Yield: 11.4%) 1H NMR (CD3OD, 400MHz) δ 8.44 (d, 1H), 8.18 (s, 1H), 8.10 (s, 1H), 7.97 (d, 2H), 7.91 (s, 1H), 6.94 (d, 1H), 5.06-4.99 (m, 3H), 3.85 (bs, 1H), 3.49 (d, 1H), 3.23 (d, 1H), 2.71-2.62 (m, 2H), 2.21-2.19 (m, 4H), 1.60 (t, 3H), 1.44-1.41 (m, 1H), 1.35 (t, 3H) MS m / z= 515.2 (M+H)+

[0612] Example 80: (S)-1-(2-((1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0613] The title compound (1.8 mg) was prepared in the same manner as in step 1 of Example 1, using reference examples A-14 and D-24 instead of reference examples A-1 and D-1, respectively. (Yield: 15.8%) 1H NMR (CD3OD, 400MHz) δ 8.45 (s, 1H), 8.44 (s, 1H), 8.19 (s, 1H), 8.10 (d, 2H), 7.89 (s, 1H), 6.95 (d, 1H), 5.03 (q, 2H), 4.59 (bs, 1H), 4.38 (d, 2H), 3.87-3.84 (m, 1H), 3.60 (d, 1H), 3.33 (d, 1H), 2.76 (t, 1H), 2.64 (t, 1H), 2.19 (d, 2H), 1.87-1.84 (m, 1H), 1.70-1.62 (m, 2H), 1.46-1.42 (m, 2H), 0.58 (d, 2H), 0.52 (m, 2H) MS m / z= 513.2 (M+H)+

[0614] Example 81: (S)-1-(2-((1-Isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0615] The title compound (2.5 mg) was prepared in the same manner as in step 1 of Example 1, using Reference Example A-14 instead of Reference Example A-1. (Yield: 22.4%) 1H NMR (CD3OD, 400MHz) δ 8.44 (s, 1H), 8.17 (s, 1H), 8.09 (s, 1H), 7.97 (d, 2H), 7.89 (s, 1H), 6.94 (d, 1H), 5.33-5.26 (m, 1H), 5.06-4.99 (q, 2H), 3.88-3.83 (m, 1H), 3.51 (d, 1H), 3.24 (d, 1H), 2.66 (t, 2H), 2.05 (bs, 2H), 1.81-1.71 (m, 1H), 1.62 (d, 6H), 1.44-1.40 (m, 1H) MS m / z= 501.2 (M+H)+

[0616] Example 82: (S)-1-(2-((1-(3-fluoropropyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0617] The title compound (5.1 mg) was prepared in the same manner as in step 1 of Example 1, using reference examples A-14 and D-10 instead of reference examples A-1 and D-1, respectively. (Yield: 33.6%) 1H NMR (CD3OD, 400MHz) δ 8.41 (s, 1H), 8.18 (s, 1H), 8.09 (s, 1H), 7.97 (d, 2H), 7.91 (s, 1H), 6.96 (d, 1H), 5.02 (q, 2H), 4.64 (t, 2H), 4.55 (t, 1H), 4.44 (t, 1H), 3.86-3.83 (m, 1H), 3.48 (d, 1H), 3.21 (d, 1H), 2.75-2.63 (m, 2H), 2.40-2.33 (m, 2H), 2.03 (d, 2H), 1.84-1.80 (m, 1H), 1.67-1.63 (m, 1H), 1.50-1.44 (m, 1H) MS m / z= 519.2 (M+H)+

[0618] Example 83: (S)-1-(5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-2-((1-(3,3,3-trifluoropropyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)pyridin-4-yl)piperidin-3-ol

[0619] The title compound (3.8 mg) was prepared in the same manner as in step 1 of Example 1, using reference examples A-14 and D-25 instead of reference examples A-1 and D-1, respectively. (Yield: 23.4%) 1H NMR (CD3OD, 400MHz) δ 8.30 (s, 1H), 8.18 (s, 1H), 8.10 (s, 1H), 7.99-7.96 (d, 2H), 7.93 (d, 1H), 7.01 (d, 1H), 5.02 (q, 2H), 4.76 (t, 2H), 3.85-3.83 (m, 1H), 3.47 (d, 1H), 3.21 (d, 1H), 2.96-2.91 (m, 2H), 2.74 (t, 1H), 2.62 (t, 1H), 2.06-2.01 (m, 2H), 1.86-1.81 (m, 1H), 1.45-1.41 (m, 1H), 1.35-1.30 (m, 1H) MS m / z= 555.2 (M+H)+

[0620] Example 84: (3S)-1-(2-((1-(sec-butyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0621] The title compound (3.8 mg) was prepared in the same manner as in step 1 of Example 1, using reference examples A-15 and D-9 instead of reference examples A-1 and D-1, respectively. (Yield: 23.4%) 1H NMR (CD3OD, 400MHz) δ 8.46 (d, 2H), 8.14 (d, 2H), 7.98 (d, 1H), 7.91 (s, 1H), 7.70-7.40 (m, 1H), 6.95 (d, 1H), 5.05 (bs, 1H), 3.84 (bs, 1H), 3.47 (d, 1H), 3.22 (d, 1H), 2.74-2.62 (m, 2H), 2.05-1.99 (m, 4H), 1.82 (bs, 1H), 1.69-1.65 (m, 1H), 1.60 (d, 3H), 1.50-1.41 (m, 1H), 0.80 (t, 3H) MS m / z= 483.2 (M+H)+

[0622] Example 85: (S)-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((1-(3-fluoropropyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)pyridin-4-yl)piperidin-3-ol

[0623] The title compound (3.9 mg) was prepared in the same manner as in step 1 of Example 1, using reference examples A-15 and D-10 instead of reference examples A-1 and D-1, respectively. (Yield: 27.6%) 1H NMR (CD3OD, 400MHz) δ 8.44 (s, 2H), 8.14 (d, 2H), 7.98 (d, 1H), 7.91 (s, 1H), 7.70-7.40 (m, 1H), 6.96 (d, 1H), 4.64 (t, 2H), 4.56 (t, 1H), 4.44 (t, 1H), 3.85-3.82 (m, 1H), 3.45 (d, 1H), 3.20 (d, 1H), 2.76 (t, 1H), 2.65 (t, 1H), 2.40 (t, 1H), 2.33 (t, 1H), 2.05-2.02 (m, 1H), 1.87-1.83 (m, 1H), 1.66-1.63 (m, 1H), 1.45-1.41 (m, 1H), 1.35-1.30 (m, 1H) MS m / z= 487.2 (M+H)+

[0624] Example 86: (S)-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)pyridin-4-yl)piperidin-3-ol

[0625] The title compound (2.1 mg) was prepared in the same manner as in step 1 of Example 1, using Reference Example A-15 instead of Reference Example A-1. (Yield: 15.4%) 1H NMR (CD3OD, 400MHz) δ 8.45 (d, 2H), 8.14 (d, 1H), 7.97 (d, 1H), 7.89 (d, 1H), 7.70-7.41 (m, 1H), 6.95 (d, 1H), 5.33-5.26 (m, 1H), 3.86-3.82 (m, 1H), 3.49 (d, 1H), 3.24 (d, 1H), 2.67 (q, 2H), 2.06 (bs, 2H), 1.85-1.80 (m, 1H), 1.63 (d, 6H), 1.52 (d, 3H), 1.48-1.41 (m, 1H) MS m / z= 469.2 (M+H)+

[0626] Example 87: (S)-1-(2-((1-ethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0627] The title compound (2.0 mg) was prepared in the same manner as in step 1 of Example 1, using reference examples A-16 and D-8 instead of reference examples A-1 and D-1, respectively. (Yield: 15.9%) 1H NMR (CD3OD, 400MHz) δ 8.44 (s, 1H), 8.08 (d, 2H), 7.97 (d, 1H), 4.63-4.57 (m, 1H), 4.57-4.52 (m, 2H), 3.87-3.82 (m, 1H), 3.52 (d, 1H), 3.27 (d, 1H), 3.31 (d, 1H), 2.71-2.06 (m, 2H), 2.22-2.19 (m, 2H), 2.06-2.04 (m, 2H), 1.85-1.81 (m, 1H), 1.68-1.62 (m, 1H), 1.58-1.52 (m, 9H) MS m / z= 447.2 (M+H)+

[0628] Example 88: (3S)-1-(2-((1-(sec-butyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0629] The title compound (3.3 mg) was prepared in the same manner as in step 1 of Example 1, using reference examples A-16 and D-9 instead of reference examples A-1 and D-1, respectively. (Yield: 24.7%) 1H NMR (CD3OD, 400MHz) δ 8.41 (d, 1H), 8.09 (d, 2H), 7.91 (s, 1H), 7.86 (s, 1H), 6.93 (d, 1H), 5.06-5.04 (m, 1H), 4.63-4.59 (m, 1H), 3.84 (bs, 1H), 3.50 (d, 1H), 3.25 (d, 1H), 2.70 (t, 1H), 2.63-1.97 (m, 4H), 1.86-1.82 (m, 1H), 1.69-1.61 (m, 1H), 1.58 (t, 3H), 1.45-1.41 (m, 1H), 0.81 (t, 3H) MS m / z= 475.3 (M+H)+

[0630] Example 89: (S)-1-(2-((1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0631] The title compound (2.3 mg) was prepared in the same manner as in step 1 of Example 1, using reference examples A-16 and D-24 instead of reference examples A-1 and D-1, respectively. (Yield: 17.3%) 1H NMR (CD3OD, 400MHz) δ 8.43 (s, 1H), 8.09 (d, 2H), 7.97 (d, 2H), 6.93 (d, 1H), 4.63-4.57 (m, 2H), 4.38 (d, 2H), 3.84-3.83 (m, 1H), 3.47 (d, 2H), 3.23 (d, 1H), 2.80-2.74 (m, 1H), 2.60 (t, 2H), 2.05 (bs, 2H), 1.57 (d, 6H), 1.46-1.44 (m, 1H), 1.58 (d, 2H), 1.52 (d, 2H) MS m / z= 473.2 (M+H)+

[0632] Example 90: (S)-1-(2-((1-(3-fluoropropyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0633] The title compound (2.6 mg) was prepared in the same manner as in step 1 of Example 1, using reference examples A-16 and D-10 instead of reference examples A-1 and D-1, respectively. (Yield: 19.3%) 1H NMR (CD3OD, 400MHz) δ 8.40 (s, 1H), 8.09 (d, 2H), 7.97 (d, 1H), 7.91 (s, 1H), 7.86 (s, 1H), 6.95 (d, 1H), 4.66-4.60 (m, 3H), 4.56 (t, 2H), 4.44 (t, 1H), 3.85-3.83 (m, 1H), 3.49 (d, 1H), 3.23 (d, 1H), 2.74 (t, 1H), 2.63 (t, 1H), 2.41 (t, 1H), 2.39 (t, 2H), 2.20 (t, 1H), 2.05 (d, 3H), 1.84 (bs, 1H), 1.61 (bs, 1H), 1.57 (d, 6H) MS m / z= 479.2 (M+H)+

[0634] Example 91: (S)-1-(5-(1-Isopropyl-1H-pyrazol-4-yl)-2-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)pyridin-4-yl)piperidin-3-ol

[0635] The title compound (1.4 mg) was prepared in the same manner as in step 1 of Example 1, using Reference Example A-16 instead of Reference Example A-1. (Yield: 10.8%) 1H NMR (CD3OD, 400MHz) δ 8.41 (s, 1H), 8.08 (s, 2H), 7.96 (d, 1H), 7.89 (s, 1H), 7.85 (s, 1H), 6.93 (d, 1H), 5.31-5.27 (m, 1H), 4.63-4.58 (m, 1H), 3.84-3.83 (m, 1H), 3.52 (d, 1H), 3.25 (d, 1H), 2.70-2.60 (m, 2H), 2.23-2.17 (m, 1H), 2.06-2.04 (m, 3H), 1.84-1.81 (m, 2H), 1.82 (d, 6H), 1.57 (d, 6H), 1.58-1.56 (m, 1H) MS m / z= 461.2 (M+H)+

[0636] Example 92: N4'-((1R,4R)-4-aminocyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-((1-methylpiperidin-4-yl)oxy)-[2,3'-bipyridine]-4',6'-diamine

[0637] The title compound (12.6 mg) was prepared in the same manner as in Example 6 using Reference Example B-27 instead of Reference Example B-1. (Yield: 82.6%) 1H NMR (CDCl3, 400MHz) δ 8.31-8.26 (m, 2H), 7.96 (d, 1H), 7.90 (s, 1H), 7.77-7.72 (m, 2H), 7.52 (dd, 1H), 6.94 (d, 1H), 5.30-5.21 (m, 1H), 4.56 (br, 1H), 3.58 (br, 1H), 2.84-2.77 (m, 3H), 2.46-2.40 (m, 2H), 2.35 (s, 3H), 2.31-2.28 (m, 2H), 2.07-2.04 (m, 2H), 1.89-1.87 (m, 4H), 1.65-1.63 (m, 2H), 1.57 (d, 6H), 1.48-1.37 (m, 4H) MS m / z= 556.3 (M+H)+

[0638] Example 93: N4'-((1S,4S)-4-(aminomethyl)cyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-((1-methylpiperidin-4-yl)oxy)-[2,3'-bipyridine]-4',6'-diamine

[0639] The title compound (9.6 mg) was prepared in the same manner as in Example 6 using Reference Example B-28 instead of Reference Example B-1. (Yield: 77.3%) 1H NMR (CD3OD, 400MHz) δ 8.33-8.31 (m, 2H), 8.11 (s, 1H), 7.96 (d, 1H), 7.89 (s, 1H), 7.82 (d, 1H), 7.53 (dd, 1H), 6.90 (d, 1H), 5.29-5.26 (m, 1H), 4.57 (br, 1H), 4.06 (s. 1H), 2.77 (br, 2H), 2.60 (d, 1H), 2.44 (br, 1H), 2.35 (s, 3H), 2.13-2.10 (m, 4H), 1.90-1.88 (m, 2H), 1.80-1.74 (m, 4H), 1.61 (d, 6H), 1.60 (br, 1H), 1.41-1.36 (m, 2H) MS m / z= 570.4 (M+H)+

[0640] Example 94: (S)-N-(4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-3-(3-(difluoromethyl)azetidin-1-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0641] The title compound (23 mg) was prepared in the same manner as in Example 1, using Reference Examples A-7 and D-12 instead of Reference Examples A-1 and D-1, respectively. (Yield: 68.7%) 1H NMR (CDCl3, 400MHz) δ 8.24 (s, 1H), 8.07 (s, 1H), 7.91-7.86 (m, 2H), 7.66 (d, 1H), 7.53 (s, 1H), 6.52 (d, 1H), 6.15 (td, 1H), 5.09-5.05 (m, 1H), 4.80-4.76 (m, 2H), 4.29-4.25 (m, 2H), 4.15-4.12 (m, 2H), 3.41-3.39 (m, 1H), 3.32-3.29 (m, 1H), 3.22-3.20 (m, 1H), 2.67 (t, 1H), 2.40 (t, 1H), 2.04-2.00 (m, 1H), 1.77 (br, 1H), 1.57 (d, 6H), 1.47-1.40 (m, 1H), 1.30-1.20 (m, 2H) MS m / z= 605.3 (M+H)+

[0642] Example 95: N4'-((1s,4s)-4-aminocyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(trifluoromethyl)-[2,3'-bipyridine]-4',6'-diamine

[0643] The title compound (9.6 mg, yield: 63.3%) was prepared in the same manner as in Example 6 using intermediate B-32 instead of intermediate B-1. 1H NMR (CDCl3, 400MHz) δ 9.78 (d, 1H), 8.86 (s, 1H), 8.53 (s, 1H), 8.02 (s, 1H), 7.95 (d, 1H), 7.92-7.84 (m, 3H), 7.58 (br, 1H), 6.70 (d, 1H), 5.28-5.21 (m, 1H), 3.98 (br, 1H), 2.94-2.90 (m, 1H), 2.15-2.12 (m, 2H), 1.87-1.74 (m, 4H), 1.64 (d, 6H), 1.53-1.48 (m, 2H), 0.91-0.83 (m, 2H) MS m / z = 511.2 (M+H)+

[0644] Example 96: N4'-((1s,4s)-4-aminocyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-N5,N5-dimethyl-[2,3'-bipyridine]-4',5,6'-triamine The title compound (11.9 mg, yield: 73.5%) was prepared in the same manner as in Example 6 using intermediate B-33 instead of intermediate B-1. 1H NMR (CDCl3, 400MHz) δ 9.63 (d, 1H), 8.32 (s, 1H), 8.11 (d, 1H), 7.91 (s, 1H), 7.86 (d, 1H), 7.83 (s, 1H), 7.63 (d, 1H), 7.52 (br, 1H), 7.16 (dd, 1H), 6.69 (d, 1H), 5.28-5.21 (m, 1H), 3.94 (br, 1H), 3.05 (s, 6H), 2.91-2.86 (m, 1H), 2.14-2.11 (m, 2H), 1.84-1.72 (m, 5H), 1.62 (d, 6H), 1.55-1.50 (m, 2H), 0.90-0.83 (m, 1H) MS m / z = 486.3 (M+H)+

[0645] Example 97: N4'-((1s,4s)-4-aminohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(tetrahydro-2H-pyran-4-yl)-[2,3'-bipyridin]-4',6'-diamine

[0646] The title compound (12.7 mg, yield: 77.4%) was prepared in the same manner as in Example 6 using intermediate B-34 instead of intermediate B-1. 1H NMR (CDCl3, 400MHz) δ 9.89 (d, 1H), 9.48 (s, 1H), 8.44 (s, 1H), 7.97 (s, 1H), 7.87-7.85 (m, 2H), 7.75 (d, 1H), 7.65 (d, 1H), 7.55 (br, 1H), 6.69 (d, 1H), 5.28-5.21 (m, 1H), 4.17-4.14 (m, 2H), 3.96 (br, 1H), 3.62-3.56 (m, 2H), 2.93-2.83 (m, 2H), 2.15-2.11 (m, 2H), 1.92-1.79 (m, 8H), 1.74 (d, 6H), 1.56-1.53 ​​(m, 3H), 0.91-0.83 (m, 1H) MS m / z = 527.3 (M+H)+

[0647] Example 98: N4'-((1s,4s)-4-aminocyclohexyl)-N6'-(1-isopropyl-3-methyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(morpholinomethyl)-[2,3'-bipyridine]-4',6'-diamine

[0648] The title compound (6.3 mg, yield: 61.1%) was prepared in the same manner as in the synthesis method of Example 6, using intermediate B-35 and intermediate E-5 instead of intermediate B-1 and intermediate E-1. 1H NMR (CDCl3, 400MHz) δ 9.96 (d, 1H), 8.52 (s, 1H), 8.45 (s, 1H), 7.99 (s, 1H), 7.79-7.74 (m, 4H), 6.64 (d, 1H), 5.19-5.14 (m, 1H), 3.96 (br, 1H), 3.76 (t, 4H), 3.55 (s, 2H), 2.92-2.87 (m, 1H), 2.53-2.51 (m, 7H), 2.13-2.11 (m, 2H), 1.83-1.71 (m, 6H), 1.60 (d, 6H), 1.55-1.49 (m, 2H) MS m / z = 556.4 (M+H)+

[0649] Example 99: (4'-(((1s,4s)-4-aminocyclohexyl)amino)-6'-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-[2,3'-bipyridin]-5-yl)(4-methylpiperazin-1-yl)methanone

[0650] The title compound (12.2 mg, yield: 87.5%) was prepared in the same manner as in Example 6 using intermediate B-36 instead of intermediate B-1. 1H NMR (CDCl3, 400MHz) δ 9.87 (d, 1H), 8.69 (s, 1H), 8.49 (s, 1H), 8.00 (s, 1H), 7.89-7.83 (m, 4H), 7.54 (br, 1H), 6.69 (d, 1H), 5.28-5.21 (m, 1H), 3.97 (br, 1H), 3.84 (br, 2H), 3.59 (br, 4H), 2.90 (br, 1H), 2.49 (br, 4H), 2.38 (s, 3H), 2.14-2.11 (m, 2H), 1.85-1.74 (m, 4H), 1.63 (d, 6H), 1.54-1.48 (m, 2H) MS m / z = 569.3 (M+H)+

[0651] Example 100: (4'-(((1s,4s)-4-aminocyclohexyl)amino)-6'-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-[2,3'-bipyridin]-5-yl)(morpholino)methanone

[0652] The title compound (18.0 mg, yield: 68.1%) was prepared in the same manner as in Example 6 using intermediate B-37 instead of intermediate B-1. 1H NMR (CDCl3, 400MHz) δ 9.85 (d, 1H), 8.70 (s, 1H), 8.50 (s, 1H), 8.00 (s, 1H), 7.89-7.84 (m, 4H), 7.48 (s, 1H), 6.69 (d, 1H), 5.28-5.21 (m, 1H), 3.97 (br, 1H), 3.78-3.63 (m, 8H), 2.93-2.88 (m, 1H), 2.12 (d, 2H), 1.85-1.74 (m, 4H), 1.64 (d, 6H), 1.56-1.50 (m, 4H) MS m / z = 556.3 (M+H)+

[0653] Example 101: N4'-((1s,4s)-4-aminocyclohexyl)-5-((4,4-difluoropiperidin-1-yl)methyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-[2,3'-bipyridine]-4',6'-diamine

[0654] The title compound (21.5 mg, yield: 78.7%) was prepared in the same manner as in Example 6 using intermediate B-38 instead of intermediate B-1. 1H NMR (CDCl3, 400MHz) δ 9.94 (d, 1H), 8.52 (s, 1H), 8.47 (s, 1H), 7.98 (s, 1H), 7.88-7.85 (m, 2H), 7.77 (s, 2H), 7.53 (br, 1H), 6.69 (d, 1H), 5.28-5.21 (m, 1H), 3.97 (br, 1H), 3.61 (s, 2H), 2.93-2.89 (m, 1H), 2.62-2.61 (m, 4H), 2.15-2.00 (m, 6H), 1.85-1.76 (m, 4H), 1.63 (d, 6H), 1.55-1.50 (m, 4H) MS m / z = 576.3 (M+H)+

[0655] Example 102: N4-((1s,4s)-4-aminocyclohexyl)-5-(1-isopropyl-1H-pyrazol-3-yl)-N2-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)pyridine-2,4-diamine

[0656] The title compound (13.0 mg, yield: 71.1%) was prepared in the same manner as in Example 6 using intermediate B-39 instead of intermediate B-1. 1H NMR (CDCl3, 400MHz) δ 8.57 (d, 1H), 8.32 (s, 1H), 7.96 (s, 1H), 7.86-7.83 (m, 2H), 7.70 (s, 1H), 7.48 (s, 1H), 6.70 (d, 1H), 6.61 (s, 1H), 5.57-5.21 (m, 1H), 4.59-4.52 (m, 1H), 3.98 (br, 1H), 2.90-2.86 (m, 1H), 2.16-2.12 (m, 2H), 1.86-1.75 (m, 4H), 1.63 (d, 6H), 1.60 (d, 6H), 1.57-1.55 (m, 2H) MS m / z = 474.3 (M+H)+

[0657] Example 103: N4-((1s,4s)-4-aminocyclohexyl)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-3-yl)-N2-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)pyridine-2,4-diamine

[0658] The title compound (10.0 mg, yield: 80.0%) was prepared in the same manner as in Example 6 using intermediate B-40 instead of intermediate B-1. 1H NMR (CDCl3, 400MHz) δ 8.35-8.34 (m, 2H), 7.98 (s, 1H), 7.87-7.84 (m, 2H), 7.54 (s, 1H), 6.70-6.67 (m, 2H), 6.20 (tt, 1H), 5.27-5.22 (m, 1H), 4.55 (td, 2H), 3.99 (br, 1H), 2.93-2.90 (m, 1H), 2.13-2.05 (m, 2H), 1.83-1.73 (m, 4H), 1.63 (d, 6H), 1.55-1.50 (m, 4H) MS m / z = 496.3 (M+H)+

[0659] Example 104: N-[4-[(3R,4R)-3-amino-4-fluoro-1-piperidyl]-5-(1-isopropylpyrazol-4-yl)-2-pyridyl]-1-isopropyl-pyrazolo[5,4-b]pyridin-6-amine

[0660] The title compound (7.2 mg, yield: 100%) was prepared in the same manner as in Example 6 using intermediate B-41 instead of intermediate B-1. 1H NMR (CD3OD, 400MHz) δ 8.32 (s, 1H), 8.28 (d, 1H), 8.21 (s, 1H), 8.09 (s, 1H), 7.05 (d. 2H), 5.45-5.41 (m, 1H), 4.76-4.66 (m, 2H), 4.01-3.97 (m, 1H), 3.73 (d, 1H), 3.65-3.61 (m, 1H), 3.14 (t, 1H), 3.03 (t, 1H), 2.32-2.25 (m, 1H), 1.94 (t, 1H), 1.77-1.64(m, 1H), 1.67-1.64 (m, 1H), 1.60 (s, 12H) MS m / z= 478.2 (M+H)+

[0661] Example 105: N6-[4-[(3S)-3-amino-1-piperidyl]-5-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-2-pyridyl]-1-isopropyl-pyrazolo[3,4-b]pyridine-3,6-diamine

[0662] Step 1: tert-Butyl (S)-(1-(2-((1-isopropyl-3-nitro-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0663] tert-Butyl N-[(3S)-1-[2-amino-5-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-4-pyridyl]-3-piperidyl]carbamate (Reference Example A-7, 208.7 mg, 0.47 mmol) was dissolved in anhydrous 1,4-dioxane (4.0 mL), and then 6-chloro-1-isopropyl-3-nitro-pyrazolo[5,4-b]pyridine (Reference Example D-26, 114.0 mg, 0.47 mmol) and tris(dibenzylideneacetone)dipalladium(0) (43.4 mg, 0.047 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (45.2 mg, 0.095 mol), cesium carbonate (231.6 mg, 0.71 mmol) was added dropwise. The mixed solution was then stirred in a microwave reactor at 600 W for 2 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, water was added, and the aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography to produce the title compound (193.3 mg, yield: 63.3%). 1H NMR (CD3OD, 400MHz) δ 8.32 (d, 2H), 8.18 (s, 1H), 8.14 (s, 1H), 7.96 (s, 1H), 7.25 (d, 1H), 5.40-5.33 (m, 1H), 5.09-4.99 (m ,2H), 3.75 (brs, 1H), 3.56-3.50 (m, 1H), 2.62 (t, 1H), 2.53 (brs, 1H), 1.99 (m, 1H), 1.72-1.66 (m, 7H), 1.47 (s, 9H)

[0664] Step 2: tert-Butyl N-[(3S)-1-[2-[(3-amino-1-isopropyl-pyrazolo[3,4-b]pyridin-6-yl)amino]-5-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-4-pyridyl]-3-piperidyl]carbamate

[0665] tert-Butyl N-[(3S)-1-[2-[(1-isopropyl-3-nitro-pyrazolo[5,4-b]pyridin-6-yl)amino]-5-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-4-pyridyl]-3-piperidyl]carbamate (243.0 mg, 0.38 mmol) was dissolved in methanol (9.0 ml), and palladium on carbon (200.5 mg, 1.89 mmol) was added dropwise. The mixture was stirred at room temperature for 3 hours under a hydrogen balloon. After the reaction was completed, the reaction mixture was filtered through celite, and the filtrate was concentrated. The filtrate was concentrated and purified by silica gel column chromatography to prepare the title compound (177.4 mg, yield: 75.6%). 1H NMR (CD3OD, 400MHz) δ 8.29 (brs, 1H), 8.16 (s, 1H), 8.08 (s, 1H), 7.94 (s. 1H), 7.90 (d, 1H), 6.78-6.71 (m, 2H), 5.11-5.01 (m, 3H), 3.72 (brs, 1H), 3.55-3.52 (m, 1H), 2.61-2.55 (m, 2H), 2.20 (s, 2H), 1.71 (s, 2H), 1.55-1.50 (m, 6H), 1.31 (s, 9H)

[0666] Step 3: N6-[4-[(3S)-3-amino-1-piperidyl]-5-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-2-pyridyl]-1-isopropyl-pyrazolo[3,4-b]pyridine-3,6-diamine hydrochloride

[0667] tert-Butyl N-[(3S)-1-[2-[(3-amino-1-isopropyl-pyrazolo[3,4-b]pyridin-6-yl)amino]-5-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-4-pyridyl]-3-piperidyl]carbamate (177.4 mg, 0.29 mmol) was dissolved in dichloromethane (5.0 ml), and 4.0 M 1,4-dioxane hydrochloric acid solution was added dropwise. The reaction mixture was stirred at room temperature for 3 hours. After completion of the reaction, the reaction mixture was washed with dichloromethane and filtered. The filtered solid was dried to prepare the title compound (159.1 mg, yield: 88.4%). 1H NMR (CD3OD, 400MHz) δ 8.29 (t, 2H), 8.25 (s, 1H), 7.97 (s, 1H), 7.03 (d. 2H), 5.38-5.32 (m, 1H), 5.14-4.89 (m, 2H), 3.59 (d, 1H), 3.49 (d, 1H), 3.43-3.33 (m, 1H), 2.99 (t, 1H), 2.92 (t, 1H), 2.22 (d, 1H), 1.84 (brs, 1H), 1.77-1.64(m, 1H), 1.55-1.46 (m, 1H), 1.27 (d, 6H) MS m / z= 515.2 (M+H)+

[0668] Example 106: N-(4-((3S,5R)-3-amino-5-fluoropiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0669] The title compound (8.2 mg) was prepared in the same manner as in Example 6 using Reference Example B-42 instead of Reference Example B-1. (Yield: 20.4%) 1H NMR (CDCl3, 400MHz) δ 8.47 (s, 1H), 8.17 (s, 1H), 7.91-7.87 (m, 1H), 7.87 (s, 1H), 7.85 (s, 1H), 7.78 (s, 1H), 7.74 (s, 1H), 6.71 (d, 1H), 5.29-5.19 (m, 1H), 4.88-4.77 (m, 0.5H), 4.75-4.66 (m, 0.5H), 4.64-4.52 (m, 1H), 3.70-3.58 (m, 1H), 3.44-3.34 (m, 1H), 3.09-2.97 (m, 1H), 2.95-2.84 (m, 1H), 2.49-2.36 (m, 2H), 1.69 (d, 6H), 1.62 (d, 6H) MS m / z= 478.2 (M+H)+

[0670] Example 107: N-(4-((3S,5S)-3-amino-5-fluoropiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine

[0671] The title compound (9.8 mg) was prepared in the same manner as in Example 6 using Reference Example B-43 instead of Reference Example B-1. (Yield: 35.1%) 1H NMR (CDCl3, 400MHz) δ 8.33 (s, 1H), 8.22 (s, 1H), 7.96 (s, 1H), 7.90-7.83 (m, 2H), 7.83 (s, 1H), 6.81-6.70 (m, 1H), 5.29-5.16 (m, 1H), 5.01-4.94 (m, 0.5H), 4.91-4.83 (m, 0.5H), 4.64-4.51 (m, 1H), 3.53-3.49 (m, 1H), 3.49-3.44 (m, 1H), 3.42-3.30 (m, 1H), 2.94-2.84 (m, 0.5H), 2.84-2.77 (m, 0.5H), 2.54-2.42 (m, 1H), 2.41-2.29 (m, 1H), 1.69 (d, 6H), 1.60 (d, 6H) MS m / z= 478.3 (M+H)+

[0672] Test example: Evaluation of human recombinant HPK1 inhibitory activity

[0673] The HPK1 inhibitory activity was evaluated using the fluorescence resonance energy spectrometry (TR-FRET) technology of Perkin-Elmer. The test compounds were prepared as 20 mM stock solutions in dimethyl sulfoxide (DMSO) and serially diluted in buffer to obtain a final compound concentration of 0.32–1000 nM. The inhibitory activity was evaluated at room temperature using recombinant human HPK1 (BPS Bioscience). Specifically, recombinant human HPK1, serially diluted test compounds, ULight-p70S6K peptide substrate (PerkinElmer), and various concentrations of ATP (Km and final concentration) were added to kinase buffer (50 mM HEPES pH 7.4, 10 mM MgCl2, 1 mM EGTA, 3 mM MnCl2, 2 mM DTT, and 0.01% Tween-20), and the resulting mixture was incubated in a 384-well plate (Optiplate).TM 384, white, PerkinElmer) was added to each well. The enzyme reaction was performed at room temperature for 1 hour, and the reaction was stopped by adding 4 μL of stop solution (10 mM EDTA). After stirring for 1 minute, the detection solution containing europium-labeled-anti-phosphopeptide antibody (final concentration 2 nM, PerkinElmer) was added. The time-dependent fluorescence resonance energy shift (TR-FRET) detection at the excitation wavelength (320 nm) and emission wavelength (665 nm) was measured using a microplate reader (Envision Multilabel Reader, PerkinElmer). Inhibition by the test compound was measured as the % decrease in signal compared to the control treated with DMSO only, and the IC of the compound was calculated. 50 The values ​​were calculated using the GraphPad Prism program (GraphPad Software, Inc., San Diego, CA, USA). IC for HPK1 inhibitory activity of test compounds 50 The values ​​were classified as follows:

[0674] A: IC 50 ≤ 100 nM

[0675] B: 100 nM < IC 50 ≤ 250 nM

[0676] The results are shown in Tables 1 and 2 below.

[0677] Example IC 50 Example IC 50 Example IC 50Example 1A Example 21A Example 41A Example 2A Example 22A Example 42A Example 3A Example 23A Example 43A Example 4A Example 24A Example 44A Example 5A Example 25A Example 45A Example 6A Example 26A Example 46A Example 7A Example 27A Example 47A Example 8A Example 28A Example 48A Example 9A Example 29A Example 49A Example 10A Example 30A Example 50A Example 11A Example 31A Example 51A Example 12A Example 32A Example 52B Embodiment 13A Embodiment 33A Embodiment 53A Embodiment 14A Embodiment 34A Embodiment 54A Embodiment 15A Embodiment 35A Embodiment 55A Embodiment 16A Embodiment 36A Embodiment 56B Embodiment 17A Embodiment 37A Embodiment 57B Embodiment 18A Embodiment 38A Embodiment 58A Embodiment 19A Embodiment 39A Embodiment 59A Embodiment 20A Embodiment 40A Embodiment 60A

[0678] Example IC 50 Example IC 50 Example IC 50 Example 61B Example 81A Example 101A Example 62B Example 82A Example 102A Example 63A Example 83B Example 103A Example 64B Example 84A Example 104A Example 65A Example 85A Example 105A Example 66A Example 86B Example 106A Example 67A Example 87A Example 107A Example 68B Example 88A Example 69A Example 89A Example 70A Example 90A Example 71A Example 91A Example 72A Example 92A Example 73A Example 93A Example 74A Example 94B Example 75A Example 95A Example 76A Example 96A Example 77A Example 97A Example 78A Example 98A Example 79A Example 99A Example 80A Example 100A

[0679] From the results in Tables 1 and 2 above, it can be seen that the compound according to the present invention exhibits excellent inhibitory activity against HPK1.

Claims

1. A compound of the following chemical formula 1 or a pharmaceutically acceptable salt thereof: <Chemical Formula 1> During the meal, A is (1) a 6 to 12 membered aryl group optionally substituted with 1 to 3 groups selected from the group consisting of hydroxy; halogen; amino; C1 to C6 alkyl; C1 to C6 alkyl substituted with 1 to 3 groups selected from the group consisting of hydroxy, halogen, C1 to C3 alkoxy, C3 to C6 cycloalkyl, and 4 to 7 membered heterocycloalkyl; mono- or di-C1 to C6 alkylamino; C1 to C6 alkoxy; C3 to C6 cycloalkyl; 4 to 7 membered heterocycloalkyl; and 4 to 7 membered heterocycloalkyloxy, wherein the cycloalkyl, heterocycloalkyl, or heterocycloalkyloxy is optionally substituted with halogen, C1 to C6 alkyl, or C1 to C6 alkyl substituted with halogen; (2) C1∼C6 alkyl substituted with 1 to 3 groups selected from the group consisting of hydroxy; halogen; amino; C1∼C6 alkyl; hydroxy, halogen, C1∼C3 alkoxy, C3∼C6 cycloalkyl, and 4 to 7 membered heterocycloalkyl; mono- or di-C1∼C6 alkylamino; C1∼C6 alkoxy; C3∼C6 cycloalkyl; 4 to 7 membered heterocycloalkyl; 4 to 7 membered heterocycloalkyloxy; and a 5 to 12 membered heteroaryl group optionally substituted with 1 to 3 groups selected from the group consisting of 4 to 7 membered heterocycloalkylcarbonyl (wherein the cycloalkyl, heterocycloalkyl, heterocycloalkyloxy, or heterocycloalkylcarbonyl is optionally substituted with halogen, C1 to C6 alkyl, or C1 to C6 alkyl substituted with halogen). (3) -C≡C-R1 group, wherein R1 is C1∼C6 alkyl optionally substituted with hydroxy; 4 to 7 membered heterocycloalkyl optionally substituted with halogen, C1∼C6 alkyl, or C1∼C6 alkyl substituted with 1 to 3 halogens; or 5 or 6 membered heteroaryl optionally substituted with halogen, C1∼C6 alkyl, or C1∼C6 alkyl substituted with 1 to 3 halogens, (4) -C(O)-R2 group, wherein R2 is 4 to 7 membered heterocycloalkyl optionally substituted with 1 to 2 groups selected from the group consisting of hydroxy; halogen; C1 to C6 alkyl; and C1 to C6 alkyl substituted with 1 to 3 groups selected from the group consisting of hydroxy and halogen, or (5) -C(O)NH-R3 group, wherein R3 is a 4 to 7 membered heterocycloalkyl group or C3 to C6 cycloalkyl group optionally substituted with 1 to 2 groups selected from the group consisting of hydroxy; halogen; C1 to C6 alkyl; and C1 to C6 alkyl substituted with 1 to 3 groups selected from the group consisting of hydroxy and halogen, B is (1) a 3 to 12 membered heterocycloalkyl group optionally substituted with 1 or 2 groups selected from the group consisting of halogen; C1∼C6 alkyl; C1∼C6 alkyl substituted with halogen, amino or hydroxy; hydroxy; amino; mono or di-C1∼C3 alkylamino; and C1∼C6 alkoxy; (2) a C3∼C6 cycloalkylamino group optionally substituted with one or two groups selected from the group consisting of halogen; C1∼C6 alkyl; C1∼C6 alkyl substituted with halogen, amino or hydroxy; hydroxy; amino; mono or di-C1∼C3 alkylamino; and C1∼C6 alkoxy; (3) a 3 to 12 membered heterocycloalkylamino group optionally substituted with 1 or 2 groups selected from the group consisting of halogen; C1∼C6 alkyl; C1∼C6 alkyl substituted with halogen, amino or hydroxy; hydroxy; amino; mono or di-C1∼C3 alkylamino; and C1∼C6 alkoxy, or (4) -O-(CH2)n-R4 group, wherein R4 is a 3 to 12-membered heterocycloalkyl or C3∼C6 cycloalkyl, wherein the heterocycloalkyl or cycloalkyl is optionally substituted with 1 or 2 groups selected from the group consisting of hydroxy; amino; mono or di-C1∼C3 alkylamino; and C1∼C3 alkyl optionally substituted with hydroxy or amino, and n is 0, 1, or 2, C is hydrogen; a C1∼C6 alkyl group; a C1∼C6 alkyl group substituted with 1 to 3 groups selected from the group consisting of halogen, hydroxy, C3∼C6 cycloalkyl, and hydroxycarbonyl; a C3∼C6 cycloalkyl group; a 6 to 12 membered aryl group; or a 4 to 7 membered heterocycloalkyl group, D is hydrogen; a cyano group; an amino group; a C1∼C6 alkyl group; a C1∼C6 alkyl group substituted with halogen or hydroxy; a hydroxycarbonyl group; or a 4 to 7 membered heterocycloalkyl group optionally substituted with halogen, C1∼C6 alkyl, or C1∼C6 alkyl substituted with halogen or hydroxy.

2. A compound or a pharmaceutically acceptable salt thereof, characterized in that A is a 6 to 12-membered aryl group substituted with a 4 to 7-membered heterocycloalkyl group in the first paragraph.

3. A compound or a pharmaceutically acceptable salt thereof, characterized in that A is a phenyl group substituted with morpholinyl in the second paragraph.

4. A compound or a pharmaceutically acceptable salt thereof, characterized in that in claim 1, A is a 5- or 6-membered heteroaryl group optionally substituted with 1 to 3 groups selected from the group consisting of C1-C6 alkyl; halogen, C1-C3 alkoxy, C3-C6 cycloalkyl, and 4- to 7-membered heterocycloalkyl; mono- or di-C1-C6 alkylamino; C3-C6 cycloalkyl; 4- to 7-membered heterocycloalkyl; 4- to 7-membered heterocycloalkyloxy; and 4- to 7-membered heterocycloalkylcarbonyl.

5. A compound or a pharmaceutically acceptable salt thereof, characterized in that the cycloalkyl, heterocycloalkyl, heterocycloalkyloxy or heterocycloalkylcarbonyl in the fourth paragraph is optionally substituted with halogen or C1∼C6 alkyl.

6. A compound or a pharmaceutically acceptable salt thereof, characterized in that the heterocycloalkyl in paragraph 4 is tetrahydropyranyl, piperazinyl, piperidinyl, or morpholinyl.

7. A compound or a pharmaceutically acceptable salt thereof, characterized in that the heterocycloalkyloxy in the fourth paragraph is piperidinyloxy.

8. A compound or a pharmaceutically acceptable salt thereof, characterized in that the heterocycloalkylcarbonyl in paragraph 4 is piperazinylcarbonyl or morpholinylcarbonyl.

9. A compound or a pharmaceutically acceptable salt thereof, characterized in that the heteroaryl group in paragraph 4 is a pyrazolyl group or a pyridinyl group.

10. A compound or a pharmaceutically acceptable salt thereof, characterized in that in the first paragraph, R1 is tetrahydropyranyl; or pyrazolyl substituted with C1∼C6 alkyl substituted with 1 to 3 halogens.

11. A compound or a pharmaceutically acceptable salt thereof, characterized in that in paragraph 1, B is a 3 to 12-membered heterocycloalkyl group substituted with 1 or 2 groups selected from the group consisting of halogen; C1 to C6 alkyl; hydroxy; and amino.

12. A compound or a pharmaceutically acceptable salt thereof, characterized in that the heterocycloalkyl group in claim 11 is piperidinyl, pyrrolidinyl, or 2,8-diazaspiro[4.5]decanyl.

13. A compound or a pharmaceutically acceptable salt thereof, characterized in that in paragraph 1, B is amino; or a C3-C6 cycloalkylamino group substituted with C1-C6 alkyl substituted with amino.

14. A compound or a pharmaceutically acceptable salt thereof, characterized in that B is an azetidinylamino group or a pyrrolidinylamino group in the first paragraph.

15. A compound or a pharmaceutically acceptable salt thereof, characterized in that in paragraph 1, C is a C1∼C6 alkyl group; a C1∼C6 alkyl group substituted with 1 to 3 groups selected from the group consisting of halogen, hydroxy, C3∼C6 cycloalkyl, and hydroxycarbonyl; a phenyl group; or a tetrahydrofuranyl group.

16. A compound or a pharmaceutically acceptable salt thereof, characterized in that in paragraph 1, D is hydrogen; a cyano group; an amino group; a C1∼C6 alkyl group; a hydroxycarbonyl group; or an azetidinyl group substituted with a C1∼C6 alkyl substituted with a halogen or hydroxy.

17. A compound selected from the group consisting of the following compounds or a pharmaceutically acceptable salt thereof: (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-1-(2-((1-Isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(4-morpholinophenyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; N-(4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; N-(4-((3S,5S)-3-amino-5-methylpiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-amino-3-methylpiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (3R,4R)-3-amino-1-(2-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-ol; (S)-N-(4-(3-aminopiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(2-fluoroethyl)-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(2-fluoroethyl)-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(2,2-difluoroethyl)-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(2,2-difluoroethyl)-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isobutyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopentyl-1H-pyrazolo[3,4-b]pyridin-6-amine; N4'-((1S,4S)-4-aminocyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(morpholinomethyl)-[2,3'-bipyridine]-4',6'-diamine; N-(4-((3S,5S)-3-amino-5-methylpiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-amino-3-methylpiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (3R,4R)-3-amino-1-(2-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-ol; N-(4-((S)-3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-6-((4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile; N4-((1S,3R)-3-aminocyclopentyl)-N2-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridine-2,4-diamine; N4-((1R,3R)-3-aminocyclopentyl)-N2-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridine-2,4-diamine; N-(4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; N-(4-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; N4-(azetidin-3-yl)-N2-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridine-2,4-diamine; (R)-N-(4-(3-aminopyrrolidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopyrrolidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-phenyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-neopentyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-ethyl-1H-pyrazolo[3,4-b]pyridin-6-amine; N-(4-((S)-3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(sec-butyl)-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(3-fluoropropyl)-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-2-(1-(6-((4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-3-yl)azetidin-3-yl)propan-2-ol; N4'-((1R,4R)-4-aminocyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(morpholinomethyl)-[2,3'-bipyridine]-4',6'-diamine; N4'-((1S,4S)-4-(aminomethyl)cyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(morpholinomethyl)-[2,3'-bipyridine]-4',6'-diamine; 1-Isopropyl-N-(4-(2-methyl-2,8-diazaspiro[4.5]decan-8-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-6-amine; N-(4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-amino-3-methylpiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; N-(4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; N-(4-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (3R,4R)-3-amino-1-(2-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethanyl)pyridin-4-yl)piperidin-4-ol; (S)-3-(6-((4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1H-pyrazolo[3,4-b]pyridin-1-yl)propan-1-ol; (S)-2-(6-((4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetic acid; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-ethyl-3-methyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-3-methyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(cyclopropylmethyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N2-(1-Isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-N4-(pyrrolidin-3-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridine-2,4-diamine; (S)-6-((4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-ethyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile; (R)-N2-(1-Isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-N4-(pyrrolidin-3-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridine-2,4-diamine; (S)-6-((4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile; (S)-6-((4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxylic acid; (S)-6-((4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-(2,2-difluoroethyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile; (S)-6-((4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-(2-fluoroethyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile; (S)-6-((4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-(3-fluoropropyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile; (S)-6-((4-(3-Aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-(3,3,3-trifluoropropyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-ethyl-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-6-((4-(3-aminopiperidin-1-yl)-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile; (S)-6-((4-(3-aminopiperidin-1-yl)-5-(1-ethyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile; (S)-6-((4-(3-aminopiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile; (S)-6-((4-(3-aminopiperidin-1-yl)-5-(1-cyclopropyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile; N-(4-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-4-(3-Aminopiperidin-1-yl)-N6-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-N6',N6'-dimethyl-[3,3'-bipyridine]-6,6'-diamine; (S)-N-(4-(3-aminopiperidin-1-yl)-6'-morpholino-[3,3'-bipyridin]-6-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-6'-((4-methylpiperazin-1-yl)methyl)-[3,3'-bipyridin]-6-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-6'-((4-fluoropiperidin-1-yl)methyl)-[3,3'-bipyridin]-6-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (S)-N-(4-(3-aminopiperidin-1-yl)-6'-(piperazin-1-yl)-[3,3'-bipyridin]-6-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; N-(4-((3S,5S)-3-amino-5-fluoropiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; (3S)-1-(2-((1-(sec-butyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol; (S)-1-(2-((1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol; (S)-1-(2-((1-Isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol; (S)-1-(2-((1-(3-fluoropropyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol; (S)-1-(5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-2-((1-(3,3,3-trifluoropropyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)pyridin-4-yl)piperidin-3-ol; (3S)-1-(2-((1-(sec-butyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol; (S)-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((1-(3-fluoropropyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)pyridin-4-yl)piperidin-3-ol; (S)-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)pyridin-4-yl)piperidin-3-ol; (S)-1-(2-((1-ethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol; (3S)-1-(2-((1-(sec-butyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol; (S)-1-(2-((1-(cyclopropylmethyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol; (S)-1-(2-((1-(3-fluoropropyl)-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol; (S)-1-(5-(1-Isopropyl-1H-pyrazol-4-yl)-2-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)pyridin-4-yl)piperidin-3-ol; N4'-((1R,4R)-4-aminocyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-((1-methylpiperidin-4-yl)oxy)-[2,3'-bipyridine]-4',6'-diamine; N4'-((1S,4S)-4-(aminomethyl)cyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-((1-methylpiperidin-4-yl)oxy)-[2,3'-bipyridine]-4',6'-diamine; (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-3-(3-(difluoromethyl)azetidin-1-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; N4'-((1s,4s)-4-aminocyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(trifluoromethyl)-[2,3'-bipyridine]-4',6'-diamine; N4'-((1s,4s)-4-aminocyclohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-N5,N5-dimethyl-[2,3'-bipyridine]-4',5,6'-triamine; N4'-((1s,4s)-4-aminohexyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(tetrahydro-2H-pyran-4-yl)-[2,3'-bipyridine]-4',6'-diamine; N4'-((1s,4s)-4-aminocyclohexyl)-N6'-(1-isopropyl-3-methyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-5-(morpholinomethyl)-[2,3'-bipyridine]-4',6'-diamine; (4'-(((1s,4s)-4-aminocyclohexyl)amino)-6'-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-[2,3'-bipyridin]-5-yl)(4-methylpiperazin-1-yl)methanone; (4'-(((1s,4s)-4-aminocyclohexyl)amino)-6'-((1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)amino)-[2,3'-bipyridin]-5-yl)(morpholino)methanone; N4'-((1s,4s)-4-aminocyclohexyl)-5-((4,4-difluoropiperidin-1-yl)methyl)-N6'-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-[2,3'-bipyridine]-4',6'-diamine; N4-((1s,4s)-4-aminocyclohexyl)-5-(1-isopropyl-1H-pyrazol-3-yl)-N2-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)pyridine-2,4-diamine; N4-((1s,4s)-4-aminocyclohexyl)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-3-yl)-N2-(1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-yl)pyridine-2,4-diamine; N-[4-[(3R,4R)-3-amino-4-fluoro-1-piperidyl]-5-(1-isopropylpyrazol-4-yl)-2-pyridyl]-1-isopropyl-pyrazolo[5,4-b]pyridin-6-amine; N6-[4-[(3S)-3-amino-1-piperidyl]-5-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-2-pyridyl]-1-isopropyl-pyrazolo[3,4-b]pyridine-3,6-diamine; N-(4-((3S,5R)-3-amino-5-fluoropiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine; and N-(4-((3S,5S)-3-amino-5-fluoropiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridin-6-amine.

18. A pharmaceutical composition for inhibiting hematopoietic precursor kinase 1, comprising a compound according to any one of claims 1 to 17 or a pharmaceutically acceptable salt thereof as an active ingredient.

19. A pharmaceutical composition for the prevention or treatment of blood cancer or solid cancer according to claim 18.

20. A pharmaceutical composition for the prevention or treatment of melanoma, blastoma, sarcoma, lymphoma, leukemia, bladder cancer, brain tumor, breast cancer, cervical cancer, colorectal cancer, esophageal cancer, endometrioma, liver cancer, laryngeal cancer, lung cancer, osteosarcoma, ovarian cancer, pancreatic cancer, prostate cancer, kidney cancer, thyroid cancer, ependymoma, glioblastoma, medulloblastoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma, and renal blastoma, according to claim 18.

21. A method for inhibiting hematopoietic precursor kinase 1, comprising administering to a mammal a therapeutically effective amount of a compound according to any one of claims 1 to 17 or a pharmaceutically acceptable salt thereof.

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