Novel carboxamide derivative compound and pharmaceutical composition comprising same

Abstract

The present invention relates to: a carboxamide derivative compound represented by chemical formula I; a stereoisomer thereof; a pharmaceutically acceptable salt thereof or a hydrate or solvate thereof; a composition comprising same; a method using same in the prevention or treatment of IRAK-4 or IRAK-1-related diseases; and uses thereof.

Description

[0001]

specification

[0002]

Title of invention

[0003]

Technical Field

[0004]

Background Technology

[0005] The IL-1R / TLR (IL-1 receptor / Toll-like receptor) signaling pathway plays an important role in immune and inflammatory responses, and has been reported to be involved in the development of various inflammatory and autoimmune diseases, such as sepsis, asthma, arteriosclerosis, Alzheimer's disease, rheumatoid arthritis, atopy, hidradenitis suppurativa, psoriasis, rheumatoid arthritis, ulcerative colitis, and lupus (Journal of Investigative Dermatology. 2019; 139(1) : 146-156 / Anna 1 s of the New York Academy of Sciences . 2008; 1143 : 21— 34 / Journal of Immunology research. 2019; 1824624 / Internat ional Immunopharmaco 1 ogy . 2007; 7(10) : 1271-1285) . In particular, it has been recently reported that blocking the IL-1R / TLR signaling pathway through inhibition of IRAK-4 (inter leukin-1 receptor-associated kinase 4) is effective in chronic inflammatory skin diseases such as psoriasis and atopy (Science Translational Medicine. 2023: 15: eabj3289). It has also been reported that IL-1R / TLR expression is involved in the proliferation of various cancer cells (Oncogene. 2008; 27(2): 218-224). In particular, diffuse large B-cell lymphoma

[0006] It has been reported that IL-1R / TLR signaling is overactivated due to MyD88 mutation in ABC DLBCL, a type of diabetic large B-cell 1 lymphoma (DLBCL), and Waldenstrom macroglobulinemi a (WM), a lymphocytic malignancy (Nature . 2011; 470(7332):115-119 / New England journal of medi cine . 2012; 367(9) : 826-833). Recently, IRAK-4 and IRAK-1 have also been reported to be involved in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) (Current Opinion in Hematology. 2022; 29(1):8-19). When pathogen-associated molecular patterns (PAMPs) commonly expressed by various pathogens and damage-associated molecular patterns (DAMPs) released from stressed or dying cells bind to IL-1R / TLR, downstream signaling mechanisms are activated, resulting in an inflammatory response. If this inflammatory response persists, it can lead to cancer (Nature Immunology. 2011 Jul 19; 12(8): 715-723). Based on the above reports, active research is being conducted to develop substances that block TLR itself, which plays an important role in the IL-1R / TLR signaling pathway, or inhibit IRAK, which is responsible for downstream signals of TLR. In particular, many studies are targeting IRAK-4.

[0007] IRAK is a serine / threonine carboxylic acid 0]There are four subtypes of IRAK (IRAK-1, IRAK-2, IRAK-M, IRAK-4). Among these, research is mainly focused on IRAK-4 and IRAK-1, which have kinase function. In particular, research is most focused on IRAK-4, which plays an important role in forming myddosomes in the IL-1R / TLR signaling pathway, and research on IRAK-1 is also actively underway recently. Although there are no drugs released targeting IRAK-4 or IRAK-1, phase 1 and 2 clinical trials are in progress for various diseases (autoimmune diseases, inflammatory diseases, and blood cancers).

[0008]

Detailed Description of the Invention

[0009]

Technical Problem

[0010]

Technical Solution

[0011] <Chemical Formula 1> In the above chemical formula I,

[0012] Li is a single bond or C1-C6 alkylene, and the following is thiazolidine,

[0013] Ri is H, C1-C6 alkyl, C3-C8 cycloalkyl, 6-14 membered aryl, 3-12 membered heterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of N, 0 and , 3-12 membered heterocycloalkenyl containing 1 to 3 heteroatoms independently selected from the group consisting of N, 0 and S, or 5-12 membered heteroaryl containing 1 to 3 heteroatoms independently selected from the group consisting of N, 0 and , (C=0)0-(Cl-C6 alkyl) or NRaRb, wherein Ra and Rb are each independently H, 6-14 membered aryl or 5-12 membered heterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of N, 0 and . Heteroaryl, and one or more of the above Ri may be substituted with C1-C6 alkyl, C1-C6 alkoxy, OH, NO2, NRaRb, C(=O)-(C1-C6 alkylene)- OH, CF3 or halogen, and the above Ra and Rb are each independently H or C1-C6 alkyl,

[0014] Qi and Q2 are each independently N or N- L『 R2 , but Qi and Q2 cannot be N at the same time, wherein L2 is C1-C6 alkylene or (C1-C6 alkylene)-O-(C1-C6 alkylene), R2 is a 3- to 12-membered heterocycloalkyl, NRcRd, S02Re, C(=0)NH2 or OH containing 1 to 3 heteroatoms independently selected from the group consisting of N, 0 and S in the ring, and Rc, Rd and Re are each independently H or C1-C6 alkyl, and is a 6- to 14-membered arylene or a 5- to 12-membered heteroarylene containing 1 to 3 heteroatoms independently selected from the group consisting of N, 0 and S in the ring,

[0015] L3 is a single bond, C1-C6 alkylene, - NH(C=O)-, - (C=o)-, - C(=O)NH- or - (C=0)0-,

[0016] R3 is a 3- to 12-membered heterocycloalkyl having 1 to 3 heteroatoms independently selected from the group consisting of H, halogen, C1-C6 alkyl, N, 0 and NH2, CF3 or 0H, and at least one of R3 may be substituted with a 3- to 12-membered heterocycloalkyl having 1 to 3 heteroatoms independently selected from the group consisting of OH, C(=0)NH2, C(=O)OH, C(=0)0-(Cl-C6 alkyl), C(=O)NH-(C1-C6 alkyl), N, 0 and , or a 5- to 12-membered heteroaryl having 1 to 3 heteroatoms independently selected from the group consisting of N, 0 and S, and - CH2 - of the heterocycloalkyl of R3 C=0 can be substituted. In one embodiment, in the chemical formula I,

[0017] Li is a single bond or C1-C6 alkylene, and the following is thiazolidine,

[0018] Ri is independently selected from the group consisting of H, C1-C6 alkyl, C3-C8 cycloalkyl, aryl having 6 to 14 members, 3- to 12-membered heterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of N, O and S in the ring, 3- to 12-membered heterocycloalkenyl containing 1 to 3 heteroatoms independently selected from the group consisting of N, O and S in the ring or 5- to 12-membered heteroaryl containing 1 to 3 heteroatoms independently selected from the group consisting of N, O and S in the ring, and one or more of the above Ri may be substituted with C1-C6 alkyl, C1-C6 alkoxy, OH, NO2, NRaRb,

[0019] C(=O)-(C1-C6 alkylene)-OH, CF3 or halogen, and Ra and Rb are each independently H or C1-C6 alkyl,

[0020] Qi and Q2 are each independently N or N-L2-R2, and Qi and Q2 cannot be N at the same time,

[0021] Q O R2* 12 Dou 0

[0022] When Q2 is N, the above Q 2 is N, and when Q1 is N, the above L2 is C1-C6 alkylene or (C1-C6 alkylene)-O-(C1-C6 alkylene), and R2 is 3- to 12-membered heterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of N, O and S in the ring, NRcRd, C(=0)NH2 or OH, and Rc and Rd are each independently C1-C6 alkyl, and is 6- to 14-membered arylene or 5- to 12-membered heteroarylene containing 1 to 3 heteroatoms independently selected from the group consisting of N, O and S in the ring,

[0023] L3 is a single bond, C1-C6 alkylene, - (C=0)-, -C(=O)NH- or - (C=0)0-,

[0024] R3 is a 3-membered to 4-membered ring containing 1 to 3 heteroatoms independently selected from the group consisting of H, halogen, C1-C6 alkyl, N, 0 and

[0025] 12-membered heterocycloalkyl, NH2, CF3 or 0H, and at least one of R3 is OH, C(=0)NH2, C(=O)OH, C(=0)0-(Cl-C6 alkyl),

[0026] Independently selected from the group consisting of C(=O)NH-(C1-C6 alkyl), N, 0 and

[0027] A 3- to 12-membered heterocycloalkyl containing 1 to 3 heteroatoms in the ring or independently selected from the group consisting of N, 0 and

[0028] It may be substituted with a 5- to 12-membered heteroaryl group containing 1 to 3 heteroatoms in the ring. In one embodiment, in the above formula I,

[0029] Li is a single bond or C1-C2 alkylene, and the following is thiazolidine,

[0030] Ri is H, C1-C4 alkyl, C5-C7 cycloalkyl, 6-12 membered aryl, N and

[0031] A 5- to 7-membered heterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of 0 in the ring, a 5- to 7-membered heterocycloalkenyl containing 1 or 2 heteroatoms independently selected from the group consisting of N and 0 in the ring, or a 5- or 6-membered heteroaryl containing 1 to 3 heteroatoms independently selected from the group consisting of N, 0 and in the ring, wherein at least one of Ri is C1-C3 alkyl, C1-C3 alkoxy, OH, NO2, NRaRb,

[0032] C(=0)-(C2-C4 alkylene)- OH, CF3, F or C1 may be substituted, and Ra and Rb are each independently H or C1-C3 alkyl, Qi and Q2 are each independently N or N- R2, but Qi and Q2 cannot be simultaneously.

[0033] Q O R2* L2 >O

[0034] When Q2 is N, the above Q 2 is N, and when Q1 is N, wherein L2 is C1-C6 alkylene or (C1-C2 alkylene)-O-(C1-C2 alkylene), R2 is a 4- to 7-membered heterocycloalkyl, NRcRd, C(=0)NH2 or OH containing 1 to 3 heteroatoms independently selected from the group consisting of N and 0 in the ring, Rc and Rd are each independently C1-C3 alkyl, and is a 6- to 12-membered arylene or a 5- or 6-membered heteroarylene containing 1 to 3 heteroatoms independently selected from the group consisting of N, 0 and S in the ring,

[0035] L3 is a single bond, C1-C2 alkylene, - (C=0)-, -C(=O)NH- or - (C=0)0-,

[0036] R3 is a 5-7 membered heterocycloalkyl containing 1 to 2 heteroatoms independently selected from the group consisting of H, F, Cl, C1-C3 alkyl, N and 0, NH2, CF3 or 0H, and at least one of R3 is a 5-7 membered heterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of OH, C(=0)NH2, C(=O)OH, C(=O)O-(C1-C3 alkyl), C(=O)NH-(C1-C3 alkyl), N and 0, or independently selected from the group consisting of N and 0.

[0037] It can be substituted with a 5- or 6-membered heteroaryl containing 1 or 2 heteroatoms in the ring. In the present invention, the term "Cm-Cn" (wherein m and n are each independently an integer of 1 or more) means the number of carbons, for example, 'C1-C5 alkyl' means alkyl having 1 to 5 carbon atoms. In the present invention, "substitution" or "substituted with ~" is defined to include the implicit condition that such substitution depends on the allowable valency of the substituted atom and the substituent, and that the substitution leads to a stable compound, for example, a compound that does not undergo spontaneous modification by rearrangement, cyclization, elimination, etc. In the present invention, "single bond" means a case where adjacent atoms or groups of atoms are directly bonded. In the present invention, "alkyl" means a linear (or straight-chain) saturated hydrocarbon group or a branched (or side-chain) saturated hydrocarbon group, unless otherwise specified. Examples of alkyl include, but are not limited to, one or more selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, and n-heptyl. In the present invention, unless otherwise stated, "alkylene" means a divalent functional group derived from alkyl defined as above. In the present invention, unless otherwise stated, "cycloalkyl" means a monocyclic or polycyclic saturated hydrocarbon ring. Examples of cycloalkyl include, but are not limited to, one or more selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclopentyl, bicyclohexyl, bicycloheptyl, bicyclooctyl, spiropentyl, spirohexyl, spiroheptyl, spiroctyl, and the like. In the present invention, unless otherwise stated, “cycloalkylene” means a divalent functional group derived from cycloalkyl as defined above.In the present invention, unless otherwise stated, "cycloalkenyl" means a monocyclic or polycyclic unsaturated hydrocarbon ring containing one or more double bonds. Examples of cycloalkenyl include, but are not limited to, one or more selected from cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, etc. In the present invention, unless otherwise stated, "cycloalkenylene" means a divalent functional group derived from cycloalkenyl as defined above. In the present invention, unless otherwise stated, "heterocycloalkyl" means a monocyclic or polycyclic ring in which at least one carbon atom constituting the cycloalkyl ring as defined above is substituted with a heteroatom selected from the group consisting of N, 0, and S. Examples of heterocycloalkyl include, but are not limited to, one or more selected from oxiranyl, dioxolanyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl, thiomorpholinyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, etc. In the present invention, unless otherwise stated, "heterocycloalkylene" means a divalent functional group derived from heterocycloalkyl defined as above. In the present invention, unless otherwise stated, "heterocycloalkenyl" means a monocyclic or polycyclic ring in which at least one carbon atom constituting the cycloalkenyl ring defined as above is substituted with a heteroatom selected from the group consisting of N, 0, and . Examples of heterocycloalkenyl include, but are not limited to, one or more selected from dihydropyridinyl, dihydropyranyl, and dihydrothiopyranyl.In the present invention, unless otherwise stated, "heterocycloalkenylene" means a divalent functional group derived from heterocycloalkenyl as defined above. In the present invention, "aryl" means, unless otherwise stated, a monocyclic or polycyclic aromatic cyclic group having one or more aromatic rings, which are fused or non-fused. Examples of aryl include, but are not limited to, one or more selected from phenyl, naphthalenyl, indenyl, and anthracenyl. In the present invention, unless otherwise stated, "arylene" means, unless otherwise stated, a divalent functional group derived from aryl as defined above. In the present invention, "heteroaryl" means, unless otherwise stated, a monocyclic or polycyclic aromatic heterocyclic group containing at least one heteroatom selected from the group consisting of N, 0, and S in the ring and having one or more aromatic rings, which are fused or non-fused. Examples of heteroaryl include pyridinyl, thiophenyl, triazolyl, tetrazolyl, benzothiazolyl, benzothiophenyl, quinolinyl, indolyl, isoindolyl, benzofuranyl, benzopyrrolyl, furanyl, pyrrolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, oxazolyl, isooxazolyl, pyrazinyl, pyridazinyl, pyrimidinyl, isoquinolinyl, benzoxazolyl, benzoimidazolyl, dihydrobenzothiophenyl, purinyl, indolizinyl, chromyl, pyrrolopyridinyl, pyrazolopyridinyl, thiadiazolopyridinyl, triazinyl, triazolopyrimidinyl , triazolopyridinyl, triazolopyridazinyl, indazolyl, imidazopyridinyl, imidazopyridazinyl, oxadiazolopyridinyl, bezothiadiazolyl, bezotriazolyl, benzoxadiazole, etc., but are not limited thereto. In the present invention, unless otherwise stated, "heteroarylene" means a divalent functional group derived from heteroaryl defined as above.In the present invention, "halogen" may be F, Cl, Br or I unless otherwise stated. In addition, terms and abbreviations used in this specification have their original meanings unless otherwise defined. The present invention provides a compound described in Table 1 below, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof.

[0038] [Table 1] Method for producing a compound represented by chemical formula I The present invention provides a method for producing a compound represented by chemical formula I, a compound of Table 1, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof. The compound of Chemical Formula I of the present invention, the compound of Table 1, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof can be produced, for example, according to the method of the following Reaction Scheme 1, but is not limited thereto.

[0039] <Reaction Scheme 1> In the above reaction formula 1, Ri, R2, RS, LI, L2, L3, X and Y are each represented by the chemical formula

[0040] Each is identical to that defined in the compound entry indicated by I.

[0041] [Step 1] Coupling reaction starting material (compound (0)) to produce 1 or 2-substituted indazole derivatives

[0042] (It is possible to prepare Compound (ii), Compound (vi)) (see Scheme 1 above). Useful reactions for this purpose include reactions using R2-L2-Z (Z is chloride, bromide, iodide or 4-methylbenzenesulfonate) and a base, optionally in a solvent. Optionally, when one of R2-L2-Z is chloride or bromide, it is also possible to add an alkali metal iodide, such as potassium iodide or sodium iodide. Both organic and inorganic bases can be used as the base, for example, the inorganic base can be potassium carbonate, cesium carbonate or sodium hydride. In the case of a reactive halide, it is also possible in some cases to use N-cyclohexyl-N-methylcyclohexanamine as the organic base. The solvent can be, for example, 1-methylpyrrolidin-2-one, DMF, DMSO or THF.

[0043] [Step 2,5] A step of preparing the compound (iii) or compound (vii) by stirring for 0.5 to 24 hours under heating conditions using a condensate and a coupling reaction using a palladium catalyst or a nickel catalyst; and an equal or excess amount of a boronic acid, a boronic acid pinacol ester (in the case of Suzuki-Miyaura coupling), an organotin reagent (in the case of Stille coupling), or an alkene compound (in the case of Heck reaction) in a solvent inert to the coupling reaction in a pressure tube or a general reactor in the presence of a base. Specifically, the compound (iii) or compound (vii) can be prepared by stirring for 0.5 to 24 hours at 20 to 120°C. The solvent is not particularly limited as long as it is inert to the reaction, but may include methanol, ethanol, tetrahydrofuran, 1,2-dimethoxyethane, 1,4-dioxane, water, N,N-dimethylformamide, dimethyl sulfoxide, benzene, toluene, xylene, or a mixture thereof. The palladium catalyst may include tetrakis(triphenylphosphine)palladium, [i,r-bis(diphenylphosphino)ferrocene]dichloropalladium, tris(dibenzylideneacetone)dipalladium, palladium acetate, acetylacetonepalladium, or bis(triphenylphosphine)palladium dichloride. The nickel catalyst may include [1,1'-bis(diphenylphosphino)ferrocene]nickel dichloride or bis(triphenylphosphine)nickel dichloride. Both organic and inorganic bases can be used as the base, and examples thereof include organic bases such as triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.di-7-undecene (DBU), or 1,5-diazabicyclo[4.3.di-5-nonene (DBN); or inorganic bases such as potassium bicarbonate, sodium bicarbonate, potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, potassium phosphate, or sodium phosphate.

[0044] [Step 3,6] Reduction reaction is a step of preparing the compound (iv) or compound (vii i) by stirring the compound (iii) or compound (vii) in a solvent with palladium / charcoal using hydrogen gas under cooling or heating for 3 to 96 hours. Specifically, the compound (iv) or compound (vii i) can be prepared by stirring at room temperature (10 to 25 °C) to 60 °C for 0.5 to 48 hours. The solvent is not particularly limited as long as it does not inhibit the reaction, but methanol, ethanol, tetrahydrofuran, ethyl acetate, dichloromethane, or a mixture thereof can be used.

[0045] [Step 4,7] Amidation reaction is a step of preparing the compound (v) or compound (ix) by stirring the compound (iv) or compound (vii i) in an inert solvent for 1 to 24 hours using an equivalent amount or excess of the corresponding -Li-X-Ri substituted aromatic carboxylic acid and a condensing agent under cooling or heating. Specifically, the compound (v) or compound (ix) can be prepared by stirring at room temperature to 120°C for 1 to 8 hours. The solvent is not particularly limited as long as it is inert to the reaction, but may include N,N-dimethylformamide, dimethylacetamide, dichloromethane, 1,2-dichloroethane, chloroform, tetrahydrofuran, 1,2-dimethoxyethane, acetonitrile, or a mixture thereof. As the above condensing agent, pentafluorophenyl trifluoroacetate, dicyclocarbodiimide (DCC), 3-ethyl (3-dimethylaminopropyl) carbodiimide (EDCI), 1,1'-carbonyldiimidazole, etc. can be used. In addition, an additive or base can be used in the reaction. As the above additive, N-hydroxysuccinimide (HOSu), 1-hydroxybenzotriazole (HOBt),

[0046] 1-Hydroxy-7-azabenzotriazole (HOAt), etc. can be used. As the base, an organic base such as triethylamine or diisopropylethylamine; or an inorganic base such as potassium carbonate, sodium carbonate, potassium hydroxide, or sodium hydroxide can be used. A composition comprising a compound represented by chemical formula I, a method of using a compound represented by chemical formula I, and a use of a compound represented by chemical formula I The present invention provides a pharmaceutical composition comprising a compound represented by the above chemical formula I, a compound of the above table 1, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof as an active ingredient. The present invention provides a health functional food composition comprising a compound represented by the above chemical formula I, a compound of the above table 1, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof. In the present invention, "stereoisomer" includes diastereomers and optical isomers, and optical isomers include not only enantiomers but also mixtures of enantiomers and racemates. In the present invention, "pharmaceutically acceptable" may mean that it is physiologically tolerable and does not typically cause an allergic reaction such as gastrointestinal disorder or dizziness or a similar reaction when administered to a subject. The pharmaceutically acceptable salt of the present invention can be prepared by a conventional method known to those skilled in the art. The "hydrate" of the present invention is a compound represented by Chemical Formula I, a compound of Table 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and water are bound by non-covalent intermolecular forces, and may contain a stoichiometric or non-stoichiometric amount of water. Specifically, the hydrate may contain water in a ratio of about 0.25 mol to about 10 mol based on 1 mol of the active ingredient, and more specifically, may contain water in a ratio of about 0.5 mol, about 1 mol, about 1.5 mol, about 2 mol, about 2.5 mol, about 3 mol, about 5 mol, etc. The "solvate" of the present invention is a compound represented by the chemical formula I, a compound of Table 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and a solvent other than water, which are bound by non-covalent intermolecular forces, and may include a stoichiometric or non-stoichiometric amount of the solvent.Specifically, the above solvate may contain solvent molecules in a ratio of about 0.25 mol to about 10 mol based on 1 mol of the active ingredient, and more specifically, about 0.5 mol, about 1 mol, about 1.5 mol, about 2 mol, about 2.5 mol, about 3 mol, or about.

[0047] 5 mol, etc. The compound represented by the above formula I, the compound of Table 1, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, and a pharmaceutical composition comprising the same as an active ingredient exhibit IRAK-4 and / or IRAK-1 inhibitory activity and can be used for the prevention, treatment, or improvement of IRAK-4 or IRAK-1 related diseases. In the present invention, "IRAK-4 or IRAK-1 related diseases" may be an autoimmune disease, an inflammatory disease, or a tumor. The pharmaceutical composition of the present invention may further comprise one or more pharmaceutically acceptable carriers in addition to the compound represented by the above formula I, the compound of Table 1, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof. At this time, the pharmaceutically acceptable carrier is one commonly used in the art at the time of formulation, and may be at least one selected from lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil, but is not limited thereto. In addition, the pharmaceutical composition of the present invention may additionally include a lubricant, a wetting agent, a sweetener, a flavoring agent, an emulsifier, a suspending agent, or a preservative in addition to the above components. The present invention provides a method for preventing or treating a disease associated with IRAK-4 or IRAK-1, comprising administering to a subject a compound represented by the above chemical formula I, a compound of the above table 1, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, or a pharmaceutical composition comprising the same.The method for preventing or treating an IRAK-4 or IRAK-1 related disease of the present invention may include administering a therapeutically effective amount of a compound represented by the above chemical formula I, a compound of Table 1, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, or a pharmaceutical composition comprising the same. In the present invention, “prevention” means any act of inhibiting or delaying the onset of an IRAK-4 or IRAK-1 related disease by administering a compound represented by the above chemical formula I of the present invention, a compound of Table 1, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof. In the present invention, "treatment" means any act of improving or beneficially changing the symptoms of an IRAK-4 or IRAK-1 related disease by administering a compound represented by the chemical formula I of the present invention, a compound of Table 1, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof. The present invention provides the use of a compound represented by the chemical formula I, a compound of Table 1, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, or a pharmaceutical composition comprising the same, for the prevention or treatment of an IRAK-4 or IRAK-1 related disease. The present invention provides the use of a compound represented by the chemical formula I, a compound of Table 1, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, or a pharmaceutical composition comprising the same, for the manufacture of a medicament for the prevention or treatment of an IRAK-4 or IRAK-1 related disease.

[0048]

Effect of the invention

[0049]

Form for carrying out the invention

[0050] <Example> The compound represented by the chemical formula I of the present invention, the compound of Table 1 above, can be prepared by the method described below. Unless otherwise stated, the starting materials are commercially available or can be prepared by a known method. Example 1. N-(1-(3-hydroxy-3-methylbutyl)-6-(thiophene-3-yl)-1H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide

[0051] [Step 1] Synthesis of 4-(6-bromo-5-nitro-1H-indazol-1-yl)-2-methylbutan-2-ol

[0052] 6-Bromo-5-nitro-2H-indazole (2 g, 8.26 mmol) was added to dimethylformamide (20 mL) and stirred at room temperature. While stirring at room temperature, potassium carbonate (4.57 g, 33.05 mmol) and potassium iodide (0.14 g, 0.83 mmol) were added, and 4-bromo-2-methyl-2-butanol (1.97 mL, 16.5 mmol) was added dropwise. The reaction temperature was raised to 100°C and stirred for 5 hours. Upon completion of the reaction, the internal temperature was cooled to room temperature, diluted with ethyl acetate (40 mL), and washed with purified water (40 mL). Afterwards, magnesium sulfate was added, filtered, concentrated, purified by MPLC (combiFlash NEXTGEN 300+), and concentrated to obtain the title compound (1.2 g). Blood— NMR (DMSO-d 6 ) 1.07(s, 6H) , 1.89(t, 2H) , 4.48(m, 3H) , 8.25(s, 1H), 8.28(s, 1H), 8.55(s, 1H)

[0053] [Step 2] Synthesis of 2-methyl-4-(5-nitro-6-(thiophene-3-yl)-1H-indazol-1-yl)butan-2-ol To the compound of [Step 1] (1.1 g, 3.35 mmol) was added 1,4-dioxane and purified water in a 10:1 ratio (llmL) and stirred at room temperature. Sodium carbonate (1.78 g, 16.8 mmol) and tetrakis(triphenylphosphine)palladium (0.19 g, 0.17 mmol) were added and stirred. 4,4,5,5-tetramethyl-2-(thiophene-3-yl)-1,3,2-dioxaborolane (1.06 g, 5.03 mmol) was added and stirred. The reactor was heated to 100°C and stirred for 8 hours. Upon completion of the reaction, it was cooled to room temperature, ethyl acetate (22 mL) was added, and sodium bicarbonate aqueous solution (22 mL) was added to wash. Afterwards, magnesium sulfate was added, filtered, concentrated, purified by MPLC (combiFlash NEXTGEN 300+), and concentrated to obtain the title compound (0.42 g). P— NMR (DMSO-d 6 ) 1.07(s, 6H) , 1.89(t, 2H) , 4.48(s, 1H) , 4.51(m, 2H), 7.13(s, 1H), 7.63(m, 2H) , 8.25(s, 1H) , 8.28(s, 1H) , 8.55(s, 1H)

[0054] [Step 3] Synthesis of 4-(5-amino-6-(thiophene-3-yl)-1H-indazol-1-yl)-2-methylbutan-2-ol To the compound of [Step 2] (0.54 g, 1.63 mmol) was added ethyl acetate (5.4 mL). Hydrogenation was performed with 0.11 g (0.2 w / w) of palladium on activated carbon under standard hydrogen pressure at 25°C for more than 3 hours. The reaction mixture was filtered through celite, the filter was washed with ethyl acetate (5.4 mL), and the filtrate was concentrated. The title compound (0.45 g) was obtained. 6H) , 1.96(t, 2H) , 4.36(m, 2H) , 4.43(s, 2H),

[0055] 4.45(s, 1H), 6.77(s, 1H), 7.30(m, 2H), 7.34(m, 1H), 7.62(m, 1H), 7.94(s, 1H) [Step 4] Synthesis of N-(1-(3-hydroxy-3-methylbutyl)-6-(thiophene-3-yl)-1H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 1) Dimethylformamide (1.5 mL) was added to the compound (0.15 g, 0.5 mmol) of the above [Step 3] and stirred. DIPEA (0.35 ml, 1.99 mmol), HATU (0.38 g, l.Ommol) were added and stirred. 2-(Pyridin-3-yl)thiazole-4-carboxylic acid (0.1 g, 0.5 mmol) was added and stirred at room temperature for more than 6 hours. After completion of the reaction, the mixture was washed with purified water (1.5 ml), magnesium sulfate was added, filtered, concentrated, purified by MPLC (combi Fl ash NEXTGEN 300+), concentrated, dried, and the title compound (0.12 g) was obtained. P— NMR (DMSO-d 6 ) 1.12(s, 6H) , 1.90(t, 2H) , 4.47(t, 2H) , 4.49(s, 1H), 7.42(m, 1H), 7.48(m, 1H) , 7.67(m, 1H) , 7.79(m, 1H) , 7.86(m, 1H) , 7.86(m, 1H) , 8.08(s, 1H), 8.23(m, 1H) , 8.50(s, 1H) , 8.71(m, 1H) , 9.10(d, 1H) , 9.90(s, 1H)

[0056] LC-MS (ESI, m / z) = 490.1 (M+H+) Example 2. N-(2-(3-hydroxy-3-methylbutyl)-6-(thiophene-3-yl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide

[0057] [Step 1] Synthesis of 4-(6-bromo-5-nitro-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 1] of Example 1, 6-bromo-5-nitro-2H-indazole (2 g, 8.26 mmol), dimethylformamide (20 mL), potassium carbonate (4.57 g, 33.05 mmol), potassium iodide (0.14 g, 0.83 mmol) and 4-bromo-2-methyl-2-butanol (1.97 ml,

[0058] After the reaction was carried out in the same manner using 16.5 mmol), the product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.925 g). 6H) , 2.01(t, 2H) , 4.50(s, 1H) , 4.53(m, 2H),

[0059] 8.13(s, 1H), 8.59(s, 1H), 8.75(s, 1H) [Step 2] Synthesis of 2-methyl-4-(5-nitro-6-(thiophene-3-yl)-2H-indazol-2-yl)butan-2-ol Under the same conditions as [Step 2] of Example 1, the compound of [Step 1] (0.9 g, 2.74 mmol), sodium carbonate (1.45 g, 13.7 mmol), tetrakis(triphenylphosphine)palladium (0.16 g, 0.14 mmol) and 4,4,5,5-tetramethyl-2-(thiophene-3-yl)-1,3,2-dioxaborolane (0.86 g, 4.11 mmol) were used, and the reaction was carried out in the same manner. The title compound (0.44 g) was obtained by purification by MPLC (combiFlash NEXTGEN 300+) and concentration. P— NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.04(t, 2H) , 4.50(s, 1H) , 4.53(m, 2H), 7.08(s, 1H), 7.58(s, 2H) , 8.13(s, 1H) , 8.59(s, 1H) , 8.75(s, 1H)

[0060] [Step 3] Synthesis of 4-(5-amino-6-(thiophene-3-yl)-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.4 g, 1.22 mmol) was hydrogenated with 0.08 g (0.2 w / w) of palladium on activated carbon. The resulting mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.33 g). P— NMR (DMSO-d 6 ) 1.09(s, 6H) , 1.85(t, 2H) , 3.88(s, 2H) , 4.40(s, 1H), 4.50(m, 2H), 6.94(s, 1H) , 7.34(m, 2H) , 7.66(m, 2H) , 7.70(s, 1H)

[0061] [Step 4] Synthesis of N-(2-(3-hydroxy-3-methylbutyl)-6-(thiophene-3-yl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 2) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] (0.11 g, 0.36 mmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.08 g, 0.36 mmol), HATU (0.28 g,

[0062] The reaction was carried out in the same manner using DI PEA (0.25 mL, 1.46 mmol) and purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.09 g). P— NMR (DMSO-d 6) 1.13(s, 6H) , 2.02(t, 2H) , 4.44(s, 1H) , 4.46(t, 2H), 7.38(m, 1H), 7.58(m, 2H) , 7.78(m, 1H) , 7.81(m, 1H) , 8.22(m, 1H) , 8.42(s, 1H) , 8.49(s, 1H), 8.51(s, 1H) , 8.63(s, 1H) , 9.08(s, 1H) , 9.81(s, 1H)

[0063] LC-MS (ESI, m / z) = 490.1 (M+H+) Example 3. N-(6-(furan-3-yl)-1-(2-hydroxy-2-methylpropyl)-1H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0064] [Step 1] Synthesis of 1-(6-bromo-5-nitro-1H-indazol-2-yl)-2-methylpropan-2-ol Under the same conditions as in [Step 1] of Example 1, 6-bromo-5-nitro-2H-indazole (2 g, 8.26 mmol), potassium carbonate (4.57 g, 33.05 mmol), potassium iodide (0.14 g, 0.83 mmol) and 1-bromo-2-methylpropanol (1.65 ml, 16.5 mmol) were used. The reaction mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.92 g). p- NMR (DMSO-d 6 ) 1.09(s, 6H) , 4.34(s, 2H) , 4.69(s, 1H) , 8.25(s, 1H), 8.29(s, 1H), 8.55(s, 1H)

[0065] [Step 2] Synthesis of 1-(6-(furan-3-yl)-5-nitro-1H-indazol-2-yl)-2-methylpropan-2-ol Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] (0.9 g, 2.88 mmol), sodium carbonate (1.52 g, 14.4 mmol), tetrakis(triphenylphosphine)palladium (0.17 g, 0.14 mmol), and 4,4,5,5-tetramethyl-2-(furan-3-yl)-1,3,2-dioxaborolane (0.84 g, 4.31 mmol) was used, and the reaction was carried out in the same manner. The product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.5 g). Blood— NMR (DMSO-d 6 ) 1.08(s, 6H) , 4.37(s, 2H) , 4.87(s, 1H) , 6.55(s, 1H), 7.69(s, 1H), 7.71(s, 1H) , 8.25(s, 1H) , 8.29(s, 1H) , 8.55(s, 1H)

[0066] [Step 3] Synthesis of 1-(5-amino-6-(furan-3-yl)-1H-indazol-1-yl)-2-methylpropan-2-ol Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.5 g, 1.66 mmol) was hydrogenated with 0.1 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through Celite, and the filtrate was concentrated to obtain the title compound (0.35 g). P— NMR (DMSO-d 6 ) 1.05(s, 6H) , 4.19(s, 2H) , 4.50(s, 2H) , 4.80(s, 1H), 5.96(s, 2H), 6.82(s, 1H) , 6.83(s, 1H) , 7.25(s, 1H) , 7.29(s, 1H) , 7.55(s, 1H)

[0067] [Step 4] Synthesis of N-(6-(furan-3-yl)-1-(2-hydroxy-2-methylpropyl)-1H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 3) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.11 g, 0.41 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.09 g, 0.41 mmol), HATU (0.31 g, 0.81 mmol) and DI PEA (0.28 mL, 1.62 mmol) were reacted in the same manner, and the product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to give the title compound (0.08 g). Obtained. 6H) , 4.32(t, 2H) , 4.72(s, 1H) , 6.95(s, 1H),

[0068] 7.83(m, 1H), 7.89(m, 1H) , 8.04(m, 1H) , 8.08(m, 1H) , 8.25(m, 2H) , 8.28(m, 1H) , 8.69(s, 1H), 8.93(m, 2H) , 10.14(s, 1H)

[0069] LC-MS (ESI, m / z) = 460.1 (M+H+) Example 4. N-(6-(furan-3-yl)-2-(2-hydroxy-2-methylpropyl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0070] [Step 1] Synthesis of 1-(6-bromo-5-nitro-2H-indazol-2-yl)-2-methylpropan-2-ol Under the same conditions as [Step 1] of Example 1, 6-bromo-5-nitro-2H-indazole

[0071] (2g, 8.26mmol), potassium carbonate (4.57g, 33.05mmol), potassium iodide (0.14g, 0.83mmol) and 1-bromo-2-methylpropanol (1.65ml, 16.5mmol) were used in the same manner, and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.90g). P- NMR (DMSO-d 6 ) 1.08(s, 6H) , 4.37(s, 2H) , 4.89(s, 1H) , 8.15(s, 1H), 8.61(s, 1H), 8.63(s, 1H)

[0072] [Step 2] Synthesis of 1-(6-(furan-3-yl)-5-nitro-2H-indazol-2-yl)-2-methylpropan-2-ol Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] (0.5 g,

[0073] The reaction was carried out in the same manner using sodium carbonate (0.85 g, 7.99 mmol), tetrakis(triphenylphosphine)palladium (0.09 g, 0.08 mmol) and 4,4,5,5-tetramethyl-2-(furan-3-yl)-1,3,2-dioxaborolane (0.47 g, 2.4 mmol), and the resulting mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to give the title compound (0.45 g). P— NMR (DMSO-d 6 ) 1.08(s, 6H) , 4.37(s, 2H) , 4.87(s, 1H) , 6.55(s, 1H), 7.71-7.72(m, 2H) , 8.15(s, 1H) , 8.61(s, 1H) , 8.63(s, 1H)

[0074] [Step 3] Synthesis of 1-(5-amino-6-(furan-3-yl)-2H-indazol-2-yl)-2-methylpropan-2-ol Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.45 g, 1.66 mmol) was hydrogenated with 0.09 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through Celite, and the filtrate was concentrated to obtain the title compound (0.32 g). P— NMR (DMSO-d 6 ) 1.04(s, 6H) , 4.19(s, 2H) , 4.49(s, 2H) , 4.75(s, 1H), 5.74(s, 1H), 6.72-6.73(m, 2H) , 7.05(s, 1H) , 7.10(s, 1H) , 7.44(s, 1H)

[0075] [Step 4] Synthesis of N-(6-(furan-3-yl)-2-(2-hydroxy-2-methylpropyl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 4) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.11 g, 0.41 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.09 g, 0.41 mmol), HATU (0.31 g, 0.81 mmol), and DI PEA (0.28 mL, 1.62 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.08 g). P- NMR (DMSO-d 6 ) 1.09(s, 6H) , 4.32(t, 2H) , 4.85(s, 1H) , 6.94(s, 1H), 7.69(s, 1H), 7.90(m, 3H) , 8.06(s, 1H) , 8.32(s, 1H) , 8.44(s, 1H) , 8.57(s, 1H) , 8.77(m, 2H), 9.99(s, 1H)

[0076] LC-MS (ESI, m / z) = 460.1 (M+H+) Example 5. N-(2-(2-(dimethylamino)ethyl)-6-(furan-3-yl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0077] [Step 1] Synthesis of 2-(6-bromo-5-nitro-2H-indazol-2-yl)-N,N-dimethylethan-1-amine Under the same conditions as in [Step 1] of Example 1, 6-bromo-5-nitro-2H-indazole (2 g, 8.26 mmol), potassium carbonate (4.57 g, 33.05 mmol), potassium iodide (0.14 g, 0.83 mmol) and 2-chloro-N,N-dimethylethan-1-amine hydrochloride (2.38 g, 16.5 mmol) were used. The reaction mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.93 g). P— NMR (DMSO-d 6 ) 2.12(s, 6H) , 2.77(t, 2H) , 4.55(t, 2H) , 8.15(s, 1H), 8.61(s, 1H), 8.63(s, 1H)

[0078] [Step 2] 2- (6- (furan- 3 -yl)- 5 -nitro- 2H-indazol- 2 -yl)- N, N-dimethylethane-

[0079] 1-Amine Synthesis Example 1 Under the same conditions as [Step 2], the compound of [Step 1] (0.9 g,

[0080] The reaction was carried out in the same manner using sodium carbonate (2.87 mmol), sodium hydroxide (1.52 g, 14.4 mmol), tetrakis(triphenylphosphine)palladium (0.17 g, 0.14 mmol) and 4,4,5,5-tetramethyl-2-(furan-3-yl)-1,3,2-dioxaborolane (0.84 g, 4.31 mmol), and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to give the title compound (0.73 g). P— NMR (DMSO-d 6 ) 2.12(s, 6H) , 2.77(t, 2H) , 4.55(t, 2H) , 6.55(s, 1H), 7.71-7.72(m, 2H) , 8.15(s, 1H) , 8.61(s, 1H) , 8.63(s, 1H)

[0081] [Step 3] Synthesis of 2-(2-(dimethylamino)ethyl)-6-(furan-3-yl)-2H-indazol-5-amine Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.2 g, 0.74 mmol) was hydrogenated with 0.04 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through celite, and the filtrate was concentrated to obtain the title compound (0.13 g). P— NMR (DMSO-d 6 ) 2.08(s, 6H) , 2.61(t, 2H) , 4.38(t, 2H) , 4.50(s, 2H), 6.41(s, 1H), 7.61(s, 1H), 7.64(s, 1H) , 7.66(s, 1H) , 7.95(s, 1H) , 7.99(s, 1H)

[0082] [Step 4] Synthesis of N-(2-(2-(dimethylamino)ethyl)-6-(furan-3-yl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 5) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.11 g, 0.41 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.08 g, 0.41 mmol), HATU (0.31 g, 0.81 mmol), and DI PEA (0.28 mL, 1.63 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.07 g). P- NMR (DMSO-d 6 ) 2.17(s, 6H) , 2.79(m, 2H) , 4.49(t, 2H) , 6.93(s, 1H), 7.67(s, 1H), 7.90(m, 2H) , 7.92(m, 1H) , 8.06(s, 1H) , 8.40(s, 1H) , 8.42(s, 1H) , 8.57(s, 1H), 8.77(m, 2H) , 9.99(s, 1H)

[0083] LC-MS (ESI, m / z) = 459.1 (M+H+) Example 6. N-(1-(2-(dimethylamino)ethyl)-6-(furan-3-yl)-1H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0084] [Step 1] Synthesis of 2-(6-bromo-5-nitro-1H-indazol-1-yl)-N,N-dimethylethan-1-amine Under the same conditions as in [Step 1] of Example 1, 6-bromo-5-nitro-2H-indazole (2 g, 8.26 mmol), potassium carbonate (4.57 g, 33.05 mmol), potassium iodide (0.14 g, 0.83 mmol) and 2-chloro-N,N-dimethylethan-1-amine hydrochloride (2.38 g, 16.5 mmol) were used, and the reaction was carried out in the same manner. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.91 g). P— NMR (DMSO-d 6 ) 2.12(s, 6H) , 2.77(t, 2H) , 4.55(t, 2H) , 8.25(s, 1H), 8.29(s, 1H), 8.55(s, 1H)

[0085] [Step 2] Synthesis of 2-(6-(furan-3-yl)-5-nitro-1H-indazol-1-yl)-N,N-dimethylethan-1-amine Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] (0.9 g, 2.87 mmol), sodium carbonate (1.52 g, 14.4 mmol), tetrakis(triphenylphosphine)palladium (0.17 g, 0.14 mmol), and 4,4,5,5-tetramethyl-2-(furan-3-yl)-1,3,2-dioxaborolane (0.84 g, 4.31 mmol) were used, and the reaction was carried out in the same manner.

[0086] The title compound (0.75 g) was obtained by purification by MPLC (combiFlash NEXTGEN 300+) and concentration. P— NMR (DMSO-d 6 ) 2.12(s, 6H) , 2.77(t, 2H) , 4.55(t, 2H) , 6.55(s, 1H), 7.69(s, 1H), 7.71(s, 1H) , 8.25(s, 1H) , 8.29(s, 1H) , 8.55(s, 1H)

[0087] [Step 3] Synthesis of 1-(2-(dimethylamino)ethyl)-6-(furan-3-yl)-1H-indazol-5-amine Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.2 g, 0.74 mmol) was hydrogenated with 0.04 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through Celite, and the filtrate was concentrated to obtain the title compound (0.12 g). P— NMR (DMSO-d 6 ) 2.08(s, 6H) , 2.60(t, 2H) , 4.37(t, 2H) , 4.49(s, 2H), 6.43(s, 1H), 7.66(s, 1H) , 7.69(s, 1H) , 7.72(s, 1H) , 7.74(s, 1H) , 8.02(s, 1H)

[0088] [Step 4] Synthesis of N-(1-(2-(dimethylamino)ethyl)-6-(furan-3-yl)-1H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 6) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.11 g, 0.41 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.08 g, 0.41 mmol), HATU (0.31 g, 0.81 mmol), and DI PEA (0.28 mL, 1.63 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.06 g). P- NMR (DMSO-d 6 ) 2.17(s, 6H) , 2.73(m, 2H) , 4.50(m, 2H) , 6.98(s, 1H), 7.81(s, 1H), 7.93(m, 3H) , 8.07(m, 2H) , 8.36(s, 1H) , 8.58(s, 1H) , 8.77(m, 2H) , 10.1(s, 1H)

[0089] LC-MS (ESI, m / z) = 459.1 (M+H+) Example 7. N-(6-(furan-3-yl)-2-(2-hydroxy-2-methylpropyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide

[0090] [Step 4] Synthesis of N-(6-(furan-3-yl)-2-(2-hydroxy-2-methylpropyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 7) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 4 (0.11 g, 0.41 mmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.09 g, 0.41 mmol), HATU (0.31 g, 0.81 mmol), and DI PEA (0.28 mL, 1.62 mmol) were reacted in the same manner, and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (0.08 g) was obtained. P- NMR (DMSO-d 6 ) 1.09(s, 6H) , 4.32(m, 2H) , 4.84(s, 1H) , 6.94(s, 1H), 7.60(m, 1H), 7.69(s, 1H) , 7.86(s, 1H) , 8.08(s, 1H) , 8.32(m, 2H), 8.44(s, 1H) , 8.50(s, 1H), 8.70(m, 1H) , 9.17(s, 1H) , 9.99(s, 1H) LC-MS (ESI, m / z) = 460.1 (M+H+) Example 8. N- (2- (2- (dimethylamino) ethyl)- 6- (1H-pyrazole- 3 -day)- 2H -indazole-

[0091] 5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0092] [Step 2] N,N-Dimethyl- 2- (5 -nitro- 6- (1- (tetrahydro- 2H-pyran- 2 -yl)-

[0093] Synthesis of 1H-pyrazol-5-yl)-2H-indazol-2-yl)ethan-1-amine Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] of Example 5

[0094] The reaction was carried out in the same manner using sodium carbonate (0.51 g, 4.79 mmol), tetrakis(triphenylphosphine)palladium (0.06 g, 0.05 mmol) and 3-(4, 4, 5, 5-tetramethyl-1,3, 2-dioxaborolan-2-yl)-1H-pyrazole (0.4 g, 1.44 mmol), purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to give the title compound (0.31 g). P— NMR (DMSO-d 6 ) 2.21(s, 6H) , 2.78(m, 2H) , 4.55(t, 2H) , 6.97(d, 1H), 7.92 (d, 1H), 8.60(s, 1H) , 8.77(s, 1H) , 9.01(s, 1H) , 12.4(s, 1H)

[0095] [Step 3] Synthesis of 2-(2-(dimethylamino)ethyl)-6-(1H-pyrazol-5-yl)-2H-indazol-5-amine Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.3 g, 0.78 mmol) was hydrogenated with 0.06 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through Celite, and the filtrate was concentrated to obtain the title compound (0.13 g). P— NMR (DMSO-d 6 ) 2.12(s, 6H) , 2.78 (t, 2H) , 4.49 (s, 2H) , 4.55(t, 2H), 6.53(d, 1H), 7.52(d, 1H) , 8.15(s, 1H) , 8.61(s, 1H) , 8.63(s, 1H) , 11.6(s, 1H)

[0096] [Step 4] Synthesis of N-(2-(2-(dimethylamino)ethyl)-6-(1H-pyrazol-3-yl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 8) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] (0.11 g, 0.41 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.08 g, 0.41 mmol), HATU (0.31 g, 0.81 mmol) and DI PEA (0.28 mL, 1.63 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.07 g). Obtained. Blood— NMR (DMSO-d 6 ) 2.23(s, 6H) , 2.80(m, 2H) , 4.56(t, 2H) , 6.99(d, 1H), 8.00(m, 2H), 8.02(s, 1H) , 8.08(m, 2H) , 8.61(s, 1H) , 8.79(m, 3H) , 9.03(s, 1H) , 12.4(s, 1H)

[0097] LC-MS (ESI, m / z) = 459.1 (M+H+) Example 9. N- (2- (2- (1,3 ■dioxolane- 2 -yl)ethyl)- 6- (furan- 3 -yl)- 2H -indazole- 5 -yl)- 2- (pyridin- 4 -yl)thiazole- 4 -carboxamide

[0098] [Step 1] Synthesis of 2-(2-(1,3-dioxolane-2-yl)ethyl)-6-bromo-5-nitro-2H-indazole Under the same conditions as in [Step 1] of Example 1, 6-bromo-5-nitro-2H-indazole (2 g, 8.26 mmol), potassium carbonate (4.57 g, 33.05 mmol), potassium iodide (0.14 g, 0.83 mmol) and 2-(2-bromoethyl)-1,3-dioxolane (3.0 g, 16.5 mmol) were used. The reaction mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (1.02 g). P— NMR (DMSO-d 6 ) 2.29(t, 2H) , 3.79(m, 2H) , 3.91(m, 2H) , 4.54(m, 2H), 4.81(m, 1H), 8.15(s, 1H) , 8.61(s, 1H) , 8.63(s, 1H)

[0099] [Step 2] Synthesis of 2-(2-(1,3-dioxolan-2-yl)ethyl)-6-(furan-3-yl)-5-nitro-2H-indazole Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] (1.0 g, 2.92 mmol), sodium carbonate (1.55 g, 14.6 mmol), tetrakis(triphenylphosphine)palladium (0.17 g, 0.15 mmol), and 4,4,5,5-tetramethyl-2-(furan-3-yl)-1,3,2-dioxaborolane (0.85 g, 4.38 mmol) were used, and the reaction was carried out in the same manner. The product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.79 g). Blood— NMR (DMSO-d 6 ) 2.27(t, 2H) , 3.75(m, 2H) , 3.83(m, 2H) , 4.49(m, 2H), 4.80(m, 1H), 6.55(s, 1H) , 7.71-7.72 (m, 2H) , 8.18 (s, 1H) , 8.64 (s, 1H) , 8.69 (s, 1H)

[0100] [Step 3] Synthesis of 2-(2-(1,3-dioxolan-2-yl)ethyl)-6-(furan-3-yl)-2H-indazol-5-amine Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.5 g, 1.52 mmol) was hydrogenated with 0.1 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through Celite, and the filtrate was concentrated to obtain the title compound (0.32 g). 2H) , 3.61(m, 2H) , 3.74(m, 2H) , 4.35(m, 2H),

[0101] 4.52(s, 2H), 4.61(m, 1H) , 6.49(s, 1H) , 7.50- 7.51(m, 2H) , 7.82(s, 1H) , 8.31(s, 1H), 8.35(s, 1H)

[0102] [Step 4] Synthesis of N-(2-(2-(1,3-dioxolane-2-yl)ethyl)-6-(furan-3-yl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 9) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] (0.11 g, 0.37 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.08 g, 0.37 mmol), HATU (0.28 g, 0.73 mmol), and DI PEA (0.26 mL, 1.47 mmol) were reacted in the same manner, and then purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (0.08 g) was obtained. P— NMR (DMSO-d 6) 2.25(t, 2H) , 3.77(m, 2H) , 3.89(m, 2H) , 4.50(m, 2H), 4.83(m, 1H), 6.93(s, 1H) , 7.67(s, 1H) , 7.89(m, 1H) , 7.93(m, 1H) , 8.06(s, 1H) , 8.41(s, 1H), 8.43(s, 1H) , 8.58(s, 1H) , 8.77- 8.78(m, 3H) , 9.98(s, 1H) LC-MS (ESI, m / z) = 488.1 (M+H+) Example 10. N- (1-(2-(1,3 ■dioxolane-2-yl)ethyl)-6-(furan-3-yl)-1H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0103] [Step 1] Synthesis of 1-(2-(1,3-dioxolane-2-yl)ethyl)-6-bromo-5-nitro-1H-indazole Under the same conditions as in [Step 1] of Example 1, 6-bromo-5-nitro-2H-indazole (2 g, 8.26 mmol), potassium carbonate (4.57 g, 33.05 mmol), potassium iodide (0.14 g, 0.83 mmol), and 2-(2-bromoethyl)-1,3-dioxolane (3.0 g, 16.5 mmol) were used. The reaction mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (1.23 g). p- NMR (DMSO-d 6 ) 2.14(m, 2H) , 3.75(t, 2H) , 3.88(m, 2H) , 4.48(m, 2H), 4.81(m, 1H), 8.13(s, 1H) , 8.58(s, 1H) , 8.75(s, 1H)

[0104] [Step 2] Synthesis of 1-(2-(1,3-dioxolan-2-yl)ethyl)-6-(furan-3-yl)-5-nitro-1H-indazole Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] (1.0 g, 2.92 mmol), sodium carbonate (1.55 g, 14.6 mmol), tetrakis(triphenylphosphine)palladium (0.17 g, 0.15 mmol), and 4,4,5,5-tetramethyl-2-(furan-3-yl)-1,3,2-dioxaborolane (0.85 g, 4.38 mmol) were used, and the reaction was carried out in the same manner. The product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.71 g). P- NMR (DMSO-d 6 ) 2.14(m, 2H) , 3.75(t, 2H) , 3.88(m, 2H) , 4.48(m, 2H), 4.81(m, 1H), 6.98(s, 1H) , 7.75(s, 1H) , 7.91(s, 1H) , 8.13(s, 1H) , 8.58(s, 1H) , 8.75(s, 1H)

[0105] [Step 3] Synthesis of 1-(2-(1,3-dioxolan-2-yl)ethyl)-6-(furan-3-yl)-1H-indazol-5-amine Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.5 g, 1.52 mmol) was hydrogenated with 0.1 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through Celite, and the filtrate was concentrated to obtain the title compound (0.3 g). P- NMR (DMSO-d 6 ) 2.09(m, 2H) , 3.70(m, 2H) , 3.83(m, 2H) , 4.43(m, 2H), 4.49(s, 2H), 4.76(m, 1H) , 6.93(s, 1H) , 7.69(s, 1H) , 7.86(s, 1H) , 8.07(s, 1H) , 8.53(s, 1H), 8.68(s, 1H)

[0106] [Step 4] Synthesis of N-(1-(2-(1,3-dioxolane-2-yl)ethyl)-6-(furan-3-yl)-1H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 10) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] (0.11 g, 0.37 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.08 g, 0.37 mmol), HATU (0.28 g, 0.73 mmol), and DI PEA (0.26 mL, 1.47 mmol) were reacted in the same manner, and the product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (0.07 g) was obtained. P- NMR (DMSO-d 6 ) 2.14(m, 2H) , 3.75(t, 2H) , 3.88(m, 2H) , 4.48(m, 2H), 4.81(m, 1H), 6.98(s, 1H) , 7.75(s, 1H) , 7.92(s, 1H) , 8.09 (m, 1H) , 8.13(s, 1H), 8.38(m, 2H), 8.58(s, 1H) , 8.75(s, 1H) , 8.77(m, 2H) , 10.07(s, 1H)

[0107] LC-MS (ESI, m / z) = 488.1 (M+H+) Example 11. N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0108] [Step 1] Synthesis of 4-(6-bromo-5-nitro-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as [Step 1] of Example 1, 6-bromo-5-nitro-1H-indazole

[0109] (3 g, 12.4 mmol), potassium carbonate (6.85 g, 49.6 mmol), potassium iodide (0.21 g, 1.24 mmol) and 4-bromo-2-methylbutan-2-ol (2.96 mL, 24.8 mmol) were used in the same manner. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (1.91 g). P— NMR (DMSO-d 6 ) 1.12(s, 6H), 2.02(m, 2H), 4.46— 4.49(m, 3H), 8.10(s, 1H), 8.42(s, 1H), 8.49(s, 1H)

[0110] [Step 2] Synthesis of 4-(6-(furan-3-yl)-5-nitro-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] (1.9 g, 5.79 mmol), sodium carbonate (3.07 g, 28.9 mmol), tetrakis(triphenylphosphine)palladium (0.33 g, 0.29 mmol), and 4,4,5,5-tetramethyl-2-(furan-3-yl)-1,3,2-dioxaborolane (1.69 g, 8.69 mmol) were used, and the reaction was carried out in the same manner. The product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (1.5 g). P- NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.02(m, 2H) , 4.46- 4.49(m, 3H) , 6.93(s, 1H), 7.66(s, 1H), 7.79(s, 1H) , 8.11(s, 1H) , 8.43(s, 1H) , 8.50(s, 1H)

[0111] [Step 3] Synthesis of 4-(5-amino-6-(furan-3-yl)-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (1.5 g, 4.76 mmol) was hydrogenated with 0.3 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through celite, and the filtrate was concentrated to obtain the title compound (1.06 g). P— NMR (DMSO-d 6 ) 1.09(s, 6H) , 1.94(m, 2H) , 4.32— 4.35(m, 3H) , 4.52(s, 2H), 6.72(s, 1H), 7.46(s, 1H) , 7.58(s, 1H) , 7.91(s, 1H) , 8.22(s, 1H) , 8.33(s, 1H)

[0112] [Step 4] Synthesis of N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 11) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] (0.11 g, 0.39 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.08 g, 0.39 mmol), HATU (0.29 g, 0.77 mmol) and DI PEA (0.27 mL, 1.54 mmol) were reacted in the same manner, and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to give the title compound (0.08 g). Obtained.

[0113] 1H-NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.02(m, 2H) , 4.46— 4.49(m, 3H) , 6.93(s, 1H), 7.66(s, 1H), 7.89(m, 2H) , 7.90(s, 1H) , 8.06(s, 1H) , 8.40(s, 1H) , 8.43(s, 1H), 8.50(s, 1H), 8.77(m, 2H) , 9.98(s, 1H)

[0114] LC-MS (ESI, m / z) = 474.1 (M+H+) Example 12. N-(6-(furan- 3 -yl)- 2-(3 -hydroxy- 3 -methylbutyl)- 2H -indazol- 5-yl)- 2-(pyridin- 3 -yl)thiazole- 4 -carboxamide

[0115] [Step 4] Synthesis of N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 12) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 11 (0.11 g, 0.39 mmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.08 g, 0.39 mmol), HATU (0.29 g, 0.77 mmol), and DI PEA (0.27 mL, 1.54 mmol) were reacted in the same manner, and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (0.08 g) was obtained. P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.02(t, 2H) , 4.46— 4.47(m, 3H) , 6.92(s, 1H), 7.60(m, 1H), 7.66(s, 1H) , 7.86(s, 1H) , 8.07(s, 1H) , 8.31(m, 1H) , 8.40(s, 1H), 8.43(s, 1H), 8.50(s, 1H) , 8.71(m, 1H) , 9.17(s, 1H) , 9.98(s, 1H)

[0116] LC-MS (ESI, m / z) = 474.1 (M+H+) Example 13. N-(6-(furan-3-yl)-1-(3-hydroxy-3-methylbutyl)-1H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide [Step 1] Synthesis of 4-(6-bromo-5-nitro-1H-indazol-1-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 1] of Example 1, 6-bromo-5-nitro-1H-indazole (2 g, 8.26 mmol), potassium carbonate (4.57 g, 33.1 mmol), potassium iodide (0.14 g, 0.83 mmol), and 4-bromo-2-methylbutan-2-ol (1.97 mL, 16.5 mmol) were used. The reaction mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (1.27 g). P— NMR (DMSO-d 6 ) 1.12(s, 6H), 1.90(m, 2H), 4.46— 4.49(m, 3H), 8.06(s, 1H), 8.11(s, 1H), 8.56(s, 1H)

[0117] [Step 2] Synthesis of 4-(6-(furan-3-yl)-5-nitro-1H-indazol-1-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] (1.0 g, 3.05 mmol), sodium carbonate (1.61 g, 15.2 mmol), tetrakis(triphenylphosphine)palladium (0.18 g, 0.15 mmol), and 4,4,5,5-tetramethyl-2-(furan-3-yl)-1,3,2-dioxaborolane (0.89 g, 4.57 mmol) were used, and the reaction was carried out in the same manner. The product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.75 g). Blood— NMR (DMSO-d 6 ) 1.13(s, 2H) , 4.46— 4.49(m, 3H) , 6.97(s,

[0118] 1H), 7.70(s, 1H), 7.93(s, 1H) , 8.07(s, 1H) , 8.12(s, 1H) , 8.59(s, 1H)

[0119] [Step 3] Synthesis of 4-(5-amino-6-(furan-3-yl)-1H-indazol-1-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.7 g, 2.45 mmol) was hydrogenated with 0.14 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through Celite, and the filtrate was concentrated to obtain the title compound (1.04 g). P- NMR (DMSO-d 6 ) 1.09(s, 6H) , 1.94(m, 2H) , 4.32- 4.35(m, 3H) , 4.52(s, 2H), 6.72(s, 1H), 7.46(s, 1H) , 7.58(s, 1H) , 7.93(s, 1H) , 8.01(s, 1H) , 8.22(s, 1H)

[0120] [Step 4] Synthesis of N-(6-(furan-3-yl)-1-(3-hydroxy-3-methylbutyl)-1H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 13) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.11 g, 0.39 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.09 g, 0.39 mmol), HATU (0.29 g, 0.77 mmol) and DI PEA (0.27 mL, 1.54 mmol) were reacted in the same manner, and the product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to give the title compound (0.09 g). Obtained. Blood— NMR (DMSO-d 6 ) 1.13(s, 2H) , 4.46— 4.49(m, 3H) , 6.98(s,

[0121] 1H), 7.71(s, 1H), 7.92(m, 3H) , 8.06(s, 1H) , 8.11(s, 1H) , 8.39(s, 1H) , 8.58(s, 1H), 8.77(m, 2H), 10.06(s, 1H)

[0122] LC-MS (ESI, m / z) = 474.1 (M+H+) Example 14. N-(6-(furan-3-yl)-1-(3-hydroxy-3-methylbutyl)-1H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide

[0123] [Step 4] Synthesis of N-(6-(furan-3-yl)-1-(3-hydroxy-3-methylbutyl)-1H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 14) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 13 (0.11 g, 0.39 mmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.09 g, 0.39 mmol), HATU (0.29 g, 0.77 mmol), and DI PEA (0.27 mL, 1.54 mmol) were reacted in the same manner, and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (0.08 g) was obtained. P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 1.92(t, 2H) , 4.46— 4.49(m, 3H) , 6.97(s, 1H), 7.70(m, 1H), 7.90(s, 1H) , 7.92(s, 1H) , 8.06(s, 1H) , 8.12(s, 1H) , 8.32(m, 1H), 8.39(s, 1H), 8.50(s, 1H) , 8.70(m, 1H) , 9.19(s, 1H) , 10.05(s, 1H)

[0124] LC-MS (ESI, m / z) = 474.1 (M+H+) Example 15. N-(2-(3 -hydroxy- 3 -methylbutyl)- 6-(thiophene- 3 -yl)- 2H -indazole-

[0125] 5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0126] [Step 4] Synthesis of N-(2-(3 -hydroxy-3 -methylbutyl)-6-(thiophene-3 -yl)-2H -indazol-5-yl)-2-(pyridin-4 -yl)thiazole-4-carboxamide (Compound 15) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 2 (0.11 g, 0.36 mmol), 2-(pyridin-4 -yl)thiazole-4-carboxylic acid (0.08 g, 0.36 mmol), HATU (0.28 g, 0.73 mmol), and DI PEA (0.25 mL, 1.46 mmol) were reacted in the same manner, and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (0.08 g) was obtained. 6H) , 2.03(t, 2H) , 4.46- 4.49(m, 3H) , 7.40(m,

[0127] 1H), 7.59(s, 1H), 7.80-7.82(m, 3H) , 8.42(s, 1H) , 8.56(s, 1H) , 8.63(s, 1H) , 8.75(s, 1H), 8.76(s, 1H) , 9.80(s, 1H)

[0128] LC-MS (ESI, m / z) = 490.1 (M+H+) Example 16. N-(1-(3-hydroxy-3-methylbutyl)-6-(thiophene-3-yl)-1H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0129] [Step 4] Synthesis of N-(1-(3-hydroxy-3-methylbutyl)-6-(thiophene-3-yl)-1H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 16) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] of Example 1 (0.15 g, 0.5 mmol 1), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.1 g, 0.5 mmol 1), HATU (0.38 g, l.Ommol) and DI PEA (0.35 mL, 1.99 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (COMBI FLASH NEXTGEN 300+) to obtain the title compound. (0.09 g) was obtained. P— NMR (DMSO-d 6 ) 1.12(s, 6H) , 1.90(t, 2H) , 4.45— 4.48(m, 3H) , 7.42(m, 1H), 7.67(s, 1H), 7.84(m, 4H) , 8.09(s, 1H) , 8.57(s, 1H) , 8.62(s, 1H) , 8.75(m, 2H), 9.89(s, 1H)

[0130] LC-MS (ESI, m / z) = 490.1 (M+H+) Example 17. N-(1-(2-(dimethylamino)ethyl)-6-(thiophene-3-yl)-1H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide

[0131] [Step 1] Synthesis of 2-(6-bromo-5-nitro-1H-indazol-1-yl)-N,N-dimethylethan-1-amine Under the same conditions as in [Step 1] of Example 1, 6-bromo-5-nitro-2H-indazole (2 g, 8.26 mmol), 20 mL of dimethylformamide, potassium carbonate (4.56 g, 27.30 mmol), potassium iodide (0.14 g, 0.83 mmol), and 2-chloro-N,N-dimethylethan-1-amine (1.78 g, 16.53 mmol) were used. The reaction mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (1.16 g). P— NMR (DMSO-d 6 ) 2.14(s, 6H), 2.69(m, 2H), 4.48(m, 2H), 8.08(s, 1H), 8.49(s, 1H), 8.59(s, 1H)

[0132] [Step 2] Synthesis of N,N-dimethyl-2-(5-nitro-6-(thiophene-3-yl)-1H-indazol-1-yl)ethan-1-amine Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] (0.5 g, 1.60 mmol), sodium carbonate (0.75 g, 7.04 mmol), tetrakis(triphenylphosphine)palladium (0.09 g, 0.08 mmol), and 4,4,5,5-tetramethyl-2-(thiophene-3-yl)-1,3,2-dioxaborolane (0.50 g, 2.40 mmol) were used, and the reaction was carried out in the same manner. The resultant product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.5 g). Blood— NMR (DMSO-d 6 ) 2.14(s, 6H) , 2.69(m, 2H) , 4.48(m, 2H) , 7.74(s, 1H), 7.78(m, 1H), 7.84(m, 1H) , 8.08(s, 1H) , 8.49(s, 1H) , 8.59(s, 1H)

[0133] [Step 3] Synthesis of 1-(2-(dimethylamino)ethyl)-6-(thiophene-3-yl)-1H-indazol-5-amine Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.5 g, 1.58 mmol) was hydrogenated with 0.10 g (0.093 mmol) of palladium on activated carbon. The resulting mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.4 g). P— NMR (DMSO-d 6 ) 2.14(s, 6H) , 2.69(m, 2H) , 4.48(m, 2H) , 7.41(s, 2H), 7.74(s, 1H), 7.78(m, 1H) , 7.84(m, 1H) , 8.08(s, 1H) , 8.49(s, 1H) , 8.59(s, 1H)

[0134] [Step 4] Synthesis of N-(1-(2-(dimethylamino)ethyl)-6-(thiophene-3-yl)-1H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 17) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.4 g, 1.40 mmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.29 g, 1.40 mmol), HATU (1.06 g, 2.79 mmol), and DI PEA (0.97 mL, 5.59 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.3 g). Blood— NMR (DMSO-d 6 ) 2.14(s, 6H) , 2.69(m, 2H) , 4.48(m, 2H) , 7.41(s, 1H), 7.59(m, 1H), 7.75(s, 1H) , 7.79(m, 1H) , 7.84(m, 1H) , 8.08(s, 1H) , 8.26(m, 1H) , 8.49(s, 1H), 8.60(s, 1H) , 8.69(m, 1H) , 9.11(s, 1H) , 9.91(s, 1H)

[0135] LC-MS (ESI, m / z) = 475.3 (M+H+) Example 18. N-(1-(2-(dimethylamino)ethyl)-6-(thiophene-3-yl)-1H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0136] [Step 4] Synthesis of N-(1-(2-(dimethylamino)ethyl)-6-(thiophene-3-yl)-1H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 18) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 17 (0.4 g, 1.40 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.29 g, 1.40 mmol), HATU (1.06 g, 2.79 mmol), and DI PEA (0.97 mL, 5.59 mmol) were reacted in the same manner, and the product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (0.3 g) was obtained. P— NMR (DMSO-d 6 ) 2.14(s, 6H) , 2.69(m, 2H) , 4.48(t, 2H) , 7.42(m, 1H), 7.75(m, 1H), 7.83(m, 4H) , 8.09(s, 1H) , 8.56(s, 1H) , 8.60(s, 1H) , 8.75(m, 2H) ,

[0137] 9.90(s, 1H) LC-MS (ESI, m / z) = 475.3 (M+H+) Example 19. N-(2-(2-(dimethylamino)ethyl)-6-(thiophene-3-yl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide

[0138] [Step 2] Synthesis of N,N-dimethyl-2-(5-nitro-6-(thiophene-3-yl)-2H-indazol-2-yl)ethan-1-amine Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] of Example 5 (0.5 g, 1.60 mmol), sodium carbonate (0.75 g, 7.04 mmol), tetrakis(triphenylphosphine)palladium (0.09 g, 0.08 mmol), and 4,4,5,5-tetramethyl-2-(thiophene-3-yl)-1,3,2-dioxaborolane (0.50 g, 2.40 mmol) was reacted in the same manner, and the product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. Compound (0.5 g) was obtained. P- NMR (DMSO-d 6 ) 2.46(s, 6H) , 3.60(m, 2H) , 4.80(m, 2H) , 7.62(s, 1H), 7.81(m, 1H), 7.82(m, 1H) , 8.49(s, 1H) , 8.51(s, 1H) , 8.68(s, 1H)

[0139] [Step 3] Synthesis of 2-(2-(dimethylamino)ethyl)-6-(thiophene-3-yl)-2H-indazol-5-amine Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.5 g, 1.58 mmol) was hydrogenated with palladium on activated carbon (0.10 g, 0.093 mmol). The resulting mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.4 g). P- NMR (DMSO-d 6 ) 2.46(s, 6H) , 3.60(m, 2H) , 4.80(m, 2H) , 7.38(s, 2H), 7.62(s, 1H), 7.81(m, 1H) , 7.82(m, 1H) , 8.49(s, 1H) , 8.51(s, 1H) , 8.68(s, 1H)

[0140] [Step 4] Synthesis of N-(2-(2-(dimethylamino)ethyl)-6-(thiophene-3-yl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 19) Under the same conditions as in [Step 4] of Example 1, the compound obtained in [Step 3] (0.4 g, 1.40 mmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.29 g, 1.40 mmol), HATU (1.06 g, 2.79 mmol), and DI PEA (0.97 mL, 5.59 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.3 g). P- NMR (DMSO-d 6 ) 2.46(s, 6H) , 3.60(m, 2H) , 4.80(m, 2H) , 7.38(s, 1H), 7.58(m, 1H), 7.63(m, 1H) , 7.82(m, 2H) , 8.22(m, 1H) , 8.50(m, 2H) , 8.70(m, 2H) , 9.09(s, 1H), 9.84(s, 1H)

[0141] LC-MS (ESI, m / z) = 475.3 (M+H+) Example 20. N-(2-(2-(dimethylamino)ethyl)-6-(thiophene-3-yl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0142] [Step 4] Synthesis of N-(2-(2-(dimethylamino)ethyl)-6-(thiophene-3-yl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 20) Under the same conditions as [Step 4] of Example 1, the compound obtained in [Step 3] of Example 19 (0.4 g, 1.40 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.29 g, 1.40 mmol), HATU (1.06 g, 2.79 mmol), and DI PEA (0.97 mL, 5.59 mmol) were reacted in the same manner, and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (0.3 g) was obtained. P- NMR (DMSO-d 6 ) 2.16(s, 6H) , 2.77(m, 2H) , 4.49(m, 2H) , 7.40(m, 1H), 7.59(m, 1H), 7.82(m, 4H) , 8.41(m, 1H) , 8.56(m, 1H) , 8.63(s, 1H) , 8.76(m, 2H) 9.80(s, 1H)

[0143] LC-MS (ESI, m / z) = 475.3 (M+H+) Example 21. N- (6-(furan- 3 -yl)- 2- (2 -morpholinoethyl)- 2H -indazol- 5 -yl)- 2-

[0144] (Pyridin-3-yl)thiazole-4-carboxamide

[0145] [Step 1] Synthesis of 4-(2-(6-bromo-5-nitro-2H-indazol-2-yl)ethyl)morpholine Under the same conditions as in [Step 1] of Example 1, 6-bromo-5-nitro-2H-indazole (2 g, 8.26 mmol), 20 mL of dimethylformamide, potassium carbonate (4.56 g, 27.30 mmol), potassium iodide (0.14 g, 0.83 mmol), and 4-(2-chloroethyl)morpholine hydrochloride (3.08 g, 16.53 mmol) were used. The reaction mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (1.16 g). p- NMR (DMSO-d 6 ) 2.46(m, 4H) , 2.84(m, 2H) , 3.51(m, 4H) , 4.53(2H), 7.67(s, 1H), 7.86(s, 1H) , 8.50(s, 1H)

[0146] [Step 2] Synthesis of 4-(2-(6-(furan-3-yl)-5-nitro-2H-indazol-2-yl)ethyl)morpholine Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] (0.5 g, 1.41 mmol), sodium carbonate (0.75 g, 7.04 mmol), tetrakis(triphenylphosphine)palladium (0.08 g, 0.08 mmol), and 2-(furan-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.41 g, 2.11 mmol) were used, and the reaction was carried out in the same manner. The product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.5 g). P- NMR (DMSO-d 6 ) 2.46(m, 4H) , 2.84(m, 2H) , 3.51(m, 4H) , 4.53(2H), 7.67(s, 1H), 7.86(s, 1H) , 8.07(s, 1H) , 8.31(d, 1H) , 8.50(s, 1H) , 8.70(d, 1H)

[0147] [Step 3] Synthesis of 6-(furan-3-yl)-2-(2-morpholinoethyl)-2H-indazol-5-amine Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.5 g, 1.46 mmol) was hydrogenated with palladium on activated carbon (0.10 g, 0.093 mmol). The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.4 g). P- NMR (DMSO-d 6 ) 2.46(m, 4H) , 2.84(m, 2H) , 3.51(m, 4H) , 4.53(2H), 6.93(s, 2H), 7.67(s, 1H) , 7.86(s, 1H) , 8.07(s, 1H) , 8.31(d, 1H) , 8.50(s, 1H) , 8.70(d, 1H)

[0148] [Step 4] Synthesis of N-(6-(furan-3-yl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 21) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] (0.4 g, 1.28 mmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.26 g, 1.28 mmol), HATU (0.97 g,

[0149] The reaction was carried out in the same manner using 2.56 mmol) and DI PEA (0.89 mL, 5.12 mmol), and the resulting mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.3 g). P- NMR (DMSO-d 6) 2.46(m, 4H) , 2.84(m, 2H) , 3.51(m, 4H) , 4.53(2H), 6.93(s, 1H), 7.60(m, 1H) , 7.67(s, 1H) , 7.86(s, 1H) , 8.07(s, 1H) , 8.32(m, 1H) , 8.42(m, 2H), 8.50(s, 1H) , 8.70(m, 1H) , 9.17(s, 1H) , 9.99(s, 1H)

[0150] LC-MS (ESI, m / z) = 501.2 (M+H+) Example 22. N-(6-(furan-3-yl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0151] [Step 4] Synthesis of N-(6-(furan-3-yl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 22) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 21 (0.4 g, 1.28 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.26 g, 1.28 mmol), HATU (0.97 g, 2.56 mmol), and DI PEA (0.89 mL, 5.12 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.3 g). P- NMR (DMSO-d 6 ) 2.45(m, 4H) , 2.84(m, 2H) , 3.51(m, 4H) , 4.53(m, 2H), 6.93(s, 1H), 7.67(s, 1H) , 7.90(m, 2H) , 7.93(s, 1H) , 8.06(s, 1H) , 8.42(m, 2H) ,

[0152] 8.57(s, 1H), 8.77(m, 2H) , 9.99(s, 1H)

[0153] LC-MS (ESI, m / z) = 501.3 (M+H+) Example 23. N- (2- (2-morpholinoethyl)- 6- (thiophene- 3 -yl)- 2H-indazol- 5 -yl)-

[0154] 2-(pyridin-3-yl)thiazole-4-carboxamide

[0155] [Step 1] Synthesis of 4-(2-(6-bromo-5-nitro-2H-indazol-2-yl)ethyl)morpholine Under the same conditions as in [Step 1] of Example 1, 6-bromo-5-nitro-2H-indazole

[0156] (2 g, 8.26 mmol), dimethylformamide 20 mL, potassium carbonate (4.56 g, 27.30 mmol), potassium iodide (0.14 g, 0.83 mmol), and 4-(2-chloroethyl)morpholine hydrochloride (3.08 g, 16.53 mmol) were used in the same manner, and the reaction was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (1.16 g). P- NMR (DMSO-d 6 ) 2.46(m, 4H) , 2.84(m, 2H) , 3.52(m, 4H) , 4.54(m, 2H), 7.60(s, 1H), 8.49(s, 1H) , 8.63(s, 1H)

[0157] [Step 2] Synthesis of 4-(2-(5-nitro-6-(thiophene-3-yl)-2H-indazol-2-yl)ethyl)morpholine Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] (0.5 g, 1.41 mmol), sodium carbonate (0.75 g, 7.04 mmol), tetrakis(triphenylphosphine)palladium (0.08 g, 0.07 mmol), and 4,4,5,5-tetramethyl-2-(thiophene-3-yl)-1,3,2-dioxaborolane (0.44 g, 2.11 mmol) were used, and the reaction was carried out in the same manner. The resultant product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.5 g). P- NMR (DMSO-d 6 ) 2.46(m, 4H) , 2.84(m, 2H) , 3.52(m, 4H) , 4.54(m, 2H), 7.60(s, 1H), 7.78(m, 1H) , 7.81(m, 1H) , 8.43(s, 1H) , 8.49(s, 1H) , 8.63(s, 1H)

[0158] [Step 3] Synthesis of 2-(2-morpholinoethyl)-6-(thiophene-3-yl)-2H-indazol-5-amine Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.5 g, 1.40 mmol) was hydrogenated with palladium on activated carbon (0.10 g, 0.093 mmol). The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.4 g). P- NMR (DMSO-d 6 ) 2.46(m, 4H) , 2.84(m, 2H) , 3.52(m, 4H) , 4.54(m, 2H), 7.39(s, 2H), 7.60(s, 1H) , 7.78(m, 1H) , 7.81(m, 1H) , 8.43(s, 1H) , 8.49(s, 1H) , 8.63(s, 1H)

[0159] [Step 4] Synthesis of N-(2-(2-morpholinoethyl)-6-(thiophene-3-yl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 23) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.4 g, 1.22 mmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.25 g, 1.22 mmol), HATU (0.93 g, 2.44 mmol), and DI PEA (0.85 mL, 4.87 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.3 g). P- NMR (DMSO-d 6 ) 2.46(m, 4H) , 2.84(m, 2H) , 3.52(m, 4H) , 4.54(m, 2H), 7.38(m, 1H), 7.58(m, 2H) , 7.78(m, 1H) , 7.81(m, 1H) , 8.23(m, 1H) , 8.43(s, 1H) ,

[0160] 8.49(s, 1H), 8.64(s, 1H) , 8.70(m, 1H) , 9.09(s, 1H) , 9.82(s, 1H)

[0161] LC-MS (ESI, m / z) = 517.4 (M+H+) Example 24. N- (2- (2-morpholinoethyl)- 6- (thiophene- 3 -yl)- 2H-indazol- 5 -yl)-

[0162] 2-(pyridin-4-yl)thiazole-4-carboxamide

[0163] [Step 4] Synthesis of N-(2-(2-morpholinoethyl)-6-(thiophene-3-yl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 24) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 23 (0.4 g, 1.22 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.25 g, 1.22 mmol), HATU (0.93 g, 2.44 mmol), and DI PEA (0.85 mL, 4.87 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.3 g). P- NMR (DMSO-d 6 ) 2.46(m, 4H) , 2.84(m, 2H) , 3.52(m, 4H) , 4.54(m, 2H), 7.39(m, 1H), 7.60(m, 1H) , 7.81(m, 1H) , 7.83(m, 2H) , 8.06(m, 1H) , 8.43(m, 1H) , 8.56(m, 1H), 8.64(s, 1H) , 8.76(m, 2H) , 9.82(s, 1H)

[0164] LC-MS (ESI, m / z) = 518.0 (M+H+) Example 25. N-(2-(2-(1,3 -dioxolane- 2 -yl)ethyl)- 6-(furan- 3 -yl)- 2H-indazol- 5 -yl)- 2-(pyridin- 3 -yl)thiazole- 4 -carboxamide

[0165] [Step 4] Synthesis of N-(2-(2-(1,3-dioxolane-2-yl)ethyl)-6-(furan-3-yl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 25) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 9 (0.11 g, 0.37 mmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.08 g, 0.37 mmol), HATU (0.28 g, 0.73 mmol), and DI PEA (0.26 mL, 1.47 mmol) were reacted in the same manner, and the product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (0.08 g) was obtained. P- NMR (DMSO-d 6 ) 2.24(m, 2H) , 3.76(m, 2H) , 3.89(m, 2H) , 4.50(m, 2H), 4.82(m, 1H), 6.93(s, 1H) , 7.60(m, 1H) , 7.67(s, 1H) , 7.87(s, 1H) , 8.08(s, 1H) , 8.31(m, 1H), 8.41(m, 2H) , 8.50(s, 1H) , 8.70(s, 1H) , 9.17(s, 1H) , 9.99(s, 1H) LC-MS (ESI, m / z) = 488.1 (M+H+) Example 26. N-(2-(3 -hydroxy- 3 -methylbutyl)- 6-(pyridin- 4 -yl)- 2H -indazole-

[0166] 5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0167] [Step 1] Synthesis of 4-(6-bromo-5-nitro-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 1] of Example 1, 6-bromo-5-nitro-1H-indazole

[0168] (lg, 4.13 mmol), potassium carbonate (2.28 g, 16.5 mmol), potassium iodide (0.07 g, 0.41 mmol) and 4-bromo-2-methylbutan-2-ol (0.99 mL, 8.27 mmol) were used in the same manner. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.62 g). P- NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.04(m, 2H) , 4.50(m, 3H) , 8.10(s, 1H), 8.29(s, 1H), 8.57(s, 1H)

[0169] [Step 2] Synthesis of 2-methyl-4-(5-nitro-6-(pyridin-4-yl)-2H-indazol-2-yl)butan-2-ol Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] (0.6 g, 1.83 mmol), sodium carbonate (0.97 g, 9.14 mmol), tetrakis(triphenylphosphine)palladium (0.11 g, 0.09 mmol), and 4-(4, 4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.69 g, 2.74 mmol) was used, and the reaction was carried out in the same manner. The product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.42 g). P- NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.04(m, 2H) , 4.50(m, 3H) , 8.10(s, 1H), 8.15(m, 2H), 8.29(s, 1H) , 8.57(s, 1H) , 8.65(m, 2H)

[0170] [Step 3] Synthesis of 4-(5-amino-6-(pyridin-4-yl)-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.4 g, 1.35 mmol) was hydrogenated with 0.08 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through celite, and the filtrate was concentrated to obtain the title compound (0.31 g). P— NMR (DMSO-d 6 ) 1.09(s, 6H) , 2.01(m, 2H) , 4.42(m, 3H) , 4.54(s, 2H), 8.02(s, 1H), 8.06(m, 2H) , 8.19(s, 1H) , 8.43(s, 1H) , 8.50(m, 2H)

[0171] [Step 4] Synthesis of N-(2-(3-hydroxy-3-methylbutyl)-6-(pyridin-4-yl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 26) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.2 g, 0.67 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.15 g, 0.67 mmol), HATU (0.51 g, 1.35 mmol) and DI PEA (0.47 mL, 2.70 mmol) were reacted in the same manner, and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to give the title compound (0.18 g). Obtained. P- NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.04(m, 2H) , 4.50(m, 3H) , 7.78(s, 1H), 8.11(s, 1H), 8.15(m, 2H) , 8.30(s, 1H) , 8.47(m, 2H) , 8.59(s, 1H) , 8.65(m, 2H) , 8.73(m, 2H), 9.83(s, 1H)

[0172] LC-MS (ESI, m / z) = 485.1 (M+H+) Example 27. N-(2-(3-hydroxy-3-methylbutyl)-6-(pyridin-3-yl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0173] [Step 2] Synthesis of 2-methyl-4-(5-nitro-6-(pyridin-3-yl)-2H-indazol-2-yl)butan-2-ol Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] of Example 26 (0.6 g, 1.83 mmol), sodium carbonate (0.97 g, 9.14 mmol), tetrakis(triphenylphosphine)palladium (0.11 g, 0.09 mmol), and 4-(4, 4,5,5-tetramethyl-1,3,2-dioxaborolan-3-yl)pyridine (0.69 g, 2.74 mmol) was used, and the reaction was carried out in the same manner. The product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (0.41 g) was obtained. P- NMR (DMSO-d 6 ) 1.12(s, 6H), 2.04(m, 2H), 4.50(m, 3H), 8.02(s, 1H), 8.08(d, 1H), 8.11(s, 1H), 8.12(d, 1H), 8.15(m, 1H), 8.29(s, 1H) , 8.57(s, 1H)

[0174] [Step 3] Synthesis of 4-(5-amino-6-(pyridin-3-yl)-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.4 g, 1.35 mmol) was hydrogenated with 0.08 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through celite, and the filtrate was concentrated to obtain the title compound (0.30 g). P— NMR (DMSO-d 6) 1.09(s, 6H) , 2.01(m, 2H) , 4.42(m, 3H) , 4.56(s, 2H), 7.87(s, 1H), 7.91(d, 1H) , 8.01(s, 1H) , 8.03(d, 1H) , 1H) , 8.19(s, 1H) ,

[0175] 8.27(s, 1H)

[0176] [Step 4] Synthesis of N-(2-(3-hydroxy-3-methylbutyl)-6-(pyridin-3-yl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 27) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] (0.15 g, 0.51 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.11 g, 0.51 mmol), HATU (0.38 g, l.Olmmol) and DI PEA (0.35 mL, 2.02 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to give the title compound (0.15 g). Obtained. P- NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.04(m, 2H) , 4.50(m, 3H) , 7.63(s, 1H), 7.78(m, 2H), 8.01(s, 1H) , 8.06(d, 1H) , 8.13(d, 1H) , 8.17(m, 1H) , 8.30(s, 1H) , 8.47(m, 2H), 8.65(m, 2H) , 8.73(m, 2H) , 9.83(s, 1H)

[0177] LC-MS (ESI, m / z) = 485.1 (M+H+) Example 28. N-(2-(3-hydroxy-3-methylbutyl)-6-(pyridin-3-yl)-2H-indazole boral 1-paradine 3-amino-4-methyl-2-pyridin-3-yl)thiazole trimethylamine

[0178] [Step 4] Synthesis of N-(2-(3 -hydroxy-3 -methylbutyl)-6-(pyridin-3 -yl)-2H-indazol-5-yl)-2-(pyridin-3 -yl)thiazole-4-carboxamide (Compound 28) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 27 (0.15 g, 0.51 mmol), 2-(pyridin-3 -yl)thiazole-4-carboxylic acid (0.11 g, 0.51 mmol), HATU (0.38 g, l.Olmmol) and DI PEA (0.35 mL, 2.02 mmol) was reacted in the same manner, and then purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to give the title compound. (0.15 g) was obtained. P— NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.06(t, 2H) , 4.50(m, 3H) , 7.61(s, 1H), 7.97(m, 1H), 8.03 (m, 2H) , 8.16(m, 1H) , 8.37(s, 1H) , 8.42(s, 1H) , 8.47(s, 1H), 8.65(m, 1H), 8.69(m, 1H) , 8.73(s, 1H) , 9.03(m, 1H) , 9.75(s, 1H) LC-MS (ESI, m / z) = 485.1 (M+H+) Example 29. N- (2- (3 -Hydroxy- 3 ■methylbutyl)- 6- (4 -hydroxyphenyl)- 2H- indazole- 5 -yl)- 2- (pyridin- 4 -yl) thiazole- 4 -carboxamide

[0179] [Step 2] Synthesis of 4-(2-(3-hydroxy-3-methylbutyl)-5-nitro-2H-indazol-6-yl)phenol Under the same conditions as [Step 2] of Example 1, the compound of [Step 1] of Example 26

[0180] (0.6 g, 1.83 mmol), sodium carbonate (0.97 g, 9.14 mmol), tetrakis(triphenylphosphine)palladium (0.11 g, 0.09 mmol), and 4-(4, 4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (0.60 g, 2.74 mmol) were used in the same manner. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to give the title compound (0.51 g). P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.02(t, 2H) , 4.47(m, 2H) , 4.49(s, 1H), 6.97(m, 2H), 7.38(m, 2H) , 8.13(s, 1H) , 8.42(m, 2H) , 8.45(s, 1H) , 8.65(m, 2H) , 8.68(s, 1H)

[0181] [Step 3] Synthesis of 4-(5-amino-2-(3-hydroxy-3-methylbutyl)-2H-indazol-6-yl)phenol Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.5 g, 1.46 mmol) was hydrogenated with 0.1 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through Celite, and the filtrate was concentrated to obtain the title compound (0.36 g). P— NMR (DMSO-d 6 ) 1.09(s, 6H) , 2.00(t, 2H) , 4.35(m, 2H) , 4.40(s, 1H), 4.54(s, 2H), 6.67(m, 2H) , 7.18(m, 2H) , 8.04(s, 1H) , 8.22(m, 2H) , 8.26(s, 1H) , 8.45(m, 2H), 8.51(s, 1H) , 8.53(s, 1H)

[0182] [Step 4] Synthesis of N-(2-(3-hydroxy-3-methylbutyl)-6-(4-hydroxyphenyl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 29) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] (0.15 g, 0.48 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.11 g, 0.48 mmol), HATU (0.37 g, 0.96 mmol) and DI PEA (0.34 mL, 1.93 mmol) were reacted in the same manner, and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to give the title compound (0.12 g). Obtained. Blood— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.02(t, 2H) , 4.47(m, 2H) , 4.49(s, 1H), 7.43(s, 1H), 8.14(s, 1H) , 8.39(m, 2H) , 8.42(m, 2H) , 8.45(s, 1H) , 8.62(m, 2H) , 8.68(m, 3H), 9.63(s, 1H) , 9.77(s, 1H)

[0183] LC-MS (ESI, m / z) = 500.1 (M+H+) Example 30. N- (2- (3 -hydroxy- 3 ■methylbutyl)- 6- (4 -hydroxyphenyl)- 2H- indazol- 5 -yl)- 2- (pyridin- 3 -yl) thiazole- 4 -carboxamide

[0184] [Step 4] Synthesis of N-(2-(3-hydroxy-3-methylbutyl)-6-(4-hydroxyphenyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 30) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 29 (0.15 g, 0.48 mmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.11 g, 0.48 mmol), HATU (0.37 g, 0.96 mmol), and DI PEA (0.34 mL, 1.93 mmol) were reacted in the same manner, and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (0.12 g) was obtained. P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.03(t, 2H) , 4.47(m, 2H) , 4.49(s, 1H), 7.44(s, 1H), 7.64(m, 1H) , 7.66(m, 1H) , 8.24(s, 1H) , 8.41(m, 2H) , 8.53(s, 1H) , 8.61(m, 2H), 8.73(m, 3H) , 9.63(m, 1H) , 9.86(s, 1H)

[0185] LC-MS (ESI, m / z) = 500.1 (M+H+) Example 31. Methyl 3-(2-(3-hydroxy-3-methylbutyl)-5-(2-(pyridin-3-yl)thiazole-4-carboxamido)-2H-indazol-6-yl)benzoate

[0186] [Step 1] Synthesis of 4-(6-bromo-5-nitro-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 1] of Example 1, 6-bromo-5-nitro-1H-indazole (2 g, 8.26 mmol), potassium carbonate (4.57 g, 33.1 mmol), potassium iodide (0.14 g, 0.83 mmol), and 4-bromo-2-methylbutan-2-ol (1.97 mL, 16.53 mmol) were used. The reaction mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (1.27 g). P— NMR (DMSO-d 6 ) 1.13(s, 6H), 2.04(m, 2H), 3.88(s, 3H), 4.50(m, 3H), 8.40(s, 1H), 8.51(s, 1H), 8.65(s, 1H)

[0187] [Step 2] Synthesis of methyl 3-(2-(3-hydroxy-3-methylbutyl)-5-nitro-2H-indazol-6-yl)benzoate Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] (1.2 g, 3.66 mmol), sodium carbonate (1.94 g, 18.3 mmol), tetrakis(triphenylphosphine)palladium (0.21 g, 0.18 mmol), and methyl 3-(4, 4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (1.44 g, 5.48 mmol) were used. The reaction was carried out in the same manner, and the product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (1.01 g). Blood— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.04(m, 2H) , 3.88(s, 3H) , 4.50(m, 3H), 7.43(m, 1H), 7.65(s, 1H) , 8.01(d, 1H) , 8.40(s, 1H) , 8.46(s, 1H) , 8.51(s, 1H) , 8.65(s, 1H)

[0188] [Step 3] Synthesis of methyl 3-(5-amino-2-(3-hydroxy-3-methylbutyl)-2H-indazol-6-yl)benzoate Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.9 g, 2.35 mmol) was hydrogenated with 0.18 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through Celite, and the filtrate was concentrated to obtain the title compound (0.51 g). P— NMR (DMSO-d 6 ) 1.09(s, 6H) , 2.00(m, 2H) , 3.74(s, 3H) , 4.43(m, 3H), 4.54(s, 2H), 7.23(m, 1H) , 7.49(s, 1H) , 7.90(d, 1H) , 8.21(s, 1H) , 8.31(s, 1H) ,

[0189] 8.42(s, 1H), 8.48(s, 1H) [Step 4] Synthesis of methyl 3-(2-(3-hydroxy-3-methylbutyl)-5-(2-(pyridin-3-yl)thiazole-4-carboxamido)-2H-indazol-6-yl)benzoate (Compound 31) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] (0.15 g, 0.42 mmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.09 g, 0.42 mmol), HATU (0.32 g, 0.85 mmol), and DI PEA (0.30 mL, 1.70 mmol) were used in the same manner, followed by MPLC (combiFlash NEXTGEN) 300+) and concentrated to give the title compound (0.13 g). P— NMR (DMSO-d 6) 1.13(s, 6H) , 2.04(m, 2H) , 3.88(s, 3H) , 4.50(m, 3H), 7.41(m, 1H), 7.58(s, 1H) , 7.63(s, 1H) , 7.68(s, 1H) , 8.01(d, 1H) , 8.09(d, 2H) , 8.44(s, 1H), 8.46(s, 1H) , 8.54(s, 1H) , 8.67(d, 1H) , 8.71(s, 1H) , 9.63(s, 1H) LC-MS (ESI, m / z) = 542.1 (M+H+) Example 32. N-(6-(3-aminophenyl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide

[0190] [Step 2] Synthesis of 4-(6-(3-aminophenyl)-5-nitro-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as [Step 2] of Example 1, the compound of [Step 1] of Example 11 (0.3 g, 0.91 mmol), sodium carbonate (0.48 g, 4.57 mmol), tetrakis(triphenylphosphine)palladium (0.05 g, 0.05 mmol), and 3-(4, 4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (0.30 g, 1.37 mmol) were used, and the reaction was carried out in the same manner. The resultant product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.22 g). Blood— NMR (DMSO-d 6 ) 1.14(s, 6H) , 2.05(m, 2H) , 4.50(m, 3H) , 5.99(s, 2H), 7.55(m, 1H), 7.74(s, 1H) , 7.92(s, 1H) , 7.97(m, 1H) , 8.18(s, 1H) , 8.47(s, 1H) , 8.49(s, 1H), 8.75(m, 2H)

[0191] [Step 3] Synthesis of 4-(5-amino-6-(3-aminophenyl)-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.20 g, 0.59 mmol) was hydrogenated with 0.04 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through Celite, and the filtrate was concentrated to obtain the title compound (0.12 g). 2.01(m, 2H) , 4.45(m, 3H) , 4.54 (s, 2H) ,

[0192] 5.88(s, 2H), 7.42(m, 1H) , 7.68(s, 1H) , 7.86(s, 1H) , 7.91(m, 1H) , 8.08(s, 1H) , 8.27(s, 1H), 8.29(s, 1H) , 8.75(m, 2H)

[0193] [Step 4] Synthesis of N-(6-(3-aminophenyl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 32) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.1 g, 0.32 mmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.07 g, 0.32 mmol), HATU (0.24 g, 0.64 mmol), and DI PEA (0.22 mL, 1.29 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.09 g). Blood— NMR (DMSO-d 6 ) 1.14(s, 6H) , 2.05(m, 2H) , 4.50(m, 3H) , 7.53(m, 1H), 7.62(m, 1H), 7.76(m, 2H) , 7.91(s, 1H) , 7.96(m, 1H) , 8.18(s, 1H) , 8.47(s, 1H) ,

[0194] 8.49(s, 1H), 8.71(m, 1H) , 8.75(m, 2H) , 9.75(s, 1H)

[0195] LC-MS (ESI, m / z) = 499.1 (M+H+) Example 33. 2- (2 -aminopyridin- 4 -yl)- N- (6-(furan- 3 -yl)- 2- (2 -hydroxy-

[0196] 2 ■Methylpropyl)-2H-indazole-5-yl)thiazole-4-carboxamide

[0197] [Step 4] Synthesis of 2-bromo- N- (6-(furan-3-yl)- 2- (2-hydroxy- 2-methylpropyl) -2H- indazol- 5-yl) thiazole- 4-carboxamide Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] of Example 4 (0.44 g, 1.62 mmol), 2-bromothiazole- 4-carboxylic acid (0.36 g, 1.62 mmol), HATU (1.23 g, 3.24 mmol), and DI PEA (1.13 mL, 6.49 mmol) were used, and the reaction was carried out in the same manner. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.59 g). P- NMR (DMSO-d 6 ) 1.09(s, 6H) , 4.32(m, 2H) , 4.84(s, 1H) , 6.98(s, 1H), 7.61(s, 1H), 7.97(s, 1H) , 8.16(m, 1H) , 8.41(s, 1H) , 8.74(s, 1H) , 9.03(s, 1H) , 9.75(s, 1H)

[0198] [Step 5] Synthesis of 2-(2-aminopyridin-4-yl)-N-(6-(furan-3-yl)-2-(2-hydroxy-2-methylpropyl)-2H-indazol-5-yl)thiazole-4-carboxamide (Compound 33) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] (0.12 g, 0.26 mmol), sodium carbonate (0.14 g, 1.30 mmol), tetrakis(triphenylphosphine)palladium (0.02 g, 0.001 mmol), and 4-(4, 4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (0.09 g, 0.39 mmol) were used, and the reaction was carried out in the same manner. The title compound (0.08 g) was obtained by purification by MPLC (combiFlash NEXTGEN 300+) and concentration. P— NMR (DMSO-d 6 ) 1.09(s, 6H) , 4.32(m, 2H) , 4.85(s, 1H) , 7.02 (s, 1H) , 7.61(s, 1H), 7.97(m, 1H) , 8.16(m, 1H) , 8.37(s, 1H) , 8.42(s, 1H) , 8.47(s, 1H) , 8.65(m, 1H), 8.69(m, 1H) , 8.73(s, 1H) , 9.03(m, 1H) , 9.75(s, 1H)

[0199] LC-MS (ESI, m / z) = 475.1 (M+H+) Example 34. 2-Hydroxypropane- 2-yl 4-(4-((6-(furan- 3 -yl)- 2-(2-hydroxy-2-methylpropyl)-2H-indazol- 5 -yl)carbamoyl)thiazol- 2 -yl)-3,6-dihydropyridine- 1(2H)-carboxylate

[0200] [Step 5] Synthesis of 2-hydroxypropane-2-yl 4-(4-((6-(furan-3-yl)-2-(2-hydroxy-2-methylpropyl)-2H-indazol-5-yl)carbamoyl)thiazol-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (Compound 34) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 33 (0.12 g, 0.26 mmol), sodium carbonate (0.14 g, 1.30 mmol), tetrakis(triphenylphosphine)palladium (0.02 g, O.Olmmol) and 2-hydroxypropane-2-yl 4-(4, 4,5, 5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (0.12 g, 0.39 mmol) was used in the same manner, and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.05 g). P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 1.42(s, 9H) , 2.84— 2.86(m, 2H) , 3.42— 3.44(m, 2H), 3.56- 3.58(m, 2H) , 4.32(m, 2H) , 4.84(s, 1H) , 6.29(t, 1H) , 7.02(s, 1H), 7.61(s, 1H), 7.97(s, 1H) , 8.16(s, 1H) , 8.27(s, 1H) , 8.41(s, 1H) , 8.74(s, 1H), 9.77(s, 1H)

[0201] LC-MS (ESI, m / z) = 564.1 (M+H+) Example 35. N-(6-(furan-3-yl)-2-(2-hydroxy-2-methylpropyl)-2H-indazol-5-yl)-2-(thiophene-2-yl)thiazole-4-carboxamide

[0202] [Step 5] Synthesis of N-(6-(furan-3-yl)-2-(2-hydroxy-2-methylpropyl)-2H-indazol-5-yl)-2-(thiophene-2-yl)thiazole-4-carboxamide (Compound 35) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 33 (0.12 g, 0.26 mmol), sodium carbonate (0.14 g, 1.30 mmol), tetrakis(triphenylphosphine)palladium (0.02 g, 0.001 mmol), and 4,4,5,5-tetramethyl-2-(thiophene-2-yl)-1,3,2-dioxaborolane (0.08 g, 0.39 mmol) were used. After reaction in the same manner, the title compound (0.05 g) was obtained by purification by MPLC (combiFlash NEXTGEN 300+) and concentration. P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 4.47(m, 2H) , 4.49(s, 1H) , 6.99(m, 2H), 7.31(m, 2H), 7.44(s, 1H) , 7.66(m, 2H) , 8.40(s, 1H) , 8.53(s, 1H) , 8.73(s, 1H) , 9.86(s, 1H)

[0203] LC-MS (ESI, m / z) = 465.1 (M+H+) Example 36. N-(6-(2-aminopyridin-4-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0204] [Step 2] Synthesis of 4-(6-(2-aminopyridin-4-yl)-5-nitro-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as [Step 2] of Example 1, the compound of [Step 1] of Example 11 (0.3 g, 0.91 mmol), sodium carbonate (0.48 g, 4.57 mmol), tetrakis(triphenylphosphine)palladium (0.05 g, 0.05 mmol), and 4-(4, 4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (0.30 g, 1.37 mmol) was used, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound. (0.22 g) was obtained. P— NMR (DMSO-d 6 ) 1.14(s, 6H) , 2.05(m, 2H) , 4.50(m, 3H) , 7.55(m, 1H), 7.74(s, 1H), 7.92(s, 1H) , 8.18(s, 1H) , 8.47(s, 1H) , 8.49(s, 1H) , 8.75(m, 2H)

[0205] [Step 3] Synthesis of 4-(5-amino-6-(2-aminopyridin-4-yl)-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.20 g, 0.59 mmol) was hydrogenated with 0.04 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through celite, and the filtrate was concentrated to obtain the title compound (0.12 g). 2.01(m, 2H) , 4.45(m, 3H) , 4.54 (s, 2H) ,

[0206] 7.42(m, 1H), 7.68(s, 1H) , 7.86(s, 1H) , 8.08(s, 1H) , 8.27(s, 1H) , 8.29(s, lH),8.75(m, 2H)

[0207] [Step 4] Synthesis of N-(6-(2-aminopyridin-4-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 36) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.1 g, 0.32 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.07 g, 0.32 mmol), HATU (0.24 g, 0.64 mmol), and DI PEA (0.22 mL, 1.29 mmol) were reacted in the same manner, and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (0.08 g) was obtained. P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.04(m, 2H) , 4.49(m, 3H) , 5.91(s, 2H), 6.23(m, 2H), 6.59(m, 1H) , 7.50(s, 1H) , 7.79(m, 2H) , 8.06(s, 1H) , 8.45(s, 1H) , 8.55(s, 1H), 8.75(m, 2H) , 9.67(s, 1H)

[0208] LC-MS (ESI, m / z) = 500.1 (M+H+) Example 37. N-(2-(3-hydroxy-3-methylbutyl)-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide

[0209] [Step 2] Synthesis of 2-methyl-4-(5-nitro-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)-2H-indazol-2-yl)butan-2-ol Under the same conditions as [Step 2] of Example 1, the compound of [Step 1] of Example 11 (0.6 g, 1.83 mmol), sodium carbonate (0.97 g, 9.14 mmol), tetrakis(triphenylphosphine)palladium (0.11 g, 0.09 mmol) and 1-(tetrahydro-2H-pyran-2-yl)-5-(4, 4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)- The reaction was carried out in the same manner using 1H-pyrazole (0.76 g, 2.74 mmol), purified by MPLC (combiFlash NEXTGEN 300+), and concentrated to obtain the title compound (0.45 g). P— NMR (DMSO-d 6 ) 1.14(s, 6H) , 1.37— 1.47(m, 6H) , 2.05(m, 2H) , 3.78(m, 2H), 4.51(m, 3H), 1H) , 6.58(s, 1H) , 7.61(m, 1H) , 8.25(m, 1H) , 8.46(s,

[0210] 1H), 8.56(s, 1H)

[0211] [Step 3] Synthesis of 4-(5-amino-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.45 g, 1.13 mmol) was hydrogenated with 0.09 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through Celite, and the filtrate was concentrated to obtain the title compound (0.30 g). P- NMR (DMSO-d 6 ) 1.09(s, 6H) , 1.31- 1.43(m, 6H) , 1.99(m, 2H) , 3.65(m,

[0212] 2H), 4.40(m, 3H) , 4.58 (s, 2H) , 5.01(m, 1H) , 6.50(s, 1H) , 7.52(m, 1H) , 8.16(m, 1H), 8.36(s, 1H), 8.42(s, 1H)

[0213] [Step 4] Synthesis of N-(2-(3-hydroxy-3-methylbutyl)-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 37) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] (0.2 g, 0.54 mmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.12 g, 0.54 mmol), HATU (0.41 g, 1.08 mmol), and DI PEA (0.38 mL, 2.17 mmol) were used, and the reaction was performed in the same manner, followed by MPLC (combiFlash) The title compound (0.14 g) was purified and concentrated using NEXTGEN 300+. P— NMR (DMSO-d 6 ) 1.14(s, 6H) , 1.37— 1.47(m, 6H) , 2.04(m, 2H) , 3.78(m, 2H), 4.50(m, 3H) , 5.09(m, 1H) , 6.57(s, 1H) , 7.59(m, 1H) , 7.67(s, 1H) , 7.72(s, 1H), 8.12 (s, 1H), 8.24(m, 1H) , 8.45(s, 1H) , 8.49(s, 1H) , 8.55(s, 1H) , 8.71(s, 1H), 9.64(s, 1H)

[0214] LC / MS (ESI, m / z) = 558.1 (M+H+) Example 38. N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(trifluoromethyl)thiazole-4-carboxamide

[0215] [Step 4] Synthesis of N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(trifluoromethyl)thiazole-4-carboxamide (Compound 38) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 11 was synthesized.

[0216] (0.11g, 0.39mmol), 2-(trifluoromethyl)thiazole-4-carboxylic acid (0.08g,

[0217] The reaction was carried out in the same manner using HATU (0.29 g, 0.77 mmol) and DI PEA (0.27 mL, 1.54 mmol), and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.11 g). P— NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.01(t, 2H) , 4.48(m, 3H) , 6.83(s, 1H), 7.67(s, 1H), 7.74(s, 1H) , 7.94(s, 1H) , 8.16(s, 1H) , 8.40(s, 1H) , 8.76(s, 1H) , 9.90(s, 1H)

[0218] LC-MS (ESI, m / z) = 465.1 (M+H+) Example 39. 2- (2-fluoropyridin- 4 -yl)- N- (2- (3 -hydroxy- 3 -methylbutyl)-

[0219] 6-(thiophene-3-yl)-2H-indazole-5-yl)thiazole-4-carboxamide

[0220] [Step 4] Synthesis of 2-bromo- N- (2- (3-hydroxy- 3-methylbutyl)- 6- (thiophene- 3 -yl)- 2H- indazole— 5 -yl) thiazole- 4-carboxamide Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 2 (0.5 g, 1.66 mmol), 2-bromothiazole- 4-carboxylic acid (0.37 g, 1.66 mmol), HATU (1.26 g, 3.32 mmol), and DI PEA (1.16 mL, 6.64 mmol) were used. The reaction was carried out in the same manner. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.62 g). P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.02(t, 2H) , 4.44(s, 1H) , 4.46(t, 2H), 7.38(m, 1H), 7.58(m, 2H) , 7.61(m, 1H) , 8.22(m, 1H) , 8.51(s, 1H) , 8.63(m, 1H) , 9.81(s, 1H)

[0221] [Step 5] Synthesis of 2-(2-fluoropyridin-4-yl)-N-(2-(3-hydroxy-3-methylbutyl)-6-(thiophene-3-yl)-2H-indazol-5-yl)thiazole-4-carboxamide (Compound 39) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] (0.2 g, 0.41 mmol), sodium carbonate (0.22 g, 2.03 mmol), tetrakis(triphenylphosphine)palladium (0.02 g, 0.02 mmol), and 2-fluoro-4-(4, 4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.14 g, 0.61 mmol) were used, and the reaction was carried out in the same manner. The title compound (0.15 g) was obtained by purification by MPLC (combiFlash NEXTGEN 300+) and concentration. P— NMR (DMSO-d 6) 1.12 (brs, 6H), 2.02 (m, 2H), 4.49 (m, 3H), 7.39 (m, 1H), 7.60 (m, 1H), 7.63 (m, 1H), 7.80 (m, 3H), 8.42 (m, 2H), 8.60 (m, 2H), 9.82 (s, 1H) LC-MS (ESI, m / z) = 508.1 (M+H+) Example 40. N-(2-(3-Hydroxy-3-methylbutyl)-6-(thiophen-3-yl)-2H-indazol-5-yl)-2-(6-hydroxypyridin-3-yl)thiazole-4-carboxamide

[0222] [Step 5] Synthesis of N-(2-(3-Hydroxy-3-methylbutyl)-6-(thiophen-3-yl)-2H-indazol-5-yl)-2-(6-hydroxypyridin-3-yl)thiazole-4-carboxamide (Compound 40) Under the same conditions as in [Step 2] of Example 1, the compound of [Step 4] of Example 39 (0.2 g, 0.41 mmol), sodium carbonate (0.22 g, 2.03 mmol), tetrakis(triphenylphosphine)palladium (0.02 g, 0.02 mmol) and 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-ol (0.13 g, 0.61 mmol) were used and reacted in the same manner. Purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (A0.14 g). 1H-NMR (DMSO-d 6 ) 1.12 (s, 6H), 2.01 (m, 2H), 4.45 (m, 2H), 4.48 (s, 1H), 7.31 (m, 1H), 7.54 (m, 1H), 7.57 (m, 1H), 7.67 (m, 1H), 7.70 (m, 1H), 8.40 (m, 2H), 8.64 (m, 1H), 9.38 (m, 1H), 9.69 (m, 1H), 11.63 (s, 1H)

[0223] LC-MS (ESI, m / z) = 506.1 (M+H+) Example 41. N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-phenylthiazole-4-carboxamide

[0224] [Step 4] Synthesis of N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-phenylthiazole-4-carboxamide (Compound 41) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] of Example 11 (0.11 g, 0.39 mmol), 2-phenylthiazole-4-carboxylic acid (0.09 g, 0.39 mmol), HATU (0.29 g, 0.77 mmol), and DI PEA (0.27 mL, 1.54 mmol) were used, and the reaction was carried out in the same manner. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.10 g). P— NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.01(m, 2H) , 4.47(m, 3H) , 6.92(m, 1H), 7.54(m, 3H), 7.65(s, 1H) , 7.92(m, 1H) , 7.95(m, 2H) , 8.07(m, 1H) , 8.41(m, 2H) , 8.50(m, 1H), 9.95(s, 1H)

[0225] LC-MS (ESI, m / z) = 473.1 (M+H+) Example 42. 2- (4-fluorophenyl)- N- (2- (3-hydroxy- 3-methylbutyl)- 6-

[0226] (thiophene-3-yl)-2H-indazole-5-yl)thiazole-4-carboxamide

[0227] [Step 4] Synthesis of 2-(4-fluorophenyl)-N-(2-(3-hydroxy-3-methylbutyl)-6-(thiophene-3-yl)-2H-indazol-5-yl)thiazole-4-carboxamide (Compound 42) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 2 (0.11 g, 0.36 mmol), 2-(4-fluorophenyl)thiazole-4-carboxylic acid (0.08 g, 0.36 mmol), HATU (0.28 g, 0.73 mmol), and DI PEA (0.25 mL, 1.46 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.07 g). Blood— NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.01(m, 2H) , 4.46(m, 3H) , 7.38(m, 3H), 7.57(m, 1H), 7.79(s, 1H) , 7.82(m, 1H) , 7.92(m, 2H) , 8.41(m, 2H) , 8.66(m, 1H) , 9.77(s, 1H)

[0228] LC-MS (ESI, m / z) = 507.1 (M+H+) Example 43. N-(2-(3 -hydroxy- 3 -methylbutyl)- 6-(3-(methylcarbamoyl)phenyl)-

[0229] 2H-Indazole-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide

[0230] [Step 5] Synthesis of N-(2-(3-hydroxy-3-methylbutyl)-6-(3-(methylcarbamoyl)phenyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 43) The compound of [Step 4] of Example 31 (0.12 g, 0.22 mmol) and N-methylamine in methanol (10 ml) were used, and the reaction was carried out at 120°C for more than 6 hours, and then concentrated. Afterwards, the product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.08 g). P— NMR (DMSO-d 6 ) 1.13(s, 6H), 2.04(t, 2H), 2.68(d, 3H), 4.48— 4.51(m, 3H), 7.51-7.54(m, 1H), 7.57(s, 1H), 7.61(t, 1H), 7.68(d, 1H) , 8.01(m, 1H) , 8.08(m, 2H) , 8.43(s , 1H) , 8.45(s , 1H) , 8.48(m, 1H) , 8.60(s , 1H) , 8.92(d, 1H) , 9.61(s, 1H)

[0231] LC-MS (ESI, m / z) = 541.1 (M+H+) Example 44. N-(2-(3 -hydroxy- 3 -methylbutyl)- 6-(3-(methylcarbamoyl)phenyl)-

[0232] 2H-Indazole-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0233] [Step 4] Synthesis of methyl 3-(2-(3-hydroxy-3-methylbutyl)-5-(2-(pyridin-4-yl)thiazole-4-carboxamido)-2H-indazol-6-yl)benzoate Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 31 (0.15 g, 0.42 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.09 g, 0.42 mmol), HATU (0.32 g, 0.85 mmol), and DI PEA (0.30 mL, 1.70 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.13 g). P- NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.04(t, 2H) , 3.85(s, 3H) , 4.48- 4.51(m, 3H), 7.51-7.54(m, 1H) , 7.57(s, 1H) , 7.61(t, 1H) , 7.68(d, 1H) , 8.01(m, 1H) , 8.08(m, 2H), 8.43(s, 1H) , 8.45(s, 1H) , 8.48(m, 1H) , 8.60(s, 1H) , 8.92(d, 1H) , 9.61(s, 1H)

[0234] [Step 5] Synthesis of N-(2-(3-hydroxy-3-methylbutyl)-6-(3-(methylcarbamoyl)phenyl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 44) ​​The compound of [Step 4] (0.12 g, 0.22 mmol) and N-methylamine in methanol (10 ml) were used, and the reaction was carried out at 120°C for more than 6 hours, and then concentrated. Afterwards, the product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.07 g). P- NMR (DMSO-d 6) 1.13(s, 6H) , 2.04(t, 2H) , 2.68(d, 3H) , 4.48- 4.50(m, 3H), 7.52-7.54(m, 1H) , 7.59(s, 1H) , 7.62(t, 1H) , 7.69(d, 1H) , 8.03(m, 1H) , 8.09(m, 2H), 8.45(s, 1H) , 8.46(s, 1H) , 8.49(m, 1H) , 8.62(s, 1H) , 8.90(d, 1H) ,

[0235] 9.63 (s, 1H)

[0236] LC-MS (ESI, m / z) = 541.1 (M+H+) Example 45. N-(2-(3 -hydroxy- 3 -methylbutyl)- 6-(3-(methylcarbamoyl)phenyl)-

[0237] 2H-Indazole-5-yl)-2-(trifluoromethyl)thiazole-4-carboxamide

[0238] [Step 4] Methyl 3-(2-(3 -hydroxy-3 -methylbutyl)-5-(2 -

[0239] Synthesis of (trifluoromethyl)thiazole-4-carboxamido)-2H-indazol-6-yl)benzoate Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 31

[0240] (0.15g, 0.42mmo1), 2-(trifluoromethyl)thiazole-4-carboxylic acid (0.08g,

[0241] The reaction was carried out in the same manner using HATU (0.32 g, 0.85 mmol) and DI PEA (0.30 mL, 1.70 mmol), and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.13 g). P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.04(m, 2H) , 3.88(s, 3H) , 4.50(m, 3H),

[0242] 7.58(s, 1H), 7.63(s, 1H) , 7.68(s, 1H) , 8.01(d, 1H) , 8.44(s, 1H) , 8.46(s, 1H) ,

[0243] 8.54(s, 1H), 8.67(d, 1H) , 9.63(s, 1H)

[0244] [Step 5] N-(2-(3-hydroxy-3-methylbutyl)-6-(3-(methylcarbamoyl)phenyl)-

[0245] Synthesis of 2H-indazol-5-yl)-2-(trifluoromethyl)thiazole-4-carboxamide (Compound 45) The compound of [Step 4] above (0.12 g, 0.23 mmol) and N-methylamine in methanol (10 ml) were used, and the reaction was carried out at 120°C for more than 6 hours, and then concentrated. Afterwards, the product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.08 g). P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.04(m, 2H) , 2.69(d, 3H) , 4.50(m, 3H), 7.59(s, 1H), 7.64(s, 1H) , 7.69(s, 1H) , 8.03(d, 1H) , 8.46(s, 1H) , 8.47(s, 1H) , 8.55(s, 1H), 8.68(d, 1H) , 9.64(s, 1H)

[0246] LC-MS (ESI, m / z) = 532.1 (M+H+) Example 46. 2-(4-fluorophenyl)-N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)thiazole-4-carboxamide

[0247] [Step 4] Synthesis of 2-(4-fluorophenyl)-N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)thiazole-4-carboxamide (Compound 46) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 11 (0.11 g, 0.39 mmol), 2-(4-fluorophenyl)thiazole-4-carboxylic acid (0.09 g, 0.39 mmol), HATU (0.29 g, 0.77 mmol), and DI PEA (0.27 mL, 1.54 mmol) were used in the same manner, and the reaction was then purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.11 g). Blood— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.02(m, 2H) , 4.48(m, 3H) , 6.94(m, 1H), 7.54(m, 2H), 7.67(s, 1H) , 7.93(m, 1H) , 7.96(m, 2H) , 8.06(m, 1H) , 8.39(m, 2H) ,

[0248] 8.51(m, 1H), 9.97(s, 1H)

[0249] LC-MS (ESI, m / z) = 491.1 (M+H+) Example 47, 2— (3—fluorophenyl)— N— (6—(furan— 3 —yl)— 2— (3—hydroxy- 3~ methylbutyl )-2H-indazol- 5 -yl)thiazole- 4 -carboxamide

[0250] [Step 4] Synthesis of 2-bromo-N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)thiazole-4-carboxamide Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 11 (1.0 g, 3.5 mmol), 2-bromothiazole-4-carboxylic acid (0.79 g, 3.5 mmol), HATU (2.67 g, 7.01 mmol), and DI PEA (2.44 mL, 14.02 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (1.03 g). 6H) , 2.01(t, 2H) , 4.49(m, 3H) , 6.93(s, 1H),

[0251] 7.56(s, 1H), 7.68(s, 1H) , 7.92(s, 1H) , 8.18(s, 1H) , 8.42(s, 1H) , 8.78(s, 1H) , 9.92(s, 1H)

[0252] [Step 5] Synthesis of 2-(3-fluorophenyl)-N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)thiazole-4-carboxamide (Compound 47) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] (0.1 g, 0.21 mmol), sodium carbonate (0.11 g, 1.05 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, 0.001 mmol), and 2-(3-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.07 g, 0.32 mmol) were used, and the reaction was carried out in the same manner.

[0253] The title compound (0.08 g) was obtained by purification by MPLC (combiFlash NEXTGEN 300+) and concentration. P— NMR (DMSO-d 6) 1.13(s, 6H) , 2.04(t, 2H) , 4.51(m, 3H) , 6.91(s, 1H), 7.62-7.63(m, 2H) , 7.98(s, 1H) , 8.20(s, 1H) , 8.39(s, 1H) , 8.40(d, 1H), 8.46(s, 1H), 8.52 (d, 1H), 8.55-8.56(m, 1H), 8.58(s, 1H), 9.96(s, 1H) LC-MS (ESI, m / z) = 491.1 (M+H+) Example 48. N- (6-(furan-3 -1)- 2- (3 -hydroxy- 3 -methylbutyl)- 2H -indazole- 5- yl)- 2- (3- (trifluoromethyl)phenyl)thiazole- 4 -carboxamide

[0254] [Step 5] Synthesis of N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(3-(trifluoromethyl)phenyl)thiazole-4-carboxamide (Compound 48) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 47 (0.1 g, 0.21 mmol), sodium carbonate (0.11 g, 1.05 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, 0.0lmmol), and 4,4,5,5-tetramethyl-2-(3-(trifluoromethyl)phenyl)-1,3,2-dioxaborolane (0.09 g, 0.32 mmol) was used in the same manner. After the reaction, the compound was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.08 g). P— NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.05(t, 2H) , 4.53(m, 3H) , 6.71(s, 1H), 7.65-7.67(m, 2H) , 7.90(s, 1H) , 8.11(s, 1H) , 8.30(s, 1H) , 8.38(d, 1H) , 8.39(s, 1H), 8.42 (d, 1H), 8.50-8.51(m, 1H) , 8.52(s, 1H) , 9.45(s, 1H)

[0255] LC-MS (ESI, m / z) = 541.1 (M+H+) Example 49. N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(4-(trifluoromethyl)phenyl)thiazole-4-carboxamide

[0256] [Step 5] Synthesis of N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(4-(trifluoromethyl)phenyl)thiazole-4-carboxamide (Compound 49) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 47 (0.1 g, 0.21 mmol), sodium carbonate (0.11 g, 1.05 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, 0.0lmmol), and 4,4,5,5-tetramethyl-2-(4-(trifluoromethyl)phenyl)-1,3,2-dioxaborolane (0.09 g, 0.32 mmol) were used, and the reaction was carried out in the same manner. The title compound (0.07 g) was obtained by purification by MPLC (combiFlash NEXTGEN 300+) and concentration. P— NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.05(t, 2H) , 4.53(m, 3H) , 6.71(s, 1H), 7.65-7.67(m, 2H) , 7.92(s, 1H) , 8.13(s, 1H) , 8.41(s, 1H) , 8.48(d, 2H) , 8.52(d, 2H), 8.54(s, 1H), 9.48(s, 1H)

[0257] LC-MS (ESI, m / z) = 541.1 (M+H+) Example 50. 2-Ethyl- N- (6-(furan- 3 -yl)- 2- (3 -hydroxy- 3 -methylbutyl)- 2H- indazol- 5 -yl)thiazole- 4 -carboxamide

[0258] [Step 4] Synthesis of 2-ethyl- N- (6-(furan-3-yl)- 2- (3-hydroxy- 3-methylbutyl)- 2H- indazol- 5-yl) thiazole- 4-carboxamide (Compound 50) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] of Example 11 (0.11 g, 0.39 mmol), 2-ethylthiazole- 4-carboxylic acid (0.07 g, 0.39 mmol), HATU (0.29 g, 0.77 mmol), and DI PEA (0.27 mL, 1.54 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.08 g). 3H) , 2.01(t, 2H) , 2.46— 2.47(m,

[0259] 2H), 4.49(m, 3H), 6.92(s, 1H), 7.57(s, 1H), 7.69(s, 1H), 7.91(s, 1H), 8.16(s, 1H), 8.40(s, 1H), 8.76(s, 1H), 9.94(s, 1H)

[0260] LC-MS (ESI, m / z) = 439.1 (M+H+) Example 51. N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-methylthiazole-4-carboxamide

[0261] [Step 4] Synthesis of N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-methylthiazole-4-carboxamide (Compound 51) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 11 (0.11 g, 0.39 mmol), 2-methylthiazole-4-carboxylic acid (0.06 g, 0.39 mmol), HATU (0.29 g, 0.77 mmol), and DI PEA (0.27 mL, 1.54 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.09 g). 6H) , 2.01(t, 2H) , 2.79(s, 3H) , 4.49(m, 3H),

[0262] 6.93(s, 1H), 7.56(s, 1H) , 7.68(s, 1H) , 7.92(s, 1H) , 8.18(s, 1H) , 8.42(s, 1H) , 8.78(s, 1H), 9.92(s, 1H)

[0263] LC-MS (ESI, m / z) = 411.1 (M+H+) Example 52. 2-Cyclohexyl- N-(6-(furan- 3 -yl)- 2-(3 -hydroxy- 3 -methylbutyl)-

[0264] 2H-indazole-5-yl)thiazole-4-carboxamide

[0265] [Step 4] 2-Cyclohexyl- N-(6-(furan- 3 -yl)- 2-(3 -hydroxy- 3 -methylbutyl)-

[0266] Synthesis of 2H-indazol-5-yl)thiazole-4-carboxamide (Compound 52) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 11 (0.11 g, 0.39 mmol), 2-cyclohexylthiazole-4-carboxylic acid (0.08 g, 0.39 mmol), HATU (0.29 g, 0.77 mmol), and DI PEA (0.27 mL, 1.54 mmol) were used, and the reaction was carried out in the same manner. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.07 g). P- NMR 6H) , 1.45- 1.48(m, 2H) , 1.51-1.53 ​​(m,2H),

[0267] 1.84-1.86(m, 4H), 2.01(t, 2H), 2.73(m, 1H), 4.49(m, 3H), 6.93(s, 1H), 7.56(s, 1H), 7.68(s, 1H), 7.92(s, 1H), 8.18(s, 1H) , 8.42(s, 1H) , 8.78(s, 1H) , 9.92(s, 1H)

[0268] LC-MS (ESI, m / z) = 479.1 (M+H+) Example 53. N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(3-nitrophenyl)thiazole-4-carboxamide

[0269] [Step 5] Synthesis of N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(3-nitrophenyl)thiazole-4-carboxamide (Compound 53) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 47 was prepared.

[0270] (0.1 g, 0.21 mmol), sodium carbonate (0.11 g, 1.05 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, 0.001 mmol), and 4,4,5,5-tetramethyl-2-(3-nitrophenyl)-1,3,2-dioxaborolane (0.08 g, 0.32 mmol). The reaction mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to give the title compound (0.10 g). P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.04(t, 2H) , 4.51(m, 3H) , 6.91(s, 1H), 7.62-7.63(m, 2H) , 7.99(s, 1H) , 8.27(s, 1H) , 8.42(s, 1H) , 8.48(d, 1H) , 8.50(s, 1H), 8.54 (d, 1H), 8.59-8.60(m, 1H) , 8.62(s, 1H) , 10.5(s, 1H)

[0271] LC-MS (ESI, m / z) = 518.1 (M+H+) Example 54. N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(thiophene-2-yl)thiazole-4-carboxamide

[0272] [Step 5] Synthesis of N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(thiophene-2-yl)thiazole-4-carboxamide (Compound 54) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 47 (0.1 g, 0.21 mmol), sodium carbonate (0.11 g, 1.05 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, 0.001 mmol), and 4,4,5,5-tetramethyl-2-(thiophene-2-yl)-1,3,2-dioxaborolane (0.07 g, 0.32 mmol) was used, and the reaction was carried out in the same manner. The title compound (0.09 g) was obtained by purification and concentration using MPLC (combiFlash NEXTGEN 300+). 6H) , 2.01(t, 2H) , 4.49(m, 3H) , 6.99(m, 2H), 7.59(m, 2H), 7.72— 7.73(m, 2H) , 7.91(s, 1H) , 8.16(s, 1H) , 8.40(s, 1H) , 8.68(s, 1H), 9.67(s, 1H)

[0273] LC-MS (ESI, m / z) = 479.1 (M+H+) Example 55. N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(3-methoxyphenyl)thiazole-4-carboxamide

[0274] [Step 5] Synthesis of N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(3-methoxyphenyl)thiazole-4-carboxamide (Compound 55) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 47 (0.1 g, 0.21 mmol), sodium carbonate (0.11 g, 1.05 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, 0.001 mmol), and 2-(3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.07 g, 0.32 mmol) were used, and the reaction was performed in the same manner as in [Step 2] of Example 1. After the reaction, MPLC (combiFlash) The title compound (0.09 g) was purified and concentrated using NEXTGEN 300+. P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.04(t, 2H) , 3.82(s, 3H) , 4.51(m, 3H), 6.93(s, 1H), 7.63-7.64(m, 2H) , 7.97(s, 1H) , 8.25(s, 1H) , 8.41(s, 1H) , 8.46(d, 1H), 8.49(s, 1H), 8.53 (d, 1H) , 8.56- 8.58(m, 1H) , 8.12(s, 1H) , 9.46(s, 1H) LC-MS (ESI, m / z) = 503.1 (M+H+) Example 56. N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)—2-(oxazol-4-yl)thiazole-4-carboxamide

[0275] [Step 5] Synthesis of N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(oxazol-4-yl)thiazole-4-carboxamide (Compound 56) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 47 (0.1 g, 0.21 mmol), sodium carbonate (0.11 g, 1.05 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, 0.001 mmol), and 4-(4, 4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)oxazole (0.06 g, 0.32 mmol) was used, and the reaction was performed in the same manner as in [Step 2] of Example 1, followed by MPLC (combiFlash) The residue was purified and concentrated using NEXTGEN 300+ to obtain the title compound (0.05 g). 6H) , 2.01(t, 2H) , 4.49(m, 3H) , 6.99(m, 2H),

[0276] 7.59(m, 1H), 7.72-7.75(m, 2H) , 7.90(s, 1H) , 8.15(s, 1H) , 8.38(s, 1H) , 8.66(s, 1H), 9.62(s, 1H)

[0277] LC-MS (ESI, m / z) = 464.1 (M+H+) Example 57. N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(6-methylpyridin-3-yl)thiazole-4-carboxamide

[0278] [Step 5] Synthesis of N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(6-methylpyridin-3-yl)thiazole-4-carboxamide (Compound 57) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 47 (0.1 g, 0.21 mmol), sodium carbonate (0.11 g, 1.05 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, 0.0lmmol), and 2-methyl-5-(4, 4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.07 g, 0.32 mmol) were used, and the reaction was carried out in the same manner. The title compound (0.09 g) was obtained by purification and concentration using MPLC (combiFlash NEXTGEN 300+). 6H) , 1.98(t, 2H) , 2.85(s, 3H) , 4.48(m, 3H),

[0279] 6.90(s, 1H), 7.60-7.62(m, 2H) , 7.96(s, 1H) , 8.22(s, 1H) , 8.24(s, 1H) , 8.41(s, 1H), 8.43(d, 1H), 8.48(s, 1H) , 8.53(s, 1H) , 9.82(s, 1H)

[0280] LC-MS (ESI, m / z) = 488.1 (M+H+) Example 58. 2-(6-fluoropyridin-3-yl)-N-(6-(furan-3-yl)-2-(2-hydroxy-2-methylpropyl)-2H-indazol-5-yl)thiazole-4-carboxamide

[0281] [Step 5] Synthesis of 2-(6-fluoropyridin-3-yl)-N-(6-(furan-3-yl)-2-(2-hydroxy-2-methylpropyl)-2H-indazol-5-yl)thiazole-4-carboxamide (Compound 58) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 33 (0.12 g, 0.26 mmol), sodium carbonate (0.14 g, 1.30 mmol), tetrakis(triphenylphosphine)palladium (0.02 g, O.Olmmol) and 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.09 g, 0.39 mmol) was used in the same manner, and the reaction was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.09 g). P- NMR (DMSO-d 6 ) 1.14(s, 6H) , 4.46- 4.49(m, 3H) , 7.20-7.21 (d, 2H) , 7.40(d, 1H), 7.56(s, 1H) , 8.03(s, 1H) , 8.25(s, 1H) , 8.40(s, 1H) , 8.50(s, 1H) , 8.70(s, 1H), 9.06(s, 1H) , 10.2(s, 1H)

[0282] LC-MS (ESI, m / z) = 478.1 (M+H+) Example 59. 2- (4-fluorophenyl)- N- (2- (3-hydroxy- 3-methylbutyl)- 6~ (3~

[0283] (morpholine-4-carbonyl)phenyl)-2H-indazol-5-yl)thiazole-4-carboxamide

[0284] [Step 1] Synthesis of 3-(2-(3-hydroxy-3-methylbutyl)-5-nitro-2H-indazol-6-yl)benzoic acid The compound of [Step 2] of Example 31 (0.3 g, 0.78 mmol), tetrahydrofuran (6 mL) and 2N sodium hydroxide aqueous solution (6 mL) were added and stirred at room temperature for more than 3 hours. After completion of the reaction, 2N hydrochloric acid aqueous solution was added to adjust the pH to 5-6, concentrated, filtered, washed with purified water and dried to obtain the title compound (0.26 g). P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.05(t, 2H) , 4.50(s, 1H) , 4.50(t, 2H), 7.36(s, 1H), 7.54(s, 1H) , 8.04 (s, 1H) , 8.12(m, 1H) , 8.34(s, 1H) , 8.44(s, 1H), 8.52(s, 1H)

[0285] [Step 2] Synthesis of (3-(2-(3-hydroxy-3-methylbutyl)-5-nitro-2H-indazol-6-yl)phenyl)(morpholino)methanone The compound of [Step 1] (0.2 g, 0.46 mmol), methylene chloride (2 mL), morpholine (0.04 g, 0.46 mmol), H0Bt-H20 (0.09 g, 0.69 mmol), and EDC-HC1 (0.13 g, 0.669 mmol) were added and stirred at room temperature for more than 6 hours. Purified water (2 mL) was added, dried over magnesium sulfate, and concentrated. Afterwards, the mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.12 g). P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.05(t, 2H) , 3.10— 3.25(m, 4H) , 3.58(m, 4H), 4.49- 4.51(m, 3H) , 7.37(s, 1H), 7.56(s, 1H) , 8.05 (s, 1H) , 8.14(m, 1H) , 8.30(s, 1H), 8.45(s, 1H) , 8.53(s, 1H)

[0286] [Step 3] Synthesis of (3-(5-amino-2-(3-hydroxy-3-methylbutyl)-2H-indazol-6-yl)phenyl)(morpholino)methanone Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.12 g, 0.27 mmol) was hydrogenated with 0.02 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through celite, and the filtrate was concentrated to obtain the title compound (0.1 g). P— NMR (DMSO-d 6 ) 1.09(s, 6H) , 2.01(t, 2H) , 3.01— 3.06(m, 4H) , 3.41(m, 4H), 4.32- 4.34(m, 3H) , 4.54(s, 2H) , 7.27(m, 2H) , 7.41(s, 1H) , 7.91(s, 1H) , 8.01(m, 1H), 8.23(s, 1H) , 8.30(s, 1H) , 8.41(s, 1H) , 9.42(s,lH)

[0287] [Step 4] 2-(4-fluorophenyl)- N-(2-(3-hydroxy- 3-methylbutyl)- 6-(3-

[0288] Synthesis of (morpholine-4-carbonyl)phenyl)-2H-indazol-5-yl)thiazole-4-carboxamide (Compound 59) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.1 g, 0.24 mmol), 2-(4-fluorophenyl)thiazole-4-carboxylic acid (0.05 g, 0.24 mmol), HATU (0.19 g, 0.49 mmol), and DI PEA (0.17 mL, 0.98 mmol) were used, and the reaction was carried out in the same manner. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.07 g). P— NMR (DMSO-d 6) 1.13(s, 6H) , 2.05(t, 2H) , 3.10— 3.25(m, 4H) , 3.58(m, 4H), 4.49(s, 1H), 4.50(t, 2H) , 7.37(m, 2H) , 7.46(s, 1H) , 7.54(s, 1H) , 7.61(m, 2H), 7.75(m, 2H) , 8.04 (s, 1H) , 8.12(m, 1H) , 8.34(s, 1H) , 8.44(s, 1H) , 8.52(s, 1H), 9.53(s,lH)

[0289] LC / MS (ESI, m / z) = 614.1 (M+H+) Example 60. N-(2-(3-hydroxy-3-methylbutyl)-6-(3-((2-hydroxyethyl)carbamoyl)phenyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide [Step 5] Synthesis of 3-(2-(3 -hydroxy- 3 -methylbutyl)-5-(2-(pyridin- 3 -yl)thiazole- 4-carboxamido)-2H-indazol- 6 -yl)benzoic acid The compound of [Step 4] of Example 31 (0.5 g, 0.95 mmol), tetrahydrofuran (lOmL) and 2N sodium hydroxide aqueous solution (10 mL) were added and stirred at room temperature for more than 3 hours. After completion of the reaction, 2N hydrochloric acid aqueous solution was added to adjust the pH to 4-5, concentrated, filtered, washed with purified water and dried to obtain the title compound (0.41 g). P- NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.02- 2.04(m, 3H) , 3.37- 3.38(m, 2H) , 7.53-7.55(m, 1H) , 7.57- 7.60(m, 2H) , 7.70(d, 1H) , 8.03(d, 1H) , 8.05(d, 1H) , 8.07(s, 1H), 8.43(s, 1H) , 8.45(s, 1H) , 8.53(t, 1H) , 8.62(s, 1H) , 8.71(d, 1H) , 8.95(s, 1H), 9.68(s, 1H)

[0290] [Step 6] Synthesis of N-(2-(3-hydroxy-3-methylbutyl)-6-(3-((2-hydroxyethyl)carbamoyl)phenyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 60) The compound of [Step 1] (0.2 g, 0.38 mmol), methylene chloride (2 mL), aminoethanol (0.2 mL, 0.38 mmol), HOBt-H20 (0.08 g, 0.57 mmol), and EDC-HC1 (0.11 g, 0.57 mmol) were added and stirred at room temperature for more than 6 hours. Purified water (2 mL) was added, dried over magnesium sulfate, and concentrated. Afterwards, the product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.14 g). P- NMR 6H) , 2.02- 2.05(m, 3H) , 3.36- 3.38(m, 2H) ,

[0291] 4.48- 4.51(m, 4H) , 4.64(t, 1H) , 7.52- 7.54(m, 1H) , 7.58- 7.61(m, 2H) , 7.69(d, 1H), 8.01(d, 1H), 8.03(d, 1H) , 8.05(s, 1H) , 8.44(s, 1H) , 8.46(s, 1H) , 8.51(t, 1H), 8.60(s, 1H), 8.69(d, 1H) , 8.93(s, 1H) , 9.67(s, 1H)

[0292] LC-MS (ESI, m / z) = 571.1 (M+H+) Example 61. N-(2-(3-hydroxy-3-methylbutyl)-6-(3-((2-morpholinoethyl)carbamoyl)phenyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide Synthesis of ethyl butyl)-6-(3-((2-morpholinoethyl)carbamoyl)phenyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 61) The compound of [Step 5] of Example 60 (0.2 g, 0.38 mmol), methylene chloride (2 mL), 4-(2-aminoethyl)morpholine (0.05 g, 0.38 mmol), HOBt-H20 (0.08 g, 0.57 mmol), and EDC-HC1 (0.11 g, 0.57 mmol) were added and stirred at room temperature for more than 6 hours. Purified water (2 mL) was added, dried over magnesium sulfate, and concentrated. Afterwards, it was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. Compound (0.16 g) was obtained. 2.43(m, 2H) , 2.70(br. s, 4H) , 2.71-

[0293] 2.76(m, 4H), 3.50- 3.51(m, 4H) , 4.50- 4.53(m, 3H) , 7.52- 7.54(m, 1H) , 7.58- 7.61(m, 2H), 7.69(d, 1H) , 8.01(d, 1H) , 8.03(d, 1H) , 8.05(s, 1H) , 8.44(s, 1H) , 8.46(s, 1H), 8.51(t, 1H), 8.60(s, 1H) , 8.69(d, 1H) , 8.93(s, 1H) , 9.67(s, 1H) LC-MS (ESI, m / z) = 640.1 (M+H+) Example 62. 2- (6-fluoropyridin- 3 -yl)- N- (2- (3 -hydroxy- 3 -methylbutyl)-

[0294] 6-(thiophene-3-yl)-2H-indazole-5-yl)thiazole-4-carboxamide

[0295] [Step 5] Synthesis of 2-(6-fluoropyridin-3-yl)-N-(2-(3-hydroxy-3-methylbutyl)-6-(thiophene-3-yl)-2H-indazol-5-yl)thiazole-4-carboxamide (Compound 62) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 39 (0.2 g, 0.41 mmol), sodium carbonate (0.22 g, 2.03 mmol), tetrakis(triphenylphosphine)palladium (0.02 g, 0.02 mmol), and 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.14 g, 0.61 mmol) were used. After reaction in the same manner, the title compound (0.15 g) was obtained by purification by MPLC (combiFlash NEXTGEN 300+) and concentration. P— NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.01(m, 2H) , 4.45(m, 2H) , 4.48(s, 1H), 7.31(m, 1H), 7.54(m, 1H) , 7.57(m, 1H) , 7.67(m, 1H) , 7.70(m, 1H) , 8.40(m, 1H) , 8.64(m, 1H) , 9.38(m, 1H) , 9.69(m, 1H) , 11.63(s, 1H)

[0296] LC-MS (ESI, m / z) = 508.1 (M+H+) Example 63. N-(6-(2-aminopyridin-4-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(6-fluoropyridin-3-yl)thiazole-4-carboxamide

[0297] [Step 4] Synthesis of N-(6-(2-aminopyridin-4-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-bromothiazole-4-carboxamide Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 36 (0.12 g, 0.39 mmol), 2-bromothiazole-4-carboxylic acid (0.09 g, 0.39 mmol), HATU (0.29 g, 0.77 mmol), and DI PEA (0.27 mL, 1.54 mmol) were used, and the reaction was carried out in the same manner. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.12 g). P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.05(m, 2H) , 4.48(m, 3H) , 5.93(s, 2H), 6.23(s, 1H), 6.57(s, 1H) , 7.51(s, 1H) , 7.78(m, 1H) , 8.06(s, 1H) , 8.45(s, 1H) , 8.55(s, 1H), 9.67(s, 1H)

[0298] [Step 5] Synthesis of N-(6-(2-aminopyridin-4-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(6-fluoropyridin-3-yl)thiazole-4-carboxamide (Compound 63) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] (0.11 g, 0.22 mmol), sodium carbonate (0.12 g, l.lOmmol), tetrakis(triphenylphosphine)palladium (0.01 g, O.Olmmol), and 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.07 g, 0.33 mmol) were used in the same manner as in [Step 2] of Example 1. after

[0299] The title compound (0.05 g) was obtained by purification by MPLC (combiFlash NEXTGEN 300+) and concentration. P— NMR (DMSO-d6 ) 1.13(s, 6H) , 2.05(m, 2H) , 4.48(m, 3H) , 5.93(s, 2H), 6.23(m, 2H), 6.59(m, 1H) , 7.51(s, 1H) , 7.79(m, 2H) , 8.06(s, 1H) , 8.45(s, 1H) , 8.55(s, 1H), 8.61(s, 1H) , 9.67(s, 1H)

[0300] LC-MS (ESI, m / z) = 518.1 (M+H+) Example 64. N-(2-(2-(2-amino-2-oxoethoxy)ethyl)-6-(2-aminopyridin-4-yl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide

[0301] [Step 1] Synthesis of 2-(2-(6-bromo-5-nitro-2H-indazol-2-yl)ethoxy)acetamide Under the same conditions as in [Step 1] of Example 1, 6-bromo-5-nitro-1H-indazole (3 g, 12.4 mmol), potassium carbonate (6.85 g, 49.6 mmol), potassium iodide (0.21 g, 1.24 mmol) and 2-(2-chloroethoxy)acetamide (2.56 g, 18.6 mmol) were used. The reaction mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (2.4 g). P— NMR (DMSO-d 6 ) 3.76(s, 2H) , 3.92(t, 2H) , 4.68(t, 2H) , 7.20(d, 2H), 8.14(s, 1H), 8.61(s, 1H), 8.78(s, 1H)

[0302] [Step 2] Synthesis of 2-(2-(6-(2-aminopyridin-4-yl)-5-nitro-2H-indazol-2-yl)ethoxy)acetamide Under the same conditions as [Step 2] of Example 1, the compound of [Step 1] (2.0 g, 5.83 mmol), sodium carbonate (3.09 g, 29.1 mmol), tetrakis(triphenylphosphine)palladium

[0303] (0.34 g, 0.29 mmol) and 4-(4, 4, 5, 5 -tetramethyl- 1,3, 2 -dioxaborolan- 2 -yl)pyridin- 2 -amine (1.92 g, 8.74 mmol) were used in the same manner, and the resulting mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (1.58 g). P— NMR (DMSO-d 6 ) 3.77(s, 2H) , 3.90(t, 2H) , 4.70(t, 2H) , 5.99(s, 2H), 6.37(s, 1H), 6.42(d, 1H) , 7.16— 7.21(m, 2H) , 7.62(s, 1H) , 8.15(s, 1H) , 8.60(d, 1H), 8.80(s, 1H)

[0304] [Step 3] Synthesis of 2-(2-(5-amino-6-(2-aminopyridin-4-yl)-2H-indazol-2-yl)ethoxy)acetamide Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (1.0 g, 2.81 mmol) was hydrogenated with 0.4 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through Celite, and the filtrate was concentrated to obtain the title compound (0.57 g). P— NMR (DMSO-d 6 ) 3.71(s, 2H) , 3.82(t, 2H) , 4.59 (s, 2H) , 4.64(t, 2H) , 5.91(s, 2H), 6.32(s, 1H) , 6.37(d, 1H) , 7.12(d, 2H) , 7.58(s, 1H) , 8.10(s, 1H) , 8.54(d, 1H), 8.74(s, 1H)

[0305] [Step 4] Synthesis of N-(2-(2-(2-amino-2-oxoethoxy)ethyl)-6-(2-aminopyridin-4-yl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 64) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] (0.2 g, 0.61 mmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.14 g, 0.61 mmol), HATU (0.47 g, 1.23 mmol), and DI PEA (0.43 mL, 2.45 mmol) was reacted in the same manner, and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (0.18 g) was obtained. P- NMR (DMSO-d 6 ) 3.78(s, 2H) , 3.93(t, 2H) , 4.62(t, 2H) , 6.16(s, 2H), 6.56(s, 1H), 6.62(d, 1H) , 7.23(br. S, 2H) , 7.51(s, 1H) , 7.57- 7.59(m, 1H) , 8.02(d, 1H), 8.19(d, 1H) , 8.47(d, 2H) , 8.62(s, 1H) , 8.68(d, 1H) , 9.06(s, 1H) , 9.72(s, 1H)

[0306] LC-MS (ESI, m / z) = 515.0 (M+H+) Example 65. N-(2-(2-(2-amino-2-oxoethoxy)ethyl)-6-(2-aminopyridin-4-yl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0307] [Step 4] Synthesis of N-(2-(2-(2-(2-amino-2-oxoethoxy)ethyl)-6-(2-aminopyridin-4-yl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 65) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.2 g, 0.61 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.14 g, 0.61 mmol), HATU (0.47 g, 1.23 mmol), and DI PEA (0.43 mL, 2.45 mmol) was reacted in the same manner, and then purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (0.18 g) was obtained. P— NMR (DMSO-d 6 ) 3.77(s, 6H) , 3.93(t, 2H) , 4.62(t, 2H) , 6.23(s, 2H), 6.57(s, 1H), 6.59(s, 1H) , 7.23(s, 2H) , 7.51(s, 1H) , 7.77(s, 2H) , 8.05(s, 1H) , 8.49(s, 1H), 8.54(s, 1H) , 8.67(s, 1H) , 8.74(s, 2H) , 9.70(s, 1H)

[0308] LC-MS (ESI, m / z) = 515.0 (M+H+) Example 66. N- (2- (2- (2 -amino- 2 -oxoethoxy )ethyl)- 6- (4 -fluorophenyl)-

[0309] 2H-Indazole-5-yl)-2-(2-aminopyridin-4-yl)thiazole-4-carboxamide

[0310] [Step 2] Synthesis of 2-(2-(6-(4-fluorophenyl)-5-nitro-2H-indazol-2-yl)ethoxy)acetamide Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] of Example 64 (1.0 g, 2.91 mmol), sodium carbonate (1.54 g, 14.6 mmol), tetrakis(triphenylphosphine)palladium (0.17 g, 0.15 mmol), and (4-fluorophenyl)boronic acid (0.61 g, 4.37 mmol) were used, and the reaction was carried out in the same manner. The resulting mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.79 g). P— NMR (DMSO-d 6 ) 3.77(s, 2H) , 3.94(t, 2H) , 4.63(t, 2H) , 7.22— 7.24(d, 2H), 7.37(d, 2H), 7.53(d, 2H) , 8.05(s, 1H) , 8.44(s, 1H) , 8.63(s, 1H)

[0311] [Step 3] Synthesis of 2-(2-(5-amino-6-(4-fluorophenyl)-2H-indazol-2-yl)ethoxy)acetamide Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.6 g, 1.67 mmol) was hydrogenated with 0.12 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through Celite, and the filtrate was concentrated to obtain the title compound (0.34 g). P— NMR (DMSO-d 6 ) 3.69(s, 2H) , 3.84(t, 2H) , 4.56(s, 2H) , 4.58(t, 2H), 7.13-7.14(d, 2H), 7.29(d, 2H) , 7.48(d, 2H) , 7.98(s, 1H) , 8.36(s, 1H) , 8.58(s, 1H)

[0312] [Step 4] Synthesis of N-(2-(2-(2-(2-amino-2-oxoethoxy)ethyl)-6-(4-fluorophenyl)-2H-indazol-5-yl)-2-bromothiazole-4-carboxamide Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.3 g, 0.91 mmol), 2-bromothiazole-4-carboxylic acid (0.20 g, 0.91 mmol), HATU (0.69 g, 1.83 mmol), and DI PEA (0.64 mL, 3.65 mmol) were used in the same manner. The reaction mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.34 g). P- NMR (DMSO-d 6 ) 3.78(s, 2H) , 3.93(t, 2H) , 4.63(t, 2H) , 6.70(d, 1H), 6.80(s, 1H), 6.70(d, 2H) , 7.19- 7.22(d, 2H) , 7.53- 7.56(s, 1H) , 8.00(s, 1H), 8.44(s, 1H), 8.59(s, 1H) , 9.52(s, 1H)

[0313] [Step 5] Synthesis of N-(2-(2-(2-amino-2-oxoethoxy)ethyl)-6-(4-fluorophenyl)-2H-indazol-5-yl)-2-(2-aminopyridin-4-yl)thiazole-4-carboxamide (Compound 66) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] (0.11 g, 0.21 mmol), sodium carbonate (0.11 g, 1.06 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, 0.001 mmol) and 4-(4, 4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-

[0314] 2 - The reaction was carried out in the same manner using amine (0.07 g, 0.32 mmol), and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.06 g). P- NMR (DMSO-d6 ) 3.78(s, 2H) , 3.93(t, 2H) , 4.63(t, 2H) , 6.19(s, 2H), 6.70(d, 1H), 6.80(s, 1H) , 6.70(d, 2H) , 7.19- 7.22(d, 2H) , 7.40(s, 2H) , 7.53- 7.56(m, 2H), 8.00(d, 1H) , 8.44(s, 1H) , 8.48(s, 1H) , 8.59(s, 1H) , 9.52(s, 1H)

[0315] LC-MS (ESI, m / z) = 532.0 (M+H+) Example 67. N-(2-(2-(2-amino-2-oxoethoxy)ethyl)-6-(4-fluorophenyl)-2H-indazol-5-yl)-2-(3-aminophenyl)thiazole-4-carboxamide

[0316] [Step 5] N-(2-(2-(2 -amino- 2 -oxoethoxy)ethyl)- 6-(4 -fluorophenyl)-

[0317] Synthesis of 2H-indazol-5-yl)-2-(3-aminophenyl)thiazole-4-carboxamide (compound 67) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 66

[0318] (0.11 g, 0.21 mmol), sodium carbonate (0.11 g, 1.06 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, O.Olmmol) and 3-(4, 4, 5, 5 -tetramethyl- 1,3, 2 -dioxaborolan- 2 -yl)aniline (0.07 g, 0.32 mmol) were used in the same manner. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to give the title compound (0.06 g). P— NMR (DMSO-d 6) 3.77(s, 2H) , 3.94(t, 2H) , 4.63(t, 2H) , 6.20(s, 2H), 6.70(d, 1H), 6.83(d, 1H) , 6.96(t, 1H) , 7.10(t, 1H) , 7.20- 7.23(m, 2H) , 7.38- 7.41(m, 2H), 7.51(s, 1H) , 7.55- 7.56(m, 2H) , 8.03(s, 1H) , 8.48(s, 1H) , 8.66(s, 1H), 9.51(s, 1H)

[0319] LC-MS (ESI, m / z) = 531.0 (M+H+) Example 68. N- (2- (2- (2 -amino- 2 -oxoethoxy )ethyl)- 6- (4 -fluorophenyl)-

[0320] 2H-Indazole-5-yl)-2-(3-fluorophenyl)thiazole-4-carboxamide

[0321] [Step 4] N- (2- (2- (2 -amino- 2 —oxoethoxy) ethyl)- 6- (4 -fluorophenyl)-

[0322] Synthesis of 2H-indazol-5-yl)-2-(3-fluorophenyl)thiazole-4-carboxamide (Compound 68) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] of Example 66 (0.11 g, 0.34 mmol), 2-(3-fluorophenyl)thiazole-4-carboxylic acid (0.07 g, 0.34 mmol), HATU (0.25 g, 0.67 mmol), and DI PEA (0.23 mL, 1.34 mmol) were used in the same manner. The reaction mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.10 g). P- NMR (DMSO-d 6) 3.77(s, 2H) , 3.94(t, 2H) , 4.63(t, 2H) , 7.22- 7.24(d, 2H), 7.37(d, 2H), 7.52- 7.53(m, 3 H) , 7.54- 7.59(m, 3H) , 8.05(s, 1H) , 8.43(s, 1H), 8.48(s, 1H), 8.63(s, 1H) , 9.56(s, 1H)

[0323] LC-MS (ESI, m / z) = 534.0 (M+H+) Example 69. N-(2-(2-(2-amino-2-oxoethoxy)ethyl)-6-(4-fluorophenyl)-2H-indazol-5-yl)-2-(3-hydroxyphenyl)thiazole-4-carboxamide

[0324] [Step 5] N-(2-(2-(2 -amino- 2 -oxoethoxy)ethyl)- 6-(4 -fluorophenyl)-

[0325] Synthesis of 2H-indazol-5-yl)-2-(3-hydroxyphenyl)thiazole-4-carboxamide (compound 69) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 66

[0326] (0.11 g, 0.21 mmol), sodium carbonate (0.11 g, 1.06 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, 0.001 mmol), and 3-(4, 4, 5, 5-tetramethyl-1,3, 2-dioxaborolan-2-yl)phenol (0.07 g, 0.32 mmol) were used in the same manner. The resulting mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to give the title compound (0.05 g). P— NMR (DMSO-d 6) 3.77(s, 2H) , 3.94(t, 2H) , 4.63(t, 2H) , 6.99(d, 1H), 7.08(d, 1H), 7.18(s, 1H) , 7.21- 7.25(m, 2H) , 7.38(s, 1H) , 7.50(s, 1H) , 7.56- 7.58(m, 2H), 8.03(s, 1H) , 8.48(s, 1H) , 8.62(s, 1H) , 9.54(s, 1H) , 9.59(s, 1H) LC-MS (ESI, m / z) = 532.0 (M+H+) Example 70. N-(2-(2-(2-amino-2-oxoethoxy)ethyl)-6-(4-fluorophenyl)-2H-indazol-5-yl)-2-(6-fluoropyridin-3-yl)thiazole-4-carboxamide

[0327] [Step 5] Synthesis of N-(2-(2-(2-amino-2-oxoethoxy)ethyl)-6-(4-fluorophenyl)-2H-indazol-5-yl)-2-(6-fluoropyridin-3-yl)thiazole-4-carboxamide (Compound 70) Under the same conditions as [Step 2] of Example 1, using the compound of [Step 4] of Example 66 (0.11 g, 0.21 mmol), sodium carbonate (0.11 g, 1.06 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, 0.0lmmol), and 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.07 g, 0.32 mmol). After reaction in the same manner, the title compound (0.07 g) was obtained by purification by MPLC (combiFlash NEXTGEN 300+) and concentration. P- NMR (DMSO-d 6) 3.77(s, 2H) , 3.94(t, 2H) , 4.63(t, 2H) , 7.22- 7.24(m, 2H), 7.32-7.34(m, 2H) , 7.52- 7.53(m, 1H) , 7.53- 7.54(m, 1H) , 7.55- 7.57(m, 1H) , 8.29(s, 1H), 8.45(s, 1H) , 8.46(s, 1H) , 8.49(s, 1H) , 8.53(s, 1H) , 8.67(s, 1H) , 9.60(s, 1H)

[0328] LC-MS (ESI, m / z) = 535.0 (M+H+) Example 71. N-(2-(2-(2 -amino- 2 -oxoethoxy)ethyl)- 6-(4 -fluorophenyl)-

[0329] 2H-Indazole-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide

[0330] [Step 4] N-(2-(2-(2 -amino- 2 -oxoethoxy)ethyl)- 6-(4 -fluorophenyl)-

[0331] Synthesis of 2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 71) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] of Example 66 (0.11 g, 0.34 mmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.07 g, 0.34 mmol), HATU (0.25 g, 0.67 mmol), and DI PEA (0.23 mL, 1.34 mmol) were used. The reaction mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.12 g). P— NMR (DMSO-d 6) 3.78(s, 2H) , 3.94(t, 2H) , 4.63(t, 2H) , 7.19— 7.23(d, 2H), 7.37(d, 2H), 7.50- 7.53(m, 2H) , 7.56- 7.59(m, 2H) , 8.08(s, 1H) , 8.46(s, 1H), 8.49(s, 1H), 8.59(s, 1H) , 8.70(d, 1H) , 9.59(s, 1H)

[0332] LC-MS (ESI, m / z) = 517.0 (M+H+) Example 72. N-(2-(2-(2-amino-2-oxoethoxy)ethyl)-6-(4-fluorophenyl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0333] [Step 4] Synthesis of N-(2-(2-(2-(2-amino-2-oxoethoxy)ethyl)-6-(4-fluorophenyl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 72) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] of Example 66 (0.11 g, 0.34 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.07 g, 0.34 mmol), HATU (0.25 g, 0.67 mmol), and DI PEA (0.23 mL, 1.34 mmol) were reacted in the same manner, and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to give the title compound. (0.11 g) was obtained. P— NMR (DMSO-d 6 ) 3.78 (s, 2H) , 3.93 (t, 2H) , 4.62 (t, 2H) , 7.20-7.24 (d, 2H), 7.40 (t, 2H), 7.54 (s, 1H) , 7.57-7.59 (m, 2H) , 7.67 (d, 2H) , 8.49

[0334] (s, 1H), 8.53 (s, 1H), 8.60 (s, 1H), 8.70 (d, 2H), 9.57 (s, 1H)

[0335] LC-MS (ESI, m / z) = 517.0 (M+H+) Example 73. N-(2-(2-(2-amino-2-oxoethoxy)ethyl)-6-(furan-3-yl)-2H-indazol-5-yl)-2-(trifluoromethyl)thiazole-4-carboxamide

[0336] [Step 2] Synthesis of 2-(2-(6-(furan-3-yl)-5-nitro-2H-indazol-2-yl)ethoxy)acetamide Under the same conditions as [Step 2] of Example 1, the compound of [Step 1] of Example 64 (1.0 g, 2.91 mmol), sodium carbonate (1.54 g, 14.6 mmol), tetrakis(triphenylphosphine)palladium (0.17 g, 0.15 mmol), and 2-(furan-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.85 g, 4.37 mmol) were used, and the reaction was carried out in the same manner. The product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (0.76 g) was obtained. P— NMR (DMSO-d 6 ) 3.77(s, 2H) , 3.94(t, 2H) , 4.61(t, 2H) , 6.83(s, 1H), 7.20-7.23(d, 2H), 7.74(s, 1H) , 7.95(s, 1H) , 8.10(s, 1H) , 8.49(s, 1H) , 8.76(s, 1H)

[0337] [Step 3] Synthesis of 2-(2-(5-amino-6-(furan-3-yl)-2H-indazol-2-yl)ethoxy)acetamide Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.5 g, 1.51 mmol) was hydrogenated with 0.25 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through celite, and the filtrate was concentrated to obtain the title compound (0.37 g). P— NMR (DMSO-d 6 ) 3.71(s, 2H) , 3.88(t, 2H) , 4.54(s, 2H) , 4.54(t, 2H), 6.76(s, 1H), 7.13-7.17(d, 2H) , 7.68(s, 1H) , 7.87(s, 1H) , 8.12(s, 1H) , 8.38(s, 1H), 8.70(s, 1H)

[0338] [Step 4] Synthesis of N-(2-(2-(2-amino-2-oxoethoxy)ethyl)-6-(furan-3-yl)-2H-indazol-5-yl)-2-(trifluoromethyl)thiazole-4-carboxamide (Compound 73) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.11 g, 0.37 mmol), 2-(trifluoromethyl)thiazole-4-carboxylic acid (0.08 g, 0.37 mmol), HATU (0.28 g, 0.73 mmol), and DI PEA (0.26 mL, 1.47 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.08 g). P- NMR (DMSO-d 6 ) 3.78(s, 2H) , 3.93(t, 2H) , 4.62(t, 2H) , 6.83(s, 1H), 7.20-7.23(d, 2H), 7.68(s, 1H) , 7.74(s, 1H) , 7.95(s, 1H) , 8.10(s, 1H) , 8.49(s, 1H), 8.76(s, 1H), 9.57(s, 1H)

[0339] LC-MS (ESI, m / z) = 480.0 (M+H+) Example 74. N-(2-(2-(2-amino-2-oxoethoxy)ethyl)-6-(thiophene-3-yl)-2H-indazol-5-yl)-2-(6-fluoropyridin-3-yl)thiazole-4-carboxamide

[0340] [Step 2] Synthesis of 2-(2-(5-nitro-6-(thiophene-3-yl)-2H-indazol-2-yl)ethoxy)acetamide Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] of Example 64 (1.1 g, 3.18 mmol), sodium carbonate (1.68 g, 15.9 mmol), tetrakis(triphenylphosphine)palladium (0.18 g, 0.16 mmol), and 4,4,5,5-tetramethyl-2-(thiophene-3-yl)-1,3,2-dioxaborolane (1.0 g, 4.76 mmol) were used, and the reaction was carried out in the same manner. The product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (0.84 g) was obtained. P— NMR (DMSO-d 6 ) 3.77(s, 2H) , 3.93(t, 2H) , 4.61(t, 2H) , 7.20— 7.21(d, 2H), 7.38(d, 1H), 7.78- 7.81(m, 2H), 8.47(s, 1H) , 8.64(s, 1H) , 8.78(s, 1H)

[0341] [Step 3] Synthesis of 2-(2-(5-amino-6-(thiophen-3-yl)-2H-indazol-2-yl)ethoxy)acetamide Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.8 g, 2.31 mmol) was hydrogenated with 0.4 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through Celite, and the filtrate was concentrated to obtain the title compound (0.43 g). P— NMR (DMSO-d 6) 3.71(s, 2H) , 3.87(t, 2H) , 4.56 s, 2H) , 4.55(t, 2H) , 7.13-7.14(d, 2H), 7.32(d, 1H) , 7.72- 7.73(m, 2H) , 8.41(s, 1H) , 8.58(s, 1H) , 8.72(s, 1H)

[0342] [Step 4] Synthesis of N-(2-(2-(2-(2-amino-2-oxoethoxy)ethyl)-6-(thiophene-3-yl)-2H-indazol-5-yl)-2-bromothiazole-4-carboxamide Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.2 g, 0.63 mmol), 2-bromothiazole-4-carboxylic acid (0.13 g, 0.63 mmol), HATU (0.48 g, 1.26 mmol), and DI PEA (0.44 mL, 2.53 mmol) were used in the same manner. The reaction mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.21 g). P— NMR (DMSO-d 6 ) 3.77(s, 2H) , 3.93(t, 2H) , 4.61(t, 2H) , 7.20— 7.21(d, 2H), 7.38(d, 1H), 7.60(s, 1H) , 7.78- 7.81(m, 2H) , 8.47(s, 1H) , 8.64(s, 1H) , 8.78(s, 1H), 9.81(s, 1H)

[0343] [Step 5] Synthesis of N-(2-(2-(2-(2-amino-2-oxoethoxy)ethyl)-6-(thiophene-3-yl)-2H-indazol-5-yl)-2-(6-fluoropyridin-3-yl)thiazole-4-carboxamide (Compound 74) Under the same conditions as [Step 2] of Example 1, using the compound of [Step 4] (0.2 g, 0.39 mmol), sodium carbonate (0.21 g, 1.97 mmol), tetrakis(triphenylphosphine)palladium (0.02 g, 0.02 mmol), and 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.13 g, 0.59 mmol) After reaction in the same manner, the compound was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.10 g). P— NMR (DMSO-d 6 ) 3.77(s, 2H) , 3.93(t, 2H) , 4.61(t, 2H) , 7.20— 7.21(d, 2H), 7.38(d, 1H), 7.42(d, 1H) , 7.60(s, 1H) , 7.78- 7.81(m, 2H) , 8.41- 8.42(m, 1H), 8.47(d, 2H), 8.64(s, 1H) , 8.78(s, 1H) , 9.81(s, 1H)

[0344] LC-MS (ESI, m / z) = 523.0 (M+H+) Example 75. N-(2-(2-(2-amino-2-oxoethoxy)ethyl)-6-(thiophene-3-yl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide

[0345] [Step 4] Synthesis of N-(2-(2-(2-amino-2-oxoethoxy)ethyl)-6-(thiophene-3-yl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 75) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 74 (0.1 g, 0.32 mmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.07 g, 0.63 mmol), HATU (0.24 g, 0.63 mmol), and DI PEA (0.22 mL, 1.26 mmol) were used in the same manner, and the resulting product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (0.12 g) was obtained. P— NMR (DMSO-d 6 ) 3.78(s, 2H) , 3.93(t, 2H) , 4.62(t, 2H) , 7.24(d, 2H), 7.36-7.39(m, 1H) , 7.56- 7.60(m, 2H) , 7.76- 7.79(m, 1H) , 7.80- 7.82(m, 1H) , 8.22- 8.24(m, 1H), 8.46(s, 1H) , 8.48(s, 1H) , 8.65(s, 1H) , 8.79(dd, 1H) , 9.08(d, 1H), 9.82(s, 1H)

[0346] LC-MS (ESI, m / z) = 505.0 (M+H+) Example 76. N-(2-(2-(2-amino-2-oxoethoxy)ethyl)-6-(thiophene-3-yl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0347] [Step 4] Synthesis of N-(2-(2-(2-amino-2-oxoethoxy)ethyl)-6-(thiophene-3-yl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 76) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 74 (0.1 g, 0.32 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.07 g, 0.63 mmol), HATU (0.24 g, 0.63 mmol), and DI PEA (0.22 mL, 1.26 mmol) were reacted in the same manner, and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (0.11 g) was obtained. P— NMR (DMSO-d 6 ) 3.77(s, 2H) , 3.93(t, 2H) , 4.61(t, 2H) , 7.22(d, 2H), 7.39(s, 1H), 7.60(s, 1H) , 7.81- 7.84(m, 2H) , 8.47(s, 1H) , 8.56(d, 2H) , 8.64(s, 1H), 8.75(s, 1H), 8.76(d, 2H) , 9.81(s, 1H)

[0348] LC-MS (ESI, m / z) = 505.0 (M+H+) Example 77. N-(2-(2-(dimethylamino)ethyl)- 6-(6 -fluoropyridin- 3 -yl)-

[0349] 2H-Indazole-5-yl)-2-(trifluoromethyl)thiazole-4-carboxamide

[0350] [Step 2] Synthesis of 2-(6-(6-fluoropyridin-3-yl)-5-nitro-2H-indazol-2-yl)-N,N-dimethylethan-1-amine Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] of Example 5 (0.5 g, 1.6 mmol), sodium carbonate (0.85 g, 7.98 mmol), tetrakis(triphenylphosphine)palladium (0.09 g, 0.08 mmol), and 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.53 g, 2.39 mmol) were used, and the reaction was carried out in the same manner, followed by purification by MPLC (combiFlash NEXTGEN 300+). The title compound (0.42 g) was obtained by concentration. P— NMR (DMSO-d 6 ) 2.83(s, 6H) , 3.72(t, 2H) , 4.87(t, 2H) , 7.17— 7.19(m, 1H), 8.02-8.04(m, 3H) , 8.27(s, 1H), 8.55(s, 1H) , 8.64(s, 1H)

[0351] [Step 3] Synthesis of 2-(2-(dimethylamino)ethyl)-6-(6-fluoropyridin-3-yl)-2H-indazol-5-amine Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.4 g, 1.21 mmol) was hydrogenated with 0.08 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through Celite, and the filtrate was concentrated to obtain the title compound (0.23 g). P— NMR (DMSO-d 6 ) 2.77(s, 6H), 3.66(t, 2H), 4.56(s, 2H), 4.81(t, 2H), 7.11-7.12(m, 1H), 7.96-7.98(m, 3H), 8.21(s, 1H), 8.49(s, 1H) , 8.58(s, 1H)

[0352] [Step 4] Synthesis of N-(2-(2-(dimethylamino)ethyl)-6-(6-fluoropyridin-3-yl)-2H-indazol-5-yl)-2-(trifluoromethyl)thiazole-4-carboxamide (Compound 77) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] (0.2 g, 0.67 mmol), 2-(trifluoromethyl)thiazole-4-carboxylic acid (0.13 g, 0.67 mmol), HATU (0.41 g, 1.08 mmol), and DI PEA (0.38 mL, 2.17 mmol) were reacted in the same manner, and then purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound.

[0353] (0.22 g) was obtained. P— NMR (DMSO-d 6 ) 2.83(s, 6H) , 3.72(t, 2H) , 4.87(t, 2H) , 7.17— 7.19(m,

[0354] 1H), 7.67(s, 1H), 8.02-8.04(m, 3H) , 8.27(s, 1H) , 8.55(s, 1H) , 8.64(s, 1H) , 10.0(s, 1H)

[0355] LC / MS (ESI, m / z) = 479.1 (M+H+) Example 78. N-(2-(2-(dimethylamino)ethyl)-6-(furan-3-yl)-2H-indazol-5-yl)-2-(3-hydroxyphenyl)thiazole-4-carboxamide

[0356] [Step 4] Synthesis of 2-bromo-N-(2-(2-(dimethylamino)ethyl)-6-(furan-3-yl)-2H-indazole—5-yl)thiazole-4-carboxamide Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 5 (0.2 g, 0.74 mmol), 2-bromothiazole-4-carboxylic acid (0.15 g, 0.74 mmol), HATU (0.56 g, 1.48 mmol), and DI PEA (0.52 mL, 2.96 mmol) were used, and the reaction was carried out in the same manner. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.23 g). P— NMR (DMSO-d 6 ) 2.17(s, 6H) , 2.79(m, 2H) , 4.49(t, 2H) , 6.93(s, 1H), 7.67(s, 1H), 7.90(m, 2H) , 8.06(s, 1H) , 8.40(s, 1H) , 8.42(s, 1H) , 8.52(s, 1H) , 9.99(s, 1H)

[0357] [Step 5] N-(2-(2-(dimethylamino)ethyl)-6-(furan-3-yl)-2H-indazol-5-yl)-

[0358] Synthesis of 2-(3-hydroxyphenyl)thiazole-4-carboxamide (Compound 78) Under the same conditions as in [Step 2] of Example 1, the compound of [Step 4] (0.1 g, 0.22 mmol), sodium carbonate (0.12 g, 1.09 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, 0.001 mmol), and 3-(4, 4, 5, 5-tetramethyl-1,3, 2-dioxaborolan-2-yl)phenol (0.07 g, 0.33 mmol) were used. The reaction was carried out in the same manner, and the resultant was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.06 g). P— NMR (DMSO-d 6) 2.16(s, 6H) , 2.76 t, 2H) , 4.48 (t, 2H) , 6.92 (m, 2H), 7.31-7.32 (m, 2H) , 7.35-7.37 (m, 1H) , 7.66 (s, 1H) , 7.86 (t, 1H) , 8.04 (s, 1H), 8.39 (s, 2H), 8.45 (s, 1H) , 9.80 (s, 1H) , 9.91 (s, 1H)

[0359] LC-MS (ESI, m / z) = 474.1 (M+H+) Example 79. 2-(4-aminophenyl)-N-(2-(2-(dimethylamino)ethyl)-6-(furan-3-yl)-2H-indazol-5-yl)thiazole-4-carboxamide

[0360] [Step 5] Synthesis of 2-(4-aminophenyl)-N-(2-(2-(dimethylamino)ethyl)-6-(furan-3-yl)-2H-indazol-5-yl)thiazole-4-carboxamide (Compound 79) Under the same conditions as in [Step 2] of Example 1, the compound of [Step 4] of Example 78 (0.1 g, 0.22 mmol), sodium carbonate (0.12 g, 1.09 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, 0.001 mmol), and 4-(4, 4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (0.07 g, 0.33 mmol) were used, and the reaction was performed in the same manner, followed by MPLC (combiFlash NEXTGEN) 300+) and concentrated to obtain the title compound (0.04 g). P— NMR (DMSO-d 6 ) 2.15 (s, 6H) , 2.47 (t, 2H) , 4.48 (t, 2H) , 5.77 (s, 2H), 6.89 (s, 1H), 7.56-7.58 (m, 1H) , 7.59-7.62 (m, 2H) , 7.63 (s, 1H) , 7.88 (s, 1H), 8.07 (s, 1H), 8.15 (s, 1H) , 8.38 (s, 1H) , 8.53 (s, 1H) , 9.82 (s, 1H)

[0361] LC-MS (ESI, m / z) = 473.1 (M+H+) Example 80. N- (2- (2 -hydroxy- 2 ■methylpropyl)- 6- (thiophene- 3 -yl)- 2H- indazol- 5 -yl)- 2- (pyridin- 4 -yl)thiazole- 4 -carboxamide

[0362] [Step 1] Synthesis of 1-(6-bromo-5-nitro-2H-indazol-2-yl)-2-methylpropan-2-ol

[0363] 6-Bromo-5-nitro-2H-indazole (2 g, 8.26 mmol) was added to dimethylformamide (20 mL) and stirred at room temperature. While stirring at room temperature, potassium carbonate (4.56 g, 27.30 mmol) and potassium iodide (0.14 g, 0.83 mmol) were added, and 1-chloro-2-methylpropan-2-ol (1.312 g, 12.39 mmol) was added dropwise. The reaction temperature was raised to 100°C and stirred for 5 hours. Upon completion of the reaction, the internal temperature was cooled to room temperature, diluted with 50 mL of ethyl acetate, and washed with purified water. The mixture was dried over magnesium sulfate, filtered under vacuum, and the filtrate was concentrated, purified by MPLC (combiFlash NEXTGEN 300+), and concentrated to obtain the title compound (1.16 g). P- NMR (DMSO-d 6 ) 1.09(s, 6H) , 4.32(s, 2H) , 4.85(s, 1H) , 7.81(s, 1H), 7.82(s, 1H), 8.60(s, 1H)

[0364] [Step 2] Synthesis of 2-methyl-1-(5-nitro-6-(thiophene-3-yl)-2H-indazol-2-yl)propan-2-ol To the compound of [Step 1] (1.02 g, 3.25 mmol) was added 15 mL of 1,4-dioxane and purified water in a 10:1 ratio and stirred at room temperature. Sodium carbonate (1.72 g, 16.23 mmol) and tetrakis(triphenylphosphine)palladium (0.19 g, 0.16 mmol) were added and stirred. 4,4,5,5-tetramethyl-2-(thiophene-3-yl)-1,3,2-dioxoborane was added and stirred. The reactor was heated to 100°C and stirred for 8 hours. Upon completion of the reaction, it was cooled to room temperature, ethyl acetate (20 mL) was added, and sodium bicarbonate aqueous solution (20 mL) was added to wash. Afterwards, magnesium sulfate was added, filtered, concentrated, purified by MPLC (combiFlash NEXTGEN 300+), and concentrated to obtain the title compound (0.79 g). P- NMR (DMSO-d 6 ) 1.09(s, 6H) , 4.32(s, 2H) , 4.85(s, 1H) , 7.40(d, 1H), 7.60(s, 1H), 7.81(s, 1H), 7.82(s, 1H) , 7.91(s, 1H) , 8.60(s, 1H)

[0365] [Step 3] Synthesis of 1-(5-amino-6-(thiophene-3-yl)-2H-indazol-2-yl)-2-methylpropan-2-ol Ethyl acetate (5 mL) was added to the compound of [Step 2] (0.36 g, 2 mmol). Hydrogenation was performed with 0.128 g (0.11 mmol) of palladium on activated carbon under standard hydrogen pressure at 25°C for 3 hours. The reaction mixture was filtered through Celite, the filter was washed with methanol, and the filtrate was concentrated. The title compound (0.63 g) was obtained. P— NMR (DMSO-d 6 ) 1.09(s, 6H) , 4.32(s, 2H) , 4.80(s, 2H) , 4.85(s, 1H),

[0366] 7.22(s, 1H), 7.40(d, 1H) , 7.42(s, 1H) , 7.60(s, 1H) , 7.81(s, 1H) , 7.91(s, 1H)

[0367] [Step 4] Synthesis of N-(2-(2-hydroxy-2-methylpropyl)-6-(thiophene-3-yl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 80)

[0368] 2-(Pyridin-4-yl)thiazole-4-carboxylic acid (0.1 g, 0.481 mmol) was stirred with dimethylformamide (2 mL). HATU (0.33 g, 0.88 mmol) and DI PEA (0.31 mL, 1.75 mmol) were added and stirred at room temperature for 1 hour. The compound of [Step 3] (0.126 g, 0.44 mmol) was added and stirred at room temperature for 8 hours. Upon completion of the reaction, purified water (5 mL) was added, and the resulting crystals were filtered and dried to obtain the title compound (0.101 g). P- NMR (DMSO-d 6 ) 9.81(s,lH), 8.76(d, 2H) , 8.75(s, 1H) , 8.64(s, 1H) , 8.56(s, 1H), 8.33(s, 1H) , 7.92(s, 1H) , 7.82(m, 3H) , 7.61(s, 1H) , 7.39(d, 1H) , 4.85(s, 1H), 4.32(s, 2H) , 1.09(s, 6H)

[0369] LC-MS (ESI, m / z) = 476.2 (M+H+) Example 81. 2-(6-fluoropyridin-3-yl)-N-(6-(3-hydroxyphenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)thiazole-4-carboxamide

[0370] [Step 1] Synthesis of 4-(2-(6-bromo-5-nitro-2H-indazol-2-yl)ethyl)morpholine Under the same conditions as in [Step 1] of Example 1, 6-bromo-5-nitro-1H-indazole

[0371] (3 g, 12.4 mmol), potassium carbonate (6.85 g, 49.6 mmol), potassium iodide (0.21 g, 1.24 mmol) and 4-(2-chloroethyl)morpholine hydrochloride (3.46 g, 18.6 mmol) were used in the same manner. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (2.4 g). P- NMR (DMSO-d 6 ) 2.40(br. s, 4H) , 2.83(t, 2H) , 3.49(t, 4H) , 4.61(t, 2H), 8.27(s, 1H), 8.55(s, 1H) , 8.64(s, 1H)

[0372] [Step 2] Synthesis of 3-(2-(2-morpholinoethyl)-5-nitro-2H-indazol-6-yl)phenol Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] (1.0 g, 2.82 mmol), sodium carbonate (1.49 g, 14.8 mmol), tetrakis(triphenylphosphine)palladium (0.16 g, 0.14 mmol), and 3-(4, 4, 5, 5-tetramethyl-1,3, 2-dioxaborolan-2-yl)phenol (0.93 g, 4.22 mmol) were used, and the reaction was carried out in the same manner. The product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.78 g). p- NMR (DMSO-d 6 ) 2.40(br. s, 4H) , 2.83(t, 2H) , 3.49(t, 4H) , 4.61(t, 2H), 8.27(s, 1H), 8.39(s, 1H) , 8.42(m, 2H) , 8.51(s, 1H) , 8.55(s, 1H) , 8.64(s, 1H), 9.63(s, 1H)

[0373] [Step 3] Synthesis of 3-(5-amino-2-(2-morpholinoethyl)-2H-indazol-6-yl)phenol Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.7 g, 1.90 mmol) was hydrogenated with 0.14 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through Celite, and the filtrate was concentrated to obtain the title compound (0.65 g). P— NMR (DMSO-d 6 ) 2.34(br. s, 4H) , 2.76(t, 2H) , 3.42(t, 4H) , 4.56(s, 2H), 4.55(t, 2H), 8.21(s, 1H) , 8.32(s, 1H) , 8.36(m, 2H) , 8.45(s, 1H) , 8.49(s, 1H), 8.58(s, 1H), 9.57(s, 1H)

[0374] [Step 4] Synthesis of 2-bromo-N-(6-(3-hydroxyphenyl)-2-(2-morpholinoethyl)-2H-indazole—5-yl)thiazole-4-carboxamide Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.2 g, 0.38 mmol), 2-bromothiazole-4-carboxylic acid (0.08 g, 0.38 mmol), HATU (0.29 g, 0.76 mmol), and DI PEA (0.26 mL, 1.52 mmol) were used, and the reaction was carried out in the same manner. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.15 g). P- NMR (DMSO-d 6 ) 2.40(br. s, 4H) , 2.83(t, 2H) , 3.49(t, 4H) , 4.61(t, 2H), 7.43(s, 1H), 8.27(s, 1H) , 8.39(s, 1H) , 8.42(m, 2H) , 8.51(s, 1H) , 8.55(s, 1H), 8.64(s, 1H), 9.63(s, 1H) , 10.0 (s, 1H)

[0375] [Step 5] Synthesis of 2-(6-fluoropyridin-3-yl)-N-(6-(3-hydroxyphenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)thiazole-4-carboxamide (Compound 81) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] (0.14 g, 0.26 mmol), sodium carbonate (0.14 g, 1.32 mmol), tetrakis(triphenylphosphine)palladium (0.02 g, 0.0lmmol), and 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.09 g, 0.40 mmol) were used, and the reaction was carried out in the same manner.

[0376] The title compound (0.07 g) was obtained by purification by MPLC (combiFlash NEXTGEN 300+) and concentration. P— NMR (DMSO-d 6 ) 2.40(br. s, 4H) , 2.83(t, 2H) , 3.49(t, 4H) , 4.61(t,

[0377] 2H), 7.43(s, 1H), 8.27(s, 1H) , 8.39(s, 1H) , 8.42(m, 2H) , 8.45(s, 1H) , 8.51(s, 1H), 8.55(s, 1H), 8.62(m, 2H) , 8.64(s, 1H) , 9.63(s, 1H) , 10.0 (s, 1H)

[0378] LC-MS (ESI, m / z) = 545.0 (M+H+) Example 82. N-(6-(3-hydroxyphenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide

[0379] [Step 4] Synthesis of N-(6-(3-hydroxyphenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 82) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 104 (0.1 g, 0.30 mmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.06 g, 0.30 mmol), HATU (0.22 g, 0.59 mmol), and DI PEA (0.21 mL, 1.18 mmol) were reacted in the same manner, and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (0.11 g) was obtained. P— NMR (DMSO-d 6 ) 2.40 (br. S, 4H) , 2.85 (br. S, 2H), 3.54 (br. S,

[0380] 4H), 9.72 (s, 1H), 9.66 (s, 1H) , 8.98 (s, 1H) , 8.75 (s, 1H) , 8.70 (d, 1H) ,

[0381] 4.55 (br. S, 2H) , 6.87 (s, 1H) , 6.91 (d, 1H) , 6.99 (d, 1H) , 7.35-7.38 (m,

[0382] 1H), 7.48 (s, 1H), 7.56-7.58 (m, 1H), 8.11 (d, 1H), 8.44 (s, 1H), 8.47 (s,

[0383] 1H) LC-MS (ESI, m / z) = 527.0 (M+H+) Example 83. N-(2-(3 -hydroxy- 3 -methylbutyl)- 6-(4-(morpholinomethyl)phenyl)-

[0384] 2H-Indazole-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide

[0385] [Step 2] Synthesis of 2-methyl-4-(6-nitro-6-(4-(morpholinomethyl)phenyl)-5-nitro-2H-indazol-2-yl)butan-2-ol Under the same conditions as [Step 2] of Example 1, the compound of [Step 1] of Example 11

[0386] (1.0 g, 3.05 mmol), sodium carbonate (1.61 g, 15.24 mmol), tetrakis(triphenylphosphine)palladium (0.18 g, 0.15 mmol) and 4-(4-(4, 4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoyl)morpholine (1.39, 4.57 mmol) were used in the same manner. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to give the title compound (1.10 g). P NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.02(t, 2H) , 3.61(br. S, 4H), 3.50(t,

[0387] 4H), 3.61(s, 2H), 4.48-5.10(m, 3H), 7.49- 7.50(d, 2H), 8.12(dt, 1H), 8.44(d,

[0388] 2H), 8.46(s, 1H), 8.66(s, 1H)

[0389] [Step 3] 4-(5-amino-6-(4-(trifluoromethyl)phenyl)- 2H-indazol- 2-yl)-

[0390] 2-Methylbutan-2-ol Synthesis Example 1 Under the same conditions as [Step 3], the compound of [Step 2] (1.0 g,

[0391] 2.36 mmol) was hydrogenated with 0.2 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through celite, and the filtrate was concentrated to obtain the title compound (0.72 g). P— NMR (DMSO-d 6) 1.06(s, 6H) , 1.96(t, 2H) , 3.55(br. S, 4H) , 3.44(t, 4H), 3.55(s, 2H), 4.42- 5.04(m, 3H) , 4.56(s, 2H) , 7.43- 7.54(d, 2H) , 8.06(dt, 1H), 8.38(d, 2H), 8.40(s, 1H) , 8.61(s, 1H)

[0392] [Step 4] Synthesis of N-(2-(3-hydroxy-3-methylbutyl)-6-(4-(morpholinomethyl)phenyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 83) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] (0.11 g, 0.28 mmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.06 g, 0.28 mmol), HATU (0.21 g, 0.56 mmol), and DI PEA (0.19 mL, 1.12 mmol) were reacted in the same manner, and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (0.12 g) was obtained. P— NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.02(t, 2H) , 3.61(br. S, 4H) , 3.50(t, 4H), 3.61(s, 2H), 4.48-5.10(m, 3H) , 7.49- 7.50(d, 4H) , 7.50- 7.52(m, 1H) , 8.12(dt, 1H), 8.44(d, 2H) , 8.46(s, 1H) , 8.66(s, 1H) , 8.71(d, 1H) , 8.90(s, 1H), 9.61(s, 1H)

[0393] LC-MS (ESI, m / z) = 583.0 (M+H+) Example 84. 2-(2-aminopyridin-4-yl)-N-(2-(3-hydroxy-3-methylbutyl)-6-(4-(trifluoromethyl)phenyl)-2H-indazol-5-yl)thiazole-4-carboxamide [Step 1] Synthesis of 4-(6-bromo-5-nitro-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as in Step 1 of Example 1, 6-bromo-5-nitro-2H-indazole (2 g, 8.26 mmol), 20 mL of dimethylformamide, potassium carbonate (4.56 g, 27.30 mmol), potassium iodide (0.14 g, 0.83 mmol), and 4-bromo-2-methyl-2-butanol (2.76 g, 16.53 mmol) were used. The reaction was carried out in the same manner, and the resultant was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.925 g). 6H) , 2.01(t, 2H) , 4.50(s, 1H) , 4.53(m, 2H),

[0394] 8.13(s, 1H), 8.59(s, 1H) , 8.75(s, 1H)

[0395] [Step 2] Synthesis of 2-methyl-4-(5-nitro-6-(4-(trifluoromethyl)phenyl)-2H-indazol-2-yl)butan-2-ol Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] (0.5 g, 1.52 mmol), sodium carbonate (0.81 g, 7.61 mmol), tetrakis(triphenylphosphine)palladium (0.088 g, 0.38 mmol), and 4,4,5,5-tetramethyl-2-(4-(trifluoromethyl)phenyl)-1,3,2-dioxaborolane (0.62 g, 2.29 mmol) were used, and the reaction was carried out in the same manner. After the reaction, the title compound (0.5 g) was obtained by purification by MPLC (combiFlash NEXTGEN 300+) and concentration. Blood— NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.04(t, 2H) , 4.51(s, 1H) , 4.53(m, 2H), 7.56(d, 2H), 7.69(s, 1H) , 7.76(d, 2H) , 8.66(s, 1H) , 8.79(s, 1H)

[0396] [Step 3] Synthesis of 4-(5-amino-6-(4-(trifluoromethyl)phenyl)-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.5 g, 1.27 mmol) was hydrogenated with 0.10 g (0.093 mmol) of palladium on activated carbon. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.4 g). P— NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.04(t, 2H) , 4.51(s, 1H) , 4.53(m, 2H), 6.84(s, 2H), 7.56(d, 2H) , 7.69(s, 1H) , 7.76(d, 2H) , 8.66(s, 1H) , 8.79(s, 1H) [Step 4] 2-Bromo- N- (2- (3-hydroxy- 3-methylbutyl)- 6- (4-

[0397] Synthesis of (trifluoromethyl)phenyl)-2H-indazol-5-yl)thiazole-4-carboxamide Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.4 g, l.lOmmol), 2-bromothiazole-4-carboxylic acid (0.23 g, l.lOmmol), HATU (0.84 g, 2.20 mmol) and DI PEA (0.77 mL, 4.40 mmol) were used, and the reaction was carried out in the same manner. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.5 g). P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.03(t, 2H) , 4.48(t, 2H) , 4.51(s, 1H), 6.83(s, 1H), 7.76(d, 2H) , 7.88(d, 2H) , 8.43(s, 1H) , 8.47(s, 1H) , 8.49(s, 1H) , 9.58(s, 1H)

[0398] [Step 5] Synthesis of 2-(2-aminopyridin-4-yl)-N-(2-(3-hydroxy-3-methylbutyl)-6-(4-(trifluoromethyl)phenyl)-2H-indazol-5-yl)thiazole-4-carboxamide (Compound 84) Under the same conditions as in [Step 2] of Example 1, the compound of [Step 4] (0.5 g, 0.90 mmol), sodium carbonate (0.48 g, 4.52 mmol), tetrakis(triphenylphosphine)palladium (0.05 g, 0.05 mmol) and 4-(4, 4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-

[0399] 2 - The reaction was carried out in the same manner using amine (0.3 g, 1.36 mmol), purified by MPLC (combiFlash NEXTGEN 300+), and concentrated to obtain the title compound (0.3 g). P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.03(t, 2H) , 4.48(t, 2H) , 4.51(s, 1H), 6.21(s, 2H), 6.67(d, 1H) , 6.83(s, 1H) , 7.58(s, 1H) , 7.76(d, 2H) , 7.88(d, 2H) , 7.92(d, 1H), 8.43(s, 1H) , 8.47(s, 1H) , 8.49(s, 1H) , 9.58(s, 1H)

[0400] LC-MS (ESI, m / z) = 567.0 (M+H+) Example 85. N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0401] [Step 2] Synthesis of 4-(2-(6-(4-fluorophenyl)-5-nitro-2H-indazol-2-yl)ethyl)morpholine Under the same conditions as [Step 2] of Example 1, the compound of [Step 1] of Example 104 (1.0 g, 2.82 mmol), sodium carbonate (1.49 g, 14.8 mmol), tetrakis(triphenylphosphine)palladium (0.16 g, 0.14 mmol), and (4-fluorophenyl)boronic acid (0.59 g, 4.22 mmol) were used, and the reaction was carried out in the same manner. The resulting mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.86 g). P- NMR (DMSO-d 6 ) 2.40- 2.41(br . S, 4H) , 2.84(t, 2H) , 3.50- 3.51(m, 4H) , 4.53(t, 2H), 7.39(t, 2H) , 7.67(d, 2H) , 8.44(s, 1H) , 8.52(s, 1H) , 8.57(s, 1H) [Step 3] Synthesis of 6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-amine Under the same conditions as [Step 3] of Example 1, the compound of [Step 2] (0.8 g,

[0402] 2.16 mmol) was hydrogenated with 0.16 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through celite, and the filtrate was concentrated to obtain the title compound (0.61 g). P— NMR (DMSO-d 6 ) 2.35— 2.36(br . S, 4H) , 2.84(t, 2H) , 3.45— 3.46(m, 4H) , 4.51(s, 2H), 4.53(t, 2H) , 7.34(t, 2H) , 7.63(d, 2H) , 8.40(s, 1H) , 8.48(s, 1H) , 8.52(s, 1H)

[0403] [Step 4] Synthesis of N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 85) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.2 g, 0.59 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.12 g, 0.59 mmol), HATU (0.45 g, 1.18 mmol), and DI PEA (0.41 mL, 2.35 mmol) were used, and the reaction was carried out in the same manner. The resultant was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.22 g). Blood— NMR (DMSO-d 6 ) 2.40— 2.41(br . S, 4H) , 2.84(t, 2H) , 3.50— 3.51(m, 4H) , 4.53(t, 2H), 7.31(t, 2H) , 7.39 t, 2H) , 7.51(s, 1H) , 7.55- 7.56(m, 2H) , 7.79- 7.80(m, 2H), 8.36(s, 1H) , 8.43(s, 1H) , 8.60(s, 1H) , 9.54(s, 1H)

[0404] LC-MS (ESI, m / z) = 529.0 (M+H+) Example 86. N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide

[0405] [Step 4] Synthesis of N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 86) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] of Example 85 (0.2 g, 0.59 mmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.12 g, 0.59 mmol), HATU (0.45 g, 1.18 mmol), and DI PEA (0.41 mL, 2.35 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.21 g). Blood— NMR (DMSO-d 6 ) 2.40— 2.41 (br . S, 4H) , 2.84(t, 2H) , 3.50-3 ,51(br . S, 4H), 4.53(t, 2H), 7.32- 7.34(m, 2H) , 7.52- 7.53(m, 1H) , 7.56- 7.57(m, 2H) , 8.09(d, 2H), 8.44(s, 1H) , 8.52(s, 1H) , 8.57(s, 1H) , 8.70(s, 1H) , 8.99(s, 1H) , 9.59(s, 1H)

[0406] LC-MS (ESI, m / z) = 529.0 (M+H+) Example 87. 2-(4-fluorophenyl)-N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)thiazole-4-carboxamide

[0407] [Step 4] Synthesis of 2-(4-fluorophenyl)-N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)thiazole-4-carboxamide (Compound 87) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] of Example 85 (0.2 g, 0.59 mmol), 2-(4-fluorophenyl)thiazole-4-carboxylic acid (0.14 g, 0.59 mmol), HATU (0.45 g, 1.18 mmol), and DI PEA (0.41 mL, 2.35 mmol) were used in the same manner. The reaction mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.22 g). P- NMR (DMSO-d 6 ) 2.40- 2.41 (br S, 4H) , 2.84(t, 2H) , 3.50- 3.51 (m, 4H), 4.53(t, 2H), 7.31(t, 2H) , 7.39(t, 2H) , 7.51(s, 1H) , 7.55- 7.56(m, 2H) , 7.79- 7.80(m, 2H), 8.36(s, 1H) , 8.43(s, 1H) , 8.60(s, 1H) , 9.54(s, 1H)

[0408] LC-MS (ESI, m / z) = 546.0 (M+H+) Example 88. 2-(4-amino-3-fluorophenyl)-N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)thiazole-4-carboxamide

[0409] [Step 4] Synthesis of 2-bromo-N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)thiazole-4-carboxamide Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] of Example 85 (1.0 g, 2.94 mmol), 2-bromothiazole-4-carboxylic acid (0.61 g, 2.94 mmol), HATU (2.23 g, 5.88 mmol), and DI PEA (2.05 mL, 11.8 mmol) were used, and the reaction was carried out in the same manner. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (1.12 g). P— NMR (DMSO-d 6 ) 2.47— 2.48(br . S, 4H) , 2.83(t, 2H) , 3.50— 3.51 (m, 4H) , 4.52(t, 2H), 7.38-7.39(m, 2H) , 7.49(s, 1H) , 7.55- 7.56(m, 2H) , 8.18(s, 1H), 8.42(s, 1H), 8.68(s, 1H) , 9.50(s, 1H)

[0410] [Step 5] Synthesis of 2-(4-amino-3-fluorophenyl)-N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)thiazole-4-carboxamide (Compound 88) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] (0.11 g, 0.21 mmol), sodium carbonate (0.11 g, 1.04 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, 0.01 nmol), and 2-fluoro-4-(4, 4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (0.07 g, 0.31 mmol) were used, and the reaction was performed in the same manner using MPLC (combiFlash NEXTGEN) 300+) and concentrated to give the title compound (0.04 g). P— NMR (DMSO-d 6) 2.47— 2.48(br . S, 4H) , 2.83(t, 2H) , 3.50— 3.51 (m, 4H) , 4.52(t, 2H), 5.85(s, 2H) , 6.79(t, 1H) , 7.28(d, 1H) , 7.30(d, 1H) , 7.38- 7.39(m, 2H), 7.49(s, 1H), 7.55-7.56(m, 2H), 8.18(s, 1H) , 8.42(s, 1H) , 8.68(s, 1H) , 9.50(s, 1H)

[0411] LC-MS (ESI, m / z) = 561.0 (M+H+) Example 89. 2-(3-aminophenyl)-N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)thiazole-4-carboxamide

[0412] [Step 5] Synthesis of 2-(3-aminophenyl)-N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)thiazole-4-carboxamide (Compound 89) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 88 (0.11 g, 0.21 mmol), sodium carbonate (0.11 g, 1.04 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, 0.0lmmol), and 3-(4, 4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (0.07 g, 0.31 mmol) was used, and the reaction was carried out in the same manner as in [Step 2] of Example 1, followed by MPLC (combiFlash NEXTGEN 300+). Purification and concentration gave the title compound (0.05 g). P- NMR (DMSO-d 6) 2.40- 2.41(br . S, 4H) , 2.83(t, 2H) , 3.50- 3.52(m, 4H) , 4.53(t, 2H), 5.30(s, 2H) , 6.69(d, 1H) , 6.83(d, 1H) , 6.96(s, 1H) , 7.10(t, 1H) , 7.37-7.40(t, 2H), 7.50(s, 1H) , 7.54- 7.57(m, 2H) , 8.29(s, 1H) , 8.43(s, 1H) , 8.63(s, 1H), 9.51(s, 1H)

[0413] LC-MS (ESI, m / z) = 543.0 (M+H+) Example 90. 2-(1,3 ■dimethyl- 1H-pyrazol- 4 -yl)- N- (6- (4 -fluorophenyl)- 2- (2 -morpholinoethyl )-2H-indazol- 5 -yl)thiazole- 4 -carboxamide

[0414] [Step 5] Synthesis of 2-(1,3-dimethyl-1H-pyrazol-4-yl)-N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)thiazole-4-carboxamide (Compound 90) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 88 (0.11 g, 0.21 mmol), sodium carbonate (0.11 g, 1.04 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, 0.001 mmol) and 1,3-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.07 g, 0.31 mmol) was used in the same manner, purified by MPLC (combiFlash NEXTGEN 300+), and concentrated to obtain the title compound (0.04 g). P— NMR (DMSO-d 6) 2.09 (s, 3H) , 2.40— 2.41(br . S, 4H) , 2.83(t, 2H) , 3.51-3.52(m, 4H) , 3.78(s, 3H) , 4.52(t, 2H) , 7.34(t, 2H) , 7.47(s, 1H) , 7.50- 7.51(m, 2H), 8.01(s, 1H) , 8.20(s, 1H) , 8.42(s, 1H) , 8.62(s, 1H) , 9.26(s, 1H)

[0415] LC-MS (ESI, m / z) = 546.0 (M+H+) Example 91. 2-(3-fluorophenyl)-N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)thiazole-4-carboxamide [Step 5] Synthesis of 2-(3-fluorophenyl)-N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)thiazole-4-carboxamide (Compound 91) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 88

[0416] (0.11 g, 0.21 mmol), sodium carbonate (0.11 g, 1.04 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, O.Olmmol), and 2-(3-fluorophenyl)-

[0417] The reaction was carried out in the same manner using 4, 4, 5, 5 -tetramethyl- 1,3, 2 -dioxaborolane (0.07 g, 0.31 mmol), purified by MPLC (combiFlash NEXTGEN 300+), and concentrated to obtain the title compound (0.07 g). P— NMR (DMSO-d 6 ) 2.42(br. S, 4H) , 2.83(t, 2H) , 3.52(t, 4H) , 4.53(t, 2H), 7.37(t, 2H), 7.49(s, 1H) , 7.52- 7.57(m, 5H) , 8.20(s, 1H) , 8.43(d, 2H) , 8.61(s, 1H), 9.57(s, 1H)

[0418] LC-MS (ESI, m / z) = 546.0 (M+H+) Example 92. 2-(2-aminopyridin-4-yl)-N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)thiazole-4-carboxamide

[0419] [Step 5] Synthesis of 2-(2-aminopyridin-4-yl)-N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)thiazole-4-carboxamide (Compound 92) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 88 (0.11 g, 0.21 mmol), sodium carbonate (0.11 g, 1.04 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, 0.001 mmol), and 4-(4, 4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (0.07 g, 0.31 mmol) was used, and the reaction was carried out in the same manner as in [Step 2] of Example 1, followed by MPLC (combiFlash) The title compound (0.06 g) was purified and concentrated using NEXTGEN 300+. P— NMR (DMSO-d 6 ) 2.40(br. s, 4H) , 2.84(t, 2H) , 3.52(t, 4H) , 4.53(t, 2H), 6.20(s, 2H), 6.71(d, 1H) , 6.81(s, 1H) , 7.38(t, 3H) , 7.50(s, 1H) , 7.51- 7.55(m, 2H), 7.99(d, 1H) , 8.43(s, 2H) , 8.57(s, 1H) , 9.52(s, 1H)

[0420] LC-MS (ESI, m / z) = 544.0 (M+H+) Example 93. N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)-2-(pyrimidin-5-yl)thiazole-4-carboxamide

[0421] [Step 5] Synthesis of N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)-2-(pyrimidin-5-yl)thiazole-4-carboxamide (Compound 93) Under the same conditions as in [Step 2] of Example 1, the compound of [Step 4] of Example 88 (0.11 g, 0.21 mmol), sodium carbonate (0.11 g, 1.04 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, 0.001 mmol), and 5-(4, 4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (0.06 g, 0.31 mmol) was used, and the reaction was performed in the same manner, followed by MPLC (combiFlash The title compound (0.07 g) was obtained by purification and concentration using NEXTGEN 300+. P— NMR (DMSO-d 6 ) 2.40(br. S, 4H) , 2.84(t, 2H) , 3.52(t, 4H) , 4.54(t, 2H), 7.33(t, 2H), 7.53(s, 1H) , 7.55- 7.56(m, 2H) , 8.44(s, 1H) , 8.49(s, 1H) , 8.52(s, 1H), 9.17(s, 2H) , 9.29(s, 1H) , 9.65(s, 1H)

[0422] LC-MS (ESI, m / z) = 530.0 (M+H+) Example 94. N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)-2-(thiophene-3-yl)thiazole-4-carboxamide

[0423] [Step 5] Synthesis of N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)-2-(thiophene-3-yl)thiazole-4-carboxamide (Compound 94) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 88

[0424] (0.11 g, 0.21 mmol), sodium carbonate (0.11 g, 1.04 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, O.Olmmol) and 4,4,5,5-tetramethyl-2-(thiophene-3-yl)-1,3,2-dioxaborolane (0.07 g, 0.31 mmol) were used in the same manner. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to give the title compound (0.08 g). P— NMR (DMSO-d 6 ) 2.40(br. s, 4H) , 2.84(t, 2H) , 3.52(t, 4H) , 4.54(t, 2H), 7.20-7.26(m, 4H) , 7.49- 7.52(m, 2H) , 7.53(s, 1H) , 7.85(s, 1H) , 8.27(s,

[0425] 1H), 8.48(s, 1H), 8.69(s, 1H), 9.62(s, 1H) LC-MS (ESI, m / z) = 534.0 (M+H+) Example 95. N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)-2-(2-fluoropyridin-3-yl)thiazole-4-carboxamide

[0426] [Step 5] Synthesis of N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)-2-(2-fluoropyridin-3-yl)thiazole-4-carboxamide (Compound 95) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 88

[0427] (0.11 g, 0.21 mmol), sodium carbonate (0.11 g, 1.04 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, O.Olmmol) and 2-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.07 g, 0.31 mmol) were used in the same manner. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to give the title compound (0.07 g). P— NMR (DMSO-d 6 ) 2.40(br. S, 4H) , 2.83(t, 2H) , 3.50(t, 4H) , 4.53(t, 2H), 7.22(t, 1H), 7.37(t, 1H) , 7.45- 7.49(m, 1H), 7.51(s, 1H) , 7.52- 7.58(m, 1H), 8.17(s, 1H), 8.24-8.25(m, 1H) , 8.27(s, 1H) , 8.39(s, 1H) , 8.52(s, 1H) , 8.59(s, 1H), 9.58(s, 1H)

[0428] LC-MS (ESI, m / z) = 547.0 (M+H+) Example 96. N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)-2-(5-methoxypyridin-3-yl)thiazole-4-carboxamide

[0429] [Step 5] Synthesis of N-(6-(4-fluorophenyl)-2-(2-morpholinoethyl)-2H-indazol-5-yl)-2-(5-methoxypyridin-3-yl)thiazole-4-carboxamide (Compound 96) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 88 (0.11 g, 0.21 mmol), sodium carbonate (0.11 g, 1.04 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, 0.001 mmol), and 3-methoxy-5-(4, 4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.07 g, 0.31 mmol) was used, and the reaction was carried out in the same manner. The title compound (0.07 g) was obtained by purification by MPLC (combiFlash NEXTGEN 300+) and concentration. P— NMR (DMSO-d 6 ) 2.40(br. S, 4H) , 2.84(t, 2H) , 3.52(t, 4H) , 3.90(s, 3H), 4.53(t, 2H), 7.30(t, 2H) , 7.51(s, 1H) , 7.56(t, 2H) , 7.67(s, 1H) , 8.41(s, 1H), 8.43(s, 1H), 8.45(s, 1H) , 8.48(s, 1H) , 8.59(s, 1H) , 9.62(s, 1H)

[0430] LC-MS (ESI, m / z) = 559.0 (M+H+) Example 97. N-(6-(4-fluorophenyl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0431] [Step 1] Synthesis of 4-(6-bromo-5-nitro-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 1] of Example 1, 6-bromo-5-nitro-2H-indazole (2 g, 8.26 mmol), 20 mL of dimethylformamide, potassium carbonate (4.56 g, 27.30 mmol), potassium iodide (0.14 g, 0.83 mmol), and 4-bromo-2-methyl-2-butanol (2.76 g, 16.53 mmol) were used. The reaction was carried out in the same manner, and the resultant was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.925 g). 6H) , 2.01(t, 2H) , 4.50(s, 1H) , 4.53(m, 2H),

[0432] 8.13(s, 1H), 8.59(s, 1H) , 8.75(s, 1H)

[0433] [Step 2] Synthesis of 4-(6-(4-fluorophenyl)-5-nitro-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] (0.5 g, 1.52 mmol), sodium carbonate (0.81 g, 7.61 mmol), tetrakis(triphenylphosphine)palladium (0.088 g, 0.38 mmol), and 2-(4-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.32 g, 2.29 mmol) were used, and the reaction was carried out in the same manner. The product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.5 g). P— NMR (DMSO-d 6) 1.12(s, 6H), 2.04(t, 2H), 4.51(s, 1H), 4.53(m, 2H), 7.25(d, 2H), 7.68(d, 2H), 7.69(s, 1H), 8.66(s, 1H), 8.79(s, 1H) [Step 3] 4-(5-amino- 6-(4-fluorophenyl)- 2H-indazol- 2-yl)- 2-methylbutane-

[0434] 2 - Under the same conditions as in [Step 3] of Synthesis Example 1, the compound of [Step 2] (0.5 g, 1.46 mmol) was hydrogenated with 0.10 g (0.093 mmol) of palladium on activated carbon. The compound was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.4 g). P— NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.04(t, 2H) , 4.51(s, 1H) , 4.53(m, 2H), 6.84(s, 2H), 7.25(d, 2H) , 7.68(d, 2H) , 7.69(s, 1H) , 8.66(s, 1H) , 8.79(s, 1H)

[0435] [Step 4] Synthesis of N-(6-(4-fluorophenyl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 97) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.4 g, 1.28 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.23 g, 1.28 mmol), HATU (0.97 g, 2.55 mmol), and DI PEA (0.89 mL, 5.11 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.3 g). Blood— NMR (DMSO-d 6) 1.13(s, 6H) , 2.03(t, 2H) , 4.48(t, 2H) , 4.50(s, 1H), 7.40(t, 2H), 7.56(s, 1H) , 7.57(t, 2H) , 7.68(s, 1H) , 7.69(s, 1H) , 8.44(d, 2H) , 8.58(s, 1H), 8.71(d, 2H) , 9.57(s,lH)

[0436] LC-MS (ESI, m / z) = 502.3 (M+H+) Example 98. 2-(2-aminopyridin-4-yl)-N-(6-(4-fluorophenyl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)thiazole-4-carboxamide

[0437] [Step 4] Synthesis of 2-bromo-N-(6-(4-fluorophenyl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)thiazole-4-carboxamide Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] of Example 97 (0.4 g, 1.28 mmol), 2-bromothiazole-4-carboxylic acid (0.27 g, 1.28 mmol), HATU (0.97 g, 2.55 mmol), and DI PEA (0.89 mL, 5.11 mmol) were used, and the reaction was carried out in the same manner. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.5 g). P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.03(t, 2H) , 4.48(t, 2H) , 4.50(s, 1H), 7.40(t, 2H), 7.56(s, 1H) , 7.57(t, 2H) , 7.68(s, 1H) , 7.69(s, 1H) , 8.58(s, 1H) , 9.57(s,lH)

[0438] [Step 5] Synthesis of 2-(2-aminopyridin-4-yl)-N-(6-(4-fluorophenyl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)thiazole-4-carboxamide (Compound 98) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] (0.5 g, 0.99 mmol), sodium carbonate (0.53 g, 4.97 mmol), tetrakis(triphenylphosphine)palladium (0.06 g, 0.05 mmol), and 4-(4, 4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (0.33 g, 1.49 mmol) were used to carry out the reaction in the same manner. The title compound (0.3 g) was obtained by purification by MPLC (combiFlash NEXTGEN 300+) and concentration. P— NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.02(t, 2H) , 4.47(t, 2H) , 4.50(s, 1H), 6.19(s, 1H), 6.70(d, 1H) , 6.80(s, 1H) , 7.39(t, 1H) , 7.40(t, 2H) , 7.55(s, 1H) , 7.56(t, 2H), 8.00(d, 1H) , 8.43(d, 2H) , 8.56(s, 1H) , 9.52(s, 1H)

[0439] LC-MS (ESI, m / z) = 517.0 (M+H+) Example 99. N-(6-(4-fluorophenyl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(3-(trifluoromethyl)phenyl)thiazole-4-carboxamide

[0440] [Step 5] Synthesis of N-(6-(4-fluorophenyl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(3-(trifluoromethyl)phenyl)thiazole-4-carboxamide (Compound 99) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 98 (0.5 g, 0.99 mmol), sodium carbonate (0.53 g, 4.97 mmol), tetrakis(triphenylphosphine)palladium (0.06 g, 0.05 mmol), and 4,4,5,5-tetramethyl-2-(3-(trifluoromethyl)phenyl)-1,3,2-dioxaborolane (0.41 g, 1.49 mmol) were used. After reaction in the same manner, the product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.3 g). P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.02(t, 2H) , 4.47(t, 2H) , 4.50(s, 1H), 7.33(t, 2H), 7.51(d, 1H) , 7.57(m, 2H) , 7.72(t, 1H) , 7.90(d, 2H) , 8.08(t, 2H) , 8.44(s, 1H), 8.47(s, 2H) , 8.54(s, 1H) , 9.58(s, 1H) LC-MS (ESI, m / z) = 570.1 (M+H+) Example 100. N- (2- (3 -hydroxy- 3 -methylbutyl)- 6-(4-morpholinophenyl)-2H-indazole-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide

[0441] [Step 1] Synthesis of 4-(6-bromo-5-nitro-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 1] of Example 1, 6-bromo-5-nitro-2H-indazole (2 g, 8.26 mmol), 20 mL of dimethylformamide, potassium carbonate (4.56 g, 27.30 mmol), potassium iodide (0.14 g, 0.83 mmol), and 4-bromo-2-methyl-2-butanol (2.76 g, 16.53 mmol) were used. The reaction was carried out in the same manner, and the resultant was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.925 g). 6H) , 2.01(t, 2H) , 4.50(s, 1H) , 4.53(m, 2H),

[0442] 8.13(s, 1H), 8.59(s, 1H) , 8.75(s, 1H)

[0443] [Step 2] Synthesis of 2-methyl-4-(6-(4-morpholinophenyl)-5-nitro-2H-indazol-2-yl)butan-2-ol Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] (0.5 g, 1.52 mmol), sodium carbonate (0.81 g, 7.61 mmol), tetrakis(triphenylphosphine)palladium (0.09 g, 0.08 mmol), and 4-(4-(4, 4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)morpholine (0.66 g, 2.29 mmol) was used, and the reaction was carried out in the same manner. The product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.5 g). Blood— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.03(t, 2H) , 3.20(t, 4H) , 3.76(t, 4H), 4.46(t, 2H), 4.48(s, 1H) , 7.11(d, 2H) , 7.38(d, 2H) , 7.69(s, 1H) , 8.66(s, 1H) , 8.79(s, 1H)

[0444] [Step 3] Synthesis of 4-(5-amino-6-(4-morpholinophenyl)-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.5 g, 1.22 mmol) was hydrogenated with 0.10 g (0.093 mmol) of palladium on activated carbon. The resulting mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.4 g). P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.03(t, 2H) , 3.20(t, 4H) , 3.76(t, 4H), 4.46(t, 2H), 4.48(s, 1H) , 7.11(d, 2H) , 7.38(d, 2H) , 7.43(s, 1H) , 8.40(s, 1H) , 8.47(s, 1H), 8.70(s, 2H)

[0445] [Step 4] Synthesis of N-(2-(3-hydroxy-3-methylbutyl)-6-(4-morpholinophenyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 100) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.4 g, 1.05 mmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.22 g, 1.05 mmol), HATU (0.80 g, 2.10 mmol) and DI PEA (0.73 mL, 4.21 mmol) were reacted in the same manner, and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to give the title compound (0.3 g). Obtained. Blood— NMR (DMSO-d 6) 1.13(s, 6H) , 2.03(t, 2H) , 3.20(t, 4H) , 3.76(t, 4H), 4.46(t, 2H), 4.48(s, 1H) , 7.11(d, 2H) , 7.38(d, 2H) , 7.43(s, 1H) , 7.53(m, 1H) , 8.07(d, 1H), 8.40(s, 1H) , 8.47(s, 1H) , 8.70(s, 1H) , 8.71(s, 1H) , 8.97(s, 1H) , 9.69(s,lH)

[0446] LC-MS (ESI, m / z) = 570.1 (M+H+) Example 101. N- (2- (3 -hydroxy- 3 -methylbutyl)- 6- (6-

[0447] (Trifluoromethyl)pyridin-3-yl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide

[0448] [Step 1] Synthesis of 4-(6-bromo-5-nitro-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 1] of Example 1, 6-bromo-5-nitro-2H-indazole (2 g, 8.26 mmol), 20 mL of dimethylformamide, potassium carbonate (4.56 g, 27.30 mmol), potassium iodide (0.14 g, 0.83 mmol), and 4-bromo-2-methyl-2-butanol (2.76 g, 16.53 mmol) were used. The reaction mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.925 g). 6H) , 2.01(t, 2H) , 4.50(s, 1H) , 4.53(m, 2H),

[0449] 8.13(s, 1H), 8.59(s, 1H) , 8.75(s, 1H)

[0450] [Step 2] Synthesis of 2-methyl-4-(5-nitro-6-(6-(trifluoromethyl)pyridin-3-yl)-2H-indazol-2-yl)butan-2-ol Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] (0.5 g, 1.52 mmol), sodium carbonate (0.81 g, 7.61 mmol), tetrakis(triphenylphosphine)palladium (0.09 g, 0.08 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)pyridine (0.62 g, 2.29 mmol) was used, and the reaction was carried out in the same manner. The product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (0.5 g) was obtained. P— NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.03(t, 2H) , 4.52(s, 1H) , 4.57(t, 2H),

[0451] 7.78(s, 1H), 7.95(d, 1H) , 8.08(d, 1H) , 8.76(s, 1H) , 8.78(s, 1H) , 8.83(s, 1H)

[0452] [Step 3] Synthesis of 4-(5-amino-6-(6-(trifluoromethyl)pyridin-3-yl)-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.5 g, 1.27 mmol) was hydrogenated with 0.10 g (0.093 mmol) of palladium on activated carbon. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.4 g). P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.03(t, 2H) , 4.50(s, 1H) , 4.53(t, 2H),7.50(s, 2H), 7.73(s, 1H) , 7.95(d, 1H) , 8.16(s, 1H) , 8.68(d, 1H) , 8.90(s, 1H), 9.12(s, 1H)

[0453] [Step 4] N- (2- (3 -hydroxy- 3 -methylbutyl)- 6- (6-

[0454] Synthesis of (trifluoromethyl)pyridin-3-yl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 101) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.4 g, l.lOmmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.23 g, l.lOmmol), HATU (0.83 g, 2.20 mmol), and DI PEA (0.76 mL, 4.40 mmol) were used, and the reaction was carried out in the same manner.

[0455] The title compound (0.3 g) was obtained by purification by MPLC (combiFlash NEXTGEN 300+) and concentration. P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.03(t, 2H) , 4.50(s, 1H) , 4.53(t, 2H), 7.50(m, 1H), 7.73(s, 1H) , 7.95(d, 1H) , 8.17(s, 1H) , 8.22(t, 2H) , 8.39(s, 1H) , 8.49(s, 1H), 8.69(d, 1H) , 8.90(s, 1H) , 9.13(s, 1H) , 9.94(s,lH)

[0456] LC-MS (ESI, m / z) = 553.4 (M+H+) Example 102. N-(2-(3-amino-3-oxopropyl)-6-(furan-3-yl)-2H-indazol-5-yl)-2-(6-fluoropyridin-3-yl)thiazole-4-carboxamide

[0457] [Step 1] Synthesis of 3-(6-bromo-5-nitro-2H-indazol-2-yl)propanamide Under the same conditions as in [Step 1] of Example 1, 6-bromo-5-nitro-2H-indazole (2 g, 8.26 mmol), 20 mL of dimethylformamide, potassium carbonate (4.56 g, 27.30 mmol), potassium iodide (0.14 g, 0.83 mmol), and 3-chloropropanamide (1.244 g, 11.56 mmol) were used. The reaction mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.925 g). P— NMR (DMSO-d 6 ) 2.77(t, 2H) , 4.65(t, 2H) , 6.88(s, 1H) , 7.39(s, 1H), 8.12(s, 1H), 8.60(s, 1H), 8.66(s, 1H)

[0458] [Step 2] Synthesis of 3-(6-(furan-3-yl)-5-nitro-2H-indazol-2-yl)propanamide Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] (0.5 g,

[0459] The reaction was carried out in the same manner using sodium carbonate (0.85 g, 7.98 mmol), tetrakis(triphenylphosphine)palladium (0.09 g, 0.08 mmol) and 2-(furan-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.46 g, 2.40 mmol), and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to give the title compound (0.5 g). P— NMR (DMSO-d 6 ) 2.77(t, 2H) , 4.65(t, 2H) , 6.54(s, 1H) , 6.88(s, 1H), 7.39(s, 1H), 7.70(s, 2H) , 7.87(s, 1H) , 8.49(s, 1H) , 8.62(s, 1H)

[0460] [Step 3] Synthesis of 3-(5-amino-6-(furan-3-yl)-2H-indazol-2-yl)propanamide Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.5 g, 1.67 mmol) was hydrogenated with 0.10 g (0.093 mmol) of palladium on activated carbon. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.4 g). P— NMR (DMSO-d 6 ) 2.77(t, 2H) , 4.65(t, 2H) , 6.82(d, 1H) , 6.86(s, 1H), 7.39(s, 1H), 7.64(s, 2H) , 7.75(d, 1H) , 7.92(s, 1H) , 8.10(s, 1H) , 8.30(s, 1H) , 8.36(s, 1H)

[0461] [Step 4] Synthesis of N-(2-(3-amino-3-oxopropyl)-6-(furan-3-yl)-2H-indazol-5-yl)-2-bromothiazole-4-carboxamide Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.4 g, 1.48 mmol), 2-bromothiazole-4-carboxylic acid (0.31 g, 1.48 mmol), HATU (1.13 g, 2.96 mmol), and DI PEA (1.03 mL, 5.92 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.5 g). P— NMR (DMSO-d 6 ) 2.77(t, 2H) , 4.60(t, 2H) , 6.82(d, 1H) , 6.86(s, 1H), 7.39(s, 1H), 7.64(s, 1H) , 7.75(d, 1H) , 7.92(s, 1H) , 8.10(s, 1H) , 8.30(s, 1H) , 8.36(s, 1H), 9.78(s, 1H)

[0462] [Step 5] Synthesis of N-(2-(3-amino-3-oxopropyl)-6-(furan-3-yl)-2H-indazol-5-yl)-2-(6-fluoropyridin-3-yl)thiazole-4-carboxamide (Compound 102) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] (0.5 g, 1.09 mmol), sodium carbonate (0.58 g, 5.43 mmol), tetrakis(triphenylphosphine)palladium (0.06 g, 0.05 mmol), and 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.23 g, 1.63 mmol) were used, and the reaction was carried out in the same manner.

[0463] The title compound (0.3 g) was obtained by purification by MPLC (combiFlash NEXTGEN 300+) and concentration. P— NMR (DMSO-d 6 ) 2.77(t, 2H) , 4.60(t, 2H) , 6.88(s, 2H) , 6.92(s, 1H), 7.39(m, 1H), 7.66(s, 2H) , 7.86(s, 1H) , 8.06(s, 1H) , 8.32(s, 1H) , 8.39(s, 1H) , 8.49(s, 1H), 8.86(s, 1H) , 9.98(s, 1H)

[0464] LC-MS (ESI, m / z) = 477.1 (M+H+) Example 103. N-(2-(4-amino-4-oxobutyl)-6-(furan-3-yl)-2H-indazol-5-yl)-2-(6-fluoropyridin-3-yl)thiazole-4-carboxamide

[0465] [Step 1] Synthesis of 4-(6-bromo-5-nitro-2H-indazol-2-yl)butanamide Under the same conditions as in [Step 1] of Example 1, 6-bromo-5-nitro-2H-indazole (2 g, 8.26 mmol), 20 mL of dimethylformamide, potassium carbonate (4.56 g, 27.30 mmol), potassium iodide (0.14 g, 0.83 mmol), and 4-chlorobutanamide (1.105 g, 9.09 mmol) were used. The reaction mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.96 g). P— NMR (DMSO-d 6 ) 2.00(t, 2H) , 2.08(m, 2H) , 4.47(t, 2H) , 6.73(s, 1H), 7.23(s, 1H), 8.14(s, 1H) , 8.60(s, 1H) , 8.71(s, 1H)

[0466] [Step 2] Synthesis of 4-(6-(furan-3-yl)-5-nitro-2H-indazol-2-yl)butanamide Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] (0.5 g, 1.53 mmol), sodium carbonate (0.81 g, 7.64 mmol), tetrakis(triphenylphosphine)palladium (0.09 g, 0.08 mmol), and 2-(furan-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.44 g, 2.29 mmol) were used, and the reaction was carried out in the same manner. The product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.5 g). P— NMR (DMSO-d 6 ) 2.00(t, 2H) , 2.08(m, 2H) , 4.47(t, 2H) , 6.54(s, 1H), 6.74(s, 1H), 7.23(s, 1H) , 7.70(d, 2H) , 8.14(s, 1H) , 8.49(s, 1H) , 8.67(s, 1H)

[0467] [Step 3] Synthesis of 4-(5-amino-6-(furan-3-yl)-2H-indazol-2-yl)butanamide Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.5 g, 1.59 mmol) was hydrogenated with 0.10 g (0.093 mmol) of palladium on activated carbon. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.4 g). P— NMR (DMSO-d 6 ) 2.00(t, 2H) , 2.10(m, 2H) , 4.40(t, 2H) , 6.72(s, 1H), 6.82(s, 1H), 7.24(s, 1H) , 7.67(s, 1H) , 7.74(s, 2H) , 7.92(s,lH), 8.10(s, 1H) , 8.36(d, 1H), 8.51(d, 1H)

[0468] [Step 4] Synthesis of N-(2-(4-amino-4-oxobutyl)-6-(furan-3-yl)-2H-indazol-5-yl)-2-bromothiazole-4-carboxamide Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.4 g, 1.41 mmol), 2-bromothiazole-4-carboxylic acid (0.29 g, 1.41 mmol), HATU (1.07 g, 2.81 mmol), and DI PEA (0.98 mL, 5.63 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.5 g). P— NMR (DMSO-d 6 ) 2.00(t, 2H) , 2.10(m, 2H) , 4.40(t, 2H) , 6.73(s, 1H), 6.82(s, 1H), 7.24(s, 1H) , 7.67(s, 1H) , 7.74(s, 1H) , 7.92(s, 1H) , 8.10(s, 1H) , 8.35(d, 1H), 8.51(d, 1H) , 9.97(s, 1H)

[0469] [Step 5] Synthesis of N-(2-(4-amino-4-oxobutyl)-6-(furan-3-yl)-2H-indazol-5-yl)-2-(6-fluoropyridin-3-yl)thiazole-4-carboxamide (Compound 103) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] (0.5 g, 1.05 mmol), sodium carbonate (0.56 g, 5.27 mmol), tetrakis(triphenylphosphine)palladium

[0470] (0.06 g, 0.05 nmol) and 2-fluoro-5-(4, 4, 5, 5-tetramethyl-1,3, 2-dioxaborolan-2-yl)pyridine (0.35 g, 1.58 mmol) were used in the same manner.

[0471] The title compound (0.3 g) was obtained by purification by MPLC (combiFlash NEXTGEN 300+) and concentration. P— NMR (DMSO-d 6 ) 2.01(t, 2H) , 2.10(t, 2H) , 4.40(t, 2H) , 6.74(s, 2H), 6.92(s, 1H), 7.24(s, 2H) , 7.70(s, 1H) , 7.86(s, 1H) , 8.06(s, 1H) , 8.32(s, 1H) , 8.39(s, 1H), 8.40(s, 1H) , 8.49(s, 1H) , 8.86(s, 1H) , 9.98(s, 1H)

[0472] LC-MS (ESI, m / z) = 491.0 (M+H+) Example 104. N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(3-hydroxyphenyl)thiazole-4-carboxamide

[0473] [Step 5] Synthesis of N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(3-hydroxyphenyl)thiazole-4-carboxamide (Compound 104) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 47 was synthesized.

[0474] (0.1 g, 0.21 mmol), sodium carbonate (0.11 g, 1.05 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, O.Olmmol) and 3-(4, 4, 5, 5-tetramethyl-1,3, 2-dioxaborolan-2-yl)phenol (0.07 g, 0.32 mmol) were used in the same manner. The reaction mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to give the title compound (0.10 g). P— NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.92 (t, 2H) , 4.45— 4.49(m, 3H) , 6.92- 6.93(m, 1H), 7.32-7.37(m, 3H) , 7.65(m, 1H) , 7.86(s, 1H) , 8.04(s, 1H) , 8.21(s,

[0475] 1H), 8.39(s, 1H), 8.40(s, 1H) , 8.46(s, 1H) , 9.81(s, 1H) , 9.91(s, 1H)

[0476] LC-MS (ESI, m / z) = 489.1 (M+H+) Example 105. 2-(4-amino-3-fluorophenyl)-N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)thiazole-4-carboxamide

[0477] [Step 5] Synthesis of 2-(4-amino-3-fluorophenyl)-N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)thiazole-4-carboxamide (Compound 105) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 47 was synthesized.

[0478] (0.1 g, 0.21 mmol), sodium carbonate (0.11 g, 1.05 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, O.Olmmol) and 2-fluoro-4-(4, 4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (0.07 g, 0.32 mmol) were used in the same manner. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to give the title compound (0.07 g). P— NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.02(t, 2H) , 4.45— 4.48(m, 3H) , 5.84(s, 2H), 6.82(t, 1H), 6.90(s, 1H) , 7.44(d, 1H) , 7.56(d, 1H) , 7.64(s, 1H) , 7.84(t, 1H), 8.07(s, 1H), 8.21(s, 1H) , 8.39(s, 1H) , 8.49(s, 1H) , 9.92(s, 1H)

[0479] LC-MS (ESI, m / z) = 506.1 (M+H+) Example 106. N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-morpholinothiazole-4-carboxamide

[0480] [Step 5] Synthesis of N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-morpholinothiazole-4-carboxamide (Compound 106) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 47 (0.1 g, 0.21 mmol), sodium carbonate (0.11 g, 1.05 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, 0.001 mmol), and 4-(4, 4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)morpholine (0.07 g, 0.32 mmol) was used, and the reaction was performed in the same manner as in [Step 2] of Example 1, followed by MPLC (combiFlash NEXTGEN). 300+) and concentrated to obtain the title compound (0.07 g). 6H) , 2.01(t, 2H) , 3.25(t, 4H) , 3.70(t, 4H),

[0481] 4.43(t, 2H), 4.47(s, 1H) , 6.81(s, 1H) , 7.55(s, 1H) , 7.57(s, 1H) , 7.84(s, 1H) , 7.98(s, 1H), 8.36(s, 1H) , 8.54(s, 1H) , 9.62(s, 1H)

[0482] LC-MS (ESI, m / z) = 482.1 (M+H+) Example 107. N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(4-hydroxypiperidin-1-yl)thiazole-4-carboxamide

[0483] [Step 5] Synthesis of N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-morpholinothiazole-4-carboxamide (Compound 107) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 47 (0.1 g, 0.21 mmol), sodium carbonate (0.11 g, 1.05 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, 0.0lmmol), and 1-(4, 4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)piperidin-4-ol (0.07 g, 0.32 mmol) were used, and the reaction was performed in the same manner as in [Step 2] of Example 1, followed by MPLC (combiFlash). The residue was purified and concentrated using NEXTGEN 300+ to obtain the title compound (0.07 g). 6H) , 1.44(m, 2H) , 1.79(t, 2H) , 2.02(t, 2H),

[0484] 3.16(t, 2H), 3.61(t, 2H), 3.63(m, 1H) , 4.43(t, 2H) , 4.47(s, 1H) , 4.79(d, 1H) , 6.82(s, 1H), 7.47(s, 1H) , 7.57(s, 1H) , 7.82(s, 1H) , 7.99(s, 1H) , 8.36(s, 1H) , 8.56(s, 1H), 9.63(s, 1H)

[0485] LC-MS (ESI, m / z) = 496.1 (M+H+) Example 108. 2-(4-(dimethylamino)piperidin-1-yl)-N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)thiazole-4-carboxamide [Step 5] Synthesis of 2-(4-(dimethylamino)piperidin-1-yl)-N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)thiazole-4-carboxamide (Compound 108) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 47 was prepared.

[0486] (0.1 g, 0.21 mmol), sodium carbonate (0.11 g, 1.05 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, O.Olmmol), and N,N-dimethyl-1-

[0487] (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)piperidin-4-amine (0.08g,

[0488] After the reaction was carried out in the same manner using 0.32 mmol), the product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.07 g). 6H) , 1.42(m, 2H) , 1.81(d, 2H) , 2.02(t, 2H),

[0489] 2.32(m, 1H), 2.99(t, 2H), 3.77(d, 2H), 4.43(t, 2H), 4.47(s, 1H), 6.82(s, 1H), 7.48(s, 1H), 7.57(s, 1H), 7.85(s, 1H) , 7.99(s, 1H) , 8.36(s, 1H) , 8.56(s, 1H) , 9.63(s, 1H)

[0490] LC-MS (ESI, m / z) = 523.1 (M+H+) Example 109. 2-(2-aminopyridin-4-yl)-N-(7-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)thiazole-4-carboxamide

[0491] [Step 1] Synthesis of 4-(7-bromo-5-nitro-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 1] of Example 1, 7-bromo-5-nitro-1H-indazole (2 g, 8.26 mmol), 20 mL of dimethylformamide, potassium carbonate (4.56 g, 27.30 mmol), potassium iodide (0.14 g, 0.83 mmol), and 4-bromo-2-methylbutan-2-ol (2.76 g, 16.53 mmol) were used. The reaction mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (1.16 g). P— NMR (DMSO-d 6 ) 1.14(s, 6H) , 2.07(t, 2H) , 4.49(s, 1H) , 4.51(t, 2H), 8.21(s, 1H), 8.42(s, 1H) , 8.51(s, 1H)

[0492] [Step 2] Synthesis of 4-(7-(furan-3-yl)-5-nitro-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 2] of Example 1, the compound of [Step 1] (0.5 g, 1.52 mmol), sodium carbonate (0.81 g, 7.62 mmol), tetrakis(triphenylphosphine)palladium (0.09 g, 0.08 mmol), and 2-(furan-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.44 g, 2.29 mmol) were used, and the reaction was carried out in the same manner. The product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.5 g). Blood— NMR (DMSO-d 6 ) 1.14(s, 6H) , 2.07(t, 2H) , 4.49(s, 1H) , 4.51(t, 2H), 7.21(d, 1H), 8.06(d, 1H) , 8.21(s, 1H) , 8.42(s, 1H) , 8.51(s, 1H) , 8.58(s, 1H)

[0493] [Step 3] Synthesis of 4-(5-amino-7-(furan-3-yl)-2H-indazol-2-yl)-2-methylbutan-2-ol Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.5 g, 1.59 mmol) was hydrogenated with 0.10 g (0.093 mmol) of palladium on activated carbon. The resulting mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.4 g). P— NMR (DMSO-d 6 ) 1.14(s, 6H) , 2.07(t, 2H) , 4.49(s, 1H) , 4.51(t, 2H),

[0494] 7.11(s, 2H), 7.21(d, 1H), 8.06(d, 1H) , 8.21(s, 1H) , 8.42(s, 1H) , 8.51(s, 1H) , 8.58(s, 1H)

[0495] [Step 4] Synthesis of 2-bromo- N- (7-(furan-3-yl)- 2- (3-hydroxy- 3-methylbutyl)- 2H- indazole— 5-yl) thiazole- 4-carboxamide Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] (0.4 g, 1.40 mmol), 2-bromothiazole- 4-carboxylic acid (0.29 g, 1.40 mmol), HATU (1.07 g, 2.80 mmol), and DI PEA (0.98 mL, 5.61 mmol) were used in the same manner. The reaction mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.5 g). P— NMR (DMSO-d 6 ) 1.14(s, 6H), 2.07(t, 2H), 4.49(s, 1H), 4.51(t, 2H), 7.11(s, 1H), 7.21(d, 1H), 8.06(d, 1H), 8.21(s, 1H), 8.42(s, 1H) , 8.51(s, 1H) , 8.58(s, 1H), 10.14(s, 1H)

[0496] [Step 5] Synthesis of 2-(2-aminopyridin-4-yl)-N-(7-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)thiazole-4-carboxamide (Compound 109) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] (0.5 g, 1.05 mmol), sodium carbonate (0.56 g, 5.26 mmol), tetrakis(triphenylphosphine)palladium (0.06 g, 0.05 mmol), and 4-(4, 4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (0.35 g, 1.58 mmol) were used in the same manner. After the reaction, the compound was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.3 g). P— NMR (DMSO-d 6 ) 1.14(s, 6H) , 2.07(t, 2H) , 4.49(s, 1H) , 4.51(t, 2H), 6.22(s, 2H), 7.06(s, 1H) , 7.11(s, 1H) , 7.21(d, 1H) , 7.78(s, 1H) , 7.82(s, 1H) , 8.06(d, 1H), 8.21(s, 1H) , 8.42(s, 1H) , 8.51(s, 1H) , 8.58(s, 1H) , 10.14(s, 1H)

[0497] LC-MS (ESI, m / z) = 489.1 (M+H+) Example 110. N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(1H-pyrazol-5-yl)thiazole-4-carboxamide

[0498] [Step 5] Synthesis of N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(1H-pyrazol-5-yl)thiazole-4-carboxamide (Compound 110) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] of Example 47 (0.1 g, 0.21 mmol), sodium carbonate (0.11 g, 1.05 mmol), tetrakis(triphenylphosphine)palladium (0.01 g, 0.001 mmol), and 5-(4, 4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.06 g, 0.32 mmol) were used in the same manner. After reaction, the product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.07 g). 6H) , 2.01(t, 2H) , 4.43(t, 2H) , 4.47(s, 1H),

[0499] 6.82(s, 1H), 7.21(m, 1H) , 7.24(m, 1H) , 7.37(s, 1H) , 7.54(s, 1H) , 7.56(s, 1H) , 7.83(s, 1H), 7.99(s, 1H) , 8.35(s, 1H) , 8.53(s, 1H) , 9.64(s, 1H)

[0500] LC-MS (ESI, m / z) = 463.1 (M+H+) Example 111. N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(2-(3-hydroxyphenyl)thiazol-4-yl)acetamide

[0501] [Step 4] Synthesis of 2-(2-bromothiazol-4-yl)-N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)acetamide Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 11 (0.4 g, 1.40 mmol), 2-(2-bromothiazol-4-yl)acetic acid (0.31 g, 1.40 mmol), HATU (1.07 g, 2.80 mmol), and DI PEA (0.98 mL, 5.61 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.5 g). Blood— NMR (DMSO-d 6 ) 1.10(s, 6H) , 2.01(t, 2H) , 3.83(s, 2H) , 4.43(t, 2H), 4.47(s, 1H), 6.80(s, 1H) , 6.82(m, 1H) , 7.3(d, 1H) , 7.64(d, 1H) , 7.78(s, 1H) , 7.95(s, 1H), 8.32(s, 1H) , 9.69(s, 1H)

[0502] [Step 5] Synthesis of N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(2-(3-hydroxyphenyl)thiazol-4-yl)acetamide (Compound 111) Under the same conditions as [Step 2] of Example 1, the compound of [Step 4] (0.5 g, 1.02 mmol), sodium carbonate (0.54 g, 5.11 mmol), tetrakis(triphenylphosphine)palladium (0.06 g, 0.05 mmol), and 3-(4, 4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (0.34 g, 1.53 mmol) were used, and the reaction was carried out in the same manner. The title compound (0.3 g) was obtained by purification by MPLC (combiFlash NEXTGEN 300+) and concentration. P— NMR (DMSO-d 6) 1.10(s, 6H) , 2.01(t, 2H) , 3.83(s, 2H) , 4.43(t, 2H), 4.47(s, 1H), 6.80(s, 1H) , 6.81(m, 1H) , 7.26(t, 1H) , 7.3(d, 2H) , 7.45(s, 1H) , 7.64(d, 2H), 7.78(s, 1H) , 7.96(s, 1H) , 8.32(s, 1H) , 9.42(s, 1H) , 9.69(s, 1H)

[0503] LC-MS (ESI, m / z) = 503.4 (M+H+) Example 112. Methyl 5— (2— (3—hydroxy-1 3—methylbutyl)-1 5— (2— (pyridin ~3~ yl )thiazole- 4 -carboxamido)- 2H -indazol- 6 -yl )nicotinate

[0504] [Step 2] Synthesis of methyl 5-(2-(3-hydroxy-3-methylbutyl)-5-nitro-2H-indazol-6-yl)nicotinate Under the same conditions as [Step 2] of Example 1, the compound of [Step 1] of Example 11 (1.0 g, 3,05 mmol), sodium carbonate (1.61 g, 15.24 mmol), tetrakis(triphenylphosphine)palladium (0.18 g, 0.15 mmol), and methyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinate (1.2 g, 4.57 mmol) were used, and the reaction was carried out in the same manner. The product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (1.01 g) was obtained. P— NMR (DMSO-d 6 ) 1.14(s, 6H) , 2.04(t, 2H) , 3,73(s, 3H) , 4.50— 4.54(m, 3H), 7.72(s, 1H), 8.15(s, 1H) , 8.21(d, 1H) , 8.37(s, 1H) , 8.48(s, 1H) , 8.68(d, 1H)

[0505] [Step 3] Synthesis of methyl 5-(5-amino-2-(3-hydroxy-3-methylbutyl)-2H-indazol-6-yl)nicotinate Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (1.0 g, 2.60 mmole) was hydrogenated with 0.2 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through celite, and the filtrate was concentrated to obtain the title compound (0.81 g). p- NMR (DMSO-d 6 ) 1.09(s, 6H) , 1.99(t, 2H) , 3,68(s, 3H) , 4.45- 4.50(m,

[0506] 3H), 4.59(s, 2H), 7.68(s, 1H) , 8.10(s, 1H) , 8.16(d, 1H) , 8.32(s, 1H) , 8.42(s, 1H), 8.62(d, 1H)

[0507] [Step 4] Synthesis of methyl 5-(2-(3-hydroxy-3-methylbutyl)-5-(2-(pyridin-3-yl)thiazole-4-carboxamido)-2H-indazol-6-yl)nicotinate (Compound 112) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] (0.11 g, 0.31 mmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.06 g, 0.31 mmol), HATU

[0508] (0.24 g, 0.62 mmol) and DI PEA (0.22 mL, 1.24 mmol) were used in the same manner, and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.11 g). P— NMR (DMSO-d 6) 1.14(s, 6H) , 2.04(t, 2H) , 3,73(s, 3H) , 4.50— 4.54(m, 3H), 7.72(s, 1H), 7.78(t, 1H) , 7.82(s, 2H) , 8.02(d, 1H) , 8.15(s, 1H) , 8.34(s, 1H), 8.37(s, 1H), 8.39(s, 1H) , 8.48(s, 1H) , 8.68(d, 1H) , 8.94(s, 1H) , 9.94(s, 1H)

[0509] LC-MS (ESI, m / z) = 543.0 (M+H+) Example 113. N- (2- (3 -hydroxy- 3 -methylbutyl)- 6- (5 -

[0510] (Methylcarbamoyl)pyridin-3-yl)-2H-indazole-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide

[0511] [Step 5] Synthesis of N-(2-(3-hydroxy-3-methylbutyl)-6-(5-(methylcarbamoyl)pyridin-3-yl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 113) The compound of [Step 4] of Example 112 (0.1 g, 0.18 mmole) and N-methylamine in methanol (10 ml) were used, and the reaction was carried out at 120°C for more than 6 hours, and then concentrated. Afterwards, the product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.07 g). P- NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.05(t, 2H) , 2.70(d, 3H) , 4.50- 4.53(m, 3H), 7.53(t, 1H), 7.69(s, 1H) , 8.18(d, 1H) , 8.27(s, 1H) , 8.36(s, 1H) , 8.38(s, 1H), 8.48(s, 1H), 8.61-8.62(m, 1H) , 8.69(d, 1H) , 8.84(s, 1H) , 9.06(s, 1H) , 9.83(s, 1H)

[0512] LC-MS (ESI, m / z) = 542.0 (M+H+) Example 114. Methyl 5—(2—(3—hydroxy-1-3—methylbutyl)-1-5—(2—(pyridin-4~yl)thiazole-4-carboxamido)-2H-indazol-6-yl)nicotinate [Step 4] Synthesis of methyl 5-(2-(3-hydroxy-3-methylbutyl)-5-(2-(pyridin-4-yl)thiazole-4-carboxamido)-2H-indazol-6-yl)nicotinate (Compound 114) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 3] of Example 112 (0.7 g, 1.98 mmol), 2-(pyridin-4-yl)thiazole-4-carboxylic acid (0.41 g, 1.98 mmol), HATU (1.50 g, 3.95 mmol), and DI PEA (1.38 mL, 7.90 mmol) were used in the same manner, followed by MPLC (combiFlash NEXTGEN) 300+) and concentrated to obtain the title compound (0.75 g). P- NMR (DMSO-d 6 ) 1.12(s, 6H), 2.01- 2.04(m, 2H), 4.40- 4.50(m, 2H), 4.48(s, 3H), 4.61(d, 1H), 7.68(d, 1H), 7.75(s, 1H), 8.29(d, 1H) , 8.35(s , 1H) , 8.46(d, 1H) , 8.48(d, 1H) , 8.62(s , 1H) , 8.67(s , 2H) , 8.91(d, 1H) , 9.01(d, 1H) , 9.82(d, 1H)

[0513] LC-MS (ESI, m / z) = 543.0 (M+H+) Example 115. N-(6-(5-carbamoylpyridin-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide

[0514] [Step 5-2] N-(6-(5-carbamoylpyridin-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide(compound

[0515] 115)The compound (0.1 g, 0.18 mmole) of [Step 4] of Synthetic Example 112 and ammonia in methanol (7 N) (10 ml) were reacted at 100°C for more than 12 hours, and then concentrated. Afterwards, the product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.02 g). P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.04(t, 2H) , 4.48— 4.51(m, 3H) , 7.38(s, 1H), 7.54-7.57(m, 2H) , 7.61(t, 1H) , 7.69(d, 1H) , 8.02- 7.97(m, 3H) , 8.44(s, 1H), 8.45(s, 1H), 8.62(s, 1H) , 8.68(d, 1H) , 8.93(s, 1H) , 9.60(s, 1H)

[0516] LC-MS (ESI, m / z) = 528.0 (M+H+) Example 116. N- (6- (5- (hydrazinecarbothyl) pyridin- 3 -yl)- 2- (3 -hydroxy-

[0517] 3 ■Methylbutyl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0518] [Step 4-2] Synthesis of N-(6-(5-(hydrazinecarbothyl)pyridin-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 116) The compound of [Step 4] of Example 114 (0.1 g, 0.18 mmole), methanol (6 mL), and hydrazine hydrate (4 mL) were used, and the reaction was conducted at 100°C for more than 12 hours, followed by concentration. The resulting mixture was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.03 g). P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.05(t, 2H) , 4.50— 4.53(m, 5H) , 7.68(s, 1H), 7.76(d, 1H), 8.30(s, 1H) , 8.31(s, 1H) , 8.47(d, 2H) , 8.72(d, 2H) , 8.84(s,

[0519] 1H), 9.03(s, 1H), 9.80(s, 1H) , 9.99(s, 1H) , 10.2(s, 1H)

[0520] LC-MS (ESI, m / z) = 543.0 (M+H+) Example 117. N-(6-(5-((2-amino-2-oxoethyl)carbamoyl)pyridin-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide

[0521] [Step 5] Synthesis of 5-(2-(3-hydroxy-3-methylbutyl)-5-(2-(pyridin-4-yl)thiazole-4-carboxamido)-2H-indazol-6-yl)nicotinic acid Compound of [Step 4] of Example 114 (0.7 g, 1.98 mmole), tetrahydrofuran

[0522] (7 mL) and 2N sodium hydroxide aqueous solution (7 mL) were added and stirred at room temperature for more than 3 hours. After completion of the reaction, 2N hydrochloric acid aqueous solution was added to adjust the pH to 4-5, concentrated, filtered, washed with purified water, and dried to obtain the title compound (0.49 g). P— NMR (DMSO-d 6 ) 1.13(s, 6H), 2.03(t, 2H), 4.50(s, 1H), 4.53(t, 2H),

[0523] 7.72(s, 1H), 7.79(d, 1H), 8.16(s, 1H), 8.44(s, 1H), 8.49(s, 1H), 8.71(s, 3H),

[0524] 8.72(d, 1H), 8.90(d, 1H) , 9.08(d, 1H) , 9.94(s,lH), 11.37(s, 1H)

[0525] [Step 6] N-(6-(5-((2-amino-2-oxoethyl)carbamoyl)pyridin-3-yl)-2-

[0526] Synthesis of (3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 117) Under the same conditions as in [Step 2] of Example 82, the compound of [Step 5] (0.1 g, 0.18 mmol), methylene chloride (1 ml), glycinamide hydrochloride (0.02 g, 0.18 mmol), EDC - HC1 (0.05 g, 0.27 mmol), and HOBt - H20 (0.04 g, 0.27 mmol) was used, and the reaction was carried out in the same manner. The residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.08 g). P— NMR (DMSO-d 6) 1.13(s, 6H) , 2.03(t, 2H) , 3.63(t, 2H) , 4.50(s, 1H), 4.53(t, 2H), 7.70(s, 1H) , 7.77(d, 2H) , 8.01(s, 2H) , 8.28(s, 1H) , 8.47(s, 1H) , 8.49(d, 2H), 8.71(d, 2H) , 8.86(d, 1H) , 9.10(s, 2H) , 9.87(s, 1H)

[0527] LC-MS (ESI, m / z) = 585.3 (M+H+) Example 118. 2-(4-fluorophenyl)-N-(6-(4-((furan-3-ylmethyl)carbamoyl)phenyl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)thiazole-4-carboxamide

[0528] [Step 2] N-(furan- 3 -ylmethyl)- 4-(2-(3 -hydroxy- 3 -methylbutyl)- 5 -nitro-

[0529] Synthesis of 2H-indazol-6-yl)benzamide Under the same conditions as [Step 2] of Example 1, the compound of [Step 1] of Example 11

[0530] (1.0 g, 3.05 mmol), sodium carbonate (1.61 g, 15.24 mmol), tetrakis(triphenylphosphine)palladium (0.18 g, 0.15 mmol), and N-(furan-3-ylmethyl)-4-

[0531] The reaction was carried out in the same manner using (4, 4, 5, 5 -tetramethyl- 1,3, 2 -dioxaborolan- 2 -yl)benzamide (1.5 g, 4.57 mmol), and the resulting product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (1.18 g). 6H) , 2.04(t, 2H) , 4.50(s, 1H) , 4.56(t, 2H),

[0532] 6.26(s, 1H), 6.37(s, 1H), 7.42(d, 2H), 7.55(s, 1H), 7.66(s, 1H), 7.89(s, 1H), 7.90(s, 1H), 8.61(s, 1H), 8.77(s, 1H) , 9.02(t, 1H)

[0533] [Step 3] Synthesis of 4-(5-amino-2-(3-hydroxy-3-methylbutyl)-2H-indazol-6-yl)-N-(furan-3-ylmethyl)benzamide Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (1.0 g, 2.23 mmol) was hydrogenated with 0.2 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through celite, and the filtrate was concentrated to obtain the title compound (0.77 g). P— NMR (DMSO-d 6 ) 1.07(t, 6H) , 1.97(t, 2H) , 4.45(s, 1H) , 4.52(t, 2H), 4.56(s, 2H), 6.21(s, 1H) , 6.30(s, 1H) , 7.36(d, 2H) , 7.50(s, 1H) , 7.61(s, 1H) , 7.83(s, 1H), 7.84(s, 1H) , 8.56(s, 1H) , 8.72(s, 1H) , 8.96(t, 1H)

[0534] [Step 4] Synthesis of 2-(4-fluorophenyl)-N-(6-(4-((furan-3-ylmethyl)carbamoyl)phenyl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)thiazole-4-carboxamide (Compound 118) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] (0.20 g, 0.48 mmol), 2-(4-fluorophenyl)thiazole-4-carboxylic acid (0.11 g, 0.48 mmol), HATU (0.36 g, 0.96 mmol), and DI PEA (0.33 mL, 1.91 mmol) were used in the same manner to obtain the title compound, which was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated. (0.20 g) was obtained. P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.03(t, 2H) , 4.48— 4.53(m, 5H) , 6.27(d, 1H), 6.36(d, 1H), 7.24(m, 3H) , 7.52(s, 1H) , 7.64- 7.65(m, 2H) , 7.67- 7.69(m, 2H), 8.11(d, 2H), 8.37(s, 1H) , 8.45(s, 1H) , 8.71(s, 1H) , 9.13 (t, 1H) , 9.56(s, 1H)

[0535] LC-MS (ESI, m / z) = 624.0 (M+H+) Example 119. Methyl (4-(2-(3-hydroxy-3-methylbutyl)-5-(2-(pyridin-3-yl)thiazole-4-carboxamido)-2H-indazol-6-yl)benzoyl)glycinate

[0536] [Step 2] Synthesis of methyl (4-(2-(3-hydroxy-3-methylbutyl)-5-nitro-2H-indazol-6-yl)benzoyl)glycinate Under the same conditions as [Step 2] of Example 1, the compound of [Step 1] of Example 11 (1.0 g, 3.05 mmol), sodium carbonate (1.61 g, 15.24 mmol), tetrakis(triphenylphosphine)palladium (0.18 g, 0.15 nmol), and (4-((2-methoxy-2-oxoethyl)carbamoyl)phenyl)boronic acid (1.08 g, 4.57 mmol) were used, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound. (0.86 g) was obtained. P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.04(t, 2H) , 3.64(s, 3H) , 4.05(t, 2H), 4.48- 4.51(t, 3H), 7.66(d, 2H) , 8.03(d, 2H) , 8.44(s, 1H) , 8.56(s, 1H) , 8.66(s, 1H), 9.06(t, 1H)

[0537] [Step 3] Synthesis of methyl (4-(5-amino-2-(3-hydroxy-3-methylbutyl)-2H-indazol-6-yl)benzoyl)glycinate Under the same conditions as in [Step 3] of Example 1, the compound of [Step 2] (0.8 g, 1.82 mmol) was hydrogenated with 0.16 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through Celite, and the filtrate was concentrated to obtain the title compound (0.63 g). P— NMR (DMSO-d 6 ) 1.07(s, 6H) , 1.98(t, 2H) , 3.58(s, 3H) , 3.98(t, 2H), 4.42— 4.48(t, 3H), 4.54(s, 2H) , 7.60(d, 2H) , 7.98(d, 2H) , 8.38(s, 1H) , 8.50(s, 1H), 8.61(s, 1H), 9.01(t, 1H)

[0538] [Step 4] Synthesis of methyl (4-(2-(3-hydroxy-3-methylbutyl)-5-(2-(pyridin-3-yl)thiazole-4-carboxamido)-2H-indazol-6-yl)benzoyl)glycinate (Compound 119) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] (0.6 g, 1.46 mmol), 2-(pyridin-3-yl)thiazole-4-carboxylic acid (0.32 g, 1.46 mmol), HATU (1.11 g, 2.92 mmol), and DI PEA (1.02 mL, 5.85 mmol) was reacted in the same manner, and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (0.60 g) was obtained. P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.04(t, 2H) , 3.64(s, 3H) , 4.05(t, 2H), 4.48- 4.51(t, 3H), 7.49- 7.50(m, 1H) , 7.56(s, 1H) , 7.66(d, 2H) , 7.91- 7.92(m, 1H), 8.03(d, 2H), 8.44(s, 1H) , 8.46(s, 1H) , 8.56(s, 1H) , 8.66(d, 1H) , 9.02(d,

[0539] 1H), 9.06(t, 1H), 9.69(s, 1H) LC-MS (ESI, m / z) = 599.0 (M+H+) Example 120. N-(2-(3 -hydroxy- 3 -methylbutyl)- 6-(4-((2-(methylamino)- 2-oxoethyl)carbamoyl)phenyl)- 2H-indazol- 5 -yl)- 2-(pyridin- 3 -yl)thiazole- 4-carboxamide

[0540] [Step 5-2] Synthesis of N-(2-(3-hydroxy-3-methylbutyl)-6-(4-((2-(methylamino)-2-oxoethyl)carbamoyl)phenyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 120) Under the same conditions as [Step 5] of Example 43, the compound of [Step 4] of Example 119 (0.1 g, 0.17 mmol) and N-methylamine in methanol (10 ml) were used, and the reaction was carried out at 120°C for more than 6 hours, and then concentrated. Afterwards, the mixture was purified by MPLC (combi Flash NEXTGEN 300+) and concentrated to obtain the title compound (0.08 g). P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.04(t, 2H) , 2.60(d, 3H) , 3.86(d, 2H), 4.48- 4.51(m, 3H) , 7.50- 7.51(m, 1H) , 7.55(s, 1H) , 7.65(d, 2H) , 7.83- 7.84(m, 1H), 7.95(d, 1H), 8.05(d, 2H) , 8.45(s, 1H) , 8.57(s, 1H) , 8.65 (d, 1H) , 8.88(t, 1H), 9.00(s, 1H), 9.69(s, 1H)

[0541] LC-MS (ESI, m / z) = 598.0 (M+H+) Example 121. (4- (2- (3 -hydroxy- 3 -methylbutyl)- 5- (2- (pyridin- 3 -yl)thiazole-

[0542] 4-carboxamido)- 2H-indazole- 6-yl)benzoyl)glycine

[0543] [Step 5] Synthesis of (4-(2-(3-hydroxy-3-methylbutyl)-5-(2-(pyridin-3-yl)thiazole-4-carboxamido)-2H-indazol-6-yl)benzoyl)glycine (Compound 121) Under the same conditions as in [Step 5] of Example 60, the compound of [Step 4] of Example 119 (0.5 g, 0.84 mmol), tetrahydrofuran (lOmL) and 2N sodium hydroxide aqueous solution (5 mL) were added and stirred at room temperature for more than 3 hours. After completion of the reaction, 2N hydrochloric acid aqueous solution was added to adjust the pH to 4-5, concentrated, filtered, washed with purified water and dried to obtain the title compound (0.38 g). P— NMR (DMSO-d 6 ) 1.28(s, 6H) , 2.20(t, 2H) , 4.17(s, 2H) , 4.65(t, 2H), 4.81(s, 1H), 7.63(s, 1H) , 7.70(d, 2H) , 8.09(d, 2H) , 8.22— 8.24(m, 1H) , 8.48(s, 1H), 8.52(s, 1H), 8.75(s, 1H) , 8.80(d, 1H) , 8.92(d, 1H) , 9.16(s, 1H) , 9.74(s, 1H), 12.1(s, 1H)

[0544] LC-MS (ESI, m / z) = 585.0 (M+H+) Example 122. N-(6-(4-((2-amino-2-oxoethyl)carbamoyl)phenyl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide

[0545] [Step 6] Synthesis of N-(6-(4-((2-amino-2-oxoethyl)carbamoyl)phenyl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide (Compound 122) Under the same conditions as [Step 6] of Example 117, the compound of [Step 5] of Example 121 (0.3 g, 0.51 mmol), methylene chloride (3 ml), ammonia in methanol (7 N) (1 ml), EDC - HC1 (0.15 g, 0.76 mmol), and HOBt - H20 (0.1 g, 0.76 mmol) was reacted in the same manner, and then purified by MPLC (combiFlash NEXTGEN 300+). The title compound (0.22 g) was obtained by concentration. P- NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.04(t, 2H) , 3.84(t, 2H) , 4.47- 4.50(m, 3H), 7.11(s, 1H), 7.44(s, 1H) , 7.52- 7.54(m, 1H) , 7.54(s, 1H) , 7.65(d, 2H) , 7.96(d, 1H), 8.06(d, 2H) , 8.45(s, 2H) , 8.60(s, 1H) , 8.64(d, 1H) , 8.83(t, 1H) , 8.96(s, 1H), 9.68(s, 1H)

[0546] LC-MS (ESI, m / z) = 584.0 (M+H+) Example 123. N-(6-(4-((2-amino-2-oxoethyl)carbamoyl)phenyl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-phenylthiazole-4-carboxamide

[0547] [Step 2] Synthesis of methyl 4-(2-(3-hydroxy-3-methylbutyl)-5-nitro-2H-indazol-6-yl)benzoate Under the same conditions as [Step 2] of Example 1, the compound of [Step 1] of Example 1 (2.0 g, 6.09 mmol), sodium carbonate (3.23 g, 30.47 mmol), tetrakis(triphenylphosphine)palladium (0.35 g, 0.30 mmol) and methyl 4-(4, 4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (2.40 g, 9.14 mmol) were used, and the reaction was carried out in the same manner. The product was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound. (1.68 g) was obtained. P— NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.02— 2.05(m, 2H) , 4.05(s, 3H) , 4.47— 4.50(m, 3H), 7.46— 7.47(m, 2H) , 8.10(d, 2H) , 8.31(s, 1H) , 8.45(s, 1H) , 8.70(s, 1H)

[0548] [Step 3] Synthesis of 4-(2-(3-hydroxy-3-methylbutyl)-5-nitro-2H-indazol-6-yl)benzoic acid The compound of [Step 2] (1.6 g, 4.17 mmol), tetrahydrofuran (16 mL), and 2 N sodium hydroxide aqueous solution (8 mL) were added and stirred at room temperature for more than 3 hours. After completion of the reaction, 2 N hydrochloric acid aqueous solution was added to adjust the pH to 4-5, concentrated, filtered, washed with purified water, and dried to obtain the title compound (1.05 g). p- NMR 6H) , 2.01- 2.04(m, 2H) , 4.45- 4.48(m, 3H) , 7.44— 7.45(m, 2H) , 8.08(d, 2H) , 8.28(s, 1H) , 8.42(s, 1H) , 8.68(s, 1H) , 11.9(s,

[0549] 1H)

[0550] [Step 4] Synthesis of N-(2-amino-2-oxoethyl)-4-(2-(3-hydroxy-3-methylbutyl)-5-nitro-2H-indazol-6-yl)benzamide Under the same conditions as in [Step 6] of Example 117, the compound of [Step 3] (1.0 g, 2.71 mmol), methylene chloride (10 ml), glycinamide hydrochloride (0.3 g, 2.71 mmol), EDC - HC1 (0.78 g, 4.07 mmol), and HOBt - H20 (0.55 g, 4.07 mmol) was used, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.28 g). P- NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.02- 2.05(m, 2H) , 3.87(d, 2H) , 4.47- 4.50(m, 3H), 7.46- 7.47(m, 2H) , 7.65- 7.67(m, 4H) , 8.10(d, 2H) , 8.31(s, 1H), 8.45(s, 1H), 8.70(s, 1H) , 8.80(t, 1H)

[0551] [Step 5] Synthesis of 4-(5-amino-2-(3-hydroxy-3-methylbutyl)-2H-indazol-6-yl)-N-(2-amino-2-oxoethyl)benzamide Under the same conditions as in [Step 3] of Example 1, the compound of [Step 4] (0.25 g, 0.59 mmol) was hydrogenated with 0.05 g (0.2 w / w) of palladium on activated carbon. The reaction mixture was filtered through Celite, and the filtrate was concentrated to obtain the title compound (0.19 g). P- NMR (DMSO-d 6) 1.07(s, 6H) , 1.97- 1.99(m, 2H) , 3.81(d, 2H) , 4.41- 4.43(m, 3H), 4.56(s, 2H) , 7.40- 7.41(m, 2H) , 7.60- 7.62(m, 4H) , 8.05(d, 2H), 8.26(s, 1H), 8.40(s, 1H) , 8.66(s, 1H) , 8.72(t, 1H)

[0552] [Step 6] Synthesis of N-(6-(4-((2-amino-2-oxoethyl)carbamoyl)phenyl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-phenylthiazole-4-carboxamide (Compound 123) Under the same conditions as in [Step 4] of Example 1, the compound of [Step 5] (0.09 g, 0.23 mmol), 2-phenylthiazole-4-carboxylic acid (0.05 g, 0.23 mmol), HATU (0.17 g, 0.46 mmol), and DI PEA (0.16 mL, 0.91 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.10 g). P- NMR (DMSO-d 6 ) 1.13(s, 6H) , 2.02- 2.05(m, 2H) , 3.87(d, 2H) , 4.47- 4.50(m, 3H), 7.05(s, 1H) , 7.38(s, 1H) , 7.46- 7.47(m, 3H) , 7.54(s, 1H) , 7.65- 7.67(m, 4H), 8.10(d, 2H) , 8.31(s, 1H) , 8.45(s, 1H) , 8.70(s, 1H) , 8.80(t, 1H) , 9.62(s, 1H)

[0553] LC-MS (ESI, m / z) = 583.1 (M+H+) Example 124. N-(6-(4-((2-amino-2-oxoethyl)carbamoyl)phenyl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(trifluoromethyl)thiazole-4-carboxamide

[0554] [Step 6] Synthesis of N-(6-(4-((2-amino-2-oxoethyl)carbamoyl)phenyl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-(trifluoromethyl)thiazole-4-carboxamide (Compound 124) Under the same conditions as [Step 4] of Example 1, the compound of [Step 5] of Example 123 was prepared.

[0555] (0.09g, 0.23mmol), 2-(trifluoromethyl)thiazole-4-carboxylic acid (0.05g,

[0556] The reaction was carried out in the same manner using HATU (0.17 g, 0.46 mmol) and DI PEA (0.16 mL, 0.91 mmol), and the residue was purified by MPLC (combiFlash NEXTGEN 300+) and concentrated to obtain the title compound (0.09 g). P- NMR (DMSO-d 6 ) 1.12(s, 6H) , 2.02- 2.04(m, 2H) , 3.78(br. s, 2H) , 4.49(br. s, 3H) , 6.99(s, 1H) , 7.31- 7.33(m, 2H) , 7.55- 7.56(m, 2H) , 7.88- 7.89(m, 2H), 8.07(s, 1H), 8.44(d, 1H) , 8.63- 8.64(m, 2H) , 9.88(s, 1H)

[0557] LC-MS (ESI, m / z) = 575.1 (M+H+) Example 125. N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-isopropylthiazole-4-carboxamide

[0558] [Step 4] Synthesis of N-(6-(furan-3-yl)-2-(3-hydroxy-3-methylbutyl)-2H-indazol-5-yl)-2-isopropylthiazole-4-carboxamide (Compound 125) Under the same conditions as [Step 4] of Example 1, the compound of [Step 3] of Example 11 (0.11 g, 0.39 mmol), 2-isopropylthiazole-4-carboxylic acid (0.07 g, 0.39 mmol), HATU (0.29 g, 0.77 mmol), and DI PEA (0.27 mL, 1.54 mmol) were used in the same manner, and the reaction was followed by purification by MPLC (combiFlash NEXTGEN 300+) and concentration to obtain the title compound (0.09 g). 6H) , 1.31(d, 6H) , 2.01(t, 2H) , 3.25(q, 1H),

[0559] 4.44(t, 2H), 4.48(s, 1H) , 6.82(s, 1H) , 7.61(s, 1H) , 7.82(s, 1H) , 8.00(s, 1H) , 8.24(s, 1H), 8.38(s, 1H) , 8.50(s, 1H) , 9.76(s, 1H)

[0560] LC-MS (ESI, m / z) = 439.1 (M+H+)

[0561] <Experimental Example>Evaluation of physiological efficacy Experimental Example 1. IRAK4 enzyme activity inhibition experiment An experiment on the inhibition of IRAK4 enzyme activity of the present compound was conducted.

[0562] Using the IRAK4 enzyme kit (purchased from Promega, product number: V2621), dilute 0.lug / uL of the enzyme substrate, myelin basic protein MBP (Myelin in Basic Protein) and 1.25 mM ATP mixture with reaction buffer (40 mM Tris-HCl, pH 7.5; 20 mM MgCl2; 0.1 mg / mL BSA; 50 uM DTT) according to the instructions and add 2 yAfter dispensing L into a 384-well white plate, the test compound was gradient diluted from ImM and 1 uL was added to the 384-well plate. After diluting the IRAK4 enzyme with reaction buffer to a final concentration of 5 ng / uL, 2 uL / well was dispensed into the 384-well white plate and reacted at 37°C for 60 minutes. After the reaction was completed, 5uL of ADP-Glo ​​reaction reagent was added using the ADP-Glo™ enzyme test kit (purchased from Promega, product number: V9102), and the reaction was performed at 37°C for 40 minutes. Then, 10uL of enzyme color development reagent was added again, and the luminescence signal was measured using an absorbance measurement device (THECA", Microplate Reader). The activity inhibition rate was calculated from the measured value, and the 50% inhibition concentration (IC50 value) was analyzed through nonlinear regression analysis based on the % inhibition at each concentration of the test compound, and is shown in Table 2. [Table 2]

[0563] As can be seen in Table 2 above, the compound of the present invention exhibits excellent IRAK4 inhibitory activity. Experimental Example 2. IRAKI Enzyme Activity Inhibition Experiment The IRAKI enzyme activity inhibition experiment of the compound of the present invention was conducted.

[0564] Using the IRAKI enzyme kit (purchased from Promega, product number: VA7477), dilute 0.lug / uL of the enzyme substrate protein AKT (protein kinase B) and 1.25 mM ATP mixture with reaction buffer (40 mM Tris-HCl, pH 7.5; 20 mM MgCl2; 0.1mg / mL BSA; 50uM DTT) according to the instructions and add 2 yAfter dispensing L into a 384-well white plate, the test compound was gradient diluted from ImM and luL was added to the 384-well white plate. After diluting the IRAKI enzyme with reaction buffer to a final concentration of 5 ng / uL, 2 uL / well was dispensed into the 384-well white plate and reacted at 37°C for 60 minutes. After the reaction, 5uL of ADP-Glo ​​reaction reagent was added using the ADP-G 1 oTM enzyme test kit (purchased from Promega, product number: V9102), and the reaction was performed at 37°C for 40 minutes. Then, 10uL of enzyme color development reagent was added again, and the luminescence signal was measured using an absorbance measurement device (THECA"}, Microplate Reader). The activity inhibition rate was calculated from the measured value, and the 50% inhibition concentration (IC50 value) was analyzed through nonlinear regression analysis based on the % inhibition at each concentration of the test compound, and is shown in Table 3.

[0565] [Table 3] As can be confirmed in Table 3 above, the compound of the present invention exhibits excellent IRAKI inhibitory activity. Experimental Example 3. Cell-based inflammatory cytokine secretion inhibition experiment An inflammatory cytokine secretion inhibition experiment of the present compound was conducted. 1.0 X 10 PBMC (LONZA, peripheral blood mononuclear cells) isolated from human whole blood were 5Cells were seeded into 96-well plates at a density of 10 cells / well and stabilized for 20 hours. Afterwards, test compounds diluted at four different concentrations in RPMI (Roswel 1 Park Memor i al Inst i tute) medium were added and reacted for 1 hour. LPS (Lipopolysaccharide) was treated to a final concentration of 1g / mL and reacted for another hour. hTNF- a, an inflammatory cytokine, was measured by enzyme-linked immunosorbent assay (ELISA) using an ELISA kit from Goma Biotech. Cell supernatant, standard drugs, and antibodies were added to the ELISA plate, and after a total of 4 hours of reaction, the plate was washed, streptavidin-HRP was reacted for 30 minutes, and the plate was washed again. Afterwards, TMB substrate was added and reacted in the dark. When sufficient color development was achieved, the reaction was stopped by adding stop solution. hTNF- a was measured by measuring the absorbance at 450 nM using an absorbance measuring device (BioTeK Microlate Reader). The activity inhibition rate was calculated from the measured absorbance value, and the % inhibition at each concentration of the test compound was calculated. The 50% inhibition concentration (IC50 value) was analyzed through nonlinear regression analysis, and is shown in Table 4.

[0566] [Table 4]

[0567] As can be seen in Table 4 above, the compound of the present invention exhibits an excellent inflammatory cytokine secretion inhibitory effect. While the present invention has been described in detail, it will be apparent to those skilled in the art that such specific descriptions are merely preferred embodiments and that the scope of the present invention is not limited thereby. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims

【Scope of Claims】 【 Claim 11 A compound represented by the formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof: <화학식 1> In the above chemical formula I, Li is a single bond or C1-C6 alkylene, and the following is thiazolidine, Ri is H, C1-C6 alkyl, C3-C8 cycloalkyl, 6-14 membered aryl, 3-12 membered heterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of N, 0 and , 3-12 membered heterocycloalkenyl containing 1 to 3 heteroatoms independently selected from the group consisting of N, 0 and S, or 5-12 membered heteroaryl containing 1 to 3 heteroatoms independently selected from the group consisting of N, 0 and , (C=0)0-(Cl-C6 alkyl) or NRaRb, wherein Ra and Rb are each independently H, 6-14 membered aryl or 5-12 membered heterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of N, 0 and . It is heteroaryl, One or more of the above Ri may be substituted with C1-C6 alkyl, C1-C6 alkoxy, OH, NO2, NRaRb, C(=O)-(C1-C6 alkylene)- OH, CF3 or halogen, and the above Ra and Rb are each independently H or C1-C6 alkyl, Qi and Q2 are each independently N or N- L2- R2, but Qi and Q2 cannot be N at the same time. wherein L2 is C1-C6 alkylene or (C1-C6 alkylene)-O-(C1-C6 alkylene), R2 is a 3- to 12-membered heterocycloalkyl, NRcRd, S02Re, C(=0)NH2 or OH containing 1 to 3 heteroatoms independently selected from the group consisting of N, 0 and S in the ring, and wherein Rc, Rd and Re are each independently H or C1-C6 alkyl, and is a 6- to 14-membered arylene or a 5- to 12-membered heteroarylene containing 1 to 3 heteroatoms independently selected from the group consisting of N, 0 and S in the ring, L3 is a single bond, C1-C6 alkylene, - NH(C=O)-, - (C=0)-, - C(=O)NH- or - (C=0)0-, R3 is a 3-membered ring containing 1 to 3 heteroatoms independently selected from the group consisting of H, halogen, C1-C6 alkyl, N, 0 and 12-membered heterocycloalkyl, NH2, CF3 or 0H, and at least one of R3 may be substituted with a 3-membered to 12-membered heterocycloalkyl containing 1 to 3 heteroatoms in the ring independently selected from the group consisting of OH, C(=0)NH2, C(=O)OH, C(=0)0-(Cl-C6 alkyl), C(=O)NH-(C1-C6 alkyl), N, 0 and or a 5-membered to 12-membered heteroaryl containing 1 to 3 heteroatoms in the ring independently selected from the group consisting of N, 0 and S, and - CH2 - of the heterocycloalkyl of R3 may be substituted with C=0. 【

2. In claim 1, in the chemical formula I, Li is a single bond or C1-C6 alkylene, and the following is thiazolidine, Ri is independently selected from the group consisting of H, C1-C6 alkyl, C3-C8 cycloalkyl, aryl having 6 to 14 ring members, 3- to 12-member heterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of N, O, and S in the ring, 3- to 12-member heterocycloalkenyl containing 1 to 3 heteroatoms independently selected from the group consisting of N, O, and S in the ring, or 5- to 12-member heteroaryl containing 1 to 3 heteroatoms independently selected from the group consisting of N, O, and S in the ring, and one or more of the Ri may be substituted with C1-C6 alkyl, C1-C6 alkoxy, OH, NO2, NRaRb, C(=O)-(C1-C6 alkylene)-OH, CF3, or halogen, where Ra and Rb are each independently H or C1-C6 alkyl, Qi and Q2 are each independently N or N-L2-R2, and Qi and Q2 cannot be N at the same time, Q R2* L2 >O When Q2 is N, the above Q 2 is N, and when ⑴ is N, the above / 〒 N magic Q O 5 Q2 is R2, where L2 is C1-C6 alkylene or (C1-C6 alkylene)-O-(C1-C6 alkylene), and R2 is 3- to 12-member heterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of N, O, and S in the ring, NRcRd, C(=0)NH2, or OH, where Rc and Rd are each independently C1-C6 alkyl, and is 6- to 14-member arylene or 5- to 12-member heteroarylene containing 1 to 3 heteroatoms independently selected from the group consisting of N, O, and S in the ring, L3 is a single bond, C1-C6 alkylene, -(C=0)-, -C(=O)NH-, or -(C=0)0-, R3 is a 3- to 12-membered heterocycloalkyl having 1 to 3 heteroatoms independently selected from the group consisting of H, halogen, C1-C6 alkyl, N, 0 and NH2, CF3 or OH in the ring, and at least one of R3 is independently selected from the group consisting of OH, C(=0)NH2, C(=O)OH, C(=0)0-(Cl-C6 alkyl), C(=O)NH-(C1-C6 alkyl), N, 0 and 218 A compound represented by formula I, which may be substituted with a 3- to 12-membered heterocycloalkyl containing 1 to 3 heteroatoms in the ring or a 5- to 12-membered heteroaryl containing 1 to 3 heteroatoms independently selected from the group consisting of N, 0 and S in the ring, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof. 【

3. In claim 1, in the chemical formula I, Li is a single bond or C1-C2 alkylene, and the following is thiazolidine, Ri is a 5-7 membered heterocycloalkyl having 1 to 3 heteroatoms independently selected from the group consisting of H, C1-C4 alkyl, C5-C7 cycloalkyl, 6-12 membered aryl, N and 0, a 5-7 membered heterocycloalkenyl having 1 to 2 heteroatoms independently selected from the group consisting of N and 0, or a 5-6 membered heteroaryl having 1 to 3 heteroatoms independently selected from the group consisting of N, 0 and , wherein one or more of Ri may be substituted with C1-C3 alkyl, C1-C3 alkoxy, OH, NO2, NRaRb, C(=0)-(C2-C4 alkylene)-OH, CF3, F or Cl, and wherein Ra and Rb are each independently H or It is C1-C3 alkyl, Qi and Q2 are each independently N or N- L2- R2, but Qi and Q2 are simultaneously N. Cannot be, Q Oh R2』 2 >O When Q2 is N, the above Q 2 is N, and when Qi is N, Q / Ke Wu〕 1:, J Q2 is Chi2 hour, wherein L2 is C1-C6 alkylene or (C1-C2 alkylene)-O-(C1-C2 alkylene), and R2 is 1 to independently selected from the group consisting of N and O 4- to 7-membered heterocycloalkyl containing 1 to 3 heteroatoms selected from the group consisting of N and O in the ring, NRcRd, C(=0)NH2 or OH, and Rc and Rd are each independently C1-C3 alkyl, and the following 6- to 12-membered arylene or 1 to 3 heteroatoms independently selected from the group consisting of N, O and S are contained in the ring 5- or 6-membered heteroarylene, L3 is a single bond, C1-C2 alkylene, -(C=0)-, -C(=O)NH- or -(C=0)0-, R3 is H, F, Cl, C1-C3 alkyl, 5- to 7-membered heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of N and O in the ring, NH2, CF3 or OH, and one or more of the following of R3 are OH, C(=0)NH2, C(=O)OH, C(=O)O-(C1-C3 alkyl), C(=O)NH-(C1-C3 alkyl), 5- to 7-membered heterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of N and O in the ring or 5- or 6-membered heteroaryl containing 1 or 2 heteroatoms independently selected from the group consisting of N and O in the ring 220 A compound represented by Chemical Formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, which may be substituted with

4. A compound described in the table below, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof: 【 A pharmaceutical composition comprising, as an active ingredient, a compound according to any one of claims 1 to 4, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof.

6. The pharmaceutical composition according to claim 5, wherein the pharmaceutical composition is for preventing or treating an IRAK-! 4 or IRAK-1 related disease. 【

7. A pharmaceutical composition according to claim 6, wherein the IRAK-4 or IRAK-1 related disease is an autoimmune disease, an inflammatory disease, or a tumor. 230 【

8. A method for preventing or treating an IRAK-4 or IRAK-1 related disease, comprising administering to a subject a compound according to any one of claims 1 to 4, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof. 【Claims Use of a compound according to any one of claims 1 to 4, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof for the prevention or treatment of IRAK-4 or IRAK-1 related diseases.

10. Use of a compound according to any one of claims 1 to 4, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof for the manufacture of a medicament for the prevention or treatment of a disease associated with IRAK-4 or IRAK-1. 231

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