Compound having aurkb kinase inhibitory action or salt thereof, and pharmaceutical composition containing same

Abstract

The present disclosure provides a novel compound having AURKB kinase inhibitory action. AURKB kinase can be inhibited by a compound represented by general formula (I) below or a salt thereof.

Description

Compound having AURKB kinase inhibitory activity or its salt and pharmaceutical composition containing the same

[0001] The present disclosure relates to a compound or a salt thereof having an AURKB kinase inhibitory activity, and a pharmaceutical composition containing the same.

[0002] Mammalian cells have three homologs of Aurora kinase (sometimes referred to as AURK): AURKA, AURKB, and AURKC. AURKA and AURKB are expressed in all proliferating cells, whereas AURKC is specifically expressed in the testis.

[0003] It has been reported that AURKA kinase inhibitors can resolve megakaryocytic differentiation abnormalities in myelofibrosis (MF) and serve as therapeutic targets for myelofibrosis (Non-Patent Document 1). Furthermore, aliselitib, known as a selective AURKA kinase inhibitor, improved splenomegaly, systemic symptom scores, and bone marrow fibrosis in a Phase 1 study of myelofibrosis (Non-Patent Document 2).

[0004] Myelofibrosis is an intractable disease in which megakaryocytes and granulocyte cells proliferate in the bone marrow due to genetic abnormalities at the hematopoietic stem cell level. Various cytokines produced by the proliferated megakaryocytes and monocytes act on bone marrow stromal cells, causing bone marrow fibrosis, splenomegaly due to extramedullary hematopoiesis, and ineffective hematopoiesis.

[0005] Aurora kinase B (also known as AURKB) is a serine / threonine kinase and a component of the chromosomal passenger complex, a regulator of mitosis. The chromosomal passenger complex localizes to chromosomes during mitosis and plays an important role in regulating mitotic processes such as chromosome assembly, chromosome segregation, and cytokinesis.

[0006] AURKB has been reported to be important for cancer survival in many cases. Reports of its importance in blood cancers include acute myeloid leukemia (Non-Patent Document 3), B-cell acute lymphoblastic leukemia (Non-Patent Document 4), T-cell acute lymphoblastic leukemia (Non-Patent Document 5), diffuse large B-cell lymphoma (Non-Patent Document 6), chronic myeloid leukemia (Non-Patent Document 7), Hodgkin's lymphoma (Non-Patent Document 8), Burkitt's lymphoma (Non-Patent Document 8), and multiple myeloma (Non-Patent Document 9).

[0007] Furthermore, the importance of AURKB has also been reported in solid cancers, including thyroid cancer (Non-Patent Document 10), non-small cell lung cancer (Non-Patent Document 11), squamous cell carcinoma (Non-Patent Document 12), colorectal cancer (Non-Patent Document 13), breast cancer (Non-Patent Document 14), gastric cancer (Non-Patent Document 15), prostate cancer (Non-Patent Document 16), cutaneous melanoma (Non-Patent Document 17), neuroblastoma (Non-Patent Document 18), bladder cancer (Non-Patent Document 19), intrahepatic bile duct cancer (Non-Patent Document 20), pancreatic ductal adenocarcinoma (Non-Patent Document 21), hepatocellular carcinoma (Non-Patent Document 22), uveal melanoma (Non-Patent Document 23), and retinoblastoma (Non-Patent Document 24).

[0008] AURKB has also been reported to be involved in pathological conditions such as osteoarthritis (Non-Patent Document 25), diabetic nephropathy (Non-Patent Document 26), neuropathic pain (Non-Patent Document 27), and ocular neovascular disease (Non-Patent Document 28).

[0009] Wen et al., Nat Med. 2015;21(12):1473-1480.Gangat et al., Clin Cancer Res. 2019;25(16):4898-4906.Joshi et al., Cancer Cell. 2021; 39(7)):999-1014.Poulard et al., Proc Natl Acad Sci U S A. 2019;116(8):3052-3061.Zhang et al., Blood Sci. 2020 May 19;2(2):68-69.Collins et al., Br J Haematol. 2015;170(6):886-890.Zhou et al., Leuk Lymphoma. 2020;61(14):3451-3459.Mori al.,Biochem Pharmacol. 2011;81(9):1106-1115.Evans et al., Br J Haematol. 2008;140(3):295-302.Hicks et al., Cancer Biol Ther. 2024 Dec 31;25(1):2332000.Vischioni et al., Mol Cancer Ther. 2006 Nov;5(11):2905-13.Al-Khafaji et al., Br J Cancer. 2017 Feb 28;116(5):592-599.Pohl et al., Pharmacogenomics J. 2011 Apr;11(2):93-9.Huang et al., Cancer Cell Int. 2019 Jun 18;19:166.Wang et al., Cancer Manag Res. 2020 Aug 5;12:6947-6958.Hongo et al., Prostate Cancer Prostatic Dis. 2023 Mar;26(1):59-66.Guo et al., Am J Cancer Res. 2020 Oct 1;10(10):3458-3474.Bogen et al., Oncotarget. 2015 Nov 3;6(34):35247-62.Li et al., J Transl Med. 2024 Mar 21;22(1):295. Ma et al. , Discov Oncol. 2023 Jun 15;14(1):102. Yamazaki et al. , EMBO J. 2023 Jul 17;42(14):e112614. Zhang et al. Int J Mol Sci. 2024 Feb 12;25(4):2199. Wang et al. Invest Ophthalmol Vis Sci. 2023 Apr; 64(4): 23. Borah et al. , Invest Ophthalmol Vis Sci. 2021 Mar 1;62(3):16. Ren et al. , Biomed Pharmacother. 2023 Oct; 166:115343. Wang et al. , Front Pharmacol. 2022; 13: 781806. Shen et al. , J Neurochem. 2020 Jan; 152(1):72-91. Zhu et al. , Exp Eye Res. 2024 Feb:239:109753. Kawasaki et al. , J Cell Biol. 2001;152(2):275-287. Zou et al. , Biomed Res Int. 2017;2017:2320519. ;

[0010] The present inventors have investigated new therapeutic approaches targeting AURKB, which are effective in treating these diseases, and have investigated whether they can be effectively treated.

[0011] That is, the main objective of the present disclosure is to provide novel compounds that have AURKB kinase inhibitory activity.

[0012] The present inventors have conducted extensive research to provide a novel compound having an AURKB kinase inhibitory activity. In the process, they have found that a compound represented by the following general formula (I) or a salt thereof has an AURKB kinase inhibitory activity. Further research has led to the completion of the present disclosure.

[0013] The present disclosure encompasses, for example, the subject matter described in the following sections:

[0014] Item 1. General formula (I): [In the formula, R １ and R ２ are each independently a hydrogen atom, a halogen atom, an optionally substituted alkyl group having 1 to 5 carbon atoms, or an optionally substituted phenyl group, and R ３ is a hydrogen atom or an optionally substituted alkyl group having 1 to 3 carbon atoms, or R １ and R ２ , or R １ and R ３ R together with each adjacent carbon atom constitutes an optionally substituted 5- or 6-membered aromatic ring; ４ is a hydrogen atom or an optionally substituted alkyl group having 1 to 5 carbon atoms, and R ７ and R ８ are each independently a hydrogen atom or an optionally substituted alkyl group having 1 to 3 carbon atoms, ４ and R ７ is R ４ The nitrogen atom adjacent to R ５ and R ６ the carbon atom adjacent to R ７ R may, together with the carbon atom adjacent to R, form an optionally substituted 5- or 6-membered heterocycloalkyl ring; ５ and R ６ are each independently a hydrogen atom, an optionally substituted alkyl group having 1 to 5 carbon atoms, or an optionally substituted phenyl group, ５ and R ６ may form an optionally substituted 3- to 6-membered cycloalkyl ring together with the adjacent carbon atom; L is a divalent group formed by removing two hydrogen atoms from an alkane, alkene, or alkyne having 2 to 4 carbon atoms, and when L is a divalent group formed by removing two hydrogen atoms from an alkane having 2 to 4 carbon atoms (alkylene group), one or more methylene groups (-CH ２ -) may be substituted with -NH- or -O-; Het is an aromatic heterocyclic group having at least one nitrogen atom], wherein in general formula (I), Het is represented by general formula (II): [In the formula, represents a single bond or a double bond; X １ ~X ４ are each independently a carbon atom or a nitrogen atom; Ａ１ ~R Ａ４ are each independently a hydrogen atom, a halogen atom, an amino group, or —NH—(CH ２ ) ｎ Ａ -O-CH ３ (n Ａ is a natural number from 1 to 4), a group represented by the following formula: (In the formula, R Ａ５ is an optionally substituted alkyl group having 1 to 3 carbon atoms), or a group represented by the following formula: (In the formula, R Ａ６ is an optionally substituted alkyl group having 1 to 3 carbon atoms) (wherein X ２ When R is a nitrogen atom Ａ１ does not exist, and X ３ When R is a nitrogen atom Ａ３ is absent)], or a group represented by general formula (III): [In the formula, represents a single bond or a double bond; R Ｂ１ , R Ｂ２ , and R Ｂ４ are each independently a hydrogen atom, a halogen atom, an amino group, an optionally substituted alkyl group having 1 to 3 carbon atoms, an optionally substituted alkoxy group having 1 to 3 carbon atoms, -NH-R Ｂ３ (R Ｂ３ represents an optionally substituted alkyl group having 1 to 3 carbon atoms, an optionally substituted cycloalkyl group having 3 to 6 carbon atoms, -(CH ２ ) ｎ Ｂ -O-CH ３ (n Ｂ is a natural number from 1 to 4), or an optionally substituted phenyl group), —O—R Ｂ５ (R Ｂ５ is an optionally substituted cycloalkyl group having 3 to 6 carbon atoms, or ═O, or R Ｂ１ and R Ｂ４ , or R Ｂ４ and R Ｂ２form an optionally substituted 5- or 6-membered aromatic heterocycle together with the adjacent atoms, or a group represented by general formula (IV): [In the formula, represents a single bond or a double bond; X ５ and X ６ are each independently a carbon atom or a nitrogen atom; Ｃ１ ~R Ｃ４ are each independently a hydrogen atom, a halogen atom, an amino group, a hydroxy group, a cyano group, an optionally substituted alkyl group having 1 to 3 carbon atoms, an optionally substituted alkoxy group having 1 to 3 carbon atoms, an optionally substituted cycloalkyl group having 3 to 6 carbon atoms, an optionally substituted 5- or 6-membered aromatic carbocyclic group, an optionally substituted 5- or 6-membered aromatic heterocyclic group, an optionally substituted 5- or 6-membered heterocycloalkyl group, -NH-R Ｃ８ , -SO ２ -R Ｃ１１ , —CO—NR Ｃ１４ R Ｃ１５ or =O, where R Ｃ８ represents an optionally substituted alkyl group having 1 to 3 carbon atoms, —SO ２ -R Ｃ９ , or -CO-R Ｃ１０ R Ｃ９ is an optionally substituted alkyl group having 1 to 3 carbon atoms, and R Ｃ１０ represents an optionally substituted alkyl group having 1 to 3 carbon atoms, an optionally substituted cycloalkyl group having 3 to 6 carbon atoms, or a group represented by the following formula: (In the formula, X １０ is a carbon atom or a nitrogen atom); Ｃ１１ represents an optionally substituted alkyl group having 1 to 3 carbon atoms, or —NR Ｃ１２ R Ｃ１３ and R Ｃ１２ and R Ｃ１３ are each independently a hydrogen atom or an optionally substituted alkyl group having 1 to 3 carbon atoms; R Ｃ１４ and R Ｃ１５ are each independently a hydrogen atom or an optionally substituted alkyl group having 1 to 3 carbon atoms, or R Ｃ１and R Ｃ２ (At this time X ６ is a carbon atom), or R Ｃ２ and R Ｃ３ together with the adjacent carbon atoms, form an optionally substituted 5- or 6-membered aromatic ring, an optionally substituted 5- or 6-membered cycloalkyl ring, or an optionally substituted 5- or 6-membered heterocycloalkyl ring (provided that X ５ When R is a nitrogen atom Ｃ１ does not exist, and X ５ When R is a nitrogen atom Ｃ４ is absent)], or a group represented by general formula (V): [In the formula, represents a single bond or a double bond; X ７ ~X ９ are each independently a carbon atom or a nitrogen atom; Ｄ１ and R Ｄ２ are each independently a hydrogen atom, a halogen atom, an amino group, an optionally substituted alkyl group having 1 to 3 carbon atoms, an optionally substituted alkoxy group having 1 to 3 carbon atoms, or an optionally substituted phenyl group, or R Ｄ１ and R Ｄ２ is X ７ and X ８ and together with each other, form an optionally substituted 5- or 6-membered cycloalkyl ring, an optionally substituted 5- or 6-membered heterocycloalkyl ring, or an optionally substituted 5- or 6-membered aromatic heterocyclic ring], or a group represented by general formula (VI): [In the formula, R Ｅ are each independently a halogen atom, an amino group, an optionally substituted alkyl group having 1 to 3 carbon atoms, or an optionally substituted alkoxy group having 1 to 3 carbon atoms, and p is 0 to 4, or a group represented by general formula (VIII): [In the formula, represents a single bond or a double bond; X １１ ~X １３ are each independently a carbon atom or a nitrogen atom; Ｆ１ ~R Ｆ５are each independently a hydrogen atom, a halogen atom, an amino group, an optionally substituted alkyl group having 1 to 3 carbon atoms, or an optionally substituted alkoxy group having 1 to 3 carbon atoms, or R Ｆ２ and R Ｆ３ is X １２ and X １３ and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 2 １ , and R ２ are each independently a hydrogen atom, a halogen atom, an alkyl group having 1 or 2 carbon atoms which may be substituted with a halogen atom, or a phenyl group, and R ３ is a hydrogen atom or an alkyl group having 1 or 2 carbon atoms, or R １ and R ２ , or R ２ and R ３ Item 3. The compound or salt thereof according to Item 1, wherein R together with the adjacent carbon atom forms a benzene ring or a 6-membered aromatic heterocycle containing at least one nitrogen atom in the ring, which may be substituted with at least one group selected from the group consisting of a halogen atom, a cyano group, an alkyl group having 1 or 2 carbon atoms, and an alkoxy group having 1 or 2 carbon atoms which may be substituted with a halogen atom. ４ is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and R ７ and R ８ are each independently a hydrogen atom or an alkyl group having 1 or 2 carbon atoms, ４ and R ７ is R ４ The nitrogen atom adjacent to R ５ and R ６ the carbon atom adjacent to R ７ R may, together with the carbon atom adjacent to R, form a 5-membered heterocycloalkyl ring containing one nitrogen atom in the ring; ５ and R ６ are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or a phenyl group,５ and R ６ may form a 3- or 4-membered cycloalkyl ring together with the adjacent carbon atom; L is a divalent group obtained by removing two hydrogen atoms from ethane, ethylene, or acetylene, and when L is a divalent group obtained by removing two hydrogen atoms from ethane (ethylene group), one methylene group (—CH ２ Item 4. The compound or salt thereof according to item 1 or 2, wherein Het in formula (I) is a group represented by formula (II): [In the formula, represents a single bond or a double bond; X １ ~X ４ are each independently a carbon atom or a nitrogen atom; Ａ１ ~R Ａ４ are each independently a hydrogen atom, a halogen atom, an amino group, or —NH—(CH ２ ) ２ -O-CH ３ a group represented by the following formula: (In the formula, R Ａ５ is an alkyl group having 1 or 2 carbon atoms), or a group represented by the following formula: (In the formula, R Ａ６ is a group represented by an alkyl group having 1 or 2 carbon atoms (wherein X ２ When R is a nitrogen atom Ａ１ does not exist, and X ３ When R is a nitrogen atom Ａ３ is absent)], or a group represented by general formula (III): [In the formula, represents a single bond or a double bond; R Ｂ１ , R Ｂ２、 , and R Ｂ４ are each independently a hydrogen atom, an amino group, an alkyl group having 1 to 3 carbon atoms which may be substituted with a halogen atom, an alkoxy group having 1 or 2 carbon atoms which may be substituted, -NH-R Ｂ３ (R Ｂ３ represents an alkyl group having 1 or 2 carbon atoms, a cycloalkyl group having 3 to 5 carbon atoms, -(CH ２ ) ｎ Ｂ -O-CH ３(n Ｂ is a natural number from 1 to 3), or a halogen atom or the following formula: a phenyl group optionally substituted with a group represented by the formula: Ｂ５ (R Ｂ５ is a cycloalkyl group having 3 to 5 carbon atoms), or ═O, or R Ｂ１ and R Ｂ４ , or R Ｂ４ and R Ｂ２ form a 5-membered aromatic heterocycle together with the adjacent atoms, or a group represented by general formula (IV): [In the formula, represents a single bond or a double bond; X ５ and X ６ are each independently a carbon atom or a nitrogen atom; Ｃ１ ~R Ｃ３ are each independently a hydrogen atom, a halogen atom, an amino group, a hydroxy group, a cyano group, an alkoxy group having 1 to 3 carbon atoms which may be substituted with a halogen atom, a cycloalkyl group having 3 to 5 carbon atoms, a phenyl group, a 6-membered aromatic heterocyclic group having one nitrogen atom in the ring, or a 5-membered heterocycloalkyl group having one nitrogen atom in the ring, -NH-R Ｃ８ , -SO ２ -R Ｃ１１ , —CO—NR Ｃ１４ R Ｃ１５ or =O, where R Ｃ８ is an alkyl group having 1 or 2 carbon atoms, -SO ２ -R Ｃ９ , or -CO-R Ｃ１０ R Ｃ９ is an alkyl group having 1 or 2 carbon atoms, and R Ｃ１０ is a cycloalkyl group having 3 to 5 carbon atoms, or a group represented by the following formula: (In the formula, X １０ is a carbon atom or a nitrogen atom); Ｃ１１ represents an optionally substituted alkyl group having 1 to 3 carbon atoms, or —NR Ｃ１２ R Ｃ１３ and R Ｃ１２ and R Ｃ１３ are each independently a hydrogen atom or an alkyl group having 1 or 2 carbon atoms; RＣ１４ and R Ｃ１５ are each independently a hydrogen atom or an alkyl group having 1 or 2 carbon atoms, or R Ｃ１ and R Ｃ２ (At this time X ６ is a carbon atom), or R Ｃ２ and R Ｃ３ R together with each adjacent carbon atom form an optionally substituted 5- or 6-membered aromatic ring, an optionally substituted 5- or 6-membered cycloalkyl ring, or an optionally substituted 5- or 6-membered heterocycloalkyl ring; Ｃ４ is a hydrogen atom, a halogen atom, or an amino group (provided that X ５ When R is a nitrogen atom Ｃ１ does not exist, and X ５ When R is a nitrogen atom Ｃ４ is absent)], or a group represented by the following formula: or a group represented by the following formula: (In the formula, R Ｃ５ is a hydrogen atom or a halogen atom), or a group represented by the following formula: (In the formula, R Ｃ６ and R Ｃ７ are each independently a hydrogen atom, a halogen atom, or an alkyl group having 1 or 2 carbon atoms), or a group represented by the following formula: or a group represented by the following formula: (In the formula, R Ｄ１ is a hydrogen atom or an alkoxy group having 1 or 2 carbon atoms), or a group represented by the following formula: or a group represented by the following formula: or a group represented by the following formula: or a group represented by the following formula: (In the formula, R Ｄ１ and R Ｄ２ are each independently a hydrogen atom or an alkyl group having 1 or 2 carbon atoms), or a group represented by the following formula: (In the formula, R Ｄ１ and R Ｄ２ are each independently a hydrogen atom or an alkyl group having 1 or 2 carbon atoms), or a group represented by the following formula: (In the formula, R Ｄ１ and R Ｄ２ are each independently a hydrogen atom, a halogen atom, or an amino group), or a group represented by the following formula: or a group represented by the following formula: or a group represented by the following formula: (In the formula, R Ｄ３ is a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or —CH ２ -R Ｄ４ (R Ｄ４ is a cycloalkyl group having 3 to 5 carbon atoms), or is a group represented by the following formula: or a group represented by the following formula: or a group represented by the following formula: Item 5. The compound or salt thereof according to any one of Items 1 to 3, which is a group represented by the following formula (1): Item 6. At least one compound or salt thereof selected from the group consisting of the following compounds (1) to (360): (1) 4,5-dibromo-N-{4-[6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-3-yl]but-3-yn-1-yl}-1H-imidazole-2-carboxamide, (2) 4,5-dibromo-N-(4-{8-[(1-methyl-1H-pyrazol-4-yl)amino]imidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)-1H-imidazole-2-carboxamide, (3) N-(4-{8-aminoimidazo[1,2-a]pyridin-3-yl}-2-methylbut-3-yn-1-yl)-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (4) N-(5-{8-aminoimidazo[1,2-a]pyridin-3-yl}-2-methylpent-4-yn-2-yl)-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (5) N-(4-{imidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (6) N-(4-{8-amino-6-bromoimidazo[1,2-a]pyrazin-3-yl}but-3-yn-1-yl)-5,6-difluoro-1H-1,3-benzodiazole-2-carboxamide, (7) N-(4-{8-[(2-methoxyethyl)amino]imidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (8) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (9) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclobutyl]-6-chloro-1H-1,3-benzodiazole-2-carboxamide, (10) N-(4-{2-[(3-fluorophenyl)amino]pyrimidin-5-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (11) 6,7-difluoro-N-(4-{imidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (12) N-[4-(2-{[3-(4-methylpiperazin-1-yl)phenyl]amino}pyrimidin-5-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (13) N-(4-{8-aminoimidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1-methyl-1H-1,3-benzodiazole-2-carboxamide, (14) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-4,7-dichloro-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (15) N-(4-{8-aminoimidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-N-ethyl-7-methyl-1H-1,3-benzodiazole-2-carboxamide, (16) N-(4-{8-amino-5-chloroimidazo[1,2-a]pyrazin-3-yl}but-3-yn-1-yl)-7-methoxy-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (17) N-(4-{[3,3'-bipyridin]-5-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (18) N-(4-{8-amino-5-chloro-2-methylimidazo[1,2-a]pyrazin-3-yl}but-3-yn-1-yl)-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (19) N-[4-(6-amino-5-bromopyridazin-3-yl)but-3-yn-1-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (20) 7-chloro-N-(4-{2H,3H,4H-pyrido[3,2-b][1,4]oxazin-7-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (21) N-(4-{pyrazolo[3,2-b][1,3]thiazol-7-yl}but-3-yn-1-yl)-1H-1,3-Benzodiazole-2-carboxamide, (22) N-[(3E)-4-(6-amino-5-chloropyridin-3-yl)but-3-en-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (23) 5-{2-[1-(1H-1,3-benzodiazole-2-carbonyl)pyrrolidin-3-yl]ethynyl}-3-bromopyridin-2-amine, (24) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-5-phenyl-1H-imidazole-2-carboxamide, (25) N-[(1R)-4-(6-amino-5-chloropyridin-3-yl)-1-phenylbut-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (26) N-[(2S)-5-(2-amino-4-methoxypyrimidin-5-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (27) N-[4-(8-fluoroisoquinolin-4-yl)but-3-yn-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (28) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-5-ethyl-1H-imidazole-2-carboxamide, (29) N-[(2S,4E)-5-{2-[(4-fluorophenyl)amino]pyrimidin-5-yl}pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (30) N-[(3E)-4-(2-amino-4-methoxypyrimidin-5-yl)but-3-en-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (31) N-[(2S,4E)-5-(2-amino-4-methoxypyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (32) N-[(2S)-5-[2,4-bis(methylamino)pyrimidin-5-yl]pent-4-yn-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (33) N-(4-{6-chloro-1H-pyrazolo[3,4-b]pyridin-5-yl}but-3-yn-1-yl)-1H-1,3-Benzodiazole-2-carboxamide, (34) 7-chloro-N-[4-(4-phenylpyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (35) N-[(2S)-5-(5-amino-4-ethoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (36) N-[(2S,4E)-5-{3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl}pent-4-en-2-yl]-5-(trifluoromethyl)-1H-imidazole-2-carboxamide, (37) N-[(2S,4E)-5-(6-amino-4-fluoropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (38) N-[(2S,4E)-5-(5-methoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (39) N-[(2S,4E)-5-(6-aminopyrazin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (40) N-[(2S)-5-{5H,6H,7H-pyrrolo[1,2-a]imidazol-3-yl}pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (41) N-[(2S)-5-[6-amino-5-(trifluoromethoxy)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (42) N-[(2S,4E)-5-(2-amino-5-fluoropyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (43) N-[(2S)-5-(5,6,7,8-tetrahydroisoquinolin-4-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (44) N-[(2S,4E)-5-[5-(pyrrolidin-1-yl)pyridin-3-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (45) N-[(2S,(4E)-5-(4-methoxy-1H-pyrazol-5-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (46) N-[(2S,4E)-5-(6-aminopyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (47) N-[(2S,4E)-5-{4H,5H,6H,7H-pyrazolo[1,5-a]pyridin-3-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (48) N-[(3S,5E)-6-(2-amino-4-methoxypyrimidin-5-yl)hex-5-en-3-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (49) N-[(3R,5E)-6-(5-methoxypyridin-3-yl)-2-methylhex-5-en-3-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (50) N-[(2S)-5-(6-aminopyridin-3-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (51) N-[(2S)-5-(6-amino-4,5-dimethoxypyridin-3-yl)pent-4-yn-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (52) N-[(2S,4Z)-5-(2-amino-4-methoxypyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (53) N-[(2S)-4-[(5-fluoropyridin-3-yl)amino]butan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (54) N-[(2S)-4-[(2-aminopyrimidin-5-yl)oxy]butan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (55) N-[(2S)-1-[(5-chloropyridin-3-yl)methoxy]propan-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (56) N-(4-{8-aminoimidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)-4,5-dibromo-1-methyl-1H-imidazole-2-carboxamide, (57) 4,5-dibromo-N-{4-[5-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-3-yl]but-3-yn-1-yl}-1H-imidazole-2-carboxamide, (58) N-(4-{8-[(1-methyl-1H-pyrazol-4-yl)amino]imidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (59) N-(4-{8-aminoimidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)-1-bromoimidazo[1,5-a]pyridine-3-carboxamide, (60) N-(4-{8-aminoimidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)-6-methyl-1H-1,3-benzodiazole-2-carboxamide, (61) N-(4-{8-aminoimidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)-6-fluoro-1H-1,3-benzodiazole-2-carboxamide, (62) N-(4-{8-amino-6-chloroimidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (63) N-(4-{8-aminoimidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (64) N-(4-{8-amino-7-chloroimidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (65) N-(4-{8-amino-6,7-dichloroimidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (66) 7-fluoro-N-(4-{imidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (67) 7-chloro-N-(4-{2-[(2-fluorophenyl)amino]pyrimidin-5-yl}but-3-yn-1-yl)-1H-1,3-Benzodiazole-2-carboxamide, (68) 7-chloro-N-(4-{2-[(4-fluorophenyl)amino]pyrimidin-5-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (69) 4,5-dibromo-N-{4-[7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]but-3-yn-1-yl}-1H-imidazole-2-carboxamide, (70) 7-chloro-N-[4-(2-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrimidin-5-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (71) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-bromo-1H-1,3-benzodiazole-2-carboxamide, (72) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-methoxy-1H-1,3-benzodiazole-2-carboxamide, (73) N-[1-(3-{8-amino-7-chloroimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-1H-1,3-benzodiazole-2-carboxamide, (74) N-[1-(3-{8-amino-7-chloroimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (75) N-[1-(3-{8-amino-7-chloroimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-methyl-1H-1,3-benzodiazole-2-carboxamide, (76) N-[1-(3-{8-amino-7-chloroimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-methoxy-1H-1,3-benzodiazole-2-carboxamide, (77) N-(5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl)-1H-1,3-Benzodiazole-2-carboxamide, (78) N-(5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl)-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (79) N-(5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl)-3H-imidazo[4,5-b]pyridine-2-carboxamide, (80) N-[1-(3-{8-amino-7-chloroimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (81) N-(5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl)-7-(trifluoromethoxy)-1H-1,3-benzodiazole-2-carboxamide, (82) N-(5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl)-7-methyl-1H-1,3-benzodiazole-2-carboxamide, (83) N-(5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl)-7-methoxy-1H-1,3-benzodiazole-2-carboxamide, (84) N-[(2R)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (85) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (86) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (87) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-ethoxy-1H-1,3-benzodiazole-2-carboxamide, (88) N-[1-(3-{8-amino-7-chloroimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-ethoxy-1H-1,3-Benzodiazole-2-carboxamide, (89) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-6-chloro-7-methoxy-1H-1,3-benzodiazole-2-carboxamide, (90) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-6-fluoro-7-methyl-1H-1,3-benzodiazole-2-carboxamide, (91) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-6-chloro-7-methyl-1H-1,3-benzodiazole-2-carboxamide, (92) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-6,7-dichloro-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (93) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-5,7-dichloro-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (94) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-5,6-dichloro-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (95) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-7-methoxy-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (96) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-7-chloro-1-methyl-1H-1,3-benzodiazole-2-carboxamide, (97) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-6-chloro-1-methyl-1H-1,3-benzodiazole-2-carboxamide, (98) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-5-chloro-1-methyl-1H-1,3-Benzodiazole-2-carboxamide, (99) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-4-chloro-1-methyl-1H-1,3-benzodiazole-2-carboxamide, (100) 7-chloro-N-(4-{imidazo[1,2-a]pyrazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (101) N-(4-{8-amino-7-bromoimidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-7-methoxy-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (102) N-(4-{8-aminoimidazo[1,2-a]pyrazin-3-yl}but-3-yn-1-yl)-7-chloro-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (103) N-[1-(3-{8-aminoimidazo[1,2-a]pyrazin-6-yl}prop-2-yn-1-yl)cyclopropyl]-1H-1,3-benzodiazole-2-carboxamide, (104) N-[1-(3-{8-amino-7-bromoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-methoxy-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (105) N-[4-(5-bromopyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (106) N-[4-(6-amino-5-phenylpyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (107) N-(4-{8-amino-2-methylimidazo[1,2-a]pyrazin-3-yl}but-3-yn-1-yl)-7-chloro-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (108) N-[4-(6-amino-5-bromo-4-methoxypyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (109) N-[4-(6-aminopyridazin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (110) N-[(2S)-5-(6-amino-5-bromopyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (111) N-{1-[3-(6-amino-5-bromopyridin-3-yl)prop-2-yn-1-yl]cyclopropyl}-1H-1,3-benzodiazole-2-carboxamide, (112) N-[4-(6-amino-5-bromopyridin-3-yl)but-3-yn-1-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (113) N-[(2S)-5-(6-amino-5-chloropyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (114) N-[4-(6-amino-5-chloropyridin-3-yl)but-3-yn-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (115) N-{4-[6-amino-5-(trifluoromethyl)pyridin-3-yl]but-3-yn-1-yl}-3H-imidazo[4,5-b]pyridine-2-carboxamide, (116) N-(4-{1H-pyrrolo[2,3-c]pyridin-4-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (117) N-[4-(5-amino-6-chloropyrazin-2-yl)but-3-yn-1-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (118) N-(4-{pyrazolo[1,5-a]pyridin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (119) N-[4-(1-phenyl-1H-pyrazol-4-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (120) N-[4-(5-cyclopropylpyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (121) N-[(2S,4E)-5-(6-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (122) N-[(2S,(4E)-5-(6-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (123) N-[(2S,4E)-5-(6-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-6-chloro-1H-1,3-benzodiazole-2-carboxamide, (124) N-[(2R,4E)-5-(6-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (125) N-[(2R,4E)-5-(6-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (126) N-[(3R)-6-(6-amino-5-chloropyridin-3-yl)hex-5-yn-3-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (127) N-[(3S)-6-(6-amino-5-chloropyridin-3-yl)hex-5-yn-3-yl]-1H-1,3-benzodiazole-2-carboxamide, (128) N-[(3S)-6-(6-amino-5-chloropyridin-3-yl)hex-5-yn-3-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (129) N-[(3E)-4-(6-amino-5-chloropyridin-3-yl)but-3-en-1-yl]-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (130) 7-chloro-N-[1-(3-{1H-pyrrolo[2,3-b]pyridin-5-yl}prop-2-yn-1-yl)cyclopropyl]-1H-1,3-benzodiazole-2-carboxamide, (131) 7-chloro-N-(4-{3-methyl-3H-imidazo[4,5-b]pyridin-6-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (132) 7-chloro-N-{4-[2-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-6-yl]but-3-yn-1-yl}-1H-1,3-benzodiazole-2-carboxamide, (133) N-(5-{8-aminoimidazo[1,(2-b)pyridazin-3-yl}pent-4-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (134) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (135) N-[(3S)-6-{8-aminoimidazo[1,2-b]pyridazin-3-yl}hex-5-yn-3-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (136) 7-chloro-N-(4-{5H-pyrrolo[2,3-b]pyrazin-2-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (137) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-5-bromo-1H-imidazole-2-carboxamide, (138) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-4,5-dichloro-1H-imidazole-2-carboxamide, (139) 7-chloro-N-(4-{3H-[1,2,3]triazolo[4,5-b]pyridin-6-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (140) N-(4-{3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl}but-3-yn-1-yl)-3H-imidazo[4,5-b]pyridine-2-carboxamide, (141) N-[4-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (142) N-[(3R)-6-{8-aminoimidazo[1,2-b]pyridazin-3-yl}-2-methylhex-5-yn-3-yl]-7-methoxy-1H-1,3-benzodiazole-2-carboxamide, (143) 7-chloro-N-[4-(5-methanesulfonamidopyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (144) N-[(2S)-5-(2-amino-4-methoxypyrimidin-5-yl)pent-4-yn-2-yl]-7-chloro-1H-1,3-Benzodiazole-2-carboxamide, (145) N-[(2S)-5-(2-amino-4-ethoxypyrimidin-5-yl)pent-4-yn-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (146) N-[(2S)-5-(2-amino-4-ethoxypyrimidin-5-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (147) N-[4-(isoquinolin-4-yl)but-3-yn-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (148) N-[4-(1-aminoisoquinolin-4-yl)but-3-yn-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (149) 7-chloro-N-{4-[2-(methylamino)pyrimidin-5-yl]but-3-yn-1-yl}-1H-1,3-benzodiazole-2-carboxamide, (150) 7-chloro-N-{4-[2-(ethylamino)pyrimidin-5-yl]but-3-yn-1-yl}-1H-1,3-benzodiazole-2-carboxamide, (151) 7-chloro-N-{4-[2-(cyclopropylamino)pyrimidin-5-yl]but-3-yn-1-yl}-1H-1,3-benzodiazole-2-carboxamide, (152) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-5-methyl-1H-imidazole-2-carboxamide, (153) N-[(2S,4E)-5-{2-[(4-fluorophenyl)amino]pyrimidin-5-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (154) N-[(3E)-4-{2-[(4-fluorophenyl)amino]pyrimidin-5-yl}but-3-en-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (155) 7-chloro-N-(4-{2-methyl-2H-pyrazolo[3,4-c]pyridin-4-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (156) 7-chloro-N-(4-{1-methyl-1H-pyrazolo[3,4-c]pyridin-4-yl}but-3-yn-1-yl)-1H-1,3-Benzodiazole-2-carboxamide, (157) 7-chloro-N-(4-{1H-pyrazolo[3,4-c]pyridin-4-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (158) N-[4-(5-bromo-6-cyclopropaneamidopyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (159) N-[(2S)-5-{3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (160) 7-chloro-N-[(2S)-5-{3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (161) N-[(2S)-5-{3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl}pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (162) N-[(2S)-5-[5-(methylamino)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (163) N-[4-(6-amino-4,5-dichloropyridin-3-yl)but-3-yn-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (164) N-[(2S)-5-(6-amino-4,5-dichloropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (165) N-[(2S)-5-(6-amino-4,5-dichloropyridin-3-yl)pent-4-yn-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (166) N-(4-{6-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (167) 7-chloro-N-(4-{2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (168) N-(4-{2-methyl-1H-pyrrolo[2,(3-b)pyridin-5-yl}but-3-yn-1-yl)-3H-imidazo[4,5-b]pyridine-2-carboxamide, (169) N-[(2S)-5-(6-amino-5-chloro-4-methylpyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (170) N-[(2S)-5-(6-amino-5-chloro-4-methoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (171) N-[(2S)-5-(6-amino-5-chloro-4-methylpyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (172) N-[(2S)-5-(5-amino-4-chloropyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (173) N-[(2S)-5-(5-amino-4-methoxypyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (174) N-[(2S)-5-(5-amino-4-chloropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (175) N-[(2S)-5-(5-amino-4-methoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (176) N-[4-(5-amino-4-hydroxypyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (177) N-[(2S,4E)-5-(6-amino-4,5-dichloropyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (178) N-[(2S,4E)-5-(6-amino-4,5-dichloropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (179) N-[(2S)-5-{4-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (180) N-[(2S,4E)-5-[4-methoxy-2-(methylamino)pyrimidin-5-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (181) N-{4-[4-(trifluoromethyl)pyridin-3-yl]but-3-yn-1-yl}-3H-imidazo[4,5-b]pyridine-2-carboxamide, (182) N-[4-(4-chloropyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (183) N-[(2S,4E)-5-(6-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (184) N-[(2S,4E)-5-(2-amino-4-methylpyrimidin-5-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (185) N-[(2S,4E)-5-(2-amino-4-methylpyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (186) N-[(2S,4E)-5-(2-amino-1-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)pent-4-en-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (187) N-[(2S)-5-(6-amino-5-fluoropyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (188) N-[(2S)-5-(6-amino-5-fluoropyridin-3-yl)pent-4-yn-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (189) N-[(2S)-5-(6-amino-5-fluoropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (190) N-[(2S,4E)-5-(6-amino-5-fluoropyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (191) N-[(2S,4E)-5-(6-amino-5-fluoropyridin-3-yl)pent-4-en-2-yl]-7-chloro-1H-1,3-Benzodiazole-2-carboxamide, (192) N-[(2S,4E)-5-(6-amino-5-fluoropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (193) N-[(2S,4E)-5-(2-amino-4-ethylpyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (194) N-[(2S)-5-[6-amino-4-(trifluoromethyl)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (195) N-[(2S,4E)-5-(6-amino-4-chloro-5-methoxypyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (196) N-[(2S)-5-(6-amino-4-chloro-5-methoxypyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (197) N-[(2S,4E)-5-(6-amino-4-chloro-5-methoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (198) N-[(2S)-5-(6-amino-4-chloro-5-methoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (199) N-[(2S)-5-(5-amino-6-methylpyridin-3-yl)pent-4-yn-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (200) N-[(2S,4E)-5-(5-amino-4-methoxypyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (201) N-[(2S,4E)-5-(5-amino-4-methoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (202) N-[(2S,4E)-5-(5-amino-4-ethoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (203) N-[(2S,4E)-5-(6-amino-5-methylpyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (204) N-[(2S,4E)-5-[6-amino-5-(trifluoromethyl)pyridin-3-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (205) N-[(2S,4E)-5-(6-amino-5-methoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (206) N-[(2S,4E)-5-(5-aminopyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (207) N-[(2S,4E)-5-(5-aminopyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (208) N-[(2S)-5-{3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl}pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (209) N-[(2S,4E)-5-{1H-pyrazolo[3,4-b]pyridin-5-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (210) N-[(2S,4E)-5-{3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (211) N-[(2S)-5-[5-amino-4-(methylamino)pyridin-3-yl]pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (212) N-[(2S)-5-[2-amino-4-(trifluoromethyl)pyrimidin-5-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (213) N-[(2S)-5-(4,5,6,7-tetrahydro-1H-indazol-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (214) N-[(2S,4E)-5-(5-aminopyrazin-2-yl)pent-4-en-2-yl]-1H-1,3-Benzodiazole-2-carboxamide, (215) N-[(2S,4E)-5-(5-aminopyrazin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (216) N-[(2S,4E)-5-(5-amino-6-methoxypyrazin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (217) N-[(2S,4E)-5-(5-amino-6-methylpyrazin-2-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (218) N-[(2S,4E)-5-(5-amino-6-methylpyrazin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (219) N-[(2S)-5-{5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (220) N-[(2S)-5-(2-methyl-1H-imidazol-4-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (221) N-[(2S,4E)-5-(5-fluoropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (222) N-[(2S,4E)-5-(6-methylpyrazin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (223) N-[(2S,4E)-5-(2-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (224) N-[(2S,4E)-5-(4-methoxypyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (225) N-[(2S,4E)-5-(2-amino-4-cyclopropoxypyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,(226) N-[(2S)-5-[6-amino-5-(trifluoromethoxy)pyridin-3-yl]pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (227) N-[(2S,4E)-5-(4-amino-6-methoxypyrimidin-5-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (228) N-[(2S,4E)-5-(4-amino-6-methoxypyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (229) N-[(2S)-5-{7-acetyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (230) N-[(2S,4E)-5-(5-methanesulfonylpyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (231) N-[(2S,4E)-5-(4-fluoropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (232) N-[(2S,4E)-5-{imidazo[1,2-b]pyridazin-3-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (233) N-[(2S,4E)-5-{pyrazolo[1,5-a]pyrimidin-3-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (234) N-[(2S,4E)-5-(1H-indazol-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (235) N-[(2S,4E)-5-(1H-indazol-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (236) N-[(2S)-5-(5-aminopyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (237) N-[(2S,4E)-5-[5-(morpholin-4-yl)pyridin-3-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (238) N-[(2S,4E)-5-[6-amino-5-(trifluoromethoxy)pyridin-3-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (239) N-[(2S,4E)-5-(6-aminopyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (240) N-[(2S,4E)-5-(2-aminopyrimidin-5-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (241) N-[(2S,4E)-5-(2-aminopyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (242) N-[(2S)-5-(4-chloro-5-fluoropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (243) N-[(2S)-5-(5-fluoro-4-methylpyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (244) N-[(2S,4E)-5-(5-chloropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (245) N-[(2S)-5-{7-methyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (246) N-[(2S,4E)-5-(5-cyano-4-methylpyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (247) N-[(2S,4E)-5-(6-amino-5-cyanopyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (248) N-[(2S,4E)-5-(5-carbamoylpyridin-3-yl)pent-4-en-2-yl]-1H-1,3-Benzodiazole-2-carboxamide, (249) N-[(2S,4E)-5-(5-cyanopyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (250) N-[(2S,4E)-5-(pyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (251) N-[(2S,4E)-5-(pyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (252) N-[(2S)-5-{5-[(4-methylpiperazin-1-yl)methyl]pyridin-3-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (253) N-[(2S)-5-{5-[(4-methyl-3-oxopiperazin-1-yl)methyl]pyridin-3-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (254) N-[(2S,4E)-5-[2-(ethylamino)-4-methoxypyrimidin-5-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (255) N-[(2S,4E)-5-[2-(cyclopropylamino)-4-methoxypyrimidin-5-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (256) N-[(2S,4E)-5-{4-methoxy-2-[(2-methoxyethyl)amino]pyrimidin-5-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (257) N-[(2S,4E)-5-(4,5,6,7-tetrahydro-1H-indazol-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (258) N-[(2S,4E)-5-{5H,6H,7H,8H-imidazo[1,2-a]pyridin-3-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (259) N-[(2S,4E)-5-(3-aminopyrazin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,(260) N-[(2S,4E)-5-(3-amino-1H-pyrazol-5-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (261) N-[(2S,4E)-5-(3-amino-4-chloro-1H-pyrazol-5-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (262) N-[(2S,4E)-5-(3-amino-4-chloro-1H-pyrazol-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (263) N-[(2S,4E)-5-(6-amino-4-methylpyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (264) N-[(2S,4E)-5-(6-amino-4-chloropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (265) N-[(2S,4E)-5-[4-amino-2-(methylamino)pyrimidin-5-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (266) N-[(2S,4E)-5-[2-amino-4-(methylamino)pyrimidin-5-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (267) N-[(2S,4E)-5-[2-amino-4-(ethylamino)pyrimidin-5-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (268) N-[(2S,4E)-5-(5-methyl-1H-pyrazol-4-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (269) N-{1-[(2E)-3-(2-amino-4-methoxypyrimidin-5-yl)prop-2-en-1-yl]cyclobutyl}-3H-imidazo[4,5-b]pyridine-2-carboxamide, (270) N-[(2S,4E)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (271) N-[(2S,4E)-5-(5-ethoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (272) N-{1-[(2E)-3-(5-methoxypyridin-3-yl)prop-2-en-1-yl]cyclopropyl}-1H-1,3-benzodiazole-2-carboxamide, (273) N-[(2S,4E)-5-(5-methoxypyridin-3-yl)pent-4-en-2-yl]-7-(trifluoromethyl)-1H-1,3-benzodiazole-2-carboxamide, (274) 7-cyano-N-[(2S,4E)-5-(5-methoxypyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (275) N-[(2S)-5-(6-amino-4-fluoropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (276) N-[(2S)-5-(6-amino-4-chloropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (277) N-[(2S,4E)-5-(2-amino-4-methoxypyrimidin-5-yl)pent-4-en-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (278) N-[(2S,4E)-5-(6-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (279) N-[(2S,4E)-5-(5-amino-6-methoxypyrazin-2-yl)pent-4-en-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (280) N-[(2S)-5-(2-amino-4-methoxypyrimidin-5-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (281) N-[(2S)-5-{7-ethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl}pent-4-yn-2-yl]-1H-1,3-Benzodiazole-2-carboxamide, (282) N-[(2S)-5-[5-(difluoromethoxy)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (283) N-[(2S)-5-(5-methoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (284) N-[(2S)-5-(6-amino-5-chloropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (285) N-[(2S)-5-(6-amino-5-bromopyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (286) N-[(2S)-5-(5-amino-6-methoxypyrazin-2-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (287) N-[(2S)-5-(6-amino-5-fluoropyridin-3-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (288) N-[(2S)-5-(6-amino-5-fluoropyridin-3-yl)pentan-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (289) N-[(2S)-5-[7-(cyclopropylmethyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (290) N-[(2S)-5-(6-amino-4-bromopyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (291) N-[(2S)-5-(6-amino-4-bromopyridin-3-yl)pent-4-yn-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (292) N-[(2S)-5-(6-amino-4-chloropyridin-3-yl)pent-4-yn-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (293) N-[(2S,4E)-5-(6-amino-4,(294) N-[(2S,4E)-5-(6-amino-5-chloro-4-fluoropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (295) N-[(2S,4E)-5-(6-amino-4,5-dimethoxypyridin-3-yl)pent-4-en-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (296) N-[(2S)-5-(6-amino-4,5-dimethoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (297) N-[(2S)-5-(6-amino-4-fluoropyridin-3-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (298) N-[(2S)-5-(5-amino-6-cyanopyrazin-2-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (299) N-[(2S,4E)-5-(6-amino-4-fluoro-5-methoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (300) N-[(2S)-5-(5-cyano-4-methylpyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (301) N-[(2S,4E)-5-(6-amino-4-fluoro-5-methylpyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (302) N-[(2S)-5-(6-amino-4-fluoro-5-methylpyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (303) N-[(2S)-5-(6-amino-4-fluoro-5-methoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (304) N-[(2S)-5-(2-amino-5,6-difluoropyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-Benzodiazole-2-carboxamide, (305) N-[(2S)-5-(6-amino-5-methylpyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (306) N-[(2S)-5-(6-amino-5-methylpyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (307) N-[(2S)-5-[5-(trifluoromethyl)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (308) N-[(2S)-5-[6-amino-5-(trifluoromethyl)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (309) N-[(2S)-5-(6-amino-5-methoxypyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (310) N-[(2S)-5-(6-amino-5-methoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (311) N-[(2S)-5-(6-amino-5-methoxypyridin-3-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (312) N-[(2S)-5-(6-amino-5-methylpyridin-3-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (313) N-[(2S)-5-(6-amino-5-methylpyridin-3-yl)pentan-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (314) N-[(2S)-5-[6-amino-5-(trifluoromethyl)pyridin-3-yl]pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (315) N-[(2S)-5-[6-amino-5-(trifluoromethyl)pyridin-3-yl]pentan-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (316) N-[(2S)-5-[6-amino-5-(trifluoromethoxy)pyridin-3-yl]pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (317) N-[(2S,4E)-5-(6-amino-4,5-difluoropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (318) N-[(2S)-5-(6-amino-4,5-difluoropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (319) N-[(2S,4E)-5-[6-amino-5-(hydroxymethyl)pyridin-3-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (320) N-[(2S,4E)-5-[6-amino-5-(hydroxymethyl)pyridin-3-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (321) N-[(2S,4E)-5-[6-amino-4-(hydroxymethyl)pyridin-3-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (322) N-[(2S,4E)-5-[6-amino-5-(difluoromethoxy)pyridin-3-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (323) N-[(2S,4E)-5-[6-amino-5-(difluoromethyl)pyridin-3-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (324) N-[(2S)-5-[6-amino-5-(difluoromethoxy)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (325) N-[(2S)-5-[6-amino-5-(difluoromethyl)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (326) N-[(2S)-5-(2-aminopyrimidin-5-yl)pentan-2-yl]-1H-1,3-Benzodiazole-2-carboxamide, (327) N-[(2S)-5-(2-aminopyrimidin-5-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (328) N-[(2S)-5-(2-aminopyrimidin-5-yl)pentan-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (329) N-[(2S)-5-(5-aminopyrazin-2-yl)pentan-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (330) N-[(2S)-5-(5-amino-6-methylpyrazin-2-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (331) N-[(2S)-5-(5-amino-6-methylpyrazin-2-yl)pentan-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (332) N-[(2S)-5-(6-amino-4-methoxypyridin-3-yl)pentan-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (333) N-[(2S,4E)-5-(4-methoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (334) N-[(2S,4E)-5-(pyridin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (335) N-[(2S)-4-[(6-amino-5-chloropyridin-3-yl)oxy]butan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (336) N-[(2S)-4-[(6-amino-5-chloropyridin-3-yl)oxy]butan-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (337) N-[(2S,4E)-5-(2-amino-4-methoxypyrimidin-5-yl)pent-4-en-2-yl]-4-chloro-3H-imidazo[4,5-c]pyridine-2-carboxamide, (338) N-[(2S,4E)-5-{pyrazolo[1,5-a]pyrimidin-6-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (339) N-[(2S,4E)-5-{imidazo[1,5-a]pyrimidin-3-yl}pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (340) N-[(2S,4E)-5-{1H-pyrazolo[3,4-b]pyrazin-5-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (341) N-[(2S,4E)-5-(2-amino-6-oxo-1,6-dihydropyrimidin-5-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (342) N-[(2S,4E)-5-(5-amino-6-oxo-1,6-dihydropyrazin-2-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (343) N-[(2R)-5-(6-amino-4-fluoropyridin-3-yl)-1,1,1-trifluoropent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (344) N-[(2S,4E)-5-{pyrrolo[1,2-a]pyrimidin-3-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (345) N-[(2S,4E)-5-{imidazo[1,2-b]pyridazin-7-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (346) N-[(2R,4E)-5-(6-amino-4-fluoropyridin-3-yl)-1,1,1-trifluoropent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (347) N-[5-(6-amino-5-chloropyridin-3-yl)(1,1,1-, ２ H ３ ) pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (348) N-[(4E)-5-(2-amino-4-methoxypyrimidin-5-yl)(1,1,1- ２ H ３ ) pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (349) N-[(4E)-5-(6-amino-4-fluoropyridin-3-yl)(1,1,1- ２ H３ ) pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (350) N-[(4E)-5-(5-methoxypyridin-3-yl)(1,1,1- ２ H ３ ) pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (351) N-[5-(5-methoxypyridin-3-yl)(1,1,1- ２ H ３) pentan-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (352) N-[(2S,4E)-5-[6-amino-5-(dimethylcarbamoyl)pyridin-3-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (353) N-[(2S,4E)-5-[6-amino-5-(dimethylsulfamoyl)pyridin-3-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (354) N-[(2S,4E)-5-[6-amino-5-(methylsulfamoyl)pyridin-3-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (355) N-[(2S,4E)-5-(6-amino-5-methanesulfonamidopyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (356) N-[(2S,4E)-5-[6-(1H-1,3-benzodiazol-2-amido)-5-methanesulfonamidopyridin-3-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (357) N-[(2S,4E)-5-(6-amino-5-methanesulfonamidopyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (358) N-[(2S,4E)-5-(6-{3H-imidazo[4,5-b]pyridin-2-amido}-5-methanesulfonamidopyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (359) N-[(2S,4E)-5-(6-amino-5-methanesulfonylpyridin-3-yl)pent-4-en-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, and (360) N-[(2S,4E)-5-[6-amino-5-(ethanesulfonyl)pyridin-3-yl]pent-4-en-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide. Item 6. General formula (VII): [In the formula, represents a single bond or a double bond; L represents a divalent group obtained by removing two hydrogen atoms from ethane, ethylene, or acetylene, and when L is a divalent group obtained by removing two hydrogen atoms from ethane (ethylene group), one methylene group (-CH ２ -) may have a structure substituted with -O-; １ and Y ２ are each independently a carbon atom or a nitrogen atom; Ｙ１ ~R Ｙ３and each independently represent a hydrogen atom, a halogen atom, an amino group, an alkyl group having 1 or 2 carbon atoms which may be substituted with a halogen atom, or an alkoxy group having 1 or 2 carbon atoms, or a compound or a salt thereof. At least one compound selected from the group consisting of the following compounds (31), (37), (50), and (215) or a salt thereof: (31) N-[(2S,4E)-5-(2-amino-4-methoxypyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (37) N-[(2S,4E)-5-(6-amino-4-fluoropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (50) N-[(2S)-5-(6-aminopyridin-3-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, and (215) N-[(2S,4E)-5-(5-aminopyrazin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide. Item 8. An AURKB kinase inhibitor containing the compound or salt thereof according to any one of Items 1 to 7. Item 9. A pharmaceutical composition containing the compound or salt thereof according to any one of Items 1 to 7 as an active ingredient. Item 10. Item 8. A therapeutic agent for at least one disease selected from the group consisting of myelofibrosis, acute myeloid leukemia, B-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma, chronic myeloid leukemia, Hodgkin's lymphoma, Burkitt's lymphoma, multiple myeloma, thyroid cancer, non-small cell lung cancer, squamous cell carcinoma, colorectal cancer, breast cancer, gastric cancer, prostate cancer, cutaneous melanoma, neuroblastoma, bladder cancer, intrahepatic bile duct cancer, pancreatic ductal adenocarcinoma, hepatocellular carcinoma, uveal melanoma, retinoblastoma, osteoarthritis, diabetic nephropathy, neuropathic pain, and ocular neovascular disease, comprising the compound or salt thereof according to any one of Items 1 to 7.Item 11. Use of the compound or a salt thereof according to any one of Items 1 to 7 for the manufacture of a therapeutic agent for at least one disease selected from the group consisting of myelofibrosis, acute myeloid leukemia, B-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma, chronic myeloid leukemia, Hodgkin's lymphoma, Burkitt's lymphoma, multiple myeloma, thyroid cancer, non-small cell lung cancer, squamous cell carcinoma, colon cancer, breast cancer, gastric cancer, prostate cancer, cutaneous melanoma, neuroblastoma, bladder cancer, intrahepatic bile duct cancer, pancreatic ductal adenocarcinoma, hepatocellular carcinoma, uveal melanoma, retinoblastoma, osteoarthritis, diabetic nephropathy, neuropathic pain, and ocular neovascular disease. Item 12. The compound or a salt thereof according to any one of Items 1 to 7 for use as a pharmaceutical. Item 13. Item 13. The compound or salt thereof according to any one of Items 1 to 7 for use in the treatment of at least one disease selected from the group consisting of myelofibrosis, acute myeloid leukemia, B-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma, chronic myeloid leukemia, Hodgkin's lymphoma, Burkitt's lymphoma, multiple myeloma, thyroid cancer, non-small cell lung cancer, squamous cell carcinoma, colorectal cancer, breast cancer, gastric cancer, prostate cancer, cutaneous melanoma, neuroblastoma, bladder cancer, intrahepatic bile duct cancer, pancreatic ductal adenocarcinoma, hepatocellular carcinoma, uveal melanoma, retinoblastoma, osteoarthritis, diabetic nephropathy, neuropathic pain, and ocular neovascular disease. Item 14. The compound or salt thereof according to any one of Items 1 to 7 for use in the treatment of myelofibrosis. Item 15. Item 8. A method for treating at least one disease selected from the group consisting of myelofibrosis, acute myeloid leukemia, B-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma, chronic myeloid leukemia, Hodgkin's lymphoma, Burkitt's lymphoma, multiple myeloma, thyroid cancer, non-small cell lung cancer, squamous cell carcinoma, colorectal cancer, breast cancer, gastric cancer, prostate cancer, cutaneous melanoma, neuroblastoma, bladder cancer, intrahepatic bile duct cancer, pancreatic ductal adenocarcinoma, hepatocellular carcinoma, uveal melanoma, retinoblastoma, osteoarthritis, diabetic nephropathy, neuropathic pain, and ocular neovascular disease, comprising administering to a subject in need thereof a therapeutically effective amount of the compound or a salt thereof according to any one of Items 1 to 7.

[0015] The compound represented by general formula (I) may be a tautomer thereof. In the present disclosure, the term "tautomer" refers to a structural isomer that is reversibly interconvertible. Tautomers have the same molecular formula but a different bonding sequence of atoms, and under certain conditions, multiple tautomers may coexist in equilibrium. A compound represented by general formula (I) or a salt thereof included in the present disclosure may be simply referred to as a "compound of the present disclosure." In the present disclosure, "salt" refers to a pharmaceutically acceptable salt. The term "compound of the present disclosure" also encompasses solvates of the compound of the present disclosure. That is, in this specification, the term "compound of the present disclosure" encompasses the compound represented by general formula (I) and its tautomers, as well as salts thereof and solvates thereof. The compound of the present disclosure has AURKB kinase inhibitory activity, as shown in the test examples described below. Furthermore, since the compound of the present disclosure has AURKB kinase inhibitory activity, it may have antimitotic and antitumor effects.

[0016] Incidentally, AURKB is also involved in the regulation of megakaryocyte differentiation, and it has been reported that AURKB expression decreases during the differentiation and maturation process of megakaryocytes (Non-Patent Document 29) and that compounds with AURKB kinase inhibitory activity promote the multinucleation of megakaryocytes (Non-Patent Document 30). However, it was unclear whether AURKB kinase inhibitors are effective against myelofibrosis.

[0017] The present inventors have found that compounds of the present disclosure having AURKB kinase inhibitory activity may be effective against myelofibrosis, as shown in Test Example 3 below. Therefore, the compounds of the present disclosure can be suitably used for the treatment of myelofibrosis.

[0018] Furthermore, other diseases to which the compounds of the present disclosure can be applied include, for example, acute myeloid leukemia, B-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma, chronic myeloid leukemia, Hodgkin's lymphoma, Burkitt's lymphoma, multiple myeloma, thyroid cancer, non-small cell lung cancer, squamous cell carcinoma, colon cancer, breast cancer, gastric cancer, prostate cancer, cutaneous melanoma, neuroblastoma, bladder cancer, intrahepatic bile duct cancer, pancreatic ductal adenocarcinoma, hepatocellular carcinoma, uveal melanoma, retinoblastoma, osteoarthritis, diabetic nephropathy, neuropathic pain, and ocular neovascular disease.

[0019] Each embodiment included in the present disclosure will be described in further detail below.

[0020] In the present disclosure, examples of halogen atoms include fluorine atoms, chlorine atoms, bromine atoms, and iodine atoms.

[0021] The alkyl group may be linear or branched. Specific examples of the alkyl group include a methyl group, an ethyl group, an n-propyl group, an n-butyl group, an n-pentyl group, a 1-methylethyl group, a tert-butyl group, and a 2-methylbutyl group.

[0022] The alkoxy group may also be linear or branched. Specific examples of the alkoxy group include a methoxy group, an ethoxy group, an n-propoxy group, an n-butoxy group, an n-pentyloxy group, a 1-methylethoxy group, a tert-butoxy group, and a 2-methylbutoxy group.

[0023] Specific examples of the cycloalkyl group include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, etc. Specific examples of the cycloalkyl ring include a cyclopropyl ring, a cyclobutyl ring, a cyclopentyl ring, a cyclohexyl ring, etc.

[0024] Examples of heteroatoms contained in the heterocycle include an oxygen atom, a nitrogen atom, a sulfur atom, etc. The number of heteroatoms contained in the heterocycle may be, for example, 1, 2, 3, 4, or 5.

[0025] In the present disclosure, the term "aromatic ring" includes aromatic carbocycles and aromatic heterocycles.

[0026] In the above general formula (I), R １ and R ２ are each independently a hydrogen atom, a halogen atom, an optionally substituted alkyl group having 1 to 5 carbon atoms, or an optionally substituted phenyl group, and R ３ is a hydrogen atom or an optionally substituted alkyl group having 1 to 3 carbon atoms, or R １ and R ２ or R １ and R ３ together with the adjacent carbon atoms, form an optionally substituted 5- or 6-membered aromatic ring. １ and R ２ are each independently a hydrogen atom, a halogen atom, an alkyl group having 1 or 2 carbon atoms which may be substituted with a halogen atom, or a phenyl group, and R ３ is a hydrogen atom, a methyl group, or an ethyl group, or R １ and R ２ , or R １ and R ３ together with the adjacent carbon atoms, form a benzene ring or a 6-membered heterocycle containing at least one nitrogen atom in the ring, which may be substituted with at least one group selected from the group consisting of a halogen atom, an alkyl group having 1 or 2 carbon atoms, and an alkoxy group having 1 or 2 carbon atoms. １ and R ２ are each independently a hydrogen atom, a halogen atom, a methyl group, an ethyl group, an n-propyl group, a 1-methylethyl group, a trifluoromethyl group, or a phenyl group, and R ３ is a hydrogen atom, a methyl group, or an ethyl group, or R １ and R ２ , or R １ and R ３ together with the adjacent carbon atoms, form a benzene ring which may be substituted with at least one group selected from the group consisting of a halogen atom, a methyl group, and a methoxy group, or form a 6-membered heterocycle containing one nitrogen atom in the ring.

[0027] In the above general formula (I), R ４ is a hydrogen atom or an optionally substituted alkyl group having 1 to 5 carbon atoms, and R ７ and R ８ are each independently a hydrogen atom or an optionally substituted alkyl group having 1 to 3 carbon atoms, where R ４ and R ７ is R ４ The nitrogen atom adjacent to R ５ and R ６ the carbon atom adjacent to R ７ Together with the carbon atom adjacent to R, R may form an optionally substituted 5- or 6-membered heterocycloalkyl ring. ４ is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and R ７ and R ８ are each independently a hydrogen atom or an alkyl group having 1 or 2 carbon atoms, ４ and R ７ is R ４ The nitrogen atom adjacent to R ５ and R ６ the carbon atom adjacent to R ７ and the carbon atom adjacent to R may form a 5-membered heterocycloalkyl ring containing one nitrogen atom in the ring. ４ is a hydrogen atom, and R ７ and R ８ are each independently a hydrogen atom or a methyl group, or R ４ and R ７ But, R ４ The nitrogen atom adjacent to R ５ and R ６ the carbon atom adjacent to R ７ together with the carbon atom adjacent to R, form a 5-membered heterocycloalkyl ring containing one nitrogen atom, and R ８ is a hydrogen atom.

[0028] In the above general formula (I), R ５ and R ６are each independently a hydrogen atom, an optionally substituted alkyl group having 1 to 5 carbon atoms, or an optionally substituted phenyl group, wherein R ５ and R ６ may form an optionally substituted 3- to 6-membered cycloalkyl ring together with the adjacent carbon atom. ５ and R ６ are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or a phenyl group, where R ５ and R ６ may form a 3- or 4-membered cycloalkyl ring together with the adjacent carbon atom. ５ and R ６ are each independently a hydrogen atom, a methyl group, an ethyl group, or a 1-methylethyl group, or R ５ and R ６ together with the adjacent carbon atoms form a 3- or 4-membered cycloalkyl ring.

[0029] In the above general formula (I), L is a divalent group obtained by removing two hydrogen atoms from an alkane, alkene, or alkyne having 2 to 4 carbon atoms. When L is a divalent group obtained by removing two hydrogen atoms from an alkane having 2 to 4 carbon atoms (alkylene group), one or more methylene groups (-CH ２ Preferably, L is a divalent group obtained by removing two hydrogen atoms from ethane, ethylene, or acetylene, and when L is a divalent group obtained by removing two hydrogen atoms from ethane (ethylene group), one methylene group (-CH ２ -) may have a structure in which it is substituted with -NH- or -O-.

[0030] In the above general formula (I), Het is represented by general formula (II): [In the formula, represents a single bond or a double bond; X １ ~X ４ are each independently a carbon atom or a nitrogen atom; Ａ１ ~R Ａ４are each independently a hydrogen atom, a halogen atom, an amino group, or —NH—(CH ２ ) ｎ Ａ -O-CH ３ (n Ａ is a natural number from 1 to 4), a group represented by the following formula: (In the formula, R Ａ５ is an optionally substituted alkyl group having 1 to 3 carbon atoms), or a group represented by the following formula: (In the formula, R Ａ６ is an optionally substituted alkyl group having 1 to 3 carbon atoms) (wherein X ２ When R is a nitrogen atom Ａ１ does not exist, and X ３ When R is a nitrogen atom Ａ３ is absent)], or a group represented by general formula (III): [In the formula, represents a single bond or a double bond; R Ｂ１ , R Ｂ２ , and R Ｂ４ are each independently a hydrogen atom, a halogen atom, an amino group, an optionally substituted alkyl group having 1 to 3 carbon atoms, an optionally substituted alkoxy group having 1 to 3 carbon atoms, -NH-R Ｂ３ (R Ｂ３ represents an optionally substituted alkyl group having 1 to 3 carbon atoms, an optionally substituted cycloalkyl group having 3 to 6 carbon atoms, -(CH ２ ) ｎ Ｂ -O-CH ３ (n Ｂ is a natural number from 1 to 4), or an optionally substituted phenyl group), —O—R Ｂ５ (R Ｂ５ is an optionally substituted cycloalkyl group having 3 to 6 carbon atoms, or ═O, or R Ｂ１ and R Ｂ４ , or R Ｂ４ and R Ｂ２ form an optionally substituted 5- or 6-membered aromatic heterocycle together with the adjacent atoms, or a group represented by general formula (IV): [In the formula, represents a single bond or a double bond; X ５and X ６ are each independently a carbon atom or a nitrogen atom; Ｃ１ ~R Ｃ４ are each independently a hydrogen atom, a halogen atom, an amino group, a hydroxy group, a cyano group, an optionally substituted alkyl group having 1 to 3 carbon atoms, an optionally substituted alkoxy group having 1 to 3 carbon atoms, an optionally substituted cycloalkyl group having 3 to 6 carbon atoms, an optionally substituted 5- or 6-membered aromatic carbocyclic group, an optionally substituted 5- or 6-membered aromatic heterocyclic group, an optionally substituted 5- or 6-membered heterocycloalkyl group, -NH-R Ｃ８ , -SO ２ -R Ｃ１１ , —CO—NR Ｃ１４ R Ｃ１５ or =O, where R Ｃ８ represents an optionally substituted alkyl group having 1 to 3 carbon atoms, —SO ２ -R Ｃ９ , or -CO-R Ｃ１０ R Ｃ９ is an optionally substituted alkyl group having 1 to 3 carbon atoms, and R Ｃ１０ represents an optionally substituted alkyl group having 1 to 3 carbon atoms, an optionally substituted cycloalkyl group having 3 to 6 carbon atoms, or a group represented by the following formula: (In the formula, X １０ is a carbon atom or a nitrogen atom); Ｃ１１ represents an optionally substituted alkyl group having 1 to 3 carbon atoms, or —NR Ｃ１２ R Ｃ１３ and R Ｃ１２ and R Ｃ１３ are each independently a hydrogen atom or an optionally substituted alkyl group having 1 to 3 carbon atoms; R Ｃ１４ and R Ｃ１５ are each independently a hydrogen atom or an optionally substituted alkyl group having 1 to 3 carbon atoms, or R Ｃ１ and R Ｃ２ (At this time X ６ is a carbon atom), or R Ｃ２ and R Ｃ３together with the adjacent carbon atoms, form an optionally substituted 5- or 6-membered aromatic ring, an optionally substituted 5- or 6-membered cycloalkyl ring, or an optionally substituted 5- or 6-membered heterocycloalkyl ring (provided that X ５ When R is a nitrogen atom Ｃ１ does not exist, and X ５ When R is a nitrogen atom Ｃ４ is absent)], or a group represented by general formula (V): [In the formula, represents a single bond or a double bond; X ７ ~X ９ are each independently a carbon atom or a nitrogen atom; Ｄ１ and R Ｄ２ are each independently a hydrogen atom, a halogen atom, an amino group, an optionally substituted alkyl group having 1 to 3 carbon atoms, an optionally substituted alkoxy group having 1 to 3 carbon atoms, or an optionally substituted phenyl group, or R Ｄ１ and R Ｄ２ is X ７ and X ８ and together with each other, form an optionally substituted 5- or 6-membered cycloalkyl ring, an optionally substituted 5- or 6-membered heterocycloalkyl ring, or an optionally substituted 5- or 6-membered aromatic heterocyclic ring], or a group represented by general formula (VI): [In the formula, R Ｅ are each independently a halogen atom, an amino group, an optionally substituted alkyl group having 1 to 3 carbon atoms, or an optionally substituted alkoxy group having 1 to 3 carbon atoms, and p is 0 to 4, or a group represented by general formula (VIII): [In the formula, represents a single bond or a double bond; X １１ ~X １３ are each independently a carbon atom or a nitrogen atom; Ｆ１ ~R Ｆ５ are each independently a hydrogen atom, a halogen atom, an amino group, an optionally substituted alkyl group having 1 to 3 carbon atoms, or an optionally substituted alkoxy group having 1 to 3 carbon atoms, or R Ｆ２ and RＦ３ is X １２ and X １３ together with the aryl group, form an optionally substituted 5- or 6-membered heterocycloalkyl ring, or an optionally substituted 5- or 6-membered aromatic heterocyclic ring.

[0031] When Het is a group represented by the above general formula (II), it is preferably R Ａ１ ~R Ａ４ are each independently a hydrogen atom, a halogen atom, an amino group, or —NH—(CH ２ ) ２ -O-CH ３ a group represented by the following formula: (In the formula, R Ａ５ is an alkyl group having 1 or 2 carbon atoms), or a group represented by the following formula: (In the formula, R Ａ６ is a group represented by an alkyl group having 1 or 2 carbon atoms (wherein X ２ When R is a nitrogen atom Ａ１ does not exist, and X ３ When R is a nitrogen atom Ａ３ is not present). More preferably, R Ａ１ ~R Ａ４ are each independently a hydrogen atom, a halogen atom, an amino group, or —NH—(CH ２ ) ２ -O-CH ３ a group represented by the following formula: or a group represented by the following formula: It is a group represented by the following formula:

[0032] The group represented by the above general formula (II) is preferably represented by the following formula: (R Ａ１ ~R Ａ４ and the formula (I) is as described above.

[0033] In the general formula (I), when Het is a group represented by the general formula (III), preferably, R Ｂ１ , R Ｂ２、 , and R Ｂ４are each independently a hydrogen atom, an amino group, an alkyl group having 1 to 3 carbon atoms which may be substituted with a halogen atom, an alkoxy group having 1 or 2 carbon atoms which may be substituted, -NH-R Ｂ３ (R Ｂ３ represents an alkyl group having 1 or 2 carbon atoms, a cycloalkyl group having 3 to 5 carbon atoms, -(CH ２ ) ｎ Ｂ -O-CH ３ (n Ｂ is a natural number from 1 to 3), or a halogen atom or the following formula: a phenyl group optionally substituted with a group represented by the formula: Ｂ５ (R Ｂ５ is a cycloalkyl group having 3 to 5 carbon atoms), or ═O, or R Ｂ１ and R Ｂ４ , or R Ｂ４ and R Ｂ２ together with the adjacent atoms form a 5-membered aromatic heterocycle.

[0034] In the general formula (I), when Het is a group represented by the general formula (IV), it is preferably R Ｃ１ ~R Ｃ３ are each independently a hydrogen atom, a halogen atom, an amino group, a hydroxy group, a cyano group, an alkoxy group having 1 to 3 carbon atoms which may be substituted with a halogen atom, a cycloalkyl group having 3 to 5 carbon atoms, a phenyl group, a 6-membered aromatic heterocyclic group having one nitrogen atom in the ring, or a 5-membered heterocycloalkyl group having one nitrogen atom in the ring, -NH-R Ｃ８ , -SO ２ -R Ｃ１１ , —CO—NR Ｃ１４ R Ｃ１５ or =O, where R Ｃ８ is an alkyl group having 1 or 2 carbon atoms, -SO ２ -R Ｃ９ , or -CO-R Ｃ１０ is a group represented by R Ｃ９ is an alkyl group having 1 or 2 carbon atoms, and R Ｃ１０ is a cycloalkyl group having 3 to 5 carbon atoms, or a group represented by the following formula: (In the formula, X １０is a carbon atom or a nitrogen atom); Ｃ１１ represents an optionally substituted alkyl group having 1 to 3 carbon atoms, or —NR Ｃ１２ R Ｃ１３ and R Ｃ１２ and R Ｃ１３ are each independently a hydrogen atom or an alkyl group having 1 or 2 carbon atoms; R Ｃ１４ and R Ｃ１５ are each independently a hydrogen atom or an alkyl group having 1 or 2 carbon atoms, or R Ｃ１ and R Ｃ２ (At this time X ６ is a carbon atom), or R Ｃ２ and R Ｃ３ together with each adjacent carbon atom, form an optionally substituted 5- or 6-membered aromatic ring, an optionally substituted 5- or 6-membered cycloalkyl ring, or an optionally substituted 5- or 6-membered heterocycloalkyl ring; R Ｃ４ is a hydrogen atom, a halogen atom, or an amino group (provided that X ５ When R is a nitrogen atom Ｃ１ does not exist, and X ５ When R is a nitrogen atom Ｃ４ is not present). More preferably, R Ｃ１ ~R Ｃ３ are each independently a hydrogen atom, a halogen atom, an amino group, a methoxy group, an ethoxy group, a trifluoromethoxy group, a phenyl group, a 6-membered aromatic heterocyclic group having one nitrogen atom in the ring, or a 5-membered heterocycloalkyl group having one nitrogen atom in the ring, or constitute a ring as described above; R Ｃ４ is a hydrogen atom, a halogen atom, or an amino group.

[0035] The group represented by the above general formula (IV) is preferably a group represented by the following formula: (R Ｃ１ ~R Ｃ４ and the formula (I) is as described above.

[0036] Furthermore, a preferred embodiment of the group represented by the general formula (IV) is a group represented by the following formula: a group represented by the following formula: (In the formula, RＣ５ is a hydrogen atom or a halogen atom), a group represented by the following formula: (In the formula, R Ｃ６ and R Ｃ７ are each independently a hydrogen atom, a halogen atom, or an alkyl group having 1 or 2 carbon atoms), and a group represented by the following formula: Examples of the group include a group represented by the following formula:

[0037] When Het is a group represented by the above general formula (V), it is preferably a group represented by the following formula: (In the formula, R Ｄ１ is a hydrogen atom or an alkoxy group having 1 or 2 carbon atoms), or a group represented by the following formula: or a group represented by the following formula: or a group represented by the following formula: (In the formula, R Ｄ１ and R Ｄ２ are each independently a hydrogen atom or an alkyl group having 1 or 2 carbon atoms), or a group represented by the following formula: (In the formula, R Ｄ１ and R Ｄ２ are each independently a hydrogen atom or an alkyl group having 1 or 2 carbon atoms), or a group represented by the following formula: (In the formula, R Ｄ１ and R Ｄ２ are each independently a hydrogen atom, a halogen atom, or an amino group), or a group represented by the following formula: or a group represented by the following formula: or a group represented by the following formula: (In the formula, R Ｄ３ is a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or —CH ２ -R Ｄ４ (R Ｄ４ is a cycloalkyl group having 3 to 5 carbon atoms), or is a group represented by the following formula: or a group represented by the following formula: or a group represented by the following formula: It is a group represented by the following formula:

[0038] When Het is a group represented by the above general formula (V), it is preferably a group represented by the following formula: It is a group represented by the following formula:

[0039] A preferred embodiment of the compound represented by the general formula (I) or a salt thereof is a compound represented by the general formula (VII): [In the formula, represents a single bond or a double bond; L represents a divalent group obtained by removing two hydrogen atoms from ethane, ethylene, or acetylene, and when L is a divalent group obtained by removing two hydrogen atoms from ethane (ethylene group), one methylene group (-CH ２ -) may have a structure substituted with -O-; １ and Y ２ are each independently a carbon atom or a nitrogen atom; Ｙ１ ~R Ｙ３ and each independently represent a hydrogen atom, a halogen atom, an amino group, an alkyl group having 1 or 2 carbon atoms which may be substituted with a halogen atom, or an alkoxy group having 1 or 2 carbon atoms, or a compound or a salt thereof.

[0040] A more preferred embodiment of the compound represented by the general formula (I) or a salt thereof is a compound represented by the general formula (VII'): [In the formula, L is a divalent group obtained by removing two hydrogen atoms from ethane, ethylene, or acetylene, and when L is a divalent group obtained by removing two hydrogen atoms from ethane (ethylene group), one methylene group (—CH ２ -) may have a structure substituted with -O-; Y is a carbon atom or a nitrogen atom; R Ｙ is a hydrogen atom, a halogen atom, or an alkoxy group having 1 or 2 carbon atoms], or a salt thereof.

[0041] A preferred embodiment of the compound represented by the general formula (I) or a salt thereof includes at least one compound or a salt thereof selected from the group consisting of the following compounds (1) to (360): (1) 4,5-dibromo-N-{4-[6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-3-yl]but-3-yn-1-yl}-1H-imidazole-2-carboxamide, (2) 4,5-dibromo-N-(4-{8-[(1-methyl-1H-pyrazol-4-yl)amino]imidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)-1H-imidazole-2-carboxamide, (3) N-(4-{8-aminoimidazo[1,2-a]pyridin-3-yl}-2-methylbut-3-yn-1-yl)-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (4) N-(5-{8-aminoimidazo[1,2-a]pyridin-3-yl}-2-methylpent-4-yn-2-yl)-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (5) N-(4-{imidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (6) N-(4-{8-amino-6-bromoimidazo[1,2-a]pyrazin-3-yl}but-3-yn-1-yl)-5,6-difluoro-1H-1,3-benzodiazole-2-carboxamide, (7) N-(4-{8-[(2-methoxyethyl)amino]imidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (8) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (9) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclobutyl]-6-chloro-1H-1,3-benzodiazole-2-carboxamide, (10) N-(4-{2-[(3-fluorophenyl)amino]pyrimidin-5-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (11) 6,7-difluoro-N-(4-{imidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (12) N-[4-(2-{[3-(4-methylpiperazin-1-yl)phenyl]amino}pyrimidin-5-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (13) N-(4-{8-aminoimidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1-methyl-1H-1,3-benzodiazole-2-carboxamide, (14) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-4,7-dichloro-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (15) N-(4-{8-aminoimidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-N-ethyl-7-methyl-1H-1,3-benzodiazole-2-carboxamide, (16) N-(4-{8-amino-5-chloroimidazo[1,2-a]pyrazin-3-yl}but-3-yn-1-yl)-7-methoxy-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (17) N-(4-{[3,3'-bipyridin]-5-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (18) N-(4-{8-amino-5-chloro-2-methylimidazo[1,2-a]pyrazin-3-yl}but-3-yn-1-yl)-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (19) N-[4-(6-amino-5-bromopyridazin-3-yl)but-3-yn-1-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (20) 7-chloro-N-(4-{2H,3H,4H-pyrido[3,2-b][1,4]oxazin-7-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (21) N-(4-{pyrazolo[3,2-b][1,3]thiazol-7-yl}but-3-yn-1-yl)-1H-1,3-Benzodiazole-2-carboxamide, (22) N-[(3E)-4-(6-amino-5-chloropyridin-3-yl)but-3-en-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (23) 5-{2-[1-(1H-1,3-benzodiazole-2-carbonyl)pyrrolidin-3-yl]ethynyl}-3-bromopyridin-2-amine, (24) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-5-phenyl-1H-imidazole-2-carboxamide, (25) N-[(1R)-4-(6-amino-5-chloropyridin-3-yl)-1-phenylbut-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (26) N-[(2S)-5-(2-amino-4-methoxypyrimidin-5-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (27) N-[4-(8-fluoroisoquinolin-4-yl)but-3-yn-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (28) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-5-ethyl-1H-imidazole-2-carboxamide, (29) N-[(2S,4E)-5-{2-[(4-fluorophenyl)amino]pyrimidin-5-yl}pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (30) N-[(3E)-4-(2-amino-4-methoxypyrimidin-5-yl)but-3-en-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (31) N-[(2S,4E)-5-(2-amino-4-methoxypyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (32) N-[(2S)-5-[2,4-bis(methylamino)pyrimidin-5-yl]pent-4-yn-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (33) N-(4-{6-chloro-1H-pyrazolo[3,4-b]pyridin-5-yl}but-3-yn-1-yl)-1H-1,3-Benzodiazole-2-carboxamide, (34) 7-chloro-N-[4-(4-phenylpyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (35) N-[(2S)-5-(5-amino-4-ethoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (36) N-[(2S,4E)-5-{3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl}pent-4-en-2-yl]-5-(trifluoromethyl)-1H-imidazole-2-carboxamide, (37) N-[(2S,4E)-5-(6-amino-4-fluoropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (38) N-[(2S,4E)-5-(5-methoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (39) N-[(2S,4E)-5-(6-aminopyrazin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (40) N-[(2S)-5-{5H,6H,7H-pyrrolo[1,2-a]imidazol-3-yl}pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (41) N-[(2S)-5-[6-amino-5-(trifluoromethoxy)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (42) N-[(2S,4E)-5-(2-amino-5-fluoropyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (43) N-[(2S)-5-(5,6,7,8-tetrahydroisoquinolin-4-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (44) N-[(2S,4E)-5-[5-(pyrrolidin-1-yl)pyridin-3-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (45) N-[(2S,(4E)-5-(4-methoxy-1H-pyrazol-5-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (46) N-[(2S,4E)-5-(6-aminopyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (47) N-[(2S,4E)-5-{4H,5H,6H,7H-pyrazolo[1,5-a]pyridin-3-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (48) N-[(3S,5E)-6-(2-amino-4-methoxypyrimidin-5-yl)hex-5-en-3-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (49) N-[(3R,5E)-6-(5-methoxypyridin-3-yl)-2-methylhex-5-en-3-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (50) N-[(2S)-5-(6-aminopyridin-3-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (51) N-[(2S)-5-(6-amino-4,5-dimethoxypyridin-3-yl)pent-4-yn-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (52) N-[(2S,4Z)-5-(2-amino-4-methoxypyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (53) N-[(2S)-4-[(5-fluoropyridin-3-yl)amino]butan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (54) N-[(2S)-4-[(2-aminopyrimidin-5-yl)oxy]butan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (55) N-[(2S)-1-[(5-chloropyridin-3-yl)methoxy]propan-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (56) N-(4-{8-aminoimidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)-4,5-dibromo-1-methyl-1H-imidazole-2-carboxamide, (57) 4,5-dibromo-N-{4-[5-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-3-yl]but-3-yn-1-yl}-1H-imidazole-2-carboxamide, (58) N-(4-{8-[(1-methyl-1H-pyrazol-4-yl)amino]imidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (59) N-(4-{8-aminoimidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)-1-bromoimidazo[1,5-a]pyridine-3-carboxamide, (60) N-(4-{8-aminoimidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)-6-methyl-1H-1,3-benzodiazole-2-carboxamide, (61) N-(4-{8-aminoimidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)-6-fluoro-1H-1,3-benzodiazole-2-carboxamide, (62) N-(4-{8-amino-6-chloroimidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (63) N-(4-{8-aminoimidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (64) N-(4-{8-amino-7-chloroimidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (65) N-(4-{8-amino-6,7-dichloroimidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (66) 7-fluoro-N-(4-{imidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (67) 7-chloro-N-(4-{2-[(2-fluorophenyl)amino]pyrimidin-5-yl}but-3-yn-1-yl)-1H-1,3-Benzodiazole-2-carboxamide, (68) 7-chloro-N-(4-{2-[(4-fluorophenyl)amino]pyrimidin-5-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (69) 4,5-dibromo-N-{4-[7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]but-3-yn-1-yl}-1H-imidazole-2-carboxamide, (70) 7-chloro-N-[4-(2-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrimidin-5-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (71) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-bromo-1H-1,3-benzodiazole-2-carboxamide, (72) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-methoxy-1H-1,3-benzodiazole-2-carboxamide, (73) N-[1-(3-{8-amino-7-chloroimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-1H-1,3-benzodiazole-2-carboxamide, (74) N-[1-(3-{8-amino-7-chloroimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (75) N-[1-(3-{8-amino-7-chloroimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-methyl-1H-1,3-benzodiazole-2-carboxamide, (76) N-[1-(3-{8-amino-7-chloroimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-methoxy-1H-1,3-benzodiazole-2-carboxamide, (77) N-(5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl)-1H-1,3-Benzodiazole-2-carboxamide, (78) N-(5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl)-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (79) N-(5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl)-3H-imidazo[4,5-b]pyridine-2-carboxamide, (80) N-[1-(3-{8-amino-7-chloroimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (81) N-(5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl)-7-(trifluoromethoxy)-1H-1,3-benzodiazole-2-carboxamide, (82) N-(5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl)-7-methyl-1H-1,3-benzodiazole-2-carboxamide, (83) N-(5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl)-7-methoxy-1H-1,3-benzodiazole-2-carboxamide, (84) N-[(2R)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (85) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (86) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (87) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-ethoxy-1H-1,3-benzodiazole-2-carboxamide, (88) N-[1-(3-{8-amino-7-chloroimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-ethoxy-1H-1,3-Benzodiazole-2-carboxamide, (89) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-6-chloro-7-methoxy-1H-1,3-benzodiazole-2-carboxamide, (90) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-6-fluoro-7-methyl-1H-1,3-benzodiazole-2-carboxamide, (91) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-6-chloro-7-methyl-1H-1,3-benzodiazole-2-carboxamide, (92) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-6,7-dichloro-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (93) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-5,7-dichloro-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (94) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-5,6-dichloro-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (95) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-7-methoxy-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (96) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-7-chloro-1-methyl-1H-1,3-benzodiazole-2-carboxamide, (97) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-6-chloro-1-methyl-1H-1,3-benzodiazole-2-carboxamide, (98) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-5-chloro-1-methyl-1H-1,3-Benzodiazole-2-carboxamide, (99) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-4-chloro-1-methyl-1H-1,3-benzodiazole-2-carboxamide, (100) 7-chloro-N-(4-{imidazo[1,2-a]pyrazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (101) N-(4-{8-amino-7-bromoimidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-7-methoxy-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (102) N-(4-{8-aminoimidazo[1,2-a]pyrazin-3-yl}but-3-yn-1-yl)-7-chloro-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (103) N-[1-(3-{8-aminoimidazo[1,2-a]pyrazin-6-yl}prop-2-yn-1-yl)cyclopropyl]-1H-1,3-benzodiazole-2-carboxamide, (104) N-[1-(3-{8-amino-7-bromoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-methoxy-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (105) N-[4-(5-bromopyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (106) N-[4-(6-amino-5-phenylpyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (107) N-(4-{8-amino-2-methylimidazo[1,2-a]pyrazin-3-yl}but-3-yn-1-yl)-7-chloro-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (108) N-[4-(6-amino-5-bromo-4-methoxypyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (109) N-[4-(6-aminopyridazin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (110) N-[(2S)-5-(6-amino-5-bromopyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (111) N-{1-[3-(6-amino-5-bromopyridin-3-yl)prop-2-yn-1-yl]cyclopropyl}-1H-1,3-benzodiazole-2-carboxamide, (112) N-[4-(6-amino-5-bromopyridin-3-yl)but-3-yn-1-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (113) N-[(2S)-5-(6-amino-5-chloropyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (114) N-[4-(6-amino-5-chloropyridin-3-yl)but-3-yn-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (115) N-{4-[6-amino-5-(trifluoromethyl)pyridin-3-yl]but-3-yn-1-yl}-3H-imidazo[4,5-b]pyridine-2-carboxamide, (116) N-(4-{1H-pyrrolo[2,3-c]pyridin-4-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (117) N-[4-(5-amino-6-chloropyrazin-2-yl)but-3-yn-1-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (118) N-(4-{pyrazolo[1,5-a]pyridin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (119) N-[4-(1-phenyl-1H-pyrazol-4-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (120) N-[4-(5-cyclopropylpyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (121) N-[(2S,4E)-5-(6-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (122) N-[(2S,(4E)-5-(6-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (123) N-[(2S,4E)-5-(6-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-6-chloro-1H-1,3-benzodiazole-2-carboxamide, (124) N-[(2R,4E)-5-(6-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (125) N-[(2R,4E)-5-(6-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (126) N-[(3R)-6-(6-amino-5-chloropyridin-3-yl)hex-5-yn-3-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (127) N-[(3S)-6-(6-amino-5-chloropyridin-3-yl)hex-5-yn-3-yl]-1H-1,3-benzodiazole-2-carboxamide, (128) N-[(3S)-6-(6-amino-5-chloropyridin-3-yl)hex-5-yn-3-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (129) N-[(3E)-4-(6-amino-5-chloropyridin-3-yl)but-3-en-1-yl]-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (130) 7-chloro-N-[1-(3-{1H-pyrrolo[2,3-b]pyridin-5-yl}prop-2-yn-1-yl)cyclopropyl]-1H-1,3-benzodiazole-2-carboxamide, (131) 7-chloro-N-(4-{3-methyl-3H-imidazo[4,5-b]pyridin-6-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (132) 7-chloro-N-{4-[2-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-6-yl]but-3-yn-1-yl}-1H-1,3-benzodiazole-2-carboxamide, (133) N-(5-{8-aminoimidazo[1,(2-b)pyridazin-3-yl}pent-4-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (134) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (135) N-[(3S)-6-{8-aminoimidazo[1,2-b]pyridazin-3-yl}hex-5-yn-3-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (136) 7-chloro-N-(4-{5H-pyrrolo[2,3-b]pyrazin-2-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (137) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-5-bromo-1H-imidazole-2-carboxamide, (138) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-4,5-dichloro-1H-imidazole-2-carboxamide, (139) 7-chloro-N-(4-{3H-[1,2,3]triazolo[4,5-b]pyridin-6-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (140) N-(4-{3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl}but-3-yn-1-yl)-3H-imidazo[4,5-b]pyridine-2-carboxamide, (141) N-[4-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (142) N-[(3R)-6-{8-aminoimidazo[1,2-b]pyridazin-3-yl}-2-methylhex-5-yn-3-yl]-7-methoxy-1H-1,3-benzodiazole-2-carboxamide, (143) 7-chloro-N-[4-(5-methanesulfonamidopyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (144) N-[(2S)-5-(2-amino-4-methoxypyrimidin-5-yl)pent-4-yn-2-yl]-7-chloro-1H-1,3-Benzodiazole-2-carboxamide, (145) N-[(2S)-5-(2-amino-4-ethoxypyrimidin-5-yl)pent-4-yn-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (146) N-[(2S)-5-(2-amino-4-ethoxypyrimidin-5-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (147) N-[4-(isoquinolin-4-yl)but-3-yn-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (148) N-[4-(1-aminoisoquinolin-4-yl)but-3-yn-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (149) 7-chloro-N-{4-[2-(methylamino)pyrimidin-5-yl]but-3-yn-1-yl}-1H-1,3-benzodiazole-2-carboxamide, (150) 7-chloro-N-{4-[2-(ethylamino)pyrimidin-5-yl]but-3-yn-1-yl}-1H-1,3-benzodiazole-2-carboxamide, (151) 7-chloro-N-{4-[2-(cyclopropylamino)pyrimidin-5-yl]but-3-yn-1-yl}-1H-1,3-benzodiazole-2-carboxamide, (152) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-5-methyl-1H-imidazole-2-carboxamide, (153) N-[(2S,4E)-5-{2-[(4-fluorophenyl)amino]pyrimidin-5-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (154) N-[(3E)-4-{2-[(4-fluorophenyl)amino]pyrimidin-5-yl}but-3-en-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (155) 7-chloro-N-(4-{2-methyl-2H-pyrazolo[3,4-c]pyridin-4-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (156) 7-chloro-N-(4-{1-methyl-1H-pyrazolo[3,4-c]pyridin-4-yl}but-3-yn-1-yl)-1H-1,3-Benzodiazole-2-carboxamide, (157) 7-chloro-N-(4-{1H-pyrazolo[3,4-c]pyridin-4-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (158) N-[4-(5-bromo-6-cyclopropaneamidopyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (159) N-[(2S)-5-{3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (160) 7-chloro-N-[(2S)-5-{3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (161) N-[(2S)-5-{3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl}pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (162) N-[(2S)-5-[5-(methylamino)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (163) N-[4-(6-amino-4,5-dichloropyridin-3-yl)but-3-yn-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (164) N-[(2S)-5-(6-amino-4,5-dichloropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (165) N-[(2S)-5-(6-amino-4,5-dichloropyridin-3-yl)pent-4-yn-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (166) N-(4-{6-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (167) 7-chloro-N-(4-{2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (168) N-(4-{2-methyl-1H-pyrrolo[2,(3-b)pyridin-5-yl}but-3-yn-1-yl)-3H-imidazo[4,5-b]pyridine-2-carboxamide, (169) N-[(2S)-5-(6-amino-5-chloro-4-methylpyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (170) N-[(2S)-5-(6-amino-5-chloro-4-methoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (171) N-[(2S)-5-(6-amino-5-chloro-4-methylpyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (172) N-[(2S)-5-(5-amino-4-chloropyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (173) N-[(2S)-5-(5-amino-4-methoxypyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (174) N-[(2S)-5-(5-amino-4-chloropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (175) N-[(2S)-5-(5-amino-4-methoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (176) N-[4-(5-amino-4-hydroxypyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (177) N-[(2S,4E)-5-(6-amino-4,5-dichloropyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (178) N-[(2S,4E)-5-(6-amino-4,5-dichloropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (179) N-[(2S)-5-{4-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (180) N-[(2S,4E)-5-[4-methoxy-2-(methylamino)pyrimidin-5-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (181) N-{4-[4-(trifluoromethyl)pyridin-3-yl]but-3-yn-1-yl}-3H-imidazo[4,5-b]pyridine-2-carboxamide, (182) N-[4-(4-chloropyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (183) N-[(2S,4E)-5-(6-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (184) N-[(2S,4E)-5-(2-amino-4-methylpyrimidin-5-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (185) N-[(2S,4E)-5-(2-amino-4-methylpyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (186) N-[(2S,4E)-5-(2-amino-1-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)pent-4-en-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (187) N-[(2S)-5-(6-amino-5-fluoropyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (188) N-[(2S)-5-(6-amino-5-fluoropyridin-3-yl)pent-4-yn-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (189) N-[(2S)-5-(6-amino-5-fluoropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (190) N-[(2S,4E)-5-(6-amino-5-fluoropyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (191) N-[(2S,4E)-5-(6-amino-5-fluoropyridin-3-yl)pent-4-en-2-yl]-7-chloro-1H-1,3-Benzodiazole-2-carboxamide, (192) N-[(2S,4E)-5-(6-amino-5-fluoropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (193) N-[(2S,4E)-5-(2-amino-4-ethylpyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (194) N-[(2S)-5-[6-amino-4-(trifluoromethyl)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (195) N-[(2S,4E)-5-(6-amino-4-chloro-5-methoxypyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (196) N-[(2S)-5-(6-amino-4-chloro-5-methoxypyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (197) N-[(2S,4E)-5-(6-amino-4-chloro-5-methoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (198) N-[(2S)-5-(6-amino-4-chloro-5-methoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (199) N-[(2S)-5-(5-amino-6-methylpyridin-3-yl)pent-4-yn-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (200) N-[(2S,4E)-5-(5-amino-4-methoxypyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (201) N-[(2S,4E)-5-(5-amino-4-methoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (202) N-[(2S,4E)-5-(5-amino-4-ethoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (203) N-[(2S,4E)-5-(6-amino-5-methylpyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (204) N-[(2S,4E)-5-[6-amino-5-(trifluoromethyl)pyridin-3-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (205) N-[(2S,4E)-5-(6-amino-5-methoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (206) N-[(2S,4E)-5-(5-aminopyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (207) N-[(2S,4E)-5-(5-aminopyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (208) N-[(2S)-5-{3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl}pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (209) N-[(2S,4E)-5-{1H-pyrazolo[3,4-b]pyridin-5-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (210) N-[(2S,4E)-5-{3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (211) N-[(2S)-5-[5-amino-4-(methylamino)pyridin-3-yl]pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (212) N-[(2S)-5-[2-amino-4-(trifluoromethyl)pyrimidin-5-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (213) N-[(2S)-5-(4,5,6,7-tetrahydro-1H-indazol-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (214) N-[(2S,4E)-5-(5-aminopyrazin-2-yl)pent-4-en-2-yl]-1H-1,3-Benzodiazole-2-carboxamide, (215) N-[(2S,4E)-5-(5-aminopyrazin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (216) N-[(2S,4E)-5-(5-amino-6-methoxypyrazin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (217) N-[(2S,4E)-5-(5-amino-6-methylpyrazin-2-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (218) N-[(2S,4E)-5-(5-amino-6-methylpyrazin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (219) N-[(2S)-5-{5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (220) N-[(2S)-5-(2-methyl-1H-imidazol-4-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (221) N-[(2S,4E)-5-(5-fluoropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (222) N-[(2S,4E)-5-(6-methylpyrazin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (223) N-[(2S,4E)-5-(2-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (224) N-[(2S,4E)-5-(4-methoxypyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (225) N-[(2S,4E)-5-(2-amino-4-cyclopropoxypyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,(226) N-[(2S)-5-[6-amino-5-(trifluoromethoxy)pyridin-3-yl]pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (227) N-[(2S,4E)-5-(4-amino-6-methoxypyrimidin-5-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (228) N-[(2S,4E)-5-(4-amino-6-methoxypyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (229) N-[(2S)-5-{7-acetyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (230) N-[(2S,4E)-5-(5-methanesulfonylpyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (231) N-[(2S,4E)-5-(4-fluoropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (232) N-[(2S,4E)-5-{imidazo[1,2-b]pyridazin-3-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (233) N-[(2S,4E)-5-{pyrazolo[1,5-a]pyrimidin-3-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (234) N-[(2S,4E)-5-(1H-indazol-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (235) N-[(2S,4E)-5-(1H-indazol-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (236) N-[(2S)-5-(5-aminopyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (237) N-[(2S,4E)-5-[5-(morpholin-4-yl)pyridin-3-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (238) N-[(2S,4E)-5-[6-amino-5-(trifluoromethoxy)pyridin-3-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (239) N-[(2S,4E)-5-(6-aminopyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (240) N-[(2S,4E)-5-(2-aminopyrimidin-5-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (241) N-[(2S,4E)-5-(2-aminopyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (242) N-[(2S)-5-(4-chloro-5-fluoropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (243) N-[(2S)-5-(5-fluoro-4-methylpyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (244) N-[(2S,4E)-5-(5-chloropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (245) N-[(2S)-5-{7-methyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (246) N-[(2S,4E)-5-(5-cyano-4-methylpyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (247) N-[(2S,4E)-5-(6-amino-5-cyanopyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (248) N-[(2S,4E)-5-(5-carbamoylpyridin-3-yl)pent-4-en-2-yl]-1H-1,3-Benzodiazole-2-carboxamide, (249) N-[(2S,4E)-5-(5-cyanopyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (250) N-[(2S,4E)-5-(pyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (251) N-[(2S,4E)-5-(pyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (252) N-[(2S)-5-{5-[(4-methylpiperazin-1-yl)methyl]pyridin-3-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (253) N-[(2S)-5-{5-[(4-methyl-3-oxopiperazin-1-yl)methyl]pyridin-3-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (254) N-[(2S,4E)-5-[2-(ethylamino)-4-methoxypyrimidin-5-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (255) N-[(2S,4E)-5-[2-(cyclopropylamino)-4-methoxypyrimidin-5-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (256) N-[(2S,4E)-5-{4-methoxy-2-[(2-methoxyethyl)amino]pyrimidin-5-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (257) N-[(2S,4E)-5-(4,5,6,7-tetrahydro-1H-indazol-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (258) N-[(2S,4E)-5-{5H,6H,7H,8H-imidazo[1,2-a]pyridin-3-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (259) N-[(2S,4E)-5-(3-aminopyrazin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,(260) N-[(2S,4E)-5-(3-amino-1H-pyrazol-5-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (261) N-[(2S,4E)-5-(3-amino-4-chloro-1H-pyrazol-5-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (262) N-[(2S,4E)-5-(3-amino-4-chloro-1H-pyrazol-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (263) N-[(2S,4E)-5-(6-amino-4-methylpyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (264) N-[(2S,4E)-5-(6-amino-4-chloropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (265) N-[(2S,4E)-5-[4-amino-2-(methylamino)pyrimidin-5-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (266) N-[(2S,4E)-5-[2-amino-4-(methylamino)pyrimidin-5-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (267) N-[(2S,4E)-5-[2-amino-4-(ethylamino)pyrimidin-5-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (268) N-[(2S,4E)-5-(5-methyl-1H-pyrazol-4-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (269) N-{1-[(2E)-3-(2-amino-4-methoxypyrimidin-5-yl)prop-2-en-1-yl]cyclobutyl}-3H-imidazo[4,5-b]pyridine-2-carboxamide, (270) N-[(2S,4E)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (271) N-[(2S,4E)-5-(5-ethoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (272) N-{1-[(2E)-3-(5-methoxypyridin-3-yl)prop-2-en-1-yl]cyclopropyl}-1H-1,3-benzodiazole-2-carboxamide, (273) N-[(2S,4E)-5-(5-methoxypyridin-3-yl)pent-4-en-2-yl]-7-(trifluoromethyl)-1H-1,3-benzodiazole-2-carboxamide, (274) 7-cyano-N-[(2S,4E)-5-(5-methoxypyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (275) N-[(2S)-5-(6-amino-4-fluoropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (276) N-[(2S)-5-(6-amino-4-chloropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (277) N-[(2S,4E)-5-(2-amino-4-methoxypyrimidin-5-yl)pent-4-en-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (278) N-[(2S,4E)-5-(6-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (279) N-[(2S,4E)-5-(5-amino-6-methoxypyrazin-2-yl)pent-4-en-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (280) N-[(2S)-5-(2-amino-4-methoxypyrimidin-5-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (281) N-[(2S)-5-{7-ethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl}pent-4-yn-2-yl]-1H-1,3-Benzodiazole-2-carboxamide, (282) N-[(2S)-5-[5-(difluoromethoxy)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (283) N-[(2S)-5-(5-methoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (284) N-[(2S)-5-(6-amino-5-chloropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (285) N-[(2S)-5-(6-amino-5-bromopyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (286) N-[(2S)-5-(5-amino-6-methoxypyrazin-2-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (287) N-[(2S)-5-(6-amino-5-fluoropyridin-3-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (288) N-[(2S)-5-(6-amino-5-fluoropyridin-3-yl)pentan-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (289) N-[(2S)-5-[7-(cyclopropylmethyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (290) N-[(2S)-5-(6-amino-4-bromopyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (291) N-[(2S)-5-(6-amino-4-bromopyridin-3-yl)pent-4-yn-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (292) N-[(2S)-5-(6-amino-4-chloropyridin-3-yl)pent-4-yn-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (293) N-[(2S,4E)-5-(6-amino-4,(294) N-[(2S,4E)-5-(6-amino-5-chloro-4-fluoropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (295) N-[(2S,4E)-5-(6-amino-4,5-dimethoxypyridin-3-yl)pent-4-en-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (296) N-[(2S)-5-(6-amino-4,5-dimethoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (297) N-[(2S)-5-(6-amino-4-fluoropyridin-3-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (298) N-[(2S)-5-(5-amino-6-cyanopyrazin-2-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (299) N-[(2S,4E)-5-(6-amino-4-fluoro-5-methoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (300) N-[(2S)-5-(5-cyano-4-methylpyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (301) N-[(2S,4E)-5-(6-amino-4-fluoro-5-methylpyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (302) N-[(2S)-5-(6-amino-4-fluoro-5-methylpyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (303) N-[(2S)-5-(6-amino-4-fluoro-5-methoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (304) N-[(2S)-5-(2-amino-5,6-difluoropyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-Benzodiazole-2-carboxamide, (305) N-[(2S)-5-(6-amino-5-methylpyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (306) N-[(2S)-5-(6-amino-5-methylpyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (307) N-[(2S)-5-[5-(trifluoromethyl)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (308) N-[(2S)-5-[6-amino-5-(trifluoromethyl)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (309) N-[(2S)-5-(6-amino-5-methoxypyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (310) N-[(2S)-5-(6-amino-5-methoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (311) N-[(2S)-5-(6-amino-5-methoxypyridin-3-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (312) N-[(2S)-5-(6-amino-5-methylpyridin-3-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (313) N-[(2S)-5-(6-amino-5-methylpyridin-3-yl)pentan-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (314) N-[(2S)-5-[6-amino-5-(trifluoromethyl)pyridin-3-yl]pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (315) N-[(2S)-5-[6-amino-5-(trifluoromethyl)pyridin-3-yl]pentan-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (316) N-[(2S)-5-[6-amino-5-(trifluoromethoxy)pyridin-3-yl]pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (317) N-[(2S,4E)-5-(6-amino-4,5-difluoropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (318) N-[(2S)-5-(6-amino-4,5-difluoropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (319) N-[(2S,4E)-5-[6-amino-5-(hydroxymethyl)pyridin-3-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (320) N-[(2S,4E)-5-[6-amino-5-(hydroxymethyl)pyridin-3-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (321) N-[(2S,4E)-5-[6-amino-4-(hydroxymethyl)pyridin-3-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (322) N-[(2S,4E)-5-[6-amino-5-(difluoromethoxy)pyridin-3-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (323) N-[(2S,4E)-5-[6-amino-5-(difluoromethyl)pyridin-3-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (324) N-[(2S)-5-[6-amino-5-(difluoromethoxy)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (325) N-[(2S)-5-[6-amino-5-(difluoromethyl)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (326) N-[(2S)-5-(2-aminopyrimidin-5-yl)pentan-2-yl]-1H-1,3-Benzodiazole-2-carboxamide, (327) N-[(2S)-5-(2-aminopyrimidin-5-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (328) N-[(2S)-5-(2-aminopyrimidin-5-yl)pentan-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (329) N-[(2S)-5-(5-aminopyrazin-2-yl)pentan-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (330) N-[(2S)-5-(5-amino-6-methylpyrazin-2-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (331) N-[(2S)-5-(5-amino-6-methylpyrazin-2-yl)pentan-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (332) N-[(2S)-5-(6-amino-4-methoxypyridin-3-yl)pentan-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (333) N-[(2S,4E)-5-(4-methoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (334) N-[(2S,4E)-5-(pyridin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (335) N-[(2S)-4-[(6-amino-5-chloropyridin-3-yl)oxy]butan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (336) N-[(2S)-4-[(6-amino-5-chloropyridin-3-yl)oxy]butan-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (337) N-[(2S,4E)-5-(2-amino-4-methoxypyrimidin-5-yl)pent-4-en-2-yl]-4-chloro-3H-imidazo[4,5-c]pyridine-2-carboxamide, (338) N-[(2S,4E)-5-{pyrazolo[1,5-a]pyrimidin-6-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (339) N-[(2S,4E)-5-{imidazo[1,5-a]pyrimidin-3-yl}pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (340) N-[(2S,4E)-5-{1H-pyrazolo[3,4-b]pyrazin-5-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (341) N-[(2S,4E)-5-(2-amino-6-oxo-1,6-dihydropyrimidin-5-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (342) N-[(2S,4E)-5-(5-amino-6-oxo-1,6-dihydropyrazin-2-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (343) N-[(2R)-5-(6-amino-4-fluoropyridin-3-yl)-1,1,1-trifluoropent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (344) N-[(2S,4E)-5-{pyrrolo[1,2-a]pyrimidin-3-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (345) N-[(2S,4E)-5-{imidazo[1,2-b]pyridazin-7-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (346) N-[(2R,4E)-5-(6-amino-4-fluoropyridin-3-yl)-1,1,1-trifluoropent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (347) N-[5-(6-amino-5-chloropyridin-3-yl)(1,1,1-, ２ H ３ ) pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (348) N-[(4E)-5-(2-amino-4-methoxypyrimidin-5-yl)(1,1,1- ２ H ３ ) pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (349) N-[(4E)-5-(6-amino-4-fluoropyridin-3-yl)(1,1,1- ２ H３ ) pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (350) N-[(4E)-5-(5-methoxypyridin-3-yl)(1,1,1- ２ H ３ ) pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (351) N-[5-(5-methoxypyridin-3-yl)(1,1,1- ２ H ３) pentan-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (352) N-[(2S,4E)-5-[6-amino-5-(dimethylcarbamoyl)pyridin-3-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (353) N-[(2S,4E)-5-[6-amino-5-(dimethylsulfamoyl)pyridin-3-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (354) N-[(2S,4E)-5-[6-amino-5-(methylsulfamoyl)pyridin-3-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (355) N-[(2S,4E)-5-(6-amino-5-methanesulfonamidopyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (356) N-[(2S,4E)-5-[6-(1H-1,3-benzodiazol-2-amido)-5-methanesulfonamidopyridin-3-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (357) N-[(2S,4E)-5-(6-amino-5-methanesulfonamidopyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (358) N-[(2S,4E)-5-(6-{3H-imidazo[4,5-b]pyridin-2-amido}-5-methanesulfonamidopyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (359) N-[(2S,4E)-5-(6-amino-5-methanesulfonylpyridin-3-yl)pent-4-en-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, and (360) N-[(2S,4E)-5-[6-amino-5-(ethanesulfonyl)pyridin-3-yl]pent-4-en-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide.

[0042] A more preferred embodiment of the compound represented by the general formula (I) or a salt thereof is at least one compound selected from the group consisting of the compounds (31), (37), (50), and (215) or a salt thereof.

[0043] The compound of the present disclosure can be used as a therapeutic agent for the various diseases described above in mammals such as humans, mice, rats, rabbits, dogs, cats, cows, horses, pigs, and monkeys, either as such or by mixing with a pharmaceutically acceptable carrier or the like to prepare a pharmaceutical composition containing, for example, 0.001% by weight to 99.5% by weight, preferably 0.1% by weight to 90% by weight.

[0044] The carrier may be one or more selected from the group consisting of solid, semi-solid, or liquid diluents, fillers, and other formulation auxiliaries. The pharmaceutical composition according to the present disclosure is preferably administered in a dosage unit form. The pharmaceutical composition may be administered intratissue, orally, intravenously, topically (transdermally, by ophthalmic administration, intraperitoneally, intrapleurally, etc.), or rectally. The dosage form of the pharmaceutical composition may be adjusted appropriately depending on the administration method.

[0045] The pharmaceutical dose is desirably adjusted taking into consideration the patient's condition, such as age, body weight, type and severity of disease, the route of administration, the type of compound of the present disclosure, whether or not it is a salt, and the type of salt, but typically, in the case of oral administration to an adult, the amount of the active ingredient of the compound of the present disclosure is in the range of 0.01 mg to 5 g per adult, preferably 1 mg to 500 mg per adult, per day. In some cases, a lower dose may be sufficient, or conversely, a higher dose may be required. Typically, the compound is administered once a day or in divided doses, or in the case of intravenous administration, it can be administered as a bolus or continuously for up to 24 hours.

[0046] One or more atoms constituting the compound of the present disclosure may be substituted with an isotope of the atom. That is, the term "compound of the present disclosure" also includes any isotope-labeled compound (preferably a radioisotope-labeled compound) of the compound represented by general formula (I) or a salt thereof. Examples of isotopes include, for example, ２ H. ３ H.１１ C. １３ C. １４ C. １５ N. １８ O. １７ O. ３１ P. ３２ P. ３５ S. １８ F. １２３ I and ３６ Examples include Cl.

[0047] The compounds of the present disclosure can be produced from known compounds or intermediates that can be easily synthesized from known compounds, for example, by the methods described herein or in accordance with known methods.

[0048] The compound represented by general formula (I) can be used as a pharmaceutical directly, or can be used in the form of a pharmaceutically acceptable salt, solvate, or solvate of a salt by known methods. Examples of pharmaceutically acceptable salts include salts of inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, and phosphoric acid; salts of organic acids such as acetic acid, malic acid, lactic acid, citric acid, tartaric acid, maleic acid, succinic acid, fumaric acid, p-toluenesulfonic acid, benzenesulfonic acid, and methanesulfonic acid; salts of alkali metals such as lithium, potassium, and sodium; salts of alkaline earth metals such as magnesium and calcium; and salts of inorganic bases such as ammonium salts. These salts can be formed by commonly used methods.

[0049] For example, when the compound of the present disclosure is a hydrochloride salt, it can be obtained by dissolving the compound represented by general formula (I) in an alcohol solution of hydrogen chloride, an ethyl acetate solution of hydrogen chloride, a 1,4-dioxane solution of hydrogen chloride, a cyclopentyl methyl ether solution of hydrogen chloride, or a diethyl ether solution of hydrogen chloride.

[0050] When the compound of the present disclosure is a solvate, the solvate may be a solvate with an organic solvent or a hydrate.Specific solvates include, for example, alcohol solvates such as methanol solvates and ethanol solvates, and ethyl acetate solvates.Hydrates include, for example, monohydrates and dihydrates.When forming a solvate, the compound may be coordinated with any type and number of solvents.

[0051] When the compound represented by general formula (I) has an asymmetric carbon, all stereoisomers of the compound and mixtures thereof are encompassed by the compounds of the present disclosure. When the compounds of the present disclosure are used as pharmaceuticals, it is particularly preferable that the compounds of the present disclosure consist of only a single stereoisomer. For example, a single stereoisomer can be separated from a mixture of stereoisomers by optical resolution using an optically active acid (such as tartaric acid, dibenzoyltartaric acid, mandelic acid, or 10-camphorsulfonic acid). Furthermore, compounds of the present disclosure consisting of only a single stereoisomer can also be produced by using a single stereoisomer as a starting material. Alternatively, the compounds can be produced by optical resolution using a chiral column or asymmetric synthesis.

[0052] As mentioned above, the compounds represented by general formula (I) in the present disclosure may be tautomers thereof. For example, R ３ When is a hydrogen atom, the compound represented by general formula (I) may be the following tautomer:

[0053] When the solvents, reagents, and raw materials used in each step in the following production methods are commercially available, the commercially available products can be used as they are. Furthermore, the compounds obtained in each step in the following production methods and the raw materials used may form salts, and can be converted into other types of salts or free forms by known methods. When the compounds obtained in each step in the following production methods and the raw materials used are in free forms, they can be converted into the desired salts by known methods. Examples of such salts include the same salts as those used for the compounds of the present disclosure described above.

[0054] In the production of the compounds of the present disclosure, when the raw materials have substituents that may affect the reaction, protecting groups may be introduced into these substituents in advance by known methods. When a protecting group is introduced into the substituent of the raw material, the target compound can be obtained by removing the protecting group as necessary after the reaction. Examples of such protecting groups include those described in "Greene's Protective Groups in Organic Synthesis" by Wuts and Greene, 4th Edition; John Wiley & Sons Inc., 2006; or "Protecting Groups" by P.J. Kocienski, 3rd Edition; Thieme, 2005. Protecting groups can be appropriately selected and used depending on the properties of the raw materials and the reaction conditions.

[0055] The compounds obtained in each step of the following production methods can be isolated or purified in accordance with conventional methods, such as solvent extraction, concentration, distillation, sublimation, recrystallization, reprecipitation, and chromatography, or can be used in the next step in the form of a reaction mixture or a crude product.

[0056] Unless otherwise specified, the reactions in each step in the following production methods are carried out according to known methods, for example, those described in "Comprehensive Organic Transformations: A Guide to Functional Group Preparations 2nd Edition" by R.C. Larock, John Wiley & Sons Inc. The present invention can be carried out by appropriately modifying or combining the methods described in, for example, "Experimental Chemistry Lectures" edited by the Chemical Society of Japan, 4th edition, Maruzen, 1992; "Organic Synthesis Strategies Learned from Named Reactions" by L. Kuerti and B. Czako, translated and supervised by Kiyoshi Tomioka, Kagaku Dojin, 2006; "Latest Organic Synthesis Methods: Design and Strategy" by G. S. Zweifel and M. H. Nantz, translated by Tamejiro Hiyama, Kagaku Dojin, 2009, or the methods described herein. More specific methods for producing the compounds of the present disclosure are described below.

[0057] (Production Method 1) (1) Production method when L is an alkyne having 2 to 4 carbon atoms (In the formula, R １ , R ２ , R ３ , R ４ , R ５ , R ６ , R ７ , R ８ , Het has the same meaning as above. n represents 0, 1, or 2. PG １ is a protecting group, such as a t-butoxycarbonyl group (Boc group) or a benzyloxycarbonyl group (Cbz group). X represents a leaving group, such as an iodine group, a bromine group, a chloro group, or a mesylate (OMs: CH ３ SO ３ -), triflate (OTf:CF ３ SO ３ -) and others)

[0058] Step 1: This step involves reacting compound 1a, which is commercially available or can be prepared by a known method, with compound 2a, which is commercially available or can be prepared by a known method, in an appropriate solvent in the presence of a transition metal catalyst such as palladium, a copper catalyst, and a base at 0°C to 100°C, preferably 20°C to 100°C, for 0.1 to 24 hours, preferably 1 to 12 hours, to obtain compound 3a. This step is known as the Sonogashira coupling reaction, and compound 3a can be obtained by applying a method described in the literature (Sonogashira et al., J. Organomet. Chem. 2002, 653, 46-49.; Negishi et al., Chem. Rev., 2003, 103, 1979-2017.).

[0059] Examples of solvents used in this step include hydrocarbons such as toluene and xylene, ethers such as 1,4-dioxane, THF, and 1,2-dimethoxyethane (also referred to as "DME"), amides such as DMF, dimethylacetamide (also referred to as "DMA"), and NMP, and DMSO. Two or more of these solvents can also be mixed and used. The reaction can also be carried out using the following organic bases as solvents.

[0060] The palladium catalyst used in this step is, for example, tris(dibenzylideneacetone)bispalladium chloroform adduct (hereinafter referred to as "Pd ２ (dba) ３ CHCl ３ "), tris(dibenzylideneacetone)bispalladium (hereinafter referred to as "Pd ２ (dba) ３ "), tetrakistriphenylphosphine palladium (hereinafter referred to as "Pd(PPh ３ ) ４ "), [1,1'-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) dichloromethane adduct (hereinafter referred to as "Pd(dppf)Cl ２ ・CH ２ Cl ２ "), bis(triphenylphosphine)palladium(II) dichloride (hereinafter referred to as "PdCl ２ (PPh ３ ) ２ "), [1,1'-bis(di-tert-butylphosphino)ferrocene]-dichloropalladium(II) (hereinafter referred to as "Pd(dtbpf)Cl ２ "), bis(tricyclohexylphosphine)palladium(II) dichloride (hereinafter referred to as "PdCl ２ (PCy ３ ) ２ "), palladium(II) acetate (hereinafter referred to as "Pd(OAc) ２ ") are some examples.

[0061] Examples of the base used in this step include organic bases such as triethylamine (hereinafter referred to as "TEA"), diisopropylethylamine (hereinafter referred to as "DIPEA"), diethylamine, diisopropylamine, and piperidine, and inorganic bases such as potassium carbonate, cesium carbonate, sodium carbonate, sodium bicarbonate, sodium acetate, potassium acetate, trisodium phosphate, and tripotassium phosphate.

[0062] Step 2 This step is to remove the protecting group PG of compound 3a. １to obtain Compound 4a, which can be performed with reference to, for example, Wuts and Greene, "Greene's Protective Groups in Organic Synthesis," 4th Edition, John Wiley & Sons Inc., 2006, or P.J. Kocienski, "Protecting Groups," 3rd Edition, Thieme, 2005.

[0063] Step 3: This step is a step of obtaining compound IA by reacting compound 4a with compound 5, which is commercially available or can be prepared by a known method, in an appropriate solvent in the presence of a condensing agent and a base at 0°C to 100°C, preferably 20°C to 100°C, for 0.1 to 24 hours, preferably 1 to 12 hours.

[0064] Examples of the solvent used in this step include hydrocarbons such as toluene and xylene, ethers such as 1,4-dioxane, THF, and DME, amides such as DMF and DMA, halogenated hydrocarbons such as dichloromethane and chloroform, nitriles such as acetonitrile and propionitrile, and mixed solvents thereof.

[0065] Examples of the condensing agent used in this step include 1,1'-carbonyldiimidazole (hereinafter referred to as "CDI"), 1H-benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (hereinafter referred to as "BOP"), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (also referred to as "EDCI"), diisopropylcarbodiimide (also referred to as "DIC"), diethyl cyanophosphonate, O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (hereinafter referred to as "HBTU"), and O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (hereinafter referred to as "HATU").

[0066] Examples of the base used in this step include organic bases such as TEA, DIPEA, N,N-dimethylaniline, and diazabicycloundecene (also referred to as "DBU").

[0067] In this step, the reaction can be carried out by adding an additive, if necessary. Examples of the additive to be used include 1-hydroxybenzotriazole (hereinafter referred to as "HOBt"), N-hydroxysuccinimide, and 1-hydroxy-7-azabenzotriazole (hereinafter referred to as "HOAt").

[0068] (Production Method 2) (1) Production method when L is an alkene having 2 to 4 carbon atoms (In the formula, R １ , R ２ , R ３ , R ４ , R ５ , R ６ , R ７ , R ８ , P.G. １ , Het, X, and n are as defined above. Ａ , and R Ｂ represents a hydroxy group, or R Ａ and R Ｂ Together, they form -O-C(CH ３ ) ２ -C(CH ３ ) ２ -O-, -O-(CH ２ ) ３ —O— or —O—CH ２ -C(CH ３ ) ２ -CH ２ -O-.)

[0069] Step 1: In this step, compound 1a, which is commercially available or can be prepared by a known method, is hydroborated with boron compound 6a or 6b to obtain compound 7. This reaction can be carried out in a solvent such as THF, diethyl ether, dichloromethane, dichloroethane, hexane, cyclohexane, or toluene, with compound 1 and compound 6a or 6b at 0°C to 200°C, preferably 20°C to 100°C, for 0.1 to 24 hours, preferably 1 to 12 hours, to obtain compound 7. If necessary, a catalyst such as zirconium, rhodium, or ruthenium, or a base such as TEA or sodium t-butoxide may be added to the reaction.

[0070] Step 2: This step is a step of obtaining compound 3b by reacting compound 7 with compound 2a, which is commercially available or can be prepared by a known method, in an appropriate solvent in the presence of a transition metal catalyst such as palladium and a base at 0°C to 100°C, preferably 20°C to 100°C, for 0.1 to 24 hours, preferably 1 to 12 hours. This step is known as the Suzuki coupling reaction, and compound 3b can be obtained by applying a method described in the literature (Suzuki et al., Chem. Rev., 1995, 95, 2457-2483).

[0071] Examples of solvents used in this step include hydrocarbons such as toluene and xylene, ethers such as 1,4-dioxane, THF, and DME, amides such as DMF, DMA, and NMP, alcohols such as ethanol, 2-propanol, and tert-butanol, and water. Two or more of these solvents can also be used in combination. Examples of palladium catalysts used in this step include those listed in Step 1 of Production Method 1 above. Examples of bases used in this step include inorganic bases such as potassium carbonate, cesium carbonate, sodium carbonate, sodium bicarbonate, sodium acetate, potassium acetate, trisodium phosphate, and tripotassium phosphate.

[0072] In this step, an appropriate ligand may be used as needed. Examples of the ligand that can be used include 1,1'-bis(diphenylphosphino)ferrocene (hereinafter referred to as "dppf"), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (hereinafter referred to as "Xantphos"), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (hereinafter referred to as "XPhos"), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (hereinafter referred to as "BINAP"), 2-dicyclohexylphosphino-2',6'-diisopropylbiphenyl (hereinafter referred to as "RuPhos"), triphenylphosphine (hereinafter referred to as "PPh"). ３ "), tricyclohexylphosphine (hereinafter referred to as "PCy ３ ") are some examples.

[0073] Step 3: This step is the PG of compound 3b. １ Compound 4b can be obtained by the same method as in step 2 of Production Method 1 above.

[0074] Step 4 This step is a step for obtaining compound I-B from compound 4b and compound 5, which is commercially available or can be prepared by a known method. Compound IC can be obtained by the same method as in step 3 of Production Method 1 above.

[0075] (Production Method 3) (1) Production method when L is an alkane having 2 to 4 carbon atoms (In the formula, R １ , R ２ , R ３ , R ４ , R ５ , R ６ , R ７ , R ８ , P.G. １ , Het, and n are as defined above.)

[0076] Step 1 This step is a step of reacting compound 3a or 3b in a suitable solvent in the presence of a metal catalyst such as palladium and a hydrogen source under a hydrogen pressure of 1 to 20 atmospheres at 0°C to 100°C, preferably 20°C to 100°C, for 0.1 to 24 hours, preferably 1 to 12 hours, to obtain compound 3c.

[0077] The metal catalyst used in this step is not limited as long as it is a metal catalyst commonly used in the reduction of unsaturated carbon bonds, and examples thereof include heterogeneous catalysts such as palladium-carbon, palladium black, palladium chloride, palladium hydroxide, rhodium-carbon, platinum oxide, platinum black, platinum-palladium, Raney nickel, and palladium-carbon ethylenediamine complex. Examples of the hydrogen source used in this step include hydrogen gas and ammonium formate. The solvent used in this step is not particularly limited as long as it is not involved in the reaction, and examples thereof include hydrocarbons such as toluene and xylene, ethers such as 1,4-dioxane, THF, and DME, amides such as DMF, DMA, and NMP, alcohols such as ethanol, 2-propanol, and tert-butanol, water, and mixed solvents thereof.

[0078] Step 2 This step is the PG of compound 3c １ Compound 4c can be obtained by the same method as in step 2 of Production Method 1 above.

[0079] Step 3 This step is a step for obtaining compound IC from compound 4c and compound 5, which is commercially available or can be prepared by a known method. Compound IC can be obtained by the same method as in step 3 of Production Method 1 above.

[0080] (Production Method 4) One or more methylene groups (—CH ２ -) is replaced by -O- (In the formula, R １ , R ２ , R ３ , R ４ , R ５ , R ６ , R ７ , R ８ , P.G. １ , Het has the same meaning as above. m represents 0, 1, 2, or 3.

[0081] Step 1: This step is a step of obtaining ether compound 3d by reacting compound 1b, which can be prepared by a known method, with compound 2b, which is commercially available or can be prepared by a known method, in an appropriate solvent in the presence of an azodicarboxylic acid ester reagent and a phosphine reagent at 0°C to 100°C, preferably 20°C to 100°C, for 0.1 to 24 hours, preferably 1 to 12 hours. This step is known as the Mitsunobu reaction, and compound 3d can be obtained by applying a method described in the literature (Mitsunobu, O. Synthesis 1981, 1).

[0082] Examples of the azodicarboxylate reagent used in this step include diethyl azodicarboxylate (hereinafter referred to as "DEAD"), diisopropyl azodicarboxylate (hereinafter referred to as "DIAD"), and bis(2-methoxyethyl)azodicarboxylate (hereinafter referred to as "DMEAD"). Examples of the phosphine reagent used in this step include PPh ３ The solvent used in this step is not particularly limited as long as it is inert to the reaction, and examples thereof include hydrocarbons such as toluene and xylene, ethers such as 1,4-dioxane, THF and DME, and mixed solvents thereof.

[0083] Step 2: This step is the PG of compound 3d. １ Compound 4d can be obtained by the same method as in step 2 of Production Method 1 above.

[0084] Step 3 This step is a step for obtaining compound ID from compound 4d and compound 5, which is commercially available or can be prepared by a known method. Compound ID can be obtained by the same method as in step 3 of Production Method 1 above.

[0085] (Production Method 5) One or more methylene groups (—CH ２ -) is replaced by -O- (In the formula, R １ , R ２ , R ３ , R ４ , R ５ , R６ , R ７ , R ８ , P.G. １ , Het, X, and n are as defined above.

[0086] Step 1 This step is a step of reacting compound 1c, which can be prepared by a known method, with compound 2c, which is commercially available or can be prepared by a known method, in an appropriate solvent in the presence of a base at 0°C to 200°C, preferably 20°C to 100°C, for 0.1 to 24 hours, preferably 1 to 12 hours, to obtain ether compound 3e.

[0087] Examples of the base used in this step include sodium hydride, potassium hydride, potassium carbonate, etc. The solvent used in this step is not particularly limited as long as it is inert to the reaction, and examples thereof include DMF, DMA, and acetonitrile.

[0088] Step 2 This step is the PG of compound 3e １ Compound 4e can be obtained by the same method as in step 2 of Production Method 1 above.

[0089] Step 3 This step is a step for obtaining compound IE from compound 4e and compound 5, which is commercially available or can be prepared by a known method. Compound IE can be obtained by the same method as in step 3 of Production Method 1 above.

[0090] (Production Method 6) One or more methylene groups (—CH ２ -) is replaced by -N- (In the formula, R １ , R ２ , R ３ , R ４ , R ５ , R ６ , R ７ , R ８ , P.G. １ , Het, and n are as defined above.)

[0091] Step 1 This step is a step of reacting compound 2d, which can be prepared by a known method, with compound 1d, which can be prepared by a known method, in an appropriate solvent in the presence of a reducing agent at 0°C to 200°C, preferably 20°C to 100°C, for 0.1 to 24 hours, preferably 1 to 12 hours, to obtain amino compound 3f, and can be carried out in accordance with a known method for reductive amination reaction.

[0092] Examples of reducing agents used in this step include sodium triacetoxyborohydride and sodium cyanoborohydride. The solvent used in this step is not particularly limited as long as it is inert to the reaction, and examples include hydrocarbons such as toluene and xylene, ethers such as 1,4-dioxane, THF, and DME, halogenated hydrocarbons such as dichloromethane, and mixed solvents thereof. In this step, an acid or a suitable Lewis acid may be used as needed. Examples of acids that can be used in the reaction include acetic acid, and examples of Lewis acids that can be used include tetraisopropyl orthotitanate.

[0093] Step 2 This step is the PG of compound 3f １ Compound 4f can be obtained by the same method as in step 2 of Production Method 1 above.

[0094] Step 3 This step is a step for obtaining compound IF from compound 4f and compound 5, which is commercially available or can be prepared by a known method. Compound IF can be obtained by the same method as in step 3 of Production Method 1 above.

[0095] The present disclosure will be described in more detail below with reference to examples, but the present disclosure is not limited thereto. In the following examples, "%" used in the context of concentration refers to "w / v %" unless otherwise specified.

[0096] In the following examples, the following abbreviations are used: Pd-C: palladium-carbon Pd-Fib: palladium-fibroin Pd-PEI: palladium-polyethyleneimine Pd ２ (dba) ３: Tris(dibenzylideneacetone)dipalladium(0) Pd(PPh ３ ) ４ : tetrakis(triphenylphosphine)palladium(0) PdCl ２ (PPh ３ ) ２ : Bis(triphenylphosphine)palladium(II) dichloride Pd(dppf)Cl ２ ・CH ２ Cl ２ : [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane adduct Boc ２ O: di-tert-butyl dicarbonate BOP: 1H-benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate HATU: O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate DMAP: 4-dimethylaminopyridine DIPEA: N,N-diisopropylethylamine TEA: triethylamine NCS: N-chlorosuccinimide NBS: N-bromosuccinimide NIS: N-iodosuccinimide THF: tetrahydrofuran DME: 1,2-dimethoxyethane DMF: dimethylformamide DMSO: dimethyl sulfoxide NMP: 1-methyl-2-pyrrolidone MS: mass spectrometry LCMS: high-performance liquid chromatography mass spectrometry ESI: electron impact ionization (electron spray) Ionization) M: Molar concentration (mol / L)

[0097] MS was measured by LCMS. ESI was used as the ionization method. The observed mass spectrometry values ​​are expressed as m / z.

[0098] The LCMS measurement conditions were as follows: Analytical instrument: ACQUITY UPLC MS / PDA system (Waters Corporation) Mass spectrometer: ACQUITY QDa detector Photodiode array detector: ACQUITY PDA detector (UV detection wavelength: 210 to 400 nm) Column: Acquity BEH C18, 1.7 μm, 2.1 × 50 mm Flow rate: 0.5 mL / min Column temperature: 40°C Solvent: Solution A: 0.1 v / v % formic acid / H ２ O Solution B: 0.1 v / v% formic acid / acetonitrile

[0099] １ H NMR spectra were measured using a JNM-ECS400 nuclear magnetic resonance spectrometer (manufactured by JEOL RESONANCE Co., Ltd.) or a JNM-ECZL400 nuclear magnetic resonance spectrometer (manufactured by JEOL Ltd.). The observed peaks are expressed as chemical shift values ​​δ (ppm) (s = singlet, d = doublet, t = triplet, q = quartet, brs = broad singlet, m = multiplet, dd = double doublet, dt = double triplet).

[0100] For microwave experiments, an Initiator+ (Biotage) was used, which can achieve temperatures between 40-300°C and pressures up to 30 bar.

[0101] Specific optical rotation [α] ５８９ The measurement conditions are as follows: Analytical equipment: Automatic polarimeter SEPA-500 (manufactured by Horiba Ltd.) Optical path length: 50 mm

[0102] The compound names in this specification were determined using naming software that complies with IUPAC rules, JChem for Excel (version 21.15.202, ChemAxon), or ChemBioDraw (version 19.1, Cambridge Soft), or were determined according to the IUPAC nomenclature.

[0103] The r and s (lower case) in the compound names indicate the stereochemistry of the pseudo-asymmetric carbon atom according to IUPAC rules.

[0104] Reference Example 1 4,5-Dibromo-1H-imidazole-2-carboxylic acid​ [Step 1] Preparation of methyl 4,5-dibromo-1H-imidazole-2-carboxylate A solution of bromine (2.72 g) in acetic acid (15 mL) was slowly added to a solution of methyl 1H-imidazole-2-carboxylate (1.00 g) in acetic acid (15 mL), and the mixture was stirred at room temperature over the weekend. The reaction mixture was neutralized with 10% aqueous sodium carbonate solution and extracted with ethyl acetate. The organic layer was washed with 20% aqueous sodium hydrogen thiosulfate solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (1.78 g). MS (ESI+) m / z 384.9 (M+H) ＋ [Step 2] Preparation of 4,5-dibromo-1H-imidazole-2-carboxylic acid To a mixed solution of methyl 4,5-dibromo-1H-imidazole-2-carboxylate (100 mg) in THF (1 mL) and methanol (1 mL), 1M aqueous sodium hydroxide solution (1.1 mL) was added, and the mixture was stirred at 50°C for 5 hours and at room temperature overnight. The reaction solution was neutralized with 1M hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound (92 mg). MS (ESI+) m / z 270.9 (M+H) ＋

[0105] Reference Example 2 7-chloro-1H-1,3-benzodiazole-2-carboxylic acid [Step 1] Preparation of 7-chloro-2-(trichloromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.14 mL) was added to a solution of 3-chlorobenzene-1,2-diamine (150 mg) in acetic acid (1.5 mL), and the mixture was stirred at room temperature for 12 hours. The reaction solution was diluted with water, and the resulting precipitate was collected by filtration, washed with water, and dried under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain a crude residue. The resulting residue was recrystallized from ethyl acetate to obtain the title compound (201 mg). MS (ESI+) m / z 270.7 (M+H) ＋[Step 2] Preparation of 7-chloro-1H-1,3-benzodiazole-2-carboxylic acid 2M aqueous sodium hydroxide solution (0.93 mL) was added to a solution of 7-chloro-2-(trichloromethyl)-1H-1,3-benzodiazole (100 mg) in THF (1 mL), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid, diluted with water, and the resulting precipitate was collected by filtration. The resulting residue was washed with water and dried under reduced pressure to give the title compound (74 mg). MS (ESI+) m / z 196.9 (M+H) ＋

[0106] Reference Example 3 6-chloro-1H-1,3-benzodiazole-2-carboxylic acid [Step 1] Preparation of 6-chloro-2-(trichloromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.14 mL) was added to a solution of 4-chlorobenzene-1,2-diamine (150 mg) in acetic acid (1.5 mL), and the mixture was stirred at room temperature for 12 hours. The reaction solution was diluted with water, and the resulting precipitate was collected by filtration, washed with water, and dried under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain a crude residue. The resulting residue was washed with a mixed solvent of n-hexane and ethyl acetate to obtain the title compound (182 mg). MS (ESI+) m / z 270.7 (M+H) ＋ [Step 2] Preparation of 6-chloro-1H-1,3-benzodiazole-2-carboxylic acid 2M aqueous sodium hydroxide solution (0.93 mL) was added to a solution of 6-chloro-2-(trichloromethyl)-1H-1,3-benzodiazole (100 mg) in THF (1 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid, diluted with water, and the resulting precipitate was collected by filtration. The resulting residue was washed with water and dried under reduced pressure to give the title compound (67 mg). MS (ESI+) m / z 196.9 (M+H) ＋

[0107] Reference Example 4 7-methyl-1H-1,3-benzodiazole-2-carboxylic acid [Step 1] Preparation of 7-methyl-2-(trichloromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.16 mL) was added to a solution of 3-methylbenzene-1,2-diamine (150 mg) in acetic acid (1.5 mL), and the mixture was stirred at room temperature for 12 hours. The reaction solution was diluted with water, and the resulting precipitate was collected by filtration, washed with water, and dried under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain a crude residue. The resulting residue was washed with a mixed solvent of n-hexane and diethyl ether to obtain the title compound (151 mg). MS (ESI+) m / z 250.8 (M+H) ＋ [Step 2] Preparation of 7-methyl-1H-1,3-benzodiazole-2-carboxylic acid 2M aqueous sodium hydroxide solution (1.0 mL) was added to a solution of 7-methyl-2-(trichloromethyl)-1H-1,3-benzodiazole (100 mg) in THF (1 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid, diluted with water, and the resulting precipitate was collected by filtration. The resulting residue was washed with water and dried under reduced pressure to give the title compound (66 mg). MS (ESI+) m / z 176.9 (M+H) ＋

[0108] Reference Example 5 6-methyl-1H-1,3-benzodiazole-2-carboxylic acid [Step 1] Preparation of 6-methyl-2-(trichloromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.16 mL) was added to a solution of 4-methylbenzene-1,2-diamine (150 mg) in acetic acid (1.5 mL), and the mixture was stirred at room temperature for 12 hours. The reaction solution was diluted with water, and the precipitate was collected by filtration, washed with water, and dried under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain a crude residue. The resulting residue was washed with a mixed solvent of n-hexane and diethyl ether to obtain the title compound (97 mg). MS (ESI+) m / z 250.8 (M+H) ＋[Step 2] Preparation of 6-methyl-1H-1,3-benzodiazole-2-carboxylic acid 2M aqueous sodium hydroxide solution (0.95 mL) was added to a solution of 6-methyl-2-(trichloromethyl)-1H-1,3-benzodiazole (95 mg) in THF (1 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid, diluted with water, and the resulting precipitate was collected by filtration. The resulting residue was washed with water and dried under reduced pressure to give the title compound (59 mg). MS (ESI+) m / z 176.9 (M+H) ＋

[0109] Reference Example 6 7-fluoro-1H-1,3-benzodiazole-2-carboxylic acid [Step 1] Preparation of 7-fluoro-2-(trichloromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.15 mL) was added to a solution of 3-fluorobenzene-1,2-diamine (150 mg) in acetic acid (1.5 mL), and the mixture was stirred at room temperature for 12 hours. The reaction solution was diluted with water, and the resulting precipitate was collected by filtration, washed with water, and dried under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain a crude residue. The resulting residue was washed with a mixed solvent of n-hexane and diethyl ether to obtain the title compound (269 mg). MS (ESI+) m / z 254.7 (M+H) ＋ [Step 2] Preparation of 7-fluoro-1H-1,3-benzodiazole-2-carboxylic acid 2M aqueous sodium hydroxide solution (1.7 mL) was added to a solution of 7-fluoro-2-(trichloromethyl)-1H-1,3-benzodiazole (175 mg) in THF (1 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid and then purified by reverse phase column chromatography to give the title compound (118 mg). MS (ESI+) m / z 180.9 (M+H) ＋

[0110] Reference Example 7 6-fluoro-1H-1,3-benzodiazole-2-carboxylic acid [Step 1] Preparation of 6-fluoro-2-(trichloromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.15 mL) was added to a solution of 4-fluorobenzene-1,2-diamine (150 mg) in acetic acid (1.5 mL), and the mixture was stirred at room temperature for 12 hours. The reaction solution was diluted with water, and the resulting precipitate was collected by filtration, washed with water, and dried under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain a crude residue. The resulting residue was washed with a mixed solvent of n-hexane and diethyl ether to obtain the title compound (179 mg). MS (ESI+) m / z 254.7 (M+H) ＋ [Step 2] Preparation of 6-fluoro-1H-1,3-benzodiazole-2-carboxylic acid 2M aqueous sodium hydroxide solution (1.7 mL) was added to a solution of 6-fluoro-2-(trichloromethyl)-1H-1,3-benzodiazole (175 mg) in THF (1 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid and then purified by reverse phase column chromatography to give the title compound (110 mg). MS (ESI+) m / z 180.9 (M+H) ＋

[0111] Reference Example 8 7-Methoxy-1H-1,3-benzodiazole-2-carboxylic acid [Step 1] Preparation of 7-methoxy-2-(trichloromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.24 mL) was added to a solution of 3-methoxybenzene-1,2-diamine (250 mg) in acetic acid (1.5 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (185 mg). MS (ESI+) m / z 266.8 (M+H) ＋[Step 2] Preparation of 7-methoxy-1H-1,3-benzodiazole-2-carboxylic acid 2M aqueous sodium hydroxide solution (1.7 mL) was added to a solution of 7-methoxy-2-(trichloromethyl)-1H-1,3-benzodiazole (185 mg) in THF (2.5 mL), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid and then purified by reverse phase column chromatography to give the title compound (79 mg). MS (ESI+) m / z 192.9 (M+H) ＋

[0112] Reference Example 9 7-ethoxy-1H-1,3-benzodiazole-2-carboxylic acid [Step 1] Preparation of 7-ethoxy-2-(trichloromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.18 mL) was added to a solution of 3-ethoxybenzene-1,2-diamine (205 mg) in acetic acid (2.5 mL), and the mixture was stirred at room temperature for 1 hour. The reaction solution was diluted with water, and the resulting precipitate was collected by filtration, washed with water, and dried under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (299 mg). MS (ESI+) m / z 278.8 (M+H) ＋ [Step 2] Preparation of 7-ethoxy-1H-1,3-benzodiazole-2-carboxylic acid 2M aqueous sodium hydroxide solution (2.7 mL) was added to a solution of 7-ethoxy-2-(trichloromethyl)-1H-1,3-benzodiazole (299 mg) in THF (3 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid and then purified by reverse phase column chromatography to give the title compound (143 mg). MS (ESI+) m / z 207.0 (M+H) ＋

[0113] Reference Example 10 7-bromo-1H-1,3-benzodiazole-2-carboxylic acid [Step 1] Preparation of 7-bromo-2-(trichloromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.31 mL) was added to a solution of 3-bromobenzene-1,2-diamine (450 mg) in acetic acid (2.5 mL), and the mixture was stirred at room temperature for 1 hour. The reaction solution was diluted with water, and the resulting precipitate was collected by filtration, washed with water, and dried under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain a crude residue. The resulting residue was washed with a mixed solvent of n-hexane and diethyl ether to obtain the title compound (454 mg). MS (ESI+) m / z 314.6 (M+H) ＋ [Step 2] Preparation of 7-bromo-1H-1,3-benzodiazole-2-carboxylic acid 2M aqueous sodium hydroxide solution (3.6 mL) was added to a solution of 7-bromo-2-(trichloromethyl)-1H-1,3-benzodiazole (450 mg) in THF (5 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid, diluted with water, and the resulting precipitate was collected by filtration. The resulting residue was washed with water and dried under reduced pressure to give the title compound (347 mg). MS (ESI+) m / z 240.8 (M+H) ＋

[0114] Reference Example 11 7-(trifluoromethyl)-1H-1,3-benzodiazole-2-carboxylic acid [Step 1] Preparation of 2-(trichloromethyl)-7-(trifluoromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.18 mL) was added to a solution of 3-(trifluoromethyl)benzene-1,2-diamine (250 mg) in acetic acid (1.5 mL), and the mixture was stirred at room temperature overnight. The reaction solution was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (332 mg). MS (ESI+) m / z 304.7 (M+H) ＋[Step 2] Preparation of 7-(trifluoromethyl)-1H-1,3-benzodiazole-2-carboxylic acid 2M aqueous sodium hydroxide solution (2.7 mL) was added to a solution of 2-(trichloromethyl)-7-(trifluoromethyl)-1H-1,3-benzodiazole (330 mg) in THF (5 mL), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid, diluted with water, and the resulting precipitate was collected by filtration. The resulting residue was washed with water and dried under reduced pressure to give the title compound (179 mg). MS (ESI+) m / z 230.9 (M+H) ＋

[0115] Reference Example 12 7-(trifluoromethoxy)-1H-1,3-benzodiazole-2-carboxylic acid [Step 1] Preparation of 2-(trichloromethyl)-7-(trifluoromethoxy)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.14 mL) was added to a solution of 3-(trifluoromethoxy)benzene-1,2-diamine (200 mg) in acetic acid (1.5 mL), and the mixture was stirred at room temperature for 1 hour. The reaction solution was diluted with water, and the resulting precipitate was collected by filtration, washed with water, and dried under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (301 mg). MS (ESI+) m / z 320.7 (M+H) ＋ [Step 2] Preparation of 7-(trifluoromethoxy)-1H-1,3-benzodiazole-2-carboxylic acid 2M aqueous sodium hydroxide solution (2.3 mL) was added to a solution of 2-(trichloromethyl)-7-(trifluoromethoxy)-1H-1,3-benzodiazole (300 mg) in THF (5 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid and diluted with water, and the resulting precipitate was collected by filtration. The resulting residue was washed with water and dried under reduced pressure to give the title compound (177 mg). MS (ESI+) m / z 246.9 (M+H) ＋

[0116] Reference Example 13 7-cyano-1H-1,3-benzodiazole-2-carboxylic acid [Step 1] Preparation of 2-(trichloromethyl)-1H-1,3-benzodiazole-7-carbonitrile Methyl 2,2,2-trichloroacetimidate (0.23 mL) and trifluoroacetic acid (0.29 mL) were added to a solution of 2,3-diaminobenzonitrile (200 mg) in dichloromethane (2.5 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (385 mg). MS (ESI+) m / z 259.8 (M+H) ＋ [Step 2] Preparation of 7-cyano-1H-1,3-benzodiazole-2-carboxylic acid 2M aqueous sodium hydroxide solution (2.6 mL) was added to a solution of 2-(trichloromethyl)-1H-1,3-benzodiazole-7-carbonitrile (385 mg) in THF (5 mL), and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid, diluted with water, and the resulting precipitate was collected by filtration. The resulting residue was washed with water and dried under reduced pressure to give the title compound (244 mg). MS (ESI+) m / z 187.9 (M+H) ＋

[0117] Reference Example 14 6,7-difluoro-1H-1,3-benzodiazole-2-carboxylic acid [Step 1] Preparation of 6,7-difluoro-2-(trichloromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.14 mL) was added to a solution of 3,4-difluorobenzene-1,2-diamine (150 mg) in acetic acid (1.5 mL), and the mixture was stirred at room temperature for 10 hours. The reaction solution was diluted with water, and the resulting precipitate was collected by filtration, washed with water, and dried under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain a crude residue. The resulting residue was washed with a mixed solvent of n-hexane and diethyl ether to obtain the title compound (201 mg). MS (ESI+) m / z 272.7 (M+H) ＋[Step 2] Preparation of 6,7-difluoro-1H-1,3-benzodiazole-2-carboxylic acid 2M aqueous sodium hydroxide solution (1.8 mL) was added to a solution of 6,7-difluoro-2-(trichloromethyl)-1H-1,3-benzodiazole (200 mg) in THF (2 mL), and the mixture was stirred at room temperature for 12 hours. The reaction mixture was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid, diluted with water, and the resulting precipitate was collected by filtration. The resulting residue was washed with water and dried under reduced pressure to obtain a crude residue. The resulting residue was washed with a mixed solvent of ethyl acetate and methanol to obtain the title compound (156 mg). MS (ESI+) m / z 198.9 (M+H) ＋

[0118] Reference Example 15 5,6-difluoro-1H-1,3-benzodiazole-2-carboxylic acid [Step 1] Preparation of 5,6-difluoro-2-(trichloromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.14 mL) was added to a solution of 4,5-difluorobenzene-1,2-diamine (150 mg) in acetic acid (1.5 mL), and the mixture was stirred at room temperature for 10 hours. The reaction solution was diluted with water, and the resulting precipitate was collected by filtration, washed with water, and dried under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain a crude residue. The resulting residue was washed with n-hexane to obtain the title compound (169 mg). MS (ESI+) m / z 270.7 (M+H) ＋ [Step 2] Preparation of 5,6-difluoro-1H-1,3-benzodiazole-2-carboxylic acid 2M aqueous sodium hydroxide solution (1.5 mL) was added to a solution of 5,6-difluoro-2-(trichloromethyl)-1H-1,3-benzodiazole (165 mg) in THF (2 mL), and the mixture was stirred at room temperature for 12 hours. The reaction mixture was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid, diluted with water, and the resulting precipitate was collected by filtration. The resulting residue was washed with water and dried under reduced pressure to give the title compound (124 mg). MS (ESI+) m / z 198.9 (M+H) ＋

[0119] Reference Example 16 6,7-dichloro-1H-1,3-benzodiazole-2-carboxylic acid [Step 1] Preparation of 6,7-dichloro-2-(trichloromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.12 mL) was added to a solution of 3,4-dichlorobenzene-1,2-diamine (170 mg) in acetic acid (1.5 mL), and the mixture was stirred at room temperature for 1 hour. The reaction solution was diluted with water, and the resulting precipitate was collected by filtration, washed with water, and dried under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (223 mg). MS (ESI+) m / z 304.7 (M+H) ＋ [Step 2] Preparation of 6,7-dichloro-1H-1,3-benzodiazole-2-carboxylic acid 2M aqueous sodium hydroxide solution (1.9 mL) was added to a solution of 6,7-dichloro-2-(trichloromethyl)-1H-1,3-benzodiazole (230 mg) in THF (2.5 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid and diluted with water, and the resulting precipitate was collected by filtration. The resulting residue was washed with water and dried under reduced pressure to give the title compound (176 mg). MS (ESI+) m / z 230.8 (M+H) ＋

[0120] Reference Example 17 5,7-dichloro-1H-1,3-benzodiazole-2-carboxylic acid [Step 1] Preparation of 5,7-dichloro-2-(trichloromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.15 mL) was added to a solution of 3,5-dichlorobenzene-1,2-diamine (200 mg) in acetic acid (1.5 mL), and the mixture was stirred at room temperature for 1 hour. The reaction solution was diluted with water, and the resulting precipitate was collected by filtration, washed with water, and dried under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (315 mg). MS (ESI+) m / z 304.7 (M+H) ＋[Step 2] Preparation of 5,7-dichloro-1H-1,3-benzodiazole-2-carboxylic acid 2M aqueous sodium hydroxide solution (2.5 mL) was added to a solution of 5,7-dichloro-2-(trichloromethyl)-1H-1,3-benzodiazole (310 mg) in THF (2.5 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid, diluted with water, and the resulting precipitate was collected by filtration. The resulting residue was washed with water and dried under reduced pressure to give the title compound (267 mg). MS (ESI+) m / z 230.8 (M+H) ＋

[0121] Reference Example 18 4,7-dichloro-1H-1,3-benzodiazole-2-carboxylic acid [Step 1] Preparation of 4,7-dichloro-2-(trichloromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.092 mL) was added to a solution of 3,6-dichlorobenzene-1,2-diamine (125 mg) in acetic acid (1 mL), and the mixture was stirred at room temperature for 4 hours. The reaction solution was diluted with water, and the resulting precipitate was collected by filtration, washed with water, and dried under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (172 mg). MS (ESI+) m / z 304.7 (M+H) ＋ [Step 2] Preparation of 4,7-dichloro-1H-1,3-benzodiazole-2-carboxylic acid 2M aqueous sodium hydroxide solution (1.4 mL) was added to a solution of 4,7-dichloro-2-(trichloromethyl)-1H-1,3-benzodiazole (170 mg) in THF (2.5 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid, diluted with water, and the resulting precipitate was collected by filtration. The resulting residue was washed with water and dried under reduced pressure to give the title compound (132 mg). MS (ESI+) m / z 230.8 (M+H) ＋

[0122] Reference Example 19 5,6-dichloro-1H-1,3-benzodiazole-2-carboxylic acid [Step 1] Preparation of 5,6-dichloro-2-(trichloromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.15 mL) was added to a solution of 4,5-dichlorobenzene-1,2-diamine (200 mg) in acetic acid (1.5 mL), and the mixture was stirred at room temperature for 14 hours. The reaction solution was diluted with water, and the resulting precipitate was collected by filtration, washed with water, and dried under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain a crude residue. The resulting residue was washed with n-hexane to obtain the title compound (328 mg). MS (ESI+) m / z 304.7 (M+H) ＋ [Step 2] Preparation of 5,6-dichloro-1H-1,3-benzodiazole-2-carboxylic acid 2M aqueous sodium hydroxide solution (2.6 mL) was added to a solution of 5,6-dichloro-2-(trichloromethyl)-1H-1,3-benzodiazole (320 mg) in THF (2 mL), and the mixture was stirred at room temperature for 10 hours. The reaction mixture was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid and diluted with water, and the resulting precipitate was collected by filtration. The resulting residue was washed with water and dried under reduced pressure to give the title compound (247 mg). MS (ESI+) m / z 230.8 (M+H) ＋

[0123] Reference Example 20 6-fluoro-7-methyl-1H-1,3-benzodiazole-2-carboxylic acid [Step 1] Preparation of 6-fluoro-7-methyl-2-(trichloromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.14 mL) was added to a solution of 4-fluoro-3-methylbenzene-1,2-diamine (150 mg) in acetic acid (1.5 mL), and the mixture was stirred at room temperature for 1 hour. The reaction solution was diluted with water, and the resulting precipitate was collected by filtration, washed with water, and dried under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (166 mg). MS (ESI+) m / z 266.8 (M+H) ＋[Step 2] Preparation of 6-fluoro-7-methyl-1H-1,3-benzodiazole-2-carboxylic acid 2M aqueous sodium hydroxide solution (1.5 mL) was added to a solution of 6-fluoro-7-methyl-2-(trichloromethyl)-1H-1,3-benzodiazole (165 mg) in THF (2.5 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid, diluted with water, and the resulting precipitate was collected by filtration. The resulting residue was washed with water and dried under reduced pressure to give the title compound (108 mg). MS (ESI+) m / z 195.0 (M+H) ＋

[0124] Reference Example 21 6-chloro-7-methyl-1H-1,3-benzodiazole-2-carboxylic acid [Step 1] Preparation of 6-chloro-7-methyl-2-(trichloromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.12 mL) was added to a solution of 4-chloro-3-methylbenzene-1,2-diamine (150 mg) in acetic acid (1.5 mL), and the mixture was stirred at room temperature for 1 hour. The reaction solution was diluted with water, and the resulting precipitate was collected by filtration, washed with water, and dried under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (211 mg). MS (ESI+) m / z 284.8 (M+H) ＋ [Step 2] Preparation of 6-chloro-7-methyl-1H-1,3-benzodiazole-2-carboxylic acid 2M aqueous sodium hydroxide solution (1.8 mL) was added to a solution of 6-chloro-7-methyl-2-(trichloromethyl)-1H-1,3-benzodiazole (210 mg) in THF (2.5 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid, diluted with water, and the resulting precipitate was collected by filtration. The resulting residue was washed with water and dried under reduced pressure to give the title compound (141 mg). MS (ESI+) m / z 210.9 (M+H) ＋

[0125] Reference Example 22 6-chloro-7-methoxy-1H-1,3-benzodiazole-2-carboxylic acid [Step 1] Preparation of 4-chloro-3-methoxy-2-nitroaniline To a mixed solution of 3,4-dichloro-2-nitroaniline (200 mg) in THF (2.5 mL) and methanol (0.5 mL), sodium methoxide (5 M methanol solution, 0.48 mL) was added and the mixture was stirred at room temperature for 24 hours and at 50°C for 12 hours. The reaction solution was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the resulting residue was purified by silica gel column chromatography to give the title compound (95 mg). MS (ESI+) m / z 202.9 (M+H) ＋ [Step 2] Preparation of 4-chloro-3-methoxybenzene-1,2-diamine A solution of 4-chloro-3-methoxy-2-nitroaniline (93 mg) and 1 w / w% platinum + 0.1 w / w% copper-activated carbon (Degussa type CF105R / W, 30 mg) in methanol (7.5 mL) was stirred under a hydrogen atmosphere (0.4 MPa) at room temperature for 2 hours. Insoluble matter was filtered off through Celite (registered trademark), and the obtained filtrate was concentrated to give the title compound (77 mg). MS (ESI+) m / z 172.9 (M+H) ＋ [Step 3] Preparation of 6-chloro-7-methoxy-2-(trichloromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.058 mL) was added to a solution of 4-chloro-3-methoxybenzene-1,2-diamine (77 mg) in acetic acid (1 mL), and the mixture was stirred at room temperature for 1 hour. The reaction solution was diluted with water, and the resulting precipitate was collected by filtration, washed with water, and dried under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (100 mg). MS (ESI+) m / z 300.8 (M+H) ＋[Step 4] Preparation of 6-chloro-7-methoxy-1H-1,3-benzodiazole-2-carboxylic acid 2M aqueous sodium hydroxide solution (0.83 mL) was added to a solution of 6-chloro-7-methoxy-2-(trichloromethyl)-1H-1,3-benzodiazole (210 mg) in THF (1 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid and then purified by reverse phase column chromatography to give the title compound (52 mg). MS (ESI+) m / z 226.9 (M+H) ＋

[0126] Reference Example 23 6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxylic acid hydrochloride [Step 1] Preparation of {6-fluoro-3H-imidazo[4,5-b]pyridin-2-yl}methanol Glycolic acid (1.20 g) was added to 5-fluoropyridine-2,3-diamine (1.00 g) and stirred at 150°C for 5 hours. The reaction solution was neutralized with 1M aqueous sodium hydroxide solution and then purified by silica gel column chromatography to obtain a crude residue. The obtained residue was washed with methanol to obtain the title compound (1.51 g). MS (ESI+) m / z 167.9 (M+H) ＋ [Step 2] Preparation of 6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxylic acid hydrochloride To a solution of potassium permanganate (2.50 g) in water (40 mL), a solution of {6-fluoro-3H-imidazo[4,5-b]pyridin-2-yl}methanol (1.51 g) and sodium carbonate (1.20 g) in water (40 mL) was added, and the mixture was stirred at 100°C for 3 hours. The insoluble matter was filtered off, and the resulting filtrate was neutralized with concentrated hydrochloric acid, and the resulting precipitate was collected by filtration. The resulting residue was washed with water and acetone and dried under reduced pressure to give the title compound (907 mg). MS (ESI+) m / z 181.9 (M+H) ＋

[0127] Reference Example 24 4-chloro-3H-imidazo[4,5-c]pyridine-2-carboxylic acid [Step 1] Preparation of 4-chloro-2-(trichloromethyl)-3H-imidazo[4,5-c]pyridine Methyl 2,2,2-trichloroacetimidate (0.45 mL) was added to a solution of 2-chloropyridine-3,4-diamine (500 mg) in acetic acid (2.5 mL), and the mixture was stirred at room temperature over the weekend. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (415 mg). MS (ESI+) m / z 271.8 (M+H) ＋ [Step 2] Preparation of 4-chloro-3H-imidazo[4,5-c]pyridine-2-carboxylic acid 2M aqueous sodium hydroxide solution (0.92 mL) was added to a solution of 4-chloro-2-(trichloromethyl)-3H-imidazo[4,5-c]pyridine (100 mg) in THF (1 mL), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid and then purified by reverse phase column chromatography to give the title compound (33 mg). MS (ESI+) m / z 197.9 (M+H) ＋

[0128] Reference Example 25 1-methyl-1H-1,3-benzodiazole-2-carboxylic acid [Step 1] Preparation of 1-methyl-2-(trichloromethyl)-1H-1,3-benzodiazole 1M aqueous sodium hydroxide solution (4.5 mL) was added to N1-methylbenzene-1,2-diamine dihydrochloride (350 mg) and stirred at room temperature for 30 minutes. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was dissolved in acetic acid (1.5 mL). To this solution, methyl 2,2,2-trichloroacetimidate (0.23 mL) was added and stirred at room temperature for 2 hours. The reaction mixture was diluted with water, and the resulting precipitate was collected by filtration. The resulting residue was washed with water and dried under reduced pressure to give the title compound (422 mg). MS (ESI+) m / z 250.8 (M+H) ＋[Step 2] Preparation of 1-methyl-1H-1,3-benzodiazole-2-carboxylic acid 2M aqueous sodium hydroxide solution (4.2 mL) was added to a solution of 1-methyl-2-(trichloromethyl)-1H-1,3-benzodiazole (420 mg) in THF (5 mL), and the mixture was stirred at room temperature for 2 hours. Methanol (2.5 mL) was added to the reaction solution, and the mixture was stirred at 50°C for 14 hours. The reaction solution was concentrated, and the resulting residue was neutralized with 2M hydrochloric acid and then purified by reverse phase column chromatography to obtain a crude residue. The resulting residue was washed with methanol to obtain the title compound (146 mg). MS (ESI+) m / z 176.9 (M+H) ＋

[0129] Reference Example 26 Sodium 7-chloro-1-methyl-1H-1,3-benzodiazole-2-carboxylate [Step 1] Preparation of 2-chloro-N-methyl-6-nitroaniline To a solution of 1-chloro-2-fluoro-3-nitrobenzene (300 mg) and TEA (0.60 mL) in THF (5 mL), 40% aqueous methylamine solution (0.36 mL) was added and stirred at room temperature for 1 hour. The reaction solution was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (335 mg). MS (ESI+) m / z 186.9 (M+H) ＋ [Step 2] Preparation of 6-chloro-N1-methylbenzene-1,2-diamine A solution of 2-chloro-N-methyl-6-nitroaniline (335 mg) and 1 w / w% platinum + 0.1 w / w% copper-activated carbon (Degussa type CF105R / W, 100 mg) in methanol (15 mL) was stirred under a hydrogen atmosphere (0.4 MPa) at room temperature for 6 hours. Insoluble matter was filtered off through Celite (registered trademark), and the obtained filtrate was concentrated to give the title compound (266 mg). MS (ESI+) m / z 156.9 (M+H) ＋[Step 3] Preparation of 7-chloro-1-methyl-2-(trichloromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.22 mL) was added to a solution of 6-chloro-N1-methylbenzene-1,2-diamine (265 mg) in acetic acid (1.5 mL), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (298 mg). MS (ESI+) m / z 284.8 (M+H) ＋ [Step 4] Preparation of sodium 7-chloro-1-methyl-1H-1,3-benzodiazole-2-carboxylate 2M aqueous sodium hydroxide solution (2.6 mL) was added to a solution of 7-chloro-1-methyl-2-(trichloromethyl)-1H-1,3-benzodiazole (295 mg) in THF (2.5 mL), and the mixture was stirred at room temperature for 3 hours. 2M aqueous sodium hydroxide solution (2.6 mL) and methanol (2.5 mL) were added to the reaction mixture, and the mixture was stirred at 50°C for 40 hours. The reaction mixture was concentrated, and the precipitate was collected by filtration. The resulting residue was washed with ice water and dried under reduced pressure to give the title compound (164 mg). MS (ESI+) m / z 210.9 (M+H) ＋

[0130] Reference Example 27 Sodium 6-chloro-1-methyl-1H-1,3-benzodiazole-2-carboxylate [Step 1] Preparation of 5-chloro-N-methyl-2-nitroaniline To a solution of 4-chloro-2-fluoro-1-nitrobenzene (300 mg) and TEA (0.60 mL) in THF (5 mL), 40% aqueous methylamine solution (0.36 mL) was added and stirred at room temperature for 1 hour. The reaction solution was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the resulting residue was purified by silica gel column chromatography to give the title compound (343 mg). MS (ESI+) m / z 186.9 (M+H) ＋[Step 2] Preparation of 5-chloro-N1-methylbenzene-1,2-diamine A solution of 5-chloro-N-methyl-2-nitroaniline (340 mg) and 1 w / w% platinum + 0.1 w / w% copper-activated carbon (Degussa type CF105R / W, 110 mg) in methanol (15 mL) was stirred under a hydrogen atmosphere (0.4 MPa) at room temperature for 4 hours. Insoluble matter was filtered off through Celite (registered trademark), and the obtained filtrate was concentrated to give the title compound (277 mg). MS (ESI+) m / z 156.9 (M+H) ＋ [Step 3] Preparation of 6-chloro-1-methyl-2-(trichloromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.23 mL) was added to a solution of 5-chloro-N1-methylbenzene-1,2-diamine (275 mg) in acetic acid (1.5 mL), and the mixture was stirred at room temperature for 2 hours. The reaction solution was diluted with water, and the resulting precipitate was collected by filtration, washed with water, and dried under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (467 mg). MS (ESI+) m / z 284.8 (M+H) ＋ [Step 4] Preparation of sodium 6-chloro-1-methyl-1H-1,3-benzodiazole-2-carboxylate 2M aqueous sodium hydroxide solution (4.1 mL) was added to a solution of 6-chloro-1-methyl-2-(trichloromethyl)-1H-1,3-benzodiazole (465 mg) in THF (5 mL), and the mixture was stirred at room temperature for 3 hours. 2M aqueous sodium hydroxide solution (2.0 mL) and methanol (5 mL) were added to the reaction mixture, and the mixture was stirred at 50°C for 15 hours. The reaction mixture was concentrated, and the precipitate was collected by filtration. The resulting residue was washed with ice water and dried under reduced pressure to give the title compound (313 mg). MS (ESI+) m / z 210.9 (M+H) ＋

[0131] Reference Example 28 Sodium 5-chloro-1-methyl-1H-1,3-benzodiazole-2-carboxylate [Step 1] Preparation of 4-chloro-N-methyl-2-nitroaniline To a solution of 4-chloro-1-fluoro-2-nitrobenzene (300 mg) and TEA (0.60 mL) in THF (5 mL), 40% aqueous methylamine solution (0.36 mL) was added and stirred at room temperature for 1 hour. The reaction solution was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the resulting residue was purified by silica gel column chromatography to give the title compound (351 mg). MS (ESI+) m / z 186.9 (M+H) ＋ [Step 2] Preparation of 4-chloro-N1-methylbenzene-1,2-diamine A solution of 4-chloro-N-methyl-2-nitroaniline (350 mg) and 1 w / w% platinum + 0.1 w / w% copper-activated carbon (Degussa type CF105R / W, 110 mg) in methanol (15 mL) was stirred under a hydrogen atmosphere (0.3 MPa) at room temperature for 10 hours. Insoluble matter was filtered off through Celite (registered trademark), and the obtained filtrate was concentrated to give the title compound (288 mg). MS (ESI+) m / z 156.9 (M+H) ＋ [Step 3] Preparation of 5-chloro-1-methyl-2-(trichloromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.24 mL) was added to a solution of 4-chloro-N1-methylbenzene-1,2-diamine (285 mg) in acetic acid (2 mL), and the mixture was stirred at room temperature for 2 hours. The reaction solution was diluted with water, and the resulting precipitate was collected by filtration, washed with water, and dried under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (489 mg). MS (ESI+) m / z 284.8 (M+H) ＋[Step 4] Preparation of sodium 5-chloro-1-methyl-1H-1,3-benzodiazole-2-carboxylate 2M aqueous sodium hydroxide solution (6.4 mL) was added to a mixed solution of 5-chloro-1-methyl-2-(trichloromethyl)-1H-1,3-benzodiazole (485 mg) in THF (5 mL) and methanol (5 mL), and the mixture was stirred at 50°C for 16 hours. The reaction solution was concentrated, and the resulting precipitate was collected by filtration. The resulting residue was washed with ice water and dried under reduced pressure to give the title compound (340 mg). MS (ESI+) m / z 210.9 (M+H) ＋

[0132] Reference Example 29 Sodium 4-chloro-1-methyl-1H-1,3-benzodiazole-2-carboxylate [Step 1] Preparation of 3-chloro-N-methyl-2-nitroaniline To a solution of 1-chloro-3-fluoro-2-nitrobenzene (300 mg) and TEA (0.60 mL) in THF (5 mL), 40% aqueous methylamine solution (0.36 mL) was added and stirred at room temperature for 1 hour. The reaction solution was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the resulting residue was purified by silica gel column chromatography to give the title compound (276 mg). MS (ESI+) m / z 186.9 (M+H) ＋ [Step 2] Preparation of 3-chloro-N1-methylbenzene-1,2-diamine A solution of 3-chloro-N-methyl-2-nitroaniline (360 mg) and 1 w / w% platinum + 0.1 w / w% copper-activated carbon (Degussa type CF105R / W, 110 mg) in methanol (15 mL) was stirred under a hydrogen atmosphere (0.3 MPa) at room temperature for 6 hours. Insoluble matter was filtered off through Celite (registered trademark), and the obtained filtrate was concentrated to give the title compound (304 mg). MS (ESI+) m / z 156.9 (M+H) ＋[Step 3] Preparation of 4-chloro-1-methyl-2-(trichloromethyl)-1H-1,3-benzodiazole Methyl 2,2,2-trichloroacetimidate (0.25 mL) was added to a solution of 3-chloro-N1-methylbenzene-1,2-diamine (300 mg) in acetic acid (2 mL), and the mixture was stirred at room temperature for 1 hour. The reaction solution was diluted with water, and the resulting precipitate was collected by filtration, washed with water, and dried under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain a crude residue. The resulting residue was washed with diethyl ether to obtain the title compound (383 mg). MS (ESI+) m / z 284.7 (M+H) ＋ [Step 4] Preparation of sodium 4-chloro-1-methyl-1H-1,3-benzodiazole-2-carboxylate 2M aqueous sodium hydroxide solution (5.0 mL) was added to a mixed solution of 4-chloro-1-methyl-2-(trichloromethyl)-1H-1,3-benzodiazole (380 mg) in THF (5 mL) and methanol (10 mL), and the mixture was stirred at 50°C for 60 hours. 2M aqueous sodium hydroxide solution (1.7 mL) was added to the reaction solution, and the mixture was stirred at 65°C for 40 hours. 2M aqueous sodium hydroxide solution (1.7 mL) was added to the reaction solution, and the mixture was stirred at 65°C for 20 hours. The reaction solution was concentrated, and the precipitate was collected by filtration. The resulting residue was washed with water and dried under reduced pressure to give the title compound (235 mg). MS (ESI+) m / z 210.9 (M+H) ＋

[0133] Reference Example 30 tert-butyl N-(2-methylbut-3-yn-1-yl)carbamate 1,1,1-Triacetoxy-1,1-dihydro-1,2-benzoiodoxol-3-(1H)-one (773 mg) was added to a solution of tert-butyl N-(3-hydroxy-2-methylpropyl)carbamate (300 mg) in dichloromethane (5 mL), and the mixture was stirred at room temperature for 1 hour. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, followed by dilution with water and extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. Potassium carbonate (657 mg) and dimethyl (1-diazo-2-oxopropyl)phosphonate (0.30 mL) were added to a solution of the residue obtained by distilling off the solvent under reduced pressure in methanol (10 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (245 mg).

[0134] Reference Example 31 tert-butyl N-(pent-4-yn-2-yl)carbamate [Step 1] Preparation of pent-4-yn-2-yl methanesulfonate Methanesulfonyl chloride (0.74 mL) was added to a solution of pent-4-yn-2-ol (700 mg) and TEA (1.45 mL) in diethyl ether (15 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound (1.42 g). [Step 2] Preparation of tert-butyl N-(pent-4-yn-2-yl)carbamate Sodium azide (1.71 g) was added to a solution of pent-4-yn-2-yl methanesulfonate (1.42 g) in DMF (10 mL), and the mixture was stirred at 70°C for 4 hours and at room temperature over the weekend. The reaction mixture was diluted with water and extracted with diethyl ether. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was dissolved in diethyl ether (10 mL) and PPh ３ (4.21 g) was added to the reaction mixture, and the mixture was stirred for 3 hours in an ice bath. Water (1 mL) was added to the reaction mixture, and the mixture was stirred at room temperature for 4 hours. ２0 (1.75 mL) was added and the mixture was stirred at room temperature over the weekend. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture to terminate the reaction, and the mixture was diluted with water and extracted with diethyl ether. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (331 mg).

[0135] Reference Example 32 tert-butyl N-[(2S)-pent-4-yn-2-yl]carbamate To a solution of tert-butyl N-[(2S)-4-hydroxybutan-2-yl]carbamate (575 mg) in dichloromethane (15 mL) was added 1,1,1-triacetoxy-1,1-dihydro-1,2-benzoiodoxol-3-(1H)-one (1.48 g), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was quenched by adding saturated aqueous sodium bicarbonate and 20% aqueous sodium hydrogen thiosulfate, diluted with water, and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and to a solution of the residue in methanol (10 mL), potassium carbonate (1.26 g) and dimethyl (1-diazo-2-oxopropyl)phosphonate (0.57 mL) were added, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate, and insoluble matter was filtered off. The filtrate was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (445 mg). [α] Ｄ ２４ = -66.64° (c = 0.33, chloroform)

[0136] Reference Example 33 tert-Butyl N-[(2R)-pent-4-yn-2-yl]carbamate To a solution of tert-butyl N-[(2R)-4-hydroxybutan-2-yl]carbamate (555 mg) in dichloromethane (15 mL) was added 1,1,1-triacetoxy-1,1-dihydro-1,2-benzoiodoxol-3-(1H)-one (1.43 g), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was quenched by adding saturated aqueous sodium bicarbonate and 20% aqueous sodium hydrogen thiosulfate, diluted with water, and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. Potassium carbonate (1.22 g) and dimethyl (1-diazo-2-oxopropyl)phosphonate (0.55 mL) were added to a solution of the residue obtained by distilling off the solvent under reduced pressure in methanol (10 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate, and insoluble matter was filtered off. The filtrate was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (467 mg). [α] Ｄ ２３ = +51.87° (c = 0.27, chloroform)

[0137] Reference Example 34 tert-Butyl N-[(3S)-hex-5-yn-3-yl]carbamate To a solution of tert-butyl N-[(3S)-1-hydroxypentan-3-yl]carbamate (300 mg) in dichloromethane (5 mL) was added 1,1,1-triacetoxy-1,1-dihydro-1,2-benzoiodoxol-3-(1H)-one (720 mg), and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated, and the resulting residue was diluted with ethyl acetate. After that, a saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to quench the reaction. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. To a solution of the residue obtained by distilling off the solvent under reduced pressure in methanol (5 mL), potassium carbonate (612 mg) and dimethyl (1-diazo-2-oxopropyl)phosphonate (0.28 mL) were added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate, and insoluble matter was filtered off. The filtrate was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (200 mg).

[0138] Reference Example 35 tert-Butyl N-[(3R)-hex-5-yn-3-yl]carbamate To a solution of tert-butyl N-[(3R)-1-hydroxypentan-3-yl]carbamate (260 mg) in dichloromethane (5 mL) was added 1,1,1-triacetoxy-1,1-dihydro-1,2-benzoiodoxol-3-(1H)-one (624 mg), and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated, and the resulting residue was diluted with ethyl acetate. After that, a saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to terminate the reaction. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and to a solution of the resulting residue in methanol (5 mL), potassium carbonate (530 mg) and dimethyl (1-diazo-2-oxopropyl)phosphonate (0.24 mL) were added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate, and insoluble matter was filtered off. The filtrate was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (174 mg). [α] Ｄ ２３ = +96.23° (c = 0.28, chloroform)

[0139] Reference Example 36 tert-Butyl N-[(3R)-2-methylhex-5-yn-3-yl]carbamate To a solution of tert-butyl N-[(3R)-1-hydroxy-4-methylpentan-3-yl]carbamate (300 mg) in dichloromethane (5 mL) was added 1,1,1-triacetoxy-1,1-dihydro-1,2-benzoiodoxol-3-(1H)-one (673 mg), and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated, and the resulting residue was diluted with ethyl acetate. After that, a saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to quench the reaction. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. To a solution of the residue obtained by distilling off the solvent under reduced pressure in methanol (5 mL), potassium carbonate (572 mg) and dimethyl (1-diazo-2-oxopropyl)phosphonate (0.26 mL) were added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate, and insoluble matter was filtered off. The filtrate was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (204 mg). [α] Ｄ ２４ = -86.10° (c = 0.28, chloroform)

[0140] Reference Example 37 tert-butyl N-[(1R)-1-phenylbut-3-yn-1-yl]carbamate To a solution of tert-butyl N-[(1R)-3-hydroxy-1-phenylpropyl]carbamate (300 mg) in dichloromethane (5 mL), 1,1,1-triacetoxy-1,1-dihydro-1,2-benzoiodoxol-3-(1H)-one (582 mg) was added, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the resulting residue was diluted with ethyl acetate. After that, a saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to quench the reaction. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. To a solution of the residue obtained by distilling off the solvent under reduced pressure in methanol (5 mL), potassium carbonate (495 mg) and dimethyl (1-diazo-2-oxopropyl)phosphonate (0.22 mL) were added, and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate, and insoluble matter was filtered off. The filtrate was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (255 mg). [α]Ｄ ２４ = +49.56° (c = 0.28, chloroform)

[0141] Reference Example 38 tert-Butyl N-[(1,1,1- ２ H ３ ) pent-4-yn-2-yl]carbamate [Step 1] Methyl 2-amino(3,3,3- ２ H ３ Preparation of 2-amino(3,3,3-) propanoate hydrochloride ２ H ３ To a solution of 1.99 g of 2-(tert-butoxy)-propanoic acid in 40 mL of methanol was added 7.88 mL of thionyl chloride under ice cooling, and the mixture was stirred at 90°C for 20 hours. The solvent was evaporated under reduced pressure to give the title compound (3.11 g). [Step 2] Methyl 2-{[(tert-butoxy)carbonyl]amino}(3,3,3- ２ H ３ Preparation of methyl 2-amino(3,3,3-) propanoate ２ H ３ To a solution of Boc propanoate hydrochloride (3.11 g) in dichloromethane (40 mL) was added TEA (7.60 mL) and ２ 0 (6.26 mL) was added and stirred at room temperature for 8 hours. The reaction mixture was concentrated, and the resulting residue was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound (4.71 g). [Step 3] tert-butyl N-[1-hydroxy(3,3,3- ２ H ３ Preparation of methyl 2-{[(tert-butoxy)carbonyl]amino}(3,3,3- ２ H ３) propanoate (4.71 g) in THF (25 mL) was slowly added, and the mixture was stirred in an ice bath for 1 hour. Water (1.5 mL), 4 M aqueous sodium hydroxide solution (1.5 mL), and water (4.5 mL) were added to the reaction mixture in that order to quench the reaction, and the mixture was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (3.59 g). [Step 4] tert-Butyl N-[1-(methanesulfonyloxy)(3,3,3- ２ H ３ )propan-2-yl]carbamate tert-butyl N-[1-hydroxy(3,3,3- ２ H ３ Methanesulfonyl chloride (1.71 mL) was added to a solution of tert-butyl N-[1-cyano(3,3,3-propan-2-yl)]carbamate (3.59 g) and TEA (4.21 mL) in dichloromethane (30 mL) under ice cooling, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was diluted with water and extracted with dichloromethane. The organic layer was washed with 0.1 M hydrochloric acid, saturated aqueous sodium bicarbonate solution, and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound (4.79 g). [Step 5]: tert-Butyl N-[1-cyano(3,3,3- ２ H ３ )propan-2-yl]carbamate tert-butyl N-[1-(methanesulfonyloxy)(3,3,3- ２ H ３ To a solution of 4.79 g of 3-{[(tert-butoxy)carbonyl]amino}(4,4,4-propan-2-yl)carbamate in 20 mL of DMSO, 1.97 g of sodium cyanide was added, and the mixture was stirred at 40°C for 35 hours and at room temperature over the weekend. The reaction mixture was diluted with water and extracted with diethyl ether. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (2.21 g). [Step 6]: 3-{[(tert-butoxy)carbonyl]amino}(4,4,4- ２ H ３ ) butanoic acid tert-butyl N-[1-cyano(3,3,3- ２ H ３To a solution of methyl 3-{[(tert-butoxy)carbonyl]amino}(4,4,4- methyl-3-( ... ２ H ３ Preparation of 3-{[(tert-butoxy)carbonyl]amino}(4,4,4- ２ H ３ To a mixed solution of 1.38 g of 4-hydroxybutanoic acid in 15 mL of methanol and 15 mL of toluene, trimethylsilyldiazomethane (0.6 M n-hexane solution, 17.0 mL) was added under ice cooling, and the mixture was stirred at room temperature for 3 hours. Acetic acid was added to the reaction mixture to terminate the reaction, and a saturated aqueous solution of sodium bicarbonate was added to neutralize the mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound (1.37 g). [Step 8] tert-Butyl N-[4-hydroxy(1,1,1- ２ H ３ Preparation of methyl 3-{[(tert-butoxy)carbonyl]amino}(4,4,4- ２ H ３ Lithium aluminum hydride (413 mg) was added to a solution of 1.37 g of tert-butyl N-[(1,1,1-)-butanoate in THF (30 mL) under ice cooling, and the mixture was stirred under ice cooling for 1 hour. Water (0.4 mL), 4 M aqueous sodium hydroxide solution (0.4 mL), and water (1.2 mL) were added to the reaction solution in this order to quench the reaction, and the mixture was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (961 mg). [Step 9]: Preparation of tert-butyl N-[(1,1,1-)-butanoate ２ H ３ Preparation of tert-butyl N-[4-hydroxy(1,1,1-)pent-4-yn-2-yl]carbamate ２ H ３1,1,1-Triacetoxy-1,1-dihydro-1,2-benzoiodoxol-3-(1H)-one (2.44 g) was added to a solution of [1-(2-methyl-2-propan-2-yl)-2-methylpropan-2-yl]carbamate (960 mg) in dichloromethane (20 mL), and the mixture was stirred at room temperature for 5 hours. The reaction mixture was concentrated, and the resulting residue was diluted with ethyl acetate. After that, a saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to quench the reaction. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and to a solution of the resulting residue in methanol (15 mL), potassium carbonate (2.07 g) and dimethyl (1-diazo-2-oxopropyl)phosphonate (0.94 mL) were added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate, and insoluble matter was filtered off. The filtrate was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (804 mg).

[0142] Reference Example 39 tert-Butyl N-[(2R)-1,1,1-trifluoropent-4-yn-2-yl]carbamate [Step 1] Preparation of methyl (3R)-3-{[(tert-butoxy)carbonyl]amino}-4,4,4-trifluorobutanoate To a solution of (3R)-3-{[(tert-butoxy)carbonyl]amino}-4,4,4-trifluorobutanoic acid (230 mg) in methanol (2.5 mL) and toluene (2.5 mL) was added trimethylsilyldiazomethane (0.6 M n-hexane solution, 4 mL), and the mixture was stirred at room temperature for 5 hours. Acetic acid was added to the reaction mixture to quench the reaction, and a saturated aqueous solution of sodium bicarbonate was added to neutralize the mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound (187 mg). [Step 2] Preparation of tert-butyl N-[(2R)-1,1,1-trifluoro-4-hydroxybutan-2-yl]carbamate. To a solution of methyl (3R)-3-{[(tert-butoxy)carbonyl]amino}-4,4,4-trifluorobutanoate (185 mg) in THF (5 mL) was added lithium aluminum hydride (52 mg) in an ice bath, and the mixture was stirred for 1 hour in an ice bath. Water (0.05 mL), 4 M aqueous sodium hydroxide solution (0.05 mL), and water (0.15 mL) were added sequentially to the reaction mixture to quench the reaction, and the mixture was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound (162 mg). [Step 3] Preparation of tert-butyl N-[(2R)-1,1,1-trifluoropent-4-yn-2-yl]carbamate 1,1,1-triacetoxy-1,1-dihydro-1,2-benzoiodoxol-3-(1H)-one (531 mg) was added to a solution of tert-butyl N-[(2R)-1,1,1-trifluoro-4-hydroxybutan-2-yl]carbamate (265 mg) in dichloromethane (5 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was quenched by adding saturated aqueous sodium bicarbonate and 20% aqueous sodium hydrogen thiosulfate, diluted with water, and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in methanol (5 mL), to which potassium carbonate (452 ​​mg) and dimethyl (1-diazo-2-oxopropyl)phosphonate (0.20 mL) were added, followed by stirring at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate, and insoluble matter was removed by filtration.The filtrate was concentrated and the resulting residue was purified by silica gel column chromatography to obtain the title compound (228 mg).

[0143] Reference Example 40 tert-butyl N-(2-methylpent-4-yn-2-yl)carbamate To a solution of tert-butyl N-(4-hydroxy-2-methylbutan-2-yl)carbamate (430 mg) in dichloromethane (5 mL) was added 1,1,1-triacetoxy-1,1-dihydro-1,2-benzoiodoxol-3-(1H)-one (1.03 g), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the resulting residue was diluted with ethyl acetate. Then, a saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to quench the reaction. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and to a solution of the resulting residue in methanol (10 mL), potassium carbonate (877 mg) and dimethyl (1-diazo-2-oxopropyl)phosphonate (0.40 mL) were added, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate, and insoluble matter was filtered off. The filtrate was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (335 mg).

[0144] Reference Example 41 tert-butyl N-[1-(prop-2-yn-1-yl)cyclopropyl]carbamate To a solution of tert-butyl N-[1-(2-hydroxyethyl)cyclopropyl]carbamate (350 mg) in dichloromethane (5 mL) was added 1,1,1-triacetoxy-1,1-dihydro-1,2-benzoiodoxol-3-(1H)-one (848 mg), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the resulting residue was diluted with ethyl acetate. Then, a saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to quench the reaction. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and to a solution of the resulting residue in methanol (10 mL), potassium carbonate (721 mg) and dimethyl (1-diazo-2-oxopropyl)phosphonate (0.33 mL) were added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate, and insoluble matter was filtered off. The filtrate was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (291 mg).

[0145] Reference Example 42 tert-Butyl N-[1-(prop-2-yn-1-yl)cyclobutyl]carbamate To a solution of tert-butyl N-[1-(2-hydroxyethyl)cyclobutyl]carbamate (350 mg) in dichloromethane (5 mL) was added 1,1,1-triacetoxy-1,1-dihydro-1,2-benzoiodoxol-3-(1H)-one (793 mg), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the resulting residue was diluted with ethyl acetate. Then, a saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to quench the reaction. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and to a solution of the resulting residue in methanol (10 mL), potassium carbonate (674 mg) and dimethyl (1-diazo-2-oxopropyl)phosphonate (0.31 mL) were added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate, and insoluble matter was filtered off. The filtrate was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (323 mg).

[0146] Reference Example 43 tert-butyl N-(but-3-yn-1-yl)-N-methylcarbamate 1,1,1-Triacetoxy-1,1-dihydro-1,2-benzoiodoxol-3-(1H)-one (928 mg) was added to a solution of tert-butyl N-(3-hydroxypropyl)-N-methylcarbamate (360 mg) in dichloromethane (10 mL), and the mixture was stirred at room temperature for 1 hour. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, then the mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. Potassium carbonate (788 mg) and dimethyl (1-diazo-2-oxopropyl)phosphonate (0.36 mL) were added to a solution of the residue obtained by distilling off the solvent under reduced pressure in methanol (10 mL), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate, and insoluble matter was filtered off. The filtrate was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (281 mg).

[0147] Reference Example 44 tert-Butyl N-(but-3-yn-1-yl)-N-ethylcarbamate Sodium hydride (89 mg) was added to a solution of tert-butyl N-(but-3-yn-1-yl)carbamate (250 mg) in THF (5 mL) under ice cooling, and the mixture was stirred at room temperature for 15 minutes. Ethyl iodide (0.24 mL) was added to the reaction solution, and the mixture was stirred at room temperature for 3 hours. Water was added to the reaction solution under ice cooling to quench the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (216 mg).

[0148] Reference Example 45 tert-butyl N-methyl-N-[(2S)-pent-4-yn-2-yl]carbamate To a solution of tert-butyl N-[(2S)-pent-4-yn-2-yl]carbamate (300 mg) obtained in Reference Example 32 in THF (5 mL) was added sodium hydride (98 mg) under ice cooling, and the mixture was stirred at room temperature for 15 minutes. Methyl iodide (0.20 mL) was added to the reaction solution, and the mixture was stirred at room temperature for 3 hours. Water was added to the reaction solution under ice cooling to quench the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (283 mg). [α] Ｄ ２４ = -15.28° (c = 0.25, chloroform)

[0149] Reference Example 46 tert-butyl N-methyl-N-[1-(prop-2-yn-1-yl)cyclopropyl]carbamate To a solution of tert-butyl N-[1-(prop-2-yn-1-yl)cyclopropyl]carbamate (225 mg) obtained in Reference Example 41 in THF (5 mL) was added sodium hydride (69 mg) in an ice bath, and the mixture was stirred at room temperature for 15 minutes. Methyl iodide (0.14 mL) was added to the reaction solution, and the mixture was stirred at room temperature for 4 hours. Water was added to the reaction solution in an ice bath to quench the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (280 mg).

[0150] Reference Example 47 tert-butyl N-[(3E)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-1-yl]carbamate To a solution of tert-butyl N-(but-3-yn-1-yl)carbamate (300 mg) in dichloromethane (10 mL), 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.38 mL), bis(cyclopentadienyl)zirconium(IV) chloride hydride (114 mg), and TEA (0.062 mL) were added, and the mixture was stirred for 10 hours at 40° C. The reaction solution was concentrated, and the resulting residue was purified by silica gel column chromatography to obtain the title compound (432 mg).

[0151] Reference Example 48 tert-Butyl N-[(2S,4E)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pent-4-en-2-yl]carbamate To a solution of tert-butyl N-[(2S)-pent-4-yn-2-yl]carbamate (300 mg) obtained in Reference Example 32 in dichloromethane (7.5 mL), 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.35 mL), bis(cyclopentadienyl)zirconium(IV) chloride hydride (106 mg), and TEA (0.057 mL) were added, and the mixture was stirred at 40° C. for 20 hours. The reaction solution was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (342 mg). [α] Ｄ ２４ = -25.05° (c = 0.30, chloroform)

[0152] Reference Example 49 tert-Butyl N-[(2R,4E)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pent-4-en-2-yl]carbamate To a solution of tert-butyl N-[(2R)-pent-4-yn-2-yl]carbamate (300 mg) obtained in Reference Example 33 in dichloromethane (7.5 mL), 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.35 mL), bis(cyclopentadienyl)zirconium(IV) chloride hydride (106 mg), and TEA (0.057 mL) were added, and the mixture was stirred for 20 hours at 40° C. The reaction solution was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (296 mg).

[0153] Reference Example 50 tert-butyl N-[(3S,5E)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hex-5-en-3-yl]carbamate To a dichloromethane (5 mL) solution of tert-butyl N-[(3S)-hex-5-yn-3-yl]carbamate (200 mg) obtained in Reference Example 34, 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.22 mL), bis(cyclopentadienyl)zirconium(IV) chloride hydride (65 mg), and TEA (0.035 mL) were added, and the mixture was stirred for 15 hours at 40° C. The reaction solution was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (211 mg).

[0154] Reference Example 51 tert-butyl N-[(3R,5E)-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hex-5-en-3-yl]carbamate To a solution of tert-butyl N-[(3R)-2-methylhex-5-yn-3-yl]carbamate (200 mg) obtained in Reference Example 36 in dichloromethane (5 mL), 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.20 mL), bis(cyclopentadienyl)zirconium(IV) chloride hydride (61 mg), and TEA (0.033 mL) were added, and the mixture was stirred for 15 hours at 40° C. The reaction solution was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (219 mg).

[0155] Reference Example 52 tert-butyl N-[(4E)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)(1,1,1- ２ H ３ ) pent-4-en-2-yl]carbamate tert-Butyl N-[(1,1,1- ２ H ３To a solution of [(2,4-dimethyl-2,4-dioxaborolane)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.65 mL) and bis(cyclopentadienyl)zirconium(IV) chloride hydride (194 mg) were added bis(cyclopentadienyl)zirconium(IV) chloride hydride (194 mg) in dichloromethane (20 mL), and the mixture was stirred at 40° C. for 24 hours. The reaction solution was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (628 mg).

[0156] Reference Example 53 tert-butyl N-[(2R,4E)-1,1,1-trifluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pent-4-en-2-yl]carbamate To a dichloromethane (10 mL) solution of tert-butyl N-[(2R)-1,1,1-trifluoropent-4-yn-2-yl]carbamate (430 mg) obtained in Step 3 of Reference Example 39, 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.39 mL) and bis(cyclopentadienyl)zirconium(IV) chloride hydride (117 mg) were added, and the mixture was stirred for 24 hours at 40° C. The reaction solution was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (189 mg).

[0157] Reference Example 54 tert-Butyl N-{1-[(2E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)prop-2-en-1-yl]cyclopropyl}carbamate To a dichloromethane (5 mL) solution of tert-butyl N-[1-(prop-2-yn-1-yl)cyclopropyl]carbamate (260 mg) obtained in Reference Example 41, 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.29 mL), bis(cyclopentadienyl)zirconium(IV) chloride hydride (86 mg), and TEA (0.046 mL) were added, and the mixture was stirred at 40° C. for 20 hours and at room temperature over the weekend. The reaction solution was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (330 mg).

[0158] Reference Example 55 tert-Butyl N-{1-[(2E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)prop-2-en-1-yl]cyclobutyl}carbamate To a dichloromethane (5 mL) solution of tert-butyl N-[1-(prop-2-yn-1-yl)cyclobutyl]carbamate (275 mg) obtained in Reference Example 42, 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.28 mL), bis(cyclopentadienyl)zirconium(IV) chloride hydride (85 mg), and TEA (0.046 mL) were added, and the mixture was stirred at 40° C. for 20 hours and at room temperature over the weekend. The reaction solution was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (255 mg).

[0159] Reference Example 56 tert-butyl N-methyl-N-[(3E)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-1-yl]carbamate To a solution of tert-butyl N-(but-3-yn-1-yl)-N-methylcarbamate (300 mg) obtained in Reference Example 43 in dichloromethane (7.5 mL), 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.35 mL), bis(cyclopentadienyl)zirconium(IV) chloride hydride (106 mg), and TEA (0.057 mL) were added, and the mixture was stirred for 12 hours at 40° C. The reaction solution was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (256 mg).

[0160] Reference Example 57 4,5-dibromo-N-(but-3-yn-1-yl)-1H-imidazole-2-carboxamide To a solution of 4,5-dibromo-1H-imidazole-2-carboxylic acid (275 mg) obtained in Step 2 of Reference Example 1, but-3-yn-1-amine (141 mg), and DIPEA (0.53 mL) in DMF (2.5 mL) was added HATU (581 mg), and the mixture was stirred at room temperature for 3 hours. The reaction solution was purified by reverse-phase column chromatography to give the title compound (169 mg). MS (ESI+) m / z 321.9 (M+H) ＋

[0161] Reference Example 58 N-(but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide HATU (879 mg) was added to a solution of 1H-1,3-benzodiazole-2-carboxylic acid (300 mg), but-3-yn-1-amine (160 mg), and DIPEA (0.96 mL) in DMF (2 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was purified by reverse phase column chromatography to give the title compound (221 mg). MS (ESI+) m / z 214.0 (M+H) ＋

[0162] Reference Example 59 4,5-dibromo-N-(but-3-yn-1-yl)-1-methyl-1H-imidazole-2-carboxamide [Step 1] Preparation of methyl 4,5-dibromo-1-methyl-1H-imidazole-2-carboxylate To a solution of methyl 4,5-dibromo-1H-imidazole-2-carboxylate (100 mg) obtained in Step 1 of Reference Example 1 and potassium carbonate (73 mg) in DMF (1.5 mL), methyl iodide (0.033 mL) was added and stirred at room temperature for 1 hour. The reaction solution was purified by silica gel column chromatography to obtain the title compound (105 mg). MS (ESI+) m / z 298.9 (M+H) ＋ [Step 2] Preparation of 4,5-dibromo-1-methyl-1H-imidazole-2-carboxylic acid To a mixed solution of methyl 4,5-dibromo-1-methyl-1H-imidazole-2-carboxylate (100 mg) in THF (1 mL) and methanol (1 mL), 1M aqueous sodium hydroxide solution (1.0 mL) was added and stirred at 50°C for 2 hours. The reaction solution was concentrated, and the resulting residue was neutralized with 1M hydrochloric acid and diluted with water, and the resulting precipitate was collected by filtration. The resulting residue was washed with water and dried under reduced pressure to give the title compound (91 mg). MS (ESI+) m / z 284.9 (M+H) ＋[Step 3] Preparation of 4,5-dibromo-N-(but-3-yn-1-yl)-1-methyl-1H-imidazole-2-carboxamide HATU (181 mg) was added to a solution of 4,5-dibromo-1-methyl-1H-imidazole-2-carboxylic acid (90 mg), but-3-yn-1-amine (33 mg), and DIPEA (0.27 mL) in DMF (1.5 mL), and the mixture was stirred at room temperature for 2 hours. But-3-yn-1-amine (33 mg), DIPEA (0.27 mL), and HATU (181 mg) were added to the reaction mixture, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was purified by reverse phase column chromatography to give the title compound (70 mg). MS (ESI+) m / z 335.9 (M+H)+

[0163] Reference Example 60 tert-Butyl N-[(tert-butoxy)carbonyl]-N-{3-iodoimidazo[1,2-a]pyridin-8-yl}carbamate [Step 1] Preparation of tert-butyl N-[(tert-butoxy)carbonyl]-N-{imidazo[1,2-a]pyridin-8-yl}carbamate

[0043] A solution of imidazo[1,2-a]pyridin-8-amine (1.00 g) in dichloromethane (10 mL) was added with Boc ２ 0 (5.2 mL) and DMAP (138 mg) were added, and the mixture was stirred at 30°C for 4 hours. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (2.10 g). MS (ESI+) m / z 334.1 (M+H) ＋[Step 2] Preparation of tert-butyl N-[(tert-butoxy)carbonyl]-N-{3-iodoimidazo[1,2-a]pyridin-8-yl}carbamate. NIS (1.77 g) was added to a solution of tert-butyl N-[(tert-butoxy)carbonyl]-N-{imidazo[1,2-a]pyridin-8-yl}carbamate (2.10 g) in acetonitrile (13 mL), and the mixture was stirred at 45°C for 12 hours. Saturated aqueous sodium bicarbonate and 20% aqueous sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (2.78 g). MS (ESI+) m / z 460.1 (M+H) ＋

[0164] Reference Example 61 tert-Butyl N-[(tert-butoxy)carbonyl]-N-{3-iodoimidazo[1,2-b]pyridazin-8-yl}carbamate [Step 1] Preparation of tert-butyl N-[(tert-butoxy)carbonyl]-N-{imidazo[1,2-b]pyridazin-8-yl}carbamate

[0043] To a solution of imidazo[1,2-b]pyridazin-8-amine (265 mg) and DMAP (36 mg) in THF (7.5 mL) was added Boc ２ 0 (1.4 mL) was added, and the mixture was stirred at 50° C. for 1 hour. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (624 mg). MS (ESI+) m / z 335.0 (M+H) ＋[Step 2] Preparation of tert-butyl N-[(tert-butoxy)carbonyl]-N-{3-iodoimidazo[1,2-b]pyridazin-8-yl}carbamate NIS (521 mg) was added to a solution of tert-butyl N-[(tert-butoxy)carbonyl]-N-{imidazo[1,2-b]pyridazin-8-yl}carbamate (620 mg) in acetonitrile (5 mL), and the mixture was stirred at 50°C for 10 hours. The reaction solution was allowed to cool, and the precipitate was collected by filtration to obtain a crude residue. The resulting residue was washed with acetonitrile to obtain the title compound (788 mg). MS (ESI+) m / z 460.9 (M+H) ＋

[0165] Reference Example 62 tert-butyl N-{3-iodoimidazo[1,2-b]pyridazin-8-yl}-N-(2-methoxyethyl)carbamate [Step 1] Preparation of 6-chloro-N-(2-methoxyethyl)imidazo[1,2-b]pyridazin-8-amine 2-Methoxyethan-1-amine (2.8 mL) was added to a solution of 8-bromo-6-chloroimidazo[1,2-b]pyridazine (300 mg) in NMP (2 mL), and the mixture was stirred at 140°C for 30 minutes under microwave irradiation. The reaction solution was purified by reverse phase column chromatography to give the title compound (290 mg). MS (ESI+) m / z 226.9 (M+H) ＋ [Step 2] Preparation of N-(2-methoxyethyl)imidazo[1,2-b]pyridazin-8-amine hydrochloride A solution of 6-chloro-N-(2-methoxyethyl)imidazo[1,2-b]pyridazin-8-amine (290 mg) and 5 w / w% Pd—C (75 mg) in methanol (10 mL) was stirred under a hydrogen atmosphere (0.4 MPa) at room temperature for 2 hours and at 45° C. for 2 hours. The insoluble matter was filtered off through Celite (registered trademark), and the obtained filtrate was concentrated to give the title compound (286 mg). MS (ESI+) m / z 193.0 (M+H) ＋[Step 3] Preparation of tert-butyl N-{imidazo[1,2-b]pyridazin-8-yl}-N-(2-methoxyethyl)carbamate To a solution of N-(2-methoxyethyl)imidazo[1,2-b]pyridazin-8-amine hydrochloride (285 mg), TEA (0.52 mL), and DMAP (23 mg) in THF (5 mL) was added Boc ２ 0 (0.86 mL) was added and the mixture was stirred at room temperature overnight. ２ 0 (0.86 mL) was added and the mixture was stirred at 50° C. for 24 hours. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (147 mg). MS (ESI+) m / z 293.0 (M+H) ＋ [Step 4] Preparation of tert-butyl N-{3-iodoimidazo[1,2-b]pyridazin-8-yl}-N-(2-methoxyethyl)carbamate. NIS (140 mg) was added to a solution of tert-butyl N-{imidazo[1,2-b]pyridazin-8-yl}-N-(2-methoxyethyl)carbamate (145 mg) in acetonitrile (5 mL), and the mixture was stirred at 50°C for 8 hours. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (210 mg). MS (ESI+) m / z 418.9 (M+H) ＋

[0166] Reference Example 63 tert-Butyl N-[(tert-butoxy)carbonyl]-N-{6-chloro-3-iodoimidazo[1,2-b]pyridazin-8-yl}carbamate [Step 1] Preparation of 8-bromo-6-chloro-3-iodoimidazo[1,2-b]pyridazine NIS (726 mg) and trifluoroacetic acid (0.33 mL) were added to a solution of 8-bromo-6-chloroimidazo[1,2-b]pyridazine (500 mg) in chloroform (10 mL), and the mixture was stirred at room temperature for 12 hours. The reaction mixture was concentrated, and the resulting residue was diluted with ethyl acetate. After that, a saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to terminate the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (763 mg). MS (ESI+) m / z 359.6 (M+H) ＋ [Step 2] Preparation of 6-chloro-3-iodoimidazo[1,2-b]pyridazin-8-amine To a solution of 8-bromo-6-chloro-3-iodoimidazo[1,2-b]pyridazine (300 mg) in NMP (2 mL) was added 28% aqueous ammonia (1.7 mL), and the mixture was stirred at 140°C for 30 minutes under microwave irradiation. The reaction solution was purified by reverse phase column chromatography to give the title compound (257 mg). MS (ESI+) m / z 294.7 (M+H) ＋ [Step 3] Preparation of tert-butyl N-[(tert-butoxy)carbonyl]-N-{6-chloro-3-iodoimidazo[1,2-b]pyridazin-8-yl}carbamate

[0112] A solution of 6-chloro-3-iodoimidazo[1,2-b]pyridazin-8-amine (355 mg) in dichloromethane (5 mL) was treated with Boc ２ 0 (0.78 mL) and DMAP (21 mg) were added, and the mixture was stirred at 40° C. for 1 hour. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (543 mg). MS (ESI+) m / z 494.8 (M+H) ＋

[0167] Reference Example 64 Chloriodoimidazopyridazine [Step 1] Preparation of 3-iodoimidazo[1,2-b]pyridazin-8-amine To a mixed solution of tert-butyl N-[(tert-butoxy)carbonyl]-N-{3-iodoimidazo[1,2-b]pyridazin-8-yl}carbamate (250 mg) obtained in Step 2 of Reference Example 61 in dichloromethane (2.5 mL) and methanol (2.5 mL), hydrogen chloride (4 M in 1,4-dioxane, 1.4 mL) was added and the mixture was stirred at 50°C for 10 hours. The reaction mixture was concentrated, and the resulting residue was neutralized with saturated aqueous sodium bicarbonate solution and diluted with water, and the resulting precipitate was collected by filtration. The resulting residue was washed with water and dried under reduced pressure to give the title compound (136 mg). MS (ESI+) m / z 260.8 (M+H) ＋ [Step 2] Preparation of 7-chloro-3-iodoimidazo[1,2-b]pyridazin-8-amine NCS (87 mg) was added to a solution of 3-iodoimidazo[1,2-b]pyridazin-8-amine (135 mg) in acetonitrile (5 mL), and the mixture was stirred at 75°C for 6 hours. NCS (87 mg) was further added to the reaction mixture, and the mixture was stirred at 75°C for 14 hours. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, and the mixture was diluted with water and extracted with a mixed solvent of ethyl acetate and THF. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by reverse-phase column chromatography to give the title compound (116 mg). MS (ESI+) m / z 294.7 (M+H) ＋ [Step 3] Preparation of tert-butyl N-[(tert-butoxy)carbonyl]-N-{7-chloro-3-iodoimidazo[1,2-b]pyridazin-8-yl}carbamate To a solution of 7-chloro-3-iodoimidazo[1,2-b]pyridazin-8-amine (115 mg), TEA (0.16 mL), and DMAP (7.2 mg) in THF (5 mL) was added Boc ２ 0 (0.45 mL) was added, and the mixture was stirred at 65° C. for 6 hours. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (187 mg). MS (ESI+) m / z 494.8 (M+H) ＋

[0168] Reference Example 65 tert-Butyl N-{7-bromo-3-iodoimidazo[1,2-b]pyridazin-8-yl}-N-[(tert-butoxy)carbonyl]carbamate [Step 1] Preparation of 7-bromo-3-iodoimidazo[1,2-b]pyridazin-8-amine To a solution of 3-iodoimidazo[1,2-b]pyridazin-8-amine (500 mg) obtained in Step 1 of Reference Example 64 in acetonitrile (25 mL) was added NBS (428 mg), and the mixture was stirred at 75°C for 20 hours. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, diluted with water, and extracted with a mixed solvent of ethyl acetate and THF. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was washed with acetonitrile to give the title compound (551 mg). MS (ESI+) m / z 340.6 (M+H) ＋ [Step 2] Preparation of tert-butyl N-{7-bromo-3-iodoimidazo[1,2-b]pyridazin-8-yl}-N-[(tert-butoxy)carbonyl]carbamate To a solution of 7-bromo-3-iodoimidazo[1,2-b]pyridazin-8-amine (550 mg), TEA (0.68 mL), and DMAP (30 mg) in THF (15 mL) was added Boc ２ 0 (1.9 mL) was added and the mixture was stirred at 65°C for 1 hour. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to obtain a crude residue. The resulting residue was washed with a mixed solvent of n-hexane and diethyl ether to obtain the title compound (834 mg). MS (ESI+) m / z 540.8 (M+H) ＋

[0169] Reference Example 66 tert-Butyl N-[(tert-butoxy)carbonyl]-N-{6,7-dichloro-3-iodoimidazo[1,2-b]pyridazin-8-yl}carbamate [Step 1] Preparation of 6,7-dichloro-3-iodoimidazo[1,2-b]pyridazin-8-amine. NCS (193 mg) was added to a solution of 6-chloro-3-iodoimidazo[1,2-b]pyridazin-8-amine (170 mg) obtained in Step 2 of Reference Example 63 in acetonitrile (5 mL), and the mixture was stirred at 75°C for 13 hours. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, and the mixture was diluted with water and extracted with a mixed solvent of ethyl acetate and THF. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was washed with methanol to give the title compound (135 mg). MS (ESI+) m / z 328.6 (M+H) ＋ [Step 2] Preparation of tert-butyl N-[(tert-butoxy)carbonyl]-N-{6,7-dichloro-3-iodoimidazo[1,2-b]pyridazin-8-yl}carbamate To a solution of 6,7-dichloro-3-iodoimidazo[1,2-b]pyridazin-8-amine (135 mg), TEA (0.17 mL), and DMAP (7.5 mg) in THF (5 mL) was added Boc ２ 0 (0.47 mL) was added and the mixture was stirred at 65° C. for 1 hour. The reaction mixture was concentrated and the resulting residue was purified by silica gel column chromatography to give the title compound (218 mg). MS (ESI+) m / z 528.8 (M+H) ＋

[0170] Reference Example 67 tert-Butyl N-[(tert-butoxy)carbonyl]-N-{3-iodoimidazo[1,2-a]pyrazin-8-yl}carbamate [Step 1] Preparation of 8-chloro-3-iodoimidazo[1,2-a]pyrazine NIS (916 mg) was added to a solution of 8-chloroimidazo[1,2-a]pyrazine (500 mg) in acetonitrile (15 mL), and the mixture was stirred at 50°C for 16 hours. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to terminate the reaction, and the mixture was extracted with a mixed solvent of ethyl acetate and THF. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was washed with acetonitrile to give the title compound (871 mg). MS (ESI+) m / z 279.8 (M+H) ＋ [Step 2] Preparation of 3-iodoimidazo[1,2-a]pyrazin-8-amine To a solution of 8-chloro-3-iodoimidazo[1,2-a]pyrazine (500 mg) in NMP (2.5 mL) was added 28% aqueous ammonia (1.8 mL), and the mixture was stirred at 140°C for 30 minutes under microwave irradiation. The reaction solution was purified by reverse phase column chromatography to give the title compound (417 mg). MS (ESI+) m / z 260.8 (M+H) ＋ [Step 3] Preparation of tert-butyl N-[(tert-butoxy)carbonyl]-N-{3-iodoimidazo[1,2-a]pyrazin-8-yl}carbamate

[0113] To a solution of 3-iodoimidazo[1,2-a]pyrazin-8-amine (88 mg) and DMAP (6.2 mg) in THF (5 mL) was added Boc ２ 0 (0.23 mL) was added, and the mixture was stirred at 60° C. for 2 hours. TEA (0.070 mL) and Boc ２ 0 (0.23 mL) was added and the mixture was stirred at 60° C. for 2 hours. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (113 mg). MS (ESI+) m / z 460.9 (M+H) ＋

[0171] Reference Example 68 tert-Butyl N-[(tert-butoxy)carbonyl]-N-{5-chloro-3-iodoimidazo[1,2-a]pyrazin-8-yl}carbamate [Step 1] Preparation of 5-chloro-3-iodoimidazo[1,2-a]pyrazin-8-amine To a solution of 3-iodoimidazo[1,2-a]pyrazin-8-amine (150 mg) obtained in Step 2 of Reference Example 67 in acetonitrile (5 mL) was added NCS (96 mg), and the mixture was stirred at 75°C for 10 hours. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, diluted with water, and extracted with a mixed solvent of ethyl acetate and THF. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was washed with acetonitrile to give the title compound (137 mg). MS (ESI+) m / z 294.7 (M+H) ＋ [Step 2] Preparation of tert-butyl N-[(tert-butoxy)carbonyl]-N-{5-chloro-3-iodoimidazo[1,2-a]pyrazin-8-yl}carbamate

[0111] To a solution of 5-chloro-3-iodoimidazo[1,2-a]pyrazin-8-amine (135 mg) and DMAP (8.4 mg) in THF (5 mL) was added Boc ２ 0 (0.32 mL) was added and the mixture was stirred at 60° C. for 1 hour. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (73 mg). MS (ESI+) m / z 494.9 (M+H) ＋

[0172] Reference Example 69 tert-Butyl N-{6-bromo-3-iodoimidazo[1,2-a]pyrazin-8-yl}-N-[(tert-butoxy)carbonyl]carbamate [Step 1] Preparation of tert-butyl N-{6-bromoimidazo[1,2-a]pyrazin-8-yl}-N-[(tert-butoxy)carbonyl]carbamate

[0043] To a solution of 6-bromoimidazo[1,2-a]pyrazin-8-amine (300 mg) and DMAP (26 mg) in THF (5 mL) was added Boc ２ 0 (0.97 mL) was added and the mixture was stirred at 60° C. for 1 hour. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (566 mg). MS (ESI+) m / z 414.9 (M+H) ＋[Step 2] Preparation of tert-butyl N-{6-bromo-3-iodoimidazo[1,2-a]pyrazin-8-yl}-N-[(tert-butoxy)carbonyl]carbamate. NIS (170 mg) was added to a solution of tert-butyl N-{6-bromoimidazo[1,2-a]pyrazin-8-yl}-N-[(tert-butoxy)carbonyl]carbamate (250 mg) in acetonitrile (5 mL), and the mixture was stirred at room temperature for 10 hours and at 70°C for 10 hours. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (96 mg). MS (ESI+) m / z 540.7 (M+H) ＋

[0173] Reference Example 70 tert-Butyl N-[(tert-butoxy)carbonyl]-N-{3-iodo-2-methylimidazo[1,2-a]pyrazin-8-yl}carbamate [Step 1] Preparation of 8-chloro-3-iodo-2-methylimidazo[1,2-a]pyrazine NIS (923 mg) was added to a solution of 8-chloro-2-methylimidazo[1,2-a]pyrazine (550 mg) in acetonitrile (15 mL), and the mixture was stirred at 50°C for 10 hours and at room temperature over the weekend. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, and the mixture was diluted with water and extracted with a mixed solvent of ethyl acetate and THF. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was washed with acetonitrile to give the title compound (952 mg). MS (ESI+) m / z 293.7 (M+H) ＋[Step 2] Preparation of 3-iodo-2-methylimidazo[1,2-a]pyrazin-8-amine To a solution of 8-chloro-3-iodo-2-methylimidazo[1,2-a]pyrazine (950 mg) in NMP (10 mL) was added 28% aqueous ammonia (3.3 mL), and the mixture was stirred at 140°C for 30 minutes under microwave irradiation. The reaction solution was purified by reverse phase column chromatography to give the title compound (752 mg). MS (ESI+) m / z 274.8 (M+H) ＋ [Step 3] Preparation of tert-butyl N-[(tert-butoxy)carbonyl]-N-{3-iodo-2-methylimidazo[1,2-a]pyrazin-8-yl}carbamate To a solution of 3-iodo-2-methylimidazo[1,2-a]pyrazin-8-amine (125 mg), TEA (0.19 mL), and DMAP (8.4 mg) in THF (5 mL) was added Boc ２ 0 (0.31 mL) was added, and the mixture was stirred at 60° C. for 1 hour and at room temperature overnight. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (196 mg). MS (ESI+) m / z 474.9 (M+H) ＋

[0174] Reference Example 71 tert-Butyl N-[(tert-butoxy)carbonyl]-N-{5-chloro-3-iodo-2-methylimidazo[1,2-a]pyrazin-8-yl}carbamate [Step 1] Preparation of 5-chloro-3-iodo-2-methylimidazo[1,2-a]pyrazin-8-amine. NCS (91 mg) was added to a solution of 3-iodo-2-methylimidazo[1,2-a]pyrazin-8-amine (150 mg) obtained in Step 2 of Reference Example 70 in acetonitrile (5 mL), and the mixture was stirred at 75°C for 1 hour. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, and the mixture was diluted with water and extracted with a mixed solvent of ethyl acetate and THF. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was washed with acetonitrile to give the title compound (158 mg). MS (ESI+) m / z 308.7 (M+H) ＋[Step 2] Preparation of tert-butyl N-[(tert-butoxy)carbonyl]-N-{5-chloro-3-iodo-2-methylimidazo[1,2-a]pyrazin-8-yl}carbamate To a solution of 5-chloro-3-iodo-2-methylimidazo[1,2-a]pyrazin-8-amine (158 mg), TEA (0.21 mL), and DMAP (9.4 mg) in THF (5 mL) was added Boc ２ 0 (0.35 mL) was added, and the mixture was stirred at 60° C. for 1 hour and at room temperature overnight. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (33 mg). MS (ESI+) m / z 508.9 (M+H) ＋

[0175] Reference Example 72 tert-butyl 4-iodo-2-methyl-1H-imidazole-1-carboxylate To a solution of 4-iodo-2-methyl-1H-imidazole (200 mg) and DMAP (176 mg) in THF (1 mL) was added Boc ２ 0 (0.33 mL) was added and stirred at room temperature overnight. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (262 mg). MS (ESI+) m / z 308.8 (M+H) ＋

[0176] Reference Example 73 3-bromo-7-methyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazine To a solution of 3-bromo-5H,6H,7H,8H-imidazo[1,2-a]pyrazine dihydrochloride (161 mg) and TEA (0.11 mL) in methanol (2 mL), 37% aqueous formaldehyde solution (0.088 mL) and sodium cyanoborohydride (55 mg) were added and stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane, and the organic layer was washed with saturated aqueous sodium bicarbonate solution and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound (130 mg). MS (ESI+) m / z 216.0 (M+H) ＋

[0177] Reference Example 74 3-bromo-7-ethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazine To a solution of 3-bromo-5H,6H,7H,8H-imidazo[1,2-a]pyrazine dihydrochloride (100 mg) and TEA (0.10 mL) in ethanol (1 mL), acetaldehyde (0.098 mL) and sodium cyanoborohydride (34 mg) were added and stirred at room temperature for 1 hour. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture to terminate the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (64 mg). MS (ESI+) m / z 229.9 (M+H) ＋

[0178] Reference Example 75 3-bromo-7-(cyclopropylmethyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazine To a solution of 3-bromo-5H,6H,7H,8H-imidazo[1,2-a]pyrazine dihydrochloride (80 mg) and TEA (0.081 mL) in ethanol (1 mL), cyclopropanecarbaldehyde (102 mg) and sodium cyanoborohydride (27 mg) were added and stirred at room temperature for 1 hour. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture to terminate the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (43 mg). MS (ESI+) m / z 258.1 (M+H) ＋

[0179] Reference Example 76 1-{3-bromo-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-yl}ethan-1-one Acetic anhydride (0.041 mL) was added to a solution of 3-bromo-5H,6H,7H,8H-imidazo[1,2-a]pyrazine dihydrochloride (100 mg) and TEA (0.061 mL) in ethanol (1 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated, and the resulting residue was washed with diethyl ether to give the title compound (166 mg). MS (ESI+) m / z 245.8 (M+H)＋

[0180] Reference Example 77 4-{3-iodoimidazo[1,2-a]pyridin-7-yl}-1-methyl-1H-pyrazole [Step 1] Preparation of 4-{imidazo[1,2-a]pyridin-7-yl}-1-methyl-1H-pyrazole To a mixture of 7-bromoimidazo[1,2-a]pyridine (2.00 g) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (3.17 g), Pd(dppf)Cl ２ ・CH ２ Cl ２ (1.24 g), potassium carbonate (4.21 g), 1,4-dioxane (51 mL), and water (17 mL) were added and degassed, and then stirred at 100°C under an argon atmosphere for 2 hours. The reaction solution was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give a crude residue. The resulting residue was washed with diethyl ether to give the title compound (1.84 g). MS (ESI+) m / z 199.2 (M+H) ＋ [Step 2] Preparation of 4-{3-iodoimidazo[1,2-a]pyridin-7-yl}-1-methyl-1H-pyrazole. NIS (2.30 g) was added to a solution of 4-{imidazo[1,2-a]pyridin-7-yl}-1-methyl-1H-pyrazole (1.84 g) in acetonitrile (46 mL), and the mixture was stirred at room temperature for 3 hours. The reaction mixture was quenched by adding saturated aqueous sodium bicarbonate and 20% aqueous sodium hydrogen thiosulfate, diluted with water, and the precipitate was collected by filtration. The resulting residue was washed with methanol and dried under reduced pressure to give the title compound (2.18 g). MS (ESI+) m / z 324.8 (M+H) ＋

[0181] Reference Example 78 7-iodopyrazolo[3,2-b][1,3]thiazole [Step 1] Preparation of pyrazolo[3,2-b][1,3]thiazole Sulfuric acid (6 mL) was added to a solution of pyrazolo[3,2-b][1,3]thiazole-7-carboxylic acid (1.60 g) in water (6 mL), and the mixture was stirred at 120°C overnight. In an ice bath, the reaction mixture was neutralized with 5M aqueous sodium hydroxide solution and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give the title compound (1.02 g). MS (ESI+) m / z 125.3 (M+H) ＋ [Step 2] Preparation of 7-iodopyrazolo[3,2-b][1,3]thiazole NIS (2.03 g) was added to a solution of pyrazolo[3,2-b][1,3]thiazole (1.02 g) in acetonitrile (41 mL), and the mixture was stirred at 50°C for 1 hour. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture to terminate the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (1.72 g). MS (ESI+) m / z 251.3 (M+H) ＋

[0182] Reference Example 79 4-{3-iodopyrazolo[1,5-a]pyridin-6-yl}-1-methyl-1H-pyrazole [Step 1] Preparation of 1-methyl-4-{pyrazolo[1,5-a]pyridin-6-yl}-1H-pyrazole A mixture of 6-bromopyrazolo[1,5-a]pyridine (150 mg) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (237 mg) was added with Pd(dppf)Cl ２ ・CH ２ Cl ２ (93 mg), potassium carbonate (316 mg), 1,4-dioxane (3 mL), and water (1 mL) were added and degassed, and then the mixture was stirred at 100°C under an argon atmosphere for 2 hours. The reaction mixture was purified by silica gel column chromatography to obtain a crude residue. The obtained residue was washed with diethyl ether to obtain the title compound (138 mg). MS (ESI+) m / z 199.2 (M+H) ＋[Step 2] Preparation of 4-{3-iodopyrazolo[1,5-a]pyridin-6-yl}-1-methyl-1H-pyrazole. NIS (176 mg) was added to a solution of 1-methyl-4-{pyrazolo[1,5-a]pyridin-6-yl}-1H-pyrazole (135 mg) in acetonitrile (2.5 mL), and the mixture was stirred at room temperature for 5 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, 10% aqueous sodium hydrogen thiosulfate, and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (217 mg). MS (ESI+) m / z 325.0 (M+H) ＋

[0183] Reference Example 80 4-{3-iodopyrazolo[1,5-a]pyridin-5-yl}-1-methyl-1H-pyrazole [Step 1] Preparation of 1-methyl-4-{pyrazolo[1,5-a]pyridin-5-yl}-1H-pyrazole A mixture of 5-bromopyrazolo[1,5-a]pyridine (150 mg) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (237 mg) was added with Pd(dppf)Cl ２ ・CH ２ Cl ２ (93 mg), potassium carbonate (316 mg), 1,4-dioxane (3 mL), and water (1 mL) were added and degassed, and then the mixture was stirred at 100°C under an argon atmosphere for 2 hours. The reaction mixture was purified by silica gel column chromatography to obtain a crude residue. The obtained residue was washed with n-hexane to obtain the title compound (150 mg). MS (ESI+) m / z 199.2 (M+H) ＋[Step 2] Preparation of 4-{3-iodopyrazolo[1,5-a]pyridin-5-yl}-1-methyl-1H-pyrazole. NIS (196 mg) was added to a solution of 1-methyl-4-{pyrazolo[1,5-a]pyridin-5-yl}-1H-pyrazole (150 mg) in acetonitrile (2.5 mL), and the mixture was stirred at room temperature for 10 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, 10% aqueous sodium hydrogen thiosulfate, and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (235 mg). MS (ESI+) m / z 325.0 (M+H) ＋

[0184] Reference Example 81 5-bromo-4-methoxy-1H-pyrazole NBS (286 mg) was added to a solution of 4-methoxy-1H-pyrazole (150 mg) in DMF (5 mL), and the mixture was stirred at room temperature for 4 hours. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (194 mg). MS (ESI+) m / z 176.8 (M+H) ＋

[0185] Reference Example 82 5-bromo-4-chloro-1H-pyrazol-3-amine NCS (258 mg) was added to a solution of 5-bromo-1H-pyrazol-3-amine (250 mg) in acetonitrile (5 mL), and the mixture was stirred at room temperature for 1 hour. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (223 mg). MS (ESI+) m / z 197.8 (M+H) ＋

[0186] Reference Example 83 tert-Butyl 3-iodo-4,5,6,7-tetrahydro-1H-indazole-1-carboxylate Iodine (623 mg) and potassium hydroxide (202 mg) were added to a solution of 4,5,6,7-tetrahydro-1H-indazole (200 mg) in DMF (2 mL), and the mixture was stirred at room temperature for 5 hours. The reaction mixture was diluted with saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was dissolved in dichloromethane (2 mL), and TEA (0.75 mL), DMAP (44 mg), and Boc ２ 0 (1.24 mL) was added and the mixture was stirred at room temperature overnight. ２ 0 (0.83 mL) was added and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (420 mg).

[0187] Reference Example 84 5-iodo-N-methylpyrimidin-2-amine To a solution of 2-chloro-5-iodopyrimidine (200 mg) in 2-propanol (1.5 mL), DIPEA (0.72 mL) and 40% aqueous methylamine solution (0.35 mL) were added, and the mixture was stirred at 140°C for 30 minutes under microwave irradiation. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (193 mg). MS (ESI+) m / z 235.8 (M+H) ＋

[0188] Reference Example 85 N-ethyl-5-iodopyrimidin-2-amine To a solution of 2-chloro-5-iodopyrimidine (200 mg) in 2-propanol (1.5 mL), DIPEA (0.72 mL) and 70% aqueous ethylamine (0.35 mL) were added, and the mixture was stirred at 140°C for 30 minutes under microwave irradiation. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (211 mg). MS (ESI+) m / z 249.8 (M+H) ＋

[0189] Reference Example 86 N-cyclopropyl-5-iodopyrimidin-2-amine To a solution of 2-chloro-5-iodopyrimidine (200 mg) in 2-propanol (1.5 mL), DIPEA (0.72 mL) and cyclopropanamine (119 mg) were added, and the mixture was stirred at 140°C for 30 minutes under microwave irradiation. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (215 mg). MS (ESI+) m / z 261.8 (M+H) ＋

[0190] Reference Example 87 N-(2-fluorophenyl)-5-iodopyrimidin-2-amine Methanesulfonic acid (0.040 mL) was added to a mixed solution of 2-chloro-5-iodopyrimidine (150 mg) and 2-fluoroaniline (87 mg) in 2-propanol (1.5 mL) and methanol (0.5 mL), and the mixture was stirred at 160°C for 30 minutes under microwave irradiation. The reaction mixture was concentrated, and the resulting residue was neutralized with saturated aqueous sodium bicarbonate, diluted with water, and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give a crude residue. The resulting residue was washed with n-hexane to give the title compound (136 mg). MS (ESI+) m / z 315.8 (M+H) ＋

[0191] Reference Example 88 N-(3-fluorophenyl)-5-iodopyrimidin-2-amine Methanesulfonic acid (0.054 mL) was added to a mixed solution of 2-chloro-5-iodopyrimidine (200 mg) and 3-fluoroaniline (116 mg) in 2-propanol (1.5 mL) and methanol (0.5 mL), and the mixture was stirred at 160°C for 30 minutes under microwave irradiation. The reaction mixture was concentrated, and the resulting residue was neutralized with saturated aqueous sodium bicarbonate, diluted with water, and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give a crude residue. The resulting residue was washed with n-hexane to give the title compound (176 mg). MS (ESI+) m / z 315.8 (M+H)＋

[0192] Reference Example 89 N-(4-fluorophenyl)-5-iodopyrimidin-2-amine Methanesulfonic acid (0.027 mL) was added to a mixed solution of 2-chloro-5-iodopyrimidine (200 mg) and 4-fluoroaniline (106 mg) in 2-propanol (1.5 mL) and methanol (0.5 mL), and the mixture was stirred at 160°C for 30 minutes under microwave irradiation. The reaction mixture was concentrated, and the resulting residue was neutralized with saturated aqueous sodium bicarbonate, diluted with water, and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to obtain a crude residue. The resulting residue was washed with a mixed solvent of n-hexane and diethyl ether to obtain the title compound (196 mg). MS (ESI+) m / z 315.8 (M+H) ＋

[0193] Reference Example 90 5-iodo-N-[3-(4-methylpiperazin-1-yl)phenyl]pyrimidin-2-amine Methanesulfonic acid (0.081 mL) was added to a mixed solution of 2-chloro-5-iodopyrimidine (150 mg) and 3-(4-methylpiperazin-1-yl)aniline (149 mg) in 2-propanol (1.5 mL) and methanol (0.5 mL), and the mixture was stirred at 160°C for 30 minutes under microwave irradiation. The reaction mixture was concentrated, and the resulting residue was neutralized with saturated aqueous sodium bicarbonate, diluted with water, and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by reverse-phase column chromatography to give the title compound (103 mg). MS (ESI+) m / z 395.9 (M+H) ＋

[0194] Reference Example 91 5-iodo-N-[4-(4-methylpiperazin-1-yl)phenyl]pyrimidin-2-amine Methanesulfonic acid (0.081 mL) was added to a mixed solution of 2-chloro-5-iodopyrimidine (150 mg) and 4-(4-methylpiperazin-1-yl)aniline (149 mg) in 2-propanol (1.5 mL) and methanol (0.5 mL), and the mixture was stirred at 160°C for 30 minutes under microwave irradiation. The reaction mixture was concentrated, and the resulting residue was neutralized with saturated aqueous sodium bicarbonate, diluted with water, and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by reverse-phase column chromatography to give the title compound (139 mg). MS (ESI+) m / z 395.9 (M+H) ＋

[0195] Reference Example 92 5-bromo-4-ethylpyrimidin-2-amine NBS (249 mg) was added to a solution of 4-ethylpyrimidin-2-amine (150 mg) in chloroform (5 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to obtain a crude residue. The resulting residue was washed with a mixed solvent of n-hexane and diethyl ether to obtain the title compound (246 mg). MS (ESI+) m / z 203.9 (M+H) ＋

[0196] Reference Example 93 5-bromo-4-cyclopropoxypyrimidin-2-amine [Step 1] Preparation of 4-cyclopropoxypyrimidin-2-amine Cyclopropanol (280 mg) was added to a solution of sodium hydride (232 mg) in THF (10 mL) under ice bath conditions, and the mixture was stirred for 15 minutes under ice bath conditions. 4-Chloropyrimidin-2-amine (500 mg) was added to the reaction mixture, and the mixture was stirred at 40°C for 3 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (188 mg). MS (ESI+) m / z 151.9 (M+H) ＋[Step 2] Preparation of 5-bromo-4-cyclopropoxypyrimidin-2-amine NBS (229 mg) was added to a solution of 4-cyclopropoxypyrimidin-2-amine (185 mg) in chloroform (5 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the resulting residue was diluted with ethyl acetate. After that, a saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to terminate the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (131 mg). MS (ESI+) m / z 231.8 (M+H) ＋

[0197] Reference Example 94 5-bromo-4-methoxy-N-methylpyrimidin-2-amine [Step 1] Preparation of 4-chloro-N-methylpyrimidin-2-amine To a solution of 2,4-dichloropyrimidine (25.0 g) in THF (130 mL) were added TEA (46.8 mL) and methylamine (40% methanol solution, 18.5 mL) in an ice bath, and the mixture was stirred at 90°C for 2.5 hours. After the reaction mixture was allowed to cool to room temperature, insoluble matter was filtered off and washed with THF. The residue obtained by concentrating the filtrate was purified by silica gel column chromatography to give the title compound (6.54 g). MS (ESI+) m / z 144.4 (M+H) ＋ [Step 2] Preparation of 5-bromo-4-chloro-N-methylpyrimidin-2-amine NBS (930 mg) was added to a solution of 4-chloro-N-methylpyrimidin-2-amine (500 mg) in acetonitrile (15 mL), and the mixture was stirred at 65°C for 1 hour. The reaction mixture was diluted with water, and the resulting precipitate was collected by filtration. The resulting residue was washed with water and dried under reduced pressure to give the title compound (676 mg). MS (ESI+) m / z 224.3 (M+H) ＋[Step 3] Preparation of 5-bromo-4-methoxy-N-methylpyrimidin-2-amine To a mixed solution of 5-bromo-4-chloro-N-methylpyrimidin-2-amine (250 mg) in THF (5 mL) and methanol (2.5 mL), sodium methoxide (5 M methanol solution, 0.45 mL) was added and stirred at 50°C for 3 hours. The reaction solution was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the resulting residue was purified by silica gel column chromatography to give the title compound (241 mg). MS (ESI+) m / z 219.8 (M+H) ＋

[0198] Reference Example 95 5-bromo-N-ethyl-4-methoxypyrimidin-2-amine [Step 1] Preparation of 4-chloro-N-ethylpyrimidin-2-amine To a solution of 2,4-dichloropyrimidine (750 mg) in THF (10 mL) were added TEA (1.8 mL) and 70% aqueous ethylamine solution (1.0 mL), and the mixture was stirred at 60°C for 1 hour. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (212 mg). MS (ESI+) m / z 157.9 (M+H) ＋ [Step 2] Preparation of 5-bromo-4-chloro-N-ethylpyrimidin-2-amine NBS (296 mg) was added to a solution of 4-chloro-N-ethylpyrimidin-2-amine (210 mg) in acetonitrile (5 mL), and the mixture was stirred at 50°C for 2 hours. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, diluted with water, and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (237 mg). MS (ESI+) m / z 237.8 (M+H) ＋[Step 3] Preparation of 5-bromo-N-ethyl-4-methoxypyrimidin-2-amine To a solution of 5-bromo-4-chloro-N-ethylpyrimidin-2-amine (235 mg) in methanol (5 mL) was added sodium methoxide (5 M methanol solution, 0.50 mL) and the mixture was stirred at 50°C for 1 hour. The reaction mixture was concentrated, and the resulting residue was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the resulting residue was purified by silica gel column chromatography to give the title compound (231 mg). MS (ESI+) m / z 231.9 (M+H) ＋

[0199] Reference Example 96 5-bromo-N-cyclopropyl-4-methoxypyrimidin-2-amine [Step 1] Preparation of 4-chloro-N-cyclopropylpyrimidin-2-amine To a solution of 2,4-dichloropyrimidine (700 mg) in THF (10 mL), TEA (1.6 mL) and cyclopropanamine (402 mg) were added and the mixture was stirred at 60°C for 1 hour. After the reaction mixture was allowed to cool to room temperature, insoluble matter was filtered off and washed with THF. The residue obtained by concentrating the filtrate was purified by silica gel column chromatography to give the title compound (206 mg). MS (ESI+) m / z 169.9 (M+H) ＋ [Step 2] Preparation of 5-bromo-4-chloro-N-cyclopropylpyrimidin-2-amine NBS (269 mg) was added to a solution of 4-chloro-N-cyclopropylpyrimidin-2-amine (205 mg) in acetonitrile (5 mL), and the mixture was stirred at 50°C for 2 hours. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, diluted with water, and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (95 mg). MS (ESI+) m / z 249.8 (M+H) ＋[Step 3] Preparation of 5-bromo-N-cyclopropyl-4-methoxypyrimidin-2-amine To a solution of 5-bromo-4-chloro-N-cyclopropylpyrimidin-2-amine (95 mg) in methanol (2.5 mL) was added sodium methoxide (5 M methanol solution, 0.19 mL) and stirred at 50°C for 1 hour. The reaction mixture was concentrated, and the resulting residue was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound (93 mg). MS (ESI+) m / z 245.9 (M+H) ＋

[0200] Reference Example 97 5-bromo-4-methoxy-N-(2-methoxyethyl)pyrimidin-2-amine [Step 1] Preparation of 4-chloro-N-(2-methoxyethyl)pyrimidin-2-amine To a solution of 2,4-dichloropyrimidine (650 mg) in THF (10 mL), TEA (1.5 mL) and 2-methoxyethan-1-amine (492 mg) were added and stirred at 60°C for 1 hour. After the reaction mixture was allowed to cool to room temperature, insoluble matter was filtered off and washed with THF. The residue obtained by concentrating the filtrate was purified by silica gel column chromatography to give the title compound (225 mg). MS (ESI+) m / z 188.0 (M+H) ＋ [Step 2] Preparation of 5-bromo-4-chloro-N-(2-methoxyethyl)pyrimidin-2-amine NBS (267 mg) was added to a solution of 4-chloro-N-(2-methoxyethyl)pyrimidin-2-amine (225 mg) in acetonitrile (5 mL), and the mixture was stirred at 50°C for 2 hours. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, diluted with water, and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (241 mg). MS (ESI+) m / z 267.8 (M+H) ＋[Step 3] Preparation of 5-bromo-4-methoxy-N-(2-methoxyethyl)pyrimidin-2-amine To a solution of 5-bromo-4-chloro-N-(2-methoxyethyl)pyrimidin-2-amine (240 mg) in methanol (5 mL) was added sodium methoxide (5 M methanol solution, 0.45 mL) and the mixture was stirred at 50°C for 1 hour. The reaction mixture was concentrated, and the resulting residue was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound (241 mg). MS (ESI+) m / z 263.9 (M+H) ＋

[0201] Reference Example 98 5-bromo-N2-methylpyrimidine-2,4-diamine To a solution of 5-bromo-4-chloro-N-methylpyrimidin-2-amine (185 mg) obtained in Step 2 of Reference Example 94 in NMP (1 mL) was added 28% aqueous ammonia (0.89 mL), and the mixture was stirred at 140°C for 30 minutes under microwave irradiation. The reaction solution was purified by reverse phase column chromatography to give the title compound (166 mg). MS (ESI+) m / z 204.9 (M+H) ＋

[0202] Reference Example 99 5-bromo-N4-methylpyrimidine-2,4-diamine To a solution of 5-bromo-4-chloropyrimidin-2-amine (200 mg) in NMP (1 mL) was added 40% aqueous methylamine solution (1.2 mL), and the mixture was stirred at 140°C for 30 minutes under microwave irradiation. The reaction mixture was purified by reverse phase column chromatography to give the title compound (189 mg). MS (ESI+) m / z 204.9 (M+H) ＋

[0203] Reference Example 100 5-bromo-N4-ethylpyrimidine-2,4-diamine To a solution of 5-bromo-4-chloropyrimidin-2-amine (200 mg) in NMP (1 mL) was added 70% aqueous ethylamine solution (1.2 mL), and the mixture was stirred at 140°C for 30 minutes under microwave irradiation. The reaction mixture was purified by reverse phase column chromatography to give the title compound (195 mg). MS (ESI+) m / z 218.9 (M+H) ＋

[0204] Reference Example 101 5-iodo-N2,N4-dimethylpyrimidine-2,4-diamine To a solution of 2,4-dichloro-5-iodopyrimidine (300 mg) in 2-propanol (1.5 mL) was added 40% aqueous methylamine solution (0.91 mL), and the mixture was stirred at 120°C for 30 minutes under microwave irradiation. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (277 mg). MS (ESI+) m / z 264.8 (M+H) ＋

[0205] Reference Example 102 2-amino-5-bromo-3-methyl-3,4-dihydropyrimidin-4-one [Step 1] Preparation of 5-bromo-2-chloro-3,4-dihydropyrimidin-4-one 2M aqueous sodium hydroxide solution (9.6 mL) was added to a solution of 5-bromo-2,4-dichloropyrimidine (2.50 g) in THF (15 mL), and the mixture was stirred at 50°C for 4 hours. The reaction mixture was neutralized with 12M hydrochloric acid, and then extracted with a mixed solvent of ethyl acetate and THF. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was washed with acetonitrile to give the title compound (1.29 g). MS (ESI+) m / z 210.8 (M+H) ＋ [Step 2] Preparation of 5-bromo-2-chloro-3-methyl-3,4-dihydropyrimidin-4-one Sodium hydride (143 mg) was added to a mixed solution of 5-bromo-2-chloro-3,4-dihydropyrimidin-4-one (500 mg) in DME (15 mL) and DMF (1 mL) and stirred at room temperature for 5 minutes. Lithium bromide (518 mg) was then added to the reaction solution and stirred at room temperature for 15 minutes. Methyl iodide (0.37 mL) was added to the reaction solution and stirred at room temperature for 30 minutes and then at 60°C for 2 hours. The reaction solution was diluted with water in an ice bath and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the resulting residue was purified by silica gel column chromatography to give the title compound (267 mg). MS (ESI+) m / z 224.8 (M+H) ＋[Step 3] Preparation of 2-amino-5-bromo-3-methyl-3,4-dihydropyrimidin-4-one To a solution of 5-bromo-2-chloro-3-methyl-3,4-dihydropyrimidin-4-one (260 mg) in NMP (1.5 mL) was added 28% aqueous ammonia (1.2 mL), and the mixture was stirred at 140°C for 30 minutes under microwave irradiation. The reaction solution was purified by reverse phase column chromatography to give the title compound (233 mg). MS (ESI+) m / z 205.8 (M+H) ＋

[0206] Reference Example 103 4-bromo-6-iodopyridazin-3-amine NBS (254 mg) was added to a solution of 6-iodopyridazin-3-amine (300 mg) and ammonium acetate (10 mg) in acetonitrile (5 mL), and the mixture was stirred at room temperature over the weekend. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction. The mixture was diluted with water, and insoluble matter was filtered off through Celite (registered trademark). The resulting filtrate was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (90 mg). MS (ESI+) m / z 301.7 (M+H) ＋

[0207] Reference Example 104 2-amino-5-bromo-N,N-dimethylpyridine-3-carboxamide HATU (631 mg) was added to a solution of 2-amino-5-bromopyridine-3-carboxylic acid (300 mg), dimethylamine (2 M THF solution, 2.8 mL), and DIPEA (0.72 mL) in DMF (1.5 mL), and the mixture was stirred at room temperature overnight. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, and the precipitate was collected by filtration to obtain a crude residue. The resulting residue was washed with water and dried under reduced pressure to obtain the title compound (130 mg). MS (ESI+) m / z 245.9 (M+H) ＋

[0208] Reference Example 105 5-bromo-3-methanesulfonylpyridin-2-amine Hydrazine monohydrate (922 mg) was added to a solution of 2-amino-5-bromopyridine-3-sulfonyl chloride (1.00 g) in THF (25 mL), and the mixture was stirred at room temperature for 15 minutes. The reaction mixture was concentrated, and to a solution of the resulting residue in ethanol (25 mL), sodium acetate (3.63 g) and methyl iodide (2.3 mL) were added, and the mixture was stirred at 85°C for 12 hours. The reaction mixture was concentrated, and the resulting residue was diluted with water, and the resulting precipitate was collected by filtration to obtain a crude residue. The resulting residue was washed with water and dried under reduced pressure to obtain the title compound (195 mg). MS (ESI+) m / z 252.9 (M+H) ＋

[0209] Reference Example 106 5-bromo-3-(ethanesulfonyl)pyridin-2-amine Hydrazine monohydrate (1.20 g) was added to a solution of 2-amino-5-bromopyridine-3-sulfonyl chloride (2.10 g) in THF (52 mL), and the mixture was stirred at room temperature for 15 minutes. The reaction mixture was concentrated, and to a solution of the resulting residue in ethanol (52 mL), sodium acetate (7.60 g) and methyl iodide (6.2 mL) were added, and the mixture was stirred overnight at 85°C. The reaction mixture was concentrated, and the resulting residue was diluted with water, and the resulting precipitate was collected by filtration to obtain a crude residue. The resulting residue was washed with water and dried under reduced pressure to obtain the title compound (1.10 g). MS (ESI+) m / z 267.0 (M+H) ＋

[0210] Reference Example 107 5-bromo-3,4-difluoropyridin-2-amine To a solution of 5-bromo-4-fluoropyridin-2-amine (1.00 g) in acetonitrile (40 mL), 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (11.1 g) was added, and the mixture was stirred at 40°C for 1 hour. Water was added to the reaction mixture to quench the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (224 mg). MS (ESI+) m / z 211.1 (M+H) ＋

[0211] Reference Example 108 5-bromo-3-chloro-4-fluoropyridin-2-amine NCS (199 mg) was added to a solution of 5-bromo-4-fluoropyridin-2-amine (300 mg) in acetonitrile (5 mL), and the mixture was stirred at 85° C. for 1 hour. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (196 mg). MS (ESI+) m / z 226.8 (M+H) ＋

[0212] Reference Example 109 5-bromo-4-fluoro-3-methylpyridin-2-amine NBS (111 mg) was added to a solution of 4-fluoro-3-methylpyridin-2-amine (75 mg) in acetonitrile (1.5 mL), and the mixture was stirred at 50° C. for 10 hours. The reaction mixture was purified by reverse phase column chromatography to give the title compound (21 mg). MS (ESI+) m / z 206.8 (M+H) ＋

[0213] Reference Example 110 4-fluoro-5-iodo-3-methylpyridin-2-amine NIS (167 mg) was added to a solution of 4-fluoro-3-methylpyridin-2-amine (75 mg) in acetonitrile (1.5 mL), and the mixture was stirred at room temperature overnight. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (77 mg). MS (ESI+) m / z 252.8 (M+H) ＋

[0214] Reference Example 111 5-bromo-4-fluoro-3-methoxypyridin-2-amine NBS (99 mg) was added to a solution of 4-fluoro-3-methoxypyridin-2-amine (75 mg) in acetonitrile (5 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was purified by reverse phase column chromatography to give the title compound (73 mg). MS (ESI+) m / z 222.8 (M+H) ＋

[0215] Reference Example 112 4-fluoro-5-iodo-3-methoxypyridin-2-amine NIS (148 mg) was added to a solution of 4-fluoro-3-methoxypyridin-2-amine (75 mg) in acetonitrile (5 mL), and the mixture was stirred overnight at room temperature and then at 40°C for 6 hours. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to terminate the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (73 mg). MS (ESI+) m / z 268.8 (M+H) ＋

[0216] Reference Example 113 5-bromo-3,4-dichloropyridin-2-amine NCS (338 mg) was added to a solution of 5-bromo-4-chloropyridin-2-amine (500 mg) in acetonitrile (10 mL), and the mixture was stirred at 80°C for 3 hours. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, and the mixture was extracted with a mixed solvent of ethyl acetate and THF. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give a crude residue. The resulting residue was washed with acetonitrile to give the title compound (481 mg). MS (ESI+) m / z 242.7 (M+H) ＋

[0217] Reference Example 114 5-bromo-3-chloro-4-methylpyridin-2-amine NCS (178 mg) was added to a solution of 5-bromo-4-methylpyridin-2-amine (200 mg) in DMF (1.5 mL), and the mixture was stirred at room temperature for 1 hour. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to obtain a crude residue. The resulting residue was washed with a mixed solvent of n-hexane and diethyl ether to obtain the title compound (208 mg). MS (ESI+) m / z 222.8 (M+H) ＋

[0218] Reference Example 115 5-bromo-3-chloro-4-methoxypyridin-2-amine NCS (164 mg) was added to a solution of 5-bromo-4-methoxypyridin-2-amine (200 mg) in DMF (1.5 mL), and the mixture was stirred at room temperature for 1 hour. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to obtain a crude residue. The resulting residue was washed with a mixed solvent of n-hexane and diethyl ether to obtain the title compound (181 mg). MS (ESI+) m / z 238.8 (M+H) ＋

[0219] Reference Example 116 5-bromo-4-chloro-3-methoxypyridin-2-amine NBS (194 mg) was added to a solution of 4-chloro-3-methoxypyridin-2-amine (150 mg) in acetonitrile (7.5 mL), and the mixture was stirred at room temperature for 10 hours. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (166 mg). MS (ESI+) m / z 238.8 (M+H) ＋

[0220] Reference Example 117 5-bromo-3,4-dimethoxypyridin-2-amine NBS (231 mg) was added to a solution of 3,4-dimethoxypyridin-2-amine (200 mg) in acetonitrile (5 mL), and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated, and the resulting residue was purified by reverse phase column chromatography to give the title compound (113 mg). MS (ESI+) m / z 234.8 (M+H) ＋

[0221] Reference Example 118 3-bromo-5-iodo-4-methoxypyridin-2-amine NBS (68 mg) was added to a solution of 5-iodo-4-methoxypyridin-2-amine (100 mg) in acetonitrile (2.5 mL), and the mixture was stirred at room temperature for 10 hours. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (48 mg). MS (ESI+) m / z 330.7 (M+H) ＋

[0222] Reference Example 119 N-(3-bromo-5-iodopyridin-2-yl)cyclopropanecarboxamide To a solution of 3-bromo-5-iodopyridin-2-amine (200 mg) and DIPEA (0.35 mL) in dichloromethane (5 mL), cyclopropanecarbonyl chloride (0.18 mL) was added and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated, and to a solution of the resulting residue in methanol (5 mL), potassium carbonate (277 mg) was added, and the mixture was stirred at 50°C for 2 hours. The insoluble matter was filtered off through Celite (registered trademark) and washed with methanol. The residue obtained by concentrating the filtrate was washed with ethyl acetate to give the title compound (174 mg). MS (ESI+) m / z 368.9 (M+H) ＋

[0223] Reference Example 120 3-bromo-5,6-difluoropyridin-2-amine NBS (128 mg) was added to a solution of 5,6-difluoropyridin-2-amine (75 mg) in acetonitrile (1.5 mL), and the mixture was stirred at 40°C for 3 hours. A saturated aqueous solution of sodium bicarbonate and a 20% aqueous solution of sodium hydrogen thiosulfate were added to the reaction mixture to quench the reaction, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (120 mg). MS (ESI+) m / z 210.8 (M+H) ＋

[0224] Reference Example 121 5-bromo-4-ethoxypyridin-3-amine [Step 1] Preparation of 3-bromo-4-ethoxy-5-nitropyridine Sodium ethoxide (3M ethanol solution, 1.8 mL) was added to a solution of 3-bromo-4-chloro-5-nitropyridine (500 mg) in ethanol (2.5 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (356 mg). MS (ESI+) m / z 248.8 (M+H) ＋ [Step 2] Preparation of 5-bromo-4-ethoxypyridin-3-amine Reduced iron (593 mg) and ammonium chloride (379 mg) were added to a mixed solution of 3-bromo-4-ethoxy-5-nitropyridine (350 mg) in ethanol (15 mL) and water (3 mL), and the mixture was stirred at 75°C for 1 hour. Insoluble matter was filtered off through Celite (registered trademark) and washed with methanol. The residue obtained by concentrating the filtrate was neutralized with saturated aqueous sodium bicarbonate, diluted with water, and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (293 mg). MS (ESI+) m / z 218.8 (M+H) ＋

[0225] Reference Example 122 1-[(5-bromopyridin-3-yl)methyl]-4-methylpiperazine Acetic acid (0.46 mL) was added to a solution of 5-bromopyridine-3-carbaldehyde (1.50 g) and 1-methylpiperazine (3.0 mL) in dichloromethane (32 mL), and the mixture was stirred at room temperature for 1 hour. Sodium triacetoxyborohydride (3.40 g) was added to the reaction mixture, and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (2.10 g). MS (ESI+) m / z 272.1 (M+H) ＋

[0226] Reference Example 123 4-[(5-bromopyridin-3-yl)methyl]-1-methylpiperazin-2-one Sodium triacetoxyborohydride (729 mg) was added to a solution of 5-bromopyridine-3-carbaldehyde (320 mg), 1-methylpiperazin-2-one hydrochloride (311 mg), and DIPEA (0.60 mL) in dichloromethane (7 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography to give the title compound (220 mg). MS (ESI+) m / z 284.1 (M+H) ＋

[0227] Reference Example 124 5-bromo-1-(oxan-2-yl)-1H-pyrazolo[3,4-b]pyrazine To a solution of 5-bromo-1H-pyrazolo[3,4-b]pyrazine (400 mg) in dichloromethane (7.5 mL), 3,4-dihydro-2H-pyran (0.55 mL) and p-toluenesulfonic acid monohydrate (38 mg) were added and stirred at room temperature for 2 hours. The reaction mixture was neutralized with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (567 mg). MS (ESI+) m / z 201.0 (M+H) ＋

[0228] Reference Example 125 tert-Butyl 4-bromo-1H-pyrazolo[3,4-c]pyridine-1-carboxylate To a solution of 4-bromo-1H-pyrazolo[3,4-c]pyridine (200 mg) in THF (3 mL) was added TEA (0.42 mL) and Boc ２ 0 (0.35 mL) was added and stirred at room temperature overnight. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound (345 mg). MS (ESI+) m / z 299.8 (M+H) ＋

[0229] Example 1 4,5-Dibromo-N-{4-[6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-3-yl]but-3-yn-1-yl}-1H-imidazole-2-carboxamide A mixture of 4-{3-iodopyrazolo[1,5-a]pyridin-6-yl}-1-methyl-1H-pyrazole (38 mg) obtained in Step 2 of Reference Example 79 and 4,5-dibromo-N-(but-3-yn-1-yl)-1H-imidazole-2-carboxamide (30 mg) obtained in Reference Example 57 was treated with PdCl ２ (PPh ３ ) ２ (6.5 mg), copper(I) iodide (2.7 mg), and piperidine (0.5 mL) were added and degassed, and then the mixture was stirred at 50° C. for 90 minutes under an argon atmosphere. The reaction mixture was purified by reversed-phase column chromatography to obtain a crude residue. The resulting residue was washed with methanol to obtain the title compound (16 mg). MS (ESI+) m / z 518.0 (M+H) ＋

[0230] Example 2 4,5-Dibromo-N-(4-{8-[(1-methyl-1H-pyrazol-4-yl)amino]imidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)-1H-imidazole-2-carboxamide [Step 1] Preparation of tert-butyl N-(4-{8-bromoimidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)carbamate 8-Bromo-3-iodoimidazo[1,2-a]pyridine (239 mg) and PdCl ２ (PPh ３ ) ２To a mixture of 41 mg of methylpropional and copper(I) iodide (17 mg), THF (2.5 mL), tert-butyl N-(but-3-yn-1-yl)carbamate (100 mg), and TEA (0.25 mL) were added and degassed, followed by stirring at room temperature for 2 hours under an argon atmosphere. The reaction mixture was concentrated and the resulting residue was purified by silica gel column chromatography to give the title compound (149 mg). MS (ESI+) m / z 365.9 (M+H) ＋ [Step 2] Preparation of tert-butyl N-(4-{8-[(1-methyl-1H-pyrazol-4-yl)amino]imidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)carbamate To a solution of 1-methyl-1H-pyrazol-4-amine (116 mg), tert-butyl N-(4-{8-bromoimidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)carbamate (145 mg), and cesium carbonate (389 mg) in 1,4-dioxane (5 mL) was added Pd ２ (dba) ３ (55 mg) and 2-(dicyclohexylphosphino)-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (64 mg) were added and degassed, and then stirred at 100°C under an argon atmosphere for 10 hours. The reaction solution was diluted with ethyl acetate, and insoluble matter was filtered off through Celite (registered trademark). The filtrate was concentrated and the resulting residue was purified by silica gel column chromatography to give a crude residue. The resulting residue was purified by reverse phase column chromatography to give the title compound (92 mg). MS (ESI+) m / z 381.0 (M+H) ＋[Step 3] Preparation of N-[3-(4-aminobut-1-yn-1-yl)imidazo[1,2-a]pyridin-8-yl]-1-methyl-1H-pyrazol-4-amine trihydrochloride To a solution of tert-butyl N-(4-{8-[(1-methyl-1H-pyrazol-4-yl)amino]imidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)carbamate (90 mg) in dichloromethane (2.5 mL) and methanol (1 mL) was added hydrogen chloride (4 M 1,4-dioxane solution, 0.59 mL), and the mixture was stirred at room temperature for 1 hour and at 40° C. for 1 hour. The reaction mixture was concentrated to give the title compound (91 mg). MS (ESI+) m / z 281.0 (M+H) ＋ [Step 4] Preparation of 4,5-dibromo-N-(4-{8-[(1-methyl-1H-pyrazol-4-yl)amino]imidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)-1H-imidazole-2-carboxamide To a solution of N-[3-(4-aminobut-1-yn-1-yl)imidazo[1,2-a]pyridin-8-yl]-1-methyl-1H-pyrazol-4-amine trihydrochloride (20 mg), 4,5-dibromo-1H-imidazole-2-carboxylic acid (21 mg) obtained in Step 2 of Reference Example 1, and DIPEA (0.089 mL) in DMF (0.5 mL), HATU (29 mg) was added, and the mixture was stirred at room temperature for 2 hours and at 50°C for 1 hour. The reaction solution was purified by reverse-phase column chromatography to obtain a crude residue. The resulting residue was washed with m...

Claims

1. General formula (I): [In the formula, R １ and R ２ are each independently a hydrogen atom, a halogen atom, an optionally substituted alkyl group having 1 to 5 carbon atoms, or an optionally substituted phenyl group, and R ３ is a hydrogen atom or an optionally substituted alkyl group having 1 to 3 carbon atoms, or R １ and R ２ , or R １ and R ３ R together with each adjacent carbon atom constitutes an optionally substituted 5- or 6-membered aromatic ring; ４ is a hydrogen atom or an optionally substituted alkyl group having 1 to 5 carbon atoms, and R ７ and R ８ are each independently a hydrogen atom or an optionally substituted alkyl group having 1 to 3 carbon atoms, ４ and R ７ is R ４ The nitrogen atom adjacent to R ５ and R ６ the carbon atom adjacent to R ７ R may, together with the carbon atom adjacent to R, form an optionally substituted 5- or 6-membered heterocycloalkyl ring; ５ and R ６ are each independently a hydrogen atom, an optionally substituted alkyl group having 1 to 5 carbon atoms, or an optionally substituted phenyl group, ５ and R ６ may form an optionally substituted 3- to 6-membered cycloalkyl ring together with the adjacent carbon atom; L is a divalent group formed by removing two hydrogen atoms from an alkane, alkene, or alkyne having 2 to 4 carbon atoms, and when L is a divalent group formed by removing two hydrogen atoms from an alkane having 2 to 4 carbon atoms (alkylene group), one or more methylene groups (-CH ２ -) may be substituted with -NH- or -O-; Het is an aromatic heterocyclic group having at least one nitrogen atom], wherein in general formula (I), Het is represented by general formula (II): [In the formula, represents a single bond or a double bond; X １ ~X ４ are each independently a carbon atom or a nitrogen atom; Ａ１ ~R Ａ４ are each independently a hydrogen atom, a halogen atom, an amino group, or —NH—(CH ２ ) ｎ Ａ -O-CH ３ (n Ａ is a natural number from 1 to 4), a group represented by the following formula: (In the formula, R Ａ５ is an optionally substituted alkyl group having 1 to 3 carbon atoms), or a group represented by the following formula: (In the formula, R Ａ６ is an optionally substituted alkyl group having 1 to 3 carbon atoms) (wherein X ２ When R is a nitrogen atom Ａ１ does not exist, and X ３ When R is a nitrogen atom Ａ３ is absent)], or a group represented by general formula (III): [In the formula, represents a single bond or a double bond; R Ｂ１ , R Ｂ２ , and R Ｂ４ are each independently a hydrogen atom, a halogen atom, an amino group, an optionally substituted alkyl group having 1 to 3 carbon atoms, an optionally substituted alkoxy group having 1 to 3 carbon atoms, -NH-R Ｂ３ (R Ｂ３ represents an optionally substituted alkyl group having 1 to 3 carbon atoms, an optionally substituted cycloalkyl group having 3 to 6 carbon atoms, -(CH ２ ) ｎ Ｂ -O-CH ３ (n Ｂ is a natural number from 1 to 4), or an optionally substituted phenyl group), —O—R Ｂ５ (R Ｂ５ is an optionally substituted cycloalkyl group having 3 to 6 carbon atoms, or ═O, or R Ｂ１ and R Ｂ４ , or R Ｂ４ and R Ｂ２ form an optionally substituted 5- or 6-membered aromatic heterocycle together with the adjacent atoms, or a group represented by general formula (IV): [In the formula, represents a single bond or a double bond; X ５ and X ６ are each independently a carbon atom or a nitrogen atom; Ｃ１ ~R Ｃ４ are each independently a hydrogen atom, a halogen atom, an amino group, a hydroxy group, a cyano group, an optionally substituted alkyl group having 1 to 3 carbon atoms, an optionally substituted alkoxy group having 1 to 3 carbon atoms, an optionally substituted cycloalkyl group having 3 to 6 carbon atoms, an optionally substituted 5- or 6-membered aromatic carbocyclic group, an optionally substituted 5- or 6-membered aromatic heterocyclic group, an optionally substituted 5- or 6-membered heterocycloalkyl group, -NH-R Ｃ８ , -SO ２ -R Ｃ１１ , —CO—NR Ｃ１４ R Ｃ１５ or =O, where R Ｃ８ represents an optionally substituted alkyl group having 1 to 3 carbon atoms, —SO ２ -R Ｃ９ , or -CO-R Ｃ１０ R Ｃ９ is an optionally substituted alkyl group having 1 to 3 carbon atoms, and R Ｃ１０ represents an optionally substituted alkyl group having 1 to 3 carbon atoms, an optionally substituted cycloalkyl group having 3 to 6 carbon atoms, or a group represented by the following formula: (In the formula, X １０ is a carbon atom or a nitrogen atom); Ｃ１１ represents an optionally substituted alkyl group having 1 to 3 carbon atoms, or —NR Ｃ１２ R Ｃ１３ and R Ｃ１２ and R Ｃ１３ are each independently a hydrogen atom or an optionally substituted alkyl group having 1 to 3 carbon atoms; R Ｃ１４ and R Ｃ１５ are each independently a hydrogen atom or an optionally substituted alkyl group having 1 to 3 carbon atoms, or R Ｃ１ and R Ｃ２ (At this time X ６ is a carbon atom), or R Ｃ２ and R Ｃ３ together with the adjacent carbon atoms, form an optionally substituted 5- or 6-membered aromatic ring, an optionally substituted 5- or 6-membered cycloalkyl ring, or an optionally substituted 5- or 6-membered heterocycloalkyl ring (provided that X ５ When R is a nitrogen atom Ｃ１ does not exist, and X ５ When R is a nitrogen atom Ｃ４ is absent)], or a group represented by general formula (V): [In the formula, represents a single bond or a double bond; X ７ ~X ９ are each independently a carbon atom or a nitrogen atom; Ｄ１ and R Ｄ２ are each independently a hydrogen atom, a halogen atom, an amino group, an optionally substituted alkyl group having 1 to 3 carbon atoms, an optionally substituted alkoxy group having 1 to 3 carbon atoms, or an optionally substituted phenyl group, or R Ｄ１ and R Ｄ２ is X ７ and X ８ and together with each other, form an optionally substituted 5- or 6-membered cycloalkyl ring, an optionally substituted 5- or 6-membered heterocycloalkyl ring, or an optionally substituted 5- or 6-membered aromatic heterocyclic ring], or a group represented by general formula (VI): [In the formula, R Ｅ are each independently a halogen atom, an amino group, an optionally substituted alkyl group having 1 to 3 carbon atoms, or an optionally substituted alkoxy group having 1 to 3 carbon atoms, and p is 0 to 4, or a group represented by general formula (VIII): [In the formula, represents a single bond or a double bond; X １１ ~X １３ are each independently a carbon atom or a nitrogen atom; Ｆ１ ~R Ｆ５ are each independently a hydrogen atom, a halogen atom, an amino group, an optionally substituted alkyl group having 1 to 3 carbon atoms, or an optionally substituted alkoxy group having 1 to 3 carbon atoms, or R Ｆ２ and R Ｆ３ is X １２ and X １３ together with the group represented by the formula (I) constitute an optionally substituted 5- or 6-membered heterocycloalkyl ring, or an optionally substituted 5- or 6-membered aromatic heterocyclic ring, or a salt thereof.

2. In general formula (I), R １ , and R ２ are each independently a hydrogen atom, a halogen atom, an alkyl group having 1 or 2 carbon atoms which may be substituted with a halogen atom, or a phenyl group, and R ３ is a hydrogen atom or an alkyl group having 1 or 2 carbon atoms, or R １ and R ２ , or R １ and R ３ and R 1 and R 2 together with adjacent carbon atoms form a benzene ring or a 6-membered aromatic heterocycle containing at least one nitrogen atom in the ring, which may be substituted with at least one group selected from the group consisting of a halogen atom, a cyano group, an alkyl group having 1 or 2 carbon atoms, and an alkoxy group having 1 or 2 carbon atoms which may be substituted with a halogen atom, or a salt thereof.

3. In general formula (I), R ４ is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and R ７ and R ８ are each independently a hydrogen atom or an alkyl group having 1 or 2 carbon atoms, ４ and R ７ is R ４ The nitrogen atom adjacent to R ５ and R ６ the carbon atom adjacent to R ７ R may, together with the carbon atom adjacent to R, form a 5-membered heterocycloalkyl ring containing one nitrogen atom in the ring; ５ and R ６ are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or a phenyl group, ５ and R ６ may form a 3- or 4-membered cycloalkyl ring together with the adjacent carbon atom; L is a divalent group obtained by removing two hydrogen atoms from ethane, ethylene, or acetylene, and when L is a divalent group obtained by removing two hydrogen atoms from ethane (ethylene group), one methylene group (—CH ２ 3. The compound or salt thereof according to claim 1 or 2, wherein -) may have a structure in which -) is optionally substituted with -NH- or -O-.

4. In the general formula (I), Het is represented by the general formula (II): [In the formula, represents a single bond or a double bond; X １ ~X ４ are each independently a carbon atom or a nitrogen atom; Ａ１ ~R Ａ４ are each independently a hydrogen atom, a halogen atom, an amino group, or —NH—(CH ２ ) ２ -O-CH ３ a group represented by the following formula: (In the formula, R Ａ５ is an alkyl group having 1 or 2 carbon atoms), or a group represented by the following formula: (In the formula, R Ａ６ is a group represented by an alkyl group having 1 or 2 carbon atoms (wherein X ２ When R is a nitrogen atom Ａ１ does not exist, and X ３ When R is a nitrogen atom Ａ３ is absent)], or a group represented by general formula (III): [In the formula, represents a single bond or a double bond; R Ｂ１ , R Ｂ２、 , and R Ｂ４ each independently represents a hydrogen atom, an amino group, an alkyl group having 1 to 3 carbon atoms which may be substituted with a halogen atom, an alkoxy group having 1 or 2 carbon atoms which may be substituted, -NH-R Ｂ３ (R Ｂ３ represents an alkyl group having 1 or 2 carbon atoms, a cycloalkyl group having 3 to 5 carbon atoms, -(CH ２ ) ｎ Ｂ -O-CH ３ (n Ｂ is a natural number from 1 to 3), or a halogen atom or the following formula: a phenyl group optionally substituted with a group represented by the formula: Ｂ５ (R Ｂ５ is a cycloalkyl group having 3 to 5 carbon atoms), or ═O, or R Ｂ１ and R Ｂ４ , or R Ｂ４ and R Ｂ２ form a 5-membered aromatic heterocycle together with the adjacent atoms, or a group represented by general formula (IV): [In the formula, represents a single bond or a double bond; X ５ and X ６ are each independently a carbon atom or a nitrogen atom; Ｃ１ ~R Ｃ３ are each independently a hydrogen atom, a halogen atom, an amino group, a hydroxy group, a cyano group, an alkoxy group having 1 to 3 carbon atoms which may be substituted with a halogen atom, a cycloalkyl group having 3 to 5 carbon atoms, a phenyl group, a 6-membered aromatic heterocyclic group having one nitrogen atom in the ring, or a 5-membered heterocycloalkyl group having one nitrogen atom in the ring, -NH-R Ｃ８ , -SO ２ -R Ｃ１１ , —CO—NR Ｃ１４ R Ｃ１５ or =O, where R Ｃ８ is an alkyl group having 1 or 2 carbon atoms, -SO ２ -R Ｃ９ , or -CO-R Ｃ１０ R Ｃ９ is an alkyl group having 1 or 2 carbon atoms, and R Ｃ１０ is a cycloalkyl group having 3 to 5 carbon atoms, or a group represented by the following formula: (In the formula, X １０ is a carbon atom or a nitrogen atom); Ｃ１１ represents an optionally substituted alkyl group having 1 to 3 carbon atoms, or —NR Ｃ１２ R Ｃ１３ and R Ｃ１２ and R Ｃ１３ are each independently a hydrogen atom or an alkyl group having 1 or 2 carbon atoms; R Ｃ１４ and R Ｃ１５ are each independently a hydrogen atom or an alkyl group having 1 or 2 carbon atoms, or R Ｃ１ and R Ｃ２ (At this time X ６ is a carbon atom), or R Ｃ２ and R Ｃ３ R together with each adjacent carbon atom form an optionally substituted 5- or 6-membered aromatic ring, an optionally substituted 5- or 6-membered cycloalkyl ring, or an optionally substituted 5- or 6-membered heterocycloalkyl ring; Ｃ４ is a hydrogen atom, a halogen atom, or an amino group (provided that X ５ When R is a nitrogen atom Ｃ１ does not exist, and X ５ When R is a nitrogen atom Ｃ４ is absent)], or a group represented by the following formula: or a group represented by the following formula: (In the formula, R Ｃ５ is a hydrogen atom or a halogen atom), or a group represented by the following formula: (In the formula, R Ｃ６ and R Ｃ７ are each independently a hydrogen atom, a halogen atom, or an alkyl group having 1 or 2 carbon atoms), or a group represented by the following formula: or a group represented by the following formula: (In the formula, R Ｄ１ is a hydrogen atom or an alkoxy group having 1 or 2 carbon atoms), or a group represented by the following formula: or a group represented by the following formula: or a group represented by the following formula: or a group represented by the following formula: (In the formula, R Ｄ１ and R Ｄ２ are each independently a hydrogen atom or an alkyl group having 1 or 2 carbon atoms), or a group represented by the following formula: (In the formula, R Ｄ１ and R Ｄ２ are each independently a hydrogen atom or an alkyl group having 1 or 2 carbon atoms), or a group represented by the following formula: (In the formula, R Ｄ１ and R Ｄ２ are each independently a hydrogen atom, a halogen atom, or an amino group), or a group represented by the following formula: or a group represented by the following formula: or a group represented by the following formula: (In the formula, R Ｄ３ is a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or —CH ２ -R Ｄ４ (R Ｄ４ is a cycloalkyl group having 3 to 5 carbon atoms), or is a group represented by the following formula: or a group represented by the following formula: or a group represented by the following formula: The compound or salt thereof according to claim 1 or 2, wherein the group is represented by:

5. At least one compound selected from the group consisting of the following compounds (1) to (360) or a salt thereof: (1) 4,5-dibromo-N-{4-[6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-3-yl]but-3-yn-1-yl}-1H-imidazole-2-carboxamide, (2) 4,5-dibromo-N-(4-{8-[(1-methyl-1H-pyrazol-4-yl)amino]imidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)-1H-imidazole-2-carboxamide, (3) N-(4-{8-aminoimidazo[1,2-a]pyridin-3-yl}-2-methylbut-3-yn-1-yl)-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (4) N-(5-{8-aminoimidazo[1,2-a]pyridin-3-yl}-2-methylpent-4-yn-2-yl)-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (5) N-(4-{imidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (6) N-(4-{8-amino-6-bromoimidazo[1,2-a]pyrazin-3-yl}but-3-yn-1-yl)-5,6-difluoro-1H-1,3-benzodiazole-2-carboxamide, (7) N-(4-{8-[(2-methoxyethyl)amino]imidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (8) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (9) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclobutyl]-6-chloro-1H-1,3-benzodiazole-2-carboxamide, (10) N-(4-{2-[(3-fluorophenyl)amino]pyrimidin-5-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (11) 6,7-difluoro-N-(4-{imidazo[1,(2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (12) N-[4-(2-{[3-(4-methylpiperazin-1-yl)phenyl]amino}pyrimidin-5-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (13) N-(4-{8-aminoimidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1-methyl-1H-1,3-benzodiazole-2-carboxamide, (14) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-4,7-dichloro-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (15) N-(4-{8-aminoimidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-N-ethyl-7-methyl-1H-1,3-benzodiazole-2-carboxamide, (16) N-(4-{8-amino-5-chloroimidazo[1,2-a]pyrazin-3-yl}but-3-yn-1-yl)-7-methoxy-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (17) N-(4-{[3,3'-bipyridin]-5-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (18) N-(4-{8-amino-5-chloro-2-methylimidazo[1,2-a]pyrazin-3-yl}but-3-yn-1-yl)-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (19) N-[4-(6-amino-5-bromopyridazin-3-yl)but-3-yn-1-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (20) 7-chloro-N-(4-{2H,3H,4H-pyrido[3,2-b][1,4]oxazin-7-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (21) N-(4-{pyrazolo[3,2-b][1,3]thiazol-7-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (22) N-[(3E)-4-(6-amino-5-chloropyridin-3-yl)but-3-en-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (23) 5-{2-[1-(1H-1,3-benzodiazole-2-carbonyl)pyrrolidin-3-yl]ethynyl}-3-bromopyridin-2-amine, (24) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-5-phenyl-1H-imidazole-2-carboxamide, (25) N-[(1R)-4-(6-amino-5-chloropyridin-3-yl)-1-phenylbut-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (26) N-[(2S)-5-(2-amino-4-methoxypyrimidin-5-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (27) N-[4-(8-fluoroisoquinolin-4-yl)but-3-yn-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (28) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-5-ethyl-1H-imidazole-2-carboxamide, (29) N-[(2S,4E)-5-{2-[(4-fluorophenyl)amino]pyrimidin-5-yl}pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (30) N-[(3E)-4-(2-amino-4-methoxypyrimidin-5-yl)but-3-en-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (31) N-[(2S,4E)-5-(2-amino-4-methoxypyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (32) N-[(2S)-5-[2,4-bis(methylamino)pyrimidin-5-yl]pent-4-yn-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (33) N-(4-{6-chloro-1H-pyrazolo[3,4-b]pyridin-5-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (34) 7-chloro-N-[4-(4-phenylpyridin-3-yl)but-3-yn-1-yl]-1H-1,3-Benzodiazole-2-carboxamide, (35) N-[(2S)-5-(5-amino-4-ethoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (36) N-[(2S,4E)-5-{3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl}pent-4-en-2-yl]-5-(trifluoromethyl)-1H-imidazole-2-carboxamide, (37) N-[(2S,4E)-5-(6-amino-4-fluoropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (38) N-[(2S,4E)-5-(5-methoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (39) N-[(2S,4E)-5-(6-aminopyrazin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (40) N-[(2S)-5-{5H,6H,7H-pyrrolo[1,2-a]imidazol-3-yl}pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (41) N-[(2S)-5-[6-amino-5-(trifluoromethoxy)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (42) N-[(2S,4E)-5-(2-amino-5-fluoropyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (43) N-[(2S)-5-(5,6,7,8-tetrahydroisoquinolin-4-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (44) N-[(2S,4E)-5-[5-(pyrrolidin-1-yl)pyridin-3-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (45) N-[(2S,4E)-5-(4-methoxy-1H-pyrazol-5-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (46) N-[(2S,(4E)-5-(6-aminopyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (47) N-[(2S,4E)-5-{4H,5H,6H,7H-pyrazolo[1,5-a]pyridin-3-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (48) N-[(3S,5E)-6-(2-amino-4-methoxypyrimidin-5-yl)hex-5-en-3-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (49) N-[(3R,5E)-6-(5-methoxypyridin-3-yl)-2-methylhex-5-en-3-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (50) N-[(2S)-5-(6-aminopyridin-3-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (51) N-[(2S)-5-(6-amino-4,5-dimethoxypyridin-3-yl)pent-4-yn-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (52) N-[(2S,4Z)-5-(2-amino-4-methoxypyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (53) N-[(2S)-4-[(5-fluoropyridin-3-yl)amino]butan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (54) N-[(2S)-4-[(2-aminopyrimidin-5-yl)oxy]butan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (55) N-[(2S)-1-[(5-chloropyridin-3-yl)methoxy]propan-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (56) N-(4-{8-aminoimidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)-4,5-dibromo-1-methyl-1H-imidazole-2-carboxamide, (57) 4,5-dibromo-N-{4-[5-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,(5-a]pyridin-3-yl]but-3-yn-1-yl}-1H-imidazole-2-carboxamide, (58) N-(4-{8-[(1-methyl-1H-pyrazol-4-yl)amino]imidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (59) N-(4-{8-aminoimidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)-1-bromoimidazo[1,5-a]pyridine-3-carboxamide, (60) N-(4-{8-aminoimidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)-6-methyl-1H-1,3-benzodiazole-2-carboxamide, (61) N-(4-{8-aminoimidazo[1,2-a]pyridin-3-yl}but-3-yn-1-yl)-6-fluoro-1H-1,3-benzodiazole-2-carboxamide, (62) N-(4-{8-amino-6-chloroimidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (63) N-(4-{8-aminoimidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (64) N-(4-{8-amino-7-chloroimidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (65) N-(4-{8-amino-6,7-dichloroimidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (66) 7-fluoro-N-(4-{imidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (67) 7-chloro-N-(4-{2-[(2-fluorophenyl)amino]pyrimidin-5-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (68) 7-chloro-N-(4-{2-[(4-fluorophenyl)amino]pyrimidin-5-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (69) 4,5-dibromo-N-{4-[7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]but-3-yn-1-yl}-1H-imidazole-2-carboxamide, (70) 7-chloro-N-[4-(2-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrimidin-5-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (71) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-bromo-1H-1,3-benzodiazole-2-carboxamide, (72) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-methoxy-1H-1,3-benzodiazole-2-carboxamide, (73) N-[1-(3-{8-amino-7-chloroimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-1H-1,3-benzodiazole-2-carboxamide, (74) N-[1-(3-{8-amino-7-chloroimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (75) N-[1-(3-{8-amino-7-chloroimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-methyl-1H-1,3-benzodiazole-2-carboxamide, (76) N-[1-(3-{8-amino-7-chloroimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-methoxy-1H-1,3-benzodiazole-2-carboxamide, (77) N-(5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl)-1H-1,3-benzodiazole-2-carboxamide, (78) N-(5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl)-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (79) N-(5-{8-aminoimidazo[1,(80) N-[1-(3-{8-amino-7-chloroimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (81) N-(5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl)-7-(trifluoromethoxy)-1H-1,3-benzodiazole-2-carboxamide, (82) N-(5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl)-7-methyl-1H-1,3-benzodiazole-2-carboxamide, (83) N-(5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl)-7-methoxy-1H-1,3-benzodiazole-2-carboxamide, (84) N-[(2R)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (85) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (86) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (87) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-ethoxy-1H-1,3-benzodiazole-2-carboxamide, (88) N-[1-(3-{8-amino-7-chloroimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-ethoxy-1H-1,3-benzodiazole-2-carboxamide, (89) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-6-chloro-7-methoxy-1H-1,3-Benzodiazole-2-carboxamide, (90) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-6-fluoro-7-methyl-1H-1,3-benzodiazole-2-carboxamide, (91) N-[1-(3-{8-aminoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-6-chloro-7-methyl-1H-1,3-benzodiazole-2-carboxamide, (92) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-6,7-dichloro-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (93) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-5,7-dichloro-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (94) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-5,6-dichloro-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (95) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-7-methoxy-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (96) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-7-chloro-1-methyl-1H-1,3-benzodiazole-2-carboxamide, (97) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-6-chloro-1-methyl-1H-1,3-benzodiazole-2-carboxamide, (98) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-5-chloro-1-methyl-1H-1,3-benzodiazole-2-carboxamide, (99) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-4-chloro-1-methyl-1H-1,3-Benzodiazole-2-carboxamide, (100) 7-chloro-N-(4-{imidazo[1,2-a]pyrazin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (101) N-(4-{8-amino-7-bromoimidazo[1,2-b]pyridazin-3-yl}but-3-yn-1-yl)-7-methoxy-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (102) N-(4-{8-aminoimidazo[1,2-a]pyrazin-3-yl}but-3-yn-1-yl)-7-chloro-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (103) N-[1-(3-{8-aminoimidazo[1,2-a]pyrazin-6-yl}prop-2-yn-1-yl)cyclopropyl]-1H-1,3-benzodiazole-2-carboxamide, (104) N-[1-(3-{8-amino-7-bromoimidazo[1,2-b]pyridazin-3-yl}prop-2-yn-1-yl)cyclopropyl]-7-methoxy-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (105) N-[4-(5-bromopyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (106) N-[4-(6-amino-5-phenylpyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (107) N-(4-{8-amino-2-methylimidazo[1,2-a]pyrazin-3-yl}but-3-yn-1-yl)-7-chloro-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (108) N-[4-(6-amino-5-bromo-4-methoxypyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (109) N-[4-(6-aminopyridazin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (110) N-[(2S)-5-(6-amino-5-bromopyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (111) N-{1-[3-(6-amino-5-bromopyridin-3-yl)prop-2-yn-1-yl]cyclopropyl}-1H-1,3-benzodiazole-2-carboxamide, (112) N-[4-(6-amino-5-bromopyridin-3-yl)but-3-yn-1-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (113) N-[(2S)-5-(6-amino-5-chloropyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (114) N-[4-(6-amino-5-chloropyridin-3-yl)but-3-yn-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (115) N-{4-[6-amino-5-(trifluoromethyl)pyridin-3-yl]but-3-yn-1-yl}-3H-imidazo[4,5-b]pyridine-2-carboxamide, (116) N-(4-{1H-pyrrolo[2,3-c]pyridin-4-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (117) N-[4-(5-amino-6-chloropyrazin-2-yl)but-3-yn-1-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (118) N-(4-{pyrazolo[1,5-a]pyridin-3-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (119) N-[4-(1-phenyl-1H-pyrazol-4-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (120) N-[4-(5-cyclopropylpyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (121) N-[(2S,4E)-5-(6-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (122) N-[(2S,4E)-5-(6-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (123) N-[(2S,(4E)-5-(6-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-6-chloro-1H-1,3-benzodiazole-2-carboxamide, (124) N-[(2R,4E)-5-(6-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (125) N-[(2R,4E)-5-(6-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (126) N-[(3R)-6-(6-amino-5-chloropyridin-3-yl)hex-5-yn-3-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (127) N-[(3S)-6-(6-amino-5-chloropyridin-3-yl)hex-5-yn-3-yl]-1H-1,3-benzodiazole-2-carboxamide, (128) N-[(3S)-6-(6-amino-5-chloropyridin-3-yl)hex-5-yn-3-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (129) N-[(3E)-4-(6-amino-5-chloropyridin-3-yl)but-3-en-1-yl]-N-methyl-1H-1,3-benzodiazole-2-carboxamide, (130) 7-chloro-N-[1-(3-{1H-pyrrolo[2,3-b]pyridin-5-yl}prop-2-yn-1-yl)cyclopropyl]-1H-1,3-benzodiazole-2-carboxamide, (131) 7-chloro-N-(4-{3-methyl-3H-imidazo[4,5-b]pyridin-6-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (132) 7-chloro-N-{4-[2-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-6-yl]but-3-yn-1-yl}-1H-1,3-benzodiazole-2-carboxamide, (133) N-(5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (134) N-[(2S)-5-{8-aminoimidazo[1,(135) N-[(3S)-6-{8-aminoimidazo[1,2-b]pyridazin-3-yl}hex-5-yn-3-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (136) 7-chloro-N-(4-{5H-pyrrolo[2,3-b]pyrazin-2-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (137) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-5-bromo-1H-imidazole-2-carboxamide, (138) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-4,5-dichloro-1H-imidazole-2-carboxamide, (139) 7-chloro-N-(4-{3H-[1,2,3]triazolo[4,5-b]pyridin-6-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (140) N-(4-{3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl}but-3-yn-1-yl)-3H-imidazo[4,5-b]pyridine-2-carboxamide, (141) N-[4-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (142) N-[(3R)-6-{8-aminoimidazo[1,2-b]pyridazin-3-yl}-2-methylhex-5-yn-3-yl]-7-methoxy-1H-1,3-benzodiazole-2-carboxamide, (143) 7-chloro-N-[4-(5-methanesulfonamidopyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (144) N-[(2S)-5-(2-amino-4-methoxypyrimidin-5-yl)pent-4-yn-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (145) N-[(2S)-5-(2-amino-4-ethoxypyrimidin-5-yl)pent-4-yn-2-yl]-7-chloro-1H-1,3-Benzodiazole-2-carboxamide, (146) N-[(2S)-5-(2-amino-4-ethoxypyrimidin-5-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (147) N-[4-(isoquinolin-4-yl)but-3-yn-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (148) N-[4-(1-aminoisoquinolin-4-yl)but-3-yn-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (149) 7-chloro-N-{4-[2-(methylamino)pyrimidin-5-yl]but-3-yn-1-yl}-1H-1,3-benzodiazole-2-carboxamide, (150) 7-chloro-N-{4-[2-(ethylamino)pyrimidin-5-yl]but-3-yn-1-yl}-1H-1,3-benzodiazole-2-carboxamide, (151) 7-chloro-N-{4-[2-(cyclopropylamino)pyrimidin-5-yl]but-3-yn-1-yl}-1H-1,3-benzodiazole-2-carboxamide, (152) N-[(2S)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-yn-2-yl]-5-methyl-1H-imidazole-2-carboxamide, (153) N-[(2S,4E)-5-{2-[(4-fluorophenyl)amino]pyrimidin-5-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (154) N-[(3E)-4-{2-[(4-fluorophenyl)amino]pyrimidin-5-yl}but-3-en-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (155) 7-chloro-N-(4-{2-methyl-2H-pyrazolo[3,4-c]pyridin-4-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (156) 7-chloro-N-(4-{1-methyl-1H-pyrazolo[3,4-c]pyridin-4-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (157) 7-chloro-N-(4-{1H-pyrazolo[3,4-c]pyridin-4-yl}but-3-yn-1-yl)-1H-1,3-Benzodiazole-2-carboxamide, (158) N-[4-(5-bromo-6-cyclopropaneamidopyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (159) N-[(2S)-5-{3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (160) 7-chloro-N-[(2S)-5-{3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (161) N-[(2S)-5-{3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl}pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (162) N-[(2S)-5-[5-(methylamino)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (163) N-[4-(6-amino-4,5-dichloropyridin-3-yl)but-3-yn-1-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (164) N-[(2S)-5-(6-amino-4,5-dichloropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (165) N-[(2S)-5-(6-amino-4,5-dichloropyridin-3-yl)pent-4-yn-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (166) N-(4-{6-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (167) 7-chloro-N-(4-{2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl}but-3-yn-1-yl)-1H-1,3-benzodiazole-2-carboxamide, (168) N-(4-{2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl}but-3-yn-1-yl)-3H-imidazo[4,5-b]pyridine-2-carboxamide, (169) N-[(2S)-5-(6-amino-5-chloro-4-methylpyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (170) N-[(2S)-5-(6-amino-5-chloro-4-methoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (171) N-[(2S)-5-(6-amino-5-chloro-4-methylpyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (172) N-[(2S)-5-(5-amino-4-chloropyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (173) N-[(2S)-5-(5-amino-4-methoxypyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (174) N-[(2S)-5-(5-amino-4-chloropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (175) N-[(2S)-5-(5-amino-4-methoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (176) N-[4-(5-amino-4-hydroxypyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (177) N-[(2S,4E)-5-(6-amino-4,5-dichloropyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (178) N-[(2S,4E)-5-(6-amino-4,5-dichloropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (179) N-[(2S)-5-{4-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (180) N-[(2S,4E)-5-[4-methoxy-2-(methylamino)pyrimidin-5-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (181) N-{4-[4-(trifluoromethyl)pyridin-3-yl]but-3-yn-1-yl}-3H-imidazo[4,5-b]pyridine-2-carboxamide, (182) N-[4-(4-chloropyridin-3-yl)but-3-yn-1-yl]-1H-1,3-benzodiazole-2-carboxamide, (183) N-[(2S,4E)-5-(6-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (184) N-[(2S,4E)-5-(2-amino-4-methylpyrimidin-5-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (185) N-[(2S,4E)-5-(2-amino-4-methylpyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (186) N-[(2S,4E)-5-(2-amino-1-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)pent-4-en-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (187) N-[(2S)-5-(6-amino-5-fluoropyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (188) N-[(2S)-5-(6-amino-5-fluoropyridin-3-yl)pent-4-yn-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (189) N-[(2S)-5-(6-amino-5-fluoropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (190) N-[(2S,4E)-5-(6-amino-5-fluoropyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (191) N-[(2S,4E)-5-(6-amino-5-fluoropyridin-3-yl)pent-4-en-2-yl]-7-chloro-1H-1,3-Benzodiazole-2-carboxamide, (192) N-[(2S,4E)-5-(6-amino-5-fluoropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (193) N-[(2S,4E)-5-(2-amino-4-ethylpyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (194) N-[(2S)-5-[6-amino-4-(trifluoromethyl)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (195) N-[(2S,4E)-5-(6-amino-4-chloro-5-methoxypyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (196) N-[(2S)-5-(6-amino-4-chloro-5-methoxypyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (197) N-[(2S,4E)-5-(6-amino-4-chloro-5-methoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (198) N-[(2S)-5-(6-amino-4-chloro-5-methoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (199) N-[(2S)-5-(5-amino-6-methylpyridin-3-yl)pent-4-yn-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, (200) N-[(2S,4E)-5-(5-amino-4-methoxypyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (201) N-[(2S,4E)-5-(5-amino-4-methoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (202) N-[(2S,4E)-5-(5-amino-4-ethoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (203) N-[(2S,4E)-5-(6-amino-5-methylpyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (204) N-[(2S,4E)-5-[6-amino-5-(trifluoromethyl)pyridin-3-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (205) N-[(2S,4E)-5-(6-amino-5-methoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (206) N-[(2S,4E)-5-(5-aminopyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (207) N-[(2S,4E)-5-(5-aminopyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (208) N-[(2S)-5-{3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl}pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (209) N-[(2S,4E)-5-{1H-pyrazolo[3,4-b]pyridin-5-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (210) N-[(2S,4E)-5-{3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (211) N-[(2S)-5-[5-amino-4-(methylamino)pyridin-3-yl]pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (212) N-[(2S)-5-[2-amino-4-(trifluoromethyl)pyrimidin-5-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (213) N-[(2S)-5-(4,5,6,7-tetrahydro-1H-indazol-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (214) N-[(2S,4E)-5-(5-aminopyrazin-2-yl)pent-4-en-2-yl]-1H-1,3-Benzodiazole-2-carboxamide, (215) N-[(2S,4E)-5-(5-aminopyrazin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (216) N-[(2S,4E)-5-(5-amino-6-methoxypyrazin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (217) N-[(2S,4E)-5-(5-amino-6-methylpyrazin-2-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (218) N-[(2S,4E)-5-(5-amino-6-methylpyrazin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (219) N-[(2S)-5-{5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (220) N-[(2S)-5-(2-methyl-1H-imidazol-4-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (221) N-[(2S,4E)-5-(5-fluoropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (222) N-[(2S,4E)-5-(6-methylpyrazin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (223) N-[(2S,4E)-5-(2-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (224) N-[(2S,4E)-5-(4-methoxypyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (225) N-[(2S,4E)-5-(2-amino-4-cyclopropoxypyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,(226) N-[(2S)-5-[6-amino-5-(trifluoromethoxy)pyridin-3-yl]pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (227) N-[(2S,4E)-5-(4-amino-6-methoxypyrimidin-5-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (228) N-[(2S,4E)-5-(4-amino-6-methoxypyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (229) N-[(2S)-5-{7-acetyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (230) N-[(2S,4E)-5-(5-methanesulfonylpyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (231) N-[(2S,4E)-5-(4-fluoropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (232) N-[(2S,4E)-5-{imidazo[1,2-b]pyridazin-3-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (233) N-[(2S,4E)-5-{pyrazolo[1,5-a]pyrimidin-3-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (234) N-[(2S,4E)-5-(1H-indazol-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (235) N-[(2S,4E)-5-(1H-indazol-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (236) N-[(2S)-5-(5-aminopyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (237) N-[(2S,4E)-5-[5-(morpholin-4-yl)pyridin-3-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (238) N-[(2S,4E)-5-[6-amino-5-(trifluoromethoxy)pyridin-3-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (239) N-[(2S,4E)-5-(6-aminopyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (240) N-[(2S,4E)-5-(2-aminopyrimidin-5-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (241) N-[(2S,4E)-5-(2-aminopyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (242) N-[(2S)-5-(4-chloro-5-fluoropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (243) N-[(2S)-5-(5-fluoro-4-methylpyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (244) N-[(2S,4E)-5-(5-chloropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (245) N-[(2S)-5-{7-methyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (246) N-[(2S,4E)-5-(5-cyano-4-methylpyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (247) N-[(2S,4E)-5-(6-amino-5-cyanopyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (248) N-[(2S,4E)-5-(5-carbamoylpyridin-3-yl)pent-4-en-2-yl]-1H-1,3-Benzodiazole-2-carboxamide, (249) N-[(2S,4E)-5-(5-cyanopyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (250) N-[(2S,4E)-5-(pyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (251) N-[(2S,4E)-5-(pyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (252) N-[(2S)-5-{5-[(4-methylpiperazin-1-yl)methyl]pyridin-3-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (253) N-[(2S)-5-{5-[(4-methyl-3-oxopiperazin-1-yl)methyl]pyridin-3-yl}pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (254) N-[(2S,4E)-5-[2-(ethylamino)-4-methoxypyrimidin-5-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (255) N-[(2S,4E)-5-[2-(cyclopropylamino)-4-methoxypyrimidin-5-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (256) N-[(2S,4E)-5-{4-methoxy-2-[(2-methoxyethyl)amino]pyrimidin-5-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (257) N-[(2S,4E)-5-(4,5,6,7-tetrahydro-1H-indazol-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (258) N-[(2S,4E)-5-{5H,6H,7H,8H-imidazo[1,2-a]pyridin-3-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (259) N-[(2S,4E)-5-(3-aminopyrazin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,(260) N-[(2S,4E)-5-(3-amino-1H-pyrazol-5-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (261) N-[(2S,4E)-5-(3-amino-4-chloro-1H-pyrazol-5-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (262) N-[(2S,4E)-5-(3-amino-4-chloro-1H-pyrazol-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (263) N-[(2S,4E)-5-(6-amino-4-methylpyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (264) N-[(2S,4E)-5-(6-amino-4-chloropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (265) N-[(2S,4E)-5-[4-amino-2-(methylamino)pyrimidin-5-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (266) N-[(2S,4E)-5-[2-amino-4-(methylamino)pyrimidin-5-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (267) N-[(2S,4E)-5-[2-amino-4-(ethylamino)pyrimidin-5-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (268) N-[(2S,4E)-5-(5-methyl-1H-pyrazol-4-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (269) N-{1-[(2E)-3-(2-amino-4-methoxypyrimidin-5-yl)prop-2-en-1-yl]cyclobutyl}-3H-imidazo[4,5-b]pyridine-2-carboxamide, (270) N-[(2S,4E)-5-{8-aminoimidazo[1,2-b]pyridazin-3-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (271) N-[(2S,4E)-5-(5-ethoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (272) N-{1-[(2E)-3-(5-methoxypyridin-3-yl)prop-2-en-1-yl]cyclopropyl}-1H-1,3-benzodiazole-2-carboxamide, (273) N-[(2S,4E)-5-(5-methoxypyridin-3-yl)pent-4-en-2-yl]-7-(trifluoromethyl)-1H-1,3-benzodiazole-2-carboxamide, (274) 7-cyano-N-[(2S,4E)-5-(5-methoxypyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (275) N-[(2S)-5-(6-amino-4-fluoropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (276) N-[(2S)-5-(6-amino-4-chloropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (277) N-[(2S,4E)-5-(2-amino-4-methoxypyrimidin-5-yl)pent-4-en-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (278) N-[(2S,4E)-5-(6-amino-5-chloropyridin-3-yl)pent-4-en-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (279) N-[(2S,4E)-5-(5-amino-6-methoxypyrazin-2-yl)pent-4-en-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (280) N-[(2S)-5-(2-amino-4-methoxypyrimidin-5-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (281) N-[(2S)-5-{7-ethyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl}pent-4-yn-2-yl]-1H-1,3-Benzodiazole-2-carboxamide, (282) N-[(2S)-5-[5-(difluoromethoxy)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (283) N-[(2S)-5-(5-methoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (284) N-[(2S)-5-(6-amino-5-chloropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (285) N-[(2S)-5-(6-amino-5-bromopyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (286) N-[(2S)-5-(5-amino-6-methoxypyrazin-2-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (287) N-[(2S)-5-(6-amino-5-fluoropyridin-3-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (288) N-[(2S)-5-(6-amino-5-fluoropyridin-3-yl)pentan-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (289) N-[(2S)-5-[7-(cyclopropylmethyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazin-3-yl]pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (290) N-[(2S)-5-(6-amino-4-bromopyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (291) N-[(2S)-5-(6-amino-4-bromopyridin-3-yl)pent-4-yn-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (292) N-[(2S)-5-(6-amino-4-chloropyridin-3-yl)pent-4-yn-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (293) N-[(2S,4E)-5-(6-amino-4,(294) N-[(2S,4E)-5-(6-amino-5-chloro-4-fluoropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (295) N-[(2S,4E)-5-(6-amino-4,5-dimethoxypyridin-3-yl)pent-4-en-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (296) N-[(2S)-5-(6-amino-4,5-dimethoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (297) N-[(2S)-5-(6-amino-4-fluoropyridin-3-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (298) N-[(2S)-5-(5-amino-6-cyanopyrazin-2-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (299) N-[(2S,4E)-5-(6-amino-4-fluoro-5-methoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (300) N-[(2S)-5-(5-cyano-4-methylpyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (301) N-[(2S,4E)-5-(6-amino-4-fluoro-5-methylpyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (302) N-[(2S)-5-(6-amino-4-fluoro-5-methylpyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (303) N-[(2S)-5-(6-amino-4-fluoro-5-methoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (304) N-[(2S)-5-(2-amino-5,6-difluoropyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-Benzodiazole-2-carboxamide, (305) N-[(2S)-5-(6-amino-5-methylpyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (306) N-[(2S)-5-(6-amino-5-methylpyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (307) N-[(2S)-5-[5-(trifluoromethyl)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (308) N-[(2S)-5-[6-amino-5-(trifluoromethyl)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (309) N-[(2S)-5-(6-amino-5-methoxypyridin-3-yl)pent-4-yn-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (310) N-[(2S)-5-(6-amino-5-methoxypyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (311) N-[(2S)-5-(6-amino-5-methoxypyridin-3-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (312) N-[(2S)-5-(6-amino-5-methylpyridin-3-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (313) N-[(2S)-5-(6-amino-5-methylpyridin-3-yl)pentan-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (314) N-[(2S)-5-[6-amino-5-(trifluoromethyl)pyridin-3-yl]pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (315) N-[(2S)-5-[6-amino-5-(trifluoromethyl)pyridin-3-yl]pentan-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (316) N-[(2S)-5-[6-amino-5-(trifluoromethoxy)pyridin-3-yl]pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (317) N-[(2S,4E)-5-(6-amino-4,5-difluoropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (318) N-[(2S)-5-(6-amino-4,5-difluoropyridin-3-yl)pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (319) N-[(2S,4E)-5-[6-amino-5-(hydroxymethyl)pyridin-3-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (320) N-[(2S,4E)-5-[6-amino-5-(hydroxymethyl)pyridin-3-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (321) N-[(2S,4E)-5-[6-amino-4-(hydroxymethyl)pyridin-3-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (322) N-[(2S,4E)-5-[6-amino-5-(difluoromethoxy)pyridin-3-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (323) N-[(2S,4E)-5-[6-amino-5-(difluoromethyl)pyridin-3-yl]pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (324) N-[(2S)-5-[6-amino-5-(difluoromethoxy)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (325) N-[(2S)-5-[6-amino-5-(difluoromethyl)pyridin-3-yl]pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (326) N-[(2S)-5-(2-aminopyrimidin-5-yl)pentan-2-yl]-1H-1,3-Benzodiazole-2-carboxamide, (327) N-[(2S)-5-(2-aminopyrimidin-5-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (328) N-[(2S)-5-(2-aminopyrimidin-5-yl)pentan-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (329) N-[(2S)-5-(5-aminopyrazin-2-yl)pentan-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (330) N-[(2S)-5-(5-amino-6-methylpyrazin-2-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (331) N-[(2S)-5-(5-amino-6-methylpyrazin-2-yl)pentan-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (332) N-[(2S)-5-(6-amino-4-methoxypyridin-3-yl)pentan-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (333) N-[(2S,4E)-5-(4-methoxypyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (334) N-[(2S,4E)-5-(pyridin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (335) N-[(2S)-4-[(6-amino-5-chloropyridin-3-yl)oxy]butan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (336) N-[(2S)-4-[(6-amino-5-chloropyridin-3-yl)oxy]butan-2-yl]-6-fluoro-3H-imidazo[4,5-b]pyridine-2-carboxamide, (337) N-[(2S,4E)-5-(2-amino-4-methoxypyrimidin-5-yl)pent-4-en-2-yl]-4-chloro-3H-imidazo[4,5-c]pyridine-2-carboxamide, (338) N-[(2S,4E)-5-{pyrazolo[1,5-a]pyrimidin-6-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (339) N-[(2S,4E)-5-{imidazo[1,5-a]pyrimidin-3-yl}pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (340) N-[(2S,4E)-5-{1H-pyrazolo[3,4-b]pyrazin-5-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (341) N-[(2S,4E)-5-(2-amino-6-oxo-1,6-dihydropyrimidin-5-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (342) N-[(2S,4E)-5-(5-amino-6-oxo-1,6-dihydropyrazin-2-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (343) N-[(2R)-5-(6-amino-4-fluoropyridin-3-yl)-1,1,1-trifluoropent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (344) N-[(2S,4E)-5-{pyrrolo[1,2-a]pyrimidin-3-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (345) N-[(2S,4E)-5-{imidazo[1,2-b]pyridazin-7-yl}pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (346) N-[(2R,4E)-5-(6-amino-4-fluoropyridin-3-yl)-1,1,1-trifluoropent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (347) N-[5-(6-amino-5-chloropyridin-3-yl)(1,1,1-, ２ H ３ ) pent-4-yn-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (348) N-[(4E)-5-(2-amino-4-methoxypyrimidin-5-yl)(1,1,1- ２ H ３ ) pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (349) N-[(4E)-5-(6-amino-4-fluoropyridin-3-yl)(1,1,1- ２ H ３ ) pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (350) N-[(4E)-5-(5-methoxypyridin-3-yl)(1,1,1- ２ H ３ ) pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (351) N-[5-(5-methoxypyridin-3-yl)(1,1,1- ２ H ３ ) pentan-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (352) N-[(2S,4E)-5-[6-amino-5-(dimethylcarbamoyl)pyridin-3-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (353) N-[(2S,4E)-5-[6-amino-5-(dimethylsulfamoyl)pyridin-3-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (354) N-[(2S,4E)-5-[6-amino-5-(methylsulfamoyl)pyridin-3-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (355) N-[(2S,4E)-5-(6-amino-5-methanesulfonamidopyridin-3-yl)pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (356) N-[(2S,4E)-5-[6-(1H-1,3-benzodiazol-2-amido)-5-methanesulfonamidopyridin-3-yl]pent-4-en-2-yl]-1H-1,3-benzodiazole-2-carboxamide, (357) N-[(2S,4E)-5-(6-amino-5-methanesulfonamidopyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (358) N-[(2S,4E)-5-(6-{3H-imidazo[4,5-b]pyridin-2-amido}-5-methanesulfonamidopyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (359) N-[(2S,4E)-5-(6-amino-5-methanesulfonylpyridin-3-yl)pent-4-en-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide, and (360) N-[(2S,4E)-5-[6-amino-5-(ethanesulfonyl)pyridin-3-yl]pent-4-en-2-yl]-7-chloro-1H-1,3-benzodiazole-2-carboxamide.

6. General formula (VII): (VII) [wherein, represents a single bond or a double bond; L represents a divalent group obtained by removing two hydrogen atoms from ethane, ethylene, or acetylene, and when L is a divalent group obtained by removing two hydrogen atoms from ethane (ethylene group), one methylene group (—CH ２ -) may have a structure substituted with -O-; １ and Y ２ are each independently a carbon atom or a nitrogen atom; Ｙ１ ~R Ｙ３ and each independently represents a hydrogen atom, a halogen atom, an amino group, an alkyl group having 1 or 2 carbon atoms which may be substituted with a halogen atom, or an alkoxy group having 1 or 2 carbon atoms, or a compound or a salt thereof.

7. At least one compound selected from the group consisting of the following compounds (31), (37), (50), and (215) or a salt thereof: (31) N-[(2S,4E)-5-(2-amino-4-methoxypyrimidin-5-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (37) N-[(2S,4E)-5-(6-amino-4-fluoropyridin-3-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, (50) N-[(2S)-5-(6-aminopyridin-3-yl)pentan-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide, and (215) N-[(2S,4E)-5-(5-aminopyrazin-2-yl)pent-4-en-2-yl]-3H-imidazo[4,5-b]pyridine-2-carboxamide.

8. An AURKB kinase inhibitor comprising the compound or salt thereof according to claim 1, 2, 5, 6, or 7.

9. A pharmaceutical composition containing the compound or salt thereof according to claim 1, 2, 5, 6 or 7 as an active ingredient.

10. A therapeutic agent for at least one disease selected from the group consisting of myelofibrosis, acute myeloid leukemia, B-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma, chronic myeloid leukemia, Hodgkin's lymphoma, Burkitt's lymphoma, multiple myeloma, thyroid cancer, non-small cell lung cancer, squamous cell carcinoma, colon cancer, breast cancer, gastric cancer, prostate cancer, cutaneous melanoma, neuroblastoma, bladder cancer, intrahepatic bile duct cancer, pancreatic ductal adenocarcinoma, hepatocellular carcinoma, uveal melanoma, retinoblastoma, osteoarthritis, diabetic nephropathy, neuropathic pain, and ocular neovascular disease, comprising the compound or salt thereof according to claim 1, 2, 5, 6, or 7.

11. Use of the compound or salt thereof according to any one of claims 1 to 7 for the manufacture of a therapeutic agent for myelofibrosis.

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