WO2013100672A1 - 3,6-disubstituted indazole derivative having protein kinase inhibiting activity - Google Patents

3,6-disubstituted indazole derivative having protein kinase inhibiting activity Download PDF

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WO2013100672A1
WO2013100672A1 PCT/KR2012/011655 KR2012011655W WO2013100672A1 WO 2013100672 A1 WO2013100672 A1 WO 2013100672A1 KR 2012011655 W KR2012011655 W KR 2012011655W WO 2013100672 A1 WO2013100672 A1 WO 2013100672A1
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methyl
carboxamide
indazole
phenyl
fluoro
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PCT/KR2012/011655
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French (fr)
Korean (ko)
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정경윤
최진석
김민경
박영민
심태보
노은주
진세호
이용실
김선미
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제이더블유중외제약㈜
한국과학기술연구원
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Publication of WO2013100672A1 publication Critical patent/WO2013100672A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
    • C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to a novel 3, 6-disubstituted indazole derivative or a pharmaceutically acceptable salt thereof and a pharmaceutical composition effective for inhibiting protein kinase containing the same as an active ingredient.
  • Protein kinases are enzymes that catalyze the phosphorylation of hydroxy groups located at tyrosine, serine and threonine residues of proteins and play an important role in the growth factor signal transduction that causes cell growth, differentiation and proliferation. Mutations or overexpression of these protein kinases disrupt the normal cellular signaling system (mainly in vivo), leading to a variety of diseases, including cancer, inflammation, metabolic diseases, and brain diseases.
  • Raf is a serine / threonine (Ser / Thr) protein kinase that is responsible for delivering biological signals from activated growth factor receptors in the cell membrane into the nucleus.
  • Raf proteins have three subtypes, A-Raf, B-Raf and C-Raf / Raf—1, which have three conserved regions (CRl, CR2, YV-terminal regulatory domain and C-terminal kinase domain). CR3).
  • CR1 contains a Ras-binding domain (RBD) such as a cysteine-rich domain (CRD), and CR2
  • 14-3-3 protein binds to the ' site (serum # 259 serine, etc.), CR3 contains a catalytic domain, two active-fragmentary phosphorylation sites (491 of Raf-1) Burn threonine and serine 494).
  • C-Raf is expressed in almost all tissues, while A-Raf is expressed mainly in the genitourinary tissues (kidney, uterus and prostate), and B-Raf is mainly expressed in nerves, spleen and hematopoietic tissues.
  • Mutations in B-Raf are approximately related to all human cancers. In particular, mutations of B-Raf have been observed with high frequency in melanoma, a type of skin cancer.
  • the B-Raf-V600E mutant in which valine 600, located at axon 15, is mutated to glutamic acid, is mainly known to cause melanoma.
  • B-Raf-V600E induces hyperactivation of the MAPK kinase signaling system leading to cancer.
  • the reason for the high kinase activity of B-Raf—V600E is as follows. Glutamic acid 600, substituted by point mutation, acts as a phosphate model between the phosphorylation sites (threonine 598 and serine hexavalent) located in the activation segment, resulting in a conformal conformation of the always active B-Raf kinase domain.
  • the B-Rai mutant species identified so far is about Forty individuals have a significantly lower incidence of mutant species other than V600E.
  • B-Raf is always activated when activated H-Ras binds. It is formed through the phosphorylation of serine 445.
  • the phosphorylation of C—Raf serine 338 corresponds to the phosphorylation of B-Raf serine 445.
  • the B—Raf V600E mutant interferes with the self-suppressive mechanism of B-Raf and remains active at all times.
  • B-Raf-V600E mutant species are also found with high frequency in papillary thyroid cancer. At the same time, B-Raf—V600E mutant species are closely associated with colon and uterine cancers.
  • Sorafenib (BAY 43—9006, trade name Nexavar), developed jointly by Bayer and Onyx, strongly inhibits both C-Raf and wild-type or mutant B-Rai. Sorafenib also contains platelet-derived growth factor receptors, vascular endothelial growth factor receptors 1/2/3 and fibroblast growth factor receptors, receptor tyrosine kinases. fibroblast growth factor receptor), Fit-3, c-Kit, and RET block kinase activity. Sorafenib inhibits kinases through a mechanism by which the DGF motif of the kinase domain is stabilized to have an inactive conf ormat ion. Sorafenib
  • Sorafenib was approved in 2005 for the treatment of advanced renal cell carcinoma. Sorafenib's renal cancer treatment is due to the complex inhibition of several kinases including vascular endothelial growth factor receptor 1/2/3 rather than Raf inhibition.
  • the maximum tolerated dose of Sorafenib in phase II trials was 400 mg (twice daily). Sorafenib at 600 mg (twice daily) causes grade 3 skin toxic side effects.
  • a common side effect of Sorafenib is the hand-foot syndrome of skin peeling and redness and edema.
  • Sorafenib was approved for the treatment of Hepatocellular Carcinoma (HCC) in 2008. Sorafenib
  • Sorafenib has been shown to be effective in treating thyroid cancer, hormonal refractory prostate cancer and breast cancer in phase II trials. However, Sorafenib is not effective in treating melanoma, a skin cancer.
  • PLX4720 a derivative of 7-azains from Plexxikon, is 1205Lu.
  • CHIR265 is currently a Phase 1 clinical trial in patients with melanoma
  • a substituent-substituted at the same time as the present invention is substituted at the C3 and C6 positions of the indazole parent nucleus, and a carboxamido group is particularly substituted at the C3 position.
  • Substituted indazole compounds have not been synthesized.
  • Another object of the present invention to provide a pharmaceutical composition for the prevention and treatment of abnormal cell growth diseases containing the novel compounds as an active ingredient.
  • a ⁇ - is an arylene group; Biarylene group; Divalent heteroaromatic ring groups; Or 2
  • Ar 2 is a single bond line; Arylene group; Biarylene group; Divalent heteroaromatic ring groups; Or a divalent heteroaliphatic ring group,
  • X and L are the same or different from each other and are a single bond line; C (0)-; -NR 5- ;
  • R 1 and R 2 are the same as or different from each other and are a hydrogen atom; — N0 2 ; -OR "; -NR3 ⁇ 4 fi ; -NR 5 C (0) R 8 ;
  • R 1 and R 2 are bonded to each other heteroaromatic ring group
  • R 3 is a hydrogen atom; Halogen atom; CN; -N0 2 ; -OR 4 ; -SR 4 ; -NR 5 R R ; -NR 5 (CC 10 alkylene-OR 4 ); -NR ⁇ dd ,, alkylene -NR ⁇ ); -NR : '(heteroaliphatic ring); (heteroaromatic ring); -NR 5 (CC 10 alkylene-heteroaliphatic ring); -NR r ' ( CC 10 alkylene-heteroaromatic ring); -NR ⁇ dC, alkylene-heteroaromatic ring); ⁇ NR3 ⁇ 4 (0) -heteroaliphatic ring; one NR3 ⁇ 4 (0) -heteroaromatic ring; — NR (0) R 8 ; -NR3 ⁇ 4 (0) 0R, -NR 5 C (0)-(C r C 1 ()
  • Alkylene—NR : ⁇ ); -C (0) 8 ; -C (0) 0R 4 ; Halogen, -CN, -N0 2) -OR ", -NRR (i , -NR 5 (dC 1 (1 alkylene -NR3 ⁇ 4 (i ), N (0H), NR 5 C (0) 0R 4 ,- Linear, branched or cyclic unsubstituted or substituted with substituents selected from the group consisting of C (0) R 8 , -C (0) 0R 4
  • arylene In addition, arylene, biarylene, aryl,
  • Heteroaromatic rings, or heteroaliphatic rings are each independently a hydrogen atom
  • Halogen atom Linear, branched or cyclic saturated or unsaturated alkyl groups
  • R 4 is a hydrogen atom; Linear, branched or cyclic saturated or unsaturated d-, alkyl groups; Cr ′′ C containing 1 to 10 halogen atoms (; haloalkyl group; d— C 1 () alkylene— O — ⁇ -Cu, alkyl);-(Cr ′′ C 10 alkylene) NR3 ⁇ 4 «; -(d—Cu ) alkylene) —heteroaliphatic ring; -(Ct-do alkylene) —heteroaromatic ring; heteroaliphatic ring group; or heteroaromatic ring group;
  • R 5 , R t; , R 7 and R 8 are the same as or different from each other and are a hydrogen atom; Linear, branched or cyclic saturated or unsaturated C-doalkyl groups; Or an aryl group;
  • the aryl or arylene used in the above substituent definition consists of a monocyclic, bicyclic or tricyclic, and has an aromatic hydrocarbon group of 5 to 15 nuclear atoms.
  • the heteroaromatic ring used in the above substituent definition includes 1 to 4 heteroatoms selected from N, 0 and S, and may be selected from monocyclic, bicyclic or tricyclic.
  • An aromatic heterohydrocarbon group having 5 to 15 nuclear atoms The heteroaliphatic ring used in the above substituent definition includes 1 to 4 heteroatoms selected from N, 0, and S, monocyclic, bicyclic or tricyclic
  • an aliphatic heterohydrocarbon group having 5 to 15 nuclear atoms which may or may not contain an unsaturated carbon chain.
  • novel 3,6—disubstituted indazole derivatives of the present invention or pharmaceutically acceptable salts thereof have excellent ability to inhibit the activity of protein kinases.
  • Abnormal cell growth diseases that can be prevented and treated from the compounds according to the present invention include gastric cancer lung cancer, liver cancer, colon cancer, small intestine cancer, pancreatic cancer, brain cancer, bone cancer, melanoma, breast cancer, Sclerotic adenoma, cervical cancer, cervical cancer, head and neck cancer, esophageal cancer, thyroid cancer, parathyroid gland, kidney cancer, sarcoma, prostate cancer, urethral cancer.
  • Bladder cancer leukemia, multiple myeloma,
  • tumor diseases selected from hematological cancers such as myelodysplastic syndrome, lymphomas such as Hodgkin's disease and non-Hodgkin's lymphoma, or fibroadenoma, and the like.
  • Pharmaceutically acceptable salts of 3, 6-disubstituted indazole derivatives represented by Formula 1 according to the present invention may be prepared by conventional methods in the art. Pharmaceutically acceptable salts are of low toxicity to humans and should not adversely affect the biological activity and physicochemical properties of the parent compound.
  • Pharmaceutically acceptable salts include pharmaceutically usable free acids and acid addition salts of base compounds of formula (I), alkali metal salts (such as sodium salts) and alkaline earth metal salts (such as calcium salts), and organic salts and carboxyl compounds of formula (I). It is composed of organic base addition salt of acid and amino acid addition salt.
  • Free acids that can be used to prepare pharmaceutically acceptable salts can be divided into inorganic acids and organic acids.
  • the inorganic acid may be hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, perchloric acid, bromic acid, or the like.
  • Organic acids include acetic acid, methanesulfonic acid, ethanesulfonic acid, / luenesulfonic acid and fumaric acid.
  • Maleic acid, malonic acid, phthalic acid, succinic acid, lactic acid, citric acid, citric acid, gluconic acid, tartaric acid, salicylic acid, malic acid, oxalic acid, benzoic acid, embonic acid, aspartic acid, glutamic acid and the like can be used.
  • Organic bases that can be used for the preparation of organic base addition salts are tris (hydroxymethyl) methylamine, dicyclonuxylamine and the like.
  • Amino acids that can be used to prepare amino acid addition bases are natural amino acids such as alanine, glycine and the like.
  • the 3,6-disubstituted indazole derivatives represented by Chemical Formula 1 according to the present invention include all hydrates and solvates in addition to the pharmaceutically acceptable salts described above.
  • the pharmaceutically acceptable salts described above may be prepared by the conventional methods described below.
  • the base compound of Formula 1 may be dissolved in a solvent which may be mixed with water such as methanol, ethanol, acetone, 1,4-dioxane, and then crystallized or recrystallized after adding a free acid or free base.
  • the 3, 6-disubstituted indazole derivatives represented by Formula 1 according to the present invention may have one or more asymmetric centers, and in the case of such compounds, enantiomers or diastereomers may be present. Accordingly, the present invention includes each isomer or a mixture of these isomers. Different isomers can be separated or resolved by conventional methods, or any given isomer can be obtained by conventional synthesis or by stereospecific or asymmetric synthesis.
  • the present invention includes a radioactive derivative of the compound represented by Formula 1 according to the present invention, these radioactive compounds are useful in the field of biological research.
  • halogen atom in the present invention means chloro, fluoro, bromo, iodo.
  • alkyl group means methyl, ethyl,; rpropyl, / propyl, Cyclopropyl, / ⁇ butyl, / -butyl, butyl , cyclobutyl, cyclopropylmethyl ,
  • cyclopentyl cyclobutylmethyl, / ⁇ nuclear chamber, nuclear chamber, cyclonuclear chamber, cyclopentylmethyl, heptyl, cyclonuclear methylmethyl, octyl, etc. It means an aliphatic saturated hydrocarbon group having up to 10 carbon atoms.
  • the "haloalkyl group” means an alkyl group in which a hydrogen atom is substituted by one or more halogen atoms, such as a difluoromethyl group and a trifluoromethyl group.
  • alkoxy group means methoxy, ethoxy, / ⁇ propoxy, / -propoxy, / ⁇ butoxy, 7-butoxy, group containing methoxy, C r ( 1 ( , It means a hydroxyl group in which a hydrogen atom is substituted by a substituent selected from an alkyl group.
  • aryl group in the present invention means a monocyclic, bicyclic, or tricyclic aromatic hydrocarbon group, including phenyl, naphthyl, anthracenyl, phenanthryl, and the like.
  • bias group refers to an aromatic hydrocarbon group in which two aryl groups of 5 to 7 are bonded, including biphenyl, phenoxyphenyl, benzoylphenyl, or phenyldiazenylphenyl.
  • heteromatic ring group refers to pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazol3 ⁇ 4, isocazolyl, triazolyl, oxa Diazole 3 ⁇ 4, thiadiazole 3 ⁇ 4, tetrazolyl, pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, triazolyl, indolyl, isoindolinyl, benzofuranyl, benzofurazanyl, dibenzofuranyl, Isobenzofuranyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisooxazolyl, benzo [d] [1,3] dioxyl, benzothiazolyl, dibenzothiophenyl naphthyridyl,
  • 5- to 7-membered monocyclic, bicyclic, or tricyclic aromatic heterohydrocarbon groups containing one or more heteroatoms including isoquinolinyl, quinoxalinyl, phthalazinyl, chinolinyl, quinazolinyl, and the like it means.
  • heteroaliphatic ring group includes a morpholininyl, piperidine group, piperazinyl, ⁇ protected piperazinyl, and the like. It means a heterohydrocarbon ring group.
  • 6'-substituted indazole derivatives represented by the formula (1) according to the present invention preferably,
  • the silver represents an arylene group having 5 to 7 substituted or unsubstituted nuclear atoms having 1 to 4 substituents selected from the group consisting of halogen, Cr; alkyl and d-Cs haloalkyl,
  • Ar 2 is a single bond line;
  • X and L are the same as or different from each other and are a single bond line; -NH-; -N (C)-; -NHC (O)-; -C (0) ⁇ -; -C (0) NHNH-; —C (0) ′ CH 2 —; —C (0) NHCH 2 CH 2 —; -NHC (0) NH-; -NHC (0) N (CH :! )-; -NHC (S) NH-; Or ⁇ NHS0 2 —,
  • R 1 and R 2 are the same as or different from each other as a hydrogen atom; -Ah I; d-Cfi alkyl group;
  • R 2 is a mutually bonded heteroaromatic ring group; Or a heteroaliphatic ring group, wherein the aryl, heteroaromatic ring, and heteroaliphatic ring are each independently selected from the group consisting of halogen, C, -C ( ; alkyl, and C R C (; haloalkyl).
  • halogen C, -C ( ; alkyl, and C R C (; haloalkyl).
  • R 3 is a hydrogen atom; Halogen atom; CN; -N0 2 ; —OH; -SH; — NH 2 ; -NHO ⁇ -C) alkyl);
  • Alkylene — NH ( Cl - Cl0 alkyl); — ( Cl - Cl potentiallyalkylene) — N ⁇ -C K) alkyl) 2 ; -(CC 1 ()
  • -C (0) (aryl), -C (0) (heteroaromatic ring), -C00H,-(XOXXd—C 6 alkyl), -S (0) (CC (i alkyl), -SW d-Cfialkyl ), N3 ⁇ 4, NH (dC (; alkyl), and N (dC (; alkyl) 2 ) is substituted or unsubstituted with 1 to 3 substituents selected from the group consisting of
  • the aryl or arylene used in the above substituent definition consists of a monocyclic, bicyclic or tricyclic, aromatic hydrocarbon group having 5 to 15 nuclear atoms.
  • the heteroaromatic ring used in the above substituent definition includes 1 to 4 heteroatoms selected from N, 0 and S, and may be selected from monocyclic, bicyclic or tricyclic.
  • An aromatic heterohydrocarbon group having 5 to 15 nuclear atoms The heteroaliphatic ring used in the above substituent definition includes 1 to 4 heteroatoms selected from N, 0, and S, and includes a monocyclic ring, a bicyclic ring, or a tricyclic ring.
  • An represents phenylene having 1 to 2 substituted or unsubstituted substituents selected from the group consisting of chloro, fluoro, bromo, methyl and trifluoromethyl.
  • the tax is a single bond, or chloro, fluoro, bromo, methyl and
  • X is a single bond or represents -NH-, or -N (C)-.
  • L is — NHC (O) — , — C (0) NH— , — C (0) NHNH ⁇ , — C (0) NHCH 2 — , — C (0) NHCH 2 CH 2 ⁇ ,
  • R] and R 2 are the same or different and represents hydrogen atom, a hydroxyl group, a methyl group, an ethyl group, a propyl group, an isopropyl group, a cyclo propyl, cyclo nucleus group, a hydroxyl group, the molar Poly group; Morpholinoethyl group, piperidine- 4-yl group ,
  • 2-fluoropyridin-3-yl group 5—poloropyridin-3-yl group
  • 6 fluoropyridin-3-yl group
  • pyrimidin-4-yl pyrimidin-3—yl
  • pyrimidin-4—yl pyrimidin-4—yl
  • pyrimidine 5-yl
  • Imidazole-4-yl group 1—methylimidazol-4-yl group, (imidazol—2-yl) methyl group, or pyrrolidin—3—yl group, or R 1 and are bonded to each other to pipera A zyl group or a 4-methylpiperazine—1-yl group.
  • R 3 is hydrogen atom, chloro atom, fluoro atom, bromo atom, cyano group, nitro group, hydroxy group, acetyl group, methyl group, ethyl group, isopropyl group, er-butyl bromomethyl group, cyanopropyl Group, dimethylaminomethyl group ,
  • 2-methylimidazole group 4-methylimidazole group, 2,4-dimethylimidazole group, pyridinyl group, 3-hydroxypyrrolidin ⁇ 1-yl group, 3- (dimethylamino) pyridine- Diary,
  • Methyl-6_ (methyl (2-methyl-5— (3— (4—methylpiperazin—1-yl) -5— (trimulomethyl) benz amido) phenyl) amino) ⁇ 1 // — indazole -3-carboxamide (Example 15);
  • 6- (4-fluoro-2-methyl-5— (3- (methylamino) -5— (trifluoromethyl) benzamido) phenyl)- ⁇ methyl-1 ⁇ indazole-3—carbox Amides (Example 73); 6- (5— (2— (dimethylamino) — 5- (trifluoromethyl) benzamido) -4—fluoro—2-methyl phenyl)-/ V "methyl indazole-3-carboxamide ( Example 74);
  • 6- (5- (3— (1-acetylpiperidine-4-carboxamido) -5- (trifluoromethyl) benzamido) ⁇ 4 ⁇ fluoro-2-methylphenyl) methyl-1 ⁇ Indazole-3-carboxamide (Example 93); 6- (5- (3— (2— (dimethylamino) acetamido) -5- (trifluoromethyl) benzamido) -4-fluoro-2-methylphenyl) methyl indazole-3-carbox Amide (Example 94);
  • 6- (5 ′ (3 ′ (2-amino— 2-methylpropoxy) -5- (trifluoromethyl) benzamido) —4-fluorofluoro 2-methylphenyl) methyl-1 ⁇ indazol ⁇ 3 Carboxamide (Example 131); 6- (5- (3-((l ⁇ (dimethylamino) propane_2-yl) oxy) ⁇ 5- (trifluoromethyl) benzamido) -4 -fluoro- 2 —methylphenyl methyl- ;! ⁇ Indazole 3 —carboxamide
  • Trifluoroacetic acid salt (Example 190);
  • 6- (5-((3 ⁇ ((2- (dimethylamino) ethyl) amino) -5— (trifluoromethyl) phenyl) carbamoyl) -4-fluoro-2-methylphenyl) methyl-1 ⁇ is Sol-3-carboxamide (Example 229); 6- (4-fluoro— 2-methyl— 5— ((2-morpholino-5 (trifluoromethyl) phenyl) carbamoyl) phenyl) -gmethyl indazole— 3—carboxamide (implemented Example 230);
  • 6- (5 ⁇ ((3-((2— (dimethylamino) ethyl) amino) -5- (trifluoromethyl) phenyl) carbamoyl) ⁇ 4-fluoro-2—methylphenyl) ⁇ ⁇ methyl-ly Indazole-3-carboxamide (Example 232); 6- (5 '((2-((2- (dimethylamino) ethyl) amino) -5- (trifluoromethyl) phenyl) carbamoyl) -4-fluoro-2—methylphenyl)-/ ⁇ methyl— 1 ⁇ indazole-3-carboxamide (Example 233); 6- (5— ((3—chloro-4-methoxyphenyl) carbamoyl) —4-fluoro—2-methylphenyl) methyl indazole-3-carboxamide (Example 234);
  • 6- (5- (2- (3,5-dimethoxyphenyl) acetamido) ⁇ 4-fluoro-2-methylphenyl) -methyl-1 ⁇ dazole- 3-carboxamide (Example 254); 6- (5- (2- (4-dimethoxyaminophenyl) acetamido)-4-fluoro- 2-methylphenyl) -methyl-1 ⁇ indazole-3-carboxamide (Example 255);
  • the present invention can be used as a prophylactic or therapeutic agent for diseases caused by abnormal cell growth.
  • diseases caused by abnormal cell growth include gastric cancer, lung cancer, liver cancer, colon cancer, small intestine cancer, pancreatic cancer, brain cancer, bone cancer, myeloma, breast cancer, scleroid adenomas, uterine cancer,
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a 3,6-disubstituted indazole derivative represented by Chemical Formula 1, a pharmaceutically acceptable salt thereof, a solvate thereof, and a hydrate thereof as an active ingredient, and abnormal cell growth. It is characterized by the prophylaxis and treatment of various tumor diseases caused.
  • the pharmaceutical composition of the present invention is a pharmaceutically acceptable salt thereof, solvate thereof, or hydrate thereof of the 3, 6-disubstituted indazole derivative represented by Chemical Formula 1
  • Oral such as tablets, capsules, troches, liquids, suspensions, etc., which are conventional in the pharmaceutical field by adding them as an active ingredient, and adding a conventional non-toxic pharmaceutically acceptable carrier, adjuvant, and excipient thereto.
  • Excipients that may be used in the pharmaceutical compositions of the present invention may include sweeteners, binders , solubilizers, solubilizers, wetting agents, emulsifiers, isotonic agents, adsorbents, disintegrants, antioxidants, preservatives, lubricants, layering agents, fragrances, and the like.
  • lactose for example, lactose, dextrose, sucrose, manni, solbi, salulose, glycine, silica, talc, stearic acid, sterin, magnesium stearate, magnesium aluminum silicate, starch, gelatin, tragacanth rubber, eggs Havoc, sodium alginate, methylcellulose, sodium carboxymethylcellulose, agar, water, ethanol, polyethylene glycol, polyvinylpyridone, sodium chloride, calcium chloride, orange essence , strawberry essence, vanilla flavor Can be.
  • the dosage of the compound according to the present invention to the human body may vary according to the age, weight, sex, dosage form, health condition and degree of disease of the patient, and generally 0.01 based on an adult patient having a weight of 70 kg. ⁇ 1,000 mg / day, may be divided into once or several times a day at regular intervals depending on the judgment of the doctor or pharmacist.
  • 6-Nitrojan1-indazole (5 g) and dioxane (50 ITIL) were placed in a bottom-bottom flask. 3N NaOH solution (25 mL) was added thereto and stirred. H (8.5 g) was added to the mixture. After 4 hours, water (100 ml ) was added to react Terminated. The product resulting from the addition of water was filtered to give a yellow solid product.
  • the filtrate was distilled off under reduced pressure to obtain a solid product.
  • 6-nitrojan 1-indazol-3-carboxylic acid 280 mg
  • EtOH 4.5 niL
  • Concentrated S0 4 0.04 mL was added to the mixture and heated to 100 ° C. After 3 hours, the solvent was removed by distillation under reduced pressure, and the mixture was neutralized with IN NaOH. Solid product obtained by quenching was obtained by solid filtration. The product was washed with water and dried under nitrogen gas to give 300 mg (94%) of the product.
  • 6-Bromoqen 1 / indazole (5 g) and dioxane (50 ill) were placed in a bottom-bottom flask. To this was added 3 N NaOH solution (25 niL) and stirred. (8.5 g) was added to the mixture. After 4 hours, water (100 mL) was added to terminate the reaction. The product resulting from the addition of water was filtered to give a yellow solid product. The product was washed with water and dried under nitrogen gas to give 7.1 g (80%) of the product.
  • 3-iodo-6-nitroindazole (5 g) and DMF (58 ITIL) were placed in the back bottom flask.
  • CuCN (7.5 g) was added to the mixture and heated to 250 ° C.
  • 6-Bromo-l / indazol-3-carboxylic acid 100 g
  • DMF 500 mL
  • HBTU 236 g
  • DIEA 505 mL
  • MeNH 2 — HC1 84 g
  • Methyl— 6 ′ (methyl (2—methyl-5—nitrophenyl) amino) —1— (tetrahydro-2 //-pyran— 2 ilyl indazole-3-carboxamide (352mg, 0.83 ⁇ ol)
  • MeOH MeOH
  • 10% Pd / C 35 mg was added and stirred under a hydrogen gas for 5 hours at room temperature.
  • the mixture was filtered through a pad of diatomaceous earth and the filtrate was removed by distillation under reduced pressure.
  • Dazol-3-carboxamide (6.8 nig) which was ⁇ -methyl-6- (methyl (4— (33 (3— (trifluoromethyl) phenyl) ureido) phenyl) amino shock, was obtained.
  • Example 42 A compound was synthesized in the same manner as in Example 40. MS m / z [M + H] 463. Example 42.
  • 6-Bromo-1— (tetrahydro-2 //-pyran-2—yl intazole-3-carboxylate (200 nig, 0.57 wk ol) and ethyl 3-amino—4-methylbenzoate (102 mg , 0.57 mmol), ⁇ -phos (24.5mg, 0.05 ⁇ ol), 3 ⁇ 4C (394mg, 2.85 ⁇ ol) in 2—butanol (2mL), degassed, and then Pd 2 (dba) 3 (31.3 nig, 0.03 ⁇ ol ) And heated at 90 ° C.
  • Example 43 waves were carried out in the same manner to obtain the title compound.
  • the solvent is removed by distillation under reduced pressure
  • Example 139 Example 139.
  • Example 140 Example 140.
  • Example 141 Example 141.
  • Example 142 Example 142.
  • Example 143 The title compound was obtained in the same manner as the Example 134.
  • Example 143 Example 143.

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Abstract

The present invention relates to a novel 3,6-disubstituted indazole derivative or a pharmaceutically acceptable salt thereof, to a production method for same, and to a pharmaceutical composition comprising same as an active ingredient. The pharmaceutical composition of the present invention exhibits an outstanding suppressing effect against protein kinases that induce cancer, such as B-Raf kinase, and can therefore be used to advantage in the prevention or treatment of cancer.

Description

【명세서】  【Specification】
발명의 명칭: 단백질 키나아제 저해활성을 가지는 3, 6-이치환된 인다졸 유도체 【기술분야】 NAME OF THE INVENTION: 3, 6-disubstituted indazole derivatives having protein kinase inhibitory activity
본 발명은 신규 3, 6-이치환된 인다졸 유도체 또는 이의 약학적으로 허용 가능한 염 및 이를 유효성분으로 함유하는 단백질 키나아제 저해에 유효한 약학적 조성물에 관한 것이다.  The present invention relates to a novel 3, 6-disubstituted indazole derivative or a pharmaceutically acceptable salt thereof and a pharmaceutical composition effective for inhibiting protein kinase containing the same as an active ingredient.
【발명의 배경이 되는 기술】 [Technique to become background of invention]
단백질 키나아제는 단백질의 티로신， 세린 및 트레오닌 잔기에 위치하는 하이드록시 그룹의 인산화를 촉매하는 효소로서 , 세포의 성장, 분화 및 증식을 유발하는 성장 인자 신호 전달에 중요한 역할을 담당하고 있다. 이러한 단백질 키나아제의 돌연변이나 과발현은 정상적인 세포 내 신호 전달체계를 붕괴시켜서 (주로 생체 내 신호 전달이 계속 되는 상태) 암, 염증， 대사성 질환， 뇌질환 등 다양한 질병을 유발한다.  Protein kinases are enzymes that catalyze the phosphorylation of hydroxy groups located at tyrosine, serine and threonine residues of proteins and play an important role in the growth factor signal transduction that causes cell growth, differentiation and proliferation. Mutations or overexpression of these protein kinases disrupt the normal cellular signaling system (mainly in vivo), leading to a variety of diseases, including cancer, inflammation, metabolic diseases, and brain diseases.
인간 단백질 키나아제는 크게 티로신. 단백질 키나아제와 세린 /트레오닌 단백질 키나아제로 양분된다. Raf는 세린 /트레오닌 (Ser/Thr) 단백질 키나아제로서, 세포막에서 활성화된 성장인자 수용체가 보내는 생체 신호를 핵 내로 전달하는 역할을 담당한다.  Human protein kinases are largely tyrosine. It is divided into protein kinases and serine / threonine protein kinases. Raf is a serine / threonine (Ser / Thr) protein kinase that is responsible for delivering biological signals from activated growth factor receptors in the cell membrane into the nucleus.
Raf 단백질은 A-Raf , B-Raf , C-Raf/Raf—1의 세 가지 아류형이 존재하며, 이들은 yV-말단 조절 도메인과 C—말단 키나아제 도메인에 3 개의 보존된 영역 (CRl, CR2, CR3)을 갖고 있다. CR1은 시스테인이 풍부한 도메인 (Cystein-rich domain, CRD)과 같은 Ras 결합 도메인 (Ras-binding domain, RBD)을 포함하며， CR2는 Raf proteins have three subtypes, A-Raf, B-Raf and C-Raf / Raf—1, which have three conserved regions (CRl, CR2, YV-terminal regulatory domain and C-terminal kinase domain). CR3). CR1 contains a Ras-binding domain (RBD) such as a cysteine-rich domain (CRD), and CR2
14-3-3 단백질이 결합하는 '자리 (Raf— 1의 259번 세린 등)를 갖고 있고， CR3는 촉매 도메인 (catalytic domain)을 함유하는데， 두 개의 활성—단편 인산화 자리 (Raf-1의 491번 트레오닌과 494번 세린)를 보유하고 있다. 14-3-3 protein binds to the ' site (serum # 259 serine, etc.), CR3 contains a catalytic domain, two active-fragmentary phosphorylation sites (491 of Raf-1) Burn threonine and serine 494).
Raf 단백질의 세 가지 아류형들이 발현되는 조직은 서로 다르다. C-Raf는 거의 모든 조직에서 발현되는 반면에, A-Raf는 주로 비뇨생식기 조직 (신장, 자궁， 전립선)에서 발현되고， B— Raf는 신경， 비장， 조혈 조직에서 주로 발현된다.  The tissues in which the three subtypes of Raf proteins are expressed are different. C-Raf is expressed in almost all tissues, while A-Raf is expressed mainly in the genitourinary tissues (kidney, uterus and prostate), and B-Raf is mainly expressed in nerves, spleen and hematopoietic tissues.
B-Raf의 돌연변이는 인간 암 전체의 약 Ί 정도로 연관이 있다. 특히 피부암의 일종인 혹색종에서 높은 빈도로 B-Raf의 돌연변이가 관찰된다.  Mutations in B-Raf are approximately related to all human cancers. In particular, mutations of B-Raf have been observed with high frequency in melanoma, a type of skin cancer.
B-Raf의 돌연변아 중에서 액손 15번에 위치한 발린 600번이 글루타민산으로 점돌연변이된 B-Raf-V600E 돌연변이종이 주로 혹색종을 유발하는 것으로 알려져 있다.  Among the mutants of B-Raf, the B-Raf-V600E mutant, in which valine 600, located at axon 15, is mutated to glutamic acid, is mainly known to cause melanoma.
B-Raf-V600E는 MAPK 키나아제 신호전달체계의 과활성화를 유도해서 암을 유발하게 된다. B-Raf— V600E의 키나아제 활성이 높은 이유는 다음과 같다. 점돌연변이로 치환된 글루타민산 600번이 활성단편 (activation segment)에 위치한 인산화 자리 (트레오닌 598번과 세린 6이번) 사이에서 인산기 모조 역할을 해서， 항상 활성된 B-Raf 키나아제 도메인의 입체배좌 (structural conformation)를 유발한다. 한편 현재까지 확인된 B-Rai 돌연변이종은 약 40 개인데, V600E 이외의 다른 돌연변이종의 발생 빈도는 현저하게 낮다. B-Raf-V600E induces hyperactivation of the MAPK kinase signaling system leading to cancer. The reason for the high kinase activity of B-Raf—V600E is as follows. Glutamic acid 600, substituted by point mutation, acts as a phosphate model between the phosphorylation sites (threonine 598 and serine hexavalent) located in the activation segment, resulting in a conformal conformation of the always active B-Raf kinase domain. Cause). Meanwhile, the B-Rai mutant species identified so far is about Forty individuals have a significantly lower incidence of mutant species other than V600E.
직장암에서 B— Rai 돌연변이종의 약 10% 정도가 키나아제 도메인의 G-루프에서 발생 한다. In rectal cancer, about 10% of B-Rai mutants occur in the G-loop of the kinase domain.
B一 Rai의 말단에는 자가억제 (auto-inhibition) 도메인이 존재하지만, 활성화된 H— Ras가 결합하면 B-Raf는 항상 활성화 상태가 된다. 이는 세린 445번의 인산화를 통해서 형성되는데, C— Raf 세린 338번의 인산화는 B-Raf 세린 445번의 인산화에 상응한다. B— Raf V600E돌연변이종은 B-Raf의 자가억제 기전을 방해해서 항상 활성인 상태가 유지된다.  There is an auto-inhibition domain at the end of Bl Rai, but B-Raf is always activated when activated H-Ras binds. It is formed through the phosphorylation of serine 445. The phosphorylation of C—Raf serine 338 corresponds to the phosphorylation of B-Raf serine 445. The B—Raf V600E mutant interferes with the self-suppressive mechanism of B-Raf and remains active at all times.
또한 B-Raf-V600E 돌연변이종은 소돌기성 갑상선암 (papillary thyroid cancer)에서 높은 빈도로 발견된다. 동시에 B-Raf— V600E 돌연변이종은 결장암， 자궁암 유발과 밀접한 연관이 있다. B-Raf-V600E mutant species are also found with high frequency in papillary thyroid cancer. At the same time, B-Raf—V600E mutant species are closely associated with colon and uterine cancers.
한편 종양유전적인 돌연변이종의 발현 없이， C— Raf의 과활성화는 신장암 (renal cell carcinoma)에서 약 50%, 그리고 간암 (HCC)에서 100% 정도 관찰된다. On the other hand, overexpression of C-Raf was observed about 50% in renal cancer (renal cell carcinoma) and 100% in liver cancer (HCC) without oncogenetic mutant expression.
Bayer와 Onyx 회사가 공동으로 개발한 소라페니브 (Sorafenib) (BAY 43—9006， 상표명 Nexavar)는 C— Raf와 야생형 혹은 돌연변이종 B-Rai 모두를 강하게 억제한다. 또한 소라페니브 (Sorafenib)는 수용체 티로신 키나아제인 혈소판유래성장인자수용체 (platelet-derived growth factor receptor) , 혈관내피성장인자수용체 (vascular endothelial growth factor receptor 1/2/3) , 섬유모세포성장인자수용체 (fibroblast growth factor receptor), Fit— 3, c-Kit , RET 둥의 키나아제 활성을 저해한다. 키나아제 도메인의 DGF모티프가 비활성화 배좌 (inactive conf ormat ion)를 갖도록 안정화 시키는 기전을 통해서 소라페니브 (Sorafenib)는 키나아제를 저해 한다. 소라페니브 Sorafenib (BAY 43—9006, trade name Nexavar), developed jointly by Bayer and Onyx, strongly inhibits both C-Raf and wild-type or mutant B-Rai. Sorafenib also contains platelet-derived growth factor receptors, vascular endothelial growth factor receptors 1/2/3 and fibroblast growth factor receptors, receptor tyrosine kinases. fibroblast growth factor receptor), Fit-3, c-Kit, and RET block kinase activity. Sorafenib inhibits kinases through a mechanism by which the DGF motif of the kinase domain is stabilized to have an inactive conf ormat ion. Sorafenib
(Sorafenib)는 2005년에 진행성 신장암 (advanced renal cell carcinoma) 치료제로 승인을 받았다. 그런데 소라페니브 (Sorafenib)의 신장암 치료 효과는 Raf 저해 보다 혈관내피성장인자수용체 (vascular endothelial growth factor receptor 1/2/3)를 비롯한 여러 키나아제들의 복합적 억제에 기인한다. 임상 2상 시험에서 소라페니브 (Sorafenib)의 최대허용용량은 400 mg (하루 2회 투여)이었다. 600 mg (하루 2회 투여)의 소라페니브 (Sorafenib)는 등급 3의 피부 독성 부작용을 유발한다. 소라페니브 (Sorafenib)의 흔한 부작용은 손발의 피부가 벗겨지고 홍진, 부종 증상의 손발증후군 (hand— foot Sorafenib was approved in 2005 for the treatment of advanced renal cell carcinoma. Sorafenib's renal cancer treatment is due to the complex inhibition of several kinases including vascular endothelial growth factor receptor 1/2/3 rather than Raf inhibition. The maximum tolerated dose of Sorafenib in phase II trials was 400 mg (twice daily). Sorafenib at 600 mg (twice daily) causes grade 3 skin toxic side effects. A common side effect of Sorafenib is the hand-foot syndrome of skin peeling and redness and edema.
syndrome)이다. 한편 소라페니브 (Sorafenib)는 2008년에 간세포암 (HCC, Hepatocellular Carcinoma) 치료제로 승인을 받았다. 또한소라페니브 syndrome). Sorafenib was approved for the treatment of Hepatocellular Carcinoma (HCC) in 2008. Sorafenib
(Sorafenib)는 임상 2 상 시험에서 갑상선암, 호르몬 난치성 전립선암과 유방암 치료 효능올 보였다. 그러나 소라페니브 (Sorafenib)는 피부암인 혹색종 (melanoma)에 대한 치료 효능이 없다. (Sorafenib) has been shown to be effective in treating thyroid cancer, hormonal refractory prostate cancer and breast cancer in phase II trials. However, Sorafenib is not effective in treating melanoma, a skin cancer.
한편 플렉시콘 (Plexxikon)사의 7-아자인들 유도체인 PLX4720은 1205Lu Meanwhile, PLX4720, a derivative of 7-azains from Plexxikon, is 1205Lu.
(Raf-V660E 과발현 세포주)와 같은 혹색종 세포주의 세포사멸을 유도한다. Induces apoptosis of melanoma cell lines such as (Raf-V660E overexpressing cell line).
PLX4720은 Raf-V660E의 키나아제 활성을 강하게 (IC50 = 13 nM) 저해하고， 또한 A375 혹색종 '세포주의 증식을 억제 (IC50 = 0.5 μΜ)한다. PLX4720 strongly inhibits the kinase activity of Raf-V660E (IC 50 = 13 nM) and also inhibits the proliferation of A375 myeloma 'cell lines (IC 50 = 0.5 μΜ).
노바티스 (Novartis)/카이론 (Chiron)사의 CHIR265 역시 B-Raf-V600E (IC50= 19nM) DR ( IC50 = 70 nM), PDGFR-b ( IC50 = 30 nM)， c- i t ( IC50 = 20 nM)의 키나아제 활성을 강하게 저해한다. CHIR265은 현재 혹색종 환자를 대상으로 임상 1상 시험 증이다ᅳ 현재까지 인다졸 구조를 모체로 하는 여러 화합물들이 합성된 바는 있으나， 본 발명에서와 같이 인다졸 모핵의 C3 및 C6위치에 동시에 치환기기- 치환되어 있고, 특히 C3위치에 카복스아미도 그룹이 치환된 인다졸 화합물이 합성된 바는 없으며, 더욱이 이들 화합물 또는 이의 유도체에 대한 단백질 키나아제의 저해활성을 확인하여 종양 치료 및 예방제로 사용할 수 있음에 대해서는 현재까지 어떠한 문헌에도 발표되어 있지 않고 있다. CHIR265 from Novartis / Chiron also uses B-Raf-V600E (IC 50 = 19 nM) DR (IC 50 = 70 nM), PDGFR-b (IC 50 = 30 nM), c- it (IC 50 = Strongly inhibits kinase activity of 20 nM). CHIR265 is currently a Phase 1 clinical trial in patients with melanoma To date, several compounds having an indazole structure have been synthesized, but as in the present invention, a substituent-substituted at the same time as the present invention is substituted at the C3 and C6 positions of the indazole parent nucleus, and a carboxamido group is particularly substituted at the C3 position. Substituted indazole compounds have not been synthesized. Furthermore, there have been no publications in the literature to confirm the inhibitory activity of protein kinases on these compounds or derivatives thereof and to use them as therapeutic agents for the treatment and prevention of tumors.
【발명의 요약】 [Summary of invention]
【해결하고자 하는 과제】  Problem to be solved
본 발명의 목적은 신규 3,6—이치환된 인다졸 유도체， 약학적으로 허용되는 이의 염， 이의 수화물, 이의 용매화물 및 이의 이성질체로부터 선택된 화합물을 제공하는 것이다.  It is an object of the present invention to provide compounds selected from novel 3,6—disubstituted indazole derivatives, pharmaceutically acceptable salts thereof, hydrates thereof, solvates thereof and isomers thereof.
본 발명의 다른 목적은 상기한 신규의 화합물을 유효성분으로 함유하는 비정상 세포 성장 질환의 예방 및 치료용 약학적 조성물을 제공하는 것이다.  Another object of the present invention to provide a pharmaceutical composition for the prevention and treatment of abnormal cell growth diseases containing the novel compounds as an active ingredient.
【과제의 해결 수단】 [Measures of problem]
상기 목적을 달성하기 위하여 , 본 발명은 단백질 키나아제의 활성을 저해하는 하기 화학식 1로 표시되는 3, 6-이치환된 인다졸 유도체， 약학적으로 허용되는 이의 염, 이의 수화물， 이의 용매화물 및 이의 이성질체로부터 선랙된 화합물을 그 특징으로 한다.  In order to achieve the above object, the present invention, 3, 6-disubstituted indazole derivatives represented by the following formula (1) inhibiting the activity of protein kinase, pharmaceutically acceptable salts thereof, hydrates thereof, solvates thereof and isomers thereof It is characterized by the compound selected from.
[화학식 1]  [Formula 1]
Figure imgf000004_0001
상기 화학식 1에서,
Figure imgf000004_0001
In Chemical Formula 1,
Αι-은 아릴렌기; 바이아릴렌기; 2가 헤테로방향족고리기; 또는 2가  Aι- is an arylene group; Biarylene group; Divalent heteroaromatic ring groups; Or 2
헤테로지방족고리기를 나타내고,  Heteroaliphatic ring group,
Ar2는 단일결합선이거나; 아릴렌기; 바이아릴렌기; 2가 헤테로방향족고리기; 또는 2가 헤테로지방족고리기를 나타내고, Ar 2 is a single bond line; Arylene group; Biarylene group; Divalent heteroaromatic ring groups; Or a divalent heteroaliphatic ring group,
X및 L은 서로 같거나 다른 것으로서 단일결합선이거나; C(0)-; -NR5-; X and L are the same or different from each other and are a single bond line; C (0)-; -NR 5- ;
-NRs-C(0)-; -C(0)NRr>-; -C(0)NR5NR'3-; -C(0)NR5-(CH2)n- (n은 1 내지 10의 정수);-NR s -C (0)-; -C (0) NR r> -; -C (0) NR 5 NR '3-; -C (0) NR 5- (CH 2 ) n- (n is an integer from 1 to 10);
-NR5-C(0)-NRfi; -NRr,-C(S)-NR6; 또는 -NR5-S(0)0- ； 를 나타내고， -NR 5 -C (0) -NR fi ; -NR r, -C (S) -NR 6 ; Or -NR 5 -S (0) 0- ;;
R1 및 R2는 서로 같거나 다른 것으로서 수소원자;— N02; -OR"; -NR¾fi; -NR5C(0)R8;R 1 and R 2 are the same as or different from each other and are a hydrogen atom; — N0 2 ; -OR "; -NR¾ fi ; -NR 5 C (0) R 8 ;
-C(0)R8; -C(0)0R4; -CN, -N02, -OR',—NR¾';, -NRC(0)R8, -C(0)R8, -C(0)0R4, 아릴, 헤테로방향족고리， 및 헤테로지방족고리로 이루어진 군으로부터 선택된 치환체로 치환 또는 비치환된 직쇄, 분지형 또는 환형의 ^ (^알킬기; 아릴기; 헤테로방향족고리기; 또는 해테로지방족고리기; 를 나타내고， -C (0) R 8 ; -C (0) 0R 4 ; -CN, -N0 2 , -OR ', — NR¾'; , -NRC (0) R 8 , -C (0) R 8 , -C (0) 0R 4 , straight chain, unsubstituted or substituted with a substituent selected from the group consisting of aryl, heteroaromatic ring, and heteroaliphatic ring A topographic or cyclic ^ (^ alkyl group; aryl group; heteroaromatic ring group; or heteroaliphatic ring group;
또한 상기 R1과 R2는 서로 결합하여 헤테로방향족고리기; 또는 In addition, R 1 and R 2 are bonded to each other heteroaromatic ring group; or
헤테로지방족고리기를 형성할 수 있으며，  Can form a heteroaliphatic ring group,
R3은 수소원자; 할로겐원자; CN; -N02; -OR4; -SR4; -NR5RR; -NR5(C C10알킬렌 -OR4); -NR^d-d,,알킬렌 -NR¥)； -NR:'(헤테로지방족고리 )； (해테로방향족고리 )； -NR5(C C10알킬렌―해테로지방족고리 )； -NRr'(C C10알킬렌-해테로방향족고리 )； -NR^d-C,알킬렌-헤테로방향족고리 )； ᅳ NR¾(0)-헤테로지방족고리； 一 NR¾(0)-해테로방향족고리; — NR (0)R8; -NR¾(0)0R , -NR5C(0)-(CrC1() R 3 is a hydrogen atom; Halogen atom; CN; -N0 2 ; -OR 4 ; -SR 4 ; -NR 5 R R ; -NR 5 (CC 10 alkylene-OR 4 ); -NR ^ dd ,, alkylene -NR ¥); -NR : '(heteroaliphatic ring); (heteroaromatic ring); -NR 5 (CC 10 alkylene-heteroaliphatic ring); -NR r ' ( CC 10 alkylene-heteroaromatic ring); -NR ^ dC, alkylene-heteroaromatic ring); ᅳ NR¾ (0) -heteroaliphatic ring; one NR¾ (0) -heteroaromatic ring; — NR (0) R 8 ; -NR¾ (0) 0R, -NR 5 C (0)-(C r C 1 ()
알킬렌— NR:¥); -C(0) 8; -C(0)0R4; 할로겐， -CN, -N02) -OR", -NRR(i, -NR5(d-C1(1 알킬렌 -NR¾(i), =N(0H), NR5C(0)0R4, -C(0)R8, -C(0)0R4로 이루어진 군으로부터 선랙된 치환기로 치환체로 치환 또는 비치환된 직쇄, 분지형 또는 환형의 Alkylene—NR : ¥); -C (0) 8 ; -C (0) 0R 4 ; Halogen, -CN, -N0 2) -OR ", -NRR (i , -NR 5 (dC 1 (1 alkylene -NR¾ (i ), = N (0H), NR 5 C (0) 0R 4 ,- Linear, branched or cyclic unsubstituted or substituted with substituents selected from the group consisting of C (0) R 8 , -C (0) 0R 4
(^(^알킬기; 할로겐원자가 1 내지 20개 치환된 직쇄 또는 분지형의 C广 C,„ 할로알킬기; 아릴기； 헤테로방향족고리기; 또는 해테로지방족고리기; 를 나타내고，  (^ (^ Alkyl group; linear or branched C 广 C, „haloalkyl group having 1 to 20 halogen atoms; aryl group; heteroaromatic ring group; or heteroaliphatic ring group;
또한, 상기 치환기 정의에 사용된 아릴렌， 바이아릴렌， 아릴，  In addition, arylene, biarylene, aryl,
헤테로방향족고리 , 또는 헤테로지방족고리는 각각 독립적으로 수소원자;  Heteroaromatic rings, or heteroaliphatic rings are each independently a hydrogen atom;
할로겐원자; 직쇄, 분지형 또는 환형의 포화 또는 불포화된 알킬기 ;  Halogen atom; Linear, branched or cyclic saturated or unsaturated alkyl groups;
할로겐원자가 1 내지 10개 포함된 d-Qi할로알킬기 ; 시아노기 ; 옥소 (O); -N02; -OBoc; -OR"; -(CH2)„-0R4 -0(C )„NR¾6; -NR¾(i; -NR¾(0)R8; ᅳ NR¾(0)NR 7; — C(0)R8;D-Qi haloalkyl group containing 1 to 10 halogen atoms; Cyano group; Oxo (O); -N0 2 ; -OBoc; -OR ";-(CH 2 )-0R 4 -0 (C)„ NR¾ 6 ; -NR¾ (i ; -NR¾ (0) R 8 ; ᅳ NR¾ (0) NR 7 ; — C (0) R 8 ;
-C(0)0R4; -C(0)NR¾R； -C(0)NH(CH2)nNR¾l>; — S(0)R8; -S(0)2Rs; — S(0)2NR¾"; 아릴기 ; 바이아릴기 ; 헤테로방향족고리기; 또는 해테로지방족고리기; 로 이루어진 군으로부터 선택된 1 내지 3개의 치환체로 치환 또는 비치환되며, 이때 n은 1 내지 6의 정수이고, -C (0) 0R 4 ; -C (0) NR¾ R ; -C (0) NH (CH 2 ) n NR¾ l> ; — S (0) R 8 ; -S (0) 2 R s ; — S (0) 2 NR¾ "; aryl group; biaryl group; heteroaromatic ring group; or heteroaliphatic ring group; substituted or unsubstituted with one to three substituents selected from the group consisting of n is 1 to Is an integer of 6,
R4는 수소원자; 직쇄 , 분지형 또는 환형의 포화 또는 불포화된 d- ,알킬기 ; 할로겐원자가 1 내지 10개 포함된 Cr"C(;할로알킬기 ; d— C1()알킬렌— O- ^-Cu, 알킬); -(Cr"C10알킬렌) NR¾«; -(d— Cu)알킬렌)—헤테로지방족고리 ; -(Ct-do 알킬렌)—헤테로방향족고리； 헤테로지방족고리기； 또는 해테로방향족고리기； 를 나타내고， R 4 is a hydrogen atom; Linear, branched or cyclic saturated or unsaturated d-, alkyl groups; Cr ″ C containing 1 to 10 halogen atoms (; haloalkyl group; d— C 1 () alkylene— O — ^-Cu, alkyl);-(Cr ″ C 10 alkylene) NR¾ «; -(d—Cu ) alkylene) —heteroaliphatic ring; -(Ct-do alkylene) —heteroaromatic ring; heteroaliphatic ring group; or heteroaromatic ring group;
R5, Rt;, R7 및 R8은 서로 같거나 다른 것으로서 수소원자; 직쇄, 분지형 또는 환형의 포화 또는 불포화된 C -do알킬기 ; 또는 아릴기 ; 를 나타내며， 상기 치환기 정의에 사용된 아릴 또는 아릴렌은 단일고리, 두고리 또는 세고리로 이루어지고， 핵원자수가 5 내지 15개인 방향족 탄화수소기를 R 5 , R t; , R 7 and R 8 are the same as or different from each other and are a hydrogen atom; Linear, branched or cyclic saturated or unsaturated C-doalkyl groups; Or an aryl group; The aryl or arylene used in the above substituent definition consists of a monocyclic, bicyclic or tricyclic, and has an aromatic hydrocarbon group of 5 to 15 nuclear atoms.
나타내고;  Represent;
상기 치환기 정의에 사용된 헤테로방향족고리는 N, 0 및 S 중에서 선택된 헤테로원자가 1 내지 4개 포함되고, 단일고리, 두고리 또는 세고리로  The heteroaromatic ring used in the above substituent definition includes 1 to 4 heteroatoms selected from N, 0 and S, and may be selected from monocyclic, bicyclic or tricyclic.
이루어지고, 핵원자수가 5 내지 15개인 방향족 헤테로탄화수소기를 나타내고; 상기 치환기 정의에 사용된 해테로지방족고리는 N, 0 및 S 중에서 선택된 해테로원자가 1 내지 4개 포함되고， 단일고리, 두고리 또는 세고리로  An aromatic heterohydrocarbon group having 5 to 15 nuclear atoms; The heteroaliphatic ring used in the above substituent definition includes 1 to 4 heteroatoms selected from N, 0, and S, monocyclic, bicyclic or tricyclic
이루어지고, 불포화 탄소사슬을 포함 또는 미포함할 수 있는 핵원자수가 5 내지 15개인 지방족 헤테로탄화수소기를 나타낸다.  And an aliphatic heterohydrocarbon group having 5 to 15 nuclear atoms which may or may not contain an unsaturated carbon chain.
【발명의 효과】 【Effects of the Invention】
본 발명의 신규 3,6—이치환된 인다졸 유도체 또는 이의 약학적으로 허용 가능한 염은 단백질 키나아제의 활성을 저해하는 능력이 우수하므로  The novel 3,6—disubstituted indazole derivatives of the present invention or pharmaceutically acceptable salts thereof have excellent ability to inhibit the activity of protein kinases.
비정상적인 세포 성장으로 유발되는 질환의 예방 및 치료제로서 유용하다.  It is useful as a prophylactic and therapeutic agent for diseases caused by abnormal cell growth.
본 발명에 따른 화합물로부터 예방 및 치료될 수 있는 비정상 세포 성장 질환은 위암 폐암, 간암， 대장암， 소장암， 췌장암， 뇌암， 뼈암, 혹색종， 유방암, 경화성선종， 자궁암， 자궁경부암， 두경부암， 식도암, 갑상선암， 부갑상선임-, 신장암， 육종， 전립선암, 요도암. 방광암, 백혈병, 다발성골수종， Abnormal cell growth diseases that can be prevented and treated from the compounds according to the present invention include gastric cancer lung cancer, liver cancer, colon cancer, small intestine cancer, pancreatic cancer, brain cancer, bone cancer, melanoma, breast cancer, Sclerotic adenoma, cervical cancer, cervical cancer, head and neck cancer, esophageal cancer, thyroid cancer, parathyroid gland, kidney cancer, sarcoma, prostate cancer, urethral cancer. Bladder cancer, leukemia, multiple myeloma,
골수이형성증후군과 같은 혈액암, 호치킨병과 비호치킨림프종과 같은 림프종, 또는 섬유선종 등으로부터 선택된 각종 종양 질환이 포함될 수 있다.  Various tumor diseases selected from hematological cancers such as myelodysplastic syndrome, lymphomas such as Hodgkin's disease and non-Hodgkin's lymphoma, or fibroadenoma, and the like.
【발명을 실시하기 위한 구체적인 내용】 [Specific contents to carry out invention]
본 발명에 따른 상기 화학식 1로 표시되는 3, 6-이치환된 인다졸 유도체의 약학적으로 허용 가능한 염은 당해 기술 분야에서 통상적인 방법에 의해 제조될 수 있다. 약학적으로 허용된 염은 인체에 독성이 낮고 모화합물의 생물학적 활성과 물리화학적 성질에 악영향을 주지 않아야 한다.  Pharmaceutically acceptable salts of 3, 6-disubstituted indazole derivatives represented by Formula 1 according to the present invention may be prepared by conventional methods in the art. Pharmaceutically acceptable salts are of low toxicity to humans and should not adversely affect the biological activity and physicochemical properties of the parent compound.
약학적으로 허용된 염은 약학적으로 사용 가능한 유리산과 화학식 1의 염기 화합물의 산부가염 , 그리고 알칼리 금속염 (나트륨염 등)과 알칼리 토금속염 (칼슘염 등)， 그리고 유기염과 화학식 1의 카르복실산의 유기염기부가염， 그리고 아미노산부가염으로 구성된다. 약학적으로 허용된 염 제조에 사용될 수 있는 유리산은 무기산과 유기산으로 나눌 수 있다. 무기산은 염산, 황산， 질산， 인산, 과염소산， 브롬산 등이 사용될 수 있다.  Pharmaceutically acceptable salts include pharmaceutically usable free acids and acid addition salts of base compounds of formula (I), alkali metal salts (such as sodium salts) and alkaline earth metal salts (such as calcium salts), and organic salts and carboxyl compounds of formula (I). It is composed of organic base addition salt of acid and amino acid addition salt. Free acids that can be used to prepare pharmaceutically acceptable salts can be divided into inorganic acids and organic acids. The inorganic acid may be hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, perchloric acid, bromic acid, or the like.
유기산은 초산, 메탄설폰산, 에탄설폰산, / 를루엔설폰산, 푸마린산. 말레산, 말론산, 프탈산, 숙신산, 젖산, 구연산， 시트르산, 글루콘산， 타타르산, 살리실산, 말산, 옥살산， 벤조산, 엠본산, 아스파르트산, 글루탐산 등이 사용될 수 있다. 유기염기부가염 제조에 사용될 수 있는 유기염기는 트리스 (하이드록시메틸)메틸아민, 디싸이클로핵실아민 등이다.  Organic acids include acetic acid, methanesulfonic acid, ethanesulfonic acid, / luenesulfonic acid and fumaric acid. Maleic acid, malonic acid, phthalic acid, succinic acid, lactic acid, citric acid, citric acid, gluconic acid, tartaric acid, salicylic acid, malic acid, oxalic acid, benzoic acid, embonic acid, aspartic acid, glutamic acid and the like can be used. Organic bases that can be used for the preparation of organic base addition salts are tris (hydroxymethyl) methylamine, dicyclonuxylamine and the like.
아미노산부가염기 제조에 사용될 수 있는 아미노산은 알라닌, 글라이신 등의 천연아미노산이다.  Amino acids that can be used to prepare amino acid addition bases are natural amino acids such as alanine, glycine and the like.
본 발명에 따른 상기 화학식 1로 표시되는 3 ,6-이치환된 인다졸 유도체는 상기한 약학적으로 허용된 염과 더불어 모든 수화물 그리고 용매화물도 포함한다. 상기한 약학적으로 허용된 염은 하기한 통상적인 방법으로 제조될 수 있다. 상기한 화학식 1의 염기 화합물을 메탄올, 에탄올， 아세톤, 1,4-디옥산과 같은 물과 섞일 수 있는 용매에 녹인 다음에 유리산 또는 유리염기를 가한 후에 결정화되거나 또는 재결정화될 수 있다.  The 3,6-disubstituted indazole derivatives represented by Chemical Formula 1 according to the present invention include all hydrates and solvates in addition to the pharmaceutically acceptable salts described above. The pharmaceutically acceptable salts described above may be prepared by the conventional methods described below. The base compound of Formula 1 may be dissolved in a solvent which may be mixed with water such as methanol, ethanol, acetone, 1,4-dioxane, and then crystallized or recrystallized after adding a free acid or free base.
또한, 본 발명에 따른 상기 화학식 1로 표시되는 3， 6—이치환된 인다졸 유도체는 하나 또는 그 이상의 비대칭 중심을 가질 수 있고， 이러한 화합물의 경우 거울상 이성질체 또는 부분입체이성질체가 존재할 수 있다. 따라서 , 본 발명은 각 이성질체 또는 이들 이성질체 흔합물을 포함한다. 상이한 이성질체는 통상의 방법에 의해 분리되거나 또는 분해될 수 있거나， 또는 임의의 소정 이성질체는 통상의 합성법에 의해 또는 입체특이적 또는 비대칭적 합성에 의해 수득할 수 있다.  In addition, the 3, 6-disubstituted indazole derivatives represented by Formula 1 according to the present invention may have one or more asymmetric centers, and in the case of such compounds, enantiomers or diastereomers may be present. Accordingly, the present invention includes each isomer or a mixture of these isomers. Different isomers can be separated or resolved by conventional methods, or any given isomer can be obtained by conventional synthesis or by stereospecific or asymmetric synthesis.
또한， 본 발명은 본 발명에 따른 상기 화학식 1로 표시되는 화합물의 방사성 유도체를 포함하며, 이들 방사성 화합물은 생체연구 분야에 유용하다.  In addition, the present invention includes a radioactive derivative of the compound represented by Formula 1 according to the present invention, these radioactive compounds are useful in the field of biological research.
본 발명에 따른 화합물을 정의하기 위해 사용된 치환기에 대해 보다 상세히 설명하면 다음과 같다.  The substituents used to define the compounds according to the invention are explained in more detail as follows.
본 발명에서의 '할로겐 원자' 라 함은 클로로, 플루오로, 브로모, 요오도를 의미한다 .  The term "halogen atom" in the present invention means chloro, fluoro, bromo, iodo.
본 발명에서의 '알킬기' 라 함은 메틸， 에틸， ;r프로필， /_프로필, 싸이클로프로필, /广부틸, /-부틸, 부틸， 싸이클로부틸, 싸이클로프로필메틸，In the present invention, the "alkyl group" means methyl, ethyl,; rpropyl, / propyl, Cyclopropyl, / 广 butyl, / -butyl, butyl ， cyclobutyl, cyclopropylmethyl ，
/r펜틸, /-펜틸, 네오펜틸， ev- —펜틸， 싸이클로펜틸, 싸이클로부틸메틸 , /广핵실, 핵실， 싸이클로핵실, 싸이클로펜틸메틸, 헵틸, 싸이클로핵실메틸, 옥틸 등을 포함하는 1개에서 10개까지의 탄소원자를 가지는 지방족 포화 탄화수소기를 의미한다 . / rpentyl, / -pentyl, neopentyl, ev- —pentyl, cyclopentyl, cyclobutylmethyl, / 广 nuclear chamber, nuclear chamber, cyclonuclear chamber, cyclopentylmethyl, heptyl, cyclonuclear methylmethyl, octyl, etc. It means an aliphatic saturated hydrocarbon group having up to 10 carbon atoms.
본 발명에서의 '할로알킬기' 라 함은 디플루오르메틸기， 트리플루오르메틸기와 같이 한개 이상의 할로겐 원자에 의해 수소원자가 치환된 알킬기를 의미한다. 본 발명에서의 '알콕시기' 라 함은 메톡시， 에톡시， /广프로폭시 , /-프로폭시 , /广부톡시, 7-부톡시, 기톡시를 포함하는， Cr (1(,의 알킬기에서 선택된 치환체에 의해 수소원자가 치환된 하이드록시기를 의미한다. In the present invention, the "haloalkyl group" means an alkyl group in which a hydrogen atom is substituted by one or more halogen atoms, such as a difluoromethyl group and a trifluoromethyl group. In the present invention, the term "alkoxy group" means methoxy, ethoxy, /广 propoxy, / -propoxy, / 广 butoxy, 7-butoxy, group containing methoxy, C r ( 1 ( , It means a hydroxyl group in which a hydrogen atom is substituted by a substituent selected from an alkyl group.
본 발명에서의 '아릴기' 라 함은 페닐， 나프틸， 안트라쓰닐, 페난트리닐 등을 포함하여 , 단일고리 , 두고리， 또는 세고리 방향족 탄화수소기를 의미한다. The term "aryl group" in the present invention means a monocyclic, bicyclic, or tricyclic aromatic hydrocarbon group, including phenyl, naphthyl, anthracenyl, phenanthryl, and the like.
본 발명에서의 '바이아릴기 ' 라 함은 바이페닐 , 페녹시페닐 , 벤조일페닐, 또는 페닐디아제닐페닐을 포함하여, 5 내지 7각형의 두 개의 아릴기가 결합된 방향족 탄화수소기를 의미한다. In the present invention, the term "biaryl group" refers to an aromatic hydrocarbon group in which two aryl groups of 5 to 7 are bonded, including biphenyl, phenoxyphenyl, benzoylphenyl, or phenyldiazenylphenyl.
본 발명에서의 '헤테로방향족고리기' 라 함은 피롤릴， 퓨라닐， 싸이오페닐, 피라졸릴, 이미다졸릴， 옥사졸릴, 이소옥사졸릴, 싸이아졸¾， 이소싸이아졸릴, 트리아졸릴, 옥사디아졸 ¾, 싸이아디아졸 ¾, 테트라졸릴， 피리디닐, 피라지닐， 피리다지닐, 피리미디닐, 트리아졸릴, 인돌릴， 이소인돌릴， 벤조퓨라닐, 벤조퓨라자닐 , 다이벤조퓨라닐 , 이소벤조퓨라닐， 인다졸릴， 벤즈이미다졸릴 , 벤즈옥사졸릴, 벤즈이소옥사졸릴, 벤조 [d][ 1,3]디옥솔일, 벤조싸이아졸릴, 다이벤조싸이오페닐 나프티리딜, 벤즈이소싸이아졸릴, 퀴놀리닐, In the present invention, the term "heteroaromatic ring group " refers to pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazol¾, isocazolyl, triazolyl, oxa Diazole ¾, thiadiazole ¾, tetrazolyl, pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, triazolyl, indolyl, isoindolinyl, benzofuranyl, benzofurazanyl, dibenzofuranyl, Isobenzofuranyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisooxazolyl, benzo [d] [1,3] dioxyl, benzothiazolyl, dibenzothiophenyl naphthyridyl, benzisothio Azolyl, quinolinyl,
이소퀴놀리닐, 퀴녹살리닐, 프탈라지닐， 치놀리닐， 퀴나졸리닐 등을 포함하여， 헤테로원자가 1개 이상 포함된 5 내지 7각형의 단일고리 , 두고리 , 또는 세고리 방향족 해테로탄화수소기를 의미한다. 5- to 7-membered monocyclic, bicyclic, or tricyclic aromatic heterohydrocarbon groups containing one or more heteroatoms, including isoquinolinyl, quinoxalinyl, phthalazinyl, chinolinyl, quinazolinyl, and the like it means.
본 발명에서의 '해테로지방족고리기' 라 함은 몰포리닐， 피페리딘기 , 피페라지닐， ^보호된 피페라지닐 등을 포함하여, 헤테로원자가 1개 이상 포함된 5 내지 7각형의 지방족 헤테로탄화수소 고리기를 의미한다. 본 발명에 따른 상기 화학식 1로 표시되는 3, 6ᅳ이치환된 인다졸 유도체에 있어서, 바람직하기로는 다음과 같다. In the present invention, the term "heteroaliphatic ring group" includes a morpholininyl, piperidine group, piperazinyl, ^ protected piperazinyl, and the like. It means a heterohydrocarbon ring group. In the 3, 6'-substituted indazole derivatives represented by the formula (1) according to the present invention, preferably,
상기 은 할로겐， Cr ;알킬 및 d-Cs할로알킬로 이루어진 군으로부터 선택된 치환체가 1 내지 4개 치환 또는 비치환된 핵원자수가 5 내지 7인 아릴렌기를 나타내고， The silver represents an arylene group having 5 to 7 substituted or unsubstituted nuclear atoms having 1 to 4 substituents selected from the group consisting of halogen, Cr; alkyl and d-Cs haloalkyl,
상기 Ar2는 단일결합선이거나; 할로겐， 알킬 및 d-C6할로알킬로 이루어진 군으로부터 선택된 치환체가 1 내지 4개 치환 또는 비치환된 핵원자수가 5 내지 8인 아릴렌기 ; 할로겐， d-C6알킬 및 d-C(i할로알킬로 이루어진 Ar 2 is a single bond line; An arylene group having 5 to 8 substituted or unsubstituted nuclear atoms having 1 to 4 substituents selected from the group consisting of halogen, alkyl and dC 6 haloalkyl; Halogen, dC 6 alkyl and dC (i consisting of haloalkyl
군으로부터 선택된 치환체가 1 내지 4개 치환 또는 비치환된 핵원자수가 5 내지 8인 2가 헤테로방향족고리기 ; 또는 할로겐， d- 알킬 및 d-Cs할로알킬로 이루어진 군으로부터 선택된 치환체가 1 내지 4개 치환 또는 비치환된 A divalent heteroaromatic ring group having 5 to 8 nuclear atoms having 1 to 4 substituted or unsubstituted substituents selected from the group; Or 1 to 4 substituted or unsubstituted substituents selected from the group consisting of halogen, d-alkyl and d-Cshaloalkyl
핵원자수가 5 내지 8인 2가 해테로지방족고리기; 를 나타내고, Divalent heteroaliphatic ring groups having 5 to 8 nuclear atoms; Indicates,
상기 X 및 L은 서로 같거나 다른 것으로서 단일결합선이거나; -NH-; -N(C )-; -NHC(O)-; -C(0)丽-; -C(0)NHNH-; -C(0)蘭 CH2—； -C(0)NHCH2CH2-; -NHC(0)NH-; -NHC(0)N(CH:!)-; -NHC(S)NH-; 또는 ᅳ NHS02—를 나타내고, X and L are the same as or different from each other and are a single bond line; -NH-; -N (C)-; -NHC (O)-; -C (0) 丽-; -C (0) NHNH-; —C (0) ′ CH 2 —; —C (0) NHCH 2 CH 2 —; -NHC (0) NH-; -NHC (0) N (CH :! )-; -NHC (S) NH-; Or ᅳ NHS0 2 —,
상기 R1 및 R2는 서로 같거나 다른 것으로서 수소원자; -아 I; d-Cfi알킬기 ; R 1 and R 2 are the same as or different from each other as a hydrogen atom; -Ah I; d-Cfi alkyl group;
-0-(C C6알킬); -d- 하이드록시알킬기； -(C厂 C"알킬렌)ᅳ헤테로지방족고리； -(C C„알킬렌 ) -해테로방향족고리； -(C -CE알킬렌 ) -아릴； 아릴기； . ᅳ 헤테로방향족고리기; 또는 헤테로지방족고리기를 나타내고, 또한 상기 R1과-0- (CC 6 alkyl); -d- hydroxy alkyl; - (C厂C "alkylene) eu heterocyclic aliphatic ring; - (CC" alkylene) - by interrogating ring; - (E C -C alkylene) aryl, aryl group; ᅳ heteroaromatic ring group or heteroaliphatic ring group, and R 1 and
R2는 서로 결합하여 헤테로방향족고리기; 또는 헤테로지방족고리기를 형성할 수 있으며, 이때 상기 아릴, 헤테로방향족고리, 및 헤테로지방족고리는 각각 독립적으로 할로겐, C,-C(;알킬， 및 CRC(;할로알킬로 이루어진 군으로부터 선택된 1 내지 3개의 치환체로 치환 또는 비치환될 수 있고， R 2 is a mutually bonded heteroaromatic ring group; Or a heteroaliphatic ring group, wherein the aryl, heteroaromatic ring, and heteroaliphatic ring are each independently selected from the group consisting of halogen, C, -C ( ; alkyl, and C R C (; haloalkyl). To unsubstituted or substituted with 3 substituents,
상기 R3은 수소원자; 할로겐원자; CN; -N02; —OH; -SH; — NH2; -NHO^-C )알킬);R 3 is a hydrogen atom; Halogen atom; CN; -N0 2 ; —OH; -SH; — NH 2 ; -NHO ^ -C) alkyl);
— N(d— C10알킬 )2; d—Cw알킬기 ; d-do할로알킬기 ; C,— C1()시아노알킬기 ; d- 하이드록시알킬기 ; C2-C10알콕시알킬기 ; -CKd— C1()알킬); -(XC-do할로알킬); -S(C「(： 1(,알킬); S(C广 C10할로알킬); (d— C10알킬렌)ᅳ N¾; -(CrC1(, — N (d— C 10 alkyl) 2 ; d—Cw alkyl group; d-do haloalkyl group; C, —C 1 ( ) cyanoalkyl group; d- hydroxyalkyl group; C 2 -C 10 alkoxyalkyl group; -CKd—C 1 () alkyl); -(XC-dohaloalkyl); -S (C "(： 1 ( , alkyl); S (C 广 C 10 haloalkyl); (d— C 10 alkylene) ᅳ N¾;-(CrC 1 ( ,
알킬렌)— NH(Cl-Cl0알킬); — (Cl-Cl„알킬렌)— N ^-CK)알킬 )2; -(C C1() Alkylene) — NH ( Cl - Cl0 alkyl); — ( Cl - Cl „alkylene) — N ^ -C K) alkyl) 2 ; -(CC 1 ()
알킬렌) -N[(C厂 C1()알킬렌) -N :— C1()알킬 )2] [C C1(,알킬]; -(C C Alkylene) -N [(C 厂 C 1 ( ) alkylene) -N: — C 1 () alkyl) 2 ] [CC 1 ( , alkyl];-(CC
알킬렌) - (하이드록시이미노); -0— (C厂 C1()알킬렌) -NH2; -O-Cd-do Alkylene)-(hydroxyimino); -0— (C 厂 C 1 ( ) alkylene) -NH 2 ; -O-Cd-do
알킬렌) -NH(d— C1()알킬); -O-Cd-do알킬렌) -N(d— C,„알킬 )2; -O-Cd-do 알킬렌 )一헤테로지방족고리； — 0—헤테로지방족고리； -NH(C C1()알킬렌 -N'H2)； -NH[C C1(,알킬렌 NH(C厂 C10알킬)]； -NH[CrCU)알킬렌 N(( C10알킬 )2]； -N[C C1(, 알킬 ] [d-d,,알킬렌一 NH(d— C10알킬 ) ]； -N[C C1(,알킬 ] [C厂 C10알킬렌 -N(C厂 C1() 알킬 )2]； -NFKCrCu,하이드록시알킬 )； -N(C C1(,알킬 ) (d— C10하이드록시알킬 )； ᅳ NH(헤테로지방족고리); -N(d-C1(,알킬) (헤테로지방족고리); -NHCd-d,, 알킬렌-헤테로지방족고리); -N(C C10알킬) (d-C10알킬렌-헤테로지방족고리); -NHC(0)—해테로지방족고리 ; -NHC(0)-(CrC1()알킬); -NHC(0)0-(C1-CW)알킬)， -NHC(0)-(C C1(,알킬렌 -NR¥)； -C(0)(C C1()알킬); C(0)0H; -C(0)0(C C]()알킬); 아릴기; 해테로방향족고리기; 또는 해테로지방족고리기; 를 나타내고, 이때 아릴, 헤테로방향족고리, 또는 해테로지방족고리는 각각 독립적으로 할로겐， ᅳ OH, -CN, 옥소 (=0)， CrC6알킬， d-Q;할로알킬， CrC(i알콕시， d-C6알킬렌 -(C厂 C6 알콕시)， ( c( 알킬렌 -C(O)-N¾; c— 알킬렌 -( ω-ΝΗ ( 알킬); d- 알킬렌 c(0)— N((VC6알킬 )2; C- ;알킬렌ᅳ C(0)-아릴 ; -CWKd- ;알킬)， Alkylene) -NH (d—C 1 ( ) alkyl); -O-Cd-doalkylene) -N (d— C, “alkyl) 2 ; -O-Cd-do alkylene) 헤 heteroaliphatic ring; — 0—heteroaliphatic ring; -NH (CC 1 () alkylene -N ' H 2 ); -NH [CC 1 ( , alkylene NH (C 厂C 10 alkyl)]; -NH [C r C U) alkylene N ((C 10 alkyl) 2 ]; -N [CC 1 ( , alkyl] [dd ,, alkylene Ⅰ NH (d— C 10 alkyl) ] -N [CC 1 ( , alkyl] [C 厂 C 10 alkylene -N (C 厂 C 1 ( ) alkyl) 2 ]; -NFKCrCu, hydroxyalkyl); -N (CC 1 ( , alkyl) ( d—C 10 hydroxyalkyl); ᅳ NH (heteroaliphatic ring);-N (dC 1 ( , alkyl) (heteroaliphatic ring); -NHCd-d ,, alkylene-heteroaliphatic ring);-N (CC 10 alkyl) (dC 10 alkylene-heteroaliphatic ring); -NHC (0) —heteroaliphatic ring; -NHC (0)-(C r C 1 () alkyl); -NHC (0) 0- (C 1 -C W) alkyl), -NHC (0)-(CC 1 ( , alkylene -NR ¥); -C (0) (CC 1 () alkyl); C (0) 0H; -C (0) 0 (CC] () alkyl); an aryl group; to interrogating ring group; or by interrogating an alicyclic group; represents a, wherein aryl, heteroaromatic ring, or by interrogating the aliphatic ring are each dock Typically halogen, eu OH, -CN, oxo (= 0), C r C 6 alkyl, dQ; haloalkyl, C r C (i-alkoxy, dC 6 alkylene - (C厂C 6 alkoxy), (c ( Alkylene-C (O) -N¾; c— alkylene- (ω-ΝΗ (alkyl); d-alkylene c (0) — N ((VC 6 alkyl) 2 ; C-; alkylene ᅳ C (0 ) -Aryl; -CWKd-; alkyl),
-C(0) (아릴)， -C(0) (헤테로방향족고리), -C00H, -(XOXXd— C6알킬)， -S(0)(C C(i 알킬)， -SW d-Cfi알킬), N¾, NH(d-C (；알킬)， 및 N(d-C(;알킬 )2로 이루어진 군으로부터 선택된 1내지 3개의 치환체로 치환 또는 비치환되며, -C (0) (aryl), -C (0) (heteroaromatic ring), -C00H,-(XOXXd—C 6 alkyl), -S (0) (CC (i alkyl), -SW d-Cfialkyl ), N¾, NH (dC (; alkyl), and N (dC (; alkyl) 2 ) is substituted or unsubstituted with 1 to 3 substituents selected from the group consisting of
상기 치환기 정의에 사용된 아릴 또는 아릴렌은 단일고리, 두고리 또는 세고리로 이루어지고, 핵원자수가 5내지 15개인 방향족 탄화수소기를 The aryl or arylene used in the above substituent definition consists of a monocyclic, bicyclic or tricyclic, aromatic hydrocarbon group having 5 to 15 nuclear atoms.
나타내고; Represent;
상기 치환기 정의에 사용된 헤테로방향족고리는 N, 0및 S 중에서 선택된 헤테로원자가 1 내지 4개 포함되고， 단일고리， 두고리 또는 세고리로 The heteroaromatic ring used in the above substituent definition includes 1 to 4 heteroatoms selected from N, 0 and S, and may be selected from monocyclic, bicyclic or tricyclic.
이루어지고, 핵원자수가 5내지 15개인 방향족 헤테로탄화수소기를 나타내고; 상기 치환기 정의에 사용된 헤테로지방족고리는 N, 0및 S 중에서 선택된 헤테로원자가 1 내지 4개 포함되고， 단일고리， 두고리 또는 세고리로 An aromatic heterohydrocarbon group having 5 to 15 nuclear atoms; The heteroaliphatic ring used in the above substituent definition includes 1 to 4 heteroatoms selected from N, 0, and S, and includes a monocyclic ring, a bicyclic ring, or a tricyclic ring.
이루어지고， 블포화 탄소사슬을 포함 또는 미포함할 수 있는 핵원자수가 5 내지 15개인 지방족 헤테로탄화수소기를 나타낸다. 본 발명에 따른 상기 화학식 1로 표시되는 3,6—이치환된 인다졸 유도체에 있어서, 보다 바람직하기로는 다음과 같다. And an aliphatic heterohydrocarbon group having 5 to 15 nuclear atoms which may or may not contain or contain a saturated carbon chain. In the 3,6—disubstituted indazole derivatives represented by Chemical Formula 1 according to the present invention, more preferably,
상기 An은 클로로, 플루오로， 브로모, 메틸 및 트리플루오로메틸로 이루어진 군으로부터 선택된 치환체가 1 내지 2개 치환 또는 비치환된 페닐렌을 An represents phenylene having 1 to 2 substituted or unsubstituted substituents selected from the group consisting of chloro, fluoro, bromo, methyl and trifluoromethyl.
나타낸다. ' Indicates. '
상기 세는 단일결합선이거나， 클로로， 플루오로, 브로모, 메틸 및 The tax is a single bond, or chloro, fluoro, bromo, methyl and
트리플루오로메틸로 이루어진 군으로부터 선택된 치환체가 1 내지 2개 치환 또는 비치환된 페닐렌 , 피리디닐렌 , 피라지닐렌， 피라지닐렌， 이미다졸일렌， 이미다졸일렌, 피라졸일렌, 옥사졸일렌， 이소옥사졸일렌， 티아졸일렌， 퓨란일렌 피페리딘일렌, 피를리딘일렌, 또는 벤조 [d][l,3]디옥솔 -5-일렌을 나타낸다. 상기 X는 단일결합선이거나， -NH-, 또는 -N(C )- 를 나타낸다. Substituted or unsubstituted phenylene, pyridinylene, pyrazinylene, pyrazinylene, imidazolylene, imidazolylene, pyrazolylene, oxazolylene having 1 to 2 substituents selected from the group consisting of trifluoromethyl Isooxazolylene, thiazolylene, furanylene piperidinylene, pyridinylene, or benzo [d] [l, 3] dioxol-5-ylene. X is a single bond or represents -NH-, or -N (C)-.
상기 L은 — NHC(O)—， — C(0)NH—， — C(0)NHNH―， — C(0)NHCH2—， — C(0)NHCH2CH2一, L is — NHC (O) — ， — C (0) NH— ， — C (0) NHNH― ， — C (0) NHCH 2 — ， — C (0) NHCH 2 CH 2一,
-NHC(0)NH-, -NHC(0)N(CH3)-, —NHC(S)NH―， 또는 — NHS02- 를 나타낸다. -NHC (0) NH-, -NHC (0) N (CH 3 )-, -NHC (S) NH-, or-NHS0 2- .
상기 R]및 R2는 서로 같거나 다른 것으로서 수소원자， 하이드록시기, 메틸기， 에틸기， 프로필기, 이소프로필기, 싸이클로프로필기， 싸이클로핵실기, 하이드록시에틸기， 몰포리노기 ; 몰포리노에틸기 , 피페리딘— 4-일기， Wherein R] and R 2 are the same or different and represents hydrogen atom, a hydroxyl group, a methyl group, an ethyl group, a propyl group, an isopropyl group, a cyclo propyl, cyclo nucleus group, a hydroxyl group, the molar Poly group; Morpholinoethyl group, piperidine- 4-yl group ，
1-메틸피페리딘—4-일기, 피페라진— 1-일기, 4-메틸피페라진—1-일기， 페닐기， 벤질기， 피리딘—2-일기， 피리딘 -3-일기, 피리딘—4—일기, (피리딘— 2—일)메틸기, (피리딘— 3—일)메틸기， (피리딘— 4—일)메틸기， (6-클로로피리딘 3 메틸기， 1-methylpiperidine—4-yl, piperazine— 1-yl, 4-methylpiperazin—1-yl, phenyl, benzyl, pyridine—2-yl, pyridine-3-yl, pyridine—4—diary , (Pyridine- 2-yl) methyl group, (pyridine- 3-yl) methyl group, (pyridine- 4-yl) methyl group, (6-chloropyridine 3-methyl group,
2-플루오로피리딘 -3-일기， 5—폴루오로피리딘 -3-일기, 6—플루오로피리딘 -3-일기, 4-메틸피리딘— 3—일기， 6-메틸피리딘 -3-일기， 피리미딘— 3-일기, 피리미딘 -4-일기 , (피리미딘 -3—일)메틸기, (피리미딘 -4—일)메틸기, 피리미딘— 5-일기， 2-fluoropyridin-3-yl group, 5—poloropyridin-3-yl group, 6—fluoropyridin-3-yl group, 4-methylpyridine— 3—yl group, 6-methylpyridin-3-yl group, pyri Midin— 3-yl, pyrimidin-4-yl, (pyrimidin-3—yl) methyl, (pyrimidin-4—yl) methyl, pyrimidine— 5-yl,
이미다졸 -4-일기, 1—메틸이미다졸 -4-일기, (이미다졸— 2-일)메틸기, 또는 피롤리딘— 3—일기를 나타내고, 또는 상기 R1및 가 서로 결합하여 피페라지닐기 또는 4-메틸피페라진—1-일기를 형성할 수 있다. Imidazole-4-yl group, 1—methylimidazol-4-yl group, (imidazol—2-yl) methyl group, or pyrrolidin—3—yl group, or R 1 and are bonded to each other to pipera A zyl group or a 4-methylpiperazine—1-yl group.
상기 R3은 수소원자， 클로로원자， 플루오로원자, 브로모원자, 시아노기， 니트로기， 하이드록시기, 아세틸기， 메틸기， 에틸기, 이소프로필기, er—부틸기 브로모메틸기， 시아노프로필기， 디메틸아미노메틸기， R 3 is hydrogen atom, chloro atom, fluoro atom, bromo atom, cyano group, nitro group, hydroxy group, acetyl group, methyl group, ethyl group, isopropyl group, er-butyl bromomethyl group, cyanopropyl Group, dimethylaminomethyl group ，
((2—디메틸아미노에틸) (메틸)아미노)메틸기, 1- (하이드록시이미노)에틸기, 트리폴루오로메틸기， (트리플루오로메틸)싸이오기， 메록시기， ((2-dimethylaminoethyl) (methyl) amino) methyl group, 1- (hydroxyimino) ethyl group, trifluoromethyl group, (trifluoromethyl) thio group, hydroxy group,
디플루오로메특시기， 트리플루오로메록시기， 2— (디메틸아미노)에톡시기, 피페리딘 -4ᅩ일메록시기， ( 1-메틸피페리딘 -4-일 )메톡시기, Difluoromethoxy particular time, trifluoromethoxy rock group, 2- (dimethylamino) ethoxy, piperidin-4 o yl merok group, (1-methylpiperidin-4-yl) methoxy group,
2- (피를리딘 -1-일)에록시기， 2— (1-메틸피롤리딘 -2-일)에특시기， 2- (pyridin-1-yl) ethoxy group, 2— (1-methylpyrrolidin-2-yl)
2-아미노 -2—메틸프로폭시기， 1- (디메틸아미노)프로판—2—일옥시기， 2-amino-2-methylpropoxy, 1- (dimethylamino) propane-2-2-yloxy group,
2一 (디메틸아미노) -2-메틸프로폭시기， 피페리딘 -4—일옥시기，  2 一 (dimethylamino) -2-methylpropoxy group, piperidine-4—yloxy group ，
(1-메틸피페리딘 -4-일)옥시기， 아미노기， 메틸아미노기， 디메틸아미노기， (2-아미노에틸)아미노기， (2-아미노 -2-메틸프로필 )아미노기， (1-methylpiperidin-4-yl) oxy group, amino group, methylamino group, dimethylamino group, (2-aminoethyl) amino group, (2-amino-2-methylpropyl) amino group,
(2-디메틸아미노 -2-메틸프로필)아미노기， (2-하이드록시에틸)아미노기， (2-dimethylamino-2-methylpropyl) amino group, (2-hydroxyethyl) amino group,
(2-하이드톡시프로필)아미노기 , (3—하이드록시프로필)아미노기， (2-hydroxypropyl) amino group, (3—hydroxypropyl) amino group,
(2—하이드록시부틸 )아미노기， (2-디메틸아미노에틸 )아미노기 ,  (2—hydroxybutyl) amino group, (2-dimethylaminoethyl) amino group,
(2-디메틸아미노에틸 ) (메틸)아미노기， (2—하아드록시에틸) (메틸)아미노기， (2ᅳ하이드록시ᅳ 2-메틸프로필 )아미노기 , (메틸 ) ( ( 1-메틸 피라졸—4-일 )메틸)아미노기 , (피를리딘 -1-일에틸 )아미노기 , (테트라하이드로 -2/ 피란 -4-일 )아미노기 , (2-dimethylaminoethyl) (methyl) amino group, (2—hydroxyethyl) (methyl) amino group, (2'hydroxy ᅳ 2-methylpropyl) amino group, (Methyl) ((1-methylpyrazol- 4-yl) methyl) amino group, (pyridin-1-ylethyl) amino group, (tetrahydro-2 / pyran-4-yl) amino group,
(1,2, 2, 6, 6-펜타메틸피페리딘— 4-일)아미노기， (1-메틸피페리딘 -4—일)아미노기 , (1,2, 2, 6, 6-pentamethylpiperidin- 4-yl) amino group, (1-methylpiperidin-4-yl) amino group,
1-아세틸피페리딘 -4-카복스아미도기 , 2- (디메틸아미노)아세트아미도기 , 페닐기 , 4—클로로페닐기， 4-플루오로페닐기, 4-메특시페닐기， 4-하이드록시페닐기, 피리딘 -2—일기， 피리딘—3-일기 , 피리딘—4-일기 , 피페라진 -1—일기， 1-acetylpiperidine-4-carboxamido group, 2- (dimethylamino) acetamido group, phenyl group, 4—chlorophenyl group, 4-fluorophenyl group, 4-methoxyphenyl group, 4-hydroxyphenyl group, pyridine -2—diary, pyridine—3-diary, pyridine—4-diary, piperazine -1—diary,
4一메틸피페라진 -1-일기， 4-에틸피페라진 -1-일기， 부틸피페라진 1-일기 ,4 one methyl piperazine-1-yl group, 4-ethyl piperazine-1-yl group, butyl piperazine 1-yl group,
3,5—디메틸피페라진 -1ᅳ일기 , 3, 4， 5-트리메틸피페라진 -1-일기 , 3,5—dimethylpiperazin-1 ylyl group, 3, 4, 5-trimethylpiperazin-1-yl group,
4- ( 2-메톡시에틸)피페라진 - 1-일기, 4— (메틸설포닐)피페라진 - 1-일기, 4- (2-methoxyethyl) piperazine- 1-yl group, 4— (methylsulfonyl) piperazine-1-yl group,
4—아세틸피페라진— 1-일기, 4-니코티노일피페라진—1-일기， 4—acetylpiperazine— 1-diary, 4-nicotinoylpiperazine—1-diary,
4-(2- (디메틸아미노) -2-옥소에틸 )피페라진— 1—일기，  4- (2- (dimethylamino) -2-oxoethyl) piperazine— 1—yl,
4一 ( 2—옥소 -2— (페닐아미노)에틸)피페라진— 1-일기， 4 一 (2—oxo-2— (phenylamino) ethyl) piperazine— 1-yl,
4- (이소프로필설포닐)피페라진— 1-일기， 4-벤조일피페라진 -1—일기, 이미다졸기， 4- (isopropylsulfonyl) piperazine— 1-yl, 4-benzoylpiperazine-1—yl, imidazole,
2-메틸이미다졸기, 4-메틸이미다졸기， 2,4-디메틸이미다졸기， 피를리디닐기， 3-하이드록시피롤리딘ᅳ 1-일기, 3- (디메틸아미노)피를리딘 -1-일기, 2-methylimidazole group, 4-methylimidazole group, 2,4-dimethylimidazole group, pyridinyl group, 3-hydroxypyrrolidin ᅳ 1-yl group, 3- (dimethylamino) pyridine- Diary,
3- (디에틸아미노)피롤리딘 -1-일기， 4-메틸 -1,4-디아제판 -1—일기 ,  3- (diethylamino) pyrrolidin-1-yl group, 4-methyl-1,4-diazepane-1-yl group,
핵사하이드로피를로 [1,2-a]피라진 -2(1/)-일기 , Nucleohydropyrrolo [1,2-a] pyrazine-2 (1 /)-diary,
1,4—디옥사—8-아자스피로 [4, 5]데칸 -8—일기, 몰포리노기, 피페리딘— 1-일기, 1,4—Dioxa—8-Azaspiro [4, 5] decane-8—diary, morpholino group, piperidine— 1-diary,
4-옥소피페리딘—1-일기， 4-하이드록시피페리딘 -1-일기, 4-메틸피페리딘—1-일기， 4—이소프로필피페리딘 -1-일기， 4-메특시피페리딘 -1ᅳ일기, 4-oxopiperidine- 1-yl group, 4-hydroxypiperidine-1-yl group, 4-methylpiperidine- 1-yl group, 4-isopropylpiperidine-1-yl group, 4-methopy Ferridine -1 Diary,
4—(메틸아미노)피페리딘 -1-일기 , 또는 4- (디메틸아미노)피페리딘 -1-일기를 나타낸다. 본 발명에 따른 상기 화학식 1로 표시되는 3 ,6-이치환된 인다졸 유도체를 구체적으로 예시하면 다음과 같다 ：  4— (methylamino) piperidin-1-yl group or 4- (dimethylamino) piperidin-1-yl group. Specific examples of the 3,6-disubstituted indazole derivative represented by Chemical Formula 1 according to the present invention are as follows:
6-(5ᅩ(3-(2-시아노프로판 -2-일)벤즈아미도) -2-메틸페닐아미노)— /V-메틸 -17-인다 졸 -3-카복스아미드 (실시예 1)； 6- (5 ᅩ (3- (2- cyanopropane -2-yl) benzamido) -2-methylphenylamino) — / V-methyl-17-indazol-3-carboxamide (Example 1) ;
6-(5— (3-(2-시아노프로판 -2-일)벤즈아미도) -2-메틸페닐아미노)— Λ 2-몰포리노 에틸) -1 —인다졸—3—카복스아미드 (실시예 2);  6- (5— (3- (2-cyanopropane-2-yl) benzamido) -2-methylphenylamino) — Λ 2-morpholino ethyl) -1 —indazole—3—carboxamide (implemented Example 2);
6-(5-(3-(2—시아노프로판 -2-일)벤즈아미도) -2-메틸페닐아미노 )— ᅩ(2—히드록시 에틸)—1 —인다졸 -3-카복스아미드 (실시예 3)； 6- (5- (3- (2-cyano-propane-2-yl) benz amido) -2-phenyl-amino) - o (2-hydroxyethyl) -1H-indazole-3-carboxamide ( Example 3);
6-(5— (3— (2-시아노프로판— 2—일 )벤즈아미도)—2—메틸페닐아미노) -yV- (피리딘 -4ᅳ일 )-LY-인다졸 -3-카복스아미드 (실시예 4);  6- (5— (3— (2-cyanopropane— 2—yl) benzamido) —2—methylphenylamino) -yV- (pyridin-4hexyl) -LY-indazole-3-carboxamide ( Example 4);
6一(2-메틸 -5-(3- (트리플루오로메틸)밴즈아미도)페닐아미노) -ΛΚ피리딘 -4-일) -1 -인다졸— 3—카복스아미드 (실시예 5);  6- (2-methyl-5- (3- (trifluoromethyl) banzamido) phenylamino) -ΛΚpyridin-4-yl) -1-indazole—3—carboxamide (Example 5);
yV-시클로프로필 -6-(2ᅳ메틸 -5-(3- (트리플루오로메틸)벤즈아미도)페닐아미노) -L7 -인다졸 -3-카복스아미드 (실시예 6);  yV-cyclopropyl-6- (2 ᅳ methyl-5- (3- (trifluoromethyl) benzamido) phenylamino) -L7-indazole-3-carboxamide (Example 6);
#-(2-히드록시에틸 )-6— (2-메틸 -5-(3- (트리플루오로메틸)벤즈아미도)페닐아미노 )-1 -인다졸 -3-카복스아미드 (실시예 7);  #-(2-hydroxyethyl) -6— (2-methyl-5- (3- (trifluoromethyl) benzamido) phenylamino) -1 -indazole-3-carboxamide (Example 7 );
6-(2-메틸— 5-(3- (트리플루오로메틸)벤즈아미도)페닐아미노) - —(2—몰포리노에틸 6- (2-methyl— 5- (3- (trifluoromethyl) benzamido) phenylamino)-— (2—morpholinoethyl
)-1 -인다졸 -3-카복스아미드 (실시예 8); ) -1 -indazole-3-carboxamide (Example 8);
一메틸— 6-( (2-메틸 -5ᅳ(3-(4-메틸피페라진 -1-일 )-5— (트리폴루오로메틸)벤즈아미 도)페닐)아미노 )-1 —인다졸—3—카복스아미드 (실시예 9); 6一 ( (5— (4-(4-플루오로페닐 )-2- (트리플루오로메틸 ) 이미다졸 -5-카복스아미도One-Methyl-6-((2-methyl-5 ᅳ (3- (4-methylpiperazin-1-yl) -5— (trifluoromethyl) benzamido) phenyl) amino) -1 —indazol —3—carboxamide (Example 9); 6 one ((5— (4- (4-fluorophenyl) -2- (trifluoromethyl) imidazole-5-carboxamido
)一2-메틸페닐)아미노)ᅳ/V-메틸 인다졸 -3-카복스아미드 (실시예 10)； ) 一 2-methylphenyl) amino) '/ V-methyl indazole-3-carboxamide (Example 10);
Λ/一메틸 -6-(메틸 (2-메틸 -5-(3-몰포리노—5— (트리플루오로메틸 )벤즈아미도)페닐 ) 아미노) 인다졸 -3ᅳ카복스아미드 (실시예, 11); ' Λ / 一 methyl- 6- (methyl ( 2 -methyl- 5- ( 3 -morpholino— 5 — (trifluoromethyl) benzamido) phenyl) amino) indazole-3 -carboxamide (Example, 11 ); '
/-메틸 -6- (메틸 (4- ( 3ᅳ (트리플루오로메틸)벤즈아미도)페닐)아미노 hi//—인다졸 -3/ -Methyl-6- (methyl (4- (3 '(trifluoromethyl) benzamido) phenyl) amino hi // — indazole-3
-카복스아미드 (실시예 12); Carboxamide (Example 12);
6- (( 4- ( 3-브로모페닐설폰아미도)페닐) (메틸)아미노 ) -그메틸 - 1 -인다졸 -3-카복 스아미드 (실시예 13)；  6-((4- (3-bromophenylsulfonamido) phenyl) (methyl) amino) -gmethyl-1 -indazole-3-carboxamide (Example 13);
6- (( 5— ( 3- ( 이미다졸 - 1—일) -5- (트리플루오로메틸)벤즈아미도) -2-메틸페닐) (. 메틸)아미노 메틸ᅳ 인다졸— 3—카복스아미드 (실시예 14); 6- ((5- (3- (imidazol-1- yl) methyl-5- (trifluoromethyl) benz amido) -2-methylphenyl) (methyl) amino methyl eu indazole-3-carboxamide (Example 14);
메틸 -6_ (메틸 (2-메틸 -5— (3— (4—메틸피페라진—1-일) -5— (트리물루오로메틸)벤즈 아미도)페닐)아미노 )ᅳ1//—인다졸 -3-카복스아미드 (실시예 15)；  Methyl-6_ (methyl (2-methyl-5— (3— (4—methylpiperazin—1-yl) -5— (trimulomethyl) benz amido) phenyl) amino) ᅳ 1 // — indazole -3-carboxamide (Example 15);
6—( (5-(3—(4—히드록시피페리딘 -1-일 )-5- (트리몰루오로메틸 )벤즈아미도) -2-메틸 페닐) (메틸)아미노)— -메틸— 인다졸 -3-카복스아미드 (실시예 16); 6— ((5- (3— (4—hydroxypiperidin-1-yl) -5- (trimoluromethyl) benzamido) -2-methyl phenyl) (methyl) amino) —- methyl — Indazole-3-carboxamide (Example 16);
TV-메틸 -6- (메틸 (2—메틸 -5-(3-(4-메틸 이미다졸—1—일 )-5- (트리플루오로메틸 ) 벤즈아미도)페닐)아미노 인다졸 -3—카복스아미드 (실시예 17)； TV-methyl-6- (methyl (2—methyl-5- (3- (4-methyl imidazol—1—yl) -5- (trifluoromethyl) benzamido) phenyl) amino indazole-3— Carboxamide (Example 17);
y -메틸— 6-(메릴 (2—메틸 -5-(3-(2-메틸— 1 -이미다졸—1-일 )-5-(트리플루오로메틸 ) 벤즈아미도)페닐)아미노 )—1 -인다졸— 3-카복스마이드 (실시예 18)； y-methyl— 6- (meryl (2—methyl-5- (3- (2-methyl— 1-imidazol—1-yl) -5- (trifluoromethyl) benzamido) phenyl) amino) — 1-indazole—3-carboxamide (Example 18);
6— ( (5-(3—(2 ,4—디메틸 이미다졸— 1—일 )一5— (트리플루오로메틸 )벤즈아미도) -2一 메틸페닐) (메틸)아미노) 메틸— 인다졸—3—카복스아미드 (실시예 19); 6— ((5- (3— (2,4—dimethyl imidazole— 1—yl) 一 5— (trifluoromethyl) benzamido) -2 一 methylphenyl) (methyl) amino) methyl— indazole— 3—carboxamide (Example 19);
(S)— 6-( (5— (3-(3— (디메틸아미노)피률리딘 -1-일 )-5- (트리플루오로메틸)벤즈아미 도) -2-메틸페닐) (메틸)아미노 )-/!-메틸 인다졸ᅳ 3—카복스아미드 (실시예 20); ΛΖ-메틸 -6- (메틸 (2-메틸— 5-(4— (4—메틸피페라진—1-일) -3- (트리플루오로메틸)벤즈 아미도)페닐)아미노 인다졸—3-카복스아미드 (실시예 21)；  (S) — 6- ((5— (3- (3— (dimethylamino) pyridin-1-yl) -5- (trifluoromethyl) benzamido) -2-methylphenyl) (methyl) amino) -/!-Methyl indazolazole 3—carboxamide (Example 20); ΛΖ-methyl-6- (methyl (2-methyl— 5- (4— (4—methylpiperazin—1-yl) -3- (trifluoromethyl) benz amido) phenyl) amino indazole—3- Carboxamide (Example 21);
6-( (5-(3—(2-시아노프로판 -2-일 )벤즈아미도) -2—메틸페닐) (메틸 )아미노) -/V-메틸6-((5- (3— (2-cyanopropan-2-yl) benzamido) -2-methylphenyl) (methyl) amino)-/ V-methyl
-1 -인다졸 -3-카복스아미드 (실시예 22)；-1 -indazole-3-carboxamide (Example 22);
-메틸 -6— (메틸 (2-메틸— 5— (3— (트리플루오로메틸)벤즈아미도)페닐)아미노 인다졸—3-카복스아미드 (실시예 23);  -Methyl-6- (methyl (2-methyl-5) (3— (trifluoromethyl) benzamido) phenyl) amino indazole—3-carboxamide (Example 23);
6一 ( (5-( 1— (4ᅳ메록시페닐 )—5— (트리플루오로메틸 피라졸— 4-카복스아미도 )-2- 메틸페닐) (메틸)아미노)— /V—메틸— 인다졸 -3-카복스아미드 (실시예 24);  6 一 ((5- (1— (4 ᅳ methoxyphenyl) —5— (trifluoromethyl pyrazole— 4-carboxamido) -2-methylphenyl) (methyl) amino) — / V—methyl— Sol-3-carboxamide (Example 24);
5- (4-클로로페닐 )-/V-(4-메틸 -3- (메틸 (3- (메틸카바모일 )—1 -인다졸 -6—일)아미노 )페닐)이소옥사졸 -3-카복스아미드 (실시예 25)；  5- (4-Chlorophenyl)-/ V- (4-methyl-3- (methyl (3- (methylcarbamoyl) -l-indazol-6-yl) amino) phenyl) isoxazole-3-car Voxamide (Example 25);
6- ( (5— (5— (4ᅳ메톡시페닐 )퓨란 -2-카복스아미도 )-2ᅳ메틸페닐) (메틸 )아미노)— /Vᅳ메 틸 -1^-인다졸 -3-카복스아미드 (실시예 26);  6- ((5— (5— (5— (4 ᅳ methoxyphenyl) furan-2-carboxamido) -2 ᅳ methylphenyl) (methyl) amino) — / V ᅳ methyl-1 ^ -indazole-3-carbox Amides (Example 26);
K 4-메틸 -3ᅳ (메틸 ( 3ᅳ (메틸카바모일) - 1 -인다졸 -6-일)아미노)페닐)—2- (피리딘—K 4-methyl-3 ′ (methyl (3 ′ (methylcarbamoyl) -1-indazol-6-yl) amino) phenyl) —2- (pyridine—
4—일)티아졸 -5-카복스아미드 (실시예 27);4—yl) thiazole-5-carboxamide (Example 27);
—메틸— 6- (메틸 (4-(3ᅳ몰포리노 -5- (트리플루오로메틸)벤즈아미도)페닐)아미노) - 1 -인다졸 -3-카복스아미드 (실시예 28);  —Methyl— 6- (methyl (4- (3′morpholino-5 (trifluoromethyl) benzamido) phenyl) amino) -1-indazole-3-carboxamide (Example 28);
6-((4— (3ᅳ 이미다졸— 1—일)— 5- (트리플루오로메틸)벤즈아미도)페닐) (메틸)아 미노) - -메틸 -1 —인다졸—3-카복스아미드 (실시예 29); 6-((4— (3 ′ imidazole— 1—yl) — 5- (trifluoromethyl) benzamido) phenyl) (methyl) amino)--methyl -1 -indazol- 3-carbox Amides (Example 29);
-메틸 -6- (메틸 (4-(3— (4-메틸피페라진 -1-일) -5- (트리플루오로메틸)벤즈아미도) 페닐)아미노 )-1 -인다졸— 3—카복스아미드 (실시예 30);  -Methyl-6- (methyl (4- (3— (4-methylpiperazin-1-yl) -5- (trifluoromethyl) benzamido) phenyl) amino) -1 -indazole— 3—ca Voxamide (Example 30);
6-((4-(3-(4-히드톡시피페리딘 -1-일) -5- (트리플루오로메틸)벤즈아미도)페닐 )( 메틸)아미노)— yV-메틸— 인다졸 3—카복스아미드 (실시예 31);6-((4- (3- (4-hydroxymethoxypiperidin-1-yl) -5- (trifluoromethyl) benzamido) phenyl) ( Methyl) amino) —yV-methyl—indazole 3—carboxamide (Example 31);
―메틸— 6- (메틸 (4-(3— (4一메틸 이미다졸 -1一일 )-5- (트리플루오로메틸)벤즈아 미도)페닐)아미노 )— 인다졸 -3—카복스아미드 (실시예 32)； ' -Methyl- 6- (methyl (4- (3— (4-lmethyl imidazole-l-yl) -5- (trifluoromethyl) benzamido) phenyl) amino)-indazole-3-carboxamide (example 32); '
(S)— 6— ((4-(3—(3— (디메틸아미노)피를리딘 -1-일) -5— (트리플루오로메틸)벤즈아미 도)페닐) (메틸)아미노) —메틸 인다졸— 3-카복스아미드 (실시예 33)； ―메틸— 6- (메틸 (4— (4-(4—메틸피페라진— 1-일 )-3- (트리플루오로메틸)벤즈아미도) 페닐)아미노)— I 인다졸—3—카복스아미드 (실시예 34)；  (S) — 6— ((4- (3— (3— (dimethylamino) pyridin-1-yl) -5— (trifluoromethyl) benzamido) phenyl) (methyl) amino) —methyl Indazole—3-carboxamide (Example 33); —methyl— 6- (methyl (4— (4- (4—methylpiperazin— 1-yl) -3- (trifluoromethyl) benzamido ) Phenyl) amino) —I indazole—3—carboxamide (Example 34);
6-( (4-(3— (2-시아노프로판 -2-일)벤즈아미도)페닐) (메틸)아미노) -/V—메틸 인 다졸—3—카복스아미드 (실시예 35)；  6- ((4- (3— (2-cyanopropane-2-yl) benzamido) phenyl) (methyl) amino)-/ V-methyl indazole-3 3-carboxamide (Example 35);
5-메틸— -(4- (메틸 (3— (메틸카바모일 )— 인다졸— 6—일)아미노)페닐)이소옥사졸- 3-카복스아미드 (실시예 36);  5-methyl —- (4- (methyl (3— (methylcarbamoyl) —indazol— 6—yl) amino) phenyl) isoxazole-3-carboxamide (Example 36);
7H4- (메틸 (3- (메틸카바모일 )— 인다졸 -6-일)아미노)페닐)티아졸 -4-카복스아 미드 (실시예 37);  7H4- (methyl (3- (methylcarbamoyl) —indazol-6-yl) amino) phenyl) thiazole-4-carboxamide (Example 37);
/V-메틸 -6- (메틸 (4-(5—메틸피라진— 2—카복스아미도)페닐 )아미노)— 인다졸 -3—카 복스아미드 (실시예 38);  / V-methyl-6- (methyl (4- (5—methylpyrazine— 2—carboxamido) phenyl) amino) —indazole-3—carboxamide (Example 38);
Λ/-메틸 -6- (메틸 (4-(3-(3- (트리플루오로메틸)페닐)우레이도)페닐)아미노) 인 다졸 -3—카복스아미드 (실시예 39)；  Λ / -methyl-6- (methyl (4- (3- (3- (trifluoromethyl) phenyl) ureido) phenyl) amino) indazole-3—carboxamide (Example 39);
6- ((5— (3-(4-클로로 -3-플루오로페닐)우레이도) -2-메틸페닐) (메틸)아미노) 메 틸 인다졸 -3—카복스아미드 (실시예 40)；  6- ((5— (3- (4-chloro-3-fluorophenyl) ureido) -2-methylphenyl) (methyl) amino) methyl indazole-3—carboxamide (Example 40);
6—( (5-(3— (4—클로로페닐)우레이도)—2—메틸페닐) (메틸)아미노) "메틸 인다 졸 -3-카복스아미드 (실시예 41);  6— ((5- (3— (4—chlorophenyl) ureido) —2—methylphenyl) (methyl) amino) “methyl indazole-3-carboxamide (Example 41);
6— (2-메틸 -5-(4-몰포리노페닐카바모일)페닐아미노) -ΛΚ4-몰포리노페닐 )— 인 다졸 -3-카복스아미드 (실시예 42);  6— (2-methyl-5- (4-morpholinophenylcarbamoyl) phenylamino) -ΛΚ4-morpholinophenyl) —indazole-3-carboxamide (Example 42);
6-(4-플루오로 -5— (3-플루오로 -5- (트리플루오로메틸 )벤즈아미도) -2-메틸페닐、- N 一메틸 -1^인다졸 -3—카복스아미드 (실시예 43)；  6- (4-Fluoro-5— (3-fluoro-5- (trifluoromethyl) benzamido) -2-methylphenyl 、 N 1 methyl-1 ^ indazole-3—carboxamide (implemented Example 43);
6_(4-플루오로— 2—메틸— 5— (3-메틸 -5- (트리플루오로메틸)벤즈아미도)페닐) - ^메 틸 -1^인다졸—3—카복스아미드 (실시예 44)；  6_ (4-Fluoro— 2—methyl— 5— (3-methyl-5- (trifluoromethyl) benzamido) phenyl)-^ methyl-1 ^ indazole—3—carboxamide (Example 44);
6— (4—플루오로— 5— (3—플루오로 -5-메틸벤즈아미도) -2-메틸페닐 )-그메틸 -1^인다 졸 -3-카복스아미드 (실시예 45)；  6— (4—fluoro— 5— (3—fluoro-5-methylbenzamido) -2-methylphenyl) -gmethyl-1 ^ indada sol-3-carboxamide (Example 45);
6-(4-플루오로 -2-메틸— 5— (4—메틸 -3- (트리플루오로메틸 )벤즈아미도)페닐 )-Λ ^메 틸 -1^인다졸 -3-카복스아미드 (실시예 46)；  6- (4-fluoro-2-methyl— 5— (4—methyl-3- (trifluoromethyl) benzamido) phenyl) -Λ ^ methyl-1 ^ indazole-3-carboxamide ( Example 46);
6— (5-(4-클로로 -3- (트리플루오로메틸)벤즈아미도)—4-플루오로— 2-메틸페닐) -그 메틸 -1^인다졸 -3—카복스아미드 (실시예 47);  6— (5- (4-Chloro-3- (trifluoromethyl) benzamido) —4-fluoro- 2-methylphenyl)-methyl-1 ^ indazole-3-carboxamide (Example 47 );
6 (4—플루오로 -2-메틸 -5-(3- (트리플루오로메틸)벤즈아미도)페닐) -그메틸— 1^인 다졸— 3-카복스아미드 (실시예 48);  6 (4—Fluoro-2-methyl-5 (3- (trifluoromethyl) benzamido) phenyl) -gmethyl—1 ^ dazole—3-carboxamide (Example 48);
6-(4-플루오로— 5-(4—플루오로 -3- (트리플루오로메틸 )벤즈아미도) -2—메틸페닐 Ν -메틸 -1^인다졸—3—카복스아미드 (실시예 49);  6- (4-fluoro— 5- (4—fluoro-3- (trifluoromethyl) benzamido) -2—methylphenyl Ν-methyl-1 ^ indazole—3—carboxamide (Example 49 );
6— (4-플루오로 -5-(2-플루오로 -5— (트리플루오로메틸 )벤즈아미도 )— 2 메틸페닐 一메틸 -L 인다졸 -3-카복스아미드 (실시예 50);  6— (4-fluoro-5- (2-fluoro-5— (trifluoromethyl) benzamido) — 2 methylphenyl one methyl-L indazole-3-carboxamide (Example 50);
6-(4-폴루오로— 5— (4-폴루오로— 2- (트리폴루오로메틸 )벤즈아미도) -2-메틸페닐 )-yV -메틸—l^인다졸—3 카복스아미드 (실시예 51); 6- (4-Polouro— 5— (4-Polouro— 2- (trifluoromethyl) benzamido) -2-methylphenyl) -yV-methyl-l ^ indazole—3 carboxamide (Example 51);
6-(4-플루오로 -2-메틸 -5-(4- (트리플루오로메록시)벤즈아미도)페닐) 메틸 -1^ 인다졸—3-카복스아미드 (실시예 52)； 6- (4-fluoro-2-methyl-5- (4- (trifluoromethoxy) benzamido) phenyl) methyl-1 ^ Indazole—3-carboxamide (Example 52);
6_(4-플루오로— 5— (2—메톡시 -3- (트리플루오로메틸)벤즈아미도)—2-메틸페닐 메틸— 1/ 인다졸 -3—카복스아미드 (실시예 53)；  6_ (4-fluoro— 5— (2—methoxy-3- (trifluoromethyl) benzamido) —2-methylphenyl methyl— 1 / indazole-3—carboxamide (Example 53);
6-(4-플루오로— 5-(2-메톡시— 5- (트리플루오로메틸)벤즈아미도) -2-메틸페닐 )一 메틸 -1^인다졸 -3-카복스아미드 (실시예 54);  6- (4-Fluoro— 5- (2-methoxy— 5- (trifluoromethyl) benzamido) -2-methylphenyl) l methyl-1 ^ indazole-3-carboxamide (Example 54 );
6-(4-플루오로 -5— (3-메특시 -5- (트리플루오로메틸)벤즈아미도) -2-메틸페닐) 메틸 -l^인다졸 -3—카복스아미드 (실시예 55)；  6- (4-Fluoro-5— (3-methoxy-5- (trifluoromethyl) benzamido) -2-methylphenyl) methyl-1 ^ indazole-3—carboxamide (Example 55) ;
6-(4—플루오로 -5— (2-하이드록시 -5- (트리플루오로메틸 )벤즈아미도) -2-메틸페닐) -Λ^메틸 -1 ^인다졸— 3ᅳ카복스아미드 (실시예 56);  6- (4—Fluoro-5— (2-hydroxy-5- (trifluoromethyl) benzamido) -2-methylphenyl) -Λ ^ methyl-1 ^ indazole—3′carboxamide (Example 56);
6-(4—플루오로 -5-(4-하이드록시 -3— (트리플루오로메틸)벤즈아미도)—2-메틸페닐)6- (4—fluoro-5- (4-hydroxy-3— (trifluoromethyl) benzamido) —2-methylphenyl)
-그메틸— 1/ 인다졸 -3-카복스아미드 (실시예 57); -Gmethyl— 1 / indazole-3-carboxamide (Example 57);
6-(4-플루오로— 2—메틸— 5— (3- (트리플루오로메톡시 )벤즈아미도)페닐 )-Λ ^메틸 -1/· 인다졸—3—카복스아미드 (실시예 58)；  6- (4-fluoro— 2—methyl— 5— (3- (trifluoromethoxy) benzamido) phenyl) -Λ ^ methyl-1 / · indazole—3—carboxamide (Example 58) ;
6-(5— (4-아미노— 3— (트리플루오로메틸)벤즈아미도)—4—플루오로— 2-메틸페닐 Ή 메틸— I 인다졸 -3-카복스아미드 (실시예 59);  6- (5— (4-amino— 3— (trifluoromethyl) benzamido) —4—fluoro—2-methylphenyl Ή methyl— I indazole-3-carboxamide (Example 59);
6-(5-(4-아미노— 3— (트리플루오로메록시 )벤즈아미도) -4-플루오로 -2-메틸페닐 )-N -메틸—I 인다졸—3—카복스아미드 (실시예 60);  6- (5- (4-amino— 3— (trifluoromethoxy) benzamido) -4-fluoro-2-methylphenyl) -N-methyl-I indazole—3—carboxamide (Example 60 );
6-(4-플루오로— 5— (4-플루오로 -3- (트리플루오로메톡시)벤즈아미도) -2—메틸페닐) 6- (4-fluoro— 5— (4-fluoro-3- (trifluoromethoxy) benzamido) -2—methylphenyl)
— 메틸— 1/ 인다졸— 3ᅳ카복스아미드 (실시예 61); — Methyl — 1 / indazole — 3 ᅳ carboxamide (Example 61);
6— (4—플루오로— 2—메틸 -5-(6- (트리폴루오로메틸)니코티아미도)페닐 메틸— 1/ 인다졸 -3_카복스아미드 (실시예 62); ― 6— (4—fluoro— 2—methyl-5 (6- (trifluoromethyl) nicothiamido) phenyl methyl— 1 / indazol-3_carboxamide (Example 62);
6一(4-플루오로 -2-메틸 -5-(2- (트리플루오로메틸 )이소니코틴아미도)페닐 )-그메틸 인다졸 -3—카복스아미드 (실시예 63);  6- (4-Fluoro-2-methyl-5- (2- (trifluoromethyl) isonicotinamido) phenyl) -gmethyl indazole-3—carboxamide (Example 63);
6一 (5-(6— (디메틸아미노) -5-메틸니코틴아미도) -4—플루오로— 2-메틸페닐 메틸- 1^인다졸—3-카복스아미드 (실시예 64); 6- (5- (6— (dimethylamino) -5-methylnicotinamido) -4-fluoro- 2-methylphenyl methyl-1 ^ indazole-3-carboxamide (Example 64);
6-(5— (4-클로로 -3-(2-시아노프로판 -2-일)벤즈아미도) -4-플로로—2-메틸페닐 )—그 메틸— I 인다졸 -3-카복스아미드 (실시예 65)；  6- (5— (4-Chloro-3- (2-cyanopropan-2-yl) benzamido) -4-fluoro-2-methylphenyl) —the methyl— I indazole-3-carboxamide (Example 65);
6-(5-(3-(2—시아노프로판 -2—일) -5- (트리플루오로메틸)벤즈아미도) -4-플로로 -2- 메틸페닐) 메틸 -1/ 인다졸 -3-카복스아미드 (실시예 66);  6- (5- (3- (2—Cyanopropane-2-yl) -5- (trifluoromethyl) benzamido) -4-fluoro-2-methylphenyl) methyl-1 / indazol-3 Carboxamide (Example 66);
6— (5-(3— (2-시아노프로판 -2—일) -5—플루오로벤즈아미도 )—4—플로로—2-메틸페닐 ) -6— (5- (3— (2-cyanopropane-2-yl) -5-fluorobenzamido) —4—fluoro-2-methylphenyl)-
^메틸—1^인다졸 -3-카복스아미드 (실시예 67); ^ Methyl-1 ^ indazole-3-carboxamide (Example 67);
6-(5— (3-아미노 -5- (트리플루오로메틸)벤즈아미도) -4—플루오로— 2—메틸페닐) 메틸 -1/ 인다졸 -3—카복스아미드 (실시예 68);  6- (5— (3-amino-5- (trifluoromethyl) benzamido) -4—fluoro-2-2-methylphenyl) methyl-1 / indazol-3—carboxamide (Example 68);
6-(5-(3- (디메틸아미노) -5— (트리플루오로메틸)벤즈아미도)—4-플루오로 -2-메틸 페닐) - ^메틸 -1^인다졸 -3-카복스아미드 (실시예 69);  6- (5- (3- (dimethylamino) -5— (trifluoromethyl) benzamido) —4-fluoro-2-methyl phenyl)-^ methyl-1 ^ indazole-3-carboxamide (Example 69);
6-(5—(3- ((디메틸아미노)에틸)아미노 )-5- (트리플루오로메틸)벤즈아미도) -4一플 루오로 -2—메틸페닐) - ^메틸 -1^인다졸—3-카복스아미드 (실시예 70);  6- (5— (3- ((dimethylamino) ethyl) amino) -5- (trifluoromethyl) benzamido) -4 fluoro-2-2-methylphenyl)-^ methyl-1 ^ indazole— 3-carboxamide (Example 70);
6-(5— (3— ((디메틸아미노)에틸) (메틸)아미노 )—5- (트리플루오로메틸)벤즈아미도) -4-플루오로 -2-메틸페닐)—그메틸— 1^인다졸 -3—카복스아미드 (실시예 71); 6- (5— (3— ((dimethylamino) ethyl) (methyl) amino) —5- (trifluoromethyl) benzamido) -4-fluoro-2-methylphenyl) —gmethyl— 1 ^ Sol-3—carboxamide (Example 71);
6-(4—플루오로— 2—메틸 -5-(3-몰포리노 -5- (트리플루오로메틸 )벤즈아미도)페닐 )6- (4—fluoro— 2—methyl-5- (3-morpholino-5- (trifluoromethyl) benzamido) phenyl)
-메틸 인다졸—3-카복스아미드 (실시예 72); -Methyl indazole—3-carboxamide (Example 72);
6-(4-플루오로 -2-메틸 -5— (3- (메틸아미노 )-5— (트리플루오로메틸)벤즈아미도)페 닐) - ^메틸 -1^인다졸 -3—카복스아미드 (실시예 73); 6-(5— (2— (디메틸아미노)— 5- (트리플루오로메틸)벤즈아미도) -4—플루오로— 2-메틸 페닐) -/V"메틸 인다졸 -3-카복스아미드 (실시예 74)； 6- (4-fluoro-2-methyl-5— (3- (methylamino) -5— (trifluoromethyl) benzamido) phenyl)-^ methyl-1 ^ indazole-3—carbox Amides (Example 73); 6- (5— (2— (dimethylamino) — 5- (trifluoromethyl) benzamido) -4—fluoro—2-methyl phenyl)-/ V "methyl indazole-3-carboxamide ( Example 74);
6— (4-플루오로— 2—메틸 -5— (2-(4-메틸피페라진 -1-일) -5- (트리플루오로메틸)벤즈 아미도)페닐)—^메틸ᅳ 인다졸—3-카복스아미드 (실시예 75);  6— (4-fluoro— 2—methyl-5— (2- (4-methylpiperazin-1-yl) -5- (trifluoromethyl) benz amido) phenyl) — ^ methyl ᅳ indazole— 3-carboxamide (Example 75);
6-{4-플루오로— 2—메틸— 5-[3-(2- (피롤리딘 -1-일—에틸아미노)— 5—트리플루오로메 틸-벤조일아미노]페닐 ^인다졸— 3_카복시산 메틸아미드 (실시예 76)；6- {4-fluoro— 2—methyl— 5- [3- (2- (pyrrolidin-1-yl—ethylamino) — 5—trifluoromethyl-benzoylamino] phenyl ^ indazole— 3 _ Carboxylic acid methylamide (Example 76);
6— (4—플루오로 -2—메틸 -5-(3— ((테트라하이드로 피란 -4-일)아미노 )-5- (트리플 루오로메틸)벤즈아미도)페닐) 메틸 인다졸 -3-카복스아미드 (실시예 77)； 6-(4-플루오로 -2-메틸 -5-(3— (피페라진 -1-일 )— 5— (트리플루오로메틸)벤즈아미도) 페닐)— 메틸 인다졸 -3-카복스아미드 (실시예 78); 6— (4—fluoro-2—methyl-5- (3— ((tetrahydropyran-4-yl) amino) -5- (trifluoromethyl) benzamido) phenyl) methyl indazole-3- Carboxamide (Example 77); 6- (4-Fluoro-2-methyl-5- (3— (piperazin-1-yl) -5— (trifluoromethyl) benzamido) phenyl) — Methyl indazole-3-carboxamide (Example 78);
6一 (4-플루오로 -2-메틸 -5-(3-(4—메틸피페라진— 1-일 )-5- (트리플루오로메틸 )벤즈 아미도)페닐)— 에틸ᅳ 1^인다졸 -3_카복스아미드 (실시예 79);  6- (4-Fluoro-2-methyl-5- (3- (4—methylpiperazin— 1-yl) -5- (trifluoromethyl) benz amido) phenyl) —ethyl ᅳ 1 ^ indazole -3_carboxamide (Example 79);
6一 (5-(3-(4—에틸피레라진 -1—일 ) -5- (트리플루오로메틸)벤즈아미도) -4-플루오로- 2-메틸페닐) 메틸— 1^인다졸—3—카복스아미드 (실시예 80); 6- (5- (3- (4—ethylpyreazine-1-yl) -5- (trifluoromethyl) benzamido) -4-fluoro-2-methylphenyl) methyl—1 ^ indazole—3 —Carboxamide (Example 80);
(R)— 6-(5— (3-(3- (디메틸아미노)피롤리딘 -1-일 )— 5ᅳ (트리플루오로메틸)벤즈아미 도) -4-플루오로 -2-메틸페닐)— /V"메틸 -1^인다졸 -3ᅳ카복스아미드 (실시예 81); 6-(4-플루오로 -2-메틸— 5-(3_(4-메틸 -1,4-디아제판 -1-일 ) -5- (트리플루오로메틸) 벤즈아미도)페닐) 메틸— 1/ 인다졸 -3-카복스아미드 (실시예 82)； (R) — 6- (5— (3- (3- (dimethylamino) pyrrolidin-1-yl) — 5 ′ (trifluoromethyl) benzamido) -4-fluoro-2-methylphenyl) — / V ”methyl-1 ^ indazole-3′carboxamide (Example 81); 6- (4-fluoro-2-methyl—5- (3_ (4-methyl-1,4-diazephan-1 -Yl) -5- (trifluoromethyl) benzamido) phenyl) methyl- 1 / indazole-3-carboxamide (Example 82);
6_(4-플루오로 -5-(3- (핵사하이드로피를로 [1,2-a]피라진— 2(110—일)— 5- (트리플루 오로메틸)벤즈아미도) -2-메틸페닐)— ^메틸 인다졸—3—카복스아미드 (실시예6_ (4-Fluoro-5- (3- (nucleohydropyrrolo [1,2-a] pyrazine— 2 (110-yl) — 5- (trifluoromethyl) benzamido) -2-methylphenyl) — ^ Methyl indazole-3 carboxamide (Example
83)； 83);
6_(4-플루오로— 5-(3-( ( (2-하이드록시에틸) (메틸)아미노) -5— (트리플루오로메틸 ) 벤즈아미도) -2—메틸페닐) 메틸 인다졸 -3-카복스아미드 (실시예 84); (S)-6— (5-(3-(3- (디메틸아미노)피를리딘 -1—일)— 5ᅳ (트리플루오로메틸)벤즈아미 도) -4-플루오로 -2-메틸페닐) 메틸 인다졸 -3ᅳ카복스아미드 (실시예 85); 6_ (4-Fluoro— 5- (3- (((2-hydroxyethyl) (methyl) amino) -5— (trifluoromethyl) benzamido) -2-methylphenyl) methyl indazole-3- Carboxamide (Example 84); (S) -6— (5- (3- (3- (dimethylamino) pyridin-1-yl) — 5 ′ (trifluoromethyl) benzamido) 4-fluoro-2-methylphenyl) methyl indazole-3′carboxamide (Example 85);
6-(4-플루오로 -2-메틸 -5-(3-(4-메틸설포닐)피페라진 -1-일)— 5— (트리플루오로메 틸)벤즈아미도)페닐시메틸 -1^인다졸 -3—카복스아미드 (실시예 86); 6- (4-fluoro-2-methyl-5- (3- (4-methylsulfonyl) piperazin-1-yl) — 5— (trifluoromethyl) benzamido) phenylshimethyl-1 ^ Indazole-3—carboxamide (Example 86);
6-(5-(3-(4-아세틸피페라진 -1—일 )-5_ (트리플루오로메틸)벤즈아미도)—4-플루오 로 -2-메틸페닐) 메틸 인다졸 -3-카복스아미드 (실시예 87); 6- (5- (3- (4-acetylpiperazin-1—yl) -5_ (trifluoromethyl) benzamido) —4-fluoro-2-methylphenyl) methyl indazole-3-carboxamide (Example 87);
6-(4—폴루오로 -2-메틸— 5-(3-(4-니코티노일피페라진— 1-일 )-5— (트리플루오로메틸6- (4—Polouro-2-methyl— 5- (3- (4-nicotinoylpiperazin— 1-yl) -5— (trifluoromethyl
)벤즈아미도)페닐)— 메틸 인다졸— 3-카복스아미드 (실시예 88); ) Benzamido) phenyl) —methyl indazole—3-carboxamide (Example 88);
6-(5— (3— (4— (2- (디메틸아미노) -2—옥소에틸)피페라진 -1-일 )—5- (트리플루오로메 틸)벤즈아미도) -4-플루오로 -2-메틸페닐)—^메틸— 1/ 인다졸 -3-카복스아미드 (실시예 89)； 6- (5— (3— (4— (2- (dimethylamino) -2—oxoethyl) piperazin-1-yl) —5- (trifluoromethyl) benzamido) -4-fluoro- 2-methylphenyl)-^ methyl-1 / indazole-3-carboxamide (Example 89);
6-(4-플루오로 -2—메틸 -5— (3-(4-(2—옥소 -2- (페닐아미노)에틸)피페라진—1—일 )-5_6- (4-fluoro-2—methyl-5— (3- (4- (2—oxo-2- (phenylamino) ethyl) piperazin—1—yl) -5_
(트리플루오로메틸 )벤즈아미도)페닐 )—^메틸 -L 인다졸—3-카복스아미드 (Trifluoromethyl) benzamido) phenyl) — ^ methyl-L indazole—3-carboxamide
(실시예 90); (Example 90);
6-(4-플루오로— 5— (3-(4- (이소프로필설포닐)피페라진— 1-일) -5- (트리플루오로메 틸)벤즈아미도)—2ᅳ메틸페닐시메틸 인다졸—3—카복스아미드 (실시예 91); 6-(5-(3-(4—벤조일피페라진 -1-일) -5- (트리플루오로메틸)벤즈아미도)— 4-플루오 로 -2—메틸페닐) 메틸ᅳ1^인다졸 -3-카복스아미드 (실시예 92);  6- (4-fluoro— 5— (3- (4- (isopropylsulfonyl) piperazin— 1-yl) -5 (trifluoromethyl) benzamido) —2 ᅳ methylphenylmethylmethyl indazole —3—Carboxamide (Example 91); 6- (5- (3- (4—benzoylpiperazin-1-yl) -5- (trifluoromethyl) benzamido) —4-fluoro- 2—methylphenyl) methyl ᅳ l ^ indazole-3-carboxamide (Example 92);
6-(5-(3— (1-아세틸피페리딘 -4-카복스아미도 )-5- (트리플루오로메틸)벤즈아미도) ᅳ4ᅳ플루오로 -2—메틸페닐) 메틸 -1^인다졸 -3-카복스아미드 (실시예 93); 6-(5-(3— (2— (디메틸아미노)아세트아미도 )-5- (트리플루오로메틸)벤즈아미도) -4- 플루오로 -2—메틸페닐) 메틸 인다졸 -3-카복스아미드 (실시예 94); 6- (5- (3— (1-acetylpiperidine-4-carboxamido) -5- (trifluoromethyl) benzamido) ᅳ 4 ᅳ fluoro-2-methylphenyl) methyl-1 ^ Indazole-3-carboxamide (Example 93); 6- (5- (3— (2— (dimethylamino) acetamido) -5- (trifluoromethyl) benzamido) -4-fluoro-2-methylphenyl) methyl indazole-3-carbox Amide (Example 94);
6- ( 4-플루오로 -5- ( 3- ( 4- ( 2-메톡시에틸)피페라진 - 1—일 ) -5- (트리플루오로메틸)벤 즈아미도)— 2-메틸페닐) - ^메틸 인다졸—3—카복스아미드 (실시예 95); 6- (4-Fluoro-5- (3- (4- (2-methoxyethyl) piperazine-1-yl) -5- (trifluoromethyl) benzamido)-2-methylphenyl)- ^ Methyl indazole-3 carboxamide (Example 95);
6-(4-플루오로 -2-메틸 -5-(3-(4-(1-메틸피페라진— 4—일 )_5- (트리플루오로메틸)벤 즈아미도)페닐) -그메틸 -1^인다졸 -3-카복스아미드 (실시예 96); 6- (4-Fluoro-2-methyl-5- (3- (4- (1-methylpiperazin— 4—yl) _5- (trifluoromethyl) benzamido) phenyl) -gmethyl- 1 ^ indazole-3-carboxamide (Example 96);
6-(4—플루오로-2—메틸-5-(3-((1,2,2,6,6-펜타메틸피페리딘—4-일)아미노)-5-(트 리플루오로메틸 )벤즈아미도)페닐 메틸 인다졸 -3—카복스아미드 (실시예 97)； 6- (4—fluoro-2—methyl-5- (3-((1,2,2,6,6-pentamethylpiperidin—4-yl) amino) -5- (trifluoromethyl ) Benzamido) phenyl methyl indazole-3—carboxamide (Example 97);
6-(4—플루오로 -2—메틸 -5— (3— (4-옥소피페리딘 -1-일 )—5- (트리폴루오로메틸 )벤즈 아미도)페닐)—^메틸 -1^인다졸 -3-카복스아미드 (실시예 98); 6- (4—Fluoro-2—methyl-5— (3— (4-oxopiperidin-1-yl) —5- (trifluoromethyl) benz amido) phenyl) — ^ methyl-1 ^ Indazole-3-carboxamide (Example 98);
6-(4-플루오로 -2—메틸 -5-(3-(4-메록시피페리딘 -1-일 )-5— (트리플루오로메틸 )벤 즈아미도)페닐)—^메틸— 1/ 인다졸—3—카복스아미드 (실시예 99); 6- (4-fluoro-2—methyl-5- (3- (4-methoxypiperidin-1-yl) -5— (trifluoromethyl) benzamido) phenyl) — ^ methyl— 1 Indazole-3 carboxamide (Example 99);
6— (4-플'루오로 -2-메틸 -5 (3— (3-하이드록시피를리딘— 1—일 )-5- (트리플루오로메틸 )벤즈아미도)페닐)―그메틸—1^인다졸—3—카복스아미드 (실시예 100); 6- (4-flat-2-methyl-5 (4- (3-hydroxypyrrolidine the Luo naphthyridin-methyl-1-yl) -5- (trifluoromethyl) benz amido) phenyl) that methyl- 1 ^ indazole—3—carboxamide (Example 100);
6-(5-(3-( 1,4-디옥사 -8-아자스피로 [4, 5]데칸 -8—일)— 5— (트리플루오로메틸)벤즈 아미도 )-4-플루오로 -2-메틸페닐 )—^메틸 인다졸 -3-카복스아미드 (실시예 101);  6- (5- (3- (1,4-dioxa-8-azaspiro [4,5] decane-8—yl) — 5— (trifluoromethyl) benz amido) -4-fluoro- 2-methylphenyl) — ^ methyl indazole-3-carboxamide (Example 101);
6-(4-플루오로 -2-메틸 -5-(3 (4- (메틸아미노)피페리딘— 1-일 )—5— (트리플루오로메 틸)벤즈아미도)페닐)―그메틸 인다졸 -3—카복스아미드 (실시예 102);  6- (4-fluoro-2-methyl-5- (3 (4- (methylamino) piperidin— 1-yl) —5— (trifluoromethyl) benzamido) phenyl) -gmethyl Sol-3—carboxamide (Example 102);
6-(4-플투오로 -2-메틸— 5-(3-(4— (디메틸아미노)피페리딘 -1-일 )-5- (트리플루오로 메틸)벤즈아미도)페닐) 메틸— 1/ 인다졸 -3-카복스아미드 (실시예 103);  6- (4-Pluto-2-methyl— 5- (3- (4— (dimethylamino) piperidin-1-yl) -5- (trifluoro methyl) benzamido) phenyl) methyl— 1 Indazole-3-carboxamide (Example 103);
6-(4-플루오로 -5— (3-(4-하이드록시피페리딘 -1-일) -5— (트리플루오로메틸 )벤즈아 미도) 2-메틸페닐) 메틸 인다졸 -3—카복스아미드 (실시예 104);  6- (4-fluoro-5) (3- (4-hydroxypiperidin-1-yl) -5) (trifluoromethyl) benzamido) 2-methylphenyl) methyl indazole-3 Voxamide (Example 104);
6-(4-플루오로 -2-메틸 -5-(3— ( ( 1-메틸피페리딘—4-일)아미노 )— 5- (트리플루오로메 틸)벤즈아미도)페닐) 메틸-工 ^인다졸 -3-카복스아미드 (실시예 105); 6- (4-fluoro-2-methyl-5- (3— ((1-methylpiperidin—4-yl) amino) — 5- (trifluoromethyl) benzamido) phenyl) methyl- 工^ Indazole-3-carboxamide (Example 105);
6-(4-플루오로 -2-메틸 -5— (3—피페리딘 -4-일옥시 )-5- (트리플루오로메틸)벤즈아미 도)페닐) -그메틸— 1/ 인다졸 -3—카복스아미드 (실시예 106);  6- (4-fluoro-2-methyl-5— (3—piperidin-4-yloxy) -5- (trifluoromethyl) benzamido) phenyl) -gmethyl— 1 / indazole- 3—carboxamide (Example 106);
6-(4-플루오로 -2-메틸 -5— (3— ( 1-메틸피페리딘 -4-일 )옥시 )—5— (트리플루오로메틸 ) 벤즈아미도)페닐) -그메틸 -ΙΛ^인다졸 -3—카복스아미드 (실시예 107);  6- (4-fluoro-2-methyl-5— (3— (1-methylpiperidin-4-yl) oxy) —5— (trifluoromethyl) benzamido) phenyl) -gmethyl- ΙΛ ^ indazole-3—carboxamide (Example 107);
6-(4—플루오로 -2—메틸 -5-(3-( (1-메틸피페리딘— 4—일)메톡시 )-5- (트리폴루오로메 틸)벤즈아미도)페닐) -Λ ^메틸 인다졸—3—카복스아미드  6- (4-fluoro-2-2-methyl-5- (3-((1-methylpiperidin- 4-yl) methoxy) -5- (trifluoromethyl) benzamido) phenyl)- Λ ^ methyl indazole—3—carboxamide
트리플루오로아세트산염 (실시예 108); Trifluoroacetic acid salt (Example 108);
6 (4-플루오로— 2-메틸 -5-(3- (피페리딘— 4-일메록시 )—5— (트리플루오로메틸 )벤즈 아미도)페닐)—그메틸 -1^인다졸 -3-카복스아미드 트리플루오로아세트산염 6 (4-fluoro— 2-methyl-5- (3- (piperidin— 4-ylmethoxy) —5— (trifluoromethyl) benz amido) phenyl) —gmethyl-1 ^ indazole- 3-carboxamide trifluoroacetic acid salt
(실시예 109); (Example 109);
6-(4-플루오로— 5— (3-(4-이소프로필피페리딘 -1-일 )-5— (트리플루오로메틸)벤즈아 미도)—2-메틸페닐) 메틸 -1^인다졸 -3-카복스아미드 (실시예 110);  6- (4-fluoro— 5— (3- (4-isopropylpiperidin-1-yl) -5— (trifluoromethyl) benzamido) —2-methylphenyl) methyl-1 ^ indazole -3-carboxamide (Example 110);
6-(4-폴루오로— 2—메틸 -5— (3— (4-메틸 -1，4-디아제판 -1-일) -5— (트리플루오로메틸 ) 벤즈아미도)페닐) 메틸— 1^인다졸—3—카복스아미드 (실시예 111); 6- (4-polouro— 2—methyl-5— (3— (4-methyl-1,4-diazepan-1-yl) -5— (trifluoromethyl) benzamido) phenyl) methyl — 1 ^ indazole—3—carboxamide (Example 111);
6-(5-(3-(4- e/ 부틸 ) -피페라진 -1-일 )—5- (트리플루오로메틸 )벤즈아미도) -4-폴 루오로 -2-메틸페닐) 메틸 -1^인다졸 -3—카복스아미드 (실시예 112);  6- (5- (3- (4-e / butyl) -piperazin-1-yl) —5- (trifluoromethyl) benzamido) -4-polouro-2-methylphenyl) methyl-1 ^ Indazole-3—carboxamide (Example 112);
6 (5-(3-(3- (디에틸아미노)피를리딘 -1-일) -5- (트리플루오로메틸)벤즈아미도) -4 -플루오로 -2—메틸페닐) -/ 메틸—1/ 인다졸—3-카복스아미드 (실시예 113)；6 (5- (3- (3- (diethylamino) pyridin-1-yl) -5- (trifluoromethyl) benzamido) -4 -Fluoro-2 -methylphenyl)-/ methyl-l / indazole- 3-carboxamide (Example 113);
6— (4—플루오로 -2—메틸ᅳ 5— (3— (4—메틸 -피페리딘— 1-일) -5- (트리플루오로메틸)벤즈 아미도)페닐)— ^메틸 인다졸 -3-카복스아미드 (실시예 114); 6— (4—Fluoro-2—methyl ᅳ 5— (3— (4—methyl-piperidin— 1-yl) -5 (trifluoromethyl) benz amido) phenyl) — ^ methyl indazole -3-carboxamide (Example 114);
6-(5-(3-(3， 5—디메틸피페라진— 1-일 )-5- (트리플루오로메틸)벤즈아미도) -4-플루 오로 -2-메틸페닐)ᅳ^메틸— 1/^인다졸—3-카복스아미드 트리플루오로아세트산염 6- (5- (3- (3, 5—Dimethylpiperazin— 1-yl) -5- (trifluoromethyl) benzamido) -4-fluoro-2-methylphenyl) ᅳ ^ methyl— 1 / ^ Indazole—3-carboxamide trifluoroacetate
(실시예 115); (Example 115);
6-(4-플루오로 -2-메틸ᅳ5-(3- (트리플루오로메틸 )-5-(3,4，5-트라이메틸피페라진- 1-일 )벤즈아미도)페닐 메틸 인다졸 -3-카복스아미드  6- (4-fluoro-2-methyl ᅳ 5- (3- (trifluoromethyl) -5- (3,4,5-trimethylpiperazin-1-yl) benzamido) phenyl methyl indazole -3-carboxamide
트리플루오로아세트산염 (실시예 116); Trifluoroacetic acid salt (Example 116);
6一(4—플루오로— 2-메틸ᅳ 5-(3-( (4-메틸피페라진 -1-일 )-5—트리플루오로메틸)벤즈 아미도)페닐) - ^메틸 -1^인다졸 -3-카복스아미드 (실시예 117)；  6 一 (4—Fluoro— 2-methyl ᅳ 5- (3- ((4-methylpiperazin-1-yl) -5—trifluoromethyl) benz amido) phenyl)-^ methyl-1 ^ Sol-3-carboxamide (Example 117);
6-(5-(3— (((2—디메틸아미노)에틸 (메틸)아미노)메틸) -5- (트리플루오로메틸)벤즈 아미도 )-4-플루오로 -2ᅳ메틸페닐 메틸 -ly 인다졸 -3-카복스아미드 (실시예 6- (5- (3— (((2-dimethylamino) ethyl (methyl) amino) methyl) -5- (trifluoromethyl) benz amido) -4-fluoro-2 ᅳ methylphenyl methyl-ly Sol-3-carboxamide (Example
118)； 118);
6一 (5-(3-( (2-아미노에틸)아미노 )—5- (트리플루오로메틸)벤즈아미도) -4-플루오로 -2-메틸페닐) 메틸—I 인다졸 -3-카복스아미드 (실시예 119)；  6- (5- (3- ((2-aminoethyl) amino) —5- (trifluoromethyl) benzamido) -4-fluoro-2-methylphenyl) methyl-I indazole-3-carbox Amide (Example 119);
6-(5_(3-((2-아미노—2ᅳ메틸프로필)아미노 )-5ᅳ (트리플루오로메틸)벤즈아미도) -4 —플루오로 -2—메틸페닐) -그메틸 인다졸 -3-카복스아미드 (실시예 120); 6- (5_ (3-((2-amino—2 ᅳ methylpropyl) amino) -5 ′ (trifluoromethyl) benzamido) -4 —fluoro-2-methylphenyl) -gmethyl indazole-3 Carboxamide (Example 120);
6-(5ᅳ(3-((2-디메틸아미노ᅳ 2-메틸프로필)아미노 )—5- (트리플루오로메틸)벤즈아 미도) -4—플루오로 -2—메틸페닐 )-그메틸— 인다졸 -3-카복스아미드 6- (5 ′ (3-((2-dimethylamino ᅳ 2-methylpropyl) amino) —5- (trifluoromethyl) benzamido) -4—fluoro-2-2-methylphenyl) -gmethyl— Sol-3-carboxamide
트리플루오로아세트산염 (실시예 121); Trifluoroacetic acid salt (Example 121);
6-(4-플루오로 -5-(3-( (2-하이드록시부틸)아미노) -5- (트리플루오로메틸)벤즈아 미도) -2-메틸페닐) 메틸 -1^인다졸 -3—카복스아미드 (실시예 122)；  6- (4-fluoro-5- (3-((2-hydroxybutyl) amino) -5- (trifluoromethyl) benzamido) -2-methylphenyl) methyl-1 ^ indazole-3 Carboxamide (Example 122);
6-(4—플루오로— 5-(3— ( (3-하이드록시프로필)아미노 )-5— (트리플루오로메틸)벤즈 아미도 )-2—메틸페닐)— 메틸 -1^인다졸—3-카복스아미드 (실시예 123)；  6- (4—fluoro— 5- (3— ((3-hydroxypropyl) amino) -5— (trifluoromethyl) benz amido) -2—methylphenyl) — methyl-1 ^ indazole—3 -Carboxamide (Example 123);
6-(4-플루오로— 5—(3— ( (2-하이드록시에틸)아미노 )-5- (트리플루오로메틸 )벤즈아 미도) -2-메틸페닐)—^메틸—1 ^인다졸—3-카복스아미드 (실시예 124)；  6- (4-fluoro— 5— (3— ((2-hydroxyethyl) amino) -5- (trifluoromethyl) benzamido) -2-methylphenyl) — ^ methyl—1 ^ indazole— 3-carboxamide (Example 124);
6一(4—플루오로— 5-(3-((2-하이드록시프로필)아미노 )-5- (트리플루오로메틸)벤즈 아미도 )—2-메틸페닐) - 메틸 인다졸 -3—카복스아미드 (실시예 125)；  6- (4—Fluoro— 5- (3-((2-hydroxypropyl) amino) -5- (trifluoromethyl) benz amido) -2-methylphenyl) -methyl indazole-3—carbox Amide (Example 125);
6-(4—플루오로 -5—(3-( (2-하이드록시 -2—메틸프로필)아미노)ᅳ 5- (트리플루오로메 틸)벤즈아미도) -2ᅳ메틸페닐) 메틸ᅳ 1/ 인다졸 -3—카복스아미드 (실시예 126)； 6- (4—Fluoro-5— (3- ((2-hydroxy-2—methylpropyl) amino) ᅳ 5- (trifluoromethyl) benzamido) -2 ᅳ methylphenyl) methyl ᅳ 1 / Sol-3—carboxamide (Example 126);
6- (4-플루오로 -2一메틸 -5— (3— (메틸) ( ( 1—메틸— 1/ 피라졸 -4-일 )메틸)아미노 )—5- ( 트리플루오로메틸 )벤즈아미도)페닐 )ᅳ7^메틸— 1 인다졸— 3—카복스아미드 (실시예6- (4-Fluoro-2imethyl-5— (3— (methyl) ((1—methyl— 1 / pyrazol-4-yl) methyl) amino) —5- (trifluoromethyl) benzami Phenyl) ᅳ 7 ^ methyl-1 indazole-3 carboxamide (Example
127)； 127);
6-(5—(3-(2-디메틸아미노)에록시 )— 5- (트리플루오로메틸)벤즈아미도)— 4-플루오 로 -2-메틸페닐 메틸 -1^인다졸 -3—카복스아미드 (실시예 128);  6- (5— (3- (2-dimethylamino) ethoxy) — 5- (trifluoromethyl) benzamido) — 4-fluoro-2-methylphenyl methyl-1 ^ indazole-3—carbox Amides (Example 128);
6-(4-플루오로 -2—메틸— 5-(3-(2-(1-메틸피를린— 2-일)에톡시 )-5— (트리플루오로메 틸)벤즈아미도)페닐) 메틸— 인다졸—3-카복스아미드 (실시예 129)；  6- (4-fluoro-2—methyl— 5- (3- (2- (1-methylpyrroline— 2-yl) ethoxy) -5— (trifluoromethyl) benzamido) phenyl) Methyl-indazole-3-carboxamide (Example 129);
6— (5-(3-(2- (디메틸아미노) -2-메틸프로폭시 )-5ᅳ (트리플루오로메틸)벤즈아미도) 6— (5- (3- (2- (dimethylamino) -2-methylpropoxy) -5 ᅳ (trifluoromethyl) benzamido)
-4-풀루오로 -2-메틸페닐) - 메틸 -1^인다졸 -3-카복스아미드 -4-Pluoro-2-methylphenyl) -methyl-1 ^ indazole-3-carboxamide
트리플루오로아세트산염 (실시예 130); Trifluoroacetic acid salt (Example 130);
6-(5ᅳ(3ᅳ (2-아미노— 2-메틸프로폭시 )-5- (트리플루오로메틸 )벤즈아미도)—4-플루 오로ᅳ 2-메틸페닐) 메틸 -1^인다졸ᅳ3-카복스아미드 (실시예 131); 6一 (5-(3-((lᅳ (디메틸아미노)프로판 _2-일)옥시)ᅳ 5- (트리플루오로메틸)벤즈아미 도 )-4-플루오로 -2—메틸페닐 메틸-；! ^인다졸ᅳ 3—카복스아미드 6- (5 ′ (3 ′ (2-amino— 2-methylpropoxy) -5- (trifluoromethyl) benzamido) —4-fluorofluoro 2-methylphenyl) methyl-1 ^ indazol ᅳ 3 Carboxamide (Example 131); 6- (5- (3-((l ᅳ (dimethylamino) propane_2-yl) oxy) ᅳ 5- (trifluoromethyl) benzamido) -4 -fluoro- 2 —methylphenyl methyl- ;! ^ Indazole 3 —carboxamide
트리플루오로아세트산염 (실시예 132); Trifluoroacetic acid salt (Example 132);
6-(5-(3- (피롤리딘 -1ᅳ일에톡시 )-5- (트리플루오로메틸)벤즈아미도) -4-플루오로一 2—메틸페닐 )—그메틸 -I 인다졸 -3—카복스아미드 (실시예 133);  6- (5- (3- (Pyrrolidin-l-hexyethoxy) -5- (trifluoromethyl) benzamido) -4-fluorol 2-methylphenyl) -gmethyl-I indazole-3 —Carboxamide (Example 133);
6— (4-플루오로— 5-(3-(4—플루오로 -3-메틸페닐 )우레이도)—2-메틸페닐 )- 메틸 -1^ -인다졸— 3-카복스아미드 (실시예 134)；  6— (4-fluoro— 5- (3- (4—fluoro-3-methylphenyl) ureido) —2-methylphenyl) -methyl-1 ^ -indazole— 3-carboxamide (Example 134) ;
( )-6— (4—플루오로— 5ᅳ(3-(3ᅳ(1— (하이드록시이미노)에틸)페닐 )우레이도)—2-메틸 페닐) 메틸— 1/ 인다졸 -3-카복스아미드 (실시예 135)；  () -6— (4—Fluoro— 5 ′ (3- (3 ᅳ (1— (hydroxyimino) ethyl) phenyl) ureido) —2-methyl phenyl) methyl— 1 / indazole-3-car Voxamide (Example 135);
6— (4-플루오로 -2-메틸 -5-(3-(3- (트리플투오로메틸)페닐 )우레이도)페닐 )—^메틸 인다졸 -3-카복스아미드 (실시예 136)； 6— (4-fluoro-2-methyl-5- (3- (3- (tripletomethyl) phenyl) ureido) phenyl) — ^ methyl indazole-3-carboxamide (Example 136);
6— (4-플루오로— 2—메틸 -5-(3-(4ᅳ메틸 -3- (트리플루오로메틸)페닐)우레이도)페닐) 메틸 인다졸 -3ᅳ카복스아미 (실시예 137);  6— (4-Fluoro— 2—methyl-5 (3- (4 ᅳ methyl-3- (trifluoromethyl) phenyl) ureido) phenyl) methyl indazole-3 -carboxami (Example 137) ;
6一 (5-(3-(4-클로로— 3ᅳ (트리플루오로메틸)페닐)우레이도)— 4-플루오로— 2-메틸페 닐) 메틸 인다졸 -3-카복스아미드 (실'시예 138); 6- (5- (3- (4-chloro— 3 ′ (trifluoromethyl) phenyl) ureido) — 4-fluoro— 2-methylphenyl) methyl indazole-3-carboxamide (sil ' Example 138);
6一 (5-(3— (3,5-비스 (트리플루오로메틸)페닐)우레이도) -4-플루오로 -2ᅳ메틸페닐) - 6 一 (5- (3— (3,5-bis (trifluoromethyl) phenyl) ureido) -4-fluoro-2 ᅳ methylphenyl)-
^메틸ᅳ 1 ^인다졸— 3-카복스아미드 (실시예 139)； ^ Methyl ᅳ 1 ^ indazole— 3-carboxamide (Example 139);
6一 ( 5- ( 3- ( 3.4-디메틸페닐)우레이도) -4—플루오로 -2-메틸페닐) - 메틸— 1/"인다졸 -3ᅳ카복스아미드 (실시예 140);  6- (5- (3- (3.4-dimethylphenyl) ureido) -4—fluoro-2-methylphenyl) methyl-1 / "indazol-3'carboxamide (Example 140);
6-(4-플루오로ᅩ5-(3— (3—플루오로ᅩ 5- (트리플루오로메틸)페닐)우레이도) -2-메틸 페닐) 메틸— 1/ 인다졸 -3—카복스아미드 (실시예 141)； 6- (4-fluoro ᅩ 5- (3— (3—fluoro ᅩ 5- (trifluoromethyl) phenyl) ureido) -2-methyl phenyl) methyl— 1 / indazole-3—carboxamide (Example 141);
6— (4-플루오로 -5-(3-(3-플루오로 -4—메틸페닐)우레이도)—2—메틸페닐 )— 메틸— 1// -인다졸—3-카복스아미드 (실시예 142)；  6— (4-fluoro-5- (3- (3-fluoro-4—methylphenyl) ureido) —2—methylphenyl) —methyl— 1 //-indazole—3-carboxamide (Example 142 );
6-(5— (3-(3-클로로 -4-플루오로페닐 )우레이도) -4-플루오로— 2-메틸페닐 메틸— 인다졸 -3-카복스아미드 (실시예 143);  6- (5— (3- (3-chloro-4-fluorophenyl) ureido) -4-fluoro—2-methylphenyl methyl—indazole-3-carboxamide (Example 143);
6-(5-(3-(3-( 부틸)페닐 )우레이도 )-4-플루오로 -2-메틸페닐 )-그메틸 -1^인 다졸 -3ᅳ카복스아미드 (실시예 144)；  6- (5- (3- (3- (butyl) phenyl) ureido) -4-fluoro-2-methylphenyl) -gmethyl-1 ^ indazole-3′carboxamide (Example 144);
6-(5-(3-(4-( er -부틸)페닐 )우레이도)—4-플루오로 -2—메틸페닐 )-Λ 계틸 -1 ^인 다졸 -3ᅳ카복스아미드 (실시예 145)；  6- (5- (3- (4- (er-butyl) phenyl) ureido) —4-fluoro-2-2-methylphenyl) -Λ cyltil-1 ^ indazole-3′carboxamide (Example 145);
6-(5-(3— (4-클로로페닐)우레이도) -4—플투오로— 2-메틸페닐 )ᅳ^메틸 인다졸 -36- (5- (3— (4-chlorophenyl) ureido) -4—pluturo—2-methylphenyl) ᅳ ^ methyl indazole-3
-카복스아미드 (실시예 146)； -Carboxamide (Example 146);
6-(5— (3-(3，4-디플로오로페닐)우레이도) -4-플루오로 -2—메틸페닐 )-그메틸 -ly 인 다졸 -3-카복스아미드 (실시예 147)；  6- (5— (3- (3,4-Difluorophenyl) ureido) -4-fluoro-2—methylphenyl) -gmethyl-ly indazole-3-carboxamide (Example 147);
6-(4-플루오로— 5-(3-(4-플루오로페닐)우레이도) -2-메틸페닐 메틸 -1^인다졸 -3-카복스아미드 (실시예 148);  6- (4-fluoro— 5- (3- (4-fluorophenyl) ureido) -2-methylphenyl methyl-1 ^ indazole-3-carboxamide (Example 148);
6-(4-플루오로— 5-(3-(4-플루오로 -3— (트리플루오로메틸)페닐)우레이도)—2-메틸 페닐) 메틸 -1^인다졸 -3—카복스아미드 (실시예 149);  6- (4-fluoro— 5- (3- (4-fluoro-3— (trifluoromethyl) phenyl) ureido) —2-methyl phenyl) methyl-1 ^ indazole-3—carboxamide (Example 149);
6-(5— (3-(3-시아노페닐)우레이도)— 4-플루오로ᅳ 2-메틸페닐)ᅳ 메틸 -1^인다졸ᅳ 3 -카복스아미드 (실시예 150);  6- (5— (3- (3-cyanophenyl) ureido) — 4-fluoro ᅳ 2-methylphenyl) ᅳ methyl-1 ^ indazole ᅳ 3-carboxamide (Example 150);
6— (5-(3— (3-아세틸페닐)우레이도) -4—플루오로— 2—메틸페닐)ᅳ그메틸 -1^인다졸ᅳ36— (5- (3— (3-acetylphenyl) ureido) -4-fluoro- 2-methylphenyl) dogmethyl-1 ^ indazole ᅳ 3
-카복스아미드 (실시예 151)； -Carboxamide (Example 151);
6-(4-플루오로 -2-메틸 -5— (3ᅳ(3- (트리플루오로메톡시)페닐)우레이도)페닐) - 메 틸 인다졸 -3-카복스아미드 (실시예 152); 6-(4-플루오로 -5-(3-(4ᅩ플루오로— 3—나이트로페닐)우레이도) -2-메틸페닐 )- ^메 틸 인다졸—3-카복스아미드 (실시예 153)； 6- (4-fluoro-2-methyl-5— (3 ′ (3- (trifluoromethoxy) phenyl) ureido) phenyl) -methyl indazole-3-carboxamide (Example 152); 6- (4-Fluoro-5- (3- ( 4'fluoro- 3-nitrophenyl) ureido) -2-methylphenyl)-^ methyl indazole-3-carboxamide (Example 153) ;
6-(4—플루오로— 2-메틸— 5-(3-(4-메틸 -3-니트로페닐)우레이도)페닐 )— 메틸 -1^ '인다졸— 3-카복스아미드 (실시예 154)； 6- (4—Fluoro— 2-methyl— 5- (3- (4-methyl-3-nitrophenyl) ureido) phenyl) —methyl-1 ^ ' indazole— 3-carboxamide (Example 154 );
6-(4-플루오로 -5-(3— (3-이소프로필페닐)우레이도) -2-메틸페닐) - ^메틸 인다 졸 -3-카복스아미드 (실시예 155)；  6- (4-fluoro-5- (3— (3-isopropylphenyl) ureido) -2-methylphenyl)-^ methyl indazole-3-carboxamide (Example 155);
6— (5— (3- (벤조 [d] [ 1 ,3]디옥솔—5—일 )우레이도) -4—플루오로— 2-메틸페닐 )- ^메틸- 1/ 인다졸—3-카복스아미드 (실시예 156)；  6— (5— (3- (benzo [d] [1,3] dioxol—5—yl) ureido) -4—fluoro—2-methylphenyl)-^ methyl-1 / indazol—3-car Voxamide (Example 156);
6-(5—(3—(3-(2-시아노프로판— 2ᅳ일 )페닐)우레이도) -4-플루오로— 2-메틸페닐 )-y^ 메틸— 1/ 인다졸 -3—카복스아미드 (실시예 157)；  6- (5— (3— (3- (2-cyanopropane- 2 ᅳ yl) phenyl) ureido) -4-fluoro- 2-methylphenyl) -y ^ methyl— 1 / indazole-3—carbox Amide (Example 157);
6一 (5— (3— (3— (2—시아노프로판—2—일)— 4-플루오로페닐)우레이도)— 4-플루오로 -2ᅳ메 틸페닐 메틸 -1^인다졸 -3-카복스아미드 (실시예 158)；  6 一 (5— (3— (3— (2—cyanopropane—2—yl) — 4-fluorophenyl) ureido) — 4-fluoro-2 ᅳ methylphenyl methyl-1 ^ indazole-3 -Carboxamide (Example 158);
6— (5— (3— (3— ((디메틸아미노)메틸 )—4—플루오로페닐 )우레이도) -4-플루오로— 2-메 틸페닐) 메틸 -1그인다졸 -3-카복스아미드 (실시예 159)；  6— (5— (3— (3— ((dimethylamino) methyl) —4—fluorophenyl) ureido) -4-fluoro—2-methylphenyl) methyl-1gindazol-3-car Voxamide (Example 159);
6-(4-플루오로 -5-(3-(4—플루오로 -3- (트리플루오로메톡시)페닐)우레이도) -2-메 틸페닐)— ^메틸 인다졸 -3—카복스아미드 (실시예 160);  6- (4-fluoro-5- (3- (4—fluoro-3- (trifluoromethoxy) phenyl) ureido) -2-methylphenyl) — ^ methyl indazole-3—carboxamide (Example 160);
6-(4—플루오로— 5—(3—(3- ((트리플루오로메틸)싸이오)페닐)우레이도)페닐)—^메 틸一 인다졸 -3-카복스아미드 (실시예 161);  6- (4—Fluoro— 5— (3— (3- (((trifluoromethyl) thio) phenyl) ureido) phenyl) — ^ methyl 一 indazole-3-carboxamide (Example 161 );
6- (4—플루오로— 5- (3- (3-플루오로페닐)우레이도)—2-메틸페닐) 메틸 인다졸 一 3ᅳ카복스아미드 (실시예 162)；  6- (4—Fluoro— 5- (3- (3-fluorophenyl) ureido) —2-methylphenyl) methyl indazole Ⅰ 3′carboxamide (Example 162);
6-(5-(3— (3- (디플루오로메톡시 )페닐)우레이도) -4ᅳ플루오로— 2-메틸페닐 )—^메틸 인다졸 -3-카복스아미드 (실시예 163)；  6- (5- (3— (3- (difluoromethoxy) phenyl) ureido) -4′fluoro—2-methylphenyl) — ^ methyl indazole-3-carboxamide (Example 163);
6- ( 5- ( 3- ( 2—클로로—3— (트리플루오로메틸)페닐)우레이도) -4-플루오로 -2—메틸페 닐) - ^메틸 인다졸 -3-카복스아미드 (실시예 164)； 6- (5- (3- (2—chloro—3— (trifluoromethyl) phenyl) ureido) -4-fluoro-2—methylphenyl)-^ methyl indazole-3-carboxamide ( Example 164);
6一 (5-(3— (2-클로로 -5— (트리플루오로메틸)페닐)우레이도) -4—플루오로 -2—메틸페 닐)—그메틸 -1^인다졸—3—카복스아미드 (실시예 165)；  6- (5- (3— (2-chloro-5— (trifluoromethyl) phenyl) ureido) -4—fluoro-2—methylphenyl) -gmethyl-1 ^ indazole—3—car Voxamide (Example 165);
6-(4-플루오로 -2-메틸 -5-(3— (3ᅳ(4-메틸피페라진— 1-일 )-5— (트리플루오로메틸)페 닐)우레이도)페닐) - 메틸 -1^인다졸—3-카복스아미드 (실시예 166)；  6- (4-fluoro-2-methyl-5- (3— (3 '(4-methylpiperazin— 1-yl) -5— (trifluoromethyl) phenyl) ureido) phenyl) -methyl -1 ^ indazole-3-carboxamide (Example 166);
6_(4-플루오로 -2—메틸 -5-(3— (2ᅳ몰포리노 -5— (트리플루오로메틸)페닐)우레이도) 페닐)— 메틸 인다졸 -3-카복스아미드 (실시예 167)； 6_ (4-Fluoro-2—methyl-5- (3— (2′morpholino-5— (trifluoromethyl) phenyl) ureido) phenyl) —methyl indazole-3-carboxamide (Example 167);
6_(4-플루오로 -2-메틸 -5— (3— (4ᅳ(2- (피롤리딘 -1-일 )에톡시 )-3- (트리플루오로메 틸)페닐)우레이도)페닐) 메틸— 1^인다졸—3—카복스아미드 (실시예 168)； 6-(4-폴루오로— 2一메틸 -5— (3— (3-(4—메틸피페라진— 1-일)페닐)우레이도)페닐 )-Λ 메틸— 인다졸—3-카복스아미드 (실시예 169)；  6_ (4-fluoro-2-methyl-5— (3— (4 ᅳ (2- (pyrrolidin-1-yl) ethoxy) -3- (trifluoromethyl) phenyl) ureido) phenyl) Methyl—1 ^ indazol—3—carboxamide (Example 168); 6- (4-Polouro—2imethyl-5— (3— (3- (4—methylpiperazin— 1-yl) Phenyl) ureido) phenyl) -Λ methyl-indazole-3-carboxamide (Example 169);
6-(4-플루오로 -2—메틸— 5-(3-(4ᅳ (4-메틸피페라진 -1-일 )—3- (트리플루오로메틸)페 닐 )우레이도)페닐 )— 메틸 -1^인다졸 -3-카복스아미드 트리플루오로아세트산염 (실시예 170);  6- (4-fluoro-2—methyl— 5- (3- (4 ᅳ (4-methylpiperazin-1-yl) —3- (trifluoromethyl) phenyl) ureido) phenyl) —methyl -1 ^ indazole-3-carboxamide trifluoroacetic acid salt (Example 170);
6-(4—폴루오로 -5-(3-(4-플루오로 -3-메틸페닐)싸이오우레이도) -2-메틸페닐) 메틸ᅳ 인다졸—3ᅳ카복스아미드 (실시예 171)；  6- (4—Polouro-5- (3- (4-fluoro-3-methylphenyl) thioureido) -2-methylphenyl) methylquinindazole—3′carboxamide (Example 171);
6-(5-(3-(4-클로로— 3- (트리플루오로메틸)페닐)싸이오우레이도)ᅳ 4-플루오로 2-메 틸페닐)ᅳ ^메틸— 1^인다졸 -3—카복스아미드 (실시예 172);  6- (5- (3- (4-chloro— 3- (trifluoromethyl) phenyl) thioureido) ᅳ 4-fluoro 2-methylphenyl) ᅳ ^ methyl— 1 ^ indazole -3— Carboxamide (Example 172);
6-(4-플루오로 -5-(3-(4-플루오로 -3- (트리플루오로메틸)페닐) -3-메틸우레이도) - 2-메틸페닐)ᅳ^메틸 인다졸 -3-카복스아미드 (실시예 173); 6- (4-플루오로 -5- ( 3— (4—플루오로— 3- (트리플루오로메틸)페닐) -1—메틸우레이도) - 2一메틸페닐) - ^메틸 인다졸 -3—카복스아미드 (실시예 174)； 6- (4-fluoro-5- (3- (4-fluoro-3- (trifluoromethyl) phenyl) -3-methylureido)-2-methylphenyl) ᅳ ^ methyl indazole-3-car Voxamide (Example 173); 6- (4-Fluoro-5- (3— (4—fluoro— 3- (trifluoromethyl) phenyl) -1-methylureido)-2-1 methylphenyl)-^ methyl indazole-3-ka Voxamide (Example 174);
6-(4-플루오로— 2ᅩ메틸ᅳ 5-(3— (4-메틸피페라진 -1-일 )-5ᅳ (트리플루오로메틸)페닐) 벤즈아미도)페닐) -Λ 피리딘—4-일) -1^인다졸—3—카복스아미드 (실시예 175)； 싸이클로프로필 -6— (4-플루오로 -2-메틸 -5-(3-(4ᅳ메틸피페라진 -1-일)— 5ᅳ (트리 플루오로메틸)벤즈아미도)페닐)—1그인다졸— 3-카복스아미드 (실시예 176)； 6-(4-플루오로— 2—메틸ᅳ5— (3-(4-메틸피페라진ᅳ 1-일 )—5- (트리플루오로메틸)페닐) 벤즈아미도)페닐) 인다졸 -3-카복스아미드 (실시예 177)； 6- (4-fluoro— 2 ᅩ methyl ᅳ 5- (3— (4-methylpiperazin-1-yl) -5 ᅳ (trifluoromethyl) phenyl) benzamido) phenyl) -Λ pyridine—4 -Yl) -1 ^ indazole—3—carboxamide (Example 175); cyclopropyl-6— (4-fluoro-2-methyl-5- (3- (4 ᅳ methylpiperazin-1-yl) ) —5 ′ (trifluoromethyl) benzamido) phenyl) —1gindazole—3-carboxamide (Example 176); 6- (4-fluoro—2—methyl ᅳ 5— (3- (4-methylpiperazinyl 1-yl) —5- (trifluoromethyl) phenyl) benzamido) phenyl) indazole-3-carboxamide (Example 177);
6-(4-플루오로 -2-메틸ᅳ 5— (3— (4-메틸피페라진—1-일) -5— (트리플루오로메틸)페닐) 벤즈아미도)페닐)ᅳ 디메틸 인다졸ᅳ 3—카복스아미드 (실시예 178)； Λ 2—플루오로— 4-메틸ᅳ 5— (3— (피페라진 -1ᅳ카보닐) -1/·인다졸ᅳ6—일)페닐)ᅳ 3— (4- 메틸피페라진 -1-일 )—5ᅳ (트리플루오로메틸)벤즈아미드 (실시예 179)； 6- (4-fluoro-2-methyl 5— (3— (4-methylpiperazin—1-yl) -5— (trifluoromethyl) phenyl) benzamido) phenyl) ᅳ dimethyl indazole ᅳ 3—Carboxamide (Example 178); Λ 2 —Fluoro—4-methyl ᅳ 5— (3— (piperazin-1 ᅳ carbonyl) -1 / .indazol6-yl) phenyl) ᅳ 3 — (4-Methylpiperazin-1-yl) —5 ′ (trifluoromethyl) benzamide (Example 179);
Λ 2-폴루오로— 4—메틸 -5-(3-(4-메틸피페라진 -1—카보닐 )— 인다졸— 6-일 )페닐) - 3-(4-메틸피페라진 -1-일) -5- (트리플루오로메틸)벤즈아미드 (실시예 180)； 6— (4—플루오로— 2-메틸 -5— (3— (4-메틸피페라진 -1—일)— 5- (트리플루오로메틸)페닐) 벤즈아미도)페닐) -Λ 피페리딘 -4-일) -1/"인다졸 -3-카복스아미드 (실시예 181)； 6一 (4-플루오로 -2—메틸 -5-(3-(4-메틸피페라진 -1-일 )—5- (트리플루오로메틸)페닐) 벤즈아미도)페닐)ᅳ Λ 1ᅳ메틸피페리딘— 4-일 )세인다졸 -3—카복스아미드 (실시예 Λ 2-Polouro— 4—methyl-5- (3- (4-methylpiperazin-1—carbonyl) — indazole— 6-yl) phenyl)-3- (4-methylpiperazin-1- Yl) -5- (trifluoromethyl) benzamide (Example 180); 6— (4—fluoro— 2-methyl-5— (3— (4-methylpiperazin-1—yl) — 5- (Trifluoromethyl) phenyl) benzamido) phenyl) -Λ piperidin-4-yl) -1 / "indazole-3-carboxamide (Example 181); 6 one (4-fluoro- 2—Methyl-5- (3- (4-methylpiperazin-1-yl) —5- (trifluoromethyl) phenyl) benzamido) phenyl) ᅳ Λ 1 ᅳ methylpiperidin— 4-yl) Ceindazol-3—carboxamide (Example
182)； 182);
6-(4-플루오로 -2-메틸 -5— (3— (4-메틸피페라진 -1—일 )—5- (트리플루오로메틸)페닐) 벤즈아미도)페닐) -Λ 4—메틸피페리딘 - 1—일)— 1//"인다졸ᅳ 3-카복스아미드 (실시예 6- (4-fluoro-2-methyl-5— (3— (4-methylpiperazin-1—yl) —5- (trifluoromethyl) phenyl) benzamido) phenyl) -Λ 4—methyl Piperidine-1-day-1 // "indazoljan 3-carboxamide (Example
183)； 183);
^싸이클로핵실 -6-(4-플루오로 -2-메틸— 5— (3— (4-메틸피페라진—1-일 ) -5- (트리플 루오로메틸)벤즈아미도)페닐)—1^인다졸—3-카복스아미드 (실시예 184);  ^ Cyclonuclear chamber -6- (4-fluoro-2-methyl— 5— (3— (4-methylpiperazin—1-yl) -5- (trifluoromethyl) benzamido) phenyl) —1 ^ Indazole—3-carboxamide (Example 184);
6-(4-플루오로— 2-메틸 -5-(3-(4-메틸피페라진 -1-일 )-5- (트리플루오로메틸 )페닐) 벤즈아미도)페닐)—^페닐 -1^인다졸 -3—카복스아미드 (실시예 185)； 6- (4-fluoro— 2-methyl-5- (3- (4-methylpiperazin-1-yl) -5- (trifluoromethyl) phenyl) benzamido) phenyl) — ^ phenyl-1 ^ Indazole-3—carboxamide (Example 185);
6-(4-플루오로— 2-메틸— 5-(3-(4-메틸피페라진 -1-일 )-5— (트리플루오로메틸)페닐) 벤즈아미도)페닐) -Λ 피리딘—2-일)— 1^인다졸 -3-카복스아미드 (실시예 186)； 6-(4-플루오로 -2-메틸— 5-(3— (4-메틸피페라진 -1-일) -5— (트리플루오로메틸)페닐) 벤즈아미도)페닐)—Λ 피리딘—3-일)— I 인다졸 -3-카복스아미드 (실시예 187)； 6ᅳ(4-플루오로— 2—메틸— 5-(3ᅳ (4-메틸피페라진— 1-일 )—5- (트리폴루오로메틸)페닐) 벤즈아미도)페닐) -그하이드록시 인다졸—3-카복스아미드 (실시예 188); 6- (4-fluoro— 2-methyl— 5- (3- (4-methylpiperazin-1-yl) -5— (trifluoromethyl) phenyl) benzamido) phenyl) -Λ pyridine—2 -Yl) —1 ^ indazol-3-carboxamide (Example 186); 6- (4-fluoro-2-methyl—5- (3— (4-methylpiperazin-1-yl) -5 — (Trifluoromethyl) phenyl) benzamido) phenyl) —Λ pyridin—3-yl) —I indazole-3-carboxamide (Example 187); 6 ′ (4-fluoro-2—methyl — 5- (3 ′ (4-methylpiperazin— 1-yl) —5- (trifluoromethyl) phenyl) benzamido) phenyl) -g hydroxy indazole—3-carboxamide (Example 188);
6-(4ᅳ플루오로— 2-메틸 -5— (3ᅳ(4-메틸피페라진 -1-일 )—5— (트리플루오로메틸)페닐) 벤즈아미도)페닐) ᅳ플루오로피리딘— 3—일 ) -1^인다졸—3—카복스아미드 트리플루오로아세트산염 (실시예 189); 6- (4 ᅳ fluoro- 2-methyl-5- (3 '(4-methylpiperazin-1-yl)-5— (trifluoromethyl) phenyl) benzamido) phenyl) 페닐 fluoropyridine— 3—yl) -1 ^ indazole—3—carboxamide trifluoroacetate (Example 189);
6一(4ᅳ플루오로 -2-메틸 -5— (3-(4—메틸피페라진— 1—일) -5- (트리플루오로메틸)페닐) 벤즈아미도)페닐 )-/Η6-메틸피리딘 -3-일 )—1^인다졸—3—카복스아미드  6 一 (4 ᅳ fluoro-2-methyl-5— (3- (4—methylpiperazin— 1—yl) -5 (trifluoromethyl) phenyl) benzamido) phenyl)-/ Η6-methyl Pyridin-3-yl) —1 ^ indazole—3—carboxamide
트리플루오로아세트산염 (실시예 190); Trifluoroacetic acid salt (Example 190);
6-(4-플루오로 -2ᅳ메틸 -5-(3ᅳ (4—메틸피페라진 -1-일) -5— (트리플루오로메틸)페닐) 벤즈아미도)페닐 )-Λ 4-메틸피리딘 -3-일 )—1^인다졸 -3ᅳ카복스아미드  6- (4-fluoro-2'methyl-5- (3 '(4—methylpiperazin-1-yl) -5— (trifluoromethyl) phenyl) benzamido) phenyl) -Λ 4-methyl Pyridin-3-yl) —1 ^ indazole-3 ᅳ carboxamide
트리플루오로아세트산염 (실시예 191); Trifluoroacetic acid salt (Example 191);
6_(4ᅳ플루오로 -2-메틸 -5-(3-(4—메틸피페라진 -1-일 )-5ᅳ (트리플루오로메틸)페닐 ) 벤즈아미도)페닐) -Λ 피리미딘— 5-일 )-1^인다졸 -3ᅳ카복스아미드 트리플루오로아세트산염 (실시예 192); 6_ (4'Fluoro-2-methyl-5- (3- (4—methylpiperazin-1-yl) -5 '(trifluoromethyl) phenyl) benzamido) phenyl) -Λ pyrimidine— 5 -Yl) -1 ^ indazole-3 ᅳ carboxamide Trifluoroacetic acid salt (Example 192);
^벤질 -6— (4—플루오로ᅳ 2-메틸— 5-(3— (4-메틸피페라진 -1-일) -5— (트리플루오로메 틸)벤즈아미도)페닐) -1^인다졸 -3—카복스아미드 (실시예 193)；  ^ Benzyl-6— (4—fluorophenyl 2-methyl— 5- (3— (4-methylpiperazin-1-yl) -5— (trifluoromethyl) benzamido) phenyl) -1 ^ Sol-3—carboxamide (Example 193);
6_(4-플루오로 -2-메틸ᅳ 5-(3ᅳ(4-메틸피페라진ᅳ 1-일 )-5- (트리플루오로메틸 )벤즈 아미도)페닐)—Λ 피리딘—2-일메틸 인다졸 -3-카복스아미드 (실시예 194);6_ (4-fluoro-2-methyl 5- (3 '(4-methylpiperazin ᅳ 1-yl) -5- (trifluoromethyl) benz amido) phenyl) —Λ pyridin—2-ylmethyl Indazole-3-carboxamide (Example 194);
K (6-클로로피리딘 -3ᅳ일 )메틸 )-6-(4-플루오로— 2ᅳ메틸 -5— (3-(4ᅳ메틸피페라진 -1 —일) -5- (트리플루오로메틸)벤즈아미도)페닐)ᅳ Λ 피리미딘 -5—일 ) -L 인다졸—3ᅭ 카복스아미드 (실시예 195)； K (6-Chloropyridin-3 ᅳ yl) methyl) -6- (4-fluoro—2 ᅳ methyl-5— (3- (4 ᅳ methylpiperazin-1 —yl) -5- (trifluoromethyl) Benzamido) phenyl) 'Λ pyrimidin-5-yl) -L indazole- 3'carboxamide (Example 195);
6-(4—플루오로 -2-메틸ᅳ5-(3-(4—메틸피페라진 -1-일 )—5- (트리플루오로메틸)벤즈 아미도)페닐)— 피리미딘 -4-일메틸 )—1/"인다졸 -3-카복스아미드 (실시예 196);6- (4—Fluoro-2-methyl (5- (3- (4—methylpiperazin-1-yl) —5- (trifluoromethyl) benz amido) phenyl) —pyrimidin-4-yl Methyl) —1 / " indazole-3-carboxamide (Example 196);
6— (4-플루오로— 2—메틸ᅳ 5-(3-(4ᅳ메틸피페라진ᅳ 1-일) -5- (트리플루오로메틸)벤즈 아미도)페닐) -Λ 피리미딘 -3—일메틸 )-1/ 인다졸-카복스아미드 (실시예 197)； 6-(4—플루오로— 5— (3-(4-플루오로— 3— (트리플루오로메틸)페닐 )우레이도) -2—메틸 페닐) -/H피리딘 -2-일) -1^인다졸—3-카복스아미드 (실시예 198)； 6— (4-Fluoro— 2—methyl ᅳ 5- (3- (4 ᅳ methylpiperazin ᅳ 1-yl) -5 (trifluoromethyl) benz amido) phenyl) -Λ pyrimidine-3 Monomethyl) -1 / indazole-carboxamide (Example 197); 6- (4—fluoro— 5— (3- (4-fluoro— 3— (trifluoromethyl) phenyl) ureido) -2-methyl phenyl)-/ Hpyridin-2-yl) -1 inindazol-3-carboxamide (Example 198);
6-(4-플루오로 -5— (3-(4-플루오로 -3- (트리플루오로메틸)페닐)우레이도) -2-메틸 페닐)— ^(피리딘 -3—일) 인다졸—3ᅳ카복스아미드 (실시예 199)； 6- (4-fluoro-5) (3- (4-fluoro-3- (trifluoromethyl) phenyl) ureido) -2-methyl phenyl) — ^ (pyridin-3-yl) indazole— 3′carboxamide (Example 199);
6-(4-플루오로 -5-(3-(4—플루오로— 3- (트리플루오로메틸)페닐)우레이도) -2—메틸 페닐)—Λ 4-메틸피페라진—1-일) -1^인다졸—3-카복스아미드 (실시예 200)； 6-(4-플루오로 -5-(3— (4-플루오로 -3- (트리플루오로메틸)페닐)우레이도) -2—메틸 페닐세이소프로필 인다졸 -3—카복스아미드 (실시예 201); 6- (4-fluoro-5- (3- (4—fluoro— 3- (trifluoromethyl) phenyl) ureido) -2—methyl phenyl) —Λ 4-methylpiperazin—1-yl) -1 ^ indazole—3-carboxamide (Example 200); 6- (4-fluoro-5- (3— (4-fluoro-3- (trifluoromethyl) phenyl) ureido)- 2—methyl phenylisoisopropyl indazole-3—carboxamide (Example 201);
이클로프로필 -6-(4-플루오로 -5— (3— (4ᅳ플루오로— 3- (트리플루오로메틸)페닐) 우레이도)— 2-메틸페닐)— 1/ 인다졸 -3-카복스아미드 (실시예 202)；  Iclopropyl-6- (4-fluoro-5— (3— (4 ᅳ fluoro— 3- (trifluoromethyl) phenyl) ureido) — 2-methylphenyl) — 1 / indazole-3-car Voxamide (Example 202);
6-(4-플루오로 -5-(3-(4-플루오로— 3— (트리플루오로메틸)페닐)우레이도) -2-메틸 페닐)—Λ^몰포린—1 ^인다졸— 3-카복스아미드 (실시예 203); 6- (4-fluoro-5- (3- (4-fluoro— 3— (trifluoromethyl) phenyl) ureido) -2-methyl phenyl) —Λ ^ morpholine—1 ^ indazole— 3 Carboxamide (Example 203);
6-(4ᅳ플루오로 -5-(3-(4-플루오로 -3- (트리플루오로메틸)페닐)우레이도) -2-메틸 페닐)— 피리딘—2-일메틸 )-1^인다졸 -3-카복스아미드 (실시예 204);  6- (4 ᅳ fluoro-5- (3- (4-fluoro-3- (trifluoromethyl) phenyl) ureido) -2-methyl phenyl) —pyridine-2-ylmethyl) -1 ^ Sol-3-carboxamide (Example 204);
6-(4-플루오로 -5-(3-(4-플루오로 -3— (트리플루오로메틸)페닐)우레이도) -2-메틸 페닐)—Λ 피리딘 -3-일메틸)ᅳ 인다졸—3-카복스아미드 (실시예 205); 6- (4-fluoro-5- (3- (4-fluoro-3— (trifluoromethyl) phenyl) ureido) -2-methyl phenyl) —Λ pyridin-3-ylmethyl) ᅳ indazole —3-carboxamide (Example 205);
6— (4ᅳ플루오로 -5-(3— (4-플루오로 -3- (트리플루오로메틸)페닐)우레이도) -2—메틸 페닐)—Λ 피리딘 -4—일메틸) 인다졸 -3—카복스아미드 (실시예 206); 6— (4 ᅳ fluoro-5- (3— (4-fluoro-3- (trifluoromethyl) phenyl) ureido) -2-2-methylphenyl) —Λ pyridine-4-ylmethyl) indazole- 3—carboxamide (Example 206);
(6—클로로피리딘 -3-일)메틸 )ᅳ6-(4-플루오로 -5-(3-(4—플루오로 -3— (트리플루 오로메틸)페닐)우레이도 )-2ᅳ메틸페닐 )—1^인다졸—3-카복스아미드 (실시예 207)；  (6—chloropyridin-3-yl) methyl) ᅳ 6- (4-fluoro-5- (3- (4—fluoro-3— (trifluoromethyl) phenyl) ureido) -2) methylphenyl) —1 ^ indazole—3-carboxamide (Example 207);
6-(4ᅳ플루오로 -5— (3-(4ᅳ플루오로 -3— (트리플루오로메틸)페닐 )우레이도) -2ᅳ메틸 페닐)— 피리딘 -4—일) 다졸 -3-카복스아미드 (실시예 208); 6- (4 ᅳ Fluoro-5— (3- (4 ᅳ Fluoro-3— (trifluoromethyl) phenyl) ureido) -2 ᅳ methyl phenyl) -pyridin-4-yl) dazole-3-car Voxamide (Example 208);
^에틸 -6-(4—플루오로 -5-(3-(4-플루오로— 3- (트리플루오로메틸)페닐)우레이도)一 2-메틸페닐) 인다졸ᅳ 3-카복스아미드 (실시예 209); ^ Ethyl-6- (4—fluoro-5- (3- (4-fluoro- 3- (trifluoromethyl) phenyl) ureido) l 2-methylphenyl) indazol-3-carboxamide (implemented Example 209);
( 1^이미다졸 -2—일)메틸 )-6— (4-플루오로ᅳ 5ᅳ (3-(4-플루오로 -3— (트리플루오로 메틸)페닐)우레이도) -2—메틸페닐) -1^인다졸 -3-카복스아미드 (실시예 210); (1 ^ imidazol-2-2-yl) methyl) -6— (4-fluoro ᅳ 5 ′ (3- (4-fluoro-3— (trifluoromethyl) phenyl) ureido) -2—methylphenyl) -1 ^ indazole-3-carboxamide (Example 210);
(R)-6-(4—플루오로 -5-(3— (4ᅳ플루오로ᅳ 3- (트리폴루오로메틸)페닐)우레이도) -2ᅳ 메틸페닐) -Λ 피를리딘 -3-일) -L¾L인다졸—3—카복스아미드 (실시예 211); (R) -6- (4—Fluoro-5- (3— (4 ᅳ fluoro ᅳ 3- (trifluoromethyl) phenyl) ureido) -2′methylphenyl) -Λ pyridine-3- (I) -L 3 L indazole-3 carboxamide (Example 211);
(S)-6-(4ᅳ플루오로 -5— (3-(4ᅳ플루오로 -3— (트리플루오로메틸)페닐)우레이도) -2ᅳ 메틸페닐) -Λ 피롤리딘— 3-일) 인다졸 -3—카복스아미드 (실시예 212)； (S) -6- (4 ᅳ fluoro-5— (3- (4 ᅳ fluoro-3— (trifluoromethyl) phenyl) ureido) -2 ᅳ Methylphenyl) -Λ pyrrolidin—3-yl) indazole-3—carboxamide (Example 212);
6一 (4—플루오로— 5-(3-(4—플루오로— 3- (트리플루오로메틸)페닐)우레이도)—2—메틸 페닐) -Λ 1—메틸 -1^이미다졸— 4-일) 인다졸— 3ᅳ카복스아미드 (실시예 213); 6 一 (4—fluoro— 5- (3- (4—fluoro— 3- (trifluoromethyl) phenyl) ureido) —2—methyl phenyl) -Λ 1—methyl-1 ^ imidazole— 4 -Yl) indazole—3′carboxamide (Example 213);
6一(4-플루오로 -5-(3— (4-플루오로— 3- (트리플루오로메틸)페닐)우레이도) -2—메틸 페닐) - (1^이미다졸 -4-일 인다졸 -3-카복스아미드 (실시예 214)； 6- (4-Fluoro-5- (3— (4-fluoro- 3- (trifluoromethyl) phenyl) ureido) -2-methyl phenyl)-(1 ^ imidazol-4-yl indazole) 3-carboxamide (Example 214);
6— (4-플루오로 -5-(3— (4—플루오로 -3— (트리플루오로메틸 )페닐 )우레이도) -2-메틸 페닐) -Λ 피리미딘— 4-일) -1^인다졸 -3-카복스아미드 (실시예 215)；  6— (4-Fluoro-5- (3— (4—Fluoro-3— (trifluoromethyl) phenyl) ureido) -2-methyl phenyl) -Λ pyrimidin- 4-yl) -1 ^ Indazole-3-carboxamide (Example 215);
6-(4—플루오로— 5-(3— (4—플루오로— 3- (트리플루오로메틸)페닐)우레이도) -2-메틸 페닐) 메틸피리딘 -3-일) -1/ 인다졸 -3—카복스아미드 (실시예 216)；  6- (4—Fluoro— 5- (3— (4—Fluoro— 3- (trifluoromethyl) phenyl) ureido) -2-methyl phenyl) methylpyridin-3-yl) -1 / indazole -3—carboxamide (Example 216);
6— (4-플루오로 -5-(3— (4—플루오로— 3- (트리플루오로메틸)페닐)우레이도)—2-메틸 페닐) 메틸피리딘 -3-일)— 다졸ᅳ 3—카복스아미드 (실시예 217)；  6— (4-Fluoro-5- (3— (4—Fluoro— 3- (trifluoromethyl) phenyl) ureido) —2-methyl phenyl) methylpyridin-3-yl) — dazoljan 3— Carboxamide (Example 217);
6-(4-플루오로 -5-(3— (4-플루오로 -3- (트리플루오로메틸 )페닐 )우레이도) -2—메틸 페닐) 플루오로피리딘 -3-일) -1^인다졸 -3—카복스아미드 (실시예 218); 6- (4-fluoro-5- (3— (4-fluoro-3- (trifluoromethyl) phenyl) ureido) -2-2-methylphenyl) fluoropyridin-3-yl) -1 ^ Sol-3—carboxamide (Example 218);
6-(4—플루오로— 5— (3ᅭ(4-플루오로 -3- (트리플루오로메틸)페닐)우레이도) -2-메틸 페닐) -Λ 5-플루오로피리딘 -3—일)—1^인다졸 -3—카복스아미드 (실시예 219);6- (4—Fluoro— 5— (3 ᅭ (4-fluoro-3- (trifluoromethyl) phenyl) ureido) -2-methyl phenyl) -Λ 5-fluoropyridin-3-yl) —1 ^ indazole-3—carboxamide (Example 219);
6一 (4ᅳ플루오로 -5-(3ᅳ (4-플루오로 -3- (트리플루오로메틸)페닐)우레이도) -2—메틸 페닐) -Λ 6-폴루오로피리딘 -3—일) -1/·인다졸 -3—카복스아미드 (실시예 220);6- (4'fluoro-5- (3 '(4-fluoro-3- (trifluoromethyl) phenyl) ureido) -2-2-methylphenyl) -Λ 6-polouropyridin-3-yl ) -1 / .indazole-3—carboxamide (Example 220);
6- ( 5- ( ( 3— /ᅳ 부틸페닐)카바모일 ) -4-플루오로— 2-메틸페닐) 메틸ᅳ 1^인다졸—6- (5- ((3 — / ᅳ butylphenyl) carbamoyl) -4-fluoro— 2-methylphenyl) methyl ᅳ 1 ^ indazole—
3一카복스아미드 (실시예 221)； Tribasic carboxamide (Example 221);
6-(4—플루오로 -2-메틸— 5— ( (3— (트리플루오로메틸 )페닐 )카바모일 )페닐 )— 메틸 -1 / 인다졸ᅳ 3-카복스아미드 (실시예 222)；  6- (4—fluoro-2-methyl— 5— ((3— (trifluoromethyl) phenyl) carbamoyl) phenyl) — methyl-1 / indazoljan 3-carboxamide (Example 222);
6-(4-플루오로— 5— ((4—플루오로— 3- (트리플루오로메틸)페닐)카바모일 )ᅳ2—메틸페 닐) -그메틸 인다졸—3-카복스아미드 (실시예 223)；  6- (4-fluoro— 5— ((4—fluoro— 3- (trifluoromethyl) phenyl) carbamoyl) ᅳ 2—methylphenyl) -gmethyl indazole—3-carboxamide (implemented Example 223;
6-(4—플루오로 -2—메틸 -5— ( (3—메틸 -5ᅳ (트리플루오로메틸)페닐 )카바모일)페닐 )—7V 一메틸—I 인다졸 -3—카복스아미드 (실시예 224)；  6- (4—Fluoro-2—methyl-5— ((3—methyl-5 ᅳ (trifluoromethyl) phenyl) carbamoyl) phenyl) —7V one methyl—I indazole-3—carboxamide ( Example 224);
6-(5-( (4ᅳ클로로 -3- (트리플루오로메틸)페닐)카바모일 )ᅳ4-플루오로— 2-메틸페닐 ) 메틸 인다졸 -3—카복스아미드 (실시예 225);  6- (5- ((4 ᅳ chloro-3- (trifluoromethyl) phenyl) carbamoyl) ᅳ 4-fluoro- 2-methylphenyl) methyl indazole-3-carboxamide (Example 225);
6— (5-((4ᅳ ( (2ᅳ (디메틸아미노)에틸)아미노 )-3- (트리플루오로메틸 )페닐)카바모일 )-4—플루오로ᅳ 2-메틸페닐) -/\^메틸— 1^인다졸 -3—카복스아미드 (실시예 226); 6一(4ᅳ플루오로 -2-메틸 -5— ( (3-(4-메틸피페라진— 1—일 )-5ᅳ (트리플루오로메틸)페닐 )카바모일 )-2—메틸페닐)— ^메틸ᅳ 1^인다졸 -3-카복스아미드 (실시예 227); 6— (5-((4 ᅳ ((2 ᅳ (dimethylamino) ethyl) amino) -3- (trifluoromethyl) phenyl) carbamoyl) -4—fluoro ᅳ 2-methylphenyl)-/ \ ^ methyl — 1 ^ indazole-3—carboxamide (Example 226); 6 一 (4 ᅳ fluoro-2-methyl-5 — ((3- (4-methylpiperazin— 1—yl) -5 ᅳ (trifluoromethyl) phenyl) carbamoyl) -2—methylphenyl) — ^ Methyl ᅳ 1 ^ indazole-3-carboxamide (Example 227);
6-(4—플루오로— 2—메틸 -5-(4ᅳ (2- (피롤리딘 -1-일 )에톡시 )ᅳ3- (트리플루오로메틸 ) 페닐)카바모일)페닐) 메틸— 1 인다졸 -3-카복스아미드 (실시예 228); 6- (4—fluoro— 2—methyl-5- (4 ′ (2- (pyrrolidin-1-yl) ethoxy) ᅳ 3- (trifluoromethyl) phenyl) carbamoyl) phenyl) methyl— 1 indazole-3-carboxamide (Example 228);
6-(5-((3ᅳ((2- (디메틸아미노)에틸)아미노 )-5— (트리플루오로메틸)페닐)카바모일 )-4-플루오로 -2-메틸페닐) 메틸 -1^인다졸 -3-카복스아미드 (실시예 229); 6-(4-플루오로— 2-메틸— 5— ( (2-몰포리노 -5- (트리플루오로메틸)페닐 )카바모일)페 닐) -그메틸 인다졸— 3—카복스아미드 (실시예 230); 6- (5-((3 ᅳ ((2- (dimethylamino) ethyl) amino) -5— (trifluoromethyl) phenyl) carbamoyl) -4-fluoro-2-methylphenyl) methyl-1 ^ is Sol-3-carboxamide (Example 229); 6- (4-fluoro— 2-methyl— 5— ((2-morpholino-5 (trifluoromethyl) phenyl) carbamoyl) phenyl) -gmethyl indazole— 3—carboxamide (implemented Example 230);
6-(4ᅳ플루오로-5ᅳ( (2—플루오로 -5— (트리플루오로메틸)페닐)카바모일 )2—메틸페닐 메틸 -1^인다졸—3-카복스아미드 (실시예 231);  6- (4′fluoro-5 ′ ((2—fluoro-5— (trifluoromethyl) phenyl) carbamoyl) 2—methylphenyl methyl-1 ^ indazole—3-carboxamide (Example 231) ;
6-(5ᅳ ((3-((2— (디메틸아미노)에틸)아미노 )-5- (트리플루오로메틸)페닐)카바모일 )一4-플루오로 -2—메틸페닐)ᅳ^메틸 -ly 인다졸 -3-카복스아미드 (실시예 232); 6-(5ᅳ ((2-((2- (디메틸아미노)에틸)아미노 )-5- (트리플루오로메틸)페닐)카바모일 )-4-플루오로 -2—메틸페닐 )-/^메틸— 1^인다졸 -3-카복스아미드 (실시예 233); 6-(5— ((3—클로로 -4-메톡시페닐)카바모일 )—4-플루오로— 2-메틸페닐) 메틸 인다졸 -3-카복스아미드 (실시예 234)； 6- (5 ᅳ ((3-((2— (dimethylamino) ethyl) amino) -5- (trifluoromethyl) phenyl) carbamoyl) 一 4-fluoro-2—methylphenyl) ᅳ ^ methyl-ly Indazole-3-carboxamide (Example 232); 6- (5 '((2-((2- (dimethylamino) ethyl) amino) -5- (trifluoromethyl) phenyl) carbamoyl) -4-fluoro-2—methylphenyl)-/ ^ methyl— 1 ^ indazole-3-carboxamide (Example 233); 6- (5— ((3—chloro-4-methoxyphenyl) carbamoyl) —4-fluoro—2-methylphenyl) methyl indazole-3-carboxamide (Example 234);
6- ( 5- ( (4—클로로 -3-메틸페닐)카바모일 )ᅳ4—플루오로 -2-메틸페닐) 메틸 인 다졸— 3-카복스아미드 (실시예 235)； 6- (5- ((4—chloro-3-methylphenyl) carbamoyl) 일 4—fluoro-2-methylphenyl) methyl indazole— 3-carboxamide (Example 235);
6-(4-플루오로 -5— ((4-플루오로 -3—메틸페닐)카바모일)— 2-메틸페닐) - 메틸 -1^ 인다졸 -3-카복스아미드 (실시예 236)；  6- (4-fluoro-5— ((4-fluoro-3—methylphenyl) carbamoyl) — 2-methylphenyl) -methyl-1 ^ indazole-3-carboxamide (Example 236);
6-(4-플루오로 -5-( (4ᅳ이소프로필페닐)카바모일)— 2-메틸페닐) - 메틸 -I 인다졸 -3-카복스아미드 (실시예 237)；  6- (4-fluoro-5-((4'isopropylphenyl) carbamoyl) —2-methylphenyl) -methyl-I indazole-3-carboxamide (Example 237);
6— (4-플루오로— 2—메틸— 5— "를일카바모일)페닐)—그메틸— I 인다졸 -3-카복스아 미드 (실시예 238);  6— (4-fluoro— 2—methyl— 5— “ylylcarbamoyl) phenyl) —gmethyl— I indazole-3-carboxamide (Example 238);
6- (4-플루오로 -2-메틸— 5-( (4-메틸— 3— (트리플루오로메틸)페닐)카바모일 )페닐) -/V -메틸 인다졸 -3-카복스아미드 (실시예 239)；  6- (4-Fluoro-2-methyl— 5- ((4-methyl-3 — (trifluoromethyl) phenyl) carbamoyl) phenyl)-/ V-methyl indazole-3-carboxamide (implemented Example 239);
6-(4-플루오로 -5— ( (3ᅳ플루오로ᅳ5— (트리플루오로메록시 )페닐 )카바모일 )-2—메틸 페닐)—^메틸 -1그인다졸 -3-카복스아미드 (실시예 240)；  6- (4-Fluoro-5— ((3 ᅳ fluoro ᅳ 5— (trifluoromethoxy) phenyl) carbamoyl) -2—methyl phenyl) — ^ methyl-1gidazol-3-carboxamide (Example 240);
6-(5-((3-( ―부틸 )-1-페닐 -1그피라졸— 5-일 )카바모일 )—4-플루오로 -2-메틸페 닐)— 메틸— 1^인다졸—3—카복스아미드 (실시예 241)；  6- (5-((3-(-butyl) -1-phenyl-1gpyrazole— 5-yl) carbamoyl) —4-fluoro-2-methylphenyl) — methyl— 1 ^ indazole— 3—carboxamide (Example 241);
6-(4-플루오로 -2—메틸 -5— ((1,2,2,6,6—펜타메틸피페리딘 -4-일 )카바모일 )페닐) -/V -메틸 인다졸 -3—카복스아미드 (실시예 242)；  6- (4-fluoro-2—methyl-5 — ((1,2,2,6,6—pentamethylpiperidin-4-yl) carbamoyl) phenyl)-/ V-methyl indazole-3 —Carboxamide (Example 242);
6- ( 4-폴루오로 -2-메틸 -5- (( 2— ( 1-메틸피를리딘— 2-일 )에틸)카바모일 )페닐) -그메 틸 -1^인다졸 -3—카복스아미드 (실시예 243)；  6- (4-Polouro-2-methyl-5-((2— (1-methylpyridin—2-yl) ethyl) carbamoyl) phenyl) -gmethyl-1 ^ indazole-3-car Voxamide (Example 243);
6-(4-폴루오로 -5-(2— (3-플루오로페닐)하이드라진카보닐) -2—메틸페닐 )— 메틸 -1 / 인다졸 -3—카복스아미드 (실시예 244)；  6- (4-Polouro-5- (2— (3-fluorophenyl) hydrazinecarbonyl) -2—methylphenyl) —methyl-1 / indazole-3—carboxamide (Example 244);
6-(4-폴루오로—2-메틸— 5-( (3-(4-메틸피페라진— 1-일 )—5— (트리플루오로메틸)벤질 )카바모일)페닐) 메틸 인다졸 -3—카복스아미드 (실시예 245)；  6- (4-Polouro—2-methyl— 5- ((3- (4-methylpiperazin— 1-yl) —5— (trifluoromethyl) benzyl) carbamoyl) phenyl) methyl indazole- 3—carboxamide (Example 245);
6-(4-플루오로 -2-메틸— 5-(2-페닐아세타미도)페닐) - 메틸— 1^인다졸 -3-카복스 아미드 (실시예 246)； 6- (4-fluoro-2-methyl—5- (2-phenylacetamido) phenyl) -methyl-1 ^ indazole-3-carbox amide (Example 246);
6一 (5-(2ᅭ (4-클로로—3— (트리플루오로메틸)페닐)아세타미도) -4—플루오로— 2—메틸 페닐사메틸 -1/ 인다졸— 3-카복스아미드 (실시예 247)； 6- (5- (2 ᅭ (4-chloro--3— (trifluoromethyl) phenyl) acetamido) -4-fluoro-2-methyl phenylsamethyl -1 / indazole-3-carboxamide (Example 247);
6-(4—플루오로— 5— (2— (3—메톡시페닐)아세타미도) -2-메틸페닐 )— 메틸— 1/ 인다졸 -3ᅳ카복스아미드 (실시예 248)；  6- (4—fluoro— 5— (2— (3—methoxyphenyl) acetamido) -2-methylphenyl) — methyl— 1 / indazole-3′carboxamide (Example 248);
6-(4-폴루오로 -2-메틸 -5— (2- ᅳ를일)아세타미도)페닐 )- 메틸 -1^인다졸 -3一카 복스아미드 (실시예 249)；  6- (4-Polouro-2-methyl-5— (2- phenyl) acetamido) phenyl) -methyl-1 ^ indazole-3 ylcarboxamide (Example 249);
6-(4-폴루오로— 5— (2— (4-플루오로페닐)아세타미도) -2-메틸페닐 )—^메틸 -1^인다 졸 -3—카복스아미드 (실시예 250)；  6- (4-Polouro-5— (2— (4-fluorophenyl) acetamido) -2-methylphenyl) — ^ methyl-1 ^ indada sol-3—carboxamide (Example 250);
6-(5-(2- (벤조 [d][l,3]디옥솔 -5-일)아세타미도) -4-플루오로 -2-메틸페닐)— 메 틸 인다졸 -3-카복스아미드 (실시예 251)；  6- (5- (2- (benzo [d] [l, 3] dioxol-5-yl) acetamido) -4-fluoro-2-methylphenyl) —methyl indazole-3-carboxamide (Example 251);
6一(5-(2-(3,4—디클로로페닐)아세타미도) -4-플루오로 -2-메틸페닐) - 메틸 -L^인 다졸 -3-카복스아미드 (실시예 252)；  6- (5- (2- (3,4-dichlorophenyl) acetamido) -4-fluoro-2-methylphenyl) -methyl-L ^ indazole-3-carboxamide (Example 252);
6-(4-플루오로ᅳ 5-(2— (2-메록시페닐)아세타미도)—2-메틸페닐 메틸 -L 인다졸 -3-카복스아미드 (실시예 253)；  6- (4-fluoro ᅳ 5- (2— (2-methoxyphenyl) acetamido) —2-methylphenyl methyl-L indazole-3-carboxamide (Example 253);
6-(5-(2-(3， 5—디메톡시페닐)아세타미도 )ᅳ4-플루오로 -2-메틸페닐 ) - 메틸— 1^인 다졸— 3-카복스아미드 (실시예 254)； 6-(5-(2-(4—디메특시아미노페닐)아세타미도)— 4-플루오로— 2-메틸페닐)— 메틸 -1 ^인다졸 -3—카복스아미드 (실시예 255)； 6- (5- (2- (3,5-dimethoxyphenyl) acetamido) ᅳ 4-fluoro-2-methylphenyl) -methyl-1 ^ dazole- 3-carboxamide (Example 254); 6- (5- (2- (4-dimethoxyaminophenyl) acetamido)-4-fluoro- 2-methylphenyl) -methyl-1 ^ indazole-3-carboxamide (Example 255);
6-(4-플루오로 -2-메틸 -5— (2-(4-나이트로페닐 )아세타미도)페닐 )-/^메틸— 1/ 인다 졸ᅳ 3-카복스아미드 (실시예 256)；  6- (4-Fluoro-2-methyl-5— (2- (4-nitrophenyl) acetamido) phenyl)-/ ^ methyl— 1 / indazolazole 3-carboxamide (Example 256) ;
6一 (5-(2— (4- (브로모메틸)페닐)아세타미도 )-4-플투오로 -2—메틸페닐) - ^메틸 인다졸 -3-카복스아미드 (실시예 257)；  6- (5- (2— (4- (bromomethyl) phenyl) acetamido) -4-flutuo-2-methylphenyl)-^ methyl indazole-3-carboxamide (Example 257);
6-(4-플루오로— 2—메틸 -5-(2— (3- (트리플루오로메틸)페닐 )아세타미도)페닐 )— 메 틸ᅳ 1/ 인다졸 -3—카복스아미드 (실시예 258)；  6- (4-Fluoro— 2—methyl-5- (2— (3- (trifluoromethyl) phenyl) acetamido) phenyl) — methyl 1- indazole-3—carboxamide (implemented Example 258;
6-(4-플루오로 -5-(2— (4-플루오로 -3- (트리플루오로메틸)페닐)아세타미도) -2-메 틸페닐) -Λ^메틸 인다졸 -3-카복스아미드 (실시예 259)；  6- (4-fluoro-5- (2— (4-fluoro-3- (trifluoromethyl) phenyl) acetamido) -2-methylphenyl) -Λ ^ methyl indazole-3-car Voxamide (Example 259);
6-(5— (2— (4—브로모— 3—메틸페닐)아세타미도)— 4—풀루오로 -2-메틸페닐) -Λ^메틸 -인다졸 -3—카복스아미드 (실시예 260)； 6- (5— (2— (4—Bromo— 3—methylphenyl) acetamido) — 4—Pluoro-2-methylphenyl) -Λ ^ methyl-indazole-3—carboxamide (Example 260 );
6-(4-플루오로— 5-(2-(3—플루우로페닐)아세타미도) -2—메틸페닐) - ^메틸 -1 ^인다 졸ᅳ 3-카복스아미드 (실시예 261)；  6- (4-fluoro— 5- (2- (3—flurophenyl) acetamido) -2-methylphenyl)-^ methyl-1 ^ indazolezol 3-carboxamide (Example 261);
6-(4—플루오로— 2—메틸 -5- (메틸설폰아미도)페닐 )-그메틸— 다졸 -3-카복스아 미드 (실시예 262);  6- (4—Fluoro— 2—methyl-5 (methylsulfonamido) phenyl) -gmethyl—dazole-3-carboxamide (Example 262);
6-(4—플루오로 -2-메틸 -5— (트리플루오로메틸설폰아미도)페닐)— 메틸 인다졸 —3-카복스아미드 (실시예 263)；  6- (4—fluoro-2-methyl-5— (trifluoromethylsulfonamido) phenyl)-methyl indazole —3-carboxamide (Example 263);
6-(5— (에틸설폰아미도) -4—플루오로— 2-메틸페닐) -/V "메틸 -1^인다졸 -3-카복스아 미드 (실시예 264)； 및  6- (5— (ethylsulfonamido) -4—fluoro- 2-methylphenyl)-/ V "methyl-1 ^ indazole-3-carboxamide (Example 264); and
6—(4-플루오로— 2—메틸 -5— (1-메틸에틸설폰아미도)페닐 )— 메틸 인다졸 -3—카 복스아미드 (실시예 265). 한편, 상기 화학식 1로 표시되는 3, 6-이치환된 인다졸 유도체， 약학적으로 허용되는 이의 염 , 이의 용매화물， 이의 수화물이 Raf와 같은 단백질  6— (4-fluoro— 2—methyl-5— (1-methylethylsulfonamido) phenyl) — methyl indazole-3—carboxamide (Example 265). On the other hand, 3, 6-disubstituted indazole derivatives represented by the formula (1), pharmaceutically acceptable salts thereof, solvates thereof, hydrates thereof are proteins such as Raf
키나아제에 대한 우수한 억제 활성을 나타내므로, 본 발명은 비정상적인 세포 성장에 의해 유발되는 질환의 예방제 또는 치료제로 사용될 수 있다. Since it exhibits excellent inhibitory activity against kinases, the present invention can be used as a prophylactic or therapeutic agent for diseases caused by abnormal cell growth.
비정상적인 세포 성장에 의해 유발되는 질환의 예는 위암, 폐암, 간암, 대장암, 소장암, 췌장암, 뇌암, 뼈암, 혹색종， 유방암, 경화성선종， 자궁암, Examples of diseases caused by abnormal cell growth include gastric cancer, lung cancer, liver cancer, colon cancer, small intestine cancer, pancreatic cancer, brain cancer, bone cancer, myeloma, breast cancer, scleroid adenomas, uterine cancer,
자궁경부암， 두경부암, 식도암， 갑상선암， 부갑상선암, 신장암， 육종， 전립선암， 요도암, 방광암, 백혈병, 다발성골수종， 골수이형성증후군과 같은 혈액암, 호치킨병과 비호치킨림프종과 같은 림프종, 또는 섬유선종 등의 각종 종양 질환이 포함될 수 있다. Cervical cancer, head and neck cancer, esophageal cancer, thyroid cancer, parathyroid cancer, kidney cancer, sarcoma, prostate cancer, urethral cancer, bladder cancer, leukemia, multiple myeloma, hematologic cancers such as myelodysplastic syndrome, lymphomas such as Hochkin's disease and non-Hodgkin's lymphoma, or Various tumor diseases such as fibroadenoma may be included.
따라서， 본 발명은 상기 화학식 1로 표시되는 3 ,6-이치환된 인다졸 유도체， 약학적으로 허용되는 이의 염， 이의 용매화물， 이의 수화물을 유효성분으로 포함하는 약제조성물과， 비정상적인 세포 성장에 의해 유발되는 각종 종양 질환의 예방 및 치료제를 특징으로 한다. Accordingly, the present invention provides a pharmaceutical composition comprising a 3,6-disubstituted indazole derivative represented by Chemical Formula 1, a pharmaceutically acceptable salt thereof, a solvate thereof, and a hydrate thereof as an active ingredient, and abnormal cell growth. It is characterized by the prophylaxis and treatment of various tumor diseases caused.
본 발명의 약제조성물은 상기 화학식 1로 표시되는 3， 6-이치환된 인다졸 유도체 약학적으로 허용되는 이의 염， 이의 용매화물， 이의 수화물을 The pharmaceutical composition of the present invention is a pharmaceutically acceptable salt thereof, solvate thereof, or hydrate thereof of the 3, 6-disubstituted indazole derivative represented by Chemical Formula 1
유효성분으로 함유하고, 여기에 통상의 무독성 약제학적으로 허용 가능한 담체， 보강제 및 부형제 등을 첨가하여 약제학적 분야에서 통상적인 제제, 예를 들면 정제, 캅셀제， 트로키제， 액제, 현탁제 등의 경구투여용 제제 또는 Oral, such as tablets, capsules, troches, liquids, suspensions, etc., which are conventional in the pharmaceutical field by adding them as an active ingredient, and adding a conventional non-toxic pharmaceutically acceptable carrier, adjuvant, and excipient thereto. Formulations for administration or
비경구투여용 제제로 제제화할 수 있다. 본 발명의 약제 조성물에 사용될 수 있는 부형제로는 감미제, 결합제 , 용해제, 용해보조제， 습윤제， 유화제, 등장화제, 흡착제, 붕해제, 산화방지제， 방부제, 활탁제, 층진제, 방향제 등이 포함될 수 있다. 예를 들면 락토스, 덱스트로스, 슈크로스, 만니를, 솔비를， 샐롤로오스, 글라이신, 실리카, 탈크, 스테아린산, 스테린, 마그네슘 스테아린산염 , 마그네슘 알루미늄 규산염, 녹말, 젤라틴， 트라가칸트 고무, 알지닌산， 소디움 알진산염, 메틸셀를로오스, 소디움 카르복실메틸셀롤로오스, 아가， 물， 에탄올, 폴리에틸렌글리콜， 폴리비닐피를리돈, 염화나트륨， 염화칼슘， 오렌지 엣센스, 딸기 엣센스, 바닐라 향 등을 들 수 있다. It may be formulated into a parenteral preparation. Excipients that may be used in the pharmaceutical compositions of the present invention may include sweeteners, binders , solubilizers, solubilizers, wetting agents, emulsifiers, isotonic agents, adsorbents, disintegrants, antioxidants, preservatives, lubricants, layering agents, fragrances, and the like. . For example, lactose, dextrose, sucrose, manni, solbi, salulose, glycine, silica, talc, stearic acid, sterin, magnesium stearate, magnesium aluminum silicate, starch, gelatin, tragacanth rubber, eggs Havoc, sodium alginate, methylcellulose, sodium carboxymethylcellulose, agar, water, ethanol, polyethylene glycol, polyvinylpyridone, sodium chloride, calcium chloride, orange essence , strawberry essence, vanilla flavor Can be.
또한， 본 발명에 따른 화합물의 인체에 대한 투여용량은 환자의 나이 , 몸무게 , 성별, 투여형태， 건강상태 및 질환정도에 따라 달라질 수 있으며， 몸무게가 70kg인 성인환자를 기준으로 할 때 일반적으로 0.01 ~ 1,000 mg/일이며 , 의사 또는 약사의 판단에 따라 일정 시간간격으로 1일 1회 내지 수회로 분할 투여할 수도 있다. In addition, the dosage of the compound according to the present invention to the human body may vary according to the age, weight, sex, dosage form, health condition and degree of disease of the patient, and generally 0.01 based on an adult patient having a weight of 70 kg. ~ 1,000 mg / day, may be divided into once or several times a day at regular intervals depending on the judgment of the doctor or pharmacist.
이상에서 설명한 바와 같은 본 발명은 하기 제조예, 실시예, 제제예, 및 실험예에 의거하여 더욱 상세히 설명하겠는 바, 하기의 제조예, 실시예, 제제예, 및 실험예는 본 발명을 예시하는 것일 뿐 본 발명의 범위가 이들에 의해 한정되는 것은 아니다. [제조예] 원료물질의 합성 제조예 1. 에틸 The present invention as described above will be described in more detail based on the following Preparation Examples, Examples, Formulation Examples, and Experimental Examples, the following Preparation Examples, Examples, Formulation Examples, and Experimental Examples illustrate the present invention. The scope of the present invention is only limited by these. Preparation Example Synthesis of Raw Material Preparation Example 1. Ethyl
6— ( 2—메틸— 5-니트로페닐아미노) - 1- (테트라하이드로 -2//—피란 -2-일)— 인다졸—3 -카르복실레이트의 제조  6— (2—methyl— 5-nitrophenylamino) -1- (tetrahydro-2 // — pyran-2-yl) — indazole—3-carboxylate
Figure imgf000024_0001
단계 1. 3ᅳ아이오도 -6-니트로 -1 ^인다졸의 제조
Figure imgf000024_0001
Step 1. Preparation of 3 \ iodo-6-nitro-1 ^ indazole
6-니트로ᅳ1 -인다졸 (5 g)과 다이옥세인 (50 ITIL)을 등근 바닥 플라스크에 넣었다ᅳ 여기에 3 N NaOH 용액 (25 mL)을 가하고 교반하였다. 흔합물에 h (8.5 g)을 가해주었다. 4 시간 후에, 물 (100 mL)을 가해 반응을 종결하였다. 물을 가하여 생긴 생성물은 여과를 하여 노란색 고체 생성물을 얻었다. 생성물은 물로 닦아주고 질소 기체 하에서 건조하여 생성물 7.1 g (8(»)을 얻었다. Ή NMR (400 MHz, DMSO-flf;) δ 14.69 (bs, 1H), 8.97 (d, J 1.7 Hz, 1H), 8.48 (dd, J 8.9, 1.8 Hz, 1H), 8.18 (d, J = 8.9 Hz, 1H), MS m/z [M+H] 290. 단계 2. 6—니트로 인다졸—3—카보니트릴의 제조 6-Nitrojan1-indazole (5 g) and dioxane (50 ITIL) were placed in a bottom-bottom flask. 3N NaOH solution (25 mL) was added thereto and stirred. H (8.5 g) was added to the mixture. After 4 hours, water (100 ml ) was added to react Terminated. The product resulting from the addition of water was filtered to give a yellow solid product. The product was washed with water and dried under nitrogen gas to give 7.1 g (8 (») of the product.Ή NMR (400 MHz, DMSO-flf;) δ 14.69 (bs, 1H), 8.97 (d, J 1.7 Hz, 1H) , 8.48 (dd, J 8.9, 1.8 Hz, 1H), 8.18 (d, J = 8.9 Hz, 1H), MS m / z [M + H] 290. Step 2. 6—Nitroindazole—3—carbonitrile Manufacture
3-아이오도— 6-니트로— 인다졸 (5 g)과 디메틸포름아미드 (DMF; 58 ml )를 등근 바닥 플라스크에 넣었다. 혼합물에 CuCN (7.5 g)을 넣어주고 250 °C로 가열하였다. 2 시간 후에 흔합물을 여과하여 부유물을 제거하였다. 3-iodo- 6-nitro- indazole (5 g) and dimethylformamide (DMF; 58 ml) were placed in the back bottom flask. CuCN (7.5 g) was added to the mixture and heated to 250 ° C. After 2 hours the mixture was filtered to remove suspended solids.
여과용액은 감압증류로 용매를 제거하여 고체 생성물을 얻었다. The filtrate was distilled off under reduced pressure to obtain a solid product.
목적화합물을 정제 없이 다음 반웅에 사용하였다. MS m/z [M+H] 189. 단계 3. 6-니트로—1 -인다졸— 3-카르복실산의 제조의 제조 The target compound was used in the next reaction without purification. MS m / z [M + H] 189. Step 3. Preparation of 6-Nitro—1-Indazole—3-carboxylic Acid
6—니트로 -LY-인다졸 -3-카보니트릴 (3 g)에 물 (10 i L)을 가하였다. To the 6-nitro-LY-indazole-3-carbonitrile (3 g) was added water (10 i L).
흔합물에 K0H (9.5 g)을 가하고 100 °C로 가열하였다. 5 시간 후에 . K0H (9.5 g) was added to the mixture and heated to 100 ° C. After 5 hours.
흔합물의 온도를 낮추고 6 N HC1로 용액을 중화하였다. 얻어진 고체 생성물을 고체여과를 통해 얻었다. 생성물은 물로 닦아주고 질소 기체 하에서 건조하여 생성물 2.6 g (37.3%)을 얻었다. lH NMR (400 MHz, DMSO- ) δ 14.89 (bs, 1Η), 8.58 (d, J= 1.8 Hz, 1H), 8.32 (d, /= 8.9 Hz, 1H), 8.04The temperature of the mixture was lowered and the solution was neutralized with 6 N HC1. The obtained solid product was obtained by solid filtration. The product was washed with water and dried under nitrogen gas to give 2.6 g (37.3%) of the product. l H NMR (400 MHz, DMSO- ) δ 14.89 (bs, 1Η), 8.58 (d, J = 1.8 Hz, 1H), 8.32 (d, / = 8.9 Hz, 1H), 8.04
(del, J = 8.9, 1.8 Hz, 1H). MS m/z [M+H] 208. 단계 4. 에틸 6—니트로 인다졸—3ᅩ카르복실레이트의 제조 (del, J = 8.9, 1.8 Hz, 1H). MS m / z [M + H ] 208. Step 4. Preparation of ethyl 6-nitro-indazol-o -3-carboxylate
6一니트로ᅳ 1 -인다졸 -3-카르복실산 (280 mg)과 EtOH (4.5 niL)을 등근 바닥 플라스크에 넣었다. 혼합물에 진한 S04 (0.04 mL)을 넣어주고 100 °C로 가열하였다. 3 시간 후에 감압증류로 용매를 제거하고， IN NaOH로 흔합액을 중성으로 중화하였다. 증화해서 얻어진 고체 생성물은 고체여과를 통해 얻었다. 생성물은 물로 닦아주고 질소 기체 하에서 건조하여 생성물 300 mg (94%)을 얻었다. ¾ NMR (400 MHz , DMSO— c¾) δ 14.67 (bs, 1H), 8.58 (cl, J = 1.7 Hz, 1H), 8.27 (d, /= 8.9 Hz, 1H), 8.13 (dd, J= 9.0， 1.8 Hz, 1H), 4.436-nitrojan 1-indazol-3-carboxylic acid (280 mg) and EtOH (4.5 niL) were placed in a back-bottom flask. Concentrated S0 4 (0.04 mL) was added to the mixture and heated to 100 ° C. After 3 hours, the solvent was removed by distillation under reduced pressure, and the mixture was neutralized with IN NaOH. Solid product obtained by quenching was obtained by solid filtration. The product was washed with water and dried under nitrogen gas to give 300 mg (94%) of the product. ¾ NMR (400 MHz, DMSO— c¾) δ 14.67 (bs, 1H), 8.58 (cl, J = 1.7 Hz, 1H), 8.27 (d, / = 8.9 Hz, 1H), 8.13 (dd, J = 9.0, 1.8 Hz, 1H), 4.43
(q, / = 7.1 Hz, 2H), 1.40 (t, J = 7.1 Hz, 3H), MS m/z [M+H] 236. 단계 5. 에틸 (q, / = 7.1 Hz, 2H), 1.40 (t, J = 7.1 Hz, 3H), MS m / z [M + H] 236. Step 5. Ethyl
6-니트로 -1- (테트라하이드로— 2 ᅳ피란 -2-일 )-1 -인다졸ᅳ 3—카르복실레이트의 제조  Preparation of 6-nitro-1- (tetrahydro— 2 cappyran-2-yl) -1 -indazol ᅳ 3—carboxylate
에틸 6-니트로—1 —인다졸 -3ᅳ카르복실레이트 (130 mg)과 아세토나이트릴 (1.8 mL)를 등근 바닥 플라스크에 넣었다. 흔합물에 TsOH H20 (10 mg)과 Ethyl 6-nitro-l-indazole-3xcarboxylate (130 mg) and acetonitrile (1.8 mL) were placed in a back bottom flask. TsOH H 2 0 (10 mg) and
3,4—디하이드로 -2 —피란 (0.1 mL)을 넣어 주었다. 3 시간후에 감압증류로 용매를 제거하고， 탄산수소나트륨 수용액을 사용하고 에틸아세테이트로 추출한 다음에 유기층을 무수 황산마그네슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거한 후 획득한 잔사를 관 크로마토그래피 3,4—dihydro-2—pyran (0.1 mL) was added. After 3 hours, the solvent was removed by distillation under reduced pressure, an aqueous sodium bicarbonate solution was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and filtered. The residue obtained after the solvent was removed by distillation under reduced pressure was subjected to column chromatography.
(Et0Ac:n4iexane=l:4)를 통해 정제하여 목적화합물 에틸 Purified via (Et0Ac: n4iexane = l: 4) to give the title compound ethyl
6-니트로 -1- (테트라하이드로 -2 ᅳ피란 -2-일 )— 1 -인다졸 -3-카르복실레이트 130 mg (72¾)을 얻었다. Ή NMR (400 MHz, DMSO-^) δ 8.89 (d, J= 1.6 Hz, 1H), 8.29 (d, /= 8.9 Hz, 1H), 8.18 (del, J 8.9, 1.8 Hz, 1H), 6.40 (d J= 9.1 Hz, 1H), 4.45 (q, J = 7.2 Hz, 2H), 3.89 (m, 2H), 2.38(m, 1H), 2.07 (m, 1H), 1.78 (m, 1H), 1.62 (m, 2H), 1.40 (t, J = 7.1 Hz, 3H), MS m/z [M+H] 320. . ' 단계 6. 에틸 6-nitro-1- (tetrahydro-2 cappyran-2-yl) — 1-indazole-3-carboxylate 130 mg (72¾) was obtained. Ή NMR (400 MHz, DMSO- ^) δ 8.89 (d, J = 1.6 Hz, 1H), 8.29 (d, / = 8.9 Hz, 1H), 8.18 (del, J 8.9, 1.8 Hz, 1H), 6.40 ( d J = 9.1 Hz, 1H), 4.45 (q, J = 7.2 Hz, 2H), 3.89 (m, 2H), 2.38 (m, 1H), 2.07 (m, 1H), 1.78 (m, 1H), 1.62 (m, 2H), 1.40 (t, J = 7.1 Hz, 3H), MS m / z [M + H] 320.. "Step 6. Ethyl
6—아미노 -1— (테트라하이드로 -2 -피란 -2-일 )-1 —인다졸 -3-카르복실레이트의 제조  Preparation of 6—amino-1— (tetrahydro-2-pyran-2-yl) -1—indazole-3-carboxylate
에틸 6-니트로 -1— (테트라하이드로 -2//-피란 -2-일 인다졸 -3—카르복실레이트 (90 mg)를 MeOH에 용해시킨 다음， 10% Pd/C를 넣고 수소 기체 하에서 2 시간 동안 실온에서 교반하였다. 반웅이 종결하면 규조토 패드로 여과한 후 여과액을 감압 증류로 제거하여 목적화합물 에틸 Ethyl 6-nitro-1— (tetrahydro-2 //-pyran-2-yl indazole-3—carboxylate (90 mg) was dissolved in MeOH, then 10% Pd / C was added and under hydrogen gas. After stirring, the reaction mixture was filtered through a pad of diatomaceous earth, and the filtrate was removed by distillation under reduced pressure.
6一아미노— 1— (테트라하이드로 -2 -피란— 2-일) 인다졸 -3-카르복실레이트 75 mg (93%)를 얻었다. lH NMR (400 MHz, DMSO—οί;) δ 7.69(d, /= 8.1 Hz, 1H), 6.71 (m. 2H), 5.67 (dd, ./ = 9.6. 2.5 Hz, 1H), 5.58 (s, 2H), 4.35 (q, J = 7.1 Hz,75 mg (93%) of 6-amino-l- (tetrahydro-2-pyran- 2-yl) indazole-3-carboxylate were obtained. l H NMR (400 MHz, DMSO -οί;) δ 7.69 (d, / = 8.1 Hz, 1H), 6.71 (. m 2H), 5.67 (. dd, ./ = 9.6 2.5 Hz, 1H), 5.58 (s , 2H), 4.35 (q, J = 7.1 Hz,
2H), 3.89 (m, 1H), 3.70(m, 1H), 2.33 (in, 1H), 2.01 (m, 1H), 1.93 (m, 1H)， 1.74 (m, 1H), 1.58 (in, 2H), 1.34 (t , / = 7.1 Hz, 3H). MS m/z [M+H] 290. 단계 7. 에틸 2H), 3.89 (m, 1H), 3.70 (m, 1H), 2.33 (in, 1H), 2.01 (m, 1H), 1.93 (m, 1H), 1.74 (m, 1H), 1.58 (in, 2H ), 1.34 (t, / = 7.1 Hz, 3H). MS m / z [M + H] 290. Step 7. Ethyl
6一 (2-메틸 -5-니트로페닐아미노) -1- (테트라하이드로 -2//-피란 -2-일 인다졸 -3 -카르복실레이트의 제조  Preparation of 6- (2-methyl-5-nitrophenylamino) -1- (tetrahydro-2 //-pyran-2-yl indazole-3-carboxylate
에틸 6—아미노 -1- (테트라하이드로—2//ᅳ피란 -2-일 )ᅳ1//-인다졸ᅳ 3-카르복실레이트 (1000 mg, 3.4隱01)와 2-브로모 -1—메틸— 4-니트로벤젠 (730 mg, 3.6 mmo 1 ) , χ-phos (140 mg, 0.30 mmol), NaOie i^u (650 mg, 6.8讓 ol)을 를루엔 (15 mL)에 녹여 탈기한 후 Pd2(dba), (186 mg, 0.20睡 ol)을 넣고 90 °C에서 가열하였다. 5 시간 후 반웅이 종결하면 규조토 패드로 여과한 후 에틸아세테이트와 물로 추출하고 모아진 유기층을 무수 황산마그네슘으로 건조하여 여과하였다. Ethyl 6-amino-1- (tetrahydro—2 // pypyran-2-yl) ᅳ 1 //-indazole ᅳ 3-carboxylate (1000 mg, 3.4 隱 01) and 2-bromo-1 Methyl— 4-nitrobenzene (730 mg, 3.6 mmo 1), χ-phos (140 mg, 0.30 mmol) and NaOie i ^ u (650 mg, 6.8 讓 ol) are dissolved in toluene (15 mL) and degassed. Pd 2 (dba), (186 mg, 0.20 睡 ol) was added thereto and heated at 90 ° C. After the reaction was completed after 5 hours, the mixture was filtered through a pad of diatomaceous earth, extracted with ethyl acetate and water, and the combined organic layers were dried over anhydrous magnesium sulfate and filtered.
용매를 감압 증류로 제거한 다음에 획득한 잔사를 관 크로마토그래피 After removing the solvent by distillation under reduced pressure, the obtained residue was subjected to column chromatography.
(실리카겔， EtOAc:rHiexane = 1:4 → 1:2)를 통해 정제하여 목적화합물인 에틸 6-(2-메틸 -5ᅳ트로페닐아미노)—1— (테트라하이드로 -2 -피란— 2—일 인다졸 -3- 카르복실레이트 (980 mg, 68%)를 얻었다. NMR (400 MHz , DMS으 ) δ 8.20 (s, 1H), 8.01 (d, J = 2.3 Hz, 1H), 7.97 (d, J = 8.8 Hz, 1H), 7.74 (dd, J = 2.3, 8.3 Hz, 1H), 7.49 (d, J = 8.3 Hz, 1H), 7.36 (d, J 1.5 Hz, 1H), 7.19 (dd, J= 1.7, 8.8 Hz, 1H), 5.80 (dd, J= 2.3， 9.5 Hz, 1H), 4.40 (q, J = 2.9 Hz, 2H), 3.87 (m, 1H), 3.69 (m, 1H), 2.37 (s, 3H), 1.99 (m, 3H), 1.74 (m, 1H), 1.57 (m, 2H), 1.38 (t, J = 7.1, 3H), MS m/z [M+H] 425. 제조예 2. 에틸 Purification via (silica gel, EtOAc: rHiexane = 1: 4 → 1: 2) yielded the target compound ethyl 6- (2-methyl-5pentrophenylamino) —1— (tetrahydro-2-pyran— 2—yl Indazole-3-carboxylate (980 mg, 68%) was obtained: NMR (400 MHz, DMS) δ 8.20 (s, 1H), 8.01 (d, J = 2.3 Hz, 1H), 7.97 (d, J = 8.8 Hz, 1H), 7.74 (dd, J = 2.3, 8.3 Hz, 1H), 7.49 (d, J = 8.3 Hz, 1H), 7.36 (d, J 1.5 Hz, 1H), 7.19 (dd, J = 1.7, 8.8 Hz, 1H), 5.80 (dd, J = 2.3, 9.5 Hz, 1H), 4.40 (q, J = 2.9 Hz, 2H), 3.87 (m, 1H), 3.69 (m, 1H), 2.37 (s, 3H), 1.99 (m, 3H), 1.74 (m, 1H), 1.57 (m, 2H), 1.38 (t, J = 7.1, 3H), MS m / z [M + H] 425. Preparation Example 2. Ethyl
6-(2-메틸 -5-니트로페닐아미노) -1— (테트라하이드로— 2//—피란ᅳ 2-일) -1 인다졸ᅳ3 —카르복실레이트의 제조
Figure imgf000027_0001
단계 1. 6-브로모 인다졸 -3-카르복실산의 제조 6- (2-Methyl-5-nitrophenylamino) -1— (tetrahydro— 2 // — pyranjan 2-yl) -1 indazole ᅳ 3 —preparation of carboxylate
Figure imgf000027_0001
Step 1. Preparation of 6-bromo indazole-3-carboxylic acid
1 N 수산화나트륨 (48 mL)에 녹인 6-브로모이사틴 (10 g, 22 mmol) 용액을 50 °C에서 1 시간 동안 교반하고 실은에서 1 시간 동안 교반하였다. 반응 흔합물을 0 1로 내리고， 물 (11 mL)에 녹인 아질산나트륨 (3 g, 22 mmoU을 10-15분 동안 적가하였다. 반웅 흔합물을 0 'C 하에서 물 (90 inL)와 황산 (4.6 mL)의 흔합 용액의 표면 아래로 10-15분 동안 적가하면서 격렬하게 교반하였다. 적가가 끝난 후, 발생한 디아조늄 수용액을 진한 염산 (40 mL)에 녹인 염화주석 (53画 ol, 24 g; SnCl2 · 2H20) 수용액에 천천히 적가하면서 격렬하게 교반하였다. 1 시간 동안 교반 후 발생한 침전물을 여과하였다. 걸러진 침전물을 물로 세척하고 건조하여 목적화합물인 A solution of 6-bromoissatin (10 g, 22 mmol) dissolved in 1 N sodium hydroxide (48 mL) was stirred at 50 ° C for 1 hour and at room temperature for 1 hour. Down the reaction to 0 first common compound, sodium nitrite (3 g, 22 mmoU gt; C for 10 to 15 minutes. Sulfuric acid, water (90 inL) and the compound under common 0 'C banung dissolved in water (11 mL) (4.6 vigorously stirred for 10-15 minutes dropwise below the surface of the mixed solution of mL) After completion of the dropwise addition, the resulting diazonium aqueous solution was dissolved in concentrated hydrochloric acid (40 mL) (53 画 ol, 24 g; SnCl). 2 · 2H 2 0) Slowly added dropwise to the aqueous solution, followed by vigorous stirring, and the precipitate formed after stirring for 1 hour was filtered The filtered precipitate was washed with water and dried to obtain the desired compound.
6-브로모 인다졸 -3—카르복실산 (8.98 g)을 얻었다. }W NMR (300 MHz, DMS0-oi5) δ 13.76 (bs, 1Η), 7.87 (s, 1H)， 7.55 (d, J= 8 Hz, 1H), 7.27 (d, J = 8 Hz, 1H), 2.44 (s, 3H), MS m/z [M+H] 242, 244. 단계 2. 에틸 6-브로모 인다졸 -3-카르복실레이트의 제조 6-Bromo indazole-3—carboxylic acid (8.98 g) was obtained. } W NMR (300 MHz, DMS0-oi 5 ) δ 13.76 (bs, 1Η), 7.87 (s, 1H), 7.55 (d, J = 8 Hz, 1H), 7.27 (d, J = 8 Hz, 1H) , 2.44 (s, 3H), MS m / z [M + H] 242, 244. Step 2. Preparation of ethyl 6-bromoindazole-3-carboxylate
에탄을 (160 mL)에 녹인 6-브로모 -1 ᅳ인다졸 -3-카르복실산 (5 g, 21 mmol) 용액에 0 °C에서 황산 (2 niL)을 천천히 첨가하였다. 이 혼합물을 4 시간 동안 환류 교반한 후 실온으로 냉각하여 감압 하에서 농축하여 잔류 에탄올을 제거하였다. 잔사에 물을 넣어 묽힌 후 생성된 고체 화합물을 여과하여 건조하였다. 건조된 고체 화합물을 컬럼 크로마토그래피 (실리카겔, 메틸렌클로라이드:메탄올 =9:1)로 정제하여 목적 화합물인 To sulfuric acid (2 niL) was slowly added to a solution of 6-bromo-1 disindazol-3-carboxylic acid (5 g, 21 mmol) in ethane (160 mL) at 0 ° C. The mixture was stirred at reflux for 4 hours, then cooled to room temperature and concentrated under reduced pressure to remove residual ethanol. Water was added to the residue, diluted, and the resulting solid compound was filtered and dried. The dried solid compound was purified by column chromatography (silica gel, methylene chloride: methanol = 9: 1) to obtain the target compound.
에틸 -6—브로모—1 —인다졸 -3-카르복실레이트 (2.8 g)를 얻었다. Hi NMR (300 MHz, CDC13) δ 14.04 (br s, 1 H), 8.00 (d, J= 8.4 Hz, 1 H), 7.91 (d, J = 1.2Ethyl-6-bromo-1-indazole-3-carboxylate (2.8 g) was obtained. Hi NMR (300 MHz, CDC1 3 ) δ 14.04 (br s, 1 H), 8.00 (d, J = 8.4 Hz, 1 H), 7.91 (d, J = 1.2
Hz, 1 H), 7.45 (dd, J = 1.5， 8.7 Hz, 1 H), 4.39 (q, / = 7.2 Hz, 2 H), 1.35 (t, J= 7.2 Hz, 3 H), MS m/z [M+H] 270, 272. 단계 3. 에틸 Hz, 1H), 7.45 (dd, J = 1.5, 8.7 Hz, 1H), 4.39 (q, / = 7.2 Hz, 2H), 1.35 (t, J = 7.2 Hz, 3H), MS m / z [M + H] 270, 272. Step 3. Ethyl
6-브로모—1- (테트라하이드로— 2 -피란 -2-일 ) -1 -인타졸— 3-카르복실레이트의 제조 Preparation of 6-Bromo-l- (tetrahydro— 2-pyran-2-yl) -l-inazole- 3-carboxylate
에틸 -6-브로모 -1 -인다졸 -3-카르복실레이트 (385 mg, 1.43 隱 ol)와 With ethyl-6-bromo-1-indazole-3-carboxylate (385 mg, 1.43 μl ol)
3，4-디하이드로—2 -피란 (0.26 mL, 2.86 隱 ol), /广를루엔설폰산 (27 mg, 0. 14 ιοΐ)을 아세토니트릴 (4.5 niL)에 녹이고 실온에서 교반하였다. 3 시간 후 반웅이 종결하면 탄산수소나트륨 수용액을 사용하고 에틸아세테이트로 추출한 다음에 유기층을 무수 황산마그네슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거하여 농축하여 목적화합물 ' 3,4-dihydro—2-pyran (0.26 mL, 2.86 隱 ol), / 广 luenesulfonic acid (27 mg, 0. 14 ιοΐ) was dissolved in acetonitrile (4.5 niL) and stirred at room temperature. When the reaction was terminated after 3 hours, an aqueous sodium hydrogen carbonate solution was used, extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and filtered. The solvent was removed by distillation under reduced pressure and concentrated .
6一브로모— 1- (테트라하이드로 -2//—피란— 2—일 ) -1 —인타졸 -3 르복실레이트 (501 mg, 99%)를 얻었다. ¾ NMR (400 MHz , DMSO— ) δ 8.21 (d, J= 1.6 Hz, 1H), 8.01 (d, J= 8.7 Hz, 1H) 7.52 (dd, , / = 1.6， 8.6 Hz, 1H), 6.02 (dd, /= 2.5, 9.8 Hz, 1H), 4.41 (1, J 7.3 Hz, 2H), 3.88 (m, 1H) , 3.80 (m, 1H), 2.01 (m, 2H), 2.33 (111， IH), 1.73 (m, 1H), 1.59 (m, 2H), 1.37 (t, J 7.Ϊ Hz, 3H), MS m/z [M+H] 354, 356. 단계 4. 에틸 6-I bromo- 1- (tetrahydro-2 //-pyran- 2-day) -1-intazole -3 carboxylate (501 mg, 99%) was obtained. ¾ NMR (400 MHz, DMSO—) δ 8.21 (d, J = 1.6 Hz, 1H), 8.01 (d, J = 8.7 Hz, 1H) 7.52 (dd,, / = 1.6, 8.6 Hz, 1H), 6.02 ( dd, / = 2.5, 9.8 Hz, 1H), 4.41 (1, J 7.3 Hz, 2H), 3.88 (m, 1H), 3.80 (m, 1H), 2.01 (m, 2H), 2.33 (111, IH) , 1.73 (m, 1H), 1.59 (m, 2H), 1.37 (t, J 7. Ϊ Hz, 3H), MS m / z [M + H] 354, 356. Step 4. Ethyl
6-(2—메틸— 5—니트로페닐아미노) -1- (테트라하이드로— 2 ―피란 -2-일 ) 인다졸 -3 -카르복실레이트의 제조 ' Preparation of 6- (2—methyl— 5—nitrophenylamino) -1- (tetrahydro— 2-pyran-2-yl) indazole-3-carboxylate ''
6-브로모—1- (테트라하이드로 -2//-피란 -2—일 ) 인타졸 3-카르복실레이트 (1.7 g 4.81 ol)와 2-메틸— 5—니트로아닐린 C659 mg, 4.33 mniol), χ-phos (206 mg, 0.43 ol), 2C03 (3.3 g, 24.1 o I)을 2—부탄올 (20 niL)에 녹여 탈기한 후 Pcl2(dba)3 (264 mg, 0.29 ol)을 넣고 90 °C에서 가열하였다. 5 시간 후 반응이 종결하면 규조토 패드로 여과한 후 에틸아세테이트와 물로 추출하고 모아진 유기층을 무수 황산마그네슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거한 다음에 획득한 잔사를 관 크로마토그래피 (실리카겔， 6-bromo-l- (tetrahydro-2 //-pyran-2-yl) intazole 3-carboxylate (1.7 g 4.81 ol) and 2-methyl--5-nitroaniline C659 mg, 4.33 mniol), Dissolve χ-phos (206 mg, 0.43 ol), 2 C0 3 (3.3 g, 24.1 o I) in 2—butanol (20 niL), degas and add Pcl 2 (dba) 3 (264 mg, 0.29 ol) Heated at 90 ° C. After 5 hours, the reaction was terminated, filtered through a pad of diatomaceous earth, extracted with ethyl acetate and water, and the combined organic layers were dried over anhydrous magnesium sulfate and filtered. After removing the solvent by distillation under reduced pressure, the obtained residue was subjected to column chromatography (silica gel,
EtOAc:n^exane = 1:4 → 1:2)를 통해 정제하여 목적화합물인 에틸 Ethyl: n ^ exane = 1: 4 → 1: 2)
6—(2-메틸 -5—트로페닐아미노)— 1- (테트라하이드로 -2//—피란 -2-일 )-1 -인다졸 -3— 카르복실레이트 (998 mg, 49%)을 얻었다. Hi NMR (400 MHz, DMS0— δ 8.20 (s, 1Η), 8.01 (d, J 2.3 Hz, IH), 7.97 (d, J 8.8 Hz, 1H) , 7.74 (dd, J = 2.3, 8.3 Hz, IH), 7.49 (d, J = 8.3 Hz, IH) , 7.36 (d, J = 1.5 Hz, IH), 7.19 (del, J= 1.7， 8.8 Hz, IH), 5.80 (dd, /= 2.3, 9.5 Hz, IH), 4.40 (q, J = 2.9 Hz, 2H), 3.87 (m, IH), 3.69 (m, IH), 2.37 (s, 3H), 1.99 (m, 3H), 1.74 (m, IH), 1.57 (m, 2H), 1.38 (t, / = 7.1, 3H), MS m/z [M+H] 425. 제조예 3. 메틸 6- (2-Methyl-5-trophenylamino) -l- (tetrahydro-2 //-pyran-2-yl) -l-indazole-3-carboxylate (998 mg, 49%) was obtained . Hi NMR (400 MHz, DMS0— δ 8.20 (s, 1Η), 8.01 (d, J 2.3 Hz, IH), 7.97 (d, J 8.8 Hz, 1H), 7.74 (dd, J = 2.3, 8.3 Hz, IH ), 7.49 (d, J = 8.3 Hz, IH), 7.36 (d, J = 1.5 Hz, IH), 7.19 (del, J = 1.7, 8.8 Hz, IH), 5.80 (dd, / = 2.3, 9.5 Hz , IH), 4.40 (q, J = 2.9 Hz, 2H), 3.87 (m, IH), 3.69 (m, IH), 2.37 (s, 3H), 1.99 (m, 3H), 1.74 (m, IH) , 1.57 (m, 2H), 1.38 (t, / = 7.1, 3H), MS m / z [M + H] 425. Preparation Example 3 Methyl
6-(2—메틸— 4-플루오로 -5-페닐아미노)—1- (테트라하이드로— 2^피란 -2-일 )-1^인 다졸 -3-카복스아미드의 제조
Figure imgf000029_0001
단계 1. 3-아이오도 -6-브로모 인다졸의 제조 Preparation of 6- (2—methyl— 4-fluoro-5-phenylamino) —1- (tetrahydro— 2 ^ pyran-2-yl) -1 ^ indazole-3-carboxamide
Figure imgf000029_0001
Step 1. Preparation of 3-iodo-6-bromo indazole
6-브로모ᅳ 1/ 인다졸 (5 g)과 다이옥세인 (50 ill)을 등근 바닥 플라스크에 넣었다. 여기에 3 N NaOH 용액 (25 niL)을 가하고 교반하였다. 흔합물에 (8.5 g)을 가해주었다. 4시간 후에, 물 (100 mL)을 가해 반응을 종결하였다. 물을 가하여 생긴 생성물은 여과를 하여 노란색 고체 생성물을 얻었다. 생성물은 물로 닦아주고 질소 기체 하에서 건조하여 생성물 7.1 g (80%)을 얻었다. 匿 (400 MHz, DMS0— ) δ 14.69 (bs, 1H), 8.97 (d, J = 1.7 Hz, 1H), 8.48 (del, J = 8.9, 1.8 Hz, 1H), 8.18 (d, J 8.9 Hz, 1H), MS m/z [M+H] 290. 단계 2. 6-브로모 인다졸 -3-카보니트릴의 제조  6-Bromoqen 1 / indazole (5 g) and dioxane (50 ill) were placed in a bottom-bottom flask. To this was added 3 N NaOH solution (25 niL) and stirred. (8.5 g) was added to the mixture. After 4 hours, water (100 mL) was added to terminate the reaction. The product resulting from the addition of water was filtered to give a yellow solid product. The product was washed with water and dried under nitrogen gas to give 7.1 g (80%) of the product. 400 (400 MHz, DMS0—) δ 14.69 (bs, 1H), 8.97 (d, J = 1.7 Hz, 1H), 8.48 (del, J = 8.9, 1.8 Hz, 1H), 8.18 (d, J 8.9 Hz, 1H), MS m / z [M + H] 290. Step 2. Preparation of 6-bromo indazole-3-carbonitrile
3-아이오도 -6-니트로 인다졸 (5 g)과 DMF (58 ITIL)을 등근 바닥 플라스크에 넣었다. 혼합물에 CuCN (7.5 g)을 넣어주고 250 °C로 가열하였다.  3-iodo-6-nitroindazole (5 g) and DMF (58 ITIL) were placed in the back bottom flask. CuCN (7.5 g) was added to the mixture and heated to 250 ° C.
2시간 후에 흔합물을 여과하여 부유물을 제거하였다. 여과용액은  After 2 hours the mixture was filtered to remove suspended solids. Filtration solution
감압증류로 용매를 제거하여 고체 생성물을 얻었다. 목적화합물을 정제 없이 다음 반웅에 사용하였다. MS m/z [M+H] 189. 단계 3. 6-브로모—l^인다졸 -3-카르복실산의 제조 The solvent was removed by distillation under reduced pressure to obtain a solid product. The target compound was used in the next reaction without purification. MS m / z [M + H] 189. Step 3. Preparation of 6-Bromo—l ^ indazole-3-carboxylic acid
6-브로모 -1^인다졸 -3-카보니트릴 (3 g)에 물 (10 mL)을 가하였다.  To 6-bromo-1 ^ indazole-3-carbonitrile (3 g) was added water (10 mL).
흔합물에 K0H (9.5 g)을 가하고 100 °C로 가열하였다. 5시간 후에 흔합물의 온도를 낮추고 6 N HCI로 용액을 중화하였다. 얻어진 고체 생성물을 고체여과를 통해 얻었다. 생성물은 물로 닦아주고 질소 기체 하에서 건조하여 생성물 2.6 g (단계 2-37 )을 얻었다. ¾匪 R (400 MHz, DMSO-^) δ 14.89 (bs, 1H), 8.58 (d, J = 1.8 Hz, 1H), 8.32 (d, J= 8.9 Hz, 1H), 8.04K0H (9.5 g) was added to the mixture and heated to 100 ° C. After 5 hours the temperature of the mixture was lowered and the solution was neutralized with 6 N HCI. The obtained solid product was obtained by solid filtration. The product was washed with water and dried under nitrogen gas to give 2.6 g (step 2-37) of the product. ¾ 匪 R (400 MHz, DMSO- ^) δ 14.89 (bs, 1H), 8.58 (d, J = 1.8 Hz, 1H), 8.32 (d, J = 8.9 Hz, 1H), 8.04
(dd, J = 8.9， 1.8 Hz, 1H). MS m/z [M+H] 208. 단계 4. 6-브로모- ^메틸 -1/ 인다졸 -3-카복스아미드의 제조 (dd, J = 8.9, 1.8 Hz, 1H). MS m / z [M + H] 208. Step 4. Preparation of 6-Bromo- ^ methyl-1 / indazol-3-carboxamide
6-브로모—1/ 인다졸 -3-카르복실산 (100 g)과 DMF (500 mL)을 등근 바닥 플라스크에 넣었다. 흔합물에 HBTU (236 g), DIEA (505 mL)와 MeNH2— HC1 (84 g)을 넣어주고 50—60 °C에서 교반하였다. 12시간 후에 온도를 낮추고 물에 천천히 넣었다. 얻어진 고체 생성물은 고체여과를 통해 얻었다. 6-Bromo-l / indazol-3-carboxylic acid (100 g) and DMF (500 mL) were placed in the equipotential bottom flask. HBTU (236 g), DIEA (505 mL) and MeNH 2 — HC1 (84 g) were added to the mixture and stirred at 50—60 ° C. After 12 hours the temperature was lowered and slowly added to water. The obtained solid product was obtained by solid filtration.
생성물은 물로 닦아주고 질소 기체 하에서 건조하여 생성물 70 g (67%)을 얻었다. MS m/z [M+H] 255. 257 단계 5.  The product was washed with water and dried under nitrogen gas to give 70 g (67%) of the product. MS m / z [M + H] 255. 257 Step 5.
6-브로모 -그메틸— 1— (테트라하이드로 피란 -2—일)— 1/ 인다졸 -3—카복스아미드 의 제조  Preparation of 6-bromo-gmethyl— 1— (tetrahydropyran-2—yl) — 1 / indazole-3—carboxamide
6-브로모―그메틸 -1^인다졸 -3-카복스아미드 (115 g)와 에틸아세테이트 (500 mL)를 등근 바닥 플라스크에 넣었다. 흔합물에 TsOH.H20 (8 g)과. 6-Bromo-glymethyl-1 ^ indazole-3-carboxamide (115 g) and ethyl acetate (500 mL) were placed in a back bottom flask. TsOH.H 2 0 (8 g) and the mixture.
3, 4-디하이드로— 2 피란 (83 mL)을 넣고 환류하였다. 한 시간 후에 감압증류로 용매를 제거하고, 탄산수소나트륨 수용액을 사용하고  3, 4-dihydro— 2 pyran (83 mL) was added and refluxed. After an hour, the solvent was removed by distillation under reduced pressure, and an aqueous sodium hydrogen carbonate solution was used.
에틸아세테이트로 추출한 다음에 유기층을 무수 황산마그네슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거한 후 획득한 잔사를 MeOH (400 mL)와After extraction with ethyl acetate, the organic layer was dried over anhydrous magnesium sulfate and filtered. The solvent was removed by distillation under reduced pressure, and the obtained residue was washed with MeOH (400 mL).
Hexane (200 mL) 조건에서 재결정하여 목적화합물 Target compound by recrystallization under Hexane (200 mL)
6-브로모 메틸 -1- (테트라하이드로 -2/ 피란— 2—일)— 인다졸—3-카복스아미드 114 g (75%)를 얻었다. MS m/z [M+H] 339. 단계 6.  114 g (75%) of 6-bromo methyl-1- (tetrahydro-2 / pyran-2—yl) —indazole—3-carboxamide were obtained. MS m / z [M + H] 339. Step 6.
그메틸—1— (테트라하이드로 -2^피란 -2-일) -6-(4,4， 5， 5-테트라메틸 -1,3 ,2-다이옥 사보란—2—일) -1^인다졸 -3-카복스아미드의 제조 Glymethyl—1— (tetrahydro-2 ^ pyran-2-yl) -6- (4,4, 5, 5-tetramethyl-1,3,2-dioxane saborane—2—yl) -1 Preparation of Sol-3-Carboxamide
6-브로모—^메틸 -1- (테트라하이드로—2^피란 -2—일) -1^인다졸 -3—카복스아미드 (114 g)을 DMF에 용해시킨 다음， OAc (100 g)， Pd(dppf)Cl2 (10 g)과 디보래인 (112 g)을 넣고 1시간 동안 110 °C에서 교반하였다. 반웅이 종결하면 에틸아세테이트를 넣어 결정화여 목적화합물 6-Bromo- ^ methyl-1- (tetrahydro—2 ^ pyran-2—yl) -1 ^ indazole-3—carboxamide (114 g) was dissolved in DMF, followed by OAc (100 g) ， Pd (dppf) Cl 2 (10 g) and diborane (112 g) were added and stirred at 110 ° C. for 1 hour. When reaction is finished, ethyl acetate is added to crystallize the target compound.
메틸 -1— (테트라하이드로 -2/ 피란— 2-일) -6-(4，4，5，5—테트라메틸 -1,3,2-다이옥 사보란—2-일) 인다졸—3—카복스아미드 114 g (88%)을 얻었다. NMR (400 MHz, DMSO-6 δ 8.39 (dd, 1H, J= 8.1, 0.9 Hz,), 8.01 (s, 1H), 7.71 (d, 1H, J = 8.1 Hz), 7.07 (q, 1H, J= 4.8 Hz), 5.81 (dd, 1H, J= 9.6， 2.7 Hz), 4.05 (m, 1H), 3.81 (in, 1H), 3.02 (d, 3H, J= 5.1 Hz), 2.58 (m, 1H), 2.13 (m, 1H), 2.00 (m, 1H), 1.78-1.62 (m, 3H), 1.36 (s, 12H), MS m/z [M+H] 386 단계 7.  Methyl-1— (tetrahydro-2 / pyran— 2-yl) -6- (4,4,5,5—tetramethyl-1,3,2-dioxane saborane-2-yl) indazole—3— 114 g (88%) of carboxamide were obtained. NMR (400 MHz, DMSO-6 δ 8.39 (dd, 1H, J = 8.1, 0.9 Hz,), 8.01 (s, 1H), 7.71 (d, 1H, J = 8.1 Hz), 7.07 (q, 1H, J = 4.8 Hz), 5.81 (dd, 1H, J = 9.6, 2.7 Hz), 4.05 (m, 1H), 3.81 (in, 1H), 3.02 (d, 3H, J = 5.1 Hz), 2.58 (m, 1H ), 2.13 (m, 1H), 2.00 (m, 1H), 1.78-1.62 (m, 3H), 1.36 (s, 12H), MS m / z [M + H] 386 Step 7.
6-(5-아미노 -4-플루오로 -2-메틸페닐 )-7^메틸 -1- (테트라하이드로 -2 ^피란 -2-일 ) -1^인다졸 -3—카르보아미드의 제조 ᅳ  Preparation of 6- (5-amino-4-fluoro-2-methylphenyl) -7 ^ methyl-1- (tetrahydro-2 ^ pyran-2-yl) -1 ^ indazole-3—carboamide ᅳ
메틸— 1- (테트라하이드로— 2y 피란— 2—일) -6-(4，4,5,5-테트라메틸 -1，3,2-다이옥 사보란 -2-일) -1^인다졸 -3-카복스아미드 (50 g)와  Methyl— 1- (tetrahydro— 2y pyran— 2—yl) -6- (4,4,5,5-tetramethyl-1,3,2-dioxane saboran-2-yl) -1 ^ indazole- With 3-carboxamide (50 g)
3-브로모 -4-메틸— 5—플루오로아닐린 (28 g), 2C03 (54 g), Pd(dppf)Cl2 (5 g)을 DMF/물 (10/1， 200 mL)에 녹여 탈기 (degassing) 후 120 °C에서 가열하였다. 1 시간 후 반웅이 종결하면 에틸아세테이트와 물로 추출하고 모아진 유기층을 무수 황산마그네슘으로 건조하여 여과하였다. 얻어진 고체 잔사를 핵산 /메틸렌클로라이드 (10/1)으로 재결정하여 목적화합물인 3-bromo-4-methyl— 5—fluoroaniline (28 g), 2 CO 3 (54 g), Pd (dppf) Cl 2 (5 g) in DMF / water (10/1, 200 mL) After melting and degassing, it was heated at 120 ° C. After 1 hour, the reaction was terminated and extracted with ethyl acetate and water, and the combined organic layers were dried over anhydrous magnesium sulfate and filtered. The obtained solid residue was recrystallized from nucleic acid / methylene chloride (10/1) to obtain the target compound.
6-(5—아미노 -4—플루오로— 2—메틸페닐 )-y 메틸 -1— (테트라하이드로 -2/ 피란 -2-일 ) -1/·인다졸—3—카르보아미드 (46g, 9 )를 얻었다. NMR (400 MHz, DMSO— ) δ 8.37 (d, 1H, J= 8.4 Hz,), 7.44 (s, 1H), 7.22 (del, 1H, /= 8.4, 1.2 Hz), 7.10 (q, 1H, /= 4.8 Hz), 6.92 (d, 1H, J 12.0 H), 6.75 (d, 1H, J= 9.3 Hz), 5.72 (del, 1H, /= 9.6, 2.4 Hz), 4.08 (m, 1H), 3.77 (m, Hi), 3.69 (s, 2H), 3.05 (d, 311, J= 4.8 Hz), 2.58 (m, 1H), 2.57 (in, 1H), 2.20-2.02 (in, 2H), 2.12 (s, 3H), 1.79一 1.65 (m, 3H). MS m/z [M+H] 383 6- (5—amino-4-fluoro- 2—methylphenyl) -y methyl-1— (tetrahydro-2 / pyran-2-yl) -1 / .indazole—3—carboamide (46 g, 9 ) NMR (400 MHz, DMSO—) δ 8.37 (d, 1H, J = 8.4 Hz,), 7.44 (s, 1H), 7.22 (del, 1H, / = 8.4, 1.2 Hz), 7.10 (q, 1H, / = 4.8 Hz), 6.92 (d, 1H, J 12.0 H), 6.75 (d, 1H, J = 9.3 Hz), 5.72 (del, 1H, / = 9.6, 2.4 Hz), 4.08 (m, 1H), 3.77 (m, Hi), 3.69 (s, 2H), 3.05 (d, 311, J = 4.8 Hz), 2.58 (m, 1H), 2.57 (in, 1H), 2.20-2.02 (in, 2H), 2.12 ( s, 3H), 1.79 一 1.65 (m, 3H). MS m / z [M + H] 383
[실시예] 화학식 1 화합물의 합성 실시예 1: EXAMPLES Synthesis of Compound of Formula 1 Example 1
6-(5—(3-(2-시아노프로판 -2-일)벤즈아미도)—2—메틸페닐아미노) -Λ-메틸 인다 졸 -3—카복스아미드 제조 Preparation of 6- (5— (3- (2-cyanopropane-2-yl) benzamido) —2-methylphenylamino) -Λ-methyl indazole-3—carboxamide
Figure imgf000031_0001
단계 1: 에틸
Figure imgf000031_0001
Step 1: ethyl
6— (5—아미노— 2—메틸페닐아미노)— 1— (테트라하이드로 -2 ^피란— 2-일 ) 인다졸 -36— (5—amino— 2—methylphenylamino) — 1— (tetrahydro-2 ^ pyran— 2-yl) indazole-3
-카르복실레이트의 제조 Preparation of Carboxylate
에틸 ethyl
6— ( 2—메틸 -5-트로페닐아미노)— 1— (테트라하이드로ᅳ 2 -피란 -2—일 ) - 1 ―인다졸 -3- 카르복실레이트 (998 mg, 2.35隱 ol)를 MeOH (10 inL)에 용해시킨 다음 10% Pd/C (100 mg)을 넣고 수소 기체 하에서 4 시간 동안 실온에서 교반하였다.  6— (2—Methyl-5-Trophenylamino) — 1— (Tetrahydrojan 2-pyran-2—yl)-1-indazol-3-carboxylate (998 mg, 2.35 隱 ol) was added to MeOH ( 10 inL) and then added 10% Pd / C (100 mg) and stirred at room temperature for 4 hours under hydrogen gas.
반응이 종결하면 규조토 패드로 여과한 후 여과액을 감압 증류로 제거하여 목적화합물인 에틸 After the reaction was completed, the mixture was filtered through a pad of diatomaceous earth, and the filtrate was removed by distillation under reduced pressure.
6-(5-아미노— 2-메틸페닐아미노) -1- (테트라하이드로 -2 -피란 -2-일 인다졸 -3 -카르복실레이트 (780 nig, 84%)을 얻었다. NMR (400 MHz, DMSO- ;) δ 7.816- (5-amino— 2-methylphenylamino) -1- (tetrahydro-2-pyran-2-yl indazole-3 -Carboxylate (780 nig, 84%) was obtained. NMR (400 MHz, DMSO-;) δ 7.81
(d, /= 8.7 Hz, 1H), 7. 67 (s, 1H), 6.97 (d, /= 8.7 Hz, 1H), 6.89 (m, 1H) , 6.51 (m, 1H), 6.25 (m, 1H), 5.70 (d, J = 9.5 Hz, 1H), 4.84 (s, 1H), 4.37 (q, J 7.3 Hz, 2H), 3.87 (m„ 1H), 3.67 (m, 1H), 3.31 (s, 3H), 2.33 (m, 2H), 1.72 (in, 1H), 1.55 (in, 3H), 1.36 (t, = 7.1 Hz, 3H), MS m/z [M+H] 395. 단계 2: 에틸 (d, / = 8.7 Hz, 1H), 7. 67 (s, 1H), 6.97 (d, / = 8.7 Hz, 1H), 6.89 (m, 1H), 6.51 (m, 1H), 6.25 (m, 1H), 5.70 (d, J = 9.5 Hz, 1H), 4.84 (s, 1H), 4.37 (q, J 7.3 Hz, 2H), 3.87 (m „1H), 3.67 (m, 1H), 3.31 (s , 3H), 2.33 (m, 2H), 1.72 (in, 1H), 1.55 (in, 3H), 1.36 (t, = 7.1 Hz, 3H), MS m / z [M + H] 395. Step 2: ethyl
6-(5-(3-(2-시아노프로판— 2-일)벤즈아미도)—2-메틸페닐아미노) 테트라하이 드로 -2//-피란—2-일 )— 인다졸 -3—카르복실레이트의 제조  6- (5- (3- (2-cyanopropane— 2-yl) benzamido) —2-methylphenylamino) tetrahydro-2 //-pyran- 2-yl)-indazole-3-carr Preparation of Cyclate
에틸 ethyl
6-(5-아미노 -2-메틸페닐아미노) -1- (테트라하이드로 -2//—피란 -2-일 인다졸 3 一카르복실레이트 (151 nig, 0.38 mmol), 3— (2 시아노프로판 -2-일)벤조산 (87 mg, 0.46 隱 ol), HATU (433 mg, 1.14 mmol), 디이소프로필에틸아민 (DIPEA; 0.2 mL, 1.14 隱 ol)를 DMF (1.5 mL)에 녹인 후 실온에서 교반하였다. 2 시간 후 반응이 종결하면 염화나트륨 수용액을 사용하고 에틸아세테이트로 추출한 다음에 모아진 유기층을 무수 황산마그네슘으로 건조하여 여과하였다.  6- (5-amino-2-methylphenylamino) -1- (tetrahydro-2 // — pyran-2-yl indazole 3 monocarboxylate (151 nig, 0.38 mmol), 3— (2 cyanopropane 2-yl) benzoic acid (87 mg, 0.46 隱 ol), HATU (433 mg, 1.14 mmol), diisopropylethylamine (DIPEA; 0.2 mL, 1.14 隱 ol) in DMF (1.5 mL) and then at room temperature After 2 hours, when the reaction was completed, an aqueous sodium chloride solution was used, extraction was performed with ethyl acetate, and the combined organic layers were dried over anhydrous magnesium sulfate and filtered.
용매를 감압 증류로 제거한 후 획득한 잔사를 관 크로마토그래피 (실리카겔, EtOAc:n-hexane = 1:2)를 통해 정제하여 목적화합물인 에틸 After distilling off the solvent under reduced pressure, the obtained residue was purified by column chromatography (silica gel, EtOAc: n-hexane = 1: 2) to obtain ethyl as the target compound.
6-(5—(3-(2-시아노프로판— 2—일)벤즈아미도) -2-메틸페닐아미노) -1- (테트라하이 드로 -2//-피란 -2-일) 인다졸 -3-카르복실레이트 (212 mg, 98%)을 얻었다. lH NMR (400 MHz, DMSO— ) δ 7.89 (m, 1H), 7.83 (m, lH), 7.77 (s, 1H), 7.70 (m, 2H), 7.61 (d, J= 7.8 Hz, 1H), 7.55 (d, J = 7.9, 1H)， 7.40 (m, 1H), 7.11 (d, J= 8.2 Hz, 1H), 7.04 (d, J = 3.8 Hz, 2H), 6.92 (d, /= 8.9 Hz, 1H), 5.61 (d, J 9.8 Hz, 1H), 4.19 (q, /= 7.7 Hz, 2H) , 3.68 (m, 1H), 3.51 (m, 1H), 2,70 (s, 3H), 1.80 (m, 3H), 1.55 (s, 6H), 1.36 (in, 2H), 1.18 (t, J 14.2 Hz,6- (5— (3- (2-cyanopropane— 2—yl) benzamido) -2-methylphenylamino) -1- (tetrahydro-2 //-pyran-2-yl) indazole- 3-carboxylate (212 mg, 98%) was obtained. l H NMR (400 MHz, DMSO—) δ 7.89 (m, 1H), 7.83 (m, lH), 7.77 (s, 1H), 7.70 (m, 2H), 7.61 (d, J = 7.8 Hz, 1H) , 7.55 (d, J = 7.9, 1H), 7.40 (m, 1H), 7.11 (d, J = 8.2 Hz, 1H), 7.04 (d, J = 3.8 Hz, 2H), 6.92 (d, / = 8.9 Hz, 1H), 5.61 (d, J 9.8 Hz, 1H), 4.19 (q, / = 7.7 Hz, 2H), 3.68 (m, 1H), 3.51 (m, 1H), 2,70 (s, 3H) , 1.80 (m, 3H), 1.55 (s, 6H), 1.36 (in, 2H), 1.18 (t, J 14.2 Hz,
3H), MS m/z [M+H] 566. 단계 3: 3H), MS m / z [M + H] 566. Step 3:
6-(5-(3-(2—시아노프로판 -2—일)벤즈아미도)—2-메틸페닐아미노)— 1- (테트라하이 드로 -2//—피란 -2—일)— 인다졸—3-카르복실산의 제조  6- (5- (3- (2-cyanopropane-2-yl) benzamido) 2-methylphenylamino) 1- (tetrahydro-2 //-pyran-2-yl) -indazole Preparation of —3-carboxylic acid
에틸 ethyl
6—(5-(3— (2—시아노프로판 -2-일)벤즈아미도) -2-메틸페닐아미노)— 1- (테트라하이 드로— 2 -피란 -2-일)—1쓰인다졸 -3-카르복실레이트 (212 mg, 0.37隱 ol)와 THF (1 mL), MeOH (1 mL) , Η20 (1 mL)을 넣고 리튬히드록사이드 일수화물 (155 mg, 3.7 I丽 ol)을 첨가하였다. 40 °C에서 15 시간 동안 교반시킨 후 반응이 종료되면 용매를 감압 증류하여 제거한 후 0 °C로 넁각시키고， 물 (3.0 mL)을 넣고， IN HC1 수용액으로 중화하였다. 생기는 고체는 필터하고 건조시켜 목적화합물인 6— (5- (3— (2—Cyanopropane-2-yl) benzamido) -2-methylphenylamino) -1- (tetrahydro— 2 -pyran-2-yl) —1 thiazole Add 3-carboxylate (212 mg, 0.37 隱 ol), THF (1 mL), MeOH (1 mL), Η 2 0 (1 mL) and add lithium hydroxide monohydrate (155 mg, 3.7 I 丽 ol) Was added. After stirring for 15 hours at 40 ° C. and the reaction was complete, the solvent was distilled off under reduced pressure, and then washed with 0 ° C., water (3.0 mL) was added, and neutralized with IN HC1 aqueous solution. The resulting solid is filtered and dried to
6-(5 (3-(2-시아노프로판— 2-일)벤즈아미도) -2-메틸페닐아미노) -1- (테트라하이 드로 -2 -피란 -2-일)— 1 -인다졸 -3-카르복실산 (130 mg)을 얻었다. MS m/z 6- (5 (3- (2-cyanopropane- 2-yl) benzamido) -2-methylphenylamino) -1- (tetrahydro-2 -pyran-2-yl) — 1-indazole- 3-carboxylic acid (130 mg) was obtained. MS m / z
[M+H] 538. 단계 4. 6一 ( 5- ( 3- ( 2-시아노프로판— 2-일)벤즈아미도)—2-메틸페닐아미노) -yV-메틸— 1— (테트 라하이드로 -2//-피란 -2-일 )— 인다졸— 3-카복스아미드의 제조 [M + H] 538. Step 4. 6 一 (5- (3- (2-cyanopropane- 2-yl) benzamido) —2-methylphenylamino) -yV-methyl— 1— (tetrahydro-2 //-pyran-2-yl ) — Indazole— Preparation of 3-carboxamide
6一(5—(3-(2-시아노프로판 -2-일)벤즈아미도) -2-메틸페닐아미노) -1- (테트라하이 드로— 2 -피란—2—일.) 인다졸—3-카르복실산 (15 mg, 0.028 mmol), 메틸아민 염화수소 (9.5 mg, 0.14誦 ol), HATU (31.8 mg, 0.084 mmol), DIPEA (14 !Λ , 0.084 nimol)를 DMF (1 niL)에 녹인 후 실은에서 교반하였다. 2 시간 후 반응이 종결하면 염화나트륨 수용액을 사용하고 에틸아세테이트로 추출한 다음에 모아진 유기충을 무수 황산마그네슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거하여 목적화합물인  6 一 (5— (3- (2-cyanopropane-2-yl) benzamido) -2-methylphenylamino) -1- (tetrahydro— 2 -pyran—2—yl.) Indazole—3 Dissolved carboxylic acid (15 mg, 0.028 mmol), methylamine hydrogen chloride (9.5 mg, 0.14 μl), HATU (31.8 mg, 0.084 mmol), DIPEA (14! Λ, 0.084 nimol) in DMF (1 niL) The thread was then stirred at. After 2 hours, the reaction was terminated, and the resultant was extracted with ethyl acetate and extracted with ethyl acetate. The collected organic worms were dried over anhydrous magnesium sulfate and filtered. The solvent is removed by distillation under reduced pressure
6-(5-(3— (2—시아노프로판 -2-일)벤즈아미도) -2-메틸페닐아미노 메틸 테트 라하이드로— 2//-피란 -2-일)— 인다졸 -3—카복스아미드 (12 nig)를 얻어 더 이상의 정제 없이 다음 반응을 진행하였다. Ή NMR (400 MHz, C 0D— ) δ 8.06 (m, 1H), 7.97 (d, J 8.8 Hz, 1H), 7.87 (d, J = 7.87 Hz, 1H) , 7.84 (s, 1H), 7.73 (m, 1H), 7.54 (t, / = 7.8 Hz, 1H) , 7.22 (s, 2H), 7.16 (d, J = 1.5 Hz, 1H), 7.02 (del, /= 1.7, 8.8 Hz, 1H), 5.73 (dd, J = 2.5, 9.7 Hz, 1H), 3.93 (m, 1H), 6- (5- (3— (2—cyanopropane-2-yl) benzamido) -2-methylphenylamino methyl tetrahydro— 2 //-pyran-2-yl)-indazole-3ka Voxamide (12 nig) was obtained to proceed to the next reaction without further purification. MR NMR (400 MHz, C 0D—) δ 8.06 (m, 1H), 7.97 (d, J 8.8 Hz, 1H), 7.87 (d, J = 7.87 Hz, 1H), 7.84 (s, 1H), 7.73 ( m, 1H), 7.54 (t, / = 7.8 Hz, 1H), 7.22 (s, 2H), 7.16 (d, J = 1.5 Hz, 1H), 7.02 (del, / = 1.7, 8.8 Hz, 1H), 5.73 (dd, J = 2.5, 9.7 Hz, 1H), 3.93 (m, 1H),
3.77 (m, 1H), 2.95 (s, 3H) , 2.51 (m, 1H) , 2.27 (s, 3H), 2.06 (m, IH), 2.00 (m, 2H), 1.76 (s, 6H), 1.61 (m, 2H), MS ni/z [M+H] 551. 단계 5. 3.77 (m, 1H), 2.95 (s, 3H), 2.51 (m, 1H), 2.27 (s, 3H), 2.06 (m, IH), 2.00 (m, 2H), 1.76 (s, 6H), 1.61 (m, 2H), MS ni / z [M + H] 551. Step 5.
6- (5— (3- (2—시아노프로판 -2-일)벤즈아미도)—2—메틸페닐아미노) -yV-메틸 인다 졸 -3-카복스아미드의 제조  Preparation of 6- (5— (3- (2—cyanopropane-2-yl) benzamido) -2-2-methylphenylamino) -yV-methyl indazole-3-carboxamide
6—(5— (3— (2-시아노프로판 -2—일)벤즈아미도) -2-메틸페닐아미노) -/V—메틸 -1— (테트 라하이드로— 2 -피란— 2-일)— 1 -인다졸 -3-카복스아미드 (12 mg)를 MeOH (1 niL)에 녹이고, 4M HC1/디옥산 (1 mL)을 첨가하여 실온에서 8 시간 동안 교반하였다. 반응이 종결하면 용매를 감압 증류하여 제거한 후 탄산수소나트륨 수용액을 사용하고 에틸아세테이트로 추출한 다음에 유기층을 무수 황산마그네슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거하여 농축하였다. Prep 6— (5— (3— (2-cyanopropane-2—yl) benzamido) -2-methylphenylamino)-/ V—methyl-1— (tetrahydro— 2 -pyran— 2-yl) — 1-Indazole-3-carboxamide (12 mg) was dissolved in MeOH (1 niL), 4M HC1 / dioxane (1 mL) was added and stirred at room temperature for 8 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, the mixture was extracted with ethyl acetate, and then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and filtered. The solvent was removed by distillation under reduced pressure and concentrated. Prep
HPLC로 정제하여 목적화합물인 Purified by HPLC
6—(5-(3-(2-시아노프로판 -2-일)벤즈아미도) -2-메틸페닐아미노)— /V—메틸 인다 졸—3—카복스아미드 (6.4 mg, 49%)을 얻었다. MS m/z [M+H] 467. 상기 실시예 1의 제조방법에 의하여 하기 표 1의 화합물을 합성하였다.  6— (5- (3- (2-cyanopropane-2-yl) benzamido) -2-methylphenylamino) — / V—methyl indazole—3—carboxamide (6.4 mg, 49%) Got it. MS m / z [M + H] 467. The compounds of Table 1 were synthesized according to the preparation method of Example 1.
【표 1】  Table 1
Figure imgf000033_0001
Figure imgf000034_0001
Figure imgf000033_0001
Figure imgf000034_0001
Figure imgf000035_0002
Figure imgf000035_0002
실시예 n. Example n.
/V一메틸—6- (메틸 (2ᅳ메틸 -5-(3-몰포리노 -5- (트리플루오로메틸)벤즈아미도)페닐) 아미노 )-1 —인다졸 -3-카복스아미드의 제조  Of methyl-6- (methyl (2 ᅳ methyl-5- (3-morpholino-5- (trifluoromethyl) benzamido) phenyl) amino) -1-indazole-3-carboxamide Produce
Figure imgf000035_0001
단계 1. 에틸
Figure imgf000035_0001
Step 1. Ethyl
6- (메틸 (2-메틸 -5-니트로페닐)아미노 )— 1-(테트라하이드로 -2//-피란ᅳ 2—일 인 다졸 -3—카르복실레이트의 제조  Preparation of 6- (methyl (2-methyl-5-nitrophenyl) amino) — 1- (tetrahydro-2 //-pyranjan 2—yl indazole-3—carboxylate
에틸 ethyl
6一 ( 2—메틸— 5-니트로페닐아미노)— 1- (테트라하이드로ᅳ 2 -피란— 2-일 )ᅳ 인다졸 -3 ᅳ카르복실레이트 (540 nig, 1.27 國 ol)와 DMF (5 niL)를 넣고 0 °C에서 60% NaH (76.3 nig. 1.91 隱 ol)을 천천히 첨가하였다. 30 분이 경과한 후에 Mel (87 βί, 1.40 國 ol)을 넣고 1 시간 동안 교반한 후 물 (0.5 mL)을 천천히 첨가하여 반응을 종결시켰다. 염화나트륨 수용액을 사용하고 에틸아세테이트로 추출한 다음에 모아진 유기층을 무수 황산마그네슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거한 후 획득한 잔사를 관 크로마토그래피 6 一 (2—methyl— 5-nitrophenylamino) — 1- (tetrahydro ᅳ 2-pyran— 2-yl) ᅳ indazole-3 carboxylate (540 nig, 1.27 ol) and DMF (5 niL) ) And 60% NaH (76.3 nig. 1.91 μl ol) was added slowly at 0 ° C. After 30 minutes, Mel (87 βί, 1.40 國 ol) was added thereto, stirred for 1 hour, and water (0.5 mL) was added slowly to terminate the reaction. An aqueous sodium chloride solution was used, followed by extraction with ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate and filtered. The residue obtained after the solvent was removed by distillation under reduced pressure was subjected to column chromatography.
(EtOAc:7l iexane=l:2)를 통해 정제하여 목적화합물인 에틸 Purified through (EtOAc: 7l iexane = l: 2), the target compound ethyl
6- (메틸 (2-메틸 -5-니트로페닐 )아미노 )-1— (테트라하이드로— 2 ^피란— 2-일 )— 인 다졸 -3-카르복실레이트 (382 mg, 69 %)를 얻었다. 讀 (400 MHz , CDCl,-c) δ 8.07 (dd. J = 2.4, 10.8 Hz, 211), 7.90 (d, / = 9.0 Hz, 1H), 7.47 (d, J = 8.1 Hz, 1H), 6.80 (d, J 1.9 Hz, 1H), 6.45 (dd, J = 2.1, 9.0 Hz, 1H), 5.74 (dd, J 2.8, 9.3 Hz, 1H), 4.47 (q, /= 7.1 Hz, 2H), 4.03 (m, 1H), 3.72 (in, 1H), 3.36 (s, 3H), 2.55 (in, 1H), 2.25 (s, 3H), 2.15 (m, 2H), 1.70 (m, 3H), 1.44 (t, J = 8.5 Hz, 3H), MS m/z [M+H] 567. 단계 2. 6- (Methyl (2-methyl-5-nitrophenyl) amino) -1— (tetrahydro— 2 ^ pyran— 2-yl) — indazole-3-carboxylate (382 mg, 69%) was obtained. 400 (400 MHz, CDCl, -c) δ 8.07 (dd. J = 2.4, 10.8 Hz, 211), 7.90 (d, / = 9.0 Hz, 1H), 7.47 (d, J = 8.1 Hz, 1H), 6.80 (d, J 1.9 Hz, 1H), 6.45 (dd, J = 2.1, 9.0 Hz, 1H), 5.74 (dd, J 2.8, 9.3 Hz, 1H), 4.47 (q, / = 7.1 Hz, 2H), 4.03 (m, 1H), 3.72 (in, 1H), 3.36 (s, 3H), 2.55 (in, 1H), 2.25 (s, 3H), 2.15 (m, 2H), 1.70 (m, 3H), 1.44 ( t, J = 8.5 Hz, 3H), MS m / z [M + H] 567. Step 2.
6- (메틸 ( 2-메틸 -5-니트로페닐)아미노 ) - 1- (테트라하이드로— 2 -피란— 2—일)— 1 -인 다졸ᅳ 3-카르복실산의 제조  Preparation of dazolox 3-carboxylic acid which is 6- (methyl (2-methyl-5-nitrophenyl) amino) -1- (tetrahydro— 2-pyran— 2—yl) — 1-
에틸 ethyl
6— (메틸 ( 2-메틸— 5—니트로페닐)아미노 ) - 1- (테트라하이드로— 2 ―피란 -2—일)— Iff—인 다졸ᅳ 3-카르복실레이트 (380 mg, 0.87 隱 ol)와 THF (1 mL) , MeOH (1 mL), H20 (1 mL)을 넣고 리튬 히드록사이드 일수화물 (364 mg, 8,67 隱 ol)를 첨가하였다. 40 °C에서 4 시간 동안 교반한 후 반웅이 종료되면 용매를 감압 증류하여 제거한 후 0 °C로 넁각시키고, 물 (3.0 mL)을 넣고， IN HC1 수용액으로 중화하였다. 에틸아세테이트로 추출하고 모아진 유기층을 무수 6— (Methyl (2-methyl— 5—nitrophenyl) amino)-1- (tetrahydro— 2 -pyran-2—yl) — Iff—Indazolazole 3-carboxylate (380 mg, 0.87 隱 ol) And THF (1 mL), MeOH (1 mL), H 2 0 (1 mL) were added and lithium hydroxide monohydrate (364 mg, 8,67 隱 ol) was added. After stirring at 40 ° C. for 4 hours, when the reaction was completed, the solvent was distilled off under reduced pressure, followed by stirring at 0 ° C., water (3.0 mL) was added thereto, and neutralized with an aqueous IN HC1 solution. The organic layer extracted with ethyl acetate and collected
황산마그네슘으로 건조하여 여과한 후 용매를 감압 증류로 제거하여 After drying over magnesium sulfate and filtration, the solvent was removed by distillation under reduced pressure.
6ᅳ (메틸 (2-메틸 -5—니트로페닐 )아미노 )-1ᅳ (테트라하이드로 -2//ᅳ피란— 2—일 )-L -인 다졸— 3-카르복실산 (346 mg, 97¾>)을 얻었다. ¾ NMR (400 MHz, DMSO-^) δ 8.11 (dd, J 2.4, 8.4 Hz, 1H), 8.02 (d, / = 2.4 Hz, 1H), 7.76 (d, J = 8.9 Hz, 1H), 7.66 (d, J= 8.5 Hz, 1H), 7.00 (s, 1H), 6.45 (dd, J= 2.0, 9.0 Hz, 1H), 5.90 (dd, J= 2.4， 9.6 Hz, 1H), 3.88 (m, 1H), 3. 77 (m, 1H), 2.37 (m, 1H), 2.21 (s, 3H), 2.06 (m, 1H), 1. 97 (m, 2H), 1.74 (m, 2H), 1.58 (s, 3H), MS m/z [M+H] 411. 단계 3. ¬ᅳ메틸— 6- (메틸 ( 2—메틸 -5-니트로페닐)아미노 ) - 1- (테트라하이드로 -2 ―피란 -2-일 )ᅳ1#-인다졸— 3—카복스아미드의 제조 6—(메틸 (2-메틸一 5-니트로페닐 )아미노 )-1- (테트라하이드로 -2//-피란— 2-일 )— 인 다졸— 3-카르복실산 ( 346 nig , 0.84 mmo 1 ) , 메틸아민 염화수소 ( 284 nig , 4.2 mmo 1 )， HATU (958 mg, 2.52 mmol), DIPEA (0.42 mL, 2.52隱 ol)을 DMF (4 niL)에 녹인 후 실온에서 교반하였다. 2 시간 후 반응이 종결하면 염화나트륨 수용액을 사용하고 에틸아세테이트로 추출한 다음에 모아진 유기층을 무수 6 '(Methyl (2-methyl-5-nitrophenyl) amino) -1' (tetrahydro-2 // pypyran— 2—yl) -L-yndazole— 3-carboxylic acid (346 mg, 97¾> ) ¾ NMR (400 MHz, DMSO- ^) δ 8.11 (dd, J 2.4, 8.4 Hz, 1H), 8.02 (d, / = 2.4 Hz, 1H), 7.76 (d, J = 8.9 Hz, 1H), 7.66 ( d, J = 8.5 Hz, 1H), 7.00 (s, 1H), 6.45 (dd, J = 2.0, 9.0 Hz, 1H), 5.90 (dd, J = 2.4, 9.6 Hz, 1H), 3.88 (m, 1H ), 3. 77 (m, 1H), 2.37 (m, 1H), 2.21 (s, 3H), 2.06 (m, 1H), 1. 97 (m, 2H), 1.74 (m, 2H), 1.58 ( s, 3H), MS m / z [M + H] 411. Step 3. ¬ ᅳ Methyl— 6- (methyl (2—methyl-5-nitrophenyl) amino) -1- (tetrahydro-2-pyran- Preparation of 2-yl) ᅳ 1 # -indazole— 3—carboxamide 6— (methyl (2-methyl 一 5-nitrophenyl) amino) -1- (tetrahydro-2 //-pyran— 2-yl) — indazole— 3-carboxylic acid (346 nig, 0.84 mmo 1) , Methylamine hydrogen chloride (284 nig, 4.2 mmol), HATU (958 mg, 2.52 mmol) and DIPEA (0.42 mL, 2.52 μl) were dissolved in DMF (4 niL) and stirred at room temperature. After 2 hours, when the reaction was completed, an aqueous sodium chloride solution was used, extraction was performed with ethyl acetate, and the combined organic layers were dried.
황산마그네슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거하여 Λ-메틸 -6- (메틸 ( 2-메틸 -5—니트로페닐)아미노) - 1- (테트라하이드로 -2 -피란 -2一일 인다졸— 3-카복스아미드 (352 mg)를 얻어 더 이상의 정제 없이 다음 반웅을 진행하였다. 'H NMR (400 MHz, DMSO—60 δ 13.8 (s, 1Η), 8.77 (d, /= 3.8 Hz, 1H), 8.54 (d, J= 8.4 Hz, 1H), 8.36 (d, /= 4.6 Hz, 1H), 8.24 (d, 8.6 Hz, 1H), 7.83 (s, 1H), 7.21 (d, J 8.5 Hz, 1H), 5.94 (d, 7.6 Hz, 1H), 3.90 (m, 1H), 3.76 (in, 1H), 3.48 (s, 3H), 2.83 (d, J = 4.6 Hz, 3H), 2.06 (ni, 1H), 2.00 (m, 2H), 1. 74 (m, 1H), 1.58 (m, 2H), 1.24 (s, 3H), MS m/z [M+H] 424. 단계 4. Dried over magnesium sulfate and filtered. The solvent was removed by distillation under reduced pressure to give Λ-methyl-6- (methyl (2-methyl-5-nitrophenyl) amino) -1- (tetrahydro-2-pyran-2 uniyl indazole— 3-carboxamide ( 352 mg) was obtained and the following reaction was carried out without further purification: 'H NMR (400 MHz, DMSO—60 δ 13.8 (s, 1Η), 8.77 (d, / = 3.8 Hz, 1H), 8.54 (d, J = 8.4 Hz, 1H), 8.36 (d, / = 4.6 Hz, 1H), 8.24 (d, 8.6 Hz, 1H), 7.83 (s, 1H), 7.21 (d, J 8.5 Hz, 1H), 5.94 (d , 7.6 Hz, 1H), 3.90 (m, 1H), 3.76 (in, 1H), 3.48 (s, 3H), 2.83 (d, J = 4.6 Hz, 3H), 2.06 (ni, 1H), 2.00 (m , 2H), 1. 74 (m, 1H), 1.58 (m, 2H), 1.24 (s, 3H), MS m / z [M + H] 424. Step 4.
6一 ( (5—아미노 -2-메틸페닐) (메틸 )아미노)— /V-메틸— 1- (테트라하이드로 -2//-피란 -2— 일) -1 -인다졸 -3-카복스아미드의 제조  6-((5—amino-2-methylphenyl) (methyl) amino) — / V-methyl— 1- (tetrahydro-2 //-pyran-2-2-yl) -1-indazole-3-carboxamide Manufacture
메틸— 6ᅳ (메틸 (2—메틸 -5—니트로페닐 )아미노 )—1— (테트라하이드로 -2//-피란— 2一일 인다졸 -3-카복스아미드 (352mg, 0.83画 ol )를 MeOH (4mL)에 용해시킨 다음, 10% Pd/C (35 mg)를 넣고 수소 기체 하에서 5 시간 동안 실은에서 교반하였다. 반응이 종결하면 규조토 패드로 여과한 후 여과액을 감압 증류로 제거하여 목적화합물 6— (( 5-아미노 -2—메틸페닐) (메틸)아미노) -V—메틸ᅳ 1— (테트라하이드로- 2//-피란 -2-일)— 인다졸 -3ᅳ카복스아미드 (325 mg, 99%)를 얻었다. x\\ NMR (400 MHz , DMS0— ) δ 8.76 Ccld, J = 1.3, 4.4 Hz, 1H), 8.53 (dd, J= 1.3, 8.4 Hz, 1H), 8.11 (m, 1H) , 7.76 (m, 1H), 6.98 (d, J= 8.1 Hz, 1H), 6.48 (ni, 1H), J 6.34 (m, 2H), 5,82 (d, J= 9.48 Hz, 1H), 3.89 (m, 1H), 3.75 (m, 1H), 2.79 (d, /= 4.7 Hz, 3H), 2.70 (s, 3H), 2.08 (in, 3H), 1.91 (s, 3H), 1.80 (111， 2H), 1.57 (m, 3H), MS m/z [M+H] 394. 단계 5. · Methyl— 6 ′ (methyl (2—methyl-5—nitrophenyl) amino) —1— (tetrahydro-2 //-pyran— 2 ilyl indazole-3-carboxamide (352mg, 0.83 画 ol) After dissolving in MeOH (4 mL), 10% Pd / C (35 mg) was added and stirred under a hydrogen gas for 5 hours at room temperature.When the reaction was completed, the mixture was filtered through a pad of diatomaceous earth and the filtrate was removed by distillation under reduced pressure. Compound 6— ((5-amino-2—methylphenyl) (methyl) amino) -V—methyl ᅳ 1— (tetrahydro-2 //-pyran-2-yl) — indazole-3 ᅳ carboxamide (325 mg , 99%) x \\ NMR (400 MHz, DMS0—) δ 8.76 Ccld, J = 1.3, 4.4 Hz, 1H), 8.53 (dd, J = 1.3, 8.4 Hz, 1H), 8.11 (m, 1H), 7.76 (m, 1H), 6.98 (d, J = 8.1 Hz, 1H), 6.48 (ni, 1H), J 6.34 (m, 2H), 5,82 (d, J = 9.48 Hz, 1H) , 3.89 (m, 1H), 3.75 (m, 1H), 2.79 (d, / = 4.7 Hz, 3H), 2.70 (s, 3H), 2.08 (in, 3H), 1.91 (s, 3H), 1.80 ( 111, 2H), 1.57 (m, 3H), MS m / z [M + H] 394. Step 5.
6-( (5—아미노— 2—메틸페닐) (메틸)아미노) 메틸— 1ᅳ (테트라하이드로 -2 ―피란一 2- 일)— 인다졸 -3—카복스아미드의 제조  Preparation of 6- ((5—amino— 2—methylphenyl) (methyl) amino) methyl— 1 ′ (tetrahydro-2 —pyran -1-yl) — indazole-3—carboxamide
6-( (5-아미노— 2-메틸페닐) (메틸 )아미노)― ―메틸 -1- (테트라하이드로 -2 -피란一 2一 일) -1 —인다졸—3—카복스아미드 (20 mg, 0.051 mmol),  6-((5-amino- 2-methylphenyl) (methyl) amino)-methyl-1- (tetrahydro-2 -pyran one 2 one day) -1 —indazol—3—carboxamide (20 mg, 0.051 mmol),
3—몰포리노— 5- (트리플루오로메틸)벤조산 (16.8 mg, 0.061睡 ol), HATU (58.2 mg, 0.15 mmol), DIPEA (25 ≠, 0.15 薩 ol)를 DMF (1 mL)에 녹인 후 실온에서 교반하였다. 4 시간 후 반응이 종결하면 염화나트륨 수용액을 사용하고 에틸아세테이트로 추출한 다음에 모아진 유기층을 무수 황산마그네슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거하여  3—morpholino— 5- (trifluoromethyl) benzoic acid (16.8 mg, 0.061 μl), HATU (58.2 mg, 0.15 mmol), DIPEA (25 ≠ 0.15 μl) in DMF (1 mL) Stir at room temperature. After 4 hours, when the reaction was completed, an aqueous sodium chloride solution was used, extraction was performed with ethyl acetate, and the combined organic layers were dried over anhydrous magnesium sulfate and filtered. The solvent is removed by distillation under reduced pressure
6-( (5-아미노 -2-메틸페닐) (메틸)아미노시메틸 -1ᅳ (테트라하이드로 -2 -피란 -2- 일 인다졸 -3—카복스아미드 (24 mg)를 얻어 더 이상의 정제 없이 다음 반응을 진행하였다. MS m/z [M+H] 651. 단계 6. 6-((5-amino-2-methylphenyl) (methyl) aminomethylmethyl-1 ′ (tetrahydro-2-pyran-2-ylindazol-3—carboxamide (24 mg) to give without further purification The reaction proceeded: MS m / z [M + H] 651. Step 6.
Λ/-메틸— 6— (메틸 (2ᅳ메틸 -5— (3-몰포리노 -5ᅳ (트리플루오로메틸 )벤즈아미도)페닐 ) 아미노 )— 인다졸 -3—카복스아미드의 제조  Λ / -methyl— 6— (Methyl (2 ᅳ methyl-5— (3-morpholino-5 ′ (trifluoromethyl) benzamido) phenyl) amino) — indazole-3—carboxamide
6一 ( (5-아미노— 2-메틸페닐) (메틸)아미노)ᅳ그메틸 -1- (테트라하이드로ᅳ2 -피란 -2- 일)— 1 -인다졸 -3-카복스아미드 (24 mg)을 MeOH (1 iiiL)에 녹이고 4M HC1/디옥산 (1 iiiL)를 첨가하여 실온에서 8 시간 동안 교반하였다. 반웅이 종결하면 용매를 감압 증류하여 제거한 후 탄산수소나트륨 수용액을 사용하고  6-((5-amino- 2-methylphenyl) (methyl) amino) dogmethyl-1- (tetrahydro ᅳ 2-pyran-2-yl)-1-indazole-3-carboxamide (24 mg) It was dissolved in MeOH (1 iiiL) and 4M HC1 / dioxane (1 iiiL) was added and stirred for 8 hours at room temperature. When the reaction was completed, the solvent was distilled off under reduced pressure, and then aqueous sodium hydrogen carbonate solution was used.
에틸아세테이트로 추출한 다음에 유기층을 무수 황산마그네슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거하여 농축하였다. Prep HPLC로 정제 하여 목적화합물 After extraction with ethyl acetate, the organic layer was dried over anhydrous magnesium sulfate and filtered. The solvent was removed by distillation under reduced pressure and concentrated. Purified by Prep HPLC to target compound
Λ/-메틸— 6- (메틸 (2ᅳ메틸—5-(3—몰포리노—5ᅳ (트리플루오로메틸)벤즈아미도)페닐) 아미노 )— 인다졸 -3—카복스아미드 (9.7 mg)를 얻었다. ¾ NMR (400 MHz , DMS0-쑈) δ 12.94 (s, 1H), 10.36 (s, 1H), 8.17 (m, 1H), 7.83 (m, 1H), 7.70 (m, 2H), 7.61. (d, 2H), 7.36 (m, 2H), 6.52 (m, 2H), 3.75 (i , 4H), 3.24 (m, 4H), 2.77 (m, 3H) , 2.09 (m, 3H), 1.23 (m, 3H)ᅳ MS m/z [M+H] 567. 실시예 12.  Λ / -methyl— 6- (methyl (2 ᅳ methyl—5- (3—morpholino—5 ′ (trifluoromethyl) benzamido) phenyl) amino) — indazole-3—carboxamide (9.7 mg ) ¾ NMR (400 MHz, DMS0-Hz) δ 12.94 (s, 1H), 10.36 (s, 1H), 8.17 (m, 1H), 7.83 (m, 1H), 7.70 (m, 2H), 7.61. (d, 2H), 7.36 (m, 2H), 6.52 (m, 2H), 3.75 (i, 4H), 3.24 (m, 4H), 2.77 (m, 3H), 2.09 (m, 3H), 1.23 ( m, 3H) ᅳ MS m / z [M + H] 567. Example 12.
Λ一메틸ᅳ 6- (메틸 ( 4ᅳ ( 3- (트리플루오로메틸)벤즈아미도)페닐)아미노) - 인다졸 -3 -카복스아미드의 제조 단계 1.  Step for the preparation of Λ 一 methyl (6- (methyl (4 ᅳ (3- (trifluoromethyl) benzamido) phenyl) amino) -indazole-3-carboxamide 1.
6-( (4-아미노페닐 ) (메틸)아미노)— /V—메틸— 1- (테트라하이드로— 2//-피란— 2-일 인다졸 -3ᅳ카복스아미드의 제조  Preparation of 6-((4-aminophenyl) (methyl) amino) — / V—methyl— 1- (tetrahydro— 2 //-pyran— 2-yl indazole-3 ᅳ carboxamide
Figure imgf000038_0001
Figure imgf000038_0001
상기 제조예 1의 단계 7 또는 상기 제조예 2의 단계 4의 방법으로 얻은 에틸 6-(4ᅳ니트로페닐아미노 )-1ᅳ (테트라하이드로— 2//-피란 -2ᅳ일 )ᅳ1//—인다졸— 3-카복실 레이트를 상기 실시예 11의 단계 1부터 4까지 반복하여 Ethyl 6- (4 ᅳ nitrophenylamino) -1 '(tetrahydro— 2 //-pyran-2 ᅳ yl) ᅳ 1 // — obtained by the method of Step 7 of Preparation Example 1 or Step 4 of Preparation Example 2 Indazole—Repeat the 3-carboxylate rate from steps 1 to 4 of Example 11 above
6-( (4—아미노페닐 ) (메틸 )아미노)— -메틸 -1- (테트라하이드로— 2 -피란 -2-일 )-1 - 인다졸—3-카복스아미드를 얻었다. lH NMR (400 MHz, DMSC ) δ 8.71 (m, 1H), 8.50 (d, / = 7.8 Hz, 1H), 8.11 (m, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.48 (m, 1H), 6.87 (m, 2Ή), 6.60 (s, 2H), 5.81 (m, 1H) , 3.89 (m, 1H), 3.74 (m, 1H), 2.68 (s, 3H), 2.08 (m, 3H), 1.92 (m, 2H), 1.75 (m, 3H), 1.58 (s, 3H), MS m/z [M+H] 380. 단계 2.6- ((4—aminophenyl) (methyl) amino) —- methyl-1- (tetrahydro—2-pyran-2-yl) -1-indazole—3-carboxamide was obtained. l H NMR (400 MHz, DMSC ) δ 8.71 (m, 1H), 8.50 (d, / = 7.8 Hz, 1H), 8.11 (m, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.48 ( m, 1H), 6.87 (m, 2Ή), 6.60 (s, 2H), 5.81 (m, 1H), 3.89 (m, 1H), 3.74 (m, 1H), 2.68 (s, 3H), 2.08 (m , 3H), 1.92 (m, 2H), 1.75 (m, 3H), 1.58 (s, 3H), MS m / z [M + H] 380. Step 2.
-메틸 -6ᅳ (메틸 (4-(3- (트리플루오로메틸)벤즈아미도)페닐)아미노) -1 -인다졸 -3 ᅳ카복스아미드의 제조
Figure imgf000039_0001
Preparation of -methyl-6 '(methyl (4- (3- (trifluoromethyl) benzamido) phenyl) amino) -1 -indazole -3 ᅳ carboxamide
Figure imgf000039_0001
6- (( 4-아미노페닐) (메틸 )아미노)— /V-메틸 - 1— (테트라하이드로— 2//-피란 -2—일)— 1 — 인다졸—3-카복스아미드 (20 nig, 0.053 ol), 3- (트리플루오로메틸)벤조일 클로라이드 (13.3 mg, 0.064 ol)를 메틸렌클로라이드 (l iiiL)에 녹인 후 피리딘 6-((4-aminophenyl) (methyl) amino) — / V-methyl-1— (tetrahydro— 2 //-pyran-2—yl) — 1 — indazole—3-carboxamide (20 nig , 0.053 ol), 3- (trifluoromethyl) benzoyl chloride (13.3 mg, 0.064 ol) in methylene chloride (l iiiL) and then pyridine
{21Λ ί, 0.27 1 )를 첨가하여 실온에서 4 시간 동안 교반하였다. 반웅이 종결하면 용매를 감압 증류하여 제거한 후 IN HC1 수용액 수용액을 사용하고 에틸아세테이트로 추출한 다음에 유기층을 무수 황산마그네슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거하여 농축하여 목적화합물 {21Λ ί, 0.27 1) was added and stirred at room temperature for 4 hours. When the reaction was completed, the solvent was distilled off under reduced pressure, the mixture was extracted with ethyl acetate solution using IN HC1 aqueous solution, and then the organic layer was dried over anhydrous magnesium sulfate and filtered. The solvent is removed by distillation under reduced pressure and concentrated.
-메틸 -6- (메틸 (4— (3ᅳ (트리플루오로메틸)벤즈아미도)페닐)아미도 )-1- (테트라하 이드로 -2 -피란 -2-일)— 인다졸 -3—카복스아미드를 얻었다. 이 얻은 화합물을 MeOH (1 mL)에 녹이고 4M HC1/디옥산 (1 mL)를 첨가하여 실온에서 7 시간 동안 교반하였다. 반응이 종결하면 용매를 감압 증류하여 제거한 후 탄산수소나트륨 수용액을 사용하고 에틸아세테이트로 추출한 다음에 유기층을 무수 황산마그네슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거하여 농축하였다. 농축 잔사를 컬럼 크로마토그래피 (실리카겔, 메틸렌클로라이드 /메탄올 =97:3)로 정제하여 목적 화합물인  -Methyl-6- (methyl (4— (3 ′ (trifluoromethyl) benzamido) phenyl) amido) -1- (tetrahydro-2-pyran-2-yl) — indazole-3— Carboxamide was obtained. The obtained compound was dissolved in MeOH (1 mL) and 4M HC1 / dioxane (1 mL) was added and stirred at room temperature for 7 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, the mixture was extracted with ethyl acetate, and then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and filtered. The solvent was removed by distillation under reduced pressure and concentrated. The concentrated residue was purified by column chromatography (silica gel, methylene chloride / methanol = 97: 3) to obtain the target compound.
一메틸 -6- (메틸 (4-(3- (트리플루오로메틸)벤즈아미도)페닐)아미노 인다졸 -3 一카복스아미드 (4.7 mg)를 얻었다. TH剛 R (400 MHz , DMS0- ) δ 13.09 (s, 1H), 10.46 (s, 1H), 8.28 (m, 2H) , 8.24 (d, J 17.2 Hz, 1H), 7.95 (cld, J = 7.5, 17.7 Hz, 2H), 7.78 (d, J = 8.2 Hz, 1H), 7.75 (d, J= 8.7 Hz, 2H), 7.16 (d, / = 8.7 Hz, 2H), 6.89 (s, 1H), 6.84 (d, J = 8.9 Hz, 1H), 3.33 (s, 3H), 2.79 (d, J 4.7 Hz, 3H), MS ιιι/ζ [ +H] 468. 실시예 13. Monomethyl-6- (methyl (4- (3- (trifluoromethyl) benzamido) phenyl) amino indazole-3 monocarboxamide (4.7 mg) was obtained. T H 剛 R (400 MHz, DMS0 δ δ 13.09 (s, 1H), 10.46 (s, 1H), 8.28 (m, 2H), 8.24 (d, J 17.2 Hz, 1H), 7.95 (cld, J = 7.5, 17.7 Hz, 2H), 7.78 (d, J = 8.2 Hz, 1H), 7.75 (d, J = 8.7 Hz, 2H), 7.16 (d, / = 8.7 Hz, 2H), 6.89 (s, 1H), 6.84 (d, J = 8.9 Hz , 1H), 3.33 (s, 3H), 2.79 (d, J 4.7 Hz, 3H), MS ιιι / ζ [+ H] 468. Example 13.
6- ( (4— (3—브로모페닐설폰아미도)페닐) (메틸)아미노시메틸 인다졸—3-카복 스아미드의 제조
Figure imgf000039_0002
Preparation of 6- ((4— (3—bromophenylsulfonamido) phenyl) (methyl) aminomethylmethyl indazole—3-carboxamide
Figure imgf000039_0002
6-( (4—아미노페닐 ) (메틸 )아미노) 메틸 -1— (테트라하이드로 -2 -피란—2—일 )-\H- 인다졸 -3—카복스아미드 (20mg, 0.053 ol), 3-브로모벤젠 -1-설포닐 클로라이드6- ((4—aminophenyl) (methyl) amino) methyl-1— (tetrahydro-2-pyran—2—yl)-\ H- indazole-3—carboxamide (20 mg, 0.053 ol), 3 Bromobenzene-1-sulfonyl chloride
(16.3 mg, 0.064 mmol)를 메틸렌클로라이드 (1 mL)에 녹인 후 피리딘 (21.4 id , 0.271 01)를 첨가하여 실온에서 4 시간 동안 교반하였다. 반웅이 종결하면 용매를 감압 증류하여 제거한 후 IN HC1 수용액 수용액을 사용하고 (16.3 mg, 0.064 mmol) was dissolved in methylene chloride (1 mL), and then pyridine (21.4 id, 0.271 0 1) was added and stirred at room temperature for 4 hours. When the reaction was completed, the solvent was distilled off under reduced pressure, and then the aqueous IN HC1 aqueous solution was used.
에틸아세테이트로 추출한 다음에 유기층을 무수 황산마그네슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거하여 After extraction with ethyl acetate, the organic layer was dried over anhydrous magnesium sulfate and filtered. The solvent is removed by distillation under reduced pressure
6-((4-(3—브로모페닐설폰아미도)페닐) (메틸)아미노) - —메틸 -1— (테트라하이드로 -2//ᅳ피란—2-일)— 인다졸—3—카복스아미드을 얻었다. 이 화합물을 정제 없이 MeOH (1 niL)에 녹이고 4M HC1/디옥산 (1 mL)을 첨가하여 실온에서 7 시간 동안 교반하였다. 반응이 종결하면 용매를 감압 증류하여 제거한 후 탄산수소나트륨 수용액을 사용하고 에틸아세테이트로 추출한 다음에 유기층을 무수 황산마그네슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거하여 농축하였다. 농축 잔사를 컬럼 크로마토그래피 (실리카겔, 메틸렌클로라이드 /메탄올 =97:3)로 정제하여 목적 화합물인 6-((4- (3—bromophenylsulfonamido) phenyl) (methyl) amino)-—methyl-1— (tetrahydro -2 // pypyran-2-day) -indazazole-3-carboxamide. This compound was taken up in MeOH (1 niL) without purification and 4M HC1 / dioxane (1 mL) was added and stirred at room temperature for 7 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, the mixture was extracted with ethyl acetate, and then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and filtered. The solvent was removed by distillation under reduced pressure and concentrated. The concentrated residue was purified by column chromatography (silica gel, methylene chloride / methanol = 97: 3) to obtain the target compound.
6一 ( (4— (3-브로모페닐설폰아미도)페닐) (메틸)아미노)— /V-메틸 인다졸ᅳ 3-카복 스아미드 (4.9 nig)를 얻었다. Ή NMR (400 MHz , DMS0— ) δ 13.10 (s, 1H), 8.22 (q, J 4.8 Hz 1H), 7.90 (d, /= 8.8 Hz 1H), 7.84-7.82 (m, 2H) , 7.71 (d, 6-((4— (3-bromophenylsulfonamido) phenyl) (methyl) amino) — / V-methyl indazol-3-carboxamide (4.9 nig) was obtained. MR NMR (400 MHz, DMS0—) δ 13.10 (s, 1H), 8.22 (q, J 4.8 Hz 1H), 7.90 (d, / = 8.8 Hz 1H), 7.84-7.82 (m, 2H), 7.71 (d ,
J 8.0 Hz, 1H), 7.54 (t, J = 8.0 Hz, 1H), 6.98-6.96 (m, 4H), 6.88 (111， 1H) , 6.76 (dd, J = 8.8, 2.0 Hz, 1H), 5.75 (s, 1H), 3.24 (s, 3H), 2.78 (cl, J= 4.8 Hz, 3H), MS m/z [M+H] 515， 517. 상기 실시예 11 내지 13의 제조방법에 의하여 하기 표 2의 화합물을 J 8.0 Hz, 1H), 7.54 (t, J = 8.0 Hz, 1H), 6.98-6.96 (m, 4H), 6.88 (111, 1H), 6.76 (dd, J = 8.8, 2.0 Hz, 1H), 5.75 (s, 1H), 3.24 (s, 3H), 2.78 (cl, J = 4.8 Hz, 3H), MS m / z [M + H] 515, 517. According to the preparation methods of Examples 11 to 13 above Compounds of Table 2
합성하였다.  Synthesized.
【표 2】  Table 2
Figure imgf000040_0001
6ᅳ ( (5一 (3ᅳ(4一하이드록시피페리딘ᅳ 1- 일 )—5- (트리플루오로메틸 )벤즈아미 실예 도)— 2-메틸페닐) (메틸)아미노)—A I 틸 인다졸 -3—카복스아미드
Figure imgf000040_0001
6 ᅳ ((55 (3 ᅳ (4 一 hydroxypiperidin ᅳ 1-yl) —5- (trifluoromethyl) benzami exemplified) — 2-methylphenyl) (methyl) amino) —AI til Sol-3—carboxamide
MS m/z [M+H] 581 실시 /ᅳ메틸 -6—(메틸 ( 2—메틸— 5ᅳ ( 3- ( 4-메 예 17 틸 이미다졸— 1-일 )-5- (트리플루 오로메틸)벤즈아미도)페닐)아미노) - 인다졸— 3-카복스아미드 MS m / z [M + H] 581 Conducted / ᅳ Methyl-6- (methyl (2—methyl—5 ᅳ (3- (4-Mey 17-methyl imidazole— 1-yl) -5- (trifluoro Methyl) benzamido) phenyl) amino) -indazole— 3-carboxamide
MS m/z [M+H] 562 ᅳ살시 MS m / z [M + H] 562 years
예 18 틸 이미다졸 -1ᅳ일 )一5- (트리플루 오로메틸)벤즈아미도)페닐)아미노) - 인다졸—3—카복스마이드 Example 18 Tyl imidazole-1 boilyl) 15- (trifluoromethyl) benzamido) phenyl) amino) -indazole—3—carboxamide
Ή NMR (400 MHz , DMS0— ( ) δ 8.37 (s, 1H), 8.24 (s, IH), 8.00 (s, 1H), 7.87 (d, /= 9.0 Hz, IH), 7.62 (m, 1H), 7.60 (d, J 1.8 Hz, IH), 7.35 (in, 2H), 7.02 (s, IH), 6.63 (s, IH), 6.53 (m, IH), 2.94 (s, 3H), 2.39 (s, 3H), 2.14 (s, 3H), 1.29 (s, 3H), MS m/z [M+H] 562 NMR (400 MHz, DMS0— () δ 8.37 (s, 1H), 8.24 (s, IH), 8.00 (s, 1H), 7.87 (d, / = 9.0 Hz, IH), 7.62 (m, 1H) , 7.60 (d, J 1.8 Hz, IH), 7.35 (in, 2H), 7.02 (s, IH), 6.63 (s, IH), 6.53 (m, IH), 2.94 (s, 3H), 2.39 (s , 3H), 2.14 (s, 3H), 1.29 (s, 3H), MS m / z [M + H] 562
실시 ^1^1^ ^-디메틸 :1 ᅩ이미다졸一 예 1 1-일 )ᅳ5— (트리플루오로메틸)벤즈아 미도) -2-메틸페닐) (메틸)아미노) -그 메틸 인다졸— 3ᅳ카복스아미드 NMR (400 MHz, DMS0— ) δ 10.51 (s, IH), 8.28 (d, J= 12.8 Hz, 2H) , 8.17 (d, J = 5.0 Hz, IH), 8.06 (s, IH), 7.90 (d, /= 8.9 Hz, IH), 7.70 (d, J = 8.3 Hz, IH), 7.61 (s, IH), 7.37 (d, J= 8.3 Hz, IH), 7.17 (s, IH), 6.51 (m, 2H), 3.24 (s, 3H), 2.64 (d, J= 4.7 Hz, 3H), 2.29 (s, 3H), 2.10 (d, J= 2.98 Hz, 6H), MS m/z [M+H] 576
Figure imgf000042_0001
5-(4-클로로페닐 )— Λ 4-메틸 -3— (메 틸 ( 3- (메틸카바모일)— 인다졸ᅩ 6— 실실실예예실예실예예 일)아미노)페닐)이소옥사졸— 3-카복 시시 22 ^ 1 ^ 1 ^ ^ -dimethyl : 1 ᅩ imidazole 一 Example 1 1-yl) ᅳ 5— (trifluoromethyl) benzamido) -2-methylphenyl) (methyl) amino)-methyl methyl indazole— 3 ᅳ carboxamide NMR (400 MHz, DMS0—) δ 10.51 (s, IH), 8.28 (d, J = 12.8 Hz, 2H), 8.17 (d, J = 5.0 Hz, IH), 8.06 (s, IH) , 7.90 (d, / = 8.9 Hz, IH), 7.70 (d, J = 8.3 Hz, IH), 7.61 (s, IH), 7.37 (d, J = 8.3 Hz, IH), 7.17 (s, IH) , 6.51 (m, 2H), 3.24 (s, 3H), 2.64 (d, J = 4.7 Hz, 3H), 2.29 (s, 3H), 2.10 (d, J = 2.98 Hz, 6H), MS m / z [M + H] 576
Figure imgf000042_0001
5- (4-Chlorophenyl) — Λ 4-methyl-3— (methyl (3- (methylcarbamoyl) — indazole ᅩ 6— silsilyl silylyl silylyl) amino) phenyl) isoxazole— 3 Carboxy Sissy 22
9 스아미드  9 samides
MS ni/z [M+H] 515 MS ni / z [M + H] 515
6- ( ( 5— ( 5- ( 4-메톡시페닐)퓨란 -2一카 복스아미도) -2-메틸페닐) (메틸)아口 노) -메틸 인다졸 -3—카복스아口 ti腿 (400 MHz , DMS0— ;) δ 12.04 (s, 1H), 9.23 (s, 1H), 7.28 (d, / = 16.7 Hz, 1H), 6.99 (m, 3H), 6.84 (m, 1H), 6.69 (s, 1H), 6.47 (m, 2H), 6.15 (in, 3H), 5.64 (cl, /= 6.1 Hz, 2H), 2.92 (d, J= 7.9 Hz, 3H), 2.37 (s, 3H), 1.90 (d, J= 4.6 Hz, 3H), 1.21 (s, 3H), MS m/z [M+H] 5106- ((5— (5- (4-methoxyphenyl) furan-2 unicarboxamido) -2-methylphenyl) (methyl) amino) -methyl indazole -3—carboxamide (400 MHz, DMS0—;) δ 12.04 (s, 1H), 9.23 (s, 1H), 7.28 (d, / = 16.7 Hz, 1H), 6.99 (m, 3H), 6.84 (m, 1H), 6.69 (s, 1H), 6.47 (m, 2H), 6.15 (in, 3H), 5.64 (cl, / = 6.1 Hz, 2H), 2.92 (d, J = 7.9 Hz, 3H), 2.37 (s, 3H) , 1.90 (d, J = 4.6 Hz, 3H), 1.21 (s, 3H), MS m / z [M + H] 510
4—메틸— 3- (메틸 ( 3- (메틸카바모일 )-1 ^인다졸 -6-일)아미노)페닐) -2-( 피리딘— 4—일 )티아졸 -5-카복스아미드 4—methyl— 3- (methyl (3- (methylcarbamoyl) -1 ^ indazol-6-yl) amino) phenyl) -2- (pyridin— 4—yl) thiazole-5-carboxamide
MS m/z [M+H] 498 MS m / z [M + H] 498
틸— 6- (메— ^(3-몰포리노 -5- Γ 트리플루오로메틸 )벤즈아미도)페닐) 아미노) 인다졸ᅳ 3—카복스아미드  Tyl- 6- (meth — ^ (3-morpholino-5-Γ trifluoromethyl) benzamido) phenyl) amino) indazolazole 3—carboxamide
MS m/z [M+H] 553 MS m / z [M + H] 553
6-((4-(3-( 1 -이미다졸— 1-일 )ᅳ5- (트 리플루오로메틸)벤즈아미도)페닐) ( 메틸 )아미노)ᅳ —메틸 -L7ᅳ인다졸 -3- 카복스아미드 6-((4- (3- (1 -imidazol— 1-yl) ᅳ 5- (trifluoromethyl) benzamido) phenyl) (methyl) amino) ᅳ —methyl-L7 ”indazole-3 -Carboxamide
Ή NMR (400 MHz, DMSO- ) δ 13.15 (s, 1H), 10.55 (s, 1H), 8.53 (s, 1H), 8.53 (s, 1H), 8.30 (s, 1H), 8.22(m, 2H), 8.02 (s, 1H), 7.91 (d, 7=8.8Hz, 2H), 7.75 (d, J=8.8Hz, 1H), 7.18 (m, 3H), 6.92 (s, 1H)， 6.85 (d, J= 8.8 Hz, 1H), 2.79 (d,
Figure imgf000044_0001
Figure imgf000045_0001
ll-I), 7.87 (d, /= 8.8 Hz, 2H), 7.14 NMR (400 MHz, DMSO-) δ 13.15 (s, 1H), 10.55 (s, 1H), 8.53 (s, 1H), 8.53 (s, 1H), 8.30 (s, 1H), 8.22 (m, 2H ), 8.02 (s, 1H), 7.91 (d, 7 = 8.8 Hz, 2H), 7.75 (d, J = 8.8 Hz, 1H), 7.18 (m, 3H), 6.92 (s, 1H), 6.85 (d , J = 8.8 Hz, 1H), 2.79 (d,
Figure imgf000044_0001
Figure imgf000045_0001
ll-I), 7.87 (d, / = 8.8 Hz, 2H), 7.14
(cl, J 8.8 Hz, 2H), 6.93 (s, H ),  (cl, J 8.8 Hz, 2H), 6.93 (s, H),
6.89 (cl, J 8.8 Hz, 1H), 3.17 (d,  6.89 (cl, J 8.8 Hz, 1H), 3.17 (d,
J: 5.2 Hz, 3H), 2.79 (d, /= 4.7 Hz, J : 5.2 Hz, 3H), 2.79 (d, / = 4.7 Hz,
3H), 2.64 (s, 3H), MS m/z [M+H] 416  3H), 2.64 (s, 3H), MS m / z [M + H] 416
실시예 39. Example 39.
一메틸—6— (메틸 ( 4- ( 3_ ( 3- (트리플루오로메틸)페닐)우레이도)페닐)아미노 )— 인 다졸— 3-카복스아미드의 제조 단계 1. Imethyl- 6 — (methyl ( 4- (3_ (3- (trifluoromethyl) phenyl) ureido) phenyl) amino) — indazole — 3-carboxamide 1.
yy—메틸— 6- (메틸 (4— (3-(3— (트리플루오로메틸)페닐)우레이도)페닐)아미노 )— 1- (테 트라하이드로— 2 -피란— 2-일 인다졸 3-카복스아미드의 제조 yy—methyl— 6- (methyl (4— (3- (3— (trifluoromethyl) phenyl) ureido) phenyl) amino) — 1- (tetrahydro— 2 -pyran— 2-yl indazole 3 Preparation of Carboxamide
Figure imgf000046_0001
Figure imgf000046_0001
6-( (4-아미노페닐) (메틸 )아미노)— ―메틸 -1- (테트라하이드로— 2 ᅳ피란 -2-일 인다졸—3-카복스아미드 (20 mg, 0.053 腦 iol), 6-((4-aminophenyl) (methyl) amino) —- methyl-1- (tetrahydro—2 cappyran-2-yl indazole—3-carboxamide (20 mg, 0.053 腦 iol),
1-이소시아나토 -3- (트리플루오로메틸)벤젠 (10.5mg, 0.056隱 ol)을 THF (lmL)에 녹인 후 DIPEA (12.6 id, 0.077 隱 ol)를 첨가하여 실온에서 2 시간 동안 교반하였다. 반응이 종결하면 용매를 감압 증류하여 제거한 후 IN HC1 수용액 수용액을 사용하고 에틸아세테이트로 추출한 다음에 유기층을 무수 황산마그네슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거하여 T -메틸 -6- (메틸 (4-(3—(3- (트리플루오로메틸)페닐)우레이도)페닐)아미노 )-1- (테 트라하이드로 -2 —피란 -2-일) 인다졸 -3-카복스아미드 (26 mg)를 얻어 더 이상의 정제 없이 다음 반웅을 진행하였다. MS m/z [M+H] 567. 단계 2. 1-isocyanato-3- (trifluoromethyl) benzene (10.5 mg, 0.056 μl) was dissolved in THF (lmL), and then DIPEA (12.6 id, 0.077 μl) was added and stirred at room temperature for 2 hours. . After completion of the reaction, the solvent was distilled off under reduced pressure, extracted with ethyl acetate solution using IN HC1 aqueous solution, and then the organic layer was dried over anhydrous magnesium sulfate and filtered. The solvent was removed by distillation under reduced pressure to give T-methyl-6- (methyl (4- (3— (3- (trifluoromethyl) phenyl) ureido) phenyl) amino) -1- (tetrahydro-2—pyran -2-yl) indazole-3-carboxamide (26 mg) was obtained and the next reaction was carried out without further purification. MS m / z [M + H] 567. Step 2.
-메틸 -6- (메틸 (4— (3— (3— (트리플루오로메틸)페닐)우레이도)페닐)아미노 )—1쯔인 다졸 -3-카복스아미드의 제조
Figure imgf000046_0002
Preparation of 4-Methyl-6- (methyl (4— (3— (3— (trifluoromethyl) phenyl) ureido) phenyl) amino) —zinezazole 3-carboxamide
Figure imgf000046_0002
―메틸 -6- (메틸 (4-(3-(3- (트리폴루오로메틸)페닐)우레이도)페닐)아미노 )ᅳ1— (테 트라하이드로 -2 -피란 -2-일) 인다졸 -3ᅳ카복스아미드 (26mg)를 MeOH (lmL)에 녹이고 4M HC1/디옥산 (1 mL)를 첨가하여 실온에서 8 시간 동안 교반하였다. 반응이 종결하면 용매를 감압 증류하여 제거한 후 탄산수소나트륨 수용액을 사용하고 에틸아세테이트로 추출한 다음에 유기충을 무수 황산마그네슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거하여 농축하였다. Prep HPLC로 정제하여 목적화합물 -Methyl-6- (methyl (4- (3- (3- (tripolouromethyl) phenyl) ureido) phenyl) amino) ᅳ 1— (tetrahydro-2-pyran-2-yl) indazole -3'Carboxamide (26 mg) was dissolved in MeOH (lmL) and 4M HC1 / dioxane (1 mL) was added and stirred for 8 hours at room temperature. After completion of the reaction, the solvent was distilled off under reduced pressure and the aqueous sodium hydrogen carbonate solution was removed. After using, the mixture was extracted with ethyl acetate and the organic insects were dried over anhydrous magnesium sulfate and filtered. The solvent was removed by distillation under reduced pressure and concentrated. Purified by Prep HPLC to target compound
Λ-메틸 -6- (메틸 (4— (3ᅳ (3— (트리플루오로메틸)페닐)우레이도)페닐)아미노 ᅳ인 다졸 -3—카복스아미드 (6.8 nig)를 얻었다. ]H NMR (400 MHz, DMSO— ) δDazol-3-carboxamide (6.8 nig), which was Λ-methyl-6- (methyl (4— (33 (3— (trifluoromethyl) phenyl) ureido) phenyl) amino shock, was obtained. ] H NMR (400 MHz, DMSO—) δ
13.04 (s, 1H), 9,38 (s, 1H), 9.11 (s, 1H), 8.29 (q, J = 4.8 Hz 1H), 8.03 (s, 1H), 7.87 (d, J 9.6 Hz 1H), 7.59 (d, J = 12.6 Hz, 1H), 7.50-7.47 (m, 3H), 7.30 (cl, J= 12.5 Hz, III), 7.11 (d, J = 8.8 Hz, 2H), 6.76 (m, 2H), 3.28 (s, 3H), 2.78 (d, J = 4.8 Hz, 3H), MS m/z [M+H] 567. 실시예 40. 13.04 (s, 1H), 9,38 (s, 1H), 9.11 (s, 1H), 8.29 (q, J = 4.8 Hz 1H), 8.03 (s, 1H), 7.87 (d, J 9.6 Hz 1H) , 7.59 (d, J = 12.6 Hz, 1H), 7.50-7.47 (m, 3H), 7.30 (cl, J = 12.5 Hz, III), 7.11 (d, J = 8.8 Hz, 2H), 6.76 (m, 2H), 3.28 (s, 3H), 2.78 (d, J = 4.8 Hz, 3H), MS m / z [M + H] 567. Example 40.
6— ( (5-(3— (4-클로로 -3—플루오로페닐)우레이도) -2ᅳ메틸페닐) (메틸)아미노)—쓰메 틸 -1 —인다졸 -3—카복스아미드의 제조 단계 1. 4-니트로페닐 ' 6— ((5- (3— (4-Chloro-3—fluorophenyl) ureido) -2 ᅳ methylphenyl) (methyl) amino) —tmethyl-1—indazol-3—carboxamide 1. 4-nitrophenyl ''
4-메틸 -3-(메틸 (3- (메틸카바모일 )ᅳ1— (테트라하이드로 -2 ―피란 -2-일 인다졸 —6-일 )아미노)페닐카바메이트  4-methyl-3- (methyl (3- (methylcarbamoyl) ᅳ 1— (tetrahydro-2-pyran-2-yl indazole —6-yl) amino) phenylcarbamate
Figure imgf000047_0001
Figure imgf000047_0001
6-( (5—아미노— 2-메틸페닐 ) (메틸 )아미노) - —메틸 -1- (테트라하이드로 -2//-피란一 2- 일) -1//-인다졸 -3-카복스아미드 (40 ing, 0.10 I画 1), 피리딘 (12.1 (Λ , 0.15 画 ΊΟΙ)을 메틸렌클로라이드 (1 mL)에 녹인 후 4—니트로페닐 카보노크로리데이트 (20.2 mg, 0.10 薩 ol)을 첨가하여 실온에서 30 분간 교반하였다. 반웅이 종결하면 용매를 감압 증류하여 제거하여 IN HC1 수용액 수용액을 사용하고 에틸아세테이트로 추출한 다음에 유기층을 무수 황산마그네슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거하여 4ᅳ니트로페닐 6- ((5—amino— 2-methylphenyl) (methyl) amino)-—methyl-1- (tetrahydro-2 //-pyranyl 2-yl) -1 //-indazole-3-carboxamide (40 ing, 0.10 I 画 1), pyridine (12.1 (Λ, 0.15 画 ΟΙ)) was dissolved in methylene chloride (1 mL), and then 4—nitrophenyl carbonochromate (20.2 mg, 0.10 薩 ol) was added to room temperature. After the reaction was complete, the solvent was distilled off under reduced pressure, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and filtered. Nitrophenyl
4-메틸— 3— (메틸 (3- (메틸카바모일 )-1— (테트라하이드로 -2 -피란 -2-일 인다졸 -6-일)아미노)페닐카바메이트 (53 mg, 94%)를 얻어 더 이상의 정제 없이 다음 반웅을 진행하였다. MS m/z [M+H] 559. 단계 2. 4-methyl— 3— (methyl (3- (methylcarbamoyl) -1— (tetrahydro-2-pyran-2-yl indazol-6-yl) amino) phenylcarbamate (53 mg, 94%) The reaction was carried out without further purification: MS m / z [M + H] 559. Step 2.
6-( (5— (3- (4-클로로 -3-플루오로페닐)우레이도) -2-메틸페닐) (메틸)아미노) -yV一메 틸一 1- (테트라하이드로— 2 -피란 -2-일 ) 인다졸 -3-카복스아미드의 제조  6- ((5— (3- (4-Chloro-3-fluorophenyl) ureido) -2-methylphenyl) (methyl) amino) -yVimethyl 一 1- (tetrahydro— 2 -pyran-2 -Yl) Preparation of indazole-3-carboxamide
Figure imgf000047_0002
4一메틸 -3- (메틸 (3- (메틸카바모일 )—1- (테트라하이드로 -2//-피란 -2-일 인다졸 —6-일)아미노)페닐카바메아트 (28 mg, 0.05 隱 ol), 4-클로로 -3ᅩ플루오로아닐린 (9 mg, 0.06 mmol), DIPEA (12.4 ≠, 0.08画 ol)를 THF (1 mL) 에 녹여 실온에서 6 시간 동안 교반하였다. 반응이 종결하면 용매를 감압 증류하여 제거하고
Figure imgf000047_0002
一4-methyl-3- (methyl (3 - (methyl-carbamoyl) -1- (tetrahydro -2 // - pyran-2-yl-indazol-6-yl) amino) phenylcarbamoyl methoxy art (28 mg, 0.05隱 ol), 4-chloro-3 ᅩ fluoroaniline (9 mg, 0.06 mmol) and DIPEA (12.4 ≠ 0.08 画 ol) were dissolved in THF (1 mL) and stirred for 6 hours at room temperature. The solvent was distilled off under reduced pressure,
IN HC1 수용액 수용액을 사용하고 에틸아세테이트로 추출한 다음에 유기층을 무수 황산마그 슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거하여 An aqueous IN HC1 solution was used and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and filtered. The solvent is removed by distillation under reduced pressure
6-((5-(3-( 4-클로로 -3-플루오로페닐)우레이도 )一2-메틸페닐) (메틸)아미노) ᅳ메 틸 -1- (테트라하이드로 -2//-피란— 2-일)— 인다졸—3—카복스아미드 (23 nig)를 얻어 더 이상의 정제 없이 다음 반웅을 진행하였다. MS m/z [M+H] 566. 단계 3.  6-((5- (3- (4-Chloro-3-fluorophenyl) ureido) 一 2-methylphenyl) (methyl) amino) methylmethyl-1- (tetrahydro-2 //-pyran— 2- I) —Indazole-3—carboxamide (23 nig) was obtained and proceeded to the next reaction without further purification. MS m / z [M + H] 566. Step 3.
6-( (5-(3-(4-클로로 -3-플루오로페닐)우레이도) -2ᅳ메틸페닐) (메틸)아미노 )— /Vᅳ메 틸 -1 -인다졸— 3—카복스아미드 의 제조
Figure imgf000048_0001
6-((5- (3- (4-chloro-3-fluorophenyl) ureido) -2) methylphenyl) (methyl) amino) — / V ᅳ methyl-1-indazole—3—carboxamide Produce
Figure imgf000048_0001
6-( (5-(3-(4-클로로 -3—플루오로페닐)우레이도) -2ᅳ메틸페닐 ) (메틸)아미노) -/Vᅳ메 틸 -1- (테트라하이드로 -2//—피란— 2—일 인다졸 -3—카복스아미드 (23 mg)를 MeOH (1 mL) 에 녹이고 4M HC1/디옥산 (1 mL)를 첨가하여 실온에서 8 시간 동안 교반하였다. 반응이 종결하면 용매를 감압 증류하여 제거한 후 6-((5- (3- (4-Chloro-3—fluorophenyl) ureido) -2 ᅳ methylphenyl) (methyl) amino)-/ V ᅳ methyl-1- (tetrahydro-2 // — pyran — 2—yl indazole-3—carboxamide (23 mg) was dissolved in MeOH (1 mL) and 4M HC1 / dioxane (1 mL) was added and stirred for 8 hours at room temperature. After distillation under reduced pressure
탄산수소나트륨 수용액을 사용하고 에틸아세테이트로 추출한 다음에 유기층을 무수 황산마그네습으로 건조하여 여과하였다. 용매를 감압 증류로 제거하여 농축하였다. Prep HPLC로 정제 하여 An aqueous sodium hydrogen carbonate solution was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and filtered. The solvent was removed by distillation under reduced pressure and concentrated. Purified by Prep HPLC
6-((5-(3-(4-클로로 3—플루오로페닐)우레이도)— 2ᅳ메틸페닐) (메틸)아미노) - ᅳ메 틸 인다졸 -3—카복스아미드 (9.3 mg)를 얻었다. MS m/z [M+H] 481. 실시예 41. 6-((5- (3- (4-Chloro 3-fluorophenyl) ureido)-2'methylphenyl) (methyl) amino)-methmethyl indazole-3-carboxamide (9.3 mg) was obtained. MS m / z [M + H] 481. Example 41.
6-((5— (3-(4-클로로페닐)우레이도)— 2-메틸페닐) (메틸)아미노)—yV-메틸 -1 -인다 졸 -3—카복스아미드의 제조  Preparation of 6-((5— (3- (4-chlorophenyl) ureido) — 2-methylphenyl) (methyl) amino) —yV-methyl-1-indazol-3—carboxamide
Figure imgf000048_0002
상기 실시예 40과 같은 방법으로 화합물을 합성하였다. MS m/z [M+H] 463. 실시예 42.
Figure imgf000048_0002
A compound was synthesized in the same manner as in Example 40. MS m / z [M + H] 463. Example 42.
6ᅳ(2-메틸 -5-(4-몰포리노페닐카바모일)페닐아미노) 몰포리노페닐 )-1 -인 다졸 -3-카복스아미드의 제조 6 '(2-Methyl-5- (4-morpholinophenylcarbamoyl) phenylamino) morpholinophenyl) -1 -phosphorus Preparation of Dozol-3-Carboxamides
Figure imgf000049_0001
단계 1. 에틸
Figure imgf000049_0001
Step 1. Ethyl
6-(5— (에록시카보닐 )-2-메틸페닐아미노)— 1- (테트라하이드로— 2//-피란—2-일 인다졸 -3-카복실레이트의 제조  Preparation of 6- (5— (Ethoxycarbonyl) -2-methylphenylamino) — 1- (tetrahydro— 2 //-pyran—2-yl indazole-3-carboxylate
6-브로모 -1— (테트라하이드로 -2//-피란 -2—일 인타졸 -3-카르복실레이트 (200 nig, 0.57國 ol)와 에틸 3—아미노—4-메틸벤조에이트 (102 mg, 0.57 mmol), χ-phos (24.5mg, 0.05隱 ol), ¾C (394mg, 2.85睡 ol)를 2—부탄올 (2mL)에 녹여 탈기한 후 Pd2(dba)3 (31.3 nig, 0.03画 ol)를 넣고 90 °C에서 가열하였다. 5 시간 후 반응이 종결하면 규조토 패드로 여과한 후 에틸아세테이트와 물로 추출하고 모아진 유기층을 무수 황산마그네슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거한 다음에 획득한 잔사를 관 크로마토그래피 (실리카겔， Et0Ac:n41exane = 1:10 → 1:4)를 통해 정제하여 목적화합물인 에틸 6-Bromo-1— (tetrahydro-2 //-pyran-2—yl intazole-3-carboxylate (200 nig, 0.57 wk ol) and ethyl 3-amino—4-methylbenzoate (102 mg , 0.57 mmol), χ-phos (24.5mg, 0.05 隱 ol), ¾C (394mg, 2.85 睡 ol) in 2—butanol (2mL), degassed, and then Pd 2 (dba) 3 (31.3 nig, 0.03 画 ol ) And heated at 90 ° C. After 5 hours, when the reaction was completed, the mixture was filtered through a pad of diatomaceous earth, extracted with ethyl acetate and water, and the combined organic layers were dried over anhydrous magnesium sulfate and filtered. One residue was purified by column chromatography (silica gel, Et0Ac: n41exane = 1:10 → 1: 4) to obtain ethyl as the target compound.
6一 (5- (에특시카보닐 )-2—메틸페닐아미노) -1- (테트라하이드로 -2//—피란— 2-일 )— 인다졸—3—카복실레이트 (107 mg, 42%)를 얻었다. ^ NMR (400 MHz , DMSO- ) δ 8.04 (s, 1H), 7.73 (d, J= 8.9 Hz, 1H), 7.85 (s, 1H), 7.55 (d, J= 8.0 Hz, 1H), 7.39 (d, J= 7.9 Hz, 1H), 7.10 (s, 1H), 7.06 (d, J 8.7 Hz, 1H), 5.76 (d, J = 9.6 Hz, 1H), 4.38 (q, / = 7.0 Hz, 2H), 4.26 (m, 2H), 3.85 (m, 1H), 3.66 (in, 1H), 2.30 (s, 3H), 2.00 (m, 3H), 1.74 (m, 2H), 1.56 (m, 3H), 1.37 (t, J = 7.1 Hz, 3H), 1.27 (t, J = 7.1 Hz, 3H), MS m/z [M+H] 452. 단계 2.  6- (5- (ethoxycarbonyl) -2—methylphenylamino) -1- (tetrahydro-2 // — pyran— 2-yl)-indazole-3 carboxylate (107 mg, 42%) Got it. ^ NMR (400 MHz, DMSO-) δ 8.04 (s, 1H), 7.73 (d, J = 8.9 Hz, 1H), 7.85 (s, 1H), 7.55 (d, J = 8.0 Hz, 1H), 7.39 ( d, J = 7.9 Hz, 1H), 7.10 (s, 1H), 7.06 (d, J 8.7 Hz, 1H), 5.76 (d, J = 9.6 Hz, 1H), 4.38 (q, / = 7.0 Hz, 2H ), 4.26 (m, 2H), 3.85 (m, 1H), 3.66 (in, 1H), 2.30 (s, 3H), 2.00 (m, 3H), 1.74 (m, 2H), 1.56 (m, 3H) , 1.37 (t, J = 7.1 Hz, 3H), 1.27 (t, J = 7.1 Hz, 3H), MS m / z [M + H] 452. Step 2.
6-(5-카복시 -2-메틸페닐아미노)— 1- (테트라하이드로 -2 —피란 -2-일) -1 ―인다졸一 3 6- (5-carboxy-2-methylphenylamino) — 1- (tetrahydro-2 —pyran-2-yl) -1-indazol 一 3
—카복실산의 제조 —Production of Carboxylic Acids
에틸  ethyl
6-(5- (에톡시카보닐 )-2—메틸페닐아미노) -1- (테트라하이드로 -2//-피란 -2-일) 인다졸—3—카복실레이트 (107 mg, 0.24隱 ol)와 THF (1 mL), MeOH (1 mL) , Η20 (1 mL)를 넣고 리튬 히드록사이드 일수화물 (101 mg, 2.4瞧 ol)를 첨가하였다. 40 °C에서 4 시간 동안 교반한 후 반웅이 종료되면 용매를 감압 증류하여 제거한 후 0 °C로 냉각시키고, 물 (3.0 mL)를 넣고, IN HC1 수용액으로 중화하였다. 에틸아세테이트로 추출하고 모아진 유기층을 무수 With 6- (5- (ethoxycarbonyl) -2—methylphenylamino) -1- (tetrahydro-2 //-pyran-2-yl) indazole—3—carboxylate (107 mg, 0.24 隱 ol) THF (1 mL), MeOH (1 mL), Η 2 0 (1 mL) was added and lithium hydroxide monohydrate (101 mg, 2.4 μL) was added. After stirring at 40 ° C. for 4 hours, when the reaction was completed, the solvent was distilled off under reduced pressure, cooled to 0 ° C., water (3.0 mL) was added thereto, and the mixture was neutralized with IN HC1 aqueous solution. The organic layer extracted with ethyl acetate and collected
황산마그네슘으로 건조하여 여과한 후 용매를 감압 증류로 제거하여 After drying over magnesium sulfate and filtration, the solvent was removed by distillation under reduced pressure.
6— (5—카복시 -2—메틸페닐아미노)— 1— (테트라하이드로— 2 ^피란 -2-일 )-L7—인다졸— 3 -카복실산 (86 nig, 91%)를 얻었다. Ή NMR (400 MHz , DMSO—o!;) δ 7.98 (d, J = 8.09 Hz, 1H), 7.81 (s, III), 7.75 (s, 1H), 7.51 (d, J 7.7 Hz, 1H), 7.15 (d, /= 7.8 Hz, 1H), 6.85 (d, /= 8.5 Hz, 2H), 5.52 (d, 7 - 9.6 Hz, 1H), 3.87 (i , 1H), 3.15 (m, 1H), 2.38 (m, 1H), 2.22 (s, 3H), 1.95 (m, 2H), 1.70 (m, 1H), 1.51 (m, 2H), MS m/z [M+H] 396. 단계 3. 6— (5—carboxy-2-methylphenylamino) -1— (tetrahydro—2 ^ pyran-2-yl) -L7-indazole—3-carboxylic acid (86 nig, 91%) was obtained. NMR (400 MHz, DMSO—o !;) δ 7.98 (d, J = 8.09 Hz, 1H), 7.81 (s, III), 7.75 (s, 1H), 7.51 (d, J 7.7 Hz, 1H), 7.15 (d, / = 7.8 Hz, 1H), 6.85 (d, / = 8.5 Hz, 2H), 5.52 (d, 7-9.6 Hz, 1H), 3.87 (i, 1H), 3.15 (m, 1H), 2.38 (m, 1H), 2.22 (s, 3H), 1.95 (m, 2H), 1.70 (m, 1H), 1.51 (m, 2H), MS m / z [M + H] 396.Step 3.
6-(2-메틸— 5-(4-몰포.리노페닐카바모일)페닐아미노) -Λ 4-몰포리노페닐 )-1— (테 트라하이드로 -2 ―피란—2—일 ) -1 —인다졸 -3-카복스아미드의 제조  6- (2-methyl— 5- (4-morpho.linophenylcarbamoyl) phenylamino) -Λ 4-morpholinophenyl) -1— (tetrahydro-2-pyran—2—yl) -1 — is Preparation of Sol-3-Carboxamide
6-(5-카복시 -2-메틸페닐아미노) -1- (테트라하이드로 -2//-피란—2-일 인다졸— 3 ᅳ카복실산 (86 mg, 0.22 mmol ), 4-몰포리노아닐린 (118 mg, 0.66 mmol ), HATU (251 nig, 0.66 mmol), DIPEA (0.11 mL, 0.66 画 ol)를 DMF (lmL)에 녹인 후 실온에서 교반하였다. 2 시간 후 반응이 종결하면 염화나트륨 수용액을 사용하고 에틸아세테이트로 추출한 다음에 모아진 유기충을 무수 황산마그네슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거하여 6- (5-carboxy-2-methylphenylamino) -1- (tetrahydro-2 //-pyran—2-yl indazole— 3 ᅳ carboxylic acid (86 mg, 0.22 mmol), 4-morpholinoaniline (118 mg , 0.66 mmol), HATU (251 nig, 0.66 mmol), DIPEA (0.11 mL, 0.66 画 ol) was dissolved in DMF (lmL), and stirred at room temperature. The collected organic worms were dried over anhydrous magnesium sulfate and filtered, and the solvent was removed by distillation under reduced pressure.
6-(2-메틸— 5-(4-몰포리노페닐카바모일)페닐아미노) -Λ 4-몰포리노페닐 )— 1— (테 트라하이드로 -2//-피란 -2—일) 인다졸 -3ᅳ카복스아미드 (127 mg)를 얻어 더 이상의 정제 없이 다음 반응을 진행하였다. MS m/z [M+H] 716. 단계 4.  6- (2-methyl— 5- (4-morpholinophenylcarbamoyl) phenylamino) -Λ 4-morpholinophenyl) — 1— (tetrahydro-2 //-pyran-2—yl) indazole- 3 ᅳ carboxamide (127 mg) was obtained to proceed to the next reaction without further purification. MS m / z [M + H] 716. Step 4.
6-(2—메틸 -5-(4-몰포리노페닐카바모일)페닐아미노) -yV-(4-몰포리노페닐 )— 1 -인 다졸 -3-카복스아미드의 제조  Preparation of 6- (2—methyl-5- (4-morpholinophenylcarbamoyl) phenylamino) -yV- (4-morpholinophenyl)-1-phosphoric diazole-3-carboxamide
6— (2—메틸 -5-(4—몰포리노페닐카바모일)페닐아미노)— Λ 4-몰포리노페닐 )-1- (테 트라하이드로 -2 -피란 -2-일) 인다졸—3-카복스아미드 (127 mg)를 MeOH (1 mL) 에 녹이고 4M HC1/디옥산 (1 mL)를 첨가하여 실온에서 8 시간동안 교반하였다. 반웅이 종결하면 용매를 감압 증류하여 제거한 후 탄산수소나트륨 수용액을 사용하고 에틸아세테이트로 추출한 다음에 유기층을 무수 황산마그네슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거하여 농축하였다. Prep HPLC로 정제 하여 목적화합물  6— (2—Methyl-5- (4—morpholinophenylcarbamoyl) phenylamino) — Λ 4-morpholinophenyl) -1- (tetrahydro-2-pyran-2-yl) indazole—3- Carboxamide (127 mg) was dissolved in MeOH (1 mL) and 4M HC1 / dioxane (1 mL) was added and stirred at rt for 8 h. When the reaction was completed, the solvent was distilled off under reduced pressure, and then extracted with ethyl acetate, and then the organic layer was dried over anhydrous magnesium sulfate and filtered. The solvent was removed by distillation under reduced pressure and concentrated. Purified by Prep HPLC to target compound
6— (2-메틸 -5— (4-몰포리노페닐카바모일 )페닐아미노) -Λ 4—몰포리노페닐 )-1 -인 다졸 -3-카복스아미드 (60 mg)를 얻었다. ^ NMR (400 MHz, DMS0- ) δ 13.12 (s, 1H), 10.00 (d, J 11.9 Hz, 2H), 8.01 (d, J= 8.7 Hz, 1H), 7.90 (m, 1H), 7.74 (d, J= 9.0 Hz, 2H), 7.61 (d, J = 8.8 Hz, 3H), 7.39 (d, J = 8.1 Hz, 1H), 7.01 (d, J= 8.8 Hz, 1H), 6. 94 (t, J= 8.7 Hz, 4H), 6.83 (m, 1H), 3.74 (m, 81)， 3.07 (m, 8H), 2.54 (s, 3H), 2.31 (s, 3H), MS m/z [M+H] 632. 실시예 43.  6- (2-Methyl-5- (4-morpholinophenylcarbamoyl) phenylamino) -Λ 4-morpholinophenyl) -1 -indazole-3-carboxamide (60 mg) was obtained. ^ NMR (400 MHz, DMS0-) δ 13.12 (s, 1H), 10.00 (d, J 11.9 Hz, 2H), 8.01 (d, J = 8.7 Hz, 1H), 7.90 (m, 1H), 7.74 (d , J = 9.0 Hz, 2H), 7.61 (d, J = 8.8 Hz, 3H), 7.39 (d, J = 8.1 Hz, 1H), 7.01 (d, J = 8.8 Hz, 1H), 6. 94 (t , J = 8.7 Hz, 4H), 6.83 (m, 1H), 3.74 (m, 81), 3.07 (m, 8H), 2.54 (s, 3H), 2.31 (s, 3H), MS m / z [M + H] 632. Example 43.
6-(4-플루오로— 5-(3—플루오로 -5— (트리플루오로메틸 )벤즈아미도) -2-메틸페닐 )-yV 一메틸 -l/ 인다졸 -3—카복스아미드의 제조 6- (4-fluoro— 5- (3—fluoro-5— (trifluoromethyl) benzamido) -2-methylphenyl) -yV Preparation of Monomethyl-1 / indazole-3—carboxamide
Figure imgf000051_0001
단계 1.
Figure imgf000051_0001
Step 1.
6-(4-플루오로 -5-(3-플루오로— 5- (트리플루오로메틸)벤즈아미도)—2—메틸페닐 )-V 6- (4-fluoro-5- (3-fluoro— 5- (trifluoromethyl) benzamido) -2-methylphenyl) -V
-메틸 -1- (테트라하이드로 -2 ^피란 -2—일)— 1/ 인다졸 -3_카복스아미드의 제조 6-(5—아미노—4—플루오로—2—메틸페닐) -그메틸— 1— (테트라하이드로 피란— 2-일 ) 一 1/ 인다졸— 3-카르보아미드 (151 mg, 0.38 mmol), -Methyl-1- (tetrahydro-2 ^ pyran-2—yl) — 1 / indazole-3_carboxamide Preparation 6- (5—amino—4—fluoro—2—methylphenyl) -gmethyl— 1— (tetrahydro pyran— 2-yl) one 1 / indazole— 3-carboamide (151 mg, 0.38 mmol),
3-플루오로 -5- (트리플루오로메틸)벤조산 (87 mg, 0.46 mmol), HATU (433 mg, 1.14 mmol), DIPEA (0.2 ml , 1.1.4i誦 ol)를 DMF (1.5 niL)에 녹인 후 실온에서 교반하였다. 3-fluoro-5 (trifluoromethyl) benzoic acid (87 mg, 0.46 mmol), HATU (433 mg, 1.14 mmol), DIPEA (0.2 ml, 1.1.4iOl) dissolved in DMF (1.5 niL) Then stirred at room temperature.
2시간 후 반웅이 종결하면 염화나트륨 수용액을 사용하고 에틸아세테이트로 추출한 다음에 모아진 유기층을 무수 황산마그네슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거한 후 획득한 잔사를 관 크로마토그래피 (실리카겔,After 2 hours, the reaction was terminated. The reaction mixture was extracted with ethyl acetate, and the combined organic layers were dried over anhydrous magnesium sulfate and filtered. The residue obtained after removing the solvent by distillation under reduced pressure was subjected to column chromatography (silica gel,
EtOAc/n-hexane = 1 ： 2)를 통해 정제하여 목적화합물인 EtOAc / n-hexane = 1: 2) to purify the target compound.
6-(4-플루오로 -5-(3-플루오로— 5— (트리플루오로메틸)벤즈아미도)— 2—메틸페닐) 6- (4-fluoro-5- (3-fluoro— 5— (trifluoromethyl) benzamido) — 2—methylphenyl)
—메틸 -1— (테트라하이드로 -2 "피란 -2-일) 인다졸—3-카복스아미드 (212 mg,—Methyl-1— (tetrahydro-2 “pyran-2-yl) indazole—3-carboxamide (212 mg,
98%)을 얻었다. 단계 2. 98%). Step 2.
6-(4—플루오로 -5-(3—플루오로 -5- (트리플루오로메틸 )벤즈아미도) -2-메틸페닐 N 6- (4—fluoro-5- (3—fluoro-5- (trifluoromethyl) benzamido) -2-methylphenyl N
-메틸 -I 인다졸 -3—카복스아미드의 제조 Preparation of -methyl-I indazole-3—carboxamide
6-(5— (3-(2-시아노프로판 -2-일)벤즈아미도) -2-메틸페닐아미노) - ^메틸 -1— (테트 라하이드로 피란— 2—일)— 1 "인다졸 -3—카복스아미드 (12 mg)를 THF (1 niL)에 녹이고 TFA (0.1 mL)을 첨가하여 실온에서 8 시간 동안 교반하였다. 반웅이 종결하면 용매를 감압 증류하여 제거한 후 탄산수소나트륨 수용액을 사용하고 에틸아세테이트로 추출한 다음에 유기층을 무수 황산마그네슘으로 건조하여 여과하였다. 용매를 감압 증류로 제거하여 농축한다ᅳ Prep HPLC로 정제하여 목적화합물인  6- (5— (3- (2-cyanopropane-2-yl) benzamido) -2-methylphenylamino)-^ methyl-1— (tetrahydropyran— 2—yl) — 1 "indazole -3—Carboxamide (12 mg) was dissolved in THF (1 niL), and TFA (0.1 mL) was added and stirred for 8 hours at room temperature. After extraction with ethyl acetate, the organic layer was dried over anhydrous magnesium sulfate and filtered, and the solvent was removed by distillation under reduced pressure, and then purified by Prep HPLC.
6-(4—플루오로 -5-(3-플루오로 -5- (트리플루오로메틸)벤즈아미도 )-2ᅳ메틸페닐 -메틸— 1/ 인다졸 -3—카복스아미드를 얻었다. 6- (4—fluoro-5- (3-fluoro-5- (trifluoromethyl) benzamido) -2) methylphenyl -Methyl-1 / indazole-3carboxamide was obtained.
Ή NMR (300 MHz , DMS0- ) δ 13.59(s, IH) , 10.51 (s, IH), 8.39 (q, J= 4.6 Hz, IH), 8.12-8.24 (m, 2H), 8.10 (d, J = 9.3 Hz, IH), 7.99 (d, J 8.4 Hz, IH), 7.53 (d, /=.8.0 Hz, IH)， 7.50 (s, IH), 7.33 (d, J 11.5 Hz, IH), 7.22 (dd, ./ = 8.5, 1.3 Hz, IH), 2.83 (d, J 4.6 Hz, 3H), 2.27 (s, 3H) 실시예 44.  NMR (300 MHz, DMS0-) δ 13.59 (s, IH), 10.51 (s, IH), 8.39 (q, J = 4.6 Hz, IH), 8.12-8.24 (m, 2H), 8.10 (d, J = 9.3 Hz, IH), 7.99 (d, J 8.4 Hz, IH), 7.53 (d, /=.8.0 Hz, IH), 7.50 (s, IH), 7.33 (d, J 11.5 Hz, IH), 7.22 (dd, ./= 8.5, 1.3 Hz, IH), 2.83 (d, J 4.6 Hz, 3H), 2.27 (s, 3H) Example 44.
6-(4—플루오로 -2—메틸ᅳ5-(3-메틸— 5- (트리플루오로메틸)벤즈아미도)페닐) -Λ^메 틸 인다졸—3-카복스아미드의 제조  Preparation of 6- (4—Fluoro-2-methyl-2-5- (3-methyl- 5- (trifluoromethyl) benzamido) phenyl) -Λ ^ methyl indazole—3-carboxamide
Figure imgf000052_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.
Figure imgf000052_0001
The title compound was obtained in the same manner as the Example 43.
Ή NMR (300 MHz , DMSC ;) δ 8.38 (q, J = 4.8 Hz, IH), 8.21 (d, J = 8.4 Hz, IH), 7.67 (s, IH), 7.56 (d, J= 7.2 Hz, IH), 7.46—7.52 (m, 2H), 7.32 (s, IH), 7.28 (s, IH), 7.21 (del, J= 8.4， 1.2 Hz, IH), 2.83 (d, /= 4.8 Hz, 3H), 2.41 (s, 3H) , 2.26 (s, 3H) 실시예 45. NMR (300 MHz, DMSC;) δ 8.38 (q, J = 4.8 Hz, IH), 8.21 (d, J = 8.4 Hz, IH), 7.67 (s, IH), 7.56 (d, J = 7.2 Hz, IH), 7.46—7.52 (m, 2H), 7.32 (s, IH), 7.28 (s, IH), 7.21 (del, J = 8.4, 1.2 Hz, IH), 2.83 (d, / = 4.8 Hz, 3H ), 2.41 (s, 3H), 2.26 (s, 3H) Example 45.
6-(4-플루오로— 5— (3—플루오로 -5-메틸벤즈아미도) -2—메틸페닐) 메틸—1/·인다 졸— 3—카복스아미드의 제조  Preparation of 6- (4-Fluoro— 5— (3—Fluoro-5-methylbenzamido) -2-methylphenyl) methyl-1 / .indazol-3carboxamide
Figure imgf000052_0002
Figure imgf000052_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 43.
NMR (300 MHz, C 0D_/4) δ 8.38 (q, /= 4.8 Hz, IH), 8.22 (d, J = 8.4 Hz, IH), 8.08-8.12 (m, 2H), 7.48—7.52 (m, 2H), 7.32 (d, J = 11.7 Hz, IH), 7.22 (dd, J= 8.4, 1.2 Hz, IH), 3.31 (s, 3H), 2.82 (d, J = 4.8 Hz, 3H), 2.26 (s, 3H) 실시예 46. NMR (300 MHz, C 0D_ / 4 ) δ 8.38 (q, / = 4.8 Hz, IH), 8.22 (d, J = 8.4 Hz, IH), 8.08-8.12 (m, 2H), 7.48—7.52 (m, 2H), 7.32 (d, J = 11.7 Hz, IH), 7.22 (dd, J = 8.4, 1.2 Hz, IH), 3.31 (s, 3H), 2.82 (d, J = 4.8 Hz, 3H), 2.26 ( s, 3H) Example 46.
6-(4ᅳ플루오로 -2-메틸— 5-(4-메틸 -3- (트리플루오로메틸)벤즈아미도)페닐) 메 틸 인다졸 -3—카복스아미드의 제조
Figure imgf000053_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. Preparation of 6- (4 ᅳ fluoro-2-methyl— 5- (4-methyl-3- (trifluoromethyl) benzamido) phenyl) methyl indazole-3—carboxamide
Figure imgf000053_0001
The title compound was obtained in the same manner as the Example 43.
'H R (300 MHz , C 0D— ri,) δ 8.38 (q, ./= 4.5 Hz, IH), 8.27 (s, IH), 8.21 (cl, J= 8.7 Hz, IH), 8.16 (del, J= 7.9 Hz, 1.8 Hz, IH), 7.62 (d, /= 8.0 Hz, IH), 7.48-7.54 (m, 2H), 7.31 (d, J= 11.5 Hz, IH), 7.22 (del, /= 8.4, 1.2 Hz, IH), 2.83 (cl, J 4.6 Hz, 3H), 2.69 (s, 3H), 2.26 (s, 3H) 실시예 47. 'HR (300 MHz, C 0D— ri,) δ 8.38 (q, ./= 4.5 Hz, IH), 8.27 (s, IH), 8.21 (cl, J = 8.7 Hz, IH), 8.16 (del, J = 7.9 Hz, 1.8 Hz, IH), 7.62 (d, / = 8.0 Hz, IH), 7.48-7.54 (m, 2H), 7.31 (d, J = 11.5 Hz, IH), 7.22 (del, / = 8.4 , 1.2 Hz, IH), 2.83 (cl, J 4.6 Hz, 3H), 2.69 (s, 3H), 2.26 (s, 3H) Example 47.
6-(5-(4-클로로 -3— (트리플루오로메틸)벤즈아미도) -4-플루오로 -2-메틸페닐)一 메틸 인다졸 -3-카복스아미드의 제조  Preparation of 6- (5- (4-chloro-3— (trifluoromethyl) benzamido) -4-fluoro-2-methylphenyl) l methyl indazole-3-carboxamide
Figure imgf000053_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.
Figure imgf000053_0002
The title compound was obtained in the same manner as the Example 43.
\ NMR (300 MHz, DMSO— d;) δ 13.57 (s, IH), 10.49 (s, IH) , 8.42 (s, IH), 8.38 (q, J= 4.8 Hz, IH), 8.26 (eld, J= 8.4, 2.1 Hz, IH), 8.21 (d, /= 8.4 Hz, IH), 7.93 (cl, J 8.3 Hz, IH), 7.53 (d, J = 7.7 Hz. IH), 7.50 (s, IH), 7.32 (d, J= 11.7 Hz, IH), 7.22 (dd, J 8.4, 1.5 Hz, IH), 2.83 (d, J= 4.5 Hz, 3H), 2.26 (s, 3H) 실시예 48.  \ NMR (300 MHz, DMSO— d;) δ 13.57 (s, IH), 10.49 (s, IH), 8.42 (s, IH), 8.38 (q, J = 4.8 Hz, IH), 8.26 (eld, J = 8.4, 2.1 Hz, IH), 8.21 (d, / = 8.4 Hz, IH), 7.93 (cl, J 8.3 Hz, IH), 7.53 (d, J = 7.7 Hz.IH), 7.50 (s, IH) , 7.32 (d, J = 11.7 Hz, IH), 7.22 (dd, J 8.4, 1.5 Hz, IH), 2.83 (d, J = 4.5 Hz, 3H), 2.26 (s, 3H) Example 48.
6-(4-플루오로— 2-메틸— 5— (3- (트리플루오로메틸)벤즈아미도)페닐) 메틸 -l^인 다졸 -3-카복스아미드의 제조  Preparation of 6- (4-fluoro— 2-methyl— 5— (3- (trifluoromethyl) benzamido) phenyl) methyl − ^ indazole-3-carboxamide
Figure imgf000053_0003
상기 실시예 43과 동일한 방법으로 수'행하여 상기 표제화합물을 얻었다.
Figure imgf000053_0003
The embodiment by performing in the same manner as in Example 43 to give the title compound.
¾ NMR (300 MHz, CD30D- ) δ 8.38 (q, J= 4.7 Hz, IH), 8.32 (s, IH), 8.27 (d, J= 7.9 Hz, IH), 8.21(d, J= 8.4 Hz, IH), 7.99 (d, J- 7.9 Hz, IH), 7.79 (t, J = 7.8 Hz, IH), 7.49-7.56 (m, 2H), 7.32 (d, J = 11.5 Hz, IH), 7.22 (dd, J = 8.4, 1.4 Hz, 1H), 2.83 (cl, J = 4.7 Hz, 3H) , 2.26 (s, 3H) 실시예 49. ¾ NMR (300 MHz, CD 3 0D-) δ 8.38 (q, J = 4.7 Hz, IH), 8.32 (s, IH), 8.27 (d, J = 7.9 Hz, IH), 8.21 (d, J = 8.4 Hz, IH), 7.99 (d, J-7.9 Hz, IH), 7.79 (t, J = 7.8 Hz, IH), 7.49-7.56 (m, 2H), 7.32 (d, J = 11.5 Hz, IH), 7.22 (dd, J = 8.4, 1.4 Hz, 1H), 2.83 (cl, J = 4.7 Hz, 3H), 2.26 (s, 3H) Example 49.
6一 (4-플'루오로—5-(4-플루오로 -3- (트리플루오로메틸)벤즈아미도) -2—메틸페닐)一 /V 一메틸 -1/ 인다졸 -3-카복스아미드의 제조 6一(4-flat in Luo 5- (4-fluoro-3- (trifluoromethyl) benz amido) -2-methylphenyl)一/ V一-l / indazole-3-carboxamide Preparation of Amides
Figure imgf000054_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.
Figure imgf000054_0001
The title compound was obtained in the same manner as the Example 43.
\\ NMR (300 MHz , C¾0D— ) δ 8.30-8.45 (m, 3Η), 8.21 (d, J 8.4 Hz, 1H), 7.47—7.56 (m, 2H), 7.71 (t, J 9.6 Hz, 1H), 7.32 (d, J= 11.5 Hz, 1H), 7.22 (del, J 8.4, 1.4 Hz, 1H), 2.83 (d, J 4.6 Hz, 3H), 2.26 (s, 3H) 실시예 50. \\ NMR (300 MHz, C¾0D—) δ 8.30-8.45 (m, 3Η), 8.21 (d, J 8.4 Hz, 1H), 7.47—7.56 (m, 2H), 7.71 (t, J 9.6 Hz, 1H) 7.32 (d, J = 11.5 Hz, 1H), 7.22 (del, J 8.4, 1.4 Hz, 1H), 2.83 (d, J 4.6 Hz, 3H), 2.26 (s, 3H) Example 50.
6- (4-플루오로— 5- (2-플루오로 -5- (트리플루오로메틸 )벤즈아미도) -2-메틸페닐) -yV -메틸 인다졸 -3-카복스아미드의 제조  Preparation of 6- (4-Fluoro— 5- (2-fluoro-5- (trifluoromethyl) benzamido) -2-methylphenyl) -yV-methyl indazole-3-carboxamide
Figure imgf000054_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.
Figure imgf000054_0002
The title compound was obtained in the same manner as the Example 43.
NMR (300 MHz, DMS0一 of;) δ 13.60 (s, 1H), 10.41 (s, 1H) , 8.37 (dd, J= 6.5, 3.0 Hz, 1H), 8.22 (cl, J 8.3 Hz, 1H) , 8.13-8.05 (m, 1H)， 8.00 (d, J = 8.1 Hz, 1H), 7.76 (d, /= 8.0 Hz, 1H), 7.61 (t, 7= 8.9 Hz, 1H), 7.54-7.47 (m, 1H), 7.31 (d, J 11.6 Hz, 1H) , 7.22 (d, J = 8.4 Hz, 1H)， 2.83 (d, J = 4.7 Hz, 3H), 2.25 (s, 3H). 실시예 51.  NMR (300 MHz, DMS0 of of) δ 13.60 (s, 1H), 10.41 (s, 1H), 8.37 (dd, J = 6.5, 3.0 Hz, 1H), 8.22 (cl, J 8.3 Hz, 1H), 8.13-8.05 (m, 1H), 8.00 (d, J = 8.1 Hz, 1H), 7.76 (d, / = 8.0 Hz, 1H), 7.61 (t, 7 = 8.9 Hz, 1H), 7.54-7.47 (m , 1H), 7.31 (d, J 11.6 Hz, 1H), 7.22 (d, J = 8.4 Hz, 1H), 2.83 (d, J = 4.7 Hz, 3H), 2.25 (s, 3H). Example 51.
6-(4—플루오로 -5-(4—플루오로ᅳ2— (트리플루오로메틸)벤즈아미도) -2—메틸페닐 )一 -메틸 -I 인다졸—3-카복스아미드의 제조  Preparation of 6- (4—Fluoro-5- (4—Fluoro ᅳ 2— (trifluoromethyl) benzamido) -2—methylphenyl) 一 -methyl-I indazole—3-carboxamide
Figure imgf000054_0003
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. \\ NM (500 MHz , DMSOrf;) δ 10.41 (s, 1H) , 8.35 (s, 1H), 8.20 (d, J= 8.4 Hz, 1H), 7.86-7.69 (in, 2H), 7.67 (d, J= 7.9 Hz, 2H), 7.48 (s, 1H), 7.28 (cl, J = 11.6 Hz, 1H), 7.20 (d, ./ = 8.4 Hz, 1H), 2.82 (cl, J= 4.6 Hz, 3H)， 2.23 (s, '3H). 실시예 52.
Figure imgf000054_0003
The title compound was obtained in the same manner as the Example 43. \\ NM (500 MHz, DMSOrf;) δ 10.41 (s, 1H), 8.35 (s, 1H), 8.20 (d, J = 8.4 Hz, 1H), 7.86-7.69 (in, 2H), 7.67 (d, J = 7.9 Hz, 2H), 7.48 (s, 1H), 7.28 (cl, J = 11.6 Hz, 1H), 7.20 (d, ./ = 8.4 Hz, 1H), 2.82 (cl, J = 4.6 Hz, 3H ), 2.23 (s, ' 3H). Example 52.
6-(4-플루오로 -2-메틸— 5— (4- (트리플루오로메톡시 )벤즈아미도)페닐 )ᅳ 메틸— 1/ 인다졸 -3-카복스아미드의 제조  Preparation of 6- (4-fluoro-2-methyl— 5— (4- (trifluoromethoxy) benzamido) phenyl) ᅳ methyl— 1 / indazole-3-carboxamide
Figure imgf000055_0001
Figure imgf000055_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
]H NMR (300 MHz, CDC1,) δ 2.25 (s, 311), 3.09 (d, J 5.0 Hz 3H), 7.07 (m, 2H), 7.21 (m, 1H), 7.37 (m, 3H), 7.94 (m, 2H), 8.03 (s, 1H), 8.31 Cd, J = 7.8 Hz: 1H), 8.40 (d, J 8.3 Hz, 1H), 10.4 (s, 1H) 실시예 53. ] H NMR (300 MHz, CDC1,) δ 2.25 (s, 311), 3.09 (d, J 5.0 Hz 3H), 7.07 (m, 2H), 7.21 (m, 1H), 7.37 (m, 3H), 7.94 (m, 2H), 8.03 (s, 1H), 8.31 Cd, J = 7.8 Hz : 1H), 8.40 (d, J 8.3 Hz, 1H), 10.4 (s, 1H) Example 53.
6— (4-플루오로 -5-(2—메톡시—3- (트리플루오로메틸)벤즈아미도) -2—메틸페닐)— 메틸 인다졸 -3-카복스아미드의 제조  6— (4-Fluoro-5- (2—methoxy—3- (trifluoromethyl) benzamido) -2—methylphenyl) — Preparation of methyl indazole-3-carboxamide
Figure imgf000055_0002
Figure imgf000055_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 43.
'Η NMR (300 MHz , C 0D— ί/4) δ 8.29 (q, /= 4.5 Hz, 1Η), 8.19 (d, /= 8.5 Hz, 1H), 7.88 (d, J = 7.6 Hz, 1H), 7.82 (dd J= 7.9， 1.7 Hz, 1H), 7.71 (d, J: 8,0 Hz, 1H), 7.51 (s, 1H), 7.40 (t, J 7.7 Hz, 1H)' 7.30 (d, J = 11.7 Hz, 1H), 7.17 (dd, J 8.3, 1.4 Hz, 1H), 3.89 (s, 3H), 2.84 (d, J= 4.5 Hz, 3H), 2.25 (s, 3H) 실시예 54. 'Η NMR (300 MHz, C 0D— ί / 4 ) δ 8.29 (q, / = 4.5 Hz, 1Η), 8.19 (d, / = 8.5 Hz, 1H), 7.88 (d, J = 7.6 Hz, 1H) , 7.82 (dd J = 7.9, 1.7 Hz, 1H), 7.71 (d, J : 8,0 Hz, 1H), 7.51 (s, 1H), 7.40 (t, J 7.7 Hz, 1H) '7.30 (d, J = 11.7 Hz, 1H), 7.17 (dd, J 8.3, 1.4 Hz, 1H), 3.89 (s, 3H), 2.84 (d, J = 4.5 Hz, 3H), 2.25 (s, 3H) Example 54.
6-(4-플루오로 -5-(2-메록시 -5- (트리플루오로메틸 )벤즈아미도) -2—메틸페닐 t 메틸 -l^인다졸—3ᅳ카복스아미드 제조  Preparation of 6- (4-fluoro-5- (2-methoxy-5- (trifluoromethyl) benzamido) -2—methylphenyl t methyl-1 ^ indazole—3′carboxamide
Figure imgf000055_0003
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.
Figure imgf000055_0003
The title compound was obtained in the same manner as the Example 43.
NMR (300 MHz , DMSO— ;) δ 10.16 (s, 1H), 8.26 (q, /= 4.7 Hz, 1H), 8.18 (d, J 8.4 Hz, 1H), 8.10 (s, 1H), 8.00 (d, J 7.9 Hz, 1H), 7.92 (del, J = 9.1, 2.4 Hz, 1H), 7.55 (s, 1H), 7.44 (d, J = 8.8 Hz, 1H), 7.30 (d, J = 11.7 Hz, 1H), 7.15 (del, J 8.4, 1.4 Hz, 1H), 4.06 (s, 3H), 2.84 (d, J 4.6 Hz, 3H), 2.25 (s, 3H) 실시예 55. NMR (300 MHz, DMSO— ; ) δ 10.16 (s, 1H), 8.26 (q, / = 4.7 Hz, 1H), 8.18 (d, J 8.4 Hz, 1H), 8.10 (s, 1H), 8.00 (d , J 7.9 Hz, 1H), 7.92 (del, J = 9.1, 2.4 Hz, 1H), 7.55 (s, 1H), 7.44 (d, J = 8.8 Hz, 1H), 7.30 (d, J = 11.7 Hz, 1H), 7.15 (del, J 8.4, 1.4 Hz, 1H), 4.06 (s, 3H), 2.84 (d, J 4.6 Hz, 3H), 2.25 (s, 3H) Example 55.
6一 (4—플루오로 -5-(3-메톡시 -5- (트리플루오로메틸)벤즈아미도) -2-메틸페닐) -yV" 메틸— 1/ 인다졸—3-카복스아미드의 제조  Preparation of 6- (4—fluoro-5- (3-methoxy-5- (trifluoromethyl) benzamido) -2-methylphenyl) -yV "methyl- 1 / indazole- 3-carboxamide
Figure imgf000056_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.
Figure imgf000056_0001
The title compound was obtained in the same manner as the Example 43.
NMR (300 MHz, C 0D— ) δ 2.27 (s, 3Η), 2.99 (s, 3H), 3.93 (s, 3H), 7.23 (m, 2H), 7.39 (s, 1H), 7.50 (s, 1H), 7.61 (d, J= 7.9 Hz , 1H), 7.76 (s, 1H), 7.83 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H) 실시예 56. .  NMR (300 MHz, C 0D—) δ 2.27 (s, 3Η), 2.99 (s, 3H), 3.93 (s, 3H), 7.23 (m, 2H), 7.39 (s, 1H), 7.50 (s, 1H ), 7.61 (d, J = 7.9 Hz, 1H), 7.76 (s, 1H), 7.83 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H) Example 56..
6-(4-플루오로— 5-(2—하이드록시 -5- (트리플루오로메틸 )벤즈아미도)—2-메틸페닐 ) — 메틸 인다졸— 3-카복스아미드의 제조  Preparation of 6- (4-fluoro— 5- (2—hydroxy-5- (trifluoromethyl) benzamido) —2-methylphenyl) —methyl indazole— 3-carboxamide
Figure imgf000056_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.
Figure imgf000056_0002
The title compound was obtained in the same manner as the Example 43.
NMR (300 MHz, DMS으 δ 13.60 (s, 1H), 12.71 (s, 1H) , 10.16 (s, 1H), 8.35 (q, J = 4.9 Hz, 1H), 8.30 (s, 1H), 8.22 (d, /= 8.4 Hz, 1H) , 8.09 (d, J= 8.0 Hz, 1H), 7.80 (dd, J= 8.4, 1.9 Hz, 1H), 7.51 (s, 1H), 7.34 (d, J 12.1 Hz, 1H), 7.22 (dd, J= 8.0, 2.5 Hz, 1H) , 3.17 (s, 3H), 2.84 (d, J= 4.7 Hz, 3H) , 2.24 (s, 3H) 실시예 57.  NMR (300 MHz, δ 13.60 (s, 1H), 12.71 (s, 1H), 10.16 (s, 1H), 8.35 (q, J = 4.9 Hz, 1H), 8.30 (s, 1H), 8.22 ( d, / = 8.4 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.80 (dd, J = 8.4, 1.9 Hz, 1H), 7.51 (s, 1H), 7.34 (d, J 12.1 Hz , 1H), 7.22 (dd, J = 8.0, 2.5 Hz, 1H), 3.17 (s, 3H), 2.84 (d, J = 4.7 Hz, 3H), 2.24 (s, 3H) Example 57.
6-(4-플루오로 -5— (4-하이드록시 -3- (트리플루오로메틸)벤즈아미도) -2—메틸페닐 ) 一 메틸— 1^인다졸—3-카복스아미드의 제조
Figure imgf000057_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. Preparation of 6- (4-fluoro-5— (4-hydroxy-3- (trifluoromethyl) benzamido) -2-methylphenyl) one methyl—1 ^ indazole—3-carboxamide
Figure imgf000057_0001
The title compound was obtained in the same manner as the Example 43.
NMR (300 MHz , DMS0— ) δ 13.62 (s, 1H), 9.87 (s, 1H), 8.30-8.40 (m, 1H), 8.20 (d, J= 8.4 Hz, 1H), 8.09 (s, 1H), 7.95 (d, J= 8.5 Hz, 1H), 7.45—7.53 (in, 2H), 7.25 (d, J = 12.0 Hz, 1H), 7.21 (d, J = 8.5 Hz, 1H), 6.86 (d, J = 8.2 Hz, 1H), 2.83 (d, J = 4.4 Hz, 3H), 2.24 (s, 3H) 실시예 58.  NMR (300 MHz, DMS0—) δ 13.62 (s, 1H), 9.87 (s, 1H), 8.30-8.40 (m, 1H), 8.20 (d, J = 8.4 Hz, 1H), 8.09 (s, 1H) , 7.95 (d, J = 8.5 Hz, 1H), 7.45—7.53 (in, 2H), 7.25 (d, J = 12.0 Hz, 1H), 7.21 (d, J = 8.5 Hz, 1H), 6.86 (d, J = 8.2 Hz, 1H), 2.83 (d, J = 4.4 Hz, 3H), 2.24 (s, 3H) Example 58.
6一 (4ᅳ플루오로— 2-메틸— 5ᅳ (3ᅳ (트리플루오로메록시)벤: ：아미도)페닐)—^메틸— 1/ 인다졸 -3—카복스아미드의 제조  Preparation of 6- (4'fluoro- 2-methyl--5 '(3' (trifluoromethoxy) ben: amido) phenyl) -methyl- 1 / indazole-3-carboxamide
Figure imgf000057_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.
Figure imgf000057_0002
The title compound was obtained in the same manner as the Example 43.
NMR (300 MHz, CD,0D-rf,) 8 8.32 (q, J 4.7 Hz, 1H), 8.21 (d, J = 8.4 Hz, 1H), 8.03 (d, J 7.6 Hz, 1H), 7.93 (s, 1H), 7.69 (t, J = 7.9 Hz, 1H)ᅳ 7.62 (cl, /= 8.3 Hz, 1H), 7.45-7.54 (m, 2H), 7.30 (d, J = 11.7 Hz, 1H), 7.21 (del, / = 8.4， 1.2 Hz, 1H), 2.83 (d, J 4.7 Hz, 3H), 2.26 (s, 3H) 실시예 59.  NMR (300 MHz, CD, 0D-rf,) 8 8.32 (q, J 4.7 Hz, 1H), 8.21 (d, J = 8.4 Hz, 1H), 8.03 (d, J 7.6 Hz, 1H), 7.93 (s , 1H), 7.69 (t, J = 7.9 Hz, 1H) ᅳ 7.62 (cl, / = 8.3 Hz, 1H), 7.45-7.54 (m, 2H), 7.30 (d, J = 11.7 Hz, 1H), 7.21 (del, / = 8.4, 1.2 Hz, 1H), 2.83 (d, J 4.7 Hz, 3H), 2.26 (s, 3H) Example 59.
6— (5-(4—아미노— 3- (트리플루오로메틸 )벤즈아미도)—4- ^루오로—2—메틸페닐)一그 메틸 -1/ 인다졸ᅳ 3-카복스아미드의 제조  6— (5- (4—amino— 3- (trifluoromethyl) benzamido) —4- ^ luoro-2-methylphenyl) IG Methyl-1 / indazolazole 3-carboxamide Preparation
Figure imgf000057_0003
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.
Figure imgf000057_0003
The title compound was obtained in the same manner as the Example 43.
lti NMR (300 MHz, CD30D-o¾) δ 2.27 (s, 3H), 2.99 (s, 3H), 6.9 (d, J= 8.8 Hz, 1H), 7.14 (d, J= 11.5 Hz, 1H), 7.25 (d, J= 8.3 Hz, 1H), 7.55 (m, 2H), 7.91 (d, J = 8.9 Hz, 1H), 8.07 (s, 1H), 8.26 (d, J = 9.5 Hz, 1H) 실시예 60. lti NMR (300 MHz, CD 3 0D-o¾) δ 2.27 (s, 3H), 2.99 (s, 3H), 6.9 (d, J = 8.8 Hz, 1H), 7.14 (d, J = 11.5 Hz, 1H) , 7.25 (d, J = 8.3 Hz, 1H), 7.55 (m, 2H), 7.91 (d, J = 8.9 Hz, 1H), 8.07 (s, 1H), 8.26 (d, J = 9.5 Hz, 1H) Example 60.
6一(5-(4-아미노 -3— (트리플루오로메톡시)벤즈아미도) -4—플루오로— 2—메틸페닐 N -메틸 -1/·인다졸—3-카복스아미드의 제조  Preparation of 6- (5- (4-amino-3— (trifluoromethoxy) benzamido) -4—fluoro-2—methylphenyl N-methyl-1 / .indazole—3-carboxamide
Figure imgf000058_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.
Figure imgf000058_0001
The title compound was obtained in the same manner as the Example 43.
] \ NMR (300 MHz , DMS0— ) δ 9.82 (s, 1H) , 8.32 (q, J = 4.4 Hz, 1H) , 8.19 (d, J 8.4 Hz, 1H), 7.76 (cld, J= 11.6， 2.4 Hz, 1H), 7.49 (s, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.26 (d, /= 11.6 Hz, 1H), 7.19 (dd, /= 8.4， 1.2 Hz, 1H), 6.85 (cl, J = 8.4 Hz, 1H), 6.09 (s, 1H), 2 (d, J = 4.7 Hz, 3H), 2.25 (s, 3H) 실시예 61. ] \ NMR (300 MHz, DMS0—) δ 9.82 (s, 1H), 8.32 (q, J = 4.4 Hz, 1H), 8.19 (d, J 8.4 Hz, 1H), 7.76 (cld, J = 11.6 ， 2.4 Hz, 1H), 7.49 (s, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.26 (d, / = 11.6 Hz, 1H), 7.19 (dd, / = 8.4, 1.2 Hz, 1H), 6.85 (cl, J = 8.4 Hz, 1H), 6.09 (s, 1H), 2 (d, J = 4.7 Hz, 3H), 2.25 (s, 3H) Example 61.
6-(4-플루오로— 5ᅳ(4-플루오로 -3- (트리플루오로메톡시)벤즈아미도)— 2-메틸페닐) — ^메틸 인다졸 -3—카복스아미드의 제조 6- (4-fluoro-5-eu (3- (trifluoromethoxy) benz amido) 4-fluoro-2-methylphenyl) - ^ Preparation of methyl indazole-3-carboxamide
Figure imgf000058_0002
Figure imgf000058_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 43.
\ NMR (300 MHz, DMS0—쑈) δ 8.46-8.37 (m, 1H), 8.21 (d, / = 8.4 Hz, 1H), 8.18-8.07 (m, 2H), 7.77—7.67 (m, 1H), 7.46-7.54 (in, 2H), 7.32 (d, J= 11.5 Hz, 1H), 7.21 (dd, /= 8.4, 0.8 Hz, 1H), 2,83 (d, J= 4.6 Hz, 3H), 2.26 (s, 3H) 실시예 62.  \ NMR (300 MHz, DMS0—Hz) δ 8.46-8.37 (m, 1H), 8.21 (d, / = 8.4 Hz, 1H), 8.18-8.07 (m, 2H), 7.77—7.67 (m, 1H), 7.46-7.54 (in, 2H), 7.32 (d, J = 11.5 Hz, 1H), 7.21 (dd, / = 8.4, 0.8 Hz, 1H), 2,83 (d, J = 4.6 Hz, 3H), 2.26 (s, 3H) Example 62.
6-(4-플루오로 -2ᅳ메틸 -5— (6- (트리플루오로메틸)니코티아미도)페닐 )—7^메틸 인다졸 -3-카복스아미드의 제조  Preparation of 6- (4-fluoro-2 ᅳ methyl-5— (6- (trifluoromethyl) nicothiamido) phenyl) —7 ^ methyl indazole-3-carboxamide
Figure imgf000058_0003
Figure imgf000058_0003
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 4 3.
NMR (300 MHz, CD30D_¾) δ 2.29 (s, 3H), 2.99 (s, 3H), 7.20 (m, 2H), 7.52 (s, 1H), 7.71 (d( J= 7.8 Hz, 1H), 7.97 (d, J= 8.2 Hz, 1H), 8.28 (d, J= 8.4 Hz, 1H), 8.56 (d, J二 6.7 Hz, 1H), 9.23 (s, 1H) 실시예 63. NMR (300 MHz, CD 3 0D_¾) δ 2.29 (s, 3H), 2.99 (s, 3H), 7.20 (m, 2H), 7.52 (s, 1H), 7.71 (d ( J = 7.8 Hz, 1H), 7.97 (d, J = 8.2 Hz, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.56 (d, J 二 6.7 Hz, 1H), 9.23 (s, 1H) Example 63.
6- (4—플루오로— 2-메틸 -5_(2- (트리플루오로메틸 )이소니코틴아미도)페닐) 메틸 — 인다졸—3-카복스아미드의 제조  Preparation of 6- (4—Fluoro— 2-methyl-5_ (2- (trifluoromethyl) isonicotinamido) phenyl) methyl — indazole—3-carboxamide
Figure imgf000059_0001
Figure imgf000059_0001
싱-기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Singh-Sep Example 43.
Ή NMR (300 MHz , CD:i0D-rf,) δ 2.29 (s, 3H), 2.99 (s, 3H), 7.25 (m, 2H), 7.50NMR (300 MHz, CD : i 0D-rf,) δ 2.29 (s, 3H), 2.99 (s, 3H), 7.25 (m, 2H), 7.50
(s, 1H), 7.69 (d, J = 7.9 Hz, 1H), 8.13 (ό, J = 4.9 Hz, 1H), 8.27 (m, 2H), 8.92 (d, 7= 5.1 Hz, 1H) 실시예 64. (s, 1H), 7.69 (d, J = 7.9 Hz, 1H), 8.13 (ό, J = 4.9 Hz, 1H), 8.27 (m, 2H), 8.92 (d, 7 = 5.1 Hz, 1H) Examples 64.
6-(5-(6- (디메틸아미노)— 5—메틸니코틴아미도) -4—플루오로 -2-메틸페닐 )-그메틸- 1/ 인다졸 -3ᅳ카복스아미드의 제조 ' Preparation of 6- (5- (6- (dimethylamino) — 5—methylnicotinamido) -4—fluoro-2-methylphenyl) -gmethyl-1 / indazole- 3 3carboxamide ''
Figure imgf000059_0002
Figure imgf000059_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 43.
Ή NMR (300 MHz , C¾0D— ί ) δ 2.27 (s, 3Η), 2.37 (s, 3H), 2.99 (s, 3H), 3.01 (s, 6H), 7.14 (d, J = 11.5 Hz, 1H), 7.24 (dd, J = 1.3 Hz, J 8.5 Hz, 1H), 7.50 (s, 1H), 7.58 (d, J 7.9 Hz, 1H), 7.95 (d, /= 2.4 Hz, 1H) , 8.26 (dd, J = 0.8 Hz, / = 8.4 Hz, 1H), 8.60 (d, J = 2.2 Hz, 1H) 실시예 65. MR NMR (300 MHz, C¾0D— ί) δ 2.27 (s, 3Η), 2.37 (s, 3H), 2.99 (s, 3H), 3.01 (s, 6H), 7.14 (d, J = 11.5 Hz, 1H) , 7.24 (dd, J = 1.3 Hz, J 8.5 Hz, 1H), 7.50 (s, 1H), 7.58 (d, J 7.9 Hz, 1H), 7.95 (d, / = 2.4 Hz, 1H), 8.26 (dd , J = 0.8 Hz, / = 8.4 Hz, 1H), 8.60 (d, J = 2.2 Hz, 1H) Example 65.
6ᅳ (5— (4—클로로—3— (2—시아노프로판— 2-일)벤즈아미도) -4ᅳ플로로 -2—메틸페닐 )- 메틸— I 인다졸 -3-카복스아미드의 제조  6 '(5— (4—Chloro—3— (2—Cyanopropane- 2-yl) benzamido) -4 ᅳ fluoro-2-2-methylphenyl) -methyl- I indazole-3-carboxamide Produce
Figure imgf000059_0003
Figure imgf000059_0003
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 43.
]H NMR (300 MHz, DMS0— ί¾) δ 13.6 (bs, 1H), 10.3 (s, 1H), 8.41 (q, 1H, /= 4.2 Hz), 8.23 (d, 1H, J = 8.4 Hz), 8.06 (d, 1H, J 1.8 Hz), 8.00 (dd, 1H, J = 8.4， 1.8 Hz), 7.75 (d, 1H, J= 8.4 Hz), 7.52 (d, 1H, J= 3.9 Hz), 7.50 (d, 1H, J = 3.9 Hz), 7.33 (d, 1H, J= 11.7 Hz), 7.23 (dd, 1H, J = 8.4, 1.2 Hz), 2.84 (d, 3H, J = 4.8 Hz), 2.26 (s, 3H), 1.86 (s, 6H) 실시예 66. ] H NMR (300 MHz, DMS0—ί¾) δ 13.6 (bs, 1H), 10.3 (s, 1H), 8.41 (q, 1H, / = 4.2 Hz), 8.23 (d, 1H, J = 8.4 Hz), 8.06 (d, 1H, J 1.8 Hz), 8.00 (dd, 1H, J = 8.4, 1.8 Hz), 7.75 (d, 1H, J = 8.4 Hz), 7.52 (d, 1H, J = 3.9 Hz), 7.50 (d, 1H, J = 3.9 Hz), 7.33 (d, 1H, J = 11.7 Hz), 7.23 (dd, 1H, J = 8.4, 1.2 Hz), 2.84 (d, 3H, J = 4.8 Hz), 2.26 (s, 3H), 1.86 (s, 6H) Example 66.
6-(5-(3— (2-시아노프로판—2-일)— 5— (트리플루오로메틸)벤즈아미도) -4-플로로 -2- 메틸페닐 )-그메틸 -1^인다졸—3—카복스아미드의 제조  6- (5- (3— (2-cyanopropane—2-yl) — 5— (trifluoromethyl) benzamido) -4-fluoro-2-methylphenyl) -gmethyl-1 ^ indazole —3—Manufacture of Carboxamides
Figure imgf000060_0001
Figure imgf000060_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
NMR (300 MHz , DMS0— ) δ 13.6 (bs, 1H), 10.5 (s, 1H), 8.40-8.38 (m, 2H), 8.32 (s, 1H), 8.23 (d, 1H, J = 8.4 Hz), 8.07 (s, 1H), 7.55 (d, 1H, J = 8.4 Hz), 7.52 (d, 1H, J = 1.2 Hz), 7.35 (d, 1H, /= 11.7 Hz), 7.24 (dd, 1H, J = 8.4, 1.2 Hz), 2.84 (d, 3H, J = 4.8 Hz), 2.27 (s, 3H), 1.80 (s, 6H) 실시예 67.  NMR (300 MHz, DMS0—) δ 13.6 (bs, 1H), 10.5 (s, 1H), 8.40-8.38 (m, 2H), 8.32 (s, 1H), 8.23 (d, 1H, J = 8.4 Hz) , 8.07 (s, 1H), 7.55 (d, 1H, J = 8.4 Hz), 7.52 (d, 1H, J = 1.2 Hz), 7.35 (d, 1H, / = 11.7 Hz), 7.24 (dd, 1H, J = 8.4, 1.2 Hz), 2.84 (d, 3H, J = 4.8 Hz), 2.27 (s, 3H), 1.80 (s, 6H) Example 67.
6-(5-(3—(2-시아노프로판 -2—일) -5—플루오로벤즈아미도 )-4—플로로—2-메틸페닐) - /V"메틸 인다졸— 3-카복스아미드의 제조  6- (5- (3— (2-cyanopropane-2—yl) -5—fluorobenzamido) -4—fluoro-2-methylphenyl)-/ V "methyl indazole— 3-carbox Preparation of Amides
Figure imgf000060_0002
Figure imgf000060_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
¾ NMR (300 MHz, DMSO—d δ 13.63 (s, 1H), 10.36 (s, 1H), 8.41-8.37 (m, 1H)， 8.22-8.20 (d, J= 8.4 Hz, 1H), 7.98—7.96 (t, J= 1.7 Hz, 1H), 7.80-7.76 (d, /= 9.6 Hz, 1H), 7.66-7.62 (m, 1H), 7.51 (s, 1H), 7.48 (s, 1H), 7.34—7.30 (d, /= 11.6 Hz, 1H), 7.24-7.20 (del, J = 8.4， 1.4 Hz, 1H), 2.84-2.82 (d, J 4.7 Hz, 3H), 2.26 (s, 3H), 1.75 (s, 6H). 실시예 68. ¾ NMR (300 MHz, DMSO—d δ 13.63 (s, 1H), 10.36 (s, 1H), 8.41-8.37 (m, 1H), 8.22-8.20 (d, J = 8.4 Hz, 1H), 7.98—7.96 (t, J = 1.7 Hz, 1H), 7.80-7.76 (d, / = 9.6 Hz, 1H), 7.66-7.62 (m, 1H), 7.51 (s, 1H), 7.48 (s, 1H), 7.34— 7.30 (d, / = 11.6 Hz, 1H), 7.24-7.20 (del, J = 8.4, 1.4 Hz, 1H), 2.84-2.82 (d, J 4.7 Hz, 3H), 2.26 (s, 3H), 1.75 ( s, 6H) Example 68.
6-(5-(3-아미노 -5- (트리플루오로메틸 )벤즈아미도)ᅳ 4-플루오로 -2-메틸페닐 )- 메틸 인다졸 -3—카복스아미드의 제조  Preparation of 6- (5- (3-amino-5- (trifluoromethyl) benzamido) ᅳ 4-fluoro-2-methylphenyl) -methyl indazole-3—carboxamide
Figure imgf000060_0003
Figure imgf000060_0003
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다ᅳ ¾刚 R (300 MHz, DMSO-οί;) δ 13.6 (bs, 1H), 10.2 (s, 1H) , 8.41 (q, 1H, J= 4.5 Hz), 8.22 (d, 1H, J= 8.4 Hz), 7.50 (s, 1H), 7.48 (d, 1H, J = 7.8 Hz), 7.38
Figure imgf000061_0001
실시예 69. The title compound was obtained by the same method as the Example 43 '¾ 刚 R (300 MHz, DMSO-οί;) δ 13.6 (bs, 1H), 10.2 (s, 1H), 8.41 (q, 1H, J = 4.5 Hz), 8.22 (d, 1H, J = 8.4 Hz), 7.50 (s, 1H), 7.48 (d, 1H, J = 7.8 Hz), 7.38
Figure imgf000061_0001
Example 69.
6一 (5-(3- (디메틸아미노) -5- (트리플루오로메틸 )벤즈아미도) -4—플루오로 -2-메틸 페닐 )— 메틸ᅳ 1/ 인다졸— 3—카복스아미드의 제조  6- (5- (3- (dimethylamino) -5- (trifluoromethyl) benzamido) -4—fluoro-2-methylphenyl) —methyl ᅳ 1 / indazole—3—carboxamide Produce
l, , 6 l,, 6
Figure imgf000061_0002
Figure imgf000061_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 43.
\ NMR (300 MHz , DMS0— ) δ 10.2 (s, 1H), 8.41 (q, 1H, / = 4.2 Hz), 8.22 (d, 1H, / = 8.4 Hz), 7.50 (s, 1H), 7.49 (d, 1H, /= 7.8 Hz), 7.40 (s, III), 7.38 (s, 1H), 7.31 (d, 1H, J 11.4 Hz), 7.23 (del, 1H, J= 8.1, 1.2 Hz), 7.08 (s, 1H), 6.26 (t, 1H, J= 5.1 Hz), 3.22 (td, 2H, J= 6.3， 5.7 Hz), 2.84 (d, 3H, J = 4.8 Hz), 2.45 (t, 2H, 6.6 Hz), 2.26 (s, 3H), 2.19 (s, 6H) 실시예 71.  \ NMR (300 MHz, DMS0—) δ 10.2 (s, 1H), 8.41 (q, 1H, / = 4.2 Hz), 8.22 (d, 1H, / = 8.4 Hz), 7.50 (s, 1H), 7.49 ( d, 1H, / = 7.8 Hz), 7.40 (s, III), 7.38 (s, 1H), 7.31 (d, 1H, J 11.4 Hz), 7.23 (del, 1H, J = 8.1, 1.2 Hz), 7.08 (s, 1H), 6.26 (t, 1H, J = 5.1 Hz), 3.22 (td, 2H, J = 6.3, 5.7 Hz), 2.84 (d, 3H, J = 4.8 Hz), 2.45 (t, 2H, 6.6 Hz), 2.26 (s, 3H), 2.19 (s, 6H) Example 71.
6-(5-(3— ((디메틸아미노)에틸) (메틸)아미노 )-5— (트리플루오로메틸)벤즈아미도) -4-플루오로 -2-메틸페닐 메틸 -1^인다졸—3-카복스아미드의 제조  6- (5- (3— ((dimethylamino) ethyl) (methyl) amino) -5— (trifluoromethyl) benzamido) -4-fluoro-2-methylphenyl methyl-1 ^ indazole—3 Preparation of Carboxamide
Figure imgf000061_0003
Figure imgf000061_0003
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. Ή NMR (300 MHz , DMSO—o δ 10.27 (s, 1H), 8.38 (q, J 4.5 Hz, 1H), 8.21 (d, J = 8.3 Hz, 1H), 7.45—7.52 (m, 4H), 7.31 (d, J= 11.4 Hz, 1H) , 7.22 (del, J = 8.4, 1.4 Hz, III), 7.06 (s, 1H), 3.54 (t, /= 6.9 Hz, 2H), 3.02 (s, 3H), 2.83 (d, J = 4.6 Hz, 3H), 2.39 (t, J = 6.9 Hz, 2H), 2.26 (s, 3H), 2.18 (s, 3H) 실시예 72. The title compound was obtained in the same manner as the Example 43 . NMR (300 MHz, DMSO—o δ 10.27 (s, 1H), 8.38 (q, J 4.5 Hz, 1H), 8.21 (d, J = 8.3 Hz, 1H), 7.45—7.52 (m, 4H), 7.31 (d, J = 11.4 Hz, 1H), 7.22 (del, J = 8.4, 1.4 Hz, III), 7.06 (s, 1H), 3.54 (t, / = 6.9 Hz, 2H), 3.02 (s, 3H) 2.83 (d, J = 4.6 Hz, 3H), 2.39 (t, J = 6.9 Hz, 2H), 2.26 (s, 3H), 2.18 (s, 3H) Example 72.
6—(4-플루오로— 2—메틸 -5ᅳ(3—몰포리노— 5- (트리플루오로메틸)벤즈아미도)페닐) -yV 一메틸 인다졸 -3-카복스아미드의 제조  Preparation of 6— (4-fluoro— 2—methyl-5 ′ (3—morpholino— 5- (trifluoromethyl) benzamido) phenyl) -yV one methyl indazole-3-carboxamide
Figure imgf000062_0001
Figure imgf000062_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
:H NMR (300 MHz , DMSO-οί;) δ 13.63 (s, 1Η), 1.0.34 (s, 1H), 8.41 (d, J 4.8 Hz, 1H), 8.21 (d, J= 8.3 Hz, 1H), 7.76 (s, 1H), 7.67 (s, 1H), 7.50 (s, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.41 (s, 1H), 7.32 (d, J 11.6 Hz, 1H), 7.22 (dd, J 8.4, 1.3 Hz, 1H), 3.75 (dd, J= 12.1, 7.1 Hz, 4H), 3.33-3.25 (i , 4H), 2.82 (d, J = 4.7 Hz, 3H), 2.26 (s, 3H). 실시예 73. : H NMR (300 MHz, DMSO-οί;) δ 13.63 (s, 1Η), 1.0.34 (s, 1H), 8.41 (d, J 4.8 Hz, 1H), 8.21 (d, J = 8.3 Hz, 1H ), 7.76 (s, 1H), 7.67 (s, 1H), 7.50 (s, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.41 (s, 1H), 7.32 (d, J 11.6 Hz, 1H), 7.22 (dd, J 8.4, 1.3 Hz, 1H), 3.75 (dd, J = 12.1, 7.1 Hz, 4H), 3.33-3.25 (i, 4H), 2.82 (d, J = 4.7 Hz, 3H) , 2.26 (s, 3 H). Example 73.
6-(4ᅳ플루오로 -2ᅳ메틸 -5-(3— (메틸아미노 )-5— (트리플루오로메틸)벤즈아미도)페 닐 메틸 -I 인다졸—3—카복스아미드의 제조  Preparation of 6- (4 ᅳ fluoro-2 ᅳ methyl-5- (3— (methylamino) -5— (trifluoromethyl) benzamido) phenyl methyl-I indazole—3—carboxamide
Figure imgf000062_0002
Figure imgf000062_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
¾ NMR (300 MHz, DMS0一^) δ 13.6 (bs, 1H), 10.2 (s, 1H), 8.35 (q, 1H, J= 4.8 Hz), 8.22 (d, 1H, J= 8.4 Hz), 7.50—7.46 (m, 211) , 7.42 (s, 1H), 7.34 (s, 1H), 7.31 (d, 1H, J= 11.4 Hz), 7.23 (d, 1H, J 8.4 Hz), 6.97 (s, 1H), 6.42 (q, 1H, J 5.1 Hz), 2.84 (d, 3H, J = 4.8 Hz), 2.78 (d, 3H, J= 4.8 Hz), 2.26 (s, 3H). 실시예 74. ¾ NMR (300 MHz, DMS0 一 ^) δ 13.6 (bs, 1H), 10.2 (s, 1H), 8.35 (q, 1H, J = 4.8 Hz), 8.22 (d, 1H, J = 8.4 Hz), 7.50 —7.46 (m, 211), 7.42 (s, 1H), 7.34 (s, 1H), 7.31 (d, 1H, J = 11.4 Hz), 7.23 (d, 1H, J 8.4 Hz), 6.97 (s, 1H ), 6.42 (q, 1H, J 5.1 Hz), 2.84 (d, 3H, J = 4.8 Hz), 2.78 (d, 3H, J = 4.8 Hz), 2.26 (s, 3H). Example 74.
6ᅳ (5— (2— (디메틸아미노) -5- (트리플루오로메틸)벤즈아미도)—4-플루오로— 2—메틸 페닐) 메틸ᅳ 1^인다졸 -3-카복스아미드의 제조 상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.Preparation of 6 ′ (5— (2— (dimethylamino) -5- (trifluoromethyl) benzamido) —4-fluoro— 2—methyl phenyl) methyl ᅳ 1 ^ indazole-3-carboxamide The title compound was obtained in the same manner as the Example 43.
i NMR (300 MHz, DMS0- ) δ 13.63(s, 1Η) , 10.34 (s, 1H), 8.41 (d, 4.8 Hz, 1H), 8.21 (d, /二 8.3 Hz, 1H), 7.76 (s, 1H), 7.67 (s, 1H), 7.50 (s, 1H) , 7.48 (d, J 8.0 Hz, III), 7.41 (s, 1H), 7.32 (d, J 11.6 Hz, 1H), 7.22 (dd, J = 8.4, 1.3 Hz, 1H), 3.75 (del, J = 12.1, 7.1 Hz, 5H), 3.33—3.25 (m, 4H), 2.82 (cl, /= 4.7 Hz, 3H), 2.26 (s, 3H). 실시예 75.  i NMR (300 MHz, DMS0-) δ 13.63 (s, 1Η), 10.34 (s, 1H), 8.41 (d, 4.8 Hz, 1H), 8.21 (d, / 2 8.3 Hz, 1H), 7.76 (s, 1H), 7.67 (s, 1H), 7.50 (s, 1H), 7.48 (d, J 8.0 Hz, III), 7.41 (s, 1H), 7.32 (d, J 11.6 Hz, 1H), 7.22 (dd, J = 8.4, 1.3 Hz, 1H), 3.75 (del, J = 12.1, 7.1 Hz, 5H), 3.33—3.25 (m, 4H), 2.82 (cl, / = 4.7 Hz, 3H), 2.26 (s, 3H ). Example 75.
6-(4-플루오로 -2ᅳ메틸 -5-(2— (4-메틸피페라진—1-일 ) -5— (트리플루오로메틸)벤즈 아미도)페닐 메틸 -1 ^인다졸 -3—카복스아미드의 제조  6- (4-Fluoro-2 ᅳ methyl-5- (2— (4-methylpiperazin—1-yl) -5— (trifluoromethyl) benz amido) phenyl methyl-1 ^ indazole-3 —Manufacture of Carboxamides
Figure imgf000063_0001
Figure imgf000063_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
¾ NMR (300 MHz, DMSO— ;) δ 13.61 (s, 1H), 10.52 (s, 1H), 8.35 (d, J = 5.3 Hz, 1H), 8.23 (d, J= 8.4 Hz, 1H)， 7.90 (cl, J 2.4 Hz, 1H), 7.82 (t , J= 8.8 Hz, 2H), 7.50 (s, 1H), 7.41 (d, J 8.7 Hz, 1H), 7.32 (d, = 11.8 Hz, 1H), 7.21 (dd, J= 8.5， 1.3 Hz, 1H), 3.66-3.55 (m, 5H ) , 3.33 (d, J= 6.5 Hz, 5H), 2.87 (s, 3H), 2.84 (d, J 4.7 Hz, 3H)， 2.26 (s, 4H), 1.81—1.73 (m, 3H). 실시예 76. ¾ NMR (300 MHz, DMSO—;) δ 13.61 (s, 1H), 10.52 (s, 1H), 8.35 (d, J = 5.3 Hz, 1H), 8.23 (d, J = 8.4 Hz, 1H), 7.90 (cl, J 2.4 Hz, 1H), 7.82 (t, J = 8.8 Hz, 2H), 7.50 (s, 1H), 7.41 (d, J 8.7 Hz, 1H), 7.32 (d, = 11.8 Hz, 1H) , 7.21 (dd, J = 8.5, 1.3 Hz, 1H), 3.66-3.55 (m, 5H), 3.33 (d, J = 6.5 Hz, 5H), 2.87 (s, 3H), 2.84 (d, J 4.7 Hz , 3H), 2.26 (s, 4H), 1.81-1.73 (m, 3H). Example 76.
6-{4—플루오로 -2ᅳ메틸 -5— [3-(2— (피를리딘— 1-일-에틸아미노)— 5—트리플루오로메 틸-벤조일아미노]페닐 인다졸 -3—카복시산 메틸아미드의 제조  6- {4—Fluoro-2 ᅳ methyl-5— [3- (2— (Pyridin— 1-yl-ethylamino) — 5—trifluoromethyl-benzoylamino] phenyl indazole-3—carboxy Preparation of Acid Methylamide
Figure imgf000063_0002
Figure imgf000063_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
¾ NMR (300 MHz, DMSO-fl [；) δ 10.18 (s, 1H), 8.34—8.31 (d, /= 5.0 Hz, 1H), 8.22-8.19 (d, J= 8.4 Hz, 1H), 7.50-7.47 (m, 2H), 7.39 (s, 2H) , 7.31-7.27 (d, J= 11.3 Hz, 1H), 7.22-7.19 (dd, J= 8.3, 1.4 Hz, 1H), 7.07 (s, 1H), 6.32-6.28 (t, J = 5.4 Hz, 1H), 3.39 (s, 1H) , 3.28-3.21 (m, 4H), 2.84-2.83 (d, J = 4.6 Hz, 3H), 2.65-2.61 (t, J= 6.7 Hz, 2H), 2.26 (s, 3H), 1.71-1.67 (p, J= 3.0 Hz, 4H), 1.23 (s, 2H). 실시예 77. ¾ NMR (300 MHz, DMSO-fl [;) δ 10.18 (s, 1H), 8.34—8.31 (d, / = 5.0 Hz, 1H), 8.22-8.19 (d, J = 8.4 Hz, 1H), 7.50- 7.47 (m, 2H), 7.39 (s, 2H), 7.31-7.27 (d, J = 11.3 Hz, 1H), 7.22-7.19 (dd, J = 8.3, 1.4 Hz, 1H), 7.07 (s, 1H) , 6.32-6.28 (t, J = 5.4 Hz, 1H), 3.39 (s, 1H), 3.28-3.21 (m, 4H), 2.84-2.83 (d, J = 4.6 Hz, 3H), 2.65-2.61 (t , J = 6.7 Hz, 2H), 2.26 (s, 3H), 1.71-1.67 (p, J = 3.0 Hz, 4H), 1.23 (s, 2H). Example 77.
6- ( 4-플루오로 -2-메틸—5— (3-( (테트라하이드로 -2/ 피란 -4—일 )아미노 ) -5- ( 루오로메틸)벤즈아미도)페닐) 메틸 - 인다졸 -3-카복스아미드의 제조  6- (4-Fluoro-2-methyl—5— (3- ((tetrahydro-2 / pyran-4-yl) amino) -5- (luoromethyl) benzamido) phenyl) methyl-indazole Preparation of 3-Carboxamide
Figure imgf000064_0001
Figure imgf000064_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
'Η隱 (300 MHz , CD,0D-i4) δ 1.55 (m, 2H), 2.03 (m, 2H), 2.27 (s, 3H), 2.99 (s, 3H), 3.56 (m, 3H), 3.95 (in, 2H), 7.05 (s, 1H), 7.15 (d, J= 11.8 Hz, 111)， 7.25 (dd, J= 1.4 Hz, /= 8.4 Hz, 7.39 (m, 2H), 7.50 (s, 1H), 7.60 (d, J 7.8 Hz, 1H), 8.27 (del, J = 1.4 Hz, J = 8.4 Hz. 1H) 실시예 78. 'Η 隱 (300 MHz, CD, 0D-i 4 ) δ 1.55 (m, 2H), 2.03 (m, 2H), 2.27 (s, 3H), 2.99 (s, 3H), 3.56 (m, 3H), 3.95 (in, 2H), 7.05 (s, 1H), 7.15 (d, J = 11.8 Hz, 111), 7.25 (dd, J = 1.4 Hz, / = 8.4 Hz, 7.39 (m, 2H), 7.50 (s , 1H), 7.60 (d, J 7.8 Hz, 1H), 8.27 (del, J = 1.4 Hz, J = 8.4 Hz. 1H) Example 78.
6-(4-플루오로 -2-메틸— 5-(3— (피페라진 -1-일 ) -5- (트리플루오로메틸)벤즈아미도)  6- (4-fluoro-2-methyl— 5- (3— (piperazin-1-yl) -5- (trifluoromethyl) benzamido)
Figure imgf000064_0002
Figure imgf000064_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
NMR (300 MHz, DMS()-d;) δ 13.7 (bs, 1H), 10.4 (s, 1H), 8.83 (s, 1H), 8.42 (q, 1H, J 4.8 Hz), 8.23 (dd, 1H, /= 8.4, 2.7 Hz), 7.78 (s, 1H), 7.74 (s, 1H), 7.51-7.47 (in, 3H), 7.34 (d, 1H, J= 11.4 Hz), 7.23 (d, 1H, J= 8.4 Hz), 3.56-3.40 (m, 4H), 3.30-3.26 (in, 4H), 2.83 (d, 3H, J= 4.5 Hz), 2.27 (s, 3H) 실시예 79.  NMR (300 MHz, DMS ()-d;) δ 13.7 (bs, 1H), 10.4 (s, 1H), 8.83 (s, 1H), 8.42 (q, 1H, J 4.8 Hz), 8.23 (dd, 1H , / = 8.4, 2.7 Hz), 7.78 (s, 1H), 7.74 (s, 1H), 7.51-7.47 (in, 3H), 7.34 (d, 1H, J = 11.4 Hz), 7.23 (d, 1H, J = 8.4 Hz), 3.56-3.40 (m, 4H), 3.30-3.26 (in, 4H), 2.83 (d, 3H, J = 4.5 Hz), 2.27 (s, 3H) Example 79.
6-(4-플루오로— 2-메틸 -5— (3-(4—메틸피페라진 -1—일 )-5— (트리플루오로메틸 )벤즈 아미도)페닐 메틸 -1^인다졸 -3-카복스아미드의 제조  6- (4-fluoro— 2-methyl-5— (3- (4—methylpiperazin-1—yl) -5— (trifluoromethyl) benz amido) phenyl methyl-1 ^ indazole-3 Preparation of Carboxamide
Figure imgf000064_0003
Figure imgf000064_0003
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
H 丽 R (300 MHz, DMSO-fiO δ 13.66 (s, 1H), 10.37 (s, 1H), 8.43 (d, J 4.7 Hz, 1H), 8.24 (d, J 8.1 Hz, 1H), 7.83 (s, l! ), 7.77 (s, 1H), 7.56 (s, 1H) 7.53 (s, 1H), 7.51 (cl, /= 8.0 Hz, H ), 7.35 (d, /= 11.6 Hz, 1H), 7.24 (dd /= 8.4， 1.3 Hz, 1H), 4.13 (cl, /= 11.0 Hz, 2H), 3.58 (d, /= 10.3 Hz, 2H) 3.17 (t, /= 11.5 Hz, 4H), 2.90 (s, 3H), 2.85 (d, J= 4'.7 Hz, 3H) , 2.30 (d J = 6.4 Hz, 3H). 실시예 80. H δ R (300 MHz, DMSO-fiO δ 13.66 (s, 1H), 10.37 (s, 1H), 8.43 (d, J 4.7 Hz, 1H), 8.24 (d, J 8.1 Hz, 1H), 7.83 (s, l!), 7.77 (s, 1H), 7.56 (s, 1H) 7.53 (s, 1H), 7.51 (cl, / = 8.0 Hz, H), 7.35 (d, / = 11.6 Hz, 1H), 7.24 (dd / = 8.4, 1.3 Hz, 1H), 4.13 (cl, / = 11.0 Hz, 2H), 3.58 (d, / = 10.3 Hz, 2H) 3.17 (t, / = 11.5 Hz, 4H), 2.90 (s, 3H), 2.85 (d, J = 4 ' .7 Hz, 3H), 2.30 (d J = 6.4 Hz, 3H). Example 80.
6一 (5— (3-(4-에틸피레라진 -1-일 ) -5- (트리플루오로메틸)벤즈아미도) -4-플루오로一 2一메틸페닐 )— 메틸 -1/·인다졸 _3-카복스아미드의 제조  6- (5-— (3- (4-ethylpyrazin-1-yl) -5- (trifluoromethyl) benzamido) -4-fluoro 一 2 一 methylphenyl) —methyl-1 / .indazole _3- Preparation of Carboxamide
Figure imgf000065_0001
Figure imgf000065_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
Ή NMR (300 MHz, DMSO—οί;) δ 13.6 (bs, 1H), 10.3 (s, 1H), 8.41 (q, 1H, J= 4.5 Hz), 8.23 (d, 1H, 8.4 Hz), 7.75 (s, 1H), 7.63 (s, 1H), 7.51 (s, 1H), 7.50 (cl, 1H, /= 8.1 Hz), 7.37 (s, 1H), 7.33 (cl, 1H, /= 11.4 Hz), 7.24 (del, 1H, J = 8.4， 1.2 Hz), 3.33-3.32 (m, 8H), 2.84 (cl, 3H, J= 4.8 Hz), 2.41 (q, 2H, J = 7.2 Hz), 2.26 (s, 3H), 1.06 (t, 3H, J = 7.2 Hz) 실시예 81. MR NMR (300 MHz, DMSO—οί;) δ 13.6 (bs, 1H), 10.3 (s, 1H), 8.41 (q, 1H, J = 4.5 Hz), 8.23 (d, 1H, 8.4 Hz), 7.75 ( s, 1H), 7.63 (s, 1H), 7.51 (s, 1H), 7.50 (cl, 1H, / = 8.1 Hz), 7.37 (s, 1H), 7.33 (cl, 1H, / = 11.4 Hz), 7.24 (del, 1H, J = 8.4, 1.2 Hz), 3.33-3.32 (m, 8H), 2.84 (cl, 3H, J = 4.8 Hz), 2.41 (q, 2H, J = 7.2 Hz), 2.26 (s , 3H), 1.06 (t, 3H, J = 7.2 Hz) Example 81.
(R)-6— (5— (3— (3- (디메틸아미노)피를리딘 -1—일 )—5— (트리플루오로메틸)벤즈아口 도) -4—플루오로 -2—메틸페닐) 메틸 인다졸 -3—카복스아미드의 제조  (R) -6— (5— (3— (3- (dimethylamino) pyridin-1—yl) —5— (trifluoromethyl) benzazide degree) -4—fluoro-2—methylphenyl ) Preparation of Methyl Indazole-3—Carboxamide
Figure imgf000065_0002
Figure imgf000065_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
¾ NMR (300 MHz, DMSO- ) δ 13.62 (s, 1H), 10.25 (s, 1H), 8.38 (q, J = 4.5 Hz, 1H), 8.21 (d, J 8.3 Hz, 1H), 7.44-7.53 (ηι, 3H), 7.34 (s, 1H), 7.31 (d, J= 11.8 Hz, 1H), 7.22 (dd, J= 8.4， 1.4 Hz, 1H), 6.93 (s, 1H), 3.44-3.62 (m, 2H), 3.20-3.40 (m, 2H), 3.13 (t, J = 8.7 Hz, 1H), 2.83 (d, J= 4.7 Hz, 3H)， 2.26(s, 3H), 2.12-2.30 (m, 1H), 2.22 (s, 6H), 1.78-1.89 (m, 1H) 실시예 82. ¾ NMR (300 MHz, DMSO-) δ 13.62 (s, 1H), 10.25 (s, 1H), 8.38 (q, J = 4.5 Hz, 1H), 8.21 (d, J 8.3 Hz, 1H), 7.44-7.53 (ηι, 3H), 7.34 (s, 1H), 7.31 (d, J = 11.8 Hz, 1H), 7.22 (dd, J = 8.4, 1.4 Hz, 1H), 6.93 (s, 1H), 3.44-3.62 ( m, 2H), 3.20-3.40 (m, 2H), 3.13 (t, J = 8.7 Hz, 1H), 2.83 (d, J = 4.7 Hz, 3H), 2.26 (s, 3H), 2.12-2.30 (m , 1H), 2.22 (s, 6H), 1.78-1.89 (m, 1H) Example 82.
6— (4—플루오로 -2-메틸 -5-(3— (4—메틸 -1，4-디아제판ᅭ1ᅳ일 )-5- (트리플루오로메틸 ) 벤즈아미도)페닐 )-^메틸— l 인다졸 -3-카복스아미드의 제조
Figure imgf000066_0001
6- (4-fluoro-2-methyl-5- (3- (4-methyl-1,4-diazepan-1 euil yo) methyl-5- (trifluoromethyl) benz amido) phenyl) methyl ^ — Preparation of indazole-3-carboxamides
Figure imgf000066_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 43 .
NMR (300 MHz, DMSO— δ 10.26 (s, 1H), 8.38 (q, /= 4.5 Hz, 1H), 8.21 (d, J 8.3 Hz, 1H), 7.43-7.52 (m, 4H) , 7.31 (d, J = 11.5 Hz, 1H), 7.22 (del, J = 8.4, 1.3 Hz, 1H), 7.07 (s, 1H), 3.62 (t, J= 4.7 Hz, 2H), 3.53 (t, J = 6.3 Hz, 2H), 2.83 (cl, /= 4.6 Hz, 3H), 2.63 (t, J= 4.7 Hz, 2H), 2.45 (t, J= 6.0 Hz, 2H), 2.26 (s, 3H), 2.25 (s, 3H), 1.85—1.96 (m, 2H) 실시예 83.  NMR (300 MHz, DMSO— δ 10.26 (s, 1H), 8.38 (q, / = 4.5 Hz, 1H), 8.21 (d, J 8.3 Hz, 1H), 7.43-7.52 (m, 4H), 7.31 (d , J = 11.5 Hz, 1H), 7.22 (del, J = 8.4, 1.3 Hz, 1H), 7.07 (s, 1H), 3.62 (t, J = 4.7 Hz, 2H), 3.53 (t, J = 6.3 Hz , 2H), 2.83 (cl, / = 4.6 Hz, 3H), 2.63 (t, J = 4.7 Hz, 2H), 2.45 (t, J = 6.0 Hz, 2H), 2.26 (s, 3H), 2.25 (s , 3H), 1.85-1.96 (m, 2H) Example 83.
6-(4-플루오로 -5-(3- (핵사하이드로피롤로 [1,2— a]피라진 2(1H)—일 )-5— (트리플루 오로메틸)벤즈아미도) -2-메틸페닐) 메틸 - 1^인다졸 -3—카복스아미드의 제조  6- (4-fluoro-5- (3- (nucleohydropyrrolo [1,2—a] pyrazine 2 (1H) —yl) -5— (trifluoromethyl) benzamido) -2-methylphenyl ) Preparation of Methyl-1 ^ indazole-3—carboxamide
Figure imgf000066_0002
Figure imgf000066_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
¾匪 R (300 MHz, CDsOD-rf,) δ 8.37 (q, J = 4.6 Hz, 1H), 8.20 (d, /= 8.3 Hz, 1H), 7.76 (s, 1H), 7.61 (s, 1H), 7.50 (s, 1H), 7.47 (d, /= 7.8 Hz, 1H), 7.39 (s, 1H), 7.31 (d, J= 11.5 Hz, 1H), 7.21 (del, J 8.6， 1.3 Hz, 1H), 4.01 (d, J= 11.2 Hz, 1H), 3.85 (d, J 11.8 Hz, 1H), 3.14-2.96 (m, 2H), 2.91—2.79 (m, 1H), 2.84 (d, J= 4.8 Hz, 3H)， 2.26 (s, 3H), 2.24-2.14 (m, 1H), 2.13-1.95 (m, 2H), 1.93-1.78 (m, 1H), 1.78-1.60 (m, 2H), 1.48-1.32 (m, 1H) 실시예 84. ¾ 匪 R (300 MHz, CDsOD-rf,) δ 8.37 (q, J = 4.6 Hz, 1H), 8.20 (d, / = 8.3 Hz, 1H), 7.76 (s, 1H), 7.61 (s, 1H) , 7.50 (s, 1H), 7.47 (d, / = 7.8 Hz, 1H), 7.39 (s, 1H), 7.31 (d, J = 11.5 Hz, 1H), 7.21 (del, J 8.6, 1.3 Hz, 1H ), 4.01 (d, J = 11.2 Hz, 1H), 3.85 (d, J 11.8 Hz, 1H), 3.14-2.96 (m, 2H), 2.91—2.79 (m, 1H), 2.84 (d, J = 4.8 Hz, 3H), 2.26 (s, 3H), 2.24-2.14 (m, 1H), 2.13-1.95 (m, 2H), 1.93-1.78 (m, 1H), 1.78-1.60 (m, 2H), 1.48- 1.32 (m, 1 H) Example 84.
6-(4-플루오로— 5— (3-( ( (2-하이드록시에틸) (메틸)아미노) -5- (트리플루오로메틸 ) 벤즈아미도)—2—메틸페닐 )—^메틸— 1/ 인다졸 -3-카복스아미드의 제조  6- (4-fluoro— 5— (3- (((2-hydroxyethyl) (methyl) amino) -5- (trifluoromethyl) benzamido) —2—methylphenyl) — ^ methyl— 1 / Preparation of indazole-3-carboxamide
Figure imgf000066_0003
Figure imgf000066_0003
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
¾ NMR (300 MHz, DMSO-애 δ 8.37 (q, J= 4.6 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 7.54-7.43(m, 3H), 7.30 (d, J= 11.4 Hz, 1H), 7.21 (dd, J= 8.3， 1.3 Hz, 1H), 7.09 (s, 1H), 3.63-3.54 (m, 2H), 3.54-3.47 (m, 2H), 2.83 (d, J= 4.7 Hz, 3H), 2.26 (s, 3H) 실시예 85. ¾ NMR (300 MHz, DMSO-A δ 8.37 (q, J = 4.6 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 7.54-7.43 (m, 3H), 7.30 (d, J = 11.4 Hz, 1H), 7.21 (dd, J = 8.3, 1.3 Hz, 1H), 7.09 (s, 1H), 3.63-3.54 (m, 2H), 3.54-3.47 (m, 2H), 2.83 (d, J = 4.7 Hz, 3H), 2.26 (s, 3H) Example 85.
(S)— 6-(5-(3—(3- (디메틸아미노)피를리딘 -1-일 )-5- (트리플루오로메틸)벤즈아口 도)— 4—폴루오로 -2-메틸페닐 )— 메틸 인다졸— 3-카복스아미드의 제조  (S) — 6- (5- (3— (3- (dimethylamino) pyridin-1-yl) -5- (trifluoromethyl) benzazide degree) — 4—Polouro-2- Methylphenyl) —Methyl Indazole—Preparation of 3-Carboxamide
Figure imgf000067_0001
Figure imgf000067_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
NMR (300 MHz , DMSO- ) δ 13.58 (s, 1Η), 10.20 (s, 1H), 8.31-8.28 (t, J = 5.0 Hz, 1H), 8.23-8.20 (cl, /= 8.3 Hz, 1H), 7.55-7.50 (m, 2H) , 7.47-7.46 (d, J= 2.9 Hz, 1H), 7.34 (s, 1H), 7.31-7.27 (d, J 11.3 Hz, 1H), 7.23—7.20 (d, J 8.4 Hz, 1H), 6.93 (s, 1H), 3.59—3.46 (m, 2H), 3.21-3.12 (del, J = 15.9, 7.5Hz, 2H), 2.85-2.83 (d, J=4.7 Hz, 3H), 2.26 (s, 3H), 2.22 (s, 6H), 1.90一 1.82 (m, 1H), 1.24 (s, 1H), 0.88—0.81 (ni, 1H). 실시예 86.  NMR (300 MHz, DMSO-) δ 13.58 (s, 1Η), 10.20 (s, 1H), 8.31-8.28 (t, J = 5.0 Hz, 1H), 8.23-8.20 (cl, / = 8.3 Hz, 1H) , 7.55-7.50 (m, 2H), 7.47-7.46 (d, J = 2.9 Hz, 1H), 7.34 (s, 1H), 7.31-7.27 (d, J 11.3 Hz, 1H), 7.23—7.20 (d, J 8.4 Hz, 1H), 6.93 (s, 1H), 3.59—3.46 (m, 2H), 3.21-3.12 (del, J = 15.9, 7.5 Hz, 2H), 2.85-2.83 (d, J = 4.7 Hz, 3H), 2.26 (s, 3H), 2.22 (s, 6H), 1.90 一 1.82 (m, 1H), 1.24 (s, 1H), 0.88—0.81 (ni, 1H). Example 86.
6-(4-플루오로 -2-메틸 -5— (3-(4—메틸설포닐)피페라진 -1-일)ᅳ 5— (트리플루오로메 틸)벤즈아미도)페닐)—^메틸— 인다졸 -3—카복스아미드의 제조  6- (4-fluoro-2-methyl-5— (3- (4—methylsulfonyl) piperazin-1-yl) ᅳ 5— (trifluoromethyl) benzamido) phenyl) — ^ methyl— Preparation of indazole-3—carboxamide
Figure imgf000067_0002
Figure imgf000067_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
¾ NMR (300 MHz , DMS으^) δ 13.6 (bs, 1H), 10.3 (s, 1H) , 8.41 (q, 1H, J 4.8 Hz), 8.23 (d, 1H, J= 8.4 Hz), 7.79 (s, 1H), 7.69 (s, 1H), 7.51 (s, 1H), 7.47 (s, 1H), 7.34 (cl, 1H, J= 11.4 Hz), 7.24 (dd, 1H, J = 8.4， 1.2 Hz), 3.48—3.45 (m, 4H), 3.28-3.27 (m, 4H), 2.94 (s, 3H), 2.84 (d, 3H, J 4.5 Hz), 2.27 (s, 3H) 실시예 87. ¾ NMR (300 MHz, DMS) δ 13.6 (bs, 1H), 10.3 (s, 1H), 8.41 (q, 1H, J 4.8 Hz), 8.23 (d, 1H, J = 8.4 Hz), 7.79 ( s, 1H), 7.69 (s, 1H), 7.51 (s, 1H), 7.47 (s, 1H), 7.34 (cl, 1H, J = 11.4 Hz), 7.24 (dd, 1H, J = 8.4, 1.2 Hz ), 3.48—3.45 (m, 4H), 3.28-3.27 (m, 4H), 2.94 (s, 3H), 2.84 (d, 3H, J 4.5 Hz), 2.27 (s, 3H) Example 87.
6— (5-(3-(4—아세틸피페라진— 1-일) -5— (트리플루오로메틸)벤즈아미도) -4-플루오 로 -2-메틸페닐 )—^메틸 -1^인다졸 -3-카복스아미드의 제조  6— (5- (3- (4—acetylpiperazin— 1-yl) -5— (trifluoromethyl) benzamido) -4-fluoro-2-methylphenyl) — ^ methyl-1 ^ indazole Preparation of 3-Carboxamide
Figure imgf000067_0003
Figure imgf000067_0003
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ΊΉ NMR (300 MHz , DMSO— ) δ 10.33 (s, 1H), 8.39 (q, /= 5.5 Hz, 1H)'8.21 (d, J 8.3 Hz, 1H), 7.76 (s, 1H), 7.66 (s, 1H), 7.52-7.39 (m, 3H), 7.32 (d, J = 11.5 Hz, 1H), 7.22 (del, /= 8.2 Hz, 1.5 Hz, 1H), 3.66-3.56 (m, 4H), 3.41-3.34 (m, 4H), 2.83 (d, J 4.5 Hz, 3H), 2.26 (s, 3H), 2.05 (s, 3H) 실시예 88. The title compound was obtained in the same manner as the Example 43. Ί Ή NMR (300 MHz, DMSO- ) δ 10.33 (s, 1H), 8.39 (q, / = 5.5 Hz, 1H) '8.21 (d, J 8.3 Hz, 1H), 7.76 (s, 1H), 7.66 ( s, 1H), 7.52-7.39 (m, 3H), 7.32 (d, J = 11.5 Hz, 1H), 7.22 (del, / = 8.2 Hz, 1.5 Hz, 1H), 3.66-3.56 (m, 4H), 3.41-3.34 (m, 4H), 2.83 (d, J 4.5 Hz, 3H), 2.26 (s, 3H), 2.05 (s, 3H) Example 88.
6一 (4—플루오로 -2-메틸— 5-(3— (4—니코티노일피페라진ᅩ 1—일) -5-(
Figure imgf000068_0001
6 一 (4—fluoro-2-methyl— 5- (3— (4—nicotinoylpiperazine ᅩ 1—day) -5- (
Figure imgf000068_0001
)벤즈아미도)페닐시메틸- /^인다졸—3—카복스아미드의 제조 ) Benzamido) Phenylmethylmethyl-/ ^ indazol-3 Preparation of Carboxamide
Figure imgf000068_0002
Figure imgf000068_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
]H NMR (300 MHz , DMSO-0 δ 8.71—8.64 (m, 2Η), 8.40 (q, /= 4.6 Hz, 1H), 8.21. (d, J= 8.4 Hz, 1H), 7.90 (dt , J 7.7， 2.0 Hz, 1H), 7.78 (s, 1H), 7.68 (s, 1H), 7.54-7.45 (m, 3H), 7.43 (s, 1H), 7.32 (d, J 11.5 Hz, 1H), 7.21 (del, J 8.5， 1.3 Hz, 1H), 3.89-3.70 (m, 2H), 3.62-3.38 (m, 6H), 2.82 (cl, J = 4.5 Hz, 3H), 2.26 (s, 3H) 실시예 89. ] H NMR (300 MHz, DMSO-0 δ 8.71—8.64 (m, 2Η), 8.40 (q, / = 4.6 Hz, 1H), 8.21. (D, J = 8.4 Hz, 1H), 7.90 (dt, J 7.7, 2.0 Hz, 1H), 7.78 (s, 1H), 7.68 (s, 1H), 7.54-7.45 (m, 3H), 7.43 (s, 1H), 7.32 (d, J 11.5 Hz, 1H), 7.21 (del, J 8.5, 1.3 Hz, 1H), 3.89-3.70 (m, 2H), 3.62-3.38 (m, 6H), 2.82 (cl, J = 4.5 Hz, 3H), 2.26 (s, 3H) Examples 89.
6-(5— (3-(4-(2- (디메틸아미노) -2-옥소에틸)피페라진 -1-일) -5- (트리플루오로메 틸 )벤즈아미도)—4-플루오로 -2-메틸페닐 )—그메틸— 1/ 인다졸 -3-카복스아미드의 제조  6- (5— (3- (4- (2- (dimethylamino) -2-oxoethyl) piperazin-1-yl) -5- (trifluoromethyl) benzamido) —4-fluoro- Preparation of 2-methylphenyl) —gmethyl— 1 / indazole-3-carboxamide
Figure imgf000068_0003
Figure imgf000068_0003
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
¾ NMR (300 MHz, DMS0— ο{;) δ 13.59 (s, 1H), 10.31 (s, 1H), 8.33 (d, / = 4.8 Hz, 1H), 8.22 (d, J= 8.4 Hz, 1H) , 7.79 (s, 1H), 7.75 (s, 1H), 7.49 (d, J = 8.1 Hz, 3H), 7.31 (d, J 11.5 Hz, 1H), 7.21 (d, J = 8.5 Hz, 1H), 4.34 (s, 2H), 4.03 (s, 2H), 3.53 (s, 1H), 2.94 (d, J = 5.9 Hz, 6H), 2.84 (d, J = 4.6 Hz, 3H), 2.27 (s, 3H). 실시예 90. ¾ NMR (300 MHz, DMS0—ο {;) δ 13.59 (s, 1H), 10.31 (s, 1H), 8.33 (d, / = 4.8 Hz, 1H), 8.22 (d, J = 8.4 Hz, 1H) , 7.79 (s, 1H), 7.75 (s, 1H), 7.49 (d, J = 8.1 Hz, 3H), 7.31 (d, J 11.5 Hz, 1H), 7.21 (d, J = 8.5 Hz, 1H), 4.34 (s, 2H), 4.03 (s, 2H), 3.53 (s, 1H), 2.94 (d, J = 5.9 Hz, 6H), 2.84 (d, J = 4.6 Hz, 3H), 2.27 (s, 3H ). Example 90.
6-(4—플루오로 -2—메틸 -5-(3-(4-(2-옥소 -2- (페닐아미노)에틸)피페라진— 1-일 )-5一 (트리플루오로메틸 )벤즈아미도)페닐 메틸 -l^인다졸 -3-카복스아미드의 제조
Figure imgf000069_0001
6- (4—Fluoro-2-methyl-5- (3- (4- (2-oxo-2- (phenylamino) ethyl) piperazin— 1-yl) -5 one (trifluoromethyl) benz Amido) Phenyl Methyl-l ^ indazole-3-carboxamide
Figure imgf000069_0001
상기 실시예 43파 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  Example 43 waves were carried out in the same manner to obtain the title compound.
LI-[ NMR (300 MHz, D O-^) δ 13.61 (s, IH), 10.55 (s, IH), 10.34 (s, IH), 8.36 (d, J = 4.6 Hz, IH), 8.22 (d, J = 8.3 Hz, IH), 7.80 (s, IH), 7.74 (s, IH), 7.61 (d, /= 8.4 Hz, 2H), 7.49 (d, /= 8.4 Hz, 3H), 7.35 (del, J= 19.9, 9.7 Hz, 3H), 7.21 (d, / = 8.4 Hz, IH) , 7.13 (t, J = 7.3 Hz, IH), 4.18 (s, 4H), 3.38-3.24 (m, 5H), 2.83 (d, J = 4.6 Hz, 3H), 2.27 (s, 4H). 실시예 91. LI- [NMR (300 MHz, D O- ^) δ 13.61 (s, IH), 10.55 (s, IH), 10.34 (s, IH), 8.36 (d, J = 4.6 Hz, IH), 8.22 (d , J = 8.3 Hz, IH), 7.80 (s, IH), 7.74 (s, IH), 7.61 (d, / = 8.4 Hz, 2H), 7.49 (d, / = 8.4 Hz, 3H), 7.35 (del , J = 19.9, 9.7 Hz, 3H), 7.21 (d, / = 8.4 Hz, IH), 7.13 (t, J = 7.3 Hz, IH), 4.18 (s, 4H), 3.38-3.24 (m, 5H) , 2.83 (d, J = 4.6 Hz, 3H), 2.27 (s, 4H). Example 91.
6-(4-플루오로ᅭ 5-(3-(4— (이소프로필설포닐)피페라진 -1-일)— 5— (트리플루오로메 틸 )벤즈아미도) -2-메틸페닐 )-/ ^메틸— I 인다졸 -3ᅳ카복스아미드의 제조 6- (4-fluoro ᅭ 5- (3- (4— (isopropylsulfonyl) piperazin-1-yl) — 5— (trifluoromethyl) benzamido) -2-methylphenyl)-/ ^ Preparation of Methyl—I Indazole-3 ᅳ Carboxamide
Figure imgf000069_0002
Figure imgf000069_0002
상기 실시예 43과'동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as in Example 43 ' .
)H NMR (300 MHz, DMSOfli δ 13.6 (bs, IH), 10.3 (s, IH) , 8.43 (q, IH, ./= 4.8 Hz), 8.23 (d, IH, /= 8.4 Hz), 7.78 (s, IH), 7.68 (s, IH), 7.51 (s, IH), 7.50 (d, IH, J=8.4Hz).7.34 (d, IH, /= 11.7 Hz), 7.24 (d, IH, 7=8.4 Hz).3.46—3.35 (m, 9H), 2.83 (d, 3H, J = 4.5 Hz), 2.26 (s, 3H), 1.26 (d, 6H, J = 6.6 Hz) 실시예 92. ) H NMR (300 MHz, DMSOfli δ 13.6 (bs, IH), 10.3 (s, IH), 8.43 (q, IH, ./= 4.8 Hz), 8.23 (d, IH, / = 8.4 Hz), 7.78 ( s, IH), 7.68 (s, IH), 7.51 (s, IH), 7.50 (d, IH, J = 8.4 Hz). 7.34 (d, IH, / = 11.7 Hz), 7.24 (d, IH, 7 = 8.4 Hz). 3.46—3.35 (m, 9H), 2.83 (d, 3H, J = 4.5 Hz), 2.26 (s, 3H), 1.26 (d, 6H, J = 6.6 Hz) Example 92.
6-(5-(3— (4-벤조일피페라진 -1-일)— 5— (트리플루오로메틸)벤즈아미도) -4-플루오 로 -2—메틸페닐 메틸ᅳ 1^인다졸 -3-카복스아미드의 제조  6- (5- (3— (4-benzoylpiperazin-1-yl) — 5— (trifluoromethyl) benzamido) -4-fluoro-2—methylphenyl methyl ᅳ 1 ^ indazole-3- Preparation of Carboxamide
Figure imgf000069_0003
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.
Figure imgf000069_0003
The title compound was obtained in the same manner as the Example 43.
匪 R (300 MHz, DMSO^) δ 13.59 (s, IH), 10.29 (s, IH), 8.39-8.29 (m, IH), 8.21 (d, J= 8.4 Hz, IH), 7.78 (s, IH), 7.67 (s, IH), 7.53—7.39 (m, 8H), 7.31 (d, J= 11.4Hz, IH), 7.22 (dd, J=8.3, 1.3Hz, IH), 3.83-3.73 (m, 4H), 3.45-3.35 (m, 4H), 2.83 (d, J = 4.6 Hz, 3H), 2.26 (s, 3H) 실시예 93. 匪 R (300 MHz, DMSO ^) δ 13.59 (s, IH), 10.29 (s, IH), 8.39-8.29 (m, IH), 8.21 (d, J = 8.4 Hz, IH), 7.78 (s, IH ), 7.67 (s, IH), 7.53—7.39 (m, 8H), 7.31 (d, J = 11.4 Hz, IH), 7.22 (dd, J = 8.3, 1.3 Hz, IH), 3.83-3.73 (m, 4H), 3.45-3.35 (m, 4H), 2.83 (d, J = 4.6 Hz, 3H), 2.26 (s, 3H) Example 93.
6-(5— (3-( 1-아세틸피페리딘— 4-카복스아미도 )-5— (트리플루오로메틸 )벤즈아미도) -4-플루오로 -2—메틸페닐 )-그메틸 -1^인다졸 -3—카복스아미드의 제조  6- (5— (3- (1-acetylpiperidine— 4-carboxamido) -5— (trifluoromethyl) benzamido) -4-fluoro-2—methylphenyl) -gmethyl- Preparation of 1 ^ indazol-3—carboxamide
Figure imgf000070_0001
Figure imgf000070_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
!H NMR (300 MHz, DMSO-d δ 10.48 (s, 1Η), 8.40—8.26 (m, 3H), 8.20 (d, / = 8.4 Hz, 1H), 8.02 (s, 1H), 7.55— (m, 2H), 7.30 (d, J= 11.4 Hz, 1H), 7.19 (d, J= 8.3 Hz, 1H), 4.39 (d, J= 13.1 Hz, 1H), 3.87 (cl, J 13.7 Hz, III), 3.18-3.01 (m, 1H), 2.84 (d, J= 4.4 Hz, 3H), 2.69-2.57 (m, 3H), 2.26 (s, 3H),! H NMR (300 MHz, DMSO-d δ 10.48 (s, 1Η), 8.40—8.26 (m, 3H), 8.20 (d, / = 8.4 Hz, 1H), 8.02 (s, 1H), 7.55— (m , 2H), 7.30 (d, J = 11.4 Hz, 1H), 7.19 (d, J = 8.3 Hz, 1H), 4.39 (d, J = 13.1 Hz, 1H), 3.87 (cl, J 13.7 Hz, III) , 3.18-3.01 (m, 1H), 2.84 (d, J = 4.4 Hz, 3H), 2.69-2.57 (m, 3H), 2.26 (s, 3H),
2.01 (s, 3H), 1.92-1.76 (m, 3H) 실시예 94. 2.01 (s, 3 H), 1.92-1.76 (m, 3 H) Example 94.
6— (5— (3— (2— (디메틸아미노)아세트아미도 )-5- (트리플루오로메틸 )벤즈아미도) -4- 플루오로— 2—메틸페닐 메틸— 1/ 인다졸—3-카복스아미드의 제조  6— (5— (3— (2— (dimethylamino) acetamido) -5- (trifluoromethyl) benzamido) -4-fluoro— 2—methylphenyl methyl— 1 / indazole—3- Preparation of Carboxamide
Figure imgf000070_0002
Figure imgf000070_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
NMR (300 MHz, DMSO-fl [；) δ 13.59 (s, 1H), 11.03 (s, 1H), 10.45 (s, 1H), 8.39-8.30 (in, 2H), 8.26 (s, 1H), 8.22 (d, J 8.3 Hz, 1H), 8.17 (s, 1H), 7.55-7.47 (m, 2H), 7.32 (d, J= 11.5 Hz, 1H), 7.21 (del, /= 8.4， 1.3 Hz, 1H): 4.16 (s, 2H), 2.89 (s, 6H), 2.84 (d, J = 4.6 Hz, 3H), 2.27 (s, 3H) 실시예 95. NMR (300 MHz, DMSO-fl [;) δ 13.59 (s, 1H), 11.03 (s, 1H), 10.45 (s, 1H), 8.39-8.30 (in, 2H), 8.26 (s, 1H), 8.22 (d, J 8.3 Hz, 1H), 8.17 (s, 1H), 7.55-7.47 (m, 2H), 7.32 (d, J = 11.5 Hz, 1H), 7.21 (del, / = 8.4, 1.3 Hz, 1H ) : 4.16 (s, 2H), 2.89 (s, 6H), 2.84 (d, J = 4.6 Hz, 3H), 2.27 (s, 3H) Example 95.
6— (4-플루오로— 5-(3-(4-(2-메록시에틸)피페라진— 1-일) -5— (트리플루오로메틸)벤 즈아미도) -2-메틸페닐) 메틸 -1^인다졸 -3-카복스아미드의 제조  6— (4-fluoro— 5- (3- (4- (2-methoxyethyl) piperazin— 1-yl) -5— (trifluoromethyl) benzamido) -2-methylphenyl) methyl Preparation of -1 ^ indazole-3-carboxamide
Figure imgf000070_0003
Figure imgf000070_0003
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
:H NMR (300 MHz, DMSC ) δ 13.6 (bs, 1H), 10.3 (s, 1H) , 8.42 (q, 1H, J= 4.5 Hz), 8.23 (d, 1H, J= 8.4 Hz), 7.78 (s, 1H), 7.68 (s, 1H), 7.51 (s, 1H), 7.50 (d, 1H, 7 = 8.1 Hz), 7.45 (s, 1H), 7.34 (d, 1H, J= 11.4 Hz), 7.24 (d, 1H, =8.4Hz), 3.43-3.40 (m, 8H), 2.83 (d, 3H, J=4.5Hz), 2.26 (s, 3H), 1.26—1.23 (m, 7H) ' 실시예 96. : H NMR (300 MHz, DMSC) δ 13.6 (bs, 1H), 10.3 (s, 1H), 8.42 (q, 1H, J = 4.5 Hz), 8.23 (d, 1H, J = 8.4 Hz), 7.78 (s, 1H), 7.68 (s, 1H), 7.51 (s, 1H), 7.50 (d, 1H, 7 = 8.1 Hz), 7.45 ( s, 1H), 7.34 (d, 1H, J = 11.4 Hz), 7.24 (d, 1H, = 8.4 Hz), 3.43-3.40 (m, 8H), 2.83 (d, 3H, J = 4.5 Hz), 2.26 (s, 3H), 1.26-1.23 (m, 7H) ' Example 96.
6一 (4-플루오로 -2-메틸 -5-(3— (4-(1—메틸피페라진 -4—일 )— 5ᅳ (트리플루오로메틸)벤 즈아미도)페닐 )— 메틸 인다졸 -3-카복스아미드의 제조  6- (4-Fluoro-2-methyl-5- (3— (4- (1-methylpiperazin-4-yl) —5 ′ (trifluoromethyl) benzamido) phenyl) —methyl is Preparation of Sol-3-Carboxamide
Figure imgf000071_0001
Figure imgf000071_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
\\ NMR (300 MHz , DMSO-rf;) δ 13.6 (bs, 1H), 10.3 (s, 1H), 8.37 (q, 1H, /= 4.5 Hz), 8.23 (d, 1H, J 8.4 Hz), 7.78 (s, 1H), 7.75 (m, 1H), 7.50—7.47 (m, 4H), 7.34 (d, 1H, /= 11.4 Hz), 7.23 (del, 1H, /= 8.4, 0.9 Hz), 3.56—3.50 (m, 5H), 3.05-2.89 (m, 4H) , 2.84 (d, 3H, J= 4.8 Hz), 2.79 (s, 3H) , 2.73 (in, 1H), 2.59 (m, 11-1)， 2.41 (m, 1H), 2.30-2.25 (m, 4H), 2.27 (s, 3H), 1.78 (m, 1H) 실시예 97.  \\ NMR (300 MHz, DMSO-rf;) δ 13.6 (bs, 1H), 10.3 (s, 1H), 8.37 (q, 1H, / = 4.5 Hz), 8.23 (d, 1H, J 8.4 Hz), 7.78 (s, 1H), 7.75 (m, 1H), 7.50—7.47 (m, 4H), 7.34 (d, 1H, / = 11.4 Hz), 7.23 (del, 1H, / = 8.4, 0.9 Hz), 3.56 —3.50 (m, 5H), 3.05-2.89 (m, 4H), 2.84 (d, 3H, J = 4.8 Hz), 2.79 (s, 3H), 2.73 (in, 1H), 2.59 (m, 11-1 ), 2.41 (m, 1H), 2.30-2.25 (m, 4H), 2.27 (s, 3H), 1.78 (m, 1H) Example 97.
6一(4-플루오로-2ᅳ메틸-5—(3-((1，2，2，6,6-펜타메틸피페리딘—4-일)아미노)—5-(트 리플루오로메틸 )벤즈아미도)페닐 )—^메틸— 1^인다졸 -3—카복스아미드의 제조  6 一 (4-fluoro-2 ᅳ methyl-5— (3-((1,2,2,6,6-pentamethylpiperidin—4-yl) amino) —5- (trifluoromethyl ) Benzamido) phenyl) — ^ methyl— 1 ^ indazole-3—carboxamide preparation
Figure imgf000071_0002
Figure imgf000071_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
!H NMR (300 MHz, DMSO-d) δ 13.59 (s, 1H), 10.16 (s, 1H), 8.54 (s, 1H), 8.35 (d, J= 5.1 Hz, 1H), 8.22 (d, J= 8.3 Hz, 1H), 7.53 (d, J= 7.9 Hz, 1H), 7.49 (t, J= 1.1 Hz, 1H), 7.44 (d, J 12.6 Hz, 2H), 7.30 (d, J 11.5 Hz, 1H), 7.21 (dd, J= 8.4, 1.4 Hz, 1H), 7.14 (s, 1H), 3.66-3.55 (m, 3H), 2.84 (d, J ! H NMR (300 MHz, DMSO-d) δ 13.59 (s, 1H), 10.16 (s, 1H), 8.54 (s, 1H), 8.35 (d, J = 5.1 Hz, 1H), 8.22 (d, J = 8.3 Hz, 1H), 7.53 (d, J = 7.9 Hz, 1H), 7.49 (t, J = 1.1 Hz, 1H), 7.44 (d, J 12.6 Hz, 2H), 7.30 (d, J 11.5 Hz, 1H), 7.21 (dd, J = 8.4, 1.4 Hz, 1H), 7.14 (s, 1H), 3.66-3.55 (m, 3H), 2.84 (d, J
= 4.6 Hz, 3H), 2.75 (d, J 4.8 Hz, 4H), 2.26 (s, 4H), 2.08 (d, J 4.6 Hz, 1H), 1.76 (ddd, J = 6.6, 5.0， 2.7 Hz, 4H), 1.47 (s, 6H), 1.41 (s, 6H). 실시예 98. = 4.6 Hz, 3H), 2.75 (d, J 4.8 Hz, 4H), 2.26 (s, 4H), 2.08 (d, J 4.6 Hz, 1H), 1.76 (ddd, J = 6.6, 5.0, 2.7 Hz, 4H ), 1.47 (s, 6H), 1.41 (s, 6H). Example 98.
6— (4-플루오로 -2-메틸 -5— (3-(4ᅳ옥소피페리딘 -1-일 )-5- (트리플루오로메틸)벤즈 아미도)페닐 메틸 -1^인다졸—3-카복스아미드의 제조
Figure imgf000072_0001
6— (4-fluoro-2-methyl-5— (3- (4 (oxopiperidin-1-yl) -5- (trifluoromethyl) benz amido) phenyl methyl-1 ^ indazole—3 Preparation of Carboxamide
Figure imgf000072_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 43 .
^-l NMR (300 MHz , DMSO—rf;) δ 13.6 (bs, 1H), 10.3 (s, 1H), 8.35 (m, 1H) , 8.23 (d, 1H, J= 8.1 Hz), 7.78 (s, 1H), 7.62 (s, 1H), 7.50—7.48 (m, 2H), 7.43 (s, 1H), 7.32 (d, 1H, J= 11.4 Hz), 7.23 (dd, IH, J 8.4， 1.2 Hz), 3.79—3.75 (m, 4H), 2.84 (d, 3H, J= 4.8 Hz), 2.68 (s, 1H), 2.50-2.48 (m, 3H), 2.26 (s, 3H) . 실시예 99. ^ -l NMR (300 MHz, DMSO—rf;) δ 13.6 (bs, 1H), 10.3 (s, 1H), 8.35 (m, 1H), 8.23 (d, 1H, J = 8.1 Hz), 7.78 (s , 1H), 7.62 (s, 1H), 7.50—7.48 (m, 2H), 7.43 (s, 1H), 7.32 (d, 1H, J = 11.4 Hz), 7.23 (dd, IH, J 8.4, 1.2 Hz ), 3.79—3.75 (m, 4H), 2.84 (d, 3H, J = 4.8 Hz), 2.68 (s, 1H), 2.50-2.48 (m, 3H), 2.26 (s, 3H). Example 99.
6-(4-플루오로 -2—메틸— 5-(3— (4—메록시피페리딘— 1-일) -5- (트리플루오로메틸)벤 즈아미도)페닐) 메틸 -1^인다졸—3-카복스아미드의 제조  6- (4-Fluoro-2—methyl— 5- (3— (4—methoxypiperidin— 1-yl) -5 (trifluoromethyl) benzamido) phenyl) methyl-1 ^ Preparation of Sol—3-Carboxamides
Figure imgf000072_0002
Figure imgf000072_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물올 얻었다.  The title compound was obtained in the same manner as in Example 43.
薩 (300 MHz, DMSO-dJ δ 13.6 (bs, 1H), 10.3 (s, 1H), 8.35 (q, IH, /= 4.8 Hz ), 8.23 (d, IH, J = 8.4 Hz), 7.75 (s, IH), 7.59 (s, IH) , 7.50—7.47 (m, 2H), 7.37 (s, IH), 7.32 (d, IH, /= 11.4 Hz), 7.23 (dd, IH, J = 8.4, 1.5 Hz), 3.69-3.62 (m, 2H), 3.40 (m, IH), 3.28 (s, 3H), 3.13 (dd, IH, /= 9.6， 3.0 Hz), 3.08 (dd, IH, J 9.6, 3.0Hz), 2.84 (d, 3H, 7=4.5 Hz), 2.26 (s, 3H), 1.98—1.92 (m, 2H), 1.58-1.51 (m, 2H) 실시예 100.  300 (300 MHz, DMSO-dJ δ 13.6 (bs, 1H), 10.3 (s, 1H), 8.35 (q, IH, / = 4.8 Hz), 8.23 (d, IH, J = 8.4 Hz), 7.75 (s , IH), 7.59 (s, IH), 7.50—7.47 (m, 2H), 7.37 (s, IH), 7.32 (d, IH, / = 11.4 Hz), 7.23 (dd, IH, J = 8.4, 1.5 Hz), 3.69-3.62 (m, 2H), 3.40 (m, IH), 3.28 (s, 3H), 3.13 (dd, IH, / = 9.6, 3.0 Hz), 3.08 (dd, IH, J 9.6, 3.0 Hz), 2.84 (d, 3H, 7 = 4.5 Hz), 2.26 (s, 3H), 1.98-1.92 (m, 2H), 1.58-1.51 (m, 2H) Example 100.
6-(4—플루오로— 2-메틸 -5-(3-(3-하이드록시피를리딘 -1—일 )-5— (트리플루오로메틸 )벤즈아미도)페닐) - 메틸 -1^인다졸 -3-카복스아미드의 제조  6- (4—fluoro— 2-methyl-5- (3- (3-hydroxypyridin-l-yl) -5— (trifluoromethyl) benzamido) phenyl) -methyl-1 ^ Preparation of indazole-3-carboxamide
Figure imgf000072_0003
Figure imgf000072_0003
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 43.
¾ NMR (300 MHz, DMS0- ) δ 13.6 (bs, IH), 10.3 (s, IH), 8.37 (q, IH, J= 4.8 Hz), 8.23 (d, IH, /= 8.4 Hz), 7.50 s, IH), 7.48 (d, IH, /= 4.8 Hz), 7.45 (s, IH), 7.32 -7.28 (m, 2H), 7.23 (dd, IH, J= 8.4, 1.2 Hz), 6.89 (s, IH), 5.01 (s, IH), 4.44 (m, IH), 3.54 (dd, IH, J= 10.5, 4.8 Hz), 3.46-3.37 (m, 2H), 3.22 (d, IH, J = 10.2 Hz), 2.84 (d, 3H, J = 4.8 Hz), 2.26 (s, 3H), 2.07 (m, 1H), 1.95 (in, 1H). 실시예 101. ¾ NMR (300 MHz, DMS0-) δ 13.6 (bs, IH), 10.3 (s, IH), 8.37 (q, IH, J = 4.8 Hz), 8.23 (d, IH, / = 8.4 Hz), 7.50 s , IH), 7.48 (d, IH, / = 4.8 Hz), 7.45 (s, IH), 7.32 -7.28 (m, 2H), 7.23 (dd, IH, J = 8.4, 1.2 Hz), 6.89 (s, IH), 5.01 (s, IH), 4.44 (m, IH), 3.54 (dd, IH, J = 10.5, 4.8 Hz), 3.46-3.37 (m, 2H), 3.22 (d, IH, J = 10.2 Hz ), 2.84 (d, 3H, J = 4.8 Hz), 2.26 (s, 3H), 2.07 (m, 1 H), 1.95 (in, 1 H). Example 101.
6-(5—(3-(1，4-디옥사—8-아자스피로[4,5]데칸ᅳ8-일)-5-(트리플루오로메틸)벤즈 아미도 )-4-플루오로— 2ᅳ메틸페닐 메틸ᅳ 1^인다졸 -3-카복스아미드의 제조  6- (5— (3- (1,4-dioxa—8-azaspiro [4,5] decane ᅳ 8-yl) -5- (trifluoromethyl) benz amido) -4-fluoro— Preparation of 2'Methylphenylmethyl'1 ^ indazole-3-carboxamide
Figure imgf000073_0001
Figure imgf000073_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
薩 (300 MHz, DMS0— ) δ 13.6 (bs, 1H), 10.3 (s, 1H) , 8.36 (q, 1H, /= 4.5 Hz), 8.23 (d, 1H, /= 8.4 Hz), 7.76 (s, 1H), 7.60 (s, 1H), 7.50 -7.48 (m, 2H), 7.40 (s, 1H), 7.33 (d, 1H, J= 11.7 Hz), 7.23 (del, 1H, J 8.4, 0.9 Hz), 3.93 300 (300 MHz, DMS0—) δ 13.6 (bs, 1H), 10.3 (s, 1H), 8.36 (q, 1H, / = 4.5 Hz), 8.23 (d, 1H, / = 8.4 Hz), 7.76 (s , 1H), 7.60 (s, 1H), 7.50 -7.48 (m, 2H), 7.40 (s, 1H), 7.33 (d, 1H, J = 11.7 Hz), 7.23 (del, 1H, J 8.4, 0.9 Hz ), 3.93
(s, 4H), 3.48-3.44 (m, 4H), 2.84 (d, 3H, J 4.5 Hz), 2.69 (s, 2H), 2.26 (s, 3H), 1.75-1.72 (ni, 4H). 실시예 102. (s, 4H), 3.48-3.44 (m, 4H), 2.84 (d, 3H, J 4.5 Hz), 2.69 (s, 2H), 2.26 (s, 3H), 1.75-1.72 (ni, 4H). Example 102.
6-(4-플루오로 -2—메틸— 5— (3— (4- (메틸아미노)피페리딘—1-일 )—5— (트리플루오로메 틸 )벤즈아미도)페닐 )— 메틸— 인다졸 -3—카복스아미드의 제조 6- (4-fluoro-2—methyl— 5— (3— (4- (methylamino) piperidin—1-yl) —5— (trifluoromethyl) benzamido) phenyl) — methyl— Preparation of indazole-3—carboxamide
Figure imgf000073_0002
Figure imgf000073_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
NMR (300 MHz , DMSO-^) δ 10.3 (s, 1H), 8.35 (q, 1H, 7= 4.5 Hz), 8.23 (d, 1H, J= 8.4 Hz), 7.75 (s, 1H), 7.61 (s, 1H), 7.49—7.47 (m, 3H), 7.38 (s, 1H) , NMR (300 MHz, DMSO- ^) δ 10.3 (s, 1H), 8.35 (q, 1H, 7 = 4.5 Hz), 8.23 (d, 1H, J = 8.4 Hz), 7.75 (s, 1H), 7.61 ( s, 1H), 7.49—7.47 (m, 3H), 7.38 (s, 1H),
7.33 (d, 1H, J= 11.7 Hz), 7.23 (dd, 1H, /= 8.4, 1.2 Hz), 3.93 (d, 2H, J = 12.9 Hz), 2.96 (t, 2H, J = 11.7 Hz), 2.84 (d, 3H, J= 4.5 Hz), 2.44 (s, 3H), 2.26 (s, 3H), 2.00-1.96 (m, 2H), 1.47-1.42 (m, 2H) . 실시예 103. 7.33 (d, 1H, J = 11.7 Hz), 7.23 (dd, 1H, / = 8.4, 1.2 Hz), 3.93 (d, 2H, J = 12.9 Hz), 2.96 (t, 2H, J = 11.7 Hz), 2.84 (d, 3H, J = 4.5 Hz), 2.44 (s, 3H), 2.26 (s, 3H), 2.00-1.96 (m, 2H), 1.47-1.42 (m, 2H). Example 103.
6— (4-플루오로— 2-메틸 -5-(3-(4— (디메틸아미노)피페리딘 -1—일) -5- (트리플루오로 메틸 )벤즈아미도)페닐 )-/ 메틸 -1^인다졸 -3—카복스아미드의 제조 상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. 6— (4-Fluoro— 2-methyl-5- (3- (4— (dimethylamino) piperidin-1-yl) -5- (trifluoromethyl) benzamido) phenyl)-/ methyl Preparation of -1 ^ indazole-3—carboxamide The title compound was obtained in the same manner as the Example 43.
Ή NMR (300 MHz, DMSO— ;) δ 10.3 (s, 1H), 8.22 (q, 1H, = 4.5 Hz), 8.22 (d, 1H, /= 8.4 Hz), 7.74 (s, 1H) 7.59 (s, 1H), 7.50—7.47 (m, 3H), 7.35 (s, 1H), 7.32 (d, 1H, 11.7 Hz), 7.23 (dd, 1H, /= 8.4， 1.2 Hz ), 3.95-3.87 (m, 2H), 3.51 (s, 2H), 2.88-2.73 (m, 2H), 2.84 (d, 3H, J 4.5 Hz), 2.26 (s, 3H), 2.19 (s, 6H), 1.88 (m, 2H), 1.49-1.45 (m, 2H) . 실시예 104. MR NMR (300 MHz, DMSO—;) δ 10.3 (s, 1H), 8.22 (q, 1H, = 4.5 Hz), 8.22 (d, 1H, / = 8.4 Hz), 7.74 (s, 1H) 7.59 (s , 1H), 7.50—7.47 (m, 3H), 7.35 (s, 1H), 7.32 (d, 1H, 11.7 Hz), 7.23 (dd, 1H, / = 8.4, 1.2 Hz), 3.95-3.87 (m, 2H), 3.51 (s, 2H), 2.88-2.73 (m, 2H), 2.84 (d, 3H, J 4.5 Hz), 2.26 (s, 3H), 2.19 (s, 6H), 1.88 (m, 2H) , 1.49-1.45 (m, 2 H). Example 104.
6一 (4-플루오로—5— (3—(4-하이드록시피페리딘 -1-일 )-5— (트리플루오로메틸 )벤즈아 미도) 2-메틸페닐 메틸— 1/ 인다졸ᅳ 3-카복스아미드의 제조  6 一 (4-fluoro—5— (3— (4-hydroxypiperidin-1-yl) -5— (trifluoromethyl) benzamido) 2-methylphenyl methyl— 1 / indazolazole 3 Preparation of Carboxamide
Figure imgf000074_0001
Figure imgf000074_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
Ή NMR (300 MHz , DMSO- ) δ 13.6 (s, 1H), 10.3 (s, 1H) , 8.35 (q, 1H, J 4.8 Hz), 8.23 (d, 1H, /= 8.1 Hz), 7.86 (s, 1H), 7.81 (s, 1H), 7.52—7.49 (ηι, 3H), 7.33 (d, 1H, J= 11.7 Hz), 7.23 (del, 1H, J 8.4, 1.5 Hz), 4.64 (m, 1H), 2.85 (d, 3H, = 4.8 Hz), 2.63-2.58 Cm, 2H), 2.26 (s, 3H), 2.26-2.23 (i , 2H), 2.19 (s, 3H), 1.99-1.93 (m, 2H), 1.73-1.66 (m, 2H). 실시예 105. NMR (300 MHz, DMSO-) δ 13.6 (s, 1H), 10.3 (s, 1H), 8.35 (q, 1H, J 4.8 Hz), 8.23 (d, 1H, / = 8.1 Hz), 7.86 (s , 1H), 7.81 (s, 1H), 7.52—7.49 (ηι, 3H), 7.33 (d, 1H, J = 11.7 Hz), 7.23 (del, 1H, J 8.4, 1.5 Hz), 4.64 (m, 1H ), 2.85 (d, 3H, = 4.8 Hz), 2.63-2.58 Cm, 2H, 2.26 (s, 3H), 2.26-2.23 (i, 2H), 2.19 (s, 3H), 1.99-1.93 (m, 2H), 1.73-1.66 (m, 2H). Example 105.
6-(4-플루오로— 2-메틸 -5— (3ᅳ( ( 1ᅳ메틸피페리딘 -4-일 )아미노 )—5- (트리플루오로메 틸 )벤즈아미도)페닐 )-그메틸— 1/ 인다졸 -3-카복스아미드의 제조  6- (4-fluoro— 2-methyl-5— (3 ′ ((1′methylpiperidin-4-yl) amino) —5- (trifluoromethyl) benzamido) phenyl) -gmethyl — 1 / Preparation of indazole-3-carboxamide
Figure imgf000074_0002
Figure imgf000074_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
NMR (300 MHz, CD30으 ) δ 0.93 (m, 2Η), 1.56 (m, 2Η), 2.09 (m, 2H), 2.27 (s, 3H), 2.38 (s, 3H), 2.91 Cm, 2H), 2.98 (s, 3H), 7.03 (s, 1H)， 7.15 (d, J = 11.4 Hz, 1H), 7.24 (d, /= 8.4 Hz, 1H), 7.38 (m, 2H), 7.50 (s, 1H), 7.57 (d, J = 8.1 Hz, 1H), 8.26 (d, J 8.4 Hz, 1H) 실시예 106. NMR (300 MHz, CD 3 0) δ 0.93 (m, 2Η), 1.56 (m, 2Η), 2.09 (m, 2H), 2.27 (s, 3H), 2.38 (s, 3H), 2.91 Cm, 2H ), 2.98 (s, 3H), 7.03 (s, 1H), 7.15 (d, J = 11.4 Hz, 1H), 7.24 (d, / = 8.4 Hz, 1H), 7.38 (m, 2H), 7.50 (s , 1H), 7.57 (d, J = 8.1 Hz, 1H), 8.26 (d, J 8.4 Hz, 1H) Example 106.
6ᅳ (4ᅳ플루오로 -2—메틸 -5-(3ᅳ피페리딘 -4—일옥시 )—5ᅳ (트리플루오로메틸 )벤즈아미 도)페닐) 메틸 -1^인다졸 -3-카복스아미드의 제조
Figure imgf000075_0001
6 '(4'fluoro-2-methyl-5- (3'piperidin-4-yloxy) -5' (trifluoromethyl) benzamido) phenyl) methyl-1 ^ indazole-3-car Preparation of Voxamide
Figure imgf000075_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
Ή NMR (300 MHz , DMS0— ) δ 10.3 (s, 1H), 8.34 (q, 1H, /= 4.8 Hz), 8.23 (cl, 1H, J 8.7 Hz), 7.85 (s, 1H), 7.80 (s, 1H), 7.52-7.48 (m, 3H), 7.33 (d, 1H, J = 11.7 Hz), 7.23 (dd, 1H, J = 8.4， 1.2 Hz), 4.66 (m, 1H), 3.00—2.93 (dt , 2H, J= 12.6, 4.2 Hz), 2.85 (cl, 3H, J= 4.8 Hz), 2.66 (ddd, 2H, J = 12.6, 9.9, 2.7 Hz), 2.26 (s, 3H), 1.97-1.92 (m, 2H), 1.53—1.47 (in. 2H). 실시예 107. MR NMR (300 MHz, DMS0—) δ 10.3 (s, 1H), 8.34 (q, 1H, / = 4.8 Hz), 8.23 (cl, 1H, J 8.7 Hz), 7.85 (s, 1H), 7.80 (s , 1H), 7.52-7.48 (m, 3H), 7.33 (d, 1H, J = 11.7 Hz), 7.23 (dd, 1H, J = 8.4, 1.2 Hz), 4.66 (m, 1H), 3.00—2.93 ( dt, 2H, J = 12.6, 4.2 Hz), 2.85 (cl, 3H, J = 4.8 Hz), 2.66 (ddd, 2H, J = 12.6, 9.9, 2.7 Hz), 2.26 (s, 3H), 1.97-1.92 (m, 2H), 1.53—1.47 (in. 2H). Example 107.
6- (4-플루오로 -2—메틸 -5- (3- (1-메틸피페리딘 -4-일 )옥시 )-5— (트리플루오로메틸 ) 벤즈아미도)페닐) 메틸 - 1 ■인다졸 -3-카복스아미드의 제조 6- (4-fluoro-2-methyl-5- (3- (1-methylpiperidin-4-yl) oxy) -5- (trifluoromethyl) benz amido) phenyl) - 1 ■ Preparation of indazole-3-carboxamide
Figure imgf000075_0002
Figure imgf000075_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
ΊΗ NMR (300 MHz, DMSO-^) δ 13.6 (s, 1H)， 10.3 (s, 1H), 8.35 (q, 1H, J 4.8 Hz), 8.23 (cl, 1H, J 8.1 Hz), 7.86 (s, 1H), 7.81 (s, 1H), 7.52-7.49 (m, 3H), 7.33 (d, 1H, J 11.7 Hz), 7.23 (dd, 1H, /= 8.4, 1.5 Hz), 4.64 (m, 1H), 2.85 (d, 3H, J= 4.8 Hz)' 2.63-2.58 (m, 2H)' 2.26 (s, 3H), 2.26-2.23 (in, 2H), 2.19 (s, 3H), 1.99-1.93 (m, 2H), 1.73—1.66 (111， 2H). 실시예 108. NMR (300 MHz, DMSO- ^) δ 13.6 (s, 1H), 10.3 (s, 1H), 8.35 (q, 1H, J 4.8 Hz), 8.23 (cl, 1H, J 8.1 Hz), 7.86 (s , 1H), 7.81 (s, 1H), 7.52-7.49 (m, 3H), 7.33 (d, 1H, J 11.7 Hz), 7.23 (dd, 1H, / = 8.4, 1.5 Hz), 4.64 (m, 1H ), 2.85 (d, 3H, J = 4.8 Hz) '2.63-2.58 (m, 2H)' 2.26 (s, 3H), 2.26-2.23 (in, 2H), 2.19 (s, 3H), 1.99-1.93 ( m, 2H), 1.73-1.66 (111, 2H). Example 108.
6-(4-플루오로 -2—메틸 -5-(3-( ( 1-메틸피페리딘— 4-일 )메톡시 )-5— (트리플루오로메 틸)벤즈아미도)페닐시메틸-] J"인다졸—3-카복스아미드  6- (4-Fluoro-2-methyl-5- (3- ((1-methylpiperidin- 4-yl) methoxy) -5— (trifluoromethyl) benzamido) phenylscimethyl- J "indazol—3-carboxamide
트리플루오로아세트산염의 제조 Preparation of Trifluoroacetic Acid
Figure imgf000075_0003
Figure imgf000075_0003
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
lW NMR (300 MHz, DMS으 ;) δ 13.6 (s, 1Η), 10.4 (s, 1H), 9.32 (bs, 110， 8.41 (q, 1H, J= 4.5 Hz), 8.23 (d, 1H, J= 8.4 Hz), 7.92 (s, 1H), 7.80 (s, 1H), 7.51-7.48 (m, 3H), 7.34 (d, 1H, J= 11.7 Hz), 7.23 (d, 1H, J= 8.7 Hz), 4.06 (d, 2H, J = 6.0 Hz), 3.50 (d, 211, / = 12.3 Hz), 3.04 (q, 2H, /= 11.4 Hz), 2.84 (d, 3H, J 4.8 Hz), 2.80-2.74 (m, 2H), 2.78 (d, 3H, J= 4.5 Hz), 2.27 (s, 3H), 2.08-1.99 (m, 3H), 1.56 (qd, 2H, J 12.3, 0.9 Hz). 실시예 109. l NMR (300 MHz, DMS;) δ 13.6 (s, 1Η), 10.4 (s, 1H), 9.32 (bs, 110, 8.41 (q, 1H, J = 4.5 Hz), 8.23 (d, 1H, J = 8.4 Hz), 7.92 (s, 1H), 7.80 (s, 1H), 7.51-7.48 (m, 3H), 7.34 (d, 1H, J = 11.7 Hz), 7.23 (d, 1H, J = 8.7 Hz ), 4.06 (d, 2H, J = 6.0 Hz), 3.50 (d, 211, / = 12.3 Hz), 3.04 (q, 2H, / = 11.4 Hz), 2.84 (d, 3H, J 4.8 Hz), 2.80-2.74 ( m, 2H), 2.78 (d, 3H, J = 4.5 Hz), 2.27 (s, 3H), 2.08-1.99 (m, 3H), 1.56 (qd, 2H, J 12.3, 0.9 Hz). Example 109.
6-(4-플루오로 -2—메틸— 5-(3— (피페리딘— 4-일메톡시) -5- (트리플루오로메틸)벤즈 아미도)페닐 메틸— 1^인다졸 -3-카복스아미드 트리플루오로아세트산염의 제조  6- (4-fluoro-2—methyl— 5- (3— (piperidin— 4-ylmethoxy) -5- (trifluoromethyl) benz amido) phenyl methyl— 1 ^ indazole-3- Preparation of Carboxamide Trifluoroacetate
Figure imgf000076_0001
Figure imgf000076_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
]H NMR (300 MHz, DMSO-rf;) δ 13.7 (s, 1Η), 10.4 (s, 1H), 8.72 (d, 1H, /= 11.1 Hz), 8.40 (q, 1H, J 4.8 Hz), 8.41 (s, 1H), 8.23 (d, 1H, J 8.4 Hz), 7.91 (s, 1H), 7.81 (s, 1H), 7.51-7.48 (m, 3H), 7.33 (d, 1H, J 11.4 Hz), 7.23 (d, 1H. / = 8.4 Hz), 4.06 (d, 2H. J = 6.3 Hz), 3.35 (d, 2H, J = 12.0 Hz), 2.95 (q, 2H, J = 11.4 Hz), 2.84 (d, 3H, J= 4.5 Hz), 2.26 (s, 3H), 2.02 (m, 1H), 1.97-1.93 (in, 2H), 1.51 (q, 2H, J 11.7 Hz), 1.23 (t, 2H, J 5.7 Hz) 실시예 110. ] H NMR (300 MHz, DMSO-rf;) δ 13.7 (s, 1Η), 10.4 (s, 1H), 8.72 (d, 1H, / = 11.1 Hz), 8.40 (q, 1H, J 4.8 Hz), 8.41 (s, 1H), 8.23 (d, 1H, J 8.4 Hz), 7.91 (s, 1H), 7.81 (s, 1H), 7.51-7.48 (m, 3H), 7.33 (d, 1H, J 11.4 Hz ), 7.23 (d, 1H. / = 8.4 Hz), 4.06 (d, 2H. J = 6.3 Hz), 3.35 (d, 2H, J = 12.0 Hz), 2.95 (q, 2H, J = 11.4 Hz), 2.84 (d, 3H, J = 4.5 Hz), 2.26 (s, 3H), 2.02 (m, 1H), 1.97-1.93 (in, 2H), 1.51 (q, 2H, J 11.7 Hz), 1.23 (t, 2H, J 5.7 Hz) Example 110.
6-(4-플루오로 -5-(3-(4-이소프로필피페리딘— 1—일) -5- (트리플루오로메틸)벤즈아 미도)—2-메틸페닐 )-/ 메틸—I 인다졸 -3—카복스아미드의 제조  6- (4-fluoro-5- (3- (4-isopropylpiperidin—1—yl) -5- (trifluoromethyl) benzamido) -2-methylphenyl)-/ methyl-I Preparation of Sol-3—Carboxamides
Figure imgf000076_0002
Figure imgf000076_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
¾ NMR (300 MHz, DMS으 οί δ 13.64 (s, 1H), 10.32 (s, 1H), 8.39 (d, J= 4.8 Hz, 1H), 8.21 (d, J = 8.4 Hz, 1H), 7.74 (s, 1H), 7.62 (s, 1H), 7.50 (s, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.36 (s, 11—1)， 7.31 (d, J = 11.5 Hz, 1H), 7.22 (d, J= 8.4 Hz, 1H), 3.32-3.26 (m, 4H), 2.83 (d, J 4.6 Hz, 3H); 2.68 (dd, J 13.0, 6.5 Hz, 1H), 2.59 (s, 4H), 2.26 (s, 3H), 1.01 (d, J = 6.5 Hz, 6H). 실시예 111. ¾ NMR (300 MHz, DMS οί δ 13.64 (s, 1H), 10.32 (s, 1H), 8.39 (d, J = 4.8 Hz, 1H), 8.21 (d, J = 8.4 Hz, 1H), 7.74 ( s, 1H), 7.62 (s, 1H), 7.50 (s, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.36 (s, 11-1), 7.31 (d, J = 11.5 Hz, 1H ), 7.22 (d, J = 8.4 Hz, 1H), 3.32-3.26 (m, 4H), 2.83 (d, J 4.6 Hz, 3H) ; 2.68 (dd, J 13.0, 6.5 Hz, 1H), 2.59 (s , 4H), 2.26 (s, 3H), 1.01 (d, J = 6.5 Hz, 6H) Example 111.
6-(4-플루오로 -2-메틸— 5-(3-(4—메틸 -1，4—디아제판ᅳ 1-일 )—5ᅳ (트리폴루오로메틸) 벤즈아미도)페닐 메틸 -1^인다졸 -3-카복스아미드의 제조
Figure imgf000077_0001
6- (4-fluoro-2-methyl— 5- (3- (4—methyl-1,4—diazepanol 1-yl) —5 ′ (trifluoromethyl) benzamido) phenyl methyl- Preparation of 1 ^ indazole-3-carboxamide
Figure imgf000077_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
'Η NMR (300 MHz, DMSO— ) δ 13.65 (s, 1Η), 10.28 Cs, 1H), 8.39 (d, J 4.8 Hz, 1H), 8.21 (cl, J 8.3 Hz, 1H), 7.47 (del, J= 12.3, 4.2 Hz, 4H), 7.31 (d, J 11.6 Hz, 1HJ, 7.22 (d, J 8.4 Hz, 1H), 7.07 (s, 1H), 3.62 (s, 2H), 3.53 (t, J = 6.1 Hz, 2H), 2.83 (d, J = 4.7 Hz, 3H), 2.63 (s, 2H), 2.44 (s, 2H), 2.26 (s, 3H), 2.25 (s, 3H), 1.89 (s, 2H) . 실시예 112. 'Η NMR (300 MHz, DMSO—) δ 13.65 (s, 1Η), 10.28 Cs, 1H, 8.39 (d, J 4.8 Hz, 1H), 8.21 (cl, J 8.3 Hz, 1H), 7.47 (del, J = 12.3, 4.2 Hz, 4H), 7.31 (d, J 11.6 Hz, 1HJ, 7.22 (d, J 8.4 Hz, 1H), 7.07 (s, 1H), 3.62 (s, 2H), 3.53 (t, J = 6.1 Hz, 2H), 2.83 (d, J = 4.7 Hz, 3H), 2.63 (s, 2H), 2.44 (s, 2H), 2.26 (s, 3H), 2.25 (s, 3H), 1.89 (s , 2H) Example 112.
6-(5-(3— (4- -부틸)—피페라진 -1-일) -5— (트리플루오로메틸)벤즈아미도) -4-플 루오로—2-메틸페닐)— ^메틸— 다졸— 3-카복스아미드의 제조  6- (5- (3— (4- -butyl) —piperazin-1-yl) -5— (trifluoromethyl) benzamido) -4-fluoro—2-methylphenyl) — ^ methyl— Doazole—Preparation of 3-Carboxamide
Figure imgf000077_0002
Figure imgf000077_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
]H 刚 R (300 MHz, DMSO-^i) δ 13.63 (s, 1H), 10.31 (s, 1H), 8.39 (d, / = 5.0 Hz, 1H), 8.21 (d, J = 8.3 Hz, 1H), 7.73 (s, 1H), 7.62 (s, 1H), 7.49 (d, J 10.4 Hz, 2H), 7.35 (s, 1H), 7.31 (d, J 11.7 Hz, 1H), 7.22 (d, J= 8.4 Hz, 1H), 3.30-3.26 (m, 4H), 2.83 (d, /= 4.7 Hz, 3H), 2.65 (s, 4H), 2.26 (s, 3H), 1.05 (s, 9H). 실시예 113. ] H 刚 R (300 MHz, DMSO- ^ i) δ 13.63 (s, 1H), 10.31 (s, 1H), 8.39 (d, / = 5.0 Hz, 1H), 8.21 (d, J = 8.3 Hz, 1H ), 7.73 (s, 1H), 7.62 (s, 1H), 7.49 (d, J 10.4 Hz, 2H), 7.35 (s, 1H), 7.31 (d, J 11.7 Hz, 1H), 7.22 (d, J = 8.4 Hz, 1H), 3.30-3.26 (m, 4H), 2.83 (d, / = 4.7 Hz, 3H), 2.65 (s, 4H), 2.26 (s, 3H), 1.05 (s, 9H). Example 113.
6-(5-(3-(3- (디에틸아미노)피롤리딘 -1-일) -5- (트리플루오로메틸)벤즈아미도)ᅳ 4 -플루오로 -2ᅳ메틸페닐 )-/^메틸— 1 ^인다졸 -3-카복스아미드의 제조  6- (5- (3- (3- (diethylamino) pyrrolidin-1-yl) -5- (trifluoromethyl) benzamido) ᅳ 4-fluoro-2 -methylphenyl)-/ ^ Preparation of methyl— 1 ^ indazole-3-carboxamide
Figure imgf000077_0003
Figure imgf000077_0003
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
lW刚 R (300 MHz, DMSO-fl!i) δ 13.62 (s, 1H), 10.30 (s, 1H), 8.39 (d, J= 4.8 Hz, 1H), 8.21 (d, J= 8.4 Hz, 1H), 7.74 (s, 1H)' 7.58 (s, 1H), 7.50 (s, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.35 (s, 1H), 7.31 (d, J= 11.6 Hz, 1H), 7.22 (dd, J= 8.4， 1.3 Hz, 1H), 3.88 (d, J= 12.5 Hz, 2H), 2.83 (d, J= 4.7 Hz, 3H), 2.78 (d, J= 12.4 Hz, 2H), 2.26 (s, 3H), 1.72 (d, J= 12.0 Hz, 2H), 1.30-1.13 (m, 3H), 0.94 (cl, J = 6.5 Hz, 311). 실시예 114. lW 刚 R (300 MHz, DMSO-fl! i) δ 13.62 (s, 1H), 10.30 (s, 1H), 8.39 (d, J = 4.8 Hz, 1H), 8.21 (d, J = 8.4 Hz, 1H ), 7.74 (s, 1H) '7.58 (s, 1H), 7.50 (s, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.35 (s, 1H), 7.31 (d, J = 11.6 Hz , 1H), 7.22 (dd, J = 8.4, 1.3 Hz, 1H), 3.88 (d, J = 12.5 Hz, 2H), 2.83 (d, J = 4.7 Hz, 3H), 2.78 (d, J = 12.4 Hz , 2H), 2.26 (s, 3H), 1.72 (d, J = 12.0 Hz, 2H), 1.30-1.13 (m, 3H), 0.94 (cl, J = 6.5 Hz, 311). Example 114.
6-(4-플루오로— 2-메틸 -5-(3— (4—메틸—피페리딘 -1-일)— 5— (트리플루오로메틸)벤즈 아미도)페닐 )-7 메틸 인다졸ᅳ 3-카복스아미드의 제조  6- (4-fluoro— 2-methyl-5- (3— (4—methyl-piperidin-1-yl) — 5— (trifluoromethyl) benz amido) phenyl) -7 methyl indazole ᅳ 3-carboxamide preparation
Figure imgf000078_0001
Figure imgf000078_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 43 .
'H NMR (300 MHz , DMS0一 δ 13.62 (s, 1H), 10.25 (s, 1H) , 8.39 (d, /= 4.8 Hz, 1H), 8.21 (d, /= 8.4 Hz, 1H), 7.52-7.44 (m, 3H), 7.34 (s, 1H), 7.31 (d, /= 11.8 Hz, 1H), 7.22 (dd, J 8.4, 1.3 Hz, 1H), 6.94 (s, 1H), 3.53 (del, J 二 28.6, 8.1 Hz, 2H), 3.12 (s, Hi), 2.83 (d, J 4.7 Hz, 3H), 2.62 (s, 3H), 2.26 (s, 4H), 2.24-2.11 (m, 2H), 1.88 (d, J 16.0 Hz, 2H), 0.98 (t, J 6.8 Hz, 6H). 실시예 115. 'H NMR (300 MHz, DMS0 δ 13.62 (s, 1H), 10.25 (s, 1H), 8.39 (d, / = 4.8 Hz, 1H), 8.21 (d, / = 8.4 Hz, 1H), 7.52- 7.44 (m, 3H), 7.34 (s, 1H), 7.31 (d, / = 11.8 Hz, 1H), 7.22 (dd, J 8.4, 1.3 Hz, 1H), 6.94 (s, 1H), 3.53 (del, J 2 28.6, 8.1 Hz, 2H), 3.12 (s, Hi), 2.83 (d, J 4.7 Hz, 3H), 2.62 (s, 3H), 2.26 (s, 4H), 2.24-2.11 (m, 2H) , 1.88 (d, J 16.0 Hz, 2H), 0.98 (t, J 6.8 Hz, 6H) Example 115.
6ᅳ(5ᅳ(3— (3,5—디메틸피페라진— 1-일 )ᅳ5— (트리플루오로메틸)벤즈아미도) -4-플루 오로ᅳ 2—메틸페닐 메틸— 1/ 인다졸ᅳ 3—카복스아미드 트리플루오로아세트산염의 제조  6 '(5' (3— (3,5—dimethylpiperazin— 1-yl) ᅳ 5— (trifluoromethyl) benzamido) -4-fluorochem 2—methylphenyl methyl— 1 / indazole ᅳ 3—Preparation of Carboxamide Trifluoroacetate
Figure imgf000078_0002
Figure imgf000078_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 43 .
Ή隱 (300 MHz, DMSO-flf;) δ 13.65 (s, 1H)， 10.34 (s, 1H), 9.15 (s, Hi) , 8.53 (d, J 10.5 Hz, 1H), 8.40 (d, J= 4.7 Hz, 1H), 8.22 (d, J= 8.4 Hz, 1H), 7.76 (d, /= 18.5 Hz, 2H), 7.51 (dd, J= 15.2, 12.0 Hz, 3H), 7.32 (d, J= 11.5 Hz, 1H), 7.22 (d, J = 8.4 Hz, 1H), 4.11 (d, J = 12.3 Hz, 2H), 2.83 (d, J = 4.6 Hz, 3H), 2.81-2.68 (m, 2H), 2.27 (s, 3H), 1.29 (d, J = 6.4 Hz, 6H). 실시예 116. 300 (300 MHz, DMSO-flf;) δ 13.65 (s, 1H), 10.34 (s, 1H), 9.15 (s, Hi), 8.53 (d, J 10.5 Hz, 1H), 8.40 (d, J = 4.7 Hz, 1H), 8.22 (d, J = 8.4 Hz, 1H), 7.76 (d, / = 18.5 Hz, 2H), 7.51 (dd, J = 15.2, 12.0 Hz, 3H), 7.32 (d, J = 11.5 Hz, 1H), 7.22 (d, J = 8.4 Hz, 1H), 4.11 (d, J = 12.3 Hz, 2H), 2.83 (d, J = 4.6 Hz, 3H), 2.81-2.68 (m, 2H) , 2.27 (s, 3 H), 1.29 (d, J = 6.4 Hz, 6 H). Example 116.
6ᅳ (4-플루오로 -2—메틸 -5-(3- (트리플루오로메틸 )ᅳ5-(3 , 4 , 5-트라이메틸피페라진- 1ᅳ일)벤즈아미도)페닐 )-그메틸 -1^인다졸 -3—카복스아미드  6 '(4-Fluoro-2-methyl-5- (3- (trifluoromethyl)' 5- (3,4,5-trimethylpiperazin-l-yl) benzamido) phenyl) -gmethyl -1 ^ indazole -3—carboxamide
트리플루오로아세트산염의 제조
Figure imgf000079_0001
Preparation of Trifluoroacetic Acid
Figure imgf000079_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
NM (300 MHz, DMSO-d) δ 13.62 (s, 1Η), 10.31 (s, IH), 9.28 (s, 1H), 8.39 (d, J = 4.8 Hz, 1H), 8.22 (d, J 8.3 Hz, 1H), 7.79 (s, 1H) , 7.74 (s, 1H), 7.58 (s, 1H), 7.49 (d, J 8.7 Hz, 2H), 7.32 (d, J= 11.5 Hz, 1H), 7.21 (d, J= 8.4 Hz, IH) , 4.17 (d, J = 12.8 Hz, 2H) , 2.92-2.85 (i , 4H), 2.83 (d, J = 4.7 Hz, 3H), 2.27 (s, 3H), 1.37 (t, J = 9.5 Hz, 5H) . 실시예 117.  NM (300 MHz, DMSO-d) δ 13.62 (s, 1Η), 10.31 (s, IH), 9.28 (s, 1H), 8.39 (d, J = 4.8 Hz, 1H), 8.22 (d, J 8.3 Hz , 1H), 7.79 (s, 1H), 7.74 (s, 1H), 7.58 (s, 1H), 7.49 (d, J 8.7 Hz, 2H), 7.32 (d, J = 11.5 Hz, 1H), 7.21 ( d, J = 8.4 Hz, IH), 4.17 (d, J = 12.8 Hz, 2H), 2.92-2.85 (i, 4H), 2.83 (d, J = 4.7 Hz, 3H), 2.27 (s, 3H), 1.37 (t, J = 9.5 Hz, 5H). Example 117.
6-(4-플루오로 -2-메틸ᅳ 5— (3— ( (4-메틸피페라진 -1—일 )-5-트리플루오로메틸)벤즈 아미도)페닐)ᅳ^메틸 - ] 인다졸 -3-카복스아미드의 제조  6- (4-fluoro-2-methyl ᅳ 5— (3— ((4-methylpiperazin-1-yl) -5-trifluoromethyl) benz amido) phenyl) ᅳ ^ methyl-] indazole Preparation of 3-Carboxamide
Figure imgf000079_0002
Figure imgf000079_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
]H NMR (300 MHz , DMSO-r^) δ 10.42 (s, 111)， 8.37 (t, J 4.8 Hz, IH), 8.20 (del, J = 9.7, 3.8 Hz, 3H) , 7.85 (s, IH), 7.51 (d, / = 6.0 Hz, 2H), 7.31 (d, / = 11.6 Hz, IH), 7.22 (dd, J = 8.4, 1.2 Hz, IH), 3.62 (s, 2H), 2.83 (t, J= 4.5 Hz, 3H), 2.36 (d, J 22.8 Hz, 6H), 2.26 (s, 4H), 2.14 (s, 3H). 실시예 118. ] H NMR (300 MHz, DMSO-r ^) δ 10.42 (s, 111), 8.37 (t, J 4.8 Hz, IH), 8.20 (del, J = 9.7, 3.8 Hz, 3H), 7.85 (s, IH ), 7.51 (d, / = 6.0 Hz, 2H), 7.31 (d, / = 11.6 Hz, IH), 7.22 (dd, J = 8.4, 1.2 Hz, IH), 3.62 (s, 2H), 2.83 (t , J = 4.5 Hz, 3H), 2.36 (d, J 22.8 Hz, 6H), 2.26 (s, 4H), 2.14 (s, 3H). Example 118.
6-(5-(3-(((2-디메틸아미노)에틸 (메틸)아미노)메틸) -5- (트리플루오로메틸)벤즈 아미도 )—4-플루오로— 2-메틸페닐 )— 메틸ᅳ 1^인다졸—3-카복스아미드의 제조  6- (5- (3-(((2-dimethylamino) ethyl (methyl) amino) methyl) -5- (trifluoromethyl) benz amido) —4-fluoro— 2-methylphenyl) — methyl ᅳ Preparation of 1 ^ indazole—3-carboxamide
Figure imgf000079_0003
Figure imgf000079_0003
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
]H NMR (300 MHz, D SO-^i) δ 8.38 (d, J= 5.0 Hz, IH), 8.20 (dd, J= 7.7， 4.7 Hz, 3H), 7.88 (s, IH), 7.51 (t, J= 3.9 Hz, 2H), 7.32 (d, J = 11.5 Hz, IH), 7.22 (d, J = 8.3 Hz, IH), 3.66 (s, 2H), 2.83 (d, J= 4.7 Hz, 3H), 2.38 (d, J= 6.4 Hz, 2H), 2.26 (s, 3H), 2.17 (s, 3H), 2.10 (d, J = 1.2 Hz, 6H) . 실시예 119. ] H NMR (300 MHz, D SO- ^ i) δ 8.38 (d, J = 5.0 Hz, IH), 8.20 (dd, J = 7.7, 4.7 Hz, 3H), 7.88 (s, IH), 7.51 (t , J = 3.9 Hz, 2H), 7.32 (d, J = 11.5 Hz, IH), 7.22 (d, J = 8.3 Hz, IH), 3.66 (s, 2H), 2.83 (d, J = 4.7 Hz, 3H ), 2.38 (d, J = 6.4 Hz, 2H), 2.26 (s, 3H), 2.17 (s, 3H), 2.10 (d, J = 1.2 Hz, 6H). Example 119.
6-(5—(3— ((2-아미노에틸)아미노 )-5- (트리플루오로메틸)벤즈아미도)ᅳ 4-플루오로 -2-메틸페닐)—그메틸ᅳ 1 ^인다졸 -3-카복스아미드의 제조  6- (5— (3— ((2-aminoethyl) amino) -5- (trifluoromethyl) benzamido) ᅳ 4-fluoro-2-methylphenyl) —glycol ᅳ 1 ^ indazole-3 Preparation of Carboxamide
Figure imgf000080_0001
Figure imgf000080_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
]H NMR (300 MHz , DMSO— ) δ 10.18 (s, 1H), 8.34 (d, J= 4.8 Hz, 1H), 8.21 (d, J 8.4 Hz, 1H), 7.48 (d, J= 8.4 Hz, 2H), 7.39 (d, J= 7.5 Hz, 2H), 7.29 (cl, 11.6 Hz, 1H), 7.25-7.18 (m, 1H), 7.03 (s, 1H), 6.37 (t, J= 5.4 Hz, 1H), 3.12 (del, J 11.8, 6.0 Hz, 2H), 2.84 (d, J= 4.6 Hz, 3H), 2.75 (t, J= 5.9 Hz, 2H), 2.26 (s, 3H). 실시예 120.  ] H NMR (300 MHz, DMSO—) δ 10.18 (s, 1H), 8.34 (d, J = 4.8 Hz, 1H), 8.21 (d, J 8.4 Hz, 1H), 7.48 (d, J = 8.4 Hz, 2H), 7.39 (d, J = 7.5 Hz, 2H), 7.29 (cl, 11.6 Hz, 1H), 7.25-7.18 (m, 1H), 7.03 (s, 1H), 6.37 (t, J = 5.4 Hz, 1H), 3.12 (del, J 11.8, 6.0 Hz, 2H), 2.84 (d, J = 4.6 Hz, 3H), 2.75 (t, J = 5.9 Hz, 2H), 2.26 (s, 3H). Example 120.
6— (5-(3— ((2-아미노— 2-메틸프로필)아미노 )-5- (트리플루오로메릴)벤즈아미도)一 4 -플루오로 -2-메틸페닐) 메틸ᅳ 인다졸—3-카복스아미드의 제조  6— (5- (3— ((2-amino— 2-methylpropyl) amino) -5- (trifluoromeryl) benzamido) 一 4 -fluoro-2-methylphenyl) methyl ᅳ indazole—3 Preparation of Carboxamide
Figure imgf000080_0002
Figure imgf000080_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
]H NMR (300 MHz, DMSOoi δ 10.16 (s, 1H)ᅳ 8.35 (s, 1H), 8.21 (cl, J 8.3 Hz, 1H), 7.52-7.43 (in, 3H), 7.38 (s, 1H), 7.29 (d, J = 11.6 Hz, 1H), 7.21 (cl, J = 8.4 Hz, 1H), 7.13 (s, 1H), 6.22 (s, 1H), 2.98 (d, J= 5.7 Hz, 2H), 2.83 (d, J = 4.6 Hz, 3H), 2.26 (sᅳ 4H)， 1.08 (s, 6H). 실시예 121.  ] H NMR (300 MHz, DMSOoi δ 10.16 (s, 1H) ᅳ 8.35 (s, 1H), 8.21 (cl, J 8.3 Hz, 1H), 7.52-7.43 (in, 3H), 7.38 (s, 1H), 7.29 (d, J = 11.6 Hz, 1H), 7.21 (cl, J = 8.4 Hz, 1H), 7.13 (s, 1H), 6.22 (s, 1H), 2.98 (d, J = 5.7 Hz, 2H), 2.83 (d, J = 4.6 Hz, 3H), 2.26 (s ᅳ 4H), 1.08 (s, 6H) Example 121.
6一 (5— (3— ( (2ᅳ디메틸아미노 -2—메틸프로필)아미노)— 5- (트리플루오로메틸 )벤즈아 미도) -4—플루오로 -2—메틸페닐 )— 메틸 -1^인다졸—3-카복스아미드 트리플루오로아세트산염의 제조  6 one (5— (3— ((2 ᅳ dimethylamino-2—methylpropyl) amino) — 5- (trifluoromethyl) benzamido) -4—fluoro-2-2-methylphenyl) —methyl-1 ^ Preparation of indazole—3-carboxamide trifluoroacetate
Figure imgf000080_0003
Figure imgf000080_0003
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
NMR (300 MHz, DMS0-¾) δ 10.21 (s, 1H), 9.23 (s, 1H), 8.35 (s, 1H), 8.25 (d, J= 8.4 Hz, 1H), 7.58 (s, 2H), 7.51 (d, J= 5.8 Hz, 2H), 7.32 (d, J= 11.6 Hz, 1H) , 7.28 (s, 1H), 7.23 (d, J 8.4 Hz, IH), 6.43 (s, 1H), 2.86 (d, J 4.7 Hz, 5H), 2.79 (d, J = 4.6 Hz, 6H), 2.29 (s, 3H), 1.37 (s, 6H). 실시예 122. NMR (300 MHz, DMS0-¾) δ 10.21 (s, 1H), 9.23 (s, 1H), 8.35 (s, 1H), 8.25 (d, J = 8.4 Hz, 1H), 7.58 (s, 2H), 7.51 (d, J = 5.8 Hz, 2H), 7.32 (d, J = 11.6 Hz, 1H), 7.28 (s, 1H), 7.23 (d, J 8.4 Hz, IH), 6.43 (s, 1H), 2.86 (d, J 4.7 Hz, 5H), 2.79 (d, J = 4.6 Hz, 6H), 2.29 (s, 3H), 1.37 (s, 6H). Example 122.
6-(4-플루오로 -5-(3—((2—하이드록시부틸)아미노 )-5— (트리플루오로메틸)벤즈아 미도) -2-메틸페닐 메틸 인다졸—3-카복스아미드의 제조  6- (4-fluoro-5- (3 — ((2—hydroxybutyl) amino) -5— (trifluoromethyl) benzamido) -2-methylphenyl methyl indazole—3-carboxamide Produce
Figure imgf000081_0001
Figure imgf000081_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
匿 (300 MHz, CD30D一 ) δ 0.99 (t, J= 7.5 Hz, 3H) , 1.48(m 2H), 2.28 (s, 3H), 2.99 (s, 3H), 3.23 (m, 2H), 3.69 (m, 1H), 7.07 (s, 1H), 7.21 (d, J= 11.3 Hz, 1H), 7.26(dd, /= 1.2 Hz, /= 8.4 Hz, 1H), 7.40(m? 2H), 7.51(s, 1H), 7.57(d, J = 7.9 Hz, 1H), 8.27(cl, J 8.4 Hz, IH) 실시예 123. 300 (300 MHz, CD 3 0D one) δ 0.99 (t, J = 7.5 Hz, 3H), 1.48 (m 2H), 2.28 (s, 3H), 2.99 (s, 3H), 3.23 (m, 2H), 3.69 (m, 1H), 7.07 (s, 1H), 7.21 (d, J = 11.3 Hz, 1H), 7.26 (dd, / = 1.2 Hz, / = 8.4 Hz, 1H), 7.40 (m ? 2H), 7.51 (s, 1 H), 7.57 (d, J = 7.9 Hz, 1 H), 8.27 (cl, J 8.4 Hz, IH) Example 123.
6一 (4-플루오로— 5-(3— ( (3-하이드록시프로필)아미노 )-5— (트리플루오로메틸 )벤즈 아미도 )-2-메틸페닐 )-y 메틸 인다졸 -3-카복스아미드의 제조  6- (4-Fluoro— 5- (3— ((3-hydroxypropyl) amino) -5— (trifluoromethyl) benz amido) -2-methylphenyl) -y methyl indazole-3-car Preparation of Voxamide
Figure imgf000081_0002
Figure imgf000081_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
NMR (300 MHz, CD30D-i4) δ 1.89(m, 2Η), 2.28(s, 3H), 2.99(s, 3H), 3.70(m, 2H), 7.03(s, IH), 7.17(d, J= 11.4 Hz, IH), 7.26(cld, J= 1.3 Hz, J 8.4 Hz, IH), 7.38(d, /= 9.8 Hz, 2H), 7.51(s, IH), 7.58(d, /= 7.9 Hz, IH), 8.27(d, J = 8.4 Hz, IH) 실시예 124. NMR (300 MHz, CD 3 0D-i 4 ) δ 1.89 (m, 2Η), 2.28 (s, 3H), 2.99 (s, 3H), 3.70 (m, 2H), 7.03 (s, IH), 7.17 ( d, J = 11.4 Hz, IH), 7.26 (cld, J = 1.3 Hz, J 8.4 Hz, IH), 7.38 (d, / = 9.8 Hz, 2H), 7.51 (s, IH), 7.58 (d, / = 7.9 Hz, IH), 8.27 (d, J = 8.4 Hz, IH) Example 124.
6-(4ᅳ플루오로 -5-(3-((2-하이드록시에틸)아미노 )-5- (트리플루오로메틸)벤즈아 미도) -2—메틸페닐)— 메틸 -1^인다졸 -3-카복스아미드의 제조  6- (4 ᅳ fluoro-5- (3-((2-hydroxyethyl) amino) -5- (trifluoromethyl) benzamido) -2—methylphenyl) —methyl-1 ^ indazole-3 Preparation of Carboxamide
Figure imgf000081_0003
Figure imgf000081_0003
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. Ή NMR (300 MHz , DMSO^) δ 13.58 (s, 1H), 10.18 (s, 1H), 8.36-8.34 (d, J = 5.1 Hz, 1H), 8.23-8.20 (d, ./= 8.4 Hz, 1H), 7.50—7.47 (m, 2H), 7.39-7.38 (d, J 3.5 Hz, 2H), 7.31-7.27 (d, J 11.6 Hz, 1H), 7.23—7.20 (dd, /= 8.3, 1.4 Hz, 1H), 7.07 (s, 1H), 6.37-6.35 (m, 1H), 4.76-4.72 (t, = 5.4 Hz, 1H), 3.61-3.55 (q, J = 5.8 Hz, 2H), 3.24-3.16 (m, 2H), 2.64-2.63 (d, J= 4.7 Hz, 3H), 2.26 (s, 3H). 실시예 125. The title compound was obtained in the same manner as the Example 43. NMR (300 MHz, DMSO ^) δ 13.58 (s, 1H), 10.18 (s, 1H), 8.36-8.34 (d, J = 5.1 Hz, 1H), 8.23-8.20 (d, ./= 8.4 Hz, 1H), 7.50—7.47 (m, 2H), 7.39-7.38 (d, J 3.5 Hz, 2H), 7.31-7.27 (d, J 11.6 Hz, 1H), 7.23—7.20 (dd, / = 8.3, 1.4 Hz , 1H), 7.07 (s, 1H), 6.37-6.35 (m, 1H), 4.76-4.72 (t, = 5.4 Hz, 1H), 3.61-3.55 (q, J = 5.8 Hz, 2H), 3.24-3.16 (m, 2H), 2.64-2.63 (d, J = 4.7 Hz, 3H), 2.26 (s, 3H). Example 125.
6-(4-플루오로 -5-(3— ( (2-하이드록시프로필)아미노 )— 5ᅳ (트리플루오로메틸)벤즈 아미도)— 2—메틸페닐)—Λ^메틸— 1/ 인다졸 -3—카복스아미드의 제조  6- (4-fluoro-5- (3— ((2-hydroxypropyl) amino) — 5 ′ (trifluoromethyl) benz amido) — 2—methylphenyl) —Λ ^ methyl— 1 / indazole -3—Manufacture of Carboxamides
Figure imgf000082_0001
Figure imgf000082_0001
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
MS ιιι/ζ [M+H] 544 실시예 126. MS ιιι / ζ [M + H] 544 Example 126.
6-(4-플루오로— 5— (3-( (2—하이드록시— 2—메틸프로필)아미노 )-5- (트리플루오로메 틸 )벤즈아미도)—2-메틸페닐 )- ^메틸 -1/ 인다졸 -3ᅳ카복스아미드의 제조  6- (4-fluoro— 5— (3- ((2—hydroxy— 2—methylpropyl) amino) -5- (trifluoromethyl) benzamido) —2-methylphenyl)-^ methyl-1 / Preparation of indazole-3 ᅳ carboxamide
Figure imgf000082_0002
Figure imgf000082_0002
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 43.
l[\ NMR (500 MHz, DMSO-d δ 10.15 (s, LH), 8.35 (d, /= 4.7 Hz, 1H), 8.19 (d, J = 8.4 Hz, 1H), 7.48 (s, 1H), 7.46 (d, J= 8.0 Hz, 1H), 7.42 (s, 1H), 7.35 (s, 1H), 7.28 (d, J 11.3 Hz, 1H), 7.20 (d, J= 8.4 Hz, 1H)， 7.16 (s, 1H), 6.18 (t, J= 5.9 Hz, 1H), 4.49 (s, 1H), 3.04 (d, J = 5.7 Hz, 2H), 2.81 (d, J= 4.7 Hz, 3H), 2.24 (s, 3H), 1.16 (s, 5H). 실시예 127. l [\ NMR (500 MHz, DMSO-d δ 10.15 (s, LH), 8.35 (d, / = 4.7 Hz, 1H), 8.19 (d, J = 8.4 Hz, 1H), 7.48 (s, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.42 (s, 1H), 7.35 (s, 1H), 7.28 (d, J 11.3 Hz, 1H), 7.20 (d, J = 8.4 Hz, 1H), 7.16 (s, 1H), 6.18 (t, J = 5.9 Hz, 1H), 4.49 (s, 1H), 3.04 (d, J = 5.7 Hz, 2H), 2.81 (d, J = 4.7 Hz, 3H), 2.24 (s, 3H), 1.16 (s, 5H) Example 127.
6-(4ᅳ플루오로— 2-메틸 -5-(3— (메틸 ) ( ( 1ᅳ메틸 -1^피라졸 -4—일)메틸)아미노 )-5一( 트리플루오로메틸)벤즈아미도)페닐) 메틸— 1^인다졸 -3-카복스아미드의 제조  6- (4 ᅳ fluoro- 2-methyl-5- (3— (methyl) ((1 ᅳ methyl-1 ^ pyrazol-4-yl) methyl) amino) -5 一 (trifluoromethyl) benzami FIG.) Preparation of Phenyl) Methyl—1 ^ indazole-3-carboxamide
Figure imgf000082_0003
상기 실시예 43과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.
Figure imgf000082_0003
The title compound was obtained in the same manner as the Example 43.
NMR (300 MHz , DMSCH ) δ 13.6 (s, 1H), 10.3 (s, 1H), 8.40 (q, 1H, /= 4.8 Hz), 8.23 (d, 1H, J 8.1 Hz), 7.57 Cs, 2H), 7.51 (s, 2H), 7.48 (d, 1H, J = 8.1 Hz), 7.32-7.29 (m, 2H), 7.24 (cld, 1H, = 8.1, 1.2 Hz), 7.17 (s, 1H), 4.52 (s, 2H), 3.75 (s, 3H), 3.04 (s, 3H), 2.84 (d, 3H, J 4.8 Hz), 2.26 (s, 3H). 실시예 128.  NMR (300 MHz, DMSCH) δ 13.6 (s, 1H), 10.3 (s, 1H), 8.40 (q, 1H, / = 4.8 Hz), 8.23 (d, 1H, J 8.1 Hz), 7.57 Cs, 2H , 7.51 (s, 2H), 7.48 (d, 1H, J = 8.1 Hz), 7.32-7.29 (m, 2H), 7.24 (cld, 1H, = 8.1, 1.2 Hz), 7.17 (s, 1H), 4.52 (s, 2H), 3.75 (s, 3H), 3.04 (s, 3H), 2.84 (d, 3H, J 4.8 Hz), 2.26 (s, 3H). Example 128.
6-(5— (3-(2-디메틸아미노)에특시)ᅳ 5- (트리플루오로메틸)벤즈아미도) -4-플루오 로— 2-메틸페닐)— 메틸 인다졸 -3-카복스아미드의 제조  6- (5— (specific to 3- (2-dimethylamino)) ᅳ 5- (trifluoromethyl) benzamido) -4-fluoro—2-methylphenyl) —methyl indazole-3-carboxamide Manufacture
Figure imgf000083_0001
단계 1:
Figure imgf000083_0001
Step 1:
6— (5ᅳ (3-(2-디메틸아미노)에톡시 )-5ᅳ (트리플루오로메틸)벤즈아미도) -4-플루오 로 _2ᅳ메틸페닐 메틸— 1— (테트라하이드로— 2/ 피란— 2-일 )—1 인다졸 -3-카복스 아미드의 제조 6— (5 '(3- (2-dimethylamino) ethoxy) -5' (trifluoromethyl) benzamido) -4-fluoro _ 2 ᅳ methylphenyl methyl— 1— (tetrahydro— 2 / pyran — 2-yl) —1 Preparation of indazole-3-carboxamide
상기 실시예 43의 단계 1의 방법으로 얻은 Obtained by the method of step 1 of Example 43 above.
6-(4-플루오로 -5-(3-플루오로— 5- (트리플루오로메틸)벤즈아미도)—2-메틸페닐 ᅳ메틸—1- (테트라하이드로— 2^피란— 2—일) -I 인다졸—3-카복스아미드 (998 mg)를 THF (10 mL)에 용해시킨 다음 10% NaH (100 mg)와 4— (디메틸아미노)에틸알콜을 넣고 1 시간 동안 마이크로웨이브 반응기 (125 °C)에서 반응하였다. 6- (4-fluoro-5- (3-fluoro— 5- (trifluoromethyl) benzamido) —2-methylphenyl 페닐 methyl- 1- (tetrahydro— 2 ^ pyran— 2—yl)- I indazole—3-carboxamide (998 mg) was dissolved in THF (10 mL), then 10% NaH (100 mg) and 4— (dimethylamino) ethyl alcohol were added to the microwave reactor (125 ° C ) for 1 hour. In C).
반웅이 종결하면 염화나트륨 수용액을 사용하고 에틸아세테이트로 추출한 다음에 모아진 유기층을 무수 황산마그네슘으로 건조하여 여과하였다. When the reaction was completed, using an aqueous sodium chloride solution, extracted with ethyl acetate, and the combined organic layers were dried over anhydrous magnesium sulfate and filtered.
용매를 감압 증류로 제거하여 목적화합물인 The solvent is removed by distillation under reduced pressure
ᅳ (5— (3-(2-디메틸아미노)에톡시 )—5- (트리플루오로메틸)벤즈아미도) -4—플루오로 -2-메틸페닐 ) - 메틸 -1ᅳ (테트라하이드로— 2 ^피란 -2ᅳ일 )—1^인다졸 -3ᅳ카복스아 미드를 얻었다. MS m/z [M+H] 642 단계 2: 5 (5— (3- (2-dimethylamino) ethoxy) —5- (trifluoromethyl) benzamido) -4—fluoro-2-methylphenyl) -methyl-1 ᅳ (tetrahydro— 2 ^ Piran -2 ᅳ day) —1 ^ indazole -3 ᅳ carbox child Mid was obtained. MS m / z [M + H] 642 Step 2:
6-(5— (3—(2—디메틸아미노)에톡시 )-5- (트리플루오로메틸)벤즈아미도) -4-플루오 로ᅳ 2—메틸페닐) 메틸— I 인다졸— 3-카복스아미드의 제조  6- (5— (3— (2—dimethylamino) ethoxy) -5- (trifluoromethyl) benzamido) -4-fluoro 플루오 2—methylphenyl) methyl— I indazole— 3-carbox Preparation of Amides
Figure imgf000084_0001
Figure imgf000084_0001
상기 실시예 43의 단계 2와 동일한 방법으로 수행하여, In the same manner as in Step 2 of Example 43,
6— (5— (3-(2-디메틸아미노)에록시 )-5- (트리플루오로메틸 )벤즈아미도)—4-플루오 로ᅳ 2-메틸페닐) -Λ^메틸 인다졸 -3—카복스아미드를 얻었다. MS m/z [M+H]6— (5— (3- (2-dimethylamino) ethoxy) -5- (trifluoromethyl) benzamido) —4-fluorophenyl 2-methylphenyl) -Λ ^ methyl indazole- 3 —ca Voxamide was obtained. MS m / z [M + H]
558 실시예 129. 558 Example 129.
6-(4—플루오로 -2-메틸 -5— (3— 메틸피를린— 2-일 )에톡시 )-5— (트리플루오로메 틸)벤즈아미도)페닐) 메틸— 1/ 인다졸—3—카복스아미드의 제조  6- (4—fluoro-2-methyl-5— (3— methylpyrroline— 2-yl) ethoxy) -5— (trifluoromethyl) benzamido) phenyl) methyl— 1 / indazole —3—Manufacture of Carboxamides
Figure imgf000084_0002
Figure imgf000084_0002
상기 실시예 128과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾ NMR (300 MHz , DMSO— of;) δ 13.59 (s, 1H), 10.38 (s, 1H), 9.47 (s, 1H), 8.35-8.33 (d, J = 4.9 Hz, 1H), 8.24-8.21 (d, /= 8.4 Hz, 1H), 7.95 (s, 1H) 7.82 (s, 1H), 7.51-7.48 (t, J 3.9 Hz, 2H) , 7.33—7.30 (d, J= 11.5 Hz, 1H) 7.23-7.19 (del, J= 8.7, 1.2 Hz, 1H), 4.30-4.25 (m, 2H), 3.63—3.57 (ni, 1H) 3.26-2.10 (m, 1H), 2.89—2.88 (d, /= 4.7 Hz, 3H), 2.84-2.83 (d, J= 4.6 Hz 3H), 2.27 (s, 3H), 2.05—1.88 (m, 3H), 1.81-1.71 (m, 1H). 실시예 130.  The title compound was obtained in the same manner as the Example 128. ¾ NMR (300 MHz, DMSO— of;) δ 13.59 (s, 1H), 10.38 (s, 1H), 9.47 (s, 1H), 8.35-8.33 (d, J = 4.9 Hz, 1H), 8.24-8.21 (d, / = 8.4 Hz, 1H), 7.95 (s, 1H) 7.82 (s, 1H), 7.51-7.48 (t, J 3.9 Hz, 2H), 7.33—7.30 (d, J = 11.5 Hz, 1H) 7.23-7.19 (del, J = 8.7, 1.2 Hz, 1H), 4.30-4.25 (m, 2H), 3.63—3.57 (ni, 1H) 3.26-2.10 (m, 1H), 2.89—2.88 (d, / = 4.7 Hz, 3H), 2.84-2.83 (d, J = 4.6 Hz 3H), 2.27 (s, 3H), 2.05—1.88 (m, 3H), 1.81-1.71 (m, 1H). Example 130.
6— (5— (3— (2- (디메틸아미노) -2-메틸프로폭시 )-5— (트리플루오로메틸)벤즈아미도) -4-플루오로 -2—메틸페닐시메틸 -1^인다졸—3-카복스아미드  6— (5— (3— (2- (dimethylamino) -2-methylpropoxy) -5— (trifluoromethyl) benzamido) -4-fluoro-2—methylphenylmethylmethyl-1 ^ is Sol—3-Carboxamide
트리플루오로아세트산염의 제조 Preparation of Trifluoroacetic Acid
Figure imgf000084_0003
Figure imgf000084_0003
상기 실시예 128과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. Ή NMR (300 MHz, DMSO— δ 13.65 (s, 1H), 10.46 (s, IH) , 9.58 (s, 1H), 8.39 (cl, J= 4.7 Hz, IH), 8.22 (d, /= 8.4 Hz, 1H) , 8.01 (s, 111)， 7.88 (s, H ), 7.59 (s, IH), 7.54-7.44 (m, 2H), 7.33 (d, J 11.4 Hz, IH), 7.21 (cl, J = 8.4 Hz, IH), 4.34 (s, 2H), 2.83 (cl, J 4.5 Hz,'3H), 2.79 (d, J = 4.7 Hz, 6H), 2.27 (s, 3H), 1.41 (s, 6H). 실시예 131. The title compound was obtained in the same manner as the Example 128. NMR (300 MHz, DMSO—δ 13.65 (s, 1H), 10.46 (s, IH), 9.58 (s, 1H), 8.39 (cl, J = 4.7 Hz, IH), 8.22 (d, / = 8.4 Hz , 1H), 8.01 (s, 111), 7.88 (s, H), 7.59 (s, IH), 7.54-7.44 (m, 2H), 7.33 (d, J 11.4 Hz, IH), 7.21 (cl, J = 8.4 Hz, IH), 4.34 (s, 2H), 2.83 (cl, J 4.5 Hz, ' 3H), 2.79 (d, J = 4.7 Hz, 6H), 2.27 (s, 3H), 1.41 (s, 6H Example 131.
6—(5— (3—(2—아미노— 2—메틸프로폭시 )-5— (트리플루오로메틸)벤즈아미도)—4-플루 오로 -2-메틸페닐 메틸 인다졸 -3-카복스아미드의 제조  6— (5— (3— (2—amino— 2—methylpropoxy) -5— (trifluoromethyl) benzamido) —4-fluoro-2-methylphenyl methyl indazole-3-carboxamide Manufacture
Figure imgf000085_0001
Figure imgf000085_0001
상기 실시예 128과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ]H NMR (300 MHz, DMSO—o! δ 13.65 (s, IH), 10.46 (s, IH), 8.39 (t, J = 4.7 Hz, IH), 8.22 (cl, /= 8.3 Hz, IH), 8.12 (s, 2H) , 8.00 (s, IH), 7.88 (s, IH), 7.52 (t, J= 14.1 Hz, 3H), 7.33 (cl, J = 11.6 Hz, IH), 7.22 (del, J 8.4， 1.3 Hz, IH), 4.15 (s, 2H), 2.83 (cl, J= 4.7 Hz, 3H) , 2.27 (s, 3H), 1.36 (s, 6H). 실시예 132. The title compound was obtained in the same manner as the Example 128. ] H NMR (300 MHz, DMSO—o! Δ 13.65 (s, IH), 10.46 (s, IH), 8.39 (t, J = 4.7 Hz, IH), 8.22 (cl, / = 8.3 Hz, IH), 8.12 (s, 2H), 8.00 (s, IH), 7.88 (s, IH), 7.52 (t, J = 14.1 Hz, 3H), 7.33 (cl, J = 11.6 Hz, IH), 7.22 (del, J 8.4, 1.3 Hz, IH), 4.15 (s, 2H), 2.83 (cl, J = 4.7 Hz, 3H), 2.27 (s, 3H), 1.36 (s, 6H) Example 132.
6-(5-(3-(( 1- (디메틸아미노)프로판 -2-일 )옥시 )-5— (트리플루오로메틸)벤즈아口 도)— 4-플루오로 -2-메틸페닐 )- 메틸 인다졸 -3-카복스아미드  6- (5- (3-((1- (dimethylamino) propan-2-yl) oxy) -5— (trifluoromethyl) benzoidal) —4-fluoro-2-methylphenyl) -methyl Indazole-3-carboxamide
트리플루오로아세트산염의 제조 Preparation of Trifluoroacetic Acid
Figure imgf000085_0002
Figure imgf000085_0002
상기 실시예 128과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. MS m/z [M+H] 669 실시예 133.  The title compound was obtained in the same manner as the Example 128. MS m / z [M + H] 669 Example 133.
6一(5-(3— (피를리딘 -1-일에록시) -5- (트리플루오로메틸)벤즈아미도) -4—플루오로— 2-메틸페닐 메틸 -I 인다졸—3-카복스아미드의 제조  6- (5- (3— (Pyridin-1-yleoxy) -5- (trifluoromethyl) benzamido) -4—fluoro—2-methylphenyl methyl-I indazole—3-car Preparation of Voxamide
Figure imgf000085_0003
Figure imgf000085_0003
상기 실시예 128과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 128.
H NMR (300 MHz, DMS0—애 δ 13.6 (bs, IH), 10.4 (s, IH)， 8.41 (q, IH, J= 4.2 Hz), 8.23 (d, 1H, J=8.1Hz), 7.75 (s, 1H), 7.87 (s, 1H), 7.83 (s, 1H), 7.51-7.48 (m, 3H), 7.33 (d, 1H, J 11.7 Hz), 7.24 (dd, 1H, J 8.4, 1.2 Hz), 4.26 (t, 2H, J= 5.7 Hz), 2.86-2.82 (m, 3H), 2.84 (cl, 3H, /= 4.8 Hz), 2.55—2.49 (m, 4H), 2.26 (s, 3H), 1.71—1.66 (m, 3H) 실시예 134. H NMR (300 MHz, DMS0—PE δ 13.6 (bs, IH), 10.4 (s, IH), 8.41 (q, IH, J = 4.2 Hz), 8.23 (d, 1H, J = 8.1 Hz), 7.75 (s, 1H), 7.87 (s, 1H), 7.83 (s, 1H), 7.51-7.48 (m, 3H), 7.33 (d, 1H , J 11.7 Hz), 7.24 (dd, 1H, J 8.4, 1.2 Hz), 4.26 (t, 2H, J = 5.7 Hz), 2.86-2.82 (m, 3H), 2.84 (cl, 3H, / = 4.8 Hz ), 2.55—2.49 (m, 4H), 2.26 (s, 3H), 1.71—1.66 (m, 3H) Example 134.
6_(4-플루오로— 5-(3-(4-플루오로 -3-메틸페닐)우레이도)—2-메틸페닐 )— 메틸 -인다졸 -3-카복스아미드의 제조  Preparation of 6_ (4-fluoro— 5- (3- (4-fluoro-3-methylphenyl) ureido) —2-methylphenyl) —methyl-indazole-3-carboxamide
Figure imgf000086_0001
Figure imgf000086_0001
트리포스젠 (19 mg, 65 ol)을 녹인 THF (2 inL) 용액에 ,  In THF (2 inL) solution with triphosphene (19 mg, 65 ol) dissolved,
6一 (5—아미노 -4_플루오로— 2-메틸페닐 )— / 메틸— 1- (테트라하이드로 피란 -2-일 ) 인다졸 -3-카르보아미드 (50 mg, 131 ol)을 녹인 THF (3 mL) 용액을 적가하였다. 30분 동안 교반한 후 상기 흔합액에 TEA (36 id, 261 mmol), 3-플루오로— 4—메틸아닐린 (18 mg, 144 ol)을 녹인 THF (5 mL) 용액을 적가하였다. 2시간 동안 교반한 후, 에틸아세테이트와 물로 분별하고 유기층을 소금물으로 2회 씻어주었다. 유기층의 물을 무수 황산나트륨으로 건조시키고 여과 및 농축하였다. 잔사를 메틸렌클로라이드 (5 mL)로 녹인 후 TFA (1 mL)를 적가하였다. 15시간 동안 교반한 후, NaHC03용액으로 염기화한 후 유기층을 분리하여 무수 황산나트륨으로 건조시키고 여과 및 농축한다. 컬럼 크로마토그래피 (silicagel, DCM: Me0H=10:l)를 통해 정제하였다. ¾ NMR (300 MHz, DMS0— δ 13.75 (s, 1H), 13.29 (s, 1H), 13.12 (d, J= 4.8 Hz, 1H), 12.93 (d, J = 8.5 Hz, 1H), 12.81 (cl, J= 8.5 Hz, 1H), 12.20 (s, 1H), 12.14-12.06 (m, 1H) , 11.95 (t, J= 9.7 Hz, 3H), 11.77 (t, J = 9.2 Hz, 1H), 7.57 (d, J = 4.7 Hz, 3H), 6.93 (s, 6H). 실시예 135. THF dissolved in 6 一 (5—amino-4_fluoro— 2-methylphenyl) — / methyl— 1- (tetrahydropyran-2-yl) indazole-3-carboamide (50 mg, 131 ol) 3 mL) was added dropwise. After stirring for 30 minutes, a THF (5 mL) solution of TEA (36 id, 261 mmol), 3-fluoro-4-4-methylaniline (18 mg, 144 ol) was added dropwise to the mixture. After stirring for 2 hours, the mixture was partitioned with ethyl acetate and water, and the organic layer was washed twice with brine. The water in the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was dissolved in methylene chloride (5 mL) and then TFA (1 mL) was added dropwise. After stirring for 15 hours, the organic layer was separated after basifying with NaHC0 3 solution, dried over anhydrous sodium sulfate, filtered and concentrated. Purification was by column chromatography (silicagel, DCM: Me0H = 10: l). ¾ NMR (300 MHz, DMS0—δ 13.75 (s, 1H), 13.29 (s, 1H), 13.12 (d, J = 4.8 Hz, 1H), 12.93 (d, J = 8.5 Hz, 1H), 12.81 (cl , J = 8.5 Hz, 1H), 12.20 (s, 1H), 12.14-12.06 (m, 1H), 11.95 (t, J = 9.7 Hz, 3H), 11.77 (t, J = 9.2 Hz, 1H), 7.57 (d, J = 4.7 Hz, 3H), 6.93 (s, 6H) Example 135.
( )-6-(4-플루오로 -5-(3— (3— ( 1- (하이드록시이미노)에틸 )페닐 )우레이도) -2-메틸 페닐) 메틸 -I 인다졸 -3-카복스아미드의 제조  () -6- (4-fluoro-5- (3— (3— (1- (hydroxyimino) ethyl) phenyl) ureido) -2-methyl phenyl) methyl-I indazole-3-carbox Preparation of Amides
Figure imgf000086_0002
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. Ή NMR (300 MHz , DMSO-rf;) δ 8.23 (d, J= 8.4 Hz, 1H), 7.98 (d, J= 8.4 Hz, 1H), 7.73 (s, 1H), 7.49 (s, 1H), 7.43—7.41 (m, 1H), 7.28一 7.20 (m, 3H), 7.08 (d, J = 12.3 Hz, 1H), 2.99 (s: 3H), 2.21 (s, 3H), 2.20 (s, 3H) 실시예 136.
Figure imgf000086_0002
The title compound was obtained in the same manner as the Example 134. NMR (300 MHz, DMSO-rf;) δ 8.23 (d, J = 8.4 Hz, 1H), 7.98 (d, J = 8.4 Hz, 1H), 7.73 (s, 1H), 7.49 (s, 1H), 7.43—7.41 (m, 1H), 7.28 7. 7.20 (m, 3H), 7.08 (d, J = 12.3 Hz, 1H), 2.99 (s: 3H), 2.21 (s, 3H), 2.20 (s, 3H) Example 136.
6-(4-플루오로 -2-메틸 -5— (3-(3- (트리플루오로메틸 )페닐)우레이도)페닐) - 메틸 -l/ 인다졸—3-카복스아미드의 제조  Preparation of 6- (4-fluoro-2-methyl-5— (3- (3- (trifluoromethyl) phenyl) ureido) phenyl) -methyl-1 / indazole—3-carboxamide
Figure imgf000087_0001
Figure imgf000087_0001
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. H NMR (300 MHz , DMSO—d;) δ 9.41 (s, 1Η), 8.67 (s, 1H) , 8.38 (cl, J 4.8 Hz, 1H), 8.20 (d, J 8.4 Hz, 1H), 8.08-7.99 (m, 210, 7.51 (d, J 5.2 Hz, 2H), 7.47 (s, 1H), 7.32 (cl, J = 4.0 Hz, 1H), 7.25 (cl, J= 12.4 Hz, 1H), 7.20 (del, / = 8.4, 1.3 Hz, 1H), 2.83 (d, J 4.7 Hz, 3H) , 2.21 (d, J = 6.4 Hz, 3H). 실시예 137.  The title compound was obtained in the same manner as the Example 134. H NMR (300 MHz, DMSO—d;) δ 9.41 (s, 1Η), 8.67 (s, 1H), 8.38 (cl, J 4.8 Hz, 1H), 8.20 (d, J 8.4 Hz, 1H), 8.08- 7.99 (m, 210, 7.51 (d, J 5.2 Hz, 2H), 7.47 (s, 1H), 7.32 (cl, J = 4.0 Hz, 1H), 7.25 (cl, J = 12.4 Hz, 1H), 7.20 ( del, / = 8.4, 1.3 Hz, 1H), 2.83 (d, J 4.7 Hz, 3H), 2.21 (d, J = 6.4 Hz, 3H) Example 137.
6-(4—플루오로— 2-메틸—5— (3-(4-메틸 -3— (트리플루오로메틸)페닐)우레이도)페닐) 메틸 - 인다졸—3-카복스아미드의 제조  Preparation of 6- (4—fluoro— 2-methyl—5— (3- (4-methyl-3— (trifluoromethyl) phenyl) ureido) phenyl) methyl-indazole—3-carboxamide
Figure imgf000087_0002
Figure imgf000087_0002
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 134.
NMR (300 MHz, DMSOfli;) δ 14.03 (s, 1H), 13.35 (s, 1H), 13.11 (s, 1H), 12.94 (d, J= 8.1 Hz, 1H), 12.77 (d, J = 8.7 Hz, 1H), 12.65 (s, 1H), 12.19 (d, J = 10.6 Hz, 2H), 12.07 (d, J= 8.1 Hz, 1H), 12.01-11.90 (m, 2H), 7.57 (d, J = 4.5 Hz, 3H), 7.10 (s, 3H), 6.93 (s, 3H). 실시예 138. NMR (300 MHz, DMSOfli;) δ 14.03 (s, 1H), 13.35 (s, 1H), 13.11 (s, 1H), 12.94 (d, J = 8.1 Hz, 1H), 12.77 (d, J = 8.7 Hz , 1H), 12.65 (s, 1H), 12.19 (d, J = 10.6 Hz, 2H), 12.07 (d, J = 8.1 Hz, 1H), 12.01-11.90 (m, 2H), 7.57 (d, J = 4.5 Hz, 3H), 7.10 (s, 3H), 6.93 (s, 3H). Example 138.
6一(5-(3-(4-클로로 -3— (트리플루오로메틸)페닐)우레이도) -4—플루오로 -2-메틸페 닐시메틸 -i 인다졸—3-카복스아미드의 제조  Preparation of 6- (5- (3- (4-chloro-3— (trifluoromethyl) phenyl) ureido) -4—fluoro-2-methylphenylmethylmethyl-i indazole—3-carboxamide
Figure imgf000087_0003
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. 1謹 R (300 MHz, DMSO-οί;) δ 18.31 (s, IH), 14.23 (s, IH), 13.42 (s, IH), 13.12 (d, J = 4.9 Hz, IH), 12.94 (d, J 8.4 Hz, IH), 12.83 (d, J = 2.0 Hz, IH), 12.74 (d, / = 8.4 Hz, IH), 12.35 (d, J 8.9 Hz, 2H), 12.21 (s, IH), 11.99 (d, J = 12.3 Hz, IH), 11.93 (del, J= 8.4， 1.3 Hz, IH) , 7.57 (d, /= 4.7 Hz, 3H), 6.94 (s, 3H). 실시예 139.
Figure imgf000087_0003
The title compound was obtained in the same manner as the Example 134. 1謹 R (300 MHz, DMSO-οί;) δ 18.31 (s, IH), 14.23 (s, IH), 13.42 (s, IH), 13.12 (d, J = 4.9 Hz, IH), 12.94 (d, J 8.4 Hz, IH), 12.83 (d, J = 2.0 Hz, IH), 12.74 (d, / = 8.4 Hz, IH), 12.35 (d, J 8.9 Hz, 2H), 12.21 (s, IH), 11.99 (d, J = 12.3 Hz, IH), 11.93 (del, J = 8.4, 1.3 Hz, IH), 7.57 (d, / = 4.7 Hz, 3H), 6.94 (s, 3H). Example 139.
6-(5— (3— (3,5-비스 (트리플루오로메틸)페닐)우레이도)— 4-플루오로— 2—메틸페닐) - 메틸— 1/ 인다졸 -3-카복스아미드의 제조  Preparation of 6- (5— (3— (3,5-bis (trifluoromethyl) phenyl) ureido) — 4-fluoro— 2—methylphenyl) -methyl— 1 / indazole-3-carboxamide
Figure imgf000088_0001
Figure imgf000088_0001
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. 'Ή NMR (300 MHz , DMSO-^) δ 8.38 (d, J = 4.8 Hz, IH), 8.20 (d, /= 8.4 Hz, IH), 8.08 (s, 2H), 7.95 (d, J= 8.4 Hz, IH), 7.65 (s, IH), 7.47 (s, IH), 7.26 (d, /= 12.2 Hz, IH), 7.19 (dd, J = 8.4, 1.3 Hz, IH), 2.83 (d, J = 4.7 Hz, 3H), 2.20 (s, 3H). 실시예 140.  The title compound was obtained in the same manner as the Example 134. 'Ή NMR (300 MHz, DMSO- ^) δ 8.38 (d, J = 4.8 Hz, IH), 8.20 (d, / = 8.4 Hz, IH), 8.08 (s, 2H), 7.95 (d, J = 8.4 Hz, IH), 7.65 (s, IH), 7.47 (s, IH), 7.26 (d, / = 12.2 Hz, IH), 7.19 (dd, J = 8.4, 1.3 Hz, IH), 2.83 (d, J = 4.7 Hz, 3H), 2.20 (s, 3H). Example 140.
6-(5— (3—(3,4—디메틸페닐)우레이도) -4-플루오로 -2ᅳ메틸페닐) 메틸 -1/ 인다졸 -3-카복스아미드의 제조  Preparation of 6- (5— (3— (3,4—dimethylphenyl) ureido) -4-fluoro-2 ᅳ methylphenyl) methyl-1 / indazole-3-carboxamide
Figure imgf000088_0002
Figure imgf000088_0002
상기 실시예■ 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. NM (300 MHz, DMSO-^) δ 13.57 (s, IH), 8.87 (s, IH), 8.50 (s, IH), 8.38 (d, J = 4.7 Hz, IH), 8.20 (d, J= 8.3 Hz, IH), 8.10 (d, J 8.5 Hz, IH), 7.46 (s, IH), 7.27-7.17 (m, 3H), 7.15—7.09 (m, IH), 7.01 (d, J= 8.2 Hz, IH), 2.83 (d, J = 4.7 Hz, 3H), 2.19 (s, 3H), 2.17 (s, 3H), 2.14 (s, 3H). 실시예 141. By the same procedure as Example 134 to give the title compound ■. NM (300 MHz, DMSO- ^) δ 13.57 (s, IH), 8.87 (s, IH), 8.50 (s, IH), 8.38 (d, J = 4.7 Hz, IH), 8.20 (d, J = 8.3 Hz, IH), 8.10 (d, J 8.5 Hz, IH), 7.46 (s, IH), 7.27-7.17 (m, 3H), 7.15—7.09 (m, IH), 7.01 (d, J = 8.2 Hz, IH), 2.83 (d, J = 4.7 Hz, 3H), 2.19 (s, 3H), 2.17 (s, 3H), 2.14 (s, 3H). Example 141.
6-(4-플루오로 -5ᅳ(3-(3ᅳ플루오로 -5- (트리플루오로메틸)페닐)우레이도) -2—메틸 페닐시메틸 -1^인다졸 -3-카복스아미드의 제조
Figure imgf000089_0001
6- (4-Fluoro-5 '(3- (3'fluoro-5- (trifluoromethyl) phenyl) ureido) -2-2-methylphenylmethylmethyl-1 ^ indazole-3-carboxamide Manufacture
Figure imgf000089_0001
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. Ή隱 (300 MHz, DMS0- ) δ 13.57 (s, 1H), 9.56 (s, 1H), 8.74 (s, 1H), 8.38 (d, /= 5.6 Hz, 11-1)， 8.20 (d, J= 8.2 Hz, 1H), 7.99 (d, 7= 8.3 Hz, 1H), 7.68 (s, 1H), 7.56 (d. J 10.8 Hz, 1H), 7.47 (s, 1H), 7.29—7.16 (m, 3H), 2.83 (d, J = 4.7 Hz, 3H), 2.20 (s, 3H). 실시예 142.  The title compound was obtained in the same manner as the Example 134. 300 (300 MHz, DMS0-) δ 13.57 (s, 1H), 9.56 (s, 1H), 8.74 (s, 1H), 8.38 (d, / = 5.6 Hz, 11-1), 8.20 (d, J = 8.2 Hz, 1H), 7.99 (d, 7 = 8.3 Hz, 1H), 7.68 (s, 1H), 7.56 (d. J 10.8 Hz, 1H), 7.47 (s, 1H), 7.29—7.16 (m, 3H), 2.83 (d, J = 4.7 Hz, 3H), 2.20 (s, 3H). Example 142.
6-(4-플루오로 -5— (3-(3-플루오로— 4-메틸페닐)우레이도) -2-메틸페닐 )-y^메틸 -1^ -인다졸 -3—카복스아미드의 제조  Preparation of 6- (4-Fluoro-5— (3- (3-fluoro- 4-methylphenyl) ureido) -2-methylphenyl) -y ^ methyl-1 ^ -indazole-3—carboxamide
Figure imgf000089_0002
Figure imgf000089_0002
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. Ή NMR (300 MHz , DMSO— ;) δ 13.91. (s, 1H), 13.34 (s, 1H), 13.12 (d, J= 4.8 Hz, 1H), 12.94 (d, J 8.3 Hz. 1H), 12.79 (d, J 8.5 Hz, 1H), 12.20 (s, 1H), 12.15 (d, J 12.3 Hz, 1H), 12.02-11.83 (m, 3H), 11.72 (d, J 8.1 Hz, 1H), 7.57 (d, J 4.7 Hz, 3H), 6.93 (s, 3H), 6.89 (s, 3H). 실시예 143.  The title compound was obtained in the same manner as the Example 134. MR NMR (300 MHz, DMSO—;) δ 13.91. (s, 1H), 13.34 (s, 1H), 13.12 (d, J = 4.8 Hz, 1H), 12.94 (d, J 8.3 Hz. 1H), 12.79 (d, J 8.5 Hz, 1H), 12.20 (s , 1H), 12.15 (d, J 12.3 Hz, 1H), 12.02-11.83 (m, 3H), 11.72 (d, J 8.1 Hz, 1H), 7.57 (d, J 4.7 Hz, 3H), 6.93 (s, 3H), 6.89 (s, 3H). Example 143.
6一 (5-(3— (3—클로로 -4-플루오로페닐)우레이도) -4-플루오로 -2—메틸페닐 메틸- 1/ 인다졸— 3—카복스아미드의 제조  Preparation of 6- (5- (3— (3—chloro-4-fluorophenyl) ureido) -4-fluoro-2—methylphenyl methyl-1 / indazole—3—carboxamide
Figure imgf000089_0003
Figure imgf000089_0003
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾ NMR (300 MHz, DMS으 ) δ 9.79 (s, 1H), 9.03 (s, 1H), 8.40 (d, J= 4.8 Hz, 1H), 8.21 (d, J= 8.4 Hz, 1H), 7.95 (d, J= 8.4 Hz, 1H), 7.83 (d, J= 7.5 Hz, 1H), 7.49 (s, 1H), 7.32-7.29 (m, 2H) , 7.23-7.17 (m, 1H)， 2.84 (d, J= 4.5 Hz, 3H), 2.19 (s, 3H) 실시예 144. 6— (5— (3-(3-( /· -부틸)페닐)우레이도) -4—플루오로 -2-메틸페닐) -그메틸— 1 ^인 다졸 -3-카복스아미드의 제조 The title compound was obtained in the same manner as the Example 134. ¾ NMR (300 MHz, DMS) δ 9.79 (s, 1H), 9.03 (s, 1H), 8.40 (d, J = 4.8 Hz, 1H), 8.21 (d, J = 8.4 Hz, 1H), 7.95 ( d, J = 8.4 Hz, 1H), 7.83 (d, J = 7.5 Hz, 1H), 7.49 (s, 1H), 7.32-7.29 (m, 2H), 7.23-7.17 (m, 1H), 2.84 (d , J = 4.5 Hz, 3H), 2.19 (s, 3H) Example 144. 6— (5— (3- (3- (/ · -Butyl) phenyl) ureido) -4-fluoro-2-methylphenyl) -gmethyl- 1 ^ indazole 3-carboxamide
Figure imgf000090_0001
Figure imgf000090_0001
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 134.
NMR (300 MHz , δ 13.60 (s, 1Η), 9.03 (s, IH), 8.51 (s, 1H), 8.39 (d, /= 4.8 Hz, 1H)ᅳ 8.22 (dm, J= 8.4 Hz, 1H), 8.07 (d, J= 8.4 Hz, 1H), 7.47 (s, 1H), 7.43 (s, 1H), 7.26—7.16 (m, 4H), 7.02—6.99 (m, 1H), 2.84 (d, J= 4.8 Hz, 3H), 2.18 (s, 3H), 1.25 (s, 9H) 실시예 145. NMR (300 MHz, δ 13.60 (s, 1Η), 9.03 (s, IH), 8.51 (s, 1H), 8.39 (d, / = 4.8 Hz, 1H) ᅳ 8.22 (dm, J = 8.4 Hz, 1H) , 8.07 (d, J = 8.4 Hz, 1H), 7.47 (s, 1H), 7.43 (s, 1H), 7.26—7.16 (m, 4H), 7.02—6.99 (m, 1H), 2.84 (d, J 4.8 Hz, 3H), 2.18 (s, 3H), 1.25 (s, 9H) Example 145.
6_(5-(3-(4— e —부틸)페닐)우레이도) -4-플루오로— 2-메틸페닐) -yV-메틸 인 다졸—3-카복스아미드의 제조  Preparation of 6_ (5- (3- (4—e —butyl) phenyl) ureido) -4-fluoro- 2-methylphenyl) -yV-methyl indazole-3-carboxamide
Figure imgf000090_0002
Figure imgf000090_0002
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 134.
NMR (300 MHz, DMSO-^) δ 13.60 (s, 1Η), 9.00 (s, 1H), 8.53 (d, J= 1.5 Hz, 1H), 8.41 (qᅳ J 4.5 Hz, 1H), 8.21 (d, J 8.4 Hz, 1H), 8.09 (d, J 8.4 Hz, 1H), 7.47 (s, 1H), 7.35-7.26 (m, 4H), 7.24 (d, / = 12.3 Hz, 1H) , 7.21 ((Id, J= 8.4 Hz, 1.2 Hz, 1H), 2.84 (d, J = 4.8 Hz, 3H), 2.18 (s, 3H), 1.24 (s, 9H) 실시예 146. NMR (300 MHz, DMSO- ^) δ 13.60 (s, 1Η), 9.00 (s, 1H), 8.53 (d, J = 1.5 Hz, 1H), 8.41 (q ᅳ J 4.5 Hz, 1H), 8.21 (d , J 8.4 Hz, 1H), 8.09 (d, J 8.4 Hz, 1H), 7.47 (s, 1H), 7.35-7.26 (m, 4H), 7.24 (d, / = 12.3 Hz, 1H), 7.21 (( Id, J = 8.4 Hz, 1.2 Hz, 1H), 2.84 (d, J = 4.8 Hz, 3H), 2.18 (s, 3H), 1.24 (s, 9H) Example 146.
6-(5-(3-(4-클로로페닐 )우레이도) -4—폴루오로— 2-메틸페닐 메틸 인다졸 -3 —카복스아미드의 제조  Preparation of 6- (5- (3- (4-chlorophenyl) ureido) -4—polouro—2-methylphenyl methyl indazole-3—carboxamide
Figure imgf000090_0003
Figure imgf000090_0003
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾ NMR (300 MHz, DMS으 fiO δ 13.59 (s, 1H), 9.18 (s, 1H), 8.59 (d, J= 1.5 Hz 1H), 8.39 (q, J= 4.5 Hz, 1H), 8.21 (d, J= 8.4 Hz, 1H), 8.06 (d, J= 8.4 Hz 1H), 7.47 (s, 1H), 7.44 (s, 1H), 7.33 (s, 1H), 7.30 (s, 1H), 7.25 (s, 1H) 7.21 (s, 1H), 7.18 (d, J = 1.5 Hz, 1H), 2.84 (d, J= 4.8 Hz, 3H), 2.19 (s 3H) 실시예 147. The title compound was obtained in the same manner as the Example 134. ¾ NMR (300 MHz, fiO δ in DMS δ 13.59 (s, 1H), 9.18 (s, 1H), 8.59 (d, J = 1.5 Hz 1H), 8.39 (q, J = 4.5 Hz, 1H), 8.21 (d , J = 8.4 Hz, 1H), 8.06 (d, J = 8.4 Hz 1H), 7.47 (s, 1H), 7.44 (s, 1H), 7.33 (s, 1H), 7.30 (s, 1H), 7.25 ( s, 1H) 7.21 (s, 1H), 7.18 (d, J = 1.5 Hz, 1H), 2.84 (d, J = 4.8 Hz, 3H), 2.19 (s 3H) Example 147.
6-(5-(3-(3,4-디플로오로페닐)우레이도) -4—플루오로 -2-메틸페닐 메틸 다졸 -3—카복스아미드의 제조  Preparation of 6- (5- (3- (3,4-difluorophenyl) ureido) -4-fluoro-2-methylphenyl methyldazole-3-carboxamide
Figure imgf000091_0001
Figure imgf000091_0001
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ]H NMR (300 MHz , D S0-rf;) δ 13.59 (s, 1H), 9.26 (s, 1H) , 8.62 (s, 1H) , 8.44-8.32 (q, J 5.3ᅳ 4.8 Hz, 1H), 8.24-8.17 (cl, J = 8.4 Hz, 1H), 8.06-7.98 (d, / = 8.5 Hz, 1H), 7.71-7.58 (clclcl, J 13.5, 7.5， 2.6 Hz, 1H), 7.49-7.44 (t , /= 1.1 Hz, 1H), 7.41-7.02 (m, 5H), 2.86-2.80 (dd, J= 4.8, 2.1 Hz, 3H), 2.19 (s, 3H). 실시예 148. The title compound was obtained in the same manner as the Example 134. ] H NMR (300 MHz, D S0-rf ; ) δ 13.59 (s, 1H), 9.26 (s, 1H), 8.62 (s, 1H), 8.44-8.32 (q, J 5.3 ᅳ 4.8 Hz, 1H), 8.24-8.17 (cl, J = 8.4 Hz, 1H), 8.06-7.98 (d, / = 8.5 Hz, 1H), 7.71-7.58 (clclcl, J 13.5, 7.5, 2.6 Hz, 1H), 7.49-7.44 (t , / = 1.1 Hz, 1H), 7.41-7.02 (m, 5H), 2.86-2.80 (dd, J = 4.8, 2.1 Hz, 3H), 2.19 (s, 3H). Example 148.
6_(4-플루오로 -5— (3-(4-플루오로페닐)우레이도) -2-메틸페닐시메틸 인다졸 -3-카복스아미드의 제조  Preparation of 6_ (4-Fluoro-5— (3- (4-fluorophenyl) ureido) -2-methylphenylmethylmethyl indazole-3-carboxamide
Figure imgf000091_0002
Figure imgf000091_0002
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. TH NMR (300 MHz, DMSO— ί;) δ 13.59 (s, 1Η), 9.10 (s, 1H), 8.55 (s, 1H), 8.42-8.34 (d, J= 4.9 Hz, 1H), 8.23-8.16 (dd, /= 8.3, 0.9 Hz, 1H), 8.09-8.01 (d, /= 8.5 Hz, 1H), 7.50-7.38 (m, 3H), 7.26—7.16 (m, 2H), 7.15-7.05 (m, 2H), 2.86-2.79 (d, J = 4.7 Hz, 3H), 2.19 (s, 3H). 실시예 149. The title compound was obtained in the same manner as the Example 134. T H NMR (300 MHz, DMSO— ί;) δ 13.59 (s, 1Η), 9.10 (s, 1H), 8.55 (s, 1H), 8.42-8.34 (d, J = 4.9 Hz, 1H), 8.23- 8.16 (dd, / = 8.3, 0.9 Hz, 1H), 8.09-8.01 (d, / = 8.5 Hz, 1H), 7.50-7.38 (m, 3H), 7.26—7.16 (m, 2H), 7.15-7.05 ( m, 2H), 2.86-2.79 (d, J = 4.7 Hz, 3H), 2.19 (s, 3H). Example 149.
6-(4—플루오로 -5-(3-(4-플루오로— 3- (트리플루오로메틸)페닐)우레이도) -2-메틸 페닐 )ᅳ^메틸— 1^인다졸 -3-카복스아미드의 제조  6- (4—Fluoro-5 (3- (4-fluoro— 3- (trifluoromethyl) phenyl) ureido) -2-methyl phenyl) ᅳ ^ methyl- 1 ^ indazole-3-car Preparation of Voxamide
Figure imgf000091_0003
Figure imgf000091_0003
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾ NMR (300 MHz, DMSO— c¾) δ 13.53 (s, 1H), 9.35 (s, 1H), 8.60 (s, 1H), 8.33 (d, J = 4.8 Hz, 1H), 8.21 (d' J = 8.4 Hz, 1H), 8.05-7.93 (m, 2H), 7.63-7.54 (m, 1H), 7.43 (dd, J 16.8, 6.8 Hz, 2H), 7.28-7.14 (m, 2H), 2.84 (d, J= 4.7 Hz, 3H), 2.20 (s, 3H). 실시예 150. The title compound was obtained in the same manner as the Example 134. ¾ NMR (300 MHz, DMSO— c¾) δ 13.53 (s, 1H), 9.35 (s, 1H), 8.60 (s, 1H), 8.33 (d, J = 4.8 Hz, 1H), 8.21 (d 'J = 8.4 Hz, 1H), 8.05-7.93 (m, 2H), 7.63-7.54 (m, 1H), 7.43 (dd, J 16.8, 6.8 Hz, 2H), 7.28-7.14 (m, 2H), 2.84 (d, J = 4.7 Hz, 3H), 2.20 (s, 3H). Example 150.
6-(5-(3-(3-시아노페닐)우레이도) -4ᅳ플루오로 -2-메틸페닐 )—^메틸 인다졸 -3 一카복스아미드의 제조  Preparation of 6- (5- (3- (3-cyanophenyl) ureido) -4 ᅳ fluoro-2-methylphenyl)-^ methyl indazole-3 unicarboxamide
Figure imgf000092_0001
Figure imgf000092_0001
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. 画 R (300 MHz , DMS0- ;) δ 9.39 (s, 1H), 8.70 (d, 7= 1.8 Hz, 1H), 8.36 (d, J= 4.8 Hz, 1H), 8.21 (d, J= 8.4 Hz, 1H), 8.03 (d, J= 8.4 Hz, 1H), 7.97 (s, 1H), 7.63 (d, J= 8.4 Hz, 1H), 7.51-7.26 (m, 3H)， 7.21—7.18 (m, 2H), 2.84 (d, J = 4.8 Hz, 3H), 2.20 (s, 3H) 실시예 151.  The title compound was obtained in the same manner as the Example 134.画 R (300 MHz, DMS0-;) δ 9.39 (s, 1H), 8.70 (d, 7 = 1.8 Hz, 1H), 8.36 (d, J = 4.8 Hz, 1H), 8.21 (d, J = 8.4 Hz , 1H), 8.03 (d, J = 8.4 Hz, 1H), 7.97 (s, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.51-7.26 (m, 3H), 7.21—7.18 (m, 2H), 2.84 (d, J = 4.8 Hz, 3H), 2.20 (s, 3H) Example 151.
6-(5-(3— (3-아세틸페닐)우레이도) -4ᅳ플루오로 -2-메틸페닐 )-그메틸 인다졸 -3 -카복스아미드의 제조  Preparation of 6- (5- (3— (3-acetylphenyl) ureido) -4 ᅳ fluoro-2-methylphenyl) -gmethyl indazole-3-carboxamide
Figure imgf000092_0002
Figure imgf000092_0002
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾ NMR (300 MHz, DMS으 οί;) δ 8.28 (d, J= 4.8 Hz, 1H), 8.17 (d, J= 8.4 Hz, 1H), 8.07-8.03 (m, 2H), 7.64 (dd, J 8.4， 2.1 Hz, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.48—7.39 (m, 2H), 7.22 (d, J 12.3 Hz, 1H), 7.14 (dd, J = 8.4， 1.5 Hz, lH), 2.83 (cl, J = 4.5 Hz, 3H), 2.54 (s, 3H), 2.20 (s, 3H) 실시예 152.  The title compound was obtained in the same manner as the Example 134. ¾ NMR (300 MHz, DMS) δ 8.28 (d, J = 4.8 Hz, 1H), 8.17 (d, J = 8.4 Hz, 1H), 8.07-8.03 (m, 2H), 7.64 (dd, J) 8.4, 2.1 Hz, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.48—7.39 (m, 2H), 7.22 (d, J 12.3 Hz, 1H), 7.14 (dd, J = 8.4, 1.5 Hz , lH), 2.83 (cl, J = 4.5 Hz, 3H), 2.54 (s, 3H), 2.20 (s, 3H) Example 152.
6一 (4ᅳ플루오로 -2—메틸— 5-(3ᅳ(3- (트리플루오로메특시 )페닐)우레이도)페닐 )— 메 틸— 1 ^인다졸 -3-카복스아미드의 제조  Preparation of 6- (4 ᅳ fluoro-2—methyl—5- (3 ᅳ (3- (trifluoromepoxy) phenyl) ureido) phenyl) —methyl—1 ^ indazole-3-carboxamide
Figure imgf000092_0003
Figure imgf000092_0003
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. i NMR (300 MHz, DMSO-o!;) δ 13.82-13.22 (m, 1H)， 9.40 (s, 1H) , 8.65 (s, 1H) , The title compound was obtained in the same manner as the Example 134. i NMR (300 MHz, DMSO-o !;) δ 13.82-13.22 (m, 1H), 9.40 (s, 1H), 8.65 (s, 1H),
8.35 (d, J= 4.8 Hz, 1H), 8.20 (d, J= 8.4 Hz, 1H), 8.03 (d, J= 8.4 Hz, 1H),8.35 (d, J = 4.8 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 8.03 (d, J = 8.4 Hz, 1H),
7.68 (s, 1H), 7.47 (s, 1H), 7.39 (t, J= 8.2 Hz, 1H), 7.28-7.21 (m, 2H)， 7.19 (del, /= 8.4, 1.3 Hz, 1H), 6.94 (d, J二 8.4 Hz, 1H), 2.84 (cl, J= 4.7 Hz, 3H) 2.20 (s, 3H). 실시예 153. 7.68 (s, 1H), 7.47 (s, 1H), 7.39 (t, J = 8.2 Hz, 1H), 7.28-7.21 (m, 2H), 7.19 (del, / = 8.4, 1.3 Hz, 1H), 6.94 (d, J2 8.4 Hz, 1H), 2.84 (cl, J = 4.7 Hz, 3H) 2.20 (s, 3H). Example 153.
6-(4-플루오로 -5-(3— (4-플루오로 -3-나이트로페닐)우레이도) -2-메틸페닐 )— 메 틸 -I 인다졸—3-카복스아미드의 제조  Preparation of 6- (4-fluoro-5- (3— (4-fluoro-3-nitrophenyl) ureido) -2-methylphenyl) —methyl-I indazole—3-carboxamide
Figure imgf000093_0001
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.
Figure imgf000093_0001
The title compound was obtained in the same manner as the Example 134.
¾ NMR'OOO MHz, DMSO-i/c) δ 13.56 1Η), 9.50 (s, 1H) , 8.68 (s, 1H), 8.41 (del, 6.8， 2.8 Hz, 1H), 8.36 (d, J= 4.8 Hz, 1H), 8.21 (d, J= 8.2 Hz, 111), 8.00 (d, J= 8.4 Hz, 1H), 7.69-7.61 (m' 1H), 7.51 (dl, J二 10.9, 9.0 Hz, 2H), 7.25 (d, J= 12.3 Hz, 1H), 7.20 (dd, J= 8.4, 1.3 Hz, 1H), 2.84 (cl, J = 4.7 Hz, 3H), 2.20 (s, 3H). 실시예 154. ¾ NMR ' OOO MHz, DMSO-i / c) δ 13.56 1Η), 9.50 (s, 1H), 8.68 (s, 1H), 8.41 (del, 6.8, 2.8 Hz, 1H), 8.36 (d, J = 4.8 Hz, 1H), 8.21 (d, J = 8.2 Hz, 111), 8.00 (d, J = 8.4 Hz, 1H), 7.69-7.61 (m ' 1H), 7.51 (dl, J 二 10.9, 9.0 Hz, 2H ), 7.25 (d, J = 12.3 Hz, 1H), 7.20 (dd, J = 8.4, 1.3 Hz, 1H), 2.84 (cl, J = 4.7 Hz, 3H), 2.20 (s, 3H). Example 154.
6-(4—플루오로ᅳ 2-메틸 -5— (3-(4-메틸 -3-니트로페닐)우레이도)페닐) 메틸— 1/ 인다졸 -3ᅳ카복스아미드의 제조  Preparation of 6- (4—fluoro ᅳ 2-methyl-5— (3- (4-methyl-3-nitrophenyl) ureido) phenyl) methyl— 1 / indazole-3 졸 carboxamide
Figure imgf000093_0002
Figure imgf000093_0002
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾ NMR (300 MHz, DMSO-^) δ 13.77-13.40 (m, 1H), 9.50 (s, 1H), 8.72 (s, 1H), 8.36 (d, J= 4.9 Hz, 1H), 8.27 (d, J= 2.2 Hz, 1H), 8.21 (d, J二 8.4 Hz, 2H), 8.02 (d, J = 8.5 Hz, 1H)， 7.50 (dd, J = 9.4, 7.2 Hz, 2H), 7.39 (d, J = 8.4 Hz, 1H), 7.22 (t, J= 10.8 Hz, 2H), 2.84 (d, J= 4.7 Hz, 3H), 2.44 (s, 3H), 2.20 (s, 3H). 실시예 155.  The title compound was obtained in the same manner as the Example 134. ¾ NMR (300 MHz, DMSO- ^) δ 13.77-13.40 (m, 1H), 9.50 (s, 1H), 8.72 (s, 1H), 8.36 (d, J = 4.9 Hz, 1H), 8.27 (d, J = 2.2 Hz, 1H), 8.21 (d, J 二 8.4 Hz, 2H), 8.02 (d, J = 8.5 Hz, 1H), 7.50 (dd, J = 9.4, 7.2 Hz, 2H), 7.39 (d, J = 8.4 Hz, 1H), 7.22 (t, J = 10.8 Hz, 2H), 2.84 (d, J = 4.7 Hz, 3H), 2.44 (s, 3H), 2.20 (s, 3H). Example 155.
6-(4ᅳ플루오로 -5— (3— (3ᅳ이소프로필페닐)우레이도 )ᅳ2-메틸페닐 )-y 메틸— l 인다 졸— 3ᅳ카복스아미드의 제조  Preparation of 6- (4 ᅳ fluoro-5— (3— (3 ᅳ isopropylphenyl) ureido) ᅳ 2-methylphenyl) -y methyl—l indazole—3 ᅳ carboxamide
Figure imgf000093_0003
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.
Figure imgf000093_0003
The title compound was obtained in the same manner as the Example 134.
]H NMR (300 MHz, DMSC ) δ 9.23 (s, 1Η) , 8.69 (s, 1H), 8.32 (d, /= 4.6 Hz, 1H), 8.19 (d, J= 8.3 Hz, 1H), 8.06 (d, J = 8.5 Hz, 1H), 7.47 (s, 1H), 7.34 (s, lH), 7.28-7.12 (m, 4H), 6.84 (d, J = 7.3 Hz, 1H), 2.82 (t, J 6.6 Hz, 4H), 2.19 (s, 3H), 1.17 (d, / = 6.9 Hz, 6H). 실시예 156.  ] H NMR (300 MHz, DMSC) δ 9.23 (s, 1Η), 8.69 (s, 1H), 8.32 (d, / = 4.6 Hz, 1H), 8.19 (d, J = 8.3 Hz, 1H), 8.06 ( d, J = 8.5 Hz, 1H), 7.47 (s, 1H), 7.34 (s, lH), 7.28-7.12 (m, 4H), 6.84 (d, J = 7.3 Hz, 1H), 2.82 (t, J 6.6 Hz, 4H), 2.19 (s, 3H), 1.17 (d, / = 6.9 Hz, 6H). Example 156.
6_(5-(3- (벤조 [cl] [1,3]디옥솔 -5-일 )우레이도) -4—플루오로ᅩ 2-메틸페닐)— ^메틸- 1/ 인다졸—3—카복스아미드의 제조 6_ (5- (3- (benzo [cl] [1,3] dioxol-5-yl) ureido) o-4-fluoro-2-methylphenyl) - methyl ^ - 1 / indazole-3-carboxamide Preparation of Amides
Figure imgf000094_0001
Figure imgf000094_0001
상기 실시예 134와 등일한 방법으로 수행하여 상기 표제화합물을 얻었다. \ NMR (300 MHz, DMSO—οί;) δ 13.58 (s, 1H), 8.93 (s, 1H), 8.48 (s, 1H), 8.39 (cl, /= 4.8 Hz, 1H), 8.19 (d, J 8.4 Hz, 1H), 8.06 (d, J 8.4 Hz, 1H), 7.46 (s, 1H), 7.24-7.17 (m, 3H), 6.82 (d, 7= 8.4 Hz, 1H) , 6.71 (dd, /= 8.4, 1.8 Hz, 1H), 5.95 (s, 2H), 2.83 (d, J = 4.5 Hz, 3H), 2.18 (s, 3H) 실시예 157. . 6-(5-(3-(3-(2-시아노프로판— 2-일)페닐)우레이도) -4-플루오로— 2-메틸페닐 메틸 -1/ 인다졸—3-카복스아미드의 제조  The title compound was obtained in the same manner as the Example 134. \ NMR (300 MHz, DMSO—οί;) δ 13.58 (s, 1H), 8.93 (s, 1H), 8.48 (s, 1H), 8.39 (cl, / = 4.8 Hz, 1H), 8.19 (d, J 8.4 Hz, 1H), 8.06 (d, J 8.4 Hz, 1H), 7.46 (s, 1H), 7.24-7.17 (m, 3H), 6.82 (d, 7 = 8.4 Hz, 1H), 6.71 (dd, / = 8.4, 1.8 Hz, 1H), 5.95 (s, 2H), 2.83 (d, J = 4.5 Hz, 3H), 2.18 (s, 3H) Example 157. Preparation of 6- (5- (3- (3- (2-cyanopropane- 2-yl) phenyl) ureido) -4-fluoro- 2-methylphenyl methyl-1 / indazol-3-carboxamide
Figure imgf000094_0002
Figure imgf000094_0002
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ^1刚 R (300 MHz , DMS0—i¾) δ 13.6 (s, 1H), 9.24 (s, 1H), 8.56 (s, 1H), 8.39 Cq, 1H, J = 4.2 Hz), 8.22 (d, 1H, J= 8.7 Hz), 8.08 (d, 1H, J= 8.7 Hz), 7.62 (s, 1H), 7.47 (s, 1H), 7.40 (dd, 1H, J= 8.4, 1.8 Hz), 7.35 (t, 1H, J= 7.5 Hz), 7.21 (d, 1H, J = 8.4 Hz), 7.18 (m, 1H), 7.12 (dd, 1H, /= 6.9, 0.9 Hz), 2.84 (d, 3H, / = 3.9 Hz), 2.19 (s, 3H) , 1.65 (s, 6H). 실시예 158.  The title compound was obtained in the same manner as the Example 134. ^ 1 刚 R (300 MHz, DMS0—i¾) δ 13.6 (s, 1H), 9.24 (s, 1H), 8.56 (s, 1H), 8.39 Cq, 1H, J = 4.2 Hz, 8.22 (d, 1H , J = 8.7 Hz), 8.08 (d, 1H, J = 8.7 Hz), 7.62 (s, 1H), 7.47 (s, 1H), 7.40 (dd, 1H, J = 8.4, 1.8 Hz), 7.35 (t , 1H, J = 7.5 Hz), 7.21 (d, 1H, J = 8.4 Hz), 7.18 (m, 1H), 7.12 (dd, 1H, / = 6.9, 0.9 Hz), 2.84 (d, 3H, / = 3.9 Hz), 2.19 (s, 3 H), 1.65 (s, 6 H). Example 158.
6-(5— (3-(3— (2-시아노프로판 -2-일)— 4ᅳ플루오로페닐)우레이도) -4-플루오로 -2-메 틸페닐) 메틸— 1/^인다졸 -3-카복스아미드의 제조
Figure imgf000095_0001
6- (5— (3- (3— (2-cyanopropan-2-yl) — 4 ᅳ fluorophenyl) ureido) -4-fluoro-2-methylphenyl) methyl— 1 / ^ Preparation of Sol-3-Carboxamide
Figure imgf000095_0001
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ]H NMR (300 MHz, DMS0— οί;) δ 9.63 (s, 1Η), 8.79 (b, 1H) , 8.37 (q, 1H, J 4.5 Hz), 8.21 (d, 1H, J= 8.4 Hz), 8.03 (d, 1H, J 8.4 Hz), 7.62 (cld, 1H, J 7.2, 2.7 Hz), 7.48 (s, 1H), 7.47 (m, 1H), 7.24 (cl, 2H, J 11.4 Hz), 7.20 (d, 1H, /= 8.1 Hz), 2.84 (d, 3H, J = 4.8 Hz), 2.19 (s, 3H), 1.71 (s, 6H). 실시예 159. The title compound was obtained in the same manner as the Example 134. ] H NMR (300 MHz, DMS0—οί;) δ 9.63 (s, 1Η), 8.79 (b, 1H), 8.37 (q, 1H, J 4.5 Hz), 8.21 (d, 1H, J = 8.4 Hz), 8.03 (d, 1H, J 8.4 Hz), 7.62 (cld, 1H, J 7.2, 2.7 Hz), 7.48 (s, 1H), 7.47 (m, 1H), 7.24 (cl, 2H, J 11.4 Hz), 7.20 (d, 1H, / = 8.1 Hz), 2.84 (d, 3H, J = 4.8 Hz), 2.19 (s, 3H), 1.71 (s, 6H). Example 159.
6-(5ᅳ (3— (3— ((디메틸아미노)메틸 )-4ᅳ플루오로페닐 )우레이도) -4ᅳ플루오로 -2-메 틸페닐 )— 메틸— 1/ 인다졸—3ᅩ카복스아미드의 제조 6- (5 ᅳ (3— (3— ((dimethylamino) methyl) -4 ᅳ fluorophenyl) ureido) -4 ᅳ fluoro-2-methylphenyl) — methyl— 1 / indazole—3 ᅩ Preparation of Carboxamide
Figure imgf000095_0002
Figure imgf000095_0002
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. 'Η NMR (300 MHz, DMSO^) δ 13.6 (s, 1H) , 9.71 (s, 1H) , 9.25 (s, 1H)， 8.86 (s, 1H), 8.39 (q, 1H, / = 4.8 Hz), 8.25 (d, 1H, J= 8.4 Hz), 8.11 (d, 1H, J = 8.1 Hz), 7.89 (dd, 1H, J= 6.3, 2.4 Hz), 7.48 (s, 1H), 7.43 (m, 1H), 7.32-7.19 (m, 3H), 4.34 (s, 2H) , 2.87 (d, 3H, /= 4.8 Hz), 2.79 (s, 6H), 2.22 (s, 3H). 실시예 160.  The title compound was obtained in the same manner as the Example 134. 'Η NMR (300 MHz, DMSO ^) δ 13.6 (s, 1H), 9.71 (s, 1H), 9.25 (s, 1H), 8.86 (s, 1H), 8.39 (q, 1H, / = 4.8 Hz) , 8.25 (d, 1H, J = 8.4 Hz), 8.11 (d, 1H, J = 8.1 Hz), 7.89 (dd, 1H, J = 6.3, 2.4 Hz), 7.48 (s, 1H), 7.43 (m, 1H), 7.32-7.19 (m, 3H), 4.34 (s, 2H), 2.87 (d, 3H, / = 4.8 Hz), 2.79 (s, 6H), 2.22 (s, 3H). Example 160.
6-(4ᅳ플루오로 -5— (3-(4-플루오로— 3- (트리플루오로메록시)페닐)우레이도)ᅳ 2-메 틸페닐) 메틸 - 인다졸 -3-카복스아미드의 제조  6- (4 ᅳ Fluoro-5— (3- (4-fluoro—3- (trifluoromethoxy) phenyl) ureido) ᅳ 2-methylphenyl) methyl-indazole-3-carboxamide Produce
Figure imgf000095_0003
Figure imgf000095_0003
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ]H NMR (300 MHz, DMSO ) δ 13.57 (s, 1Η), 9.33 (s, 1H), 8.62 (s, 1H), 8.39 (d, J= 4.6 Hz, 1H), 8.20 (d, J= 8.4 Hz, 1H), 8.01 (d, J 8.4 Hz, 1H), 7.85 (s, 1H), 7.46 (d, J = 4.0 Hz, 1H) , 7.41 (d, J = 10.1 Hz, 1H), 7.27 (dd, J = 14.1, 8.2 Hz, 2H), 7.21-7.16 (m, 1H), 2.83 (d, J= 4.7 Hz, 3H)， 2.19 (s, 3H). 실시예 161. The title compound was obtained in the same manner as the Example 134. ] H NMR (300 MHz, DMSO) δ 13.57 (s, 1Η), 9.33 (s, 1H), 8.62 (s, 1H), 8.39 (d, J = 4.6 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 8.01 (d, J 8.4 Hz, 1H), 7.85 (s, 1H), 7.46 (d, J = 4.0 Hz, 1H), 7.41 (d, J = 10.1 Hz, 1H), 7.27 (dd , J = 14.1, 8.2 Hz, 2H), 7.21-7.16 (m, 1H), 2.83 (d, J = 4.7 Hz, 3H), 2.19 (s, 3H). Example 161.
6-(4-플루오로 -5— (3-(3ᅳ ((트리플루오로메틸 )싸이오)페닐)우레이도)페닐 )ᅳ^메 틸 -1 인다졸 -3-카복스아미드의 제조
Figure imgf000096_0001
Preparation of 6- (4-fluoro-5— (3- (3 ᅳ ((trifluoromethyl) thio) phenyl) ureido) phenyl) ᅳ ^ methyl-1 indazole-3-carboxamide
Figure imgf000096_0001
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾ NMR (300 MHz, DMSO ) δ 13.58 (s, 1H), 9.34 (s, 1H), 8.63 (s, 1H), 8.39 (d, /= 4.8 Hz, 1H), 8.21 (d, 8.4 Hz, 1H), 8.04 (d, /= 8.5 Hz, 1H), 7.98 (s, 1H), 7.52-7.40 (m, 3H), 7.31 (d, J= 7.3 Hz, 1H), 7.24 (d, J = 12.4 Hz, 1H), 7.20 (dd, J= 8.4, 1.3 Hz, 1H), 2.83 (d, J = 4.7 Hz, 3H), 2.20 (s, 3H). 실시예 162.  The title compound was obtained in the same manner as the Example 134. ¾ NMR (300 MHz, DMSO) δ 13.58 (s, 1H), 9.34 (s, 1H), 8.63 (s, 1H), 8.39 (d, / = 4.8 Hz, 1H), 8.21 (d, 8.4 Hz, 1H ), 8.04 (d, / = 8.5 Hz, 1H), 7.98 (s, 1H), 7.52-7.40 (m, 3H), 7.31 (d, J = 7.3 Hz, 1H), 7.24 (d, J = 12.4 Hz , 1H), 7.20 (dd, J = 8.4, 1.3 Hz, 1H), 2.83 (d, J = 4.7 Hz, 3H), 2.20 (s, 3H). Example 162.
6一 (4-플루오로— 5-(3-(3-플루오로페닐)우레이도)— 2—메틸페닐) 메틸— I/ 인다졸 -3-카복스아미드의 제조 '
Figure imgf000096_0002
6 一 (4-fluoro— 5- (3- (3-fluorophenyl) ureido) — 2—methylphenyl) methyl— I / indazole-3-carboxamide Preparation ''
Figure imgf000096_0002
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ]H NMR (300 MHz, DMSO-^,) δ 13.59 (s, 1H), 9.34 (s, 1H), 8.66 (s, 1H), 8.39 (d, ./= 4.7 Hz, 1H), 8.20 (d, /= 8.4 Hz, 1H), 8.05 (d, /= 8.4 Hz, 1H), 7.47 (t, J 6.0 Hz, 2H), 7.26 (clt , J 23.1, 8.9 Hz, 3H), 7.08 (d, J 8.2 Hz, 1H), 6.79 (t, = 8.4 Hz, 1H), 2.83 (d, J = 4.7 Hz, 3H), 2.19 (s, 3H) . 실시예 163. The title compound was obtained in the same manner as the Example 134. ] H NMR (300 MHz, DMSO- ^,) δ 13.59 (s, 1H), 9.34 (s, 1H), 8.66 (s, 1H), 8.39 (d, ./= 4.7 Hz, 1H), 8.20 (d , / = 8.4 Hz, 1H), 8.05 (d, / = 8.4 Hz, 1H), 7.47 (t, J 6.0 Hz, 2H), 7.26 (clt, J 23.1, 8.9 Hz, 3H), 7.08 (d, J 8.2 Hz, 1H), 6.79 (t, = 8.4 Hz, 1H), 2.83 (d, J = 4.7 Hz, 3H), 2.19 (s, 3H). Example 163.
6— ( 5- (3- (3— (디플루오로메톡시 )페닐)우레이도)— 4-플루오로ᅳ 2-메틸페닐) 메틸 — l/ 인다졸—3ᅳ카복스아미드의 제조
Figure imgf000096_0003
6— (5- (3- (3— (difluoromethoxy) phenyl) ureido) — 4-fluoro ᅳ 2-methylphenyl) methyl — l / indazole—3 ᅳ carboxamide
Figure imgf000096_0003
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾赚 (300 MHz, DMS0- ) δ 13.57 (s, 1H), 9.29 (s, 1H), 8.63 (s, 1H), 8.39 (d, J= 4.8 Hz, 1H), 8.20 (d, J= 8.4 Hz,12H), 8.05 (d, /= 8.5 Hz, 1H), 7.47 (s, 1H), 7.45 (t, J= 2.1 Hz, 1H), 7.31 (t, J= 8.2 Hz, 1H)， 7.27-7.17 (m, 4H), 7.17-7.12 (m, 1H), 6.77 (dd, J= 8.0， 2.1 Hz, 1H), 2.83 (d, J = 4.7 Hz, 3H), 2.19 (s, 3H). 실시예 164.  The title compound was obtained in the same manner as the Example 134. ¾ 赚 (300 MHz, DMS0-) δ 13.57 (s, 1H), 9.29 (s, 1H), 8.63 (s, 1H), 8.39 (d, J = 4.8 Hz, 1H), 8.20 (d, J = 8.4 Hz, 12H), 8.05 (d, / = 8.5 Hz, 1H), 7.47 (s, 1H), 7.45 (t, J = 2.1 Hz, 1H), 7.31 (t, J = 8.2 Hz, 1H), 7.27- 7.17 (m, 4H), 7.17-7.12 (m, 1H), 6.77 (dd, J = 8.0, 2.1 Hz, 1H), 2.83 (d, J = 4.7 Hz, 3H), 2.19 (s, 3H). Example 164.
6-(5— (3-(2-클로로 -3— (트리플루오로메틸)페닐)우레이도) -4-플루오로— 2-메틸페 닐)— 메틸— 1/ 인다졸 -3-카복스아미드의 제조 6- (5— (3- (2-chloro-3— (trifluoromethyl) phenyl) ureido) -4-fluoro— 2-methylfe Neil) —Methyl—1 / Indazole-3-carboxamide
Figure imgf000097_0001
Figure imgf000097_0001
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. Ή NMR (300 MHz , DMS으^) δ 9.50 (s, 1H), 9.05 (s, 1H) , 8.41 (d, J= 4.1 Hz, 2H), 8.20 (cl, J 8.4 Hz, 1H)' 8.09 (d, J 8.5 Hz, 1H) ' 7.49 (d, J 9.9 Hz, 3H), 7.27 (d, / = 12.4 Hz, 1H), 7.20 (d, J = 8.5 Hz, 2H), 6.94 (d, J = 8.5 Hz, 1H), 2.83 (d, J = 4.6 Hz, 3H), 2.20 (s, 3H). 실시예 165.  The title compound was obtained in the same manner as the Example 134. Ή NMR (300 MHz, DMS) δ 9.50 (s, 1H), 9.05 (s, 1H), 8.41 (d, J = 4.1 Hz, 2H), 8.20 (cl, J 8.4 Hz, 1H) '8.09 ( d, J 8.5 Hz, 1H) '7.49 (d, J 9.9 Hz, 3H), 7.27 (d, / = 12.4 Hz, 1H), 7.20 (d, J = 8.5 Hz, 2H), 6.94 (d, J = 8.5 Hz, 1H), 2.83 (d, J = 4.6 Hz, 3H), 2.20 (s, 3H). Example 165.
6-(5-(3— (2-클로로 -5— (트리플루오로메틸)페닐)우레이도) -4-플루오로 -2-메틸페 닐) 메틸 -1 ^인다졸—3-카복스아미드의 제조 6- (5- (3— (2-chloro-5— (trifluoromethyl) phenyl) ureido) -4-fluoro-2-methylphenyl) methyl-1 ^ indazole—3-carboxamide Manufacture
Figure imgf000097_0002
Figure imgf000097_0002
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾ NMR (300 MHz , DMSO-^) δ 13.24 (s, 1H), 9.22 (s, 1H), 8.73 (s, 1H), 8.24 (d, J 1.9 Hz, 1H), 8.05 (d, 7= 4.8 Hz, 1H), 7.87 (d, J 8.3 Hz, 1H), 7.75 (cl, J = 8.4 Hz, 1H), 7.38 (d, J = 8.3 Hz, 1H), 7.14 (s, 1H), 7.03 (dd, J = 8.4, 1.8 Hz, 1H), 6.93 (d, J= 12.4 Hz, 1H), 6.86 (dd, J = 8.4, 1.3 Hz, 1H), 2.49 (d, J 4.7 Hz, 3H), 1.86 (s, 3H). 실시예 166.  The title compound was obtained in the same manner as the Example 134. ¾ NMR (300 MHz, DMSO- ^) δ 13.24 (s, 1H), 9.22 (s, 1H), 8.73 (s, 1H), 8.24 (d, J 1.9 Hz, 1H), 8.05 (d, 7 = 4.8 Hz, 1H), 7.87 (d, J 8.3 Hz, 1H), 7.75 (cl, J = 8.4 Hz, 1H), 7.38 (d, J = 8.3 Hz, 1H), 7.14 (s, 1H), 7.03 (dd , J = 8.4, 1.8 Hz, 1H), 6.93 (d, J = 12.4 Hz, 1H), 6.86 (dd, J = 8.4, 1.3 Hz, 1H), 2.49 (d, J 4.7 Hz, 3H), 1.86 ( s, 3H). Example 166.
6-(4ᅳ플루오로 -2—메틸— 5— (3-(3-(4—메틸피페라진— 1-일 )ᅳ5- (트리플루오로메틸)페 닐)우레이도)페닐) 메틸 -1/ 인다졸— 3-카복스아미드의 제조  6- (4 ᅳ Fluoro-2—methyl— 5— (3- (3- (4—methylpiperazin— 1-yl) ᅳ 5- (trifluoromethyl) phenyl) ureido) phenyl) methyl- 1 / indazole— Preparation of 3-carboxamide
Figure imgf000097_0003
Figure imgf000097_0003
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. 'Η NMR (300 MHz, DMS0- ) δ 9.27 (s, 1H)ᅳ 8.61 (s, 1H), 8.38 (d, J= 4.6 Hz, 1H), 8.20 (d, J= 8.4 Hz, 1H), 8.03 (d, J= 8.5 Hz, 1H), 7.46 (s, 1H), 7.20 (dd, J= 21.9, 9.6 Hz, 4H), 6.82 (s, 1H), 3.17 (s, 4H)， 2.83 (d, J= 4.7 Hz, 3H), 2.43 (s, 4H), 2.20 (s, 3H), 2.19 (s, 3H) . 실시에 167. The title compound was obtained in the same manner as the Example 134. 'Η NMR (300 MHz, DMS0-) δ 9.27 (s, 1H) ᅳ 8.61 (s, 1H), 8.38 (d, J = 4.6 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 8.03 (d, J = 8.5 Hz, 1H), 7.46 (s, 1H), 7.20 (dd, J = 21.9, 9.6 Hz, 4H), 6.82 (s, 1H), 3.17 (s, 4H), 2.83 (d, J = 4.7 Hz, 3H), 2.43 (s, 4H), 2.20 (s, 3H), 2.19 (s, 3H). 167 to implementation.
6一 (4-플루오로— 2—메틸ᅳ 5- (3— (2—몰포리노ᅳ 5— (트리플루오로메틸)페닐)우레이도) 페닐) 메틸— 1/^인다졸 -3—카복스아미드의 제조  6- (4-Fluoro— 2—methyl ᅳ 5- (3— (2—morpholino ᅳ 5— (trifluoromethyl) phenyl) ureido) phenyl) methyl— 1 / ^ indazole-3—carbox Preparation of Amides
Figure imgf000098_0001
Figure imgf000098_0001
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. NMR (300 MHz , DMSO- ) δ 13.58 (s, 1H), 9.54 (s, 1H), 8.62 (s, 1H), 8.43-8.32 (m, 2H), 8.23-8.16 (d, J= 8.4 Hz, 111)， 8.04 (s, 1H), 7.47 (s, 1H) 7.33 (s, 1H), 7.28-7.15 (m, 3H), 3.86 (s, 4H), 2.86 (s, 4H), 2.85—2.79 (d J = 4.6 Hz, 3H), 2.19 (s, 3H). 실시예 168.  The title compound was obtained in the same manner as the Example 134. NMR (300 MHz, DMSO-) δ 13.58 (s, 1H), 9.54 (s, 1H), 8.62 (s, 1H), 8.43-8.32 (m, 2H), 8.23-8.16 (d, J = 8.4 Hz, 111), 8.04 (s, 1H), 7.47 (s, 1H) 7.33 (s, 1H), 7.28-7.15 (m, 3H), 3.86 (s, 4H), 2.86 (s, 4H), 2.85—2.79 ( d J = 4.6 Hz, 3H), 2.19 (s, 3H). Example 168.
6— (4-플루오로 -2-메틸 -5-(3-(4— (2- (피를리딘— 1-일)에톡시)ᅳ 3- (트리플루오로메 틸)페닐)우레이도)페닐 메틸 인다졸 -3—카복스아미드의 제조  6— (4-fluoro-2-methyl-5- (3- (4— (2- (pyridin— 1-yl) ethoxy) ᅳ 3- (trifluoromethyl) phenyl) ureido) phenyl Preparation of Methyl Indazole-3—Carboxamide
Figure imgf000098_0002
Figure imgf000098_0002
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. lH NMR (300 MHz, DMSO-^) δ 18.32 (s, 1H), 13.89 (s, 1H), 13.30 (d, J= 2.3 Hz, 1H), 13.12 (d, J= 5.0 Hz, 1H), 12.94 (d, J = 8.4 Hz, 1H), 12.77 (cl, J = 8.4 Hz, 1H), 12.55 (d, J = 2.7 Hz, 1H), 12.23 (dd, J = 9.1, 2.8 Hz, 1H), 12.20 (t, /= 1.2 Hz, 1H)' 12.00—11.90 (m, 3H)， 8.88 (t, J 5.9 Hz, 2H), 7.57 (d, J = 4.6 Hz, 3H), 7.52 (t, J 5.9 Hz, 2H), 6.93 (s, 3H) , 6.40 (p, /= 3.1 Hz, 4H). 실시예 169. The title compound was obtained in the same manner as the Example 134. l H NMR (300 MHz, DMSO- ^) δ 18.32 (s, 1H), 13.89 (s, 1H), 13.30 (d, J = 2.3 Hz, 1H), 13.12 (d, J = 5.0 Hz, 1H), 12.94 (d, J = 8.4 Hz, 1H), 12.77 (cl, J = 8.4 Hz, 1H), 12.55 (d, J = 2.7 Hz, 1H), 12.23 (dd, J = 9.1, 2.8 Hz, 1H), 12.20 (t, / = 1.2 Hz, 1H) '12.00—11.90 (m, 3H), 8.88 (t, J 5.9 Hz, 2H), 7.57 (d, J = 4.6 Hz, 3H), 7.52 (t, J 5.9 Hz, 2H), 6.93 (s, 3H), 6.40 (p, / = 3.1 Hz, 4H). Example 169.
6-(4ᅳ플루오로 -2-메틸 -5-(3ᅳ (3-(4-메틸피페라진 -1ᅳ일 )페닐)우레이도)페닐 )— 메틸ᅳ 1 인다졸 -3-카복스아미드의 제조  6- (4'Fluoro-2-methyl-5- (3 '(3- (4-methylpiperazin-1xyl) phenyl) ureido) phenyl) — of methyl ᅳ 1 indazole-3-carboxamide Produce
Figure imgf000098_0003
Figure imgf000098_0003
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾匪 R (300 MHz, DMS0- ) δ 13.59 (s, 1H), 9.02 (s, 1H), 8.56 (s, 1H), 8.39 (s, 1H), 8.20 (d, J= 8.3 Hz, 1H)， 8.08 (d, J= 8.4 Hz, 1H), 7.46 (s, 1H), 7.28-7.01 (m, 4H), 6.72 (d, /= 7.6 Hz, 1H), 6.56 (d, J 8.2 Hz, Hi), 3.07 (s, 4H), 2.83 (d, J 4.7 Hz, 3H), 2.43 (s, 4H) , 2.19 (s, 3H), 2.18 (s, 3H). 실시예 170. The title compound was obtained in the same manner as the Example 134. ¾ 匪 R (300 MHz, DMS0-) δ 13.59 (s, 1H), 9.02 (s, 1H), 8.56 (s, 1H), 8.39 (s, 1H), 8.20 (d, J = 8.3 Hz, 1H) , 8.08 (d, J = 8.4 Hz, 1H), 7.46 (s, 1H), 7.28-7.01 (m, 4H), 6.72 (d, / = 7.6 Hz, 1H), 6.56 (d, J 8.2 Hz, Hi), 3.07 (s, 4H), 2.83 (d, J 4.7 Hz, 3H), 2.43 (s, 4H), 2.19 (s, 3H), 2.18 (s, 3H). Example 170.
6-(4—플루오로 -2—메틸 -5— (3— (4ᅳ(4—메틸피페라진—1-일 )—3— (트리플루오로메틸)페 닐)우레이도)페닐) - ^메틸—1 인다졸 -3-카복스아미드  6- (4—Fluoro-2—methyl-5— (3— (44 (4—methylpiperazin—1-yl) —3— (trifluoromethyl) phenyl) ureido) phenyl)-^ Methyl-1 indazole-3-carboxamide
트리플루오로아세트산염의 제조 Preparation of Trifluoroacetic Acid
Figure imgf000099_0001
Figure imgf000099_0001
상기 실시예 134와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 134.
NMR (300 MHz , DMS0— ) δ 13.59 (s, III), 9.67 (s, 1H), 9.42 (s, 1H), 8.65 (s, 1H), 8.39 (q, J = 4.3 Hz, 1H), 8.21 (d, J 8.4 Hz, 1H), 8.01 (d, J 8.5 Hz, 1H), 7.93 (d, /= 2.3 Hz, 1H), 7.59 (del, J = 8.7， 1.9 Hz, 1H), 7.50 (cl, J = 8.8 Hz, 1H), 7.47 (d, J = 0.7 Hz, 1H), 7.25 (d, J 12.3 Hz, 1H), 7.19 (dd, = 8.4, 1.2 Hz, 1H), 3.45—3.55 (m, 2H), 3.00-3.15 (m, 6H), 2.88 (s, 3H), 2.83 (cl, J = 4.7 Hz, 3H), 2.19 (s, 3H). 실시예 171. NMR (300 MHz, DMS0—) δ 13.59 (s, III), 9.67 (s, 1H), 9.42 (s, 1H), 8.65 (s, 1H), 8.39 (q, J = 4.3 Hz, 1H), 8.21 (d, J 8.4 Hz, 1H), 8.01 (d, J 8.5 Hz, 1H), 7.93 (d, / = 2.3 Hz, 1H), 7.59 (del, J = 8.7, 1.9 Hz, 1H), 7.50 (cl , J = 8.8 Hz, 1H), 7.47 (d, J = 0.7 Hz, 1H), 7.25 (d, J 12.3 Hz, 1H), 7.19 (dd, = 8.4, 1.2 Hz, 1H), 3.45—3.55 (m , 2H), 3.00-3.15 (m, 6H), 2.88 (s, 3H), 2.83 (cl, J = 4.7 Hz, 3H), 2.19 (s, 3H). Example 171.
6一 (4-플루오로— 5-(3— (4-플루오로 -3—메틸페닐)싸이오  6 one (4-fluoro- 5- (3— (4-fluoro-3-methylphenyl) thio
메틸 -1/ 인다졸 -3-카복스아미드의 제조 Preparation of Methyl-1 / indazole-3-carboxamide
Figure imgf000099_0002
Figure imgf000099_0002
6_(5-아미노— 4-플루오로 -2-메틸페닐 )— 메틸 테트라하이드로 -2/ 피란 -2-일 ) -I 인다졸 3-카르복사아마이드 (100 mg, 0.26國 ol)를 DMF에 녹인 후， 0 °C에서 4-플루오로 -3—메틸페닐 아이소싸이오시아네이트 (52.4 mg, 0.31隱 ol)을 적가하였다. 12시간 교반한 후 반웅이 종결되면 염화나트륨 수용액을 사용하고 에틸아세테이트로 추출한 다음 모아진 유기층을 무수 6_ (5-amino— 4-fluoro-2-methylphenyl) —methyl tetrahydro-2 / pyran-2-yl) -I indazole 3-carboxamide (100 mg, 0.26 ole ol) was dissolved in DMF. 4-Fluoro-3-methylphenyl isothiocyanate (52.4 mg, 0.31 'ol) was added dropwise at 0 ° C. After stirring for 12 hours, when the reaction was completed, an aqueous sodium chloride solution was used, extraction was performed with ethyl acetate, and the combined organic layers were dried.
황산마그네슘으로 건조하여 여과하였다. 용매를 감압증류로 제거한 후 획득한 잔사를 메틸렌클로라이드에 녹인 후 트리플루오로아세테이트를 적가하였다. 실은에서 12시간 교반한 후 반웅이 종결하면 소디움 Dried over magnesium sulfate and filtered. After removing the solvent by distillation under reduced pressure, the obtained residue was dissolved in methylene chloride and trifluoroacetate was added dropwise. Actually, after stirring for 12 hours at the end of the reaction, the sodium
바이카보네이트 용액을 사용하여 중화한 후 메틸렌클로라이드로 추출하였다. 추출하여 모아진 유기층을 무수 황산마그네슘으로 건조하여 여과하였다. Neutralization using bicarbonate solution followed by extraction with methylene chloride. The extracted organic layer was dried over anhydrous magnesium sulfate and filtered.
용매를 감압중류로 제거한 후 획득한 잔사를 관크로마토그래피 (실리카겔， EtOAc/n— hexane=l:2)를 통해 정제하여 목적화합물인 The solvent was removed under reduced pressure under reduced pressure, and the obtained residue was purified by column chromatography (silica gel, EtOAc / n—hexane = l: 2) to obtain the target compound.
6-(4—플루오로 -5-(3-(4—플루오로 -3-메틸페닐 )싸이오우레이도)—2-메틸페닐 메틸 인다졸—3-카복스아미드 (55 nig, 45%)를 얻었다. 'H NMR (300 MHz, CD30D- ) δ 2.25 (s, 6Η), 2.98 (s, 3H), 7.04 (t, /= 10 Hz, 1H), 7.13 (d, J = 11.1 Hz, 1H), 7.21 (dd, /= 1.3 Hz, J = 8.4 Hz, 2H) 7.24 (m, 1H), 7.49 (m, 2H), 8.25 (d, J 8.4 Hz, 1H) ' 실시예 172. 6- (4—fluoro-5- (3- (4—fluoro-3-methylphenyl) thioureido) —2-methylphenyl Methyl indazole—3-carboxamide (55 nig, 45%) was obtained. 'H NMR (300 MHz, CD 3 0D-) δ 2.25 (s, 6Η), 2.98 (s, 3H), 7.04 (t, / = 10 Hz, 1H), 7.13 (d, J = 11.1 Hz, 1H) , 7.21 (dd, / = 1.3 Hz, J = 8.4 Hz, 2H) 7.24 (m, 1H), 7.49 (m, 2H), 8.25 (d, J 8.4 Hz, 1H) ' Example 172.
6-(5-(3— (4-클로로 -3- (트리플루오로메틸)페닐 )싸이오우레이도) -4—플루오로 2ᅳ메 틸페닐 메틸— 1/ 인다졸 -3-카복스아미드의 제조  6- (5- (3— (4-chloro-3- (trifluoromethyl) phenyl) thioureido) -4—fluoro 2 ᅳ methylphenyl methyl— 1 / indazole-3-carboxamide Produce
Figure imgf000100_0001
Figure imgf000100_0001
상기 실시예 1기과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. Ή NMR (300 MHz , C 0D— ) δ 2.25 (s, 3H), 2.98 (s, 3H), 7.11 (d, J = 11.3 Hz, 1H), 7.21 (dd, = 1.3 Hz, /= 8.5 Hz, 2H), 7.52 (ιη, 3H), 7.74 (dd, J 2.3 Hz, J = 8.6 Hz, 1H), 8.02 (d, ./ = 2.3 Hz, 1H), 8.25 (d, J= 8.4 Hz, 1H) 실시예 173.  The title compound was obtained in the same manner as the Example 1 group. MR NMR (300 MHz, C 0D—) δ 2.25 (s, 3H), 2.98 (s, 3H), 7.11 (d, J = 11.3 Hz, 1H), 7.21 (dd, = 1.3 Hz, / = 8.5 Hz, 2H), 7.52 (ιη, 3H), 7.74 (dd, J 2.3 Hz, J = 8.6 Hz, 1H), 8.02 (d, ./ = 2.3 Hz, 1H), 8.25 (d, J = 8.4 Hz, 1H) Example 173.
6一 (4-플루오로 -5-(3-(4—플루오로— 3— (트리플루오로메틸)페닐 )ᅩ3ᅳ메틸우레이도) 2-메틸페닐) 메틸 -1/ 인다졸 -3-카복스아미드의 제조 ' 6- (4-Fluoro-5- (3- (4—fluoro- 3— (trifluoromethyl) phenyl) ᅩ 3 ᅳ methylureido) 2-methylphenyl) methyl-1 / indazole-3-car Preparation of Voxamide ''
Figure imgf000100_0002
단계 1. 4—플루오로 3-디메틸아닐린
Figure imgf000100_0002
Step 1. 4—Fluoro 3-dimethylaniline
4-플루오로 -3-메틸아닐린 (2.79 ol), K2C0:> (4.185 mmol) 및 아세톤 (4.0 niL)을 실드튜브에 넣고 60 °C에서 1 시간 교반하였다. 다론 폴라스크에 4-Fluoro-3-methylaniline (2.79 ol), K 2 C0:> (4.185 mmol) and acetone (4.0 niL) were added to a shield tube and stirred at 60 ° C for 1 hour. In Daron Polasque
메틸아이오다이드 (3.0431 ol)을 아세톤 (1.0 mL)에 녹인 후 교반 중인 용액에 적가하고 60°C에서 12시간 교반하였다. 반응이 모두 진행된 후에 반웅액을 필터하고 필터액을 농축한 후 컬럼 크로마토그래피 (실리카겔, Methyl iodide (3.0431 ol) was dissolved in acetone (1.0 mL) and then added dropwise to the stirring solution and stirred at 60 ° C. for 12 hours. After the reaction was completed, the reaction mixture was filtered, the filter solution was concentrated, and then column chromatography (silica gel,
에틸아세테이트：핵산 =1:10)로 정제하여 4-플루오로 3-다이메틸아닐린을 168 mg 얻었다. 1\\ NMR (300 MHz , CDC13) δ 7.01 (t, J= 9.4 Hz, 1H), 6.65-6.80 (m, 2H), 3.00 (brs, 1H), 2.84 (s, 3H) 단계 2. Ethyl acetate: nucleic acid = 1: 10) refine | purified, and 168 mg of 4-fluoro 3-dimethylanilines were obtained. 1 \\ NMR (300 MHz, CDC1 3 ) δ 7.01 (t, J = 9.4 Hz, 1H), 6.65-6.80 (m, 2H), 3.00 (brs, 1H), 2.84 (s, 3H) Step 2.
6-(4ᅳ플루오로 -5ᅳ(3-(4ᅳ플루오로 -3- (트리플루오로메틸)페닐 )-3-메틸우레이도) - 2-메틸페닐 )— 메틸 -1^인다졸 -3—카복스아미드의 제조  6- (4'Fluoro-5 '(3- (4'Fluoro-3- (trifluoromethyl) phenyl) -3-methylureido)-2-methylphenyl)-methyl-1 ^ indazole-3 —Manufacture of Carboxamides
50 mL 플라스크에 In a 50 mL flask
6一 (5ᅳ아미노 -4-플투오로 -2-메틸페닐 )- 메틸 -1— (테트라하이드로 -2^피란 -2-일 ) 인다졸—3-카복스아미드 (0.235 隱 ol)를 넣고 메틸렌클로라이드 (3.0 mL)에 녹인 후 트리포스겐 (0.094麵 ol)를 넣었디-. DIPEA (0.242隱 ol)을 넣은 후 상온에서 5분간 교반하였다. 다른 플라스크에 6- (5-aminoamino-4-pletuoro-2-methylphenyl) -methyl-1— (tetrahydro-2 ^ pyran-2-yl) Indazole—3-Carboxamide (0.235 隱 ol), dissolved in methylene chloride (3.0 mL), and triphosphogen (0.094 麵 ol). DIPEA (0.242 Pa ol) was added thereto, followed by stirring at room temperature for 5 minutes. In another flask
4-플루오로— N, 3-다이메틸아닐린 (0.282 國 ol)과 DIPEA (0.705 mmoi)을 메틸렌클로라이드 (2.0 mL)에 녹인 후 교반 중인 플라스크에 적가하고 상온에서 3시간동안 교반하였다. 반응이 모두 진행된 후 반옹액을 농축하고 컬럼 크로마토그래피 (실리카겔 , 에틸아세테이트 :핵산 =1:1)로 정제하여 4-Fluoro—N, 3-dimethylaniline (0.282 kol) and DIPEA (0.705 mmoi) were dissolved in methylene chloride (2.0 mL), and added dropwise to the stirring flask, followed by stirring at room temperature for 3 hours. After the reaction proceeded, the reaction solution was concentrated and purified by column chromatography (silica gel, ethyl acetate: nucleic acid = 1: 1).
6一 (4-플루오로ᅳ 5-(3-(4—플루오로 _3- (트리플루오로메틸)페닐 )-3-메틸우레이도) - 2一메틸페닐 )- 메틸ᅳ1-(테트라하이드로 피란— 2—일 인다졸— 3—카복스아미 드를 얻었다. 정제과정 없이 얻어진 화합물을 메틸렌클로라이드에 녹이고 TFA을 넣고 상온에서 12시간 교반하였다. 반응이 모두 진행 된 후 무수 탄산나트륨을 넣고 반웅을 중단시킨 후 메틸렌클로라이드와 물을 넣고 추출한 후 무수 황산마그네슘으로 건조시키고 농축시킨다. 결과물을 정제하여 목적하는 6- (4-Fluoro ᅳ 5- (3- (4—fluoro_3- (trifluoromethyl) phenyl) -3-methylureido)-2 一 methylphenyl) -methyl ᅳ 1- (tetrahydropyran— 2—Indazole—3—Carboxamide was obtained The compound obtained without purification was dissolved in methylene chloride, TFA was added and stirred at room temperature for 12 hours, after which the reaction was completed, anhydrous sodium carbonate was added and the reaction was stopped. Methylene chloride and water are added and extracted, dried over anhydrous magnesium sulfate and concentrated.
6一(4-플루오로 -5-(3-(4-플루오로 -3- (트리플로오르메틸)페닐 )-3—메틸우레이도)ᅳ 2-메틸페닐)ᅳ "메틸 -1 ^인다졸 -3-카복스아미드 7.0 mg을 얻었다. ]H NMR (300 MHz , DMSO-^i) δ 13.58 (s, 1H)， 8.38 (q, /= 4.3 Hz, 1H), 8.19 (d, / = 8.4 Hz, 1H), 8.15 (s, 1H), 7.70-7.80 (m, 2H), 7.60—7.49 (m, 1H), 7.44 (s, 1H), 7.32 (d, J = 8.2 Hz, 1H) , 7.18 (cl, J 11.7 Hz, 1H), 7.17 (dd, J 8.4, 1.3 Hz, 1H), 3.29 (s, 3H), 2.83 (cl, J 4.7 Hz, 3H), 2.21 (s, 3H). 실시예 174. 6- (4-Fluoro-5- (3- (4-fluoro-3- (trifluoromethyl) phenyl) -3—methylureido) ᅳ 2-methylphenyl) ᅳ methyl-1 ^ indazole- 7.0 mg of 3-carboxamide were obtained. ] H NMR (300 MHz, DMSO- ^ i) δ 13.58 (s, 1H), 8.38 (q, / = 4.3 Hz, 1H), 8.19 (d, / = 8.4 Hz) , 1H), 8.15 (s, 1H), 7.70-7.80 (m, 2H), 7.60—7.49 (m, 1H), 7.44 (s, 1H), 7.32 (d, J = 8.2 Hz, 1H), 7.18 ( cl, J 11.7 Hz, 1H), 7.17 (dd, J 8.4, 1.3 Hz, 1H), 3.29 (s, 3H), 2.83 (cl, J 4.7 Hz, 3H), 2.21 (s, 3H) Example 174 .
6-(4-플루오로— 5-(3ᅳ(4—플루오로 -3— (트리플루오로메틸)페닐 )— 1—메틸우레이도)ᅳ 2-메틸페닐 메틸 인다졸 -3-카복스아미드의 제조  6- (4-fluoro— 5- (3 ′ (4—fluoro-3— (trifluoromethyl) phenyl) -1—methylureido) ᅳ of 2-methylphenyl methyl indazole-3-carboxamide Produce
Figure imgf000101_0001
단계 1.
Figure imgf000101_0001
Step 1.
6-(4-플루오로 -2—메틸 -5- (메틸아미노)페닐 )—^메틸 -1^인다졸—3—카복스아미드 6一(5-아미노 -4-플루오로— 2-메틸페닐)— 메틸— 1- (테트라하이드로 -2^피란— 2—일) -1^인다졸—3-카복스아미드 (0.784 隱 ol), 2C03 (1.176 ramol) 및 아세톤 (4.0 mL)을 실드튜브에 넣고 60 °C에서 1 시간 교반하였다. 다른 플라스크에 메틸아이오다이드 (0.854 miiiol)을 아세톤 (1.0 mL)에 녹인 후 교반 중인 용액에 적가하고 60 °C에서 12시간 교반하였다. 반응이 모두 진행된 후에 반웅액을 필터하고 필터액을 농축한 후 컬럼 크로마토그래피 (실리카겔, 에틸아세테이트:핵산 = 1： 1.5 )로 정제하여 6- (4-fluoro-2—methyl-5- (methylamino) phenyl) — ^ methyl-1 ^ indazole—3—carboxamide 6 one (5-amino-4-fluoro— 2-methylphenyl) — Methyl— 1- (tetrahydro-2 ^ pyran— 2—yl) -1 ^ indazole—3-carboxamide (0.784 隱 ol), 2 CO 3 (1.176 ramol) and acetone (4.0 ml ) Put into the tube and stirred for 1 hour at 60 ° C. Methyl iodide (0.854 miiiol) was dissolved in acetone (1.0 mL) in another flask, and added dropwise to the stirring solution, followed by stirring at 60 ° C for 12 hours. After the reaction proceeded, the reaction mixture was filtered, the filter solution was concentrated, and then purified by column chromatography (silica gel, ethyl acetate: nucleic acid = 1: 1.5).
6ᅳ (4ᅳ플투오로 -2—메틸ᅳ 5-(메틸아미노)페닐 )ᅳ그메틸 -1^인다졸 -3-카복스아미드 를 175 mg 얻었다. 단계 2. 175 mg of 6 '(4'-pletuoro-2-methyl' 5- (methylamino) phenyl) single methyl-1 ^ indazole-3-carboxamide was obtained. Step 2.
6— (4-플루오로— 5ᅳ (3— (4ᅳ플루오로 -3- (트리플루오로메틸)페닐)—1-메틸우레이도) - 6— (4-fluoro— 5 ′ (3— (4 ᅳ fluoro-3- (trifluoromethyl) phenyl) —1-methylureido)-
2-메틸페닐 )—/^메틸 - 1//"인다졸—3—카복스아미드의 제조 Preparation of 2-methylphenyl) — / ^ methyl-1 // "indazol—3—carboxamide
50 niL 플라스크에 ' A 50 niL flask,
6一 (4-플루오로 -2-메틸— 5- (메틸아미노)페닐 )-/^메틸— 1^인다졸—3-카복스아미드 6 一 (4-fluoro-2-methyl— 5- (methylamino) phenyl)-/ ^ methyl— 1 ^ indazole—3-carboxamide
(0.22國 ol)를 넣고 THF (3.0 mL)로 녹인 후 (0.22 國 ol) and dissolve in THF (3.0 mL)
1-플루오로 -4-아이소시아네이토一 2- (트리플루오로메틸)벤젠 (0.454 mmol )을 넣고 상온에서 12시간 교반하였다. 반응진행 후 용매를 농축하고 컬럼  1-Fluoro-4-isocyanato one 2- (trifluoromethyl) benzene (0.454 mmol) was added thereto, and the mixture was stirred at room temperature for 12 hours. After the reaction, the solvent was concentrated and the column
크로마토그래피 (실리카겔 , 에틸아세테이트:핵산 =1:1)로 정제하여 Purification by chromatography (silica gel, ethyl acetate: nucleic acid = 1: 1)
6-(4—플루오로 -5ᅳ (3-4-플루오로— 3— (트리플루오로메틸)페닐) -1—메틸우레이도 )—2 一메틸페닐 )— ^메틸— 테트라하이드로— 2/ 피란 -2—일 )—1/ 인다졸 -3—카복스아미드 를 얻었다. 얻어진 중간체를 메틸렌클로라이드에 녹이고 TFA을 넣고 상온에서 12시간 교반하였다. 반응이 모두 진행된 후 무수 탄산나트륨을 넣고 반웅을 중단시킨 후， 메틸렌클로라이드와 물을 넣고 추출한 후 무수 황산나트륨으로 건조시키고 농축시켰다. 얻어진 잔사로부터  6- (4—Fluoro-5 ᅳ (3-4-fluoro— 3— (trifluoromethyl) phenyl) -1—methylureido) —2 unimethylphenyl) — ^ methyl— tetrahydro— 2 / pyran -2-yl) -1 / indazole-3 carboxamide was obtained. The obtained intermediate was dissolved in methylene chloride and TFA was added thereto, followed by stirring at room temperature for 12 hours. After the reaction proceeded, anhydrous sodium carbonate was added and reaction was stopped. Then, the mixture was extracted with methylene chloride and water, dried over anhydrous sodium sulfate and concentrated. From the obtained residue
6— (4-플루오로 -5ᅳ (3-(4ᅳ플루오로 -3- (트리플루오로메틸)페닐) -1-메틸우레이도) - 6— (4-Fluoro-5 ′ (3- (4 ᅳ fluoro-3- (trifluoromethyl) phenyl) -1-methylureido)-
2-메틸페닐) 메틸 인다졸 -3-카복스아미드 6.0 mg를 얻었다. ¾ NMR (300 MHz, DMSO-d:) δ 13.81 (s, 1H), 8.89 (s, 1H), 8.60 (q, J 4.3 Hz, 1H), 8.42 (d, J = 8.4 Hz, 1H), 8.12 (dd, J 6.6, 2.6 Hz, 1H), 8.06-7.98 (in, 1H), 7.74 (s, 1H), 7.51-7.66 (m, 3H), 7.47 (del, J 8.4， 1.1 Hz, 1H), 3.46 (s, 3H), 3.04 (d, J = 4.7 Hz, 3H), 2.50 (s, 3H). 실시예 175. 6.0 mg of 2-methylphenyl) methyl indazole-3-carboxamide were obtained. ¾ NMR (300 MHz, DMSO-d :) δ 13.81 (s, 1H), 8.89 (s, 1H), 8.60 (q, J 4.3 Hz, 1H), 8.42 (d, J = 8.4 Hz, 1H), 8.12 (dd, J 6.6, 2.6 Hz, 1H), 8.06-7.98 (in, 1H), 7.74 (s, 1H), 7.51-7.66 (m, 3H), 7.47 (del, J 8.4, 1.1 Hz, 1H), 3.46 (s, 3H), 3.04 (d, J = 4.7 Hz, 3H), 2.50 (s, 3H). Example 175.
6-(4-플루오로 -2ᅳ메틸 -5-(3— (4-메틸피페라진 -1-일 )—5- (트리플루오로메틸)페닐) 벤즈아미도)페닐)— 피리딘—4-일)— 인다졸—3-카복스아미드의 제조 6- (4-Fluoro-2 ᅳ methyl- 5- (3— (4-methylpiperazin-1-yl) —5- (trifluoromethyl) phenyl) benzamido) phenyl) —pyridine—4- I) —Indazole—Production of 3-carboxamide
Figure imgf000103_0001
단계 1. 에틸
Figure imgf000103_0001
Step 1. Ethyl
6-브로모ᅩ 1— (테트라하이드로— 2 ^피란 -2—일 )— 1 ^인다졸ᅳ 3—카복실레이트의 제조 250 mL 플라스크에 6—브로모 인다졸 -3-카복실산 (20.74誦 ol)을 넣고 에탄올6- Bromoxol 1— (Tetrahydro— 2 ^ pyran-2—yl) — 1 ^ Indazolezol 3—Carboxylate Preparation 6—Bromoindazol-3-carboxylic acid (20.74 誦 ol) in a 250 mL flask Put ethanol
(160 mL)을 넣은 후 싸이오닐클로라이드 (103.7 讓 ol)를 적가하고 3시간동안 환류시켰다 . 반웅액을 농축하고 에틸아세테이트와 소디움 바이카보네이트 용액으로 추출하고 무수 황산나트륨으로 건조시켜 더 이상의 정제과정 없이 5.5 g의 에틸 6-브로모 -1^인다졸—3—카복실레이트를 얻었다. (160 mL) was added dropwise with thionylchloride (103.7 讓 ol) and refluxed for 3 hours. The reaction mixture was concentrated, extracted with ethyl acetate, sodium bicarbonate solution and dried over anhydrous sodium sulfate to obtain 5.5 g of ethyl 6-bromo-1 ^ indazole-3 carboxylate without further purification.
250 mL 플라스크에 에틸 6—브로모—1^인다졸 -3-카복실레이트 (20.4画 ol )을 넣고 에틸아세테이트 (80 mL)를 넣은 후 3， 4—다이하이드로 피란 (61.32 薩 ol)과 广를루엔설폰산 (2.044隱 ol)을 넣고 60 °C에서 2시간 교반하였다. 반응이 모두 진행되면 반응액을 에틸아세테이트와 물로 추출하고 무수 황산나트륨으로 건조한 후 컬럼크로마토그래피 (실리카겔, Into a 250 mL flask, add ethyl 6-bromo- 1 ^ indazol-3-carboxylate (20.4) ol), add ethyl acetate (80 mL), and add 3, 4-dihydropyran (61.32) ol) and 广. Luenesulfonic acid (2.044 Pa ol) was added and stirred at 60 ° C. for 2 hours. After the reaction proceeds, the reaction solution is extracted with ethyl acetate and water, dried over anhydrous sodium sulfate, and then column chromatography (silica gel,
에틸아세테이트:핵산 =1:5)로 정제하여 에틸  Ethyl acetate: nucleic acid = 1: 5)
6-브로모 -1- (테트라하이드로 -2^피란 -2ᅳ일) -1^인다졸 -3-카복실레이트 4.9 g를 얻었다. ¾ NMR (400 MHz, DMS0— ί¾) δ 8.21 (d, J= 1.6 Hz, 1H), 8.01 (d, J = 8.7 Hz, 1H) 7.52 (dd, J = 1.6， 8.6 Hz, 1H), 6.02 (dd, J = 2.5, 9.8 Hz, 1H), 4.41 (1， J= 7.3 Hz, 2H), 3.88 (m, 1H), 3.80 (m, 1H), 2.01 (m, 2H), 2.33 (m, 1H), 1.73 (in, 1H), 1.59 (m, 2H), 1.37 (t, /= 7.1 Hz, 3H), MS m/z [M+H] 354, 356. 단계 2. 에틸 ᅳ 4.9 g of 6-bromo-1- (tetrahydro-2 ^ pyran-2xyl) -1 ^ indazole-3-carboxylate were obtained. ¾ NMR (400 MHz, DMS0—ί¾) δ 8.21 (d, J = 1.6 Hz, 1H), 8.01 (d, J = 8.7 Hz, 1H) 7.52 (dd, J = 1.6, 8.6 Hz, 1H), 6.02 ( dd, J = 2.5, 9.8 Hz, 1H), 4.41 (1, J = 7.3 Hz, 2H), 3.88 (m, 1H), 3.80 (m, 1H), 2.01 (m, 2H), 2.33 (m, 1H), 1.73 (in, 1H), 1.59 (m, 2H), 1.37 (t, / = 7.1 Hz, 3H), MS m / z [M + H] 354, 356. Step 2. Ethyl
6-(5-아미노— 4—플루오로 -2—메틸페닐 )— 1-(테트라하이드로— 란 -2ᅳ일 )— 1^인 다졸 -3-카복실레이트  6- (5-amino— 4—fluoro-2—methylphenyl) — 1- (tetrahydro—lan-2xyl) — 1 ^ indazole-3-carboxylate
상기 제조예 3의 단계 6 및 단계 7과 동일한 방법으로 에틸 Ethyl in the same manner as in Step 6 and Step 7 of Preparation Example 3
6-브로모 -1- (테트라하이드로 -2/ 피란 -2-일 인다졸 -3-카복실레이트를 반응시켜， 에틸  6-bromo-1- (tetrahydro-2 / pyran-2-yl indazole-3-carboxylate is reacted, ethyl
6一 (5—아미노 -4-플루오로 -2-메틸페닐 )-1— (테트라하이드로— 2 ^피란— 2-일 )— 1/ 인 다졸— 3-카복실레이트를 얻었다. MS m/z [M+H] 398  6 one (5—amino-4-fluoro-2-methylphenyl) -1— (tetrahydro— 2 ^ pyran— 2-yl) — 1 / indazole— 3-carboxylate was obtained. MS m / z [M + H] 398
단계 3. 에틸 Step 3. Ethyl
6-(4-플루오로 -2ᅩ메틸 -5— (3-(4-메틸피페라진 -1—일) -5- (트리플루오로메틸)벤즈 아미도)페닐 (테트라하이드로— 2/ 피란 -2-일 )-1/ 인다졸 -3-카복실레이트의 제조 6- (4-fluoro-2 ᅩ methyl-5— (3- (4-methylpiperazin-1—yl) -5- (trifluoromethyl) benz amido) phenyl (tetrahydro— 2 / pyran- Preparation of 2-yl) -1 / indazol-3-carboxylate
상기 실시예 43의 단계 1과 동일한 방법으로 에틸 Ethyl in the same manner as in Step 1 of Example 43 above
6_(5-아미노ᅳ 4-플루오로— 2—메틸페닐 )-1- (테트라하이드로 -2/ 피란 -2ᅳ일 인 다졸 -3—카복실레이트를 반웅시켜， 에틸  6_ (5-amino ᅳ 4-fluoro— 2—methylphenyl) -1- (tetrahydro-2 / pyran-2 -yl indazole-3—carboxylate, reacted with ethyl
6_(4-플루오로 -2-메틸 -5— (3— (4-메틸피페라진 -1-일)— 5— (트리플루오로메틸)벤즈 아미도)페닐) - 1- (테트라하이드로— 2/ 피란 -2-일) - l/ 인다졸 -3-카복실레이트를 얻었다. MS m/z [M+H] 668 단계 4.  6_ (4-fluoro-2-methyl-5— (3— (4-methylpiperazin-1-yl) — 5— (trifluoromethyl) benz amido) phenyl) -1- (tetrahydro— 2 / Pyran-2-yl) -1 / indazole-3-carboxylate. MS m / z [M + H] 668 Step 4.
6-(4-플루오로— 2—메틸 -5-(3-(4ᅳ메틸피페라진— 1-일) -5- (트리플루오로메틸)벤즈 아미도)페닐)—1— (테트라하이드로— 피란 -2-일) -1^인다졸 -3-카복실산  6- (4-fluoro— 2—methyl-5- (3- (4 ᅳ methylpiperazin— 1-yl) -5 (trifluoromethyl) benz amido) phenyl) —1— (tetrahydro— Pyran-2-yl) -1 ^ indazole-3-carboxylic acid
100 mL 플라스크에 에틸 Ethyl in a 100 mL flask
6一 (4-플루오로 -2-메틸— 5— (3— (4—메틸피페라진 -1-일) -5— (트리플루오로메틸)벤즈 아미도)페닐 )-1- (테트라하이드로— 2/ 피란 -2—일 인다졸 -3-카복실레이트 6 一 (4-fluoro-2-methyl— 5— (3— (4—methylpiperazin-1-yl) -5— (trifluoromethyl) benz amido) phenyl) -1- (tetrahydro— 2 / pyran-2—yl indazole-3-carboxylate
(1.78 隱 ol), 테트라하이드로퓨란 /메탄을 /물 =2/3/1의 흔합용매 (40 mL) 및 리륨하이드록사이드 모노하이드레이트 (5.35 隱 ol)를 넣은 후 상온에서 2시간 교반하였다. 반응진행 후 용매를 농축하고 물과 에틸아세테이트로 추출한 후， 수용액 층의 pH가 4 될 때까지 '1N HC1 용액을 넣어주었다. 다시 수용액 층을 에틸아세테이트로 추출한 후， 유기 층을 무수 황산나트륨으로 건조시키고 더 이상의 정제없이 (1.78 μl ol) and tetrahydrofuran / methane were added with a mixed solvent of 40 mL of water / 2/3/1 and lithium hydroxide monohydrate (5.35 μl ol), followed by stirring at room temperature for 2 hours. After the reaction was completed, the solvent was concentrated, extracted with water and ethyl acetate, and the ' 1N HC1 solution was added until the pH of the aqueous layer 4. Again, the aqueous layer was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and no further purification.
6_(4-플루오로— 2-메틸ᅳ 5-(3-(4-메틸피페라진— 1-일 )-5- (트리플루오로메틸)벤즈 아미도)페닐 )-1— (테트라하이드로— 2^피란 -2—일 )-L 인다졸ᅳ 3—카복실산 450 mg을 얻었다. MS m/z [M+H] 640 단계 5.  6_ (4-Fluoro— 2-methyl ᅳ 5- (3- (4-methylpiperazin— 1-yl) -5- (trifluoromethyl) benz amido) phenyl) -1— (tetrahydro— 2 ^ Pyran-2—yl) -L indazole ᅳ 450 mg of carboxylic acid was obtained. MS m / z [M + H] 640 Step 5.
6-(4-플루오로 -2-메틸ᅳ 5— (3-(4-메틸피페라진— 1-일 )-5- (트리플루오로메틸)페닐) 벤즈아미도)페닐)—vH피리딘 -4-일) -1^인다졸 -3-카복스아미드의 제조 50 niL 플라스크에 6- (4-fluoro-2-methyl-2- 5— (3- (4-methylpiperazin— 1-yl) -5- (trifluoromethyl) phenyl) benzamido) phenyl) —vHpyridine-4 -Yl) -1 ^ indazole-3-carboxamide In a 50 niL flask
6-(4-플루오로— 2—메틸 -5— (3— (4-메틸피페라진 -1-일 )-5ᅳ (트리플루오로메틸)벤즈 아미도)페닐) 1— (테트라하이드로 -2^피란— 2-일 ) 인다졸 -3-카복실산 (0.0625 mmol ) 및 DMF (1.0 niL)를 넣은 후, 4ᅳ아미노피리딘 (0.125 mniol),  6- (4-fluoro— 2—methyl-5— (3— (4-methylpiperazin-1-yl) -5 ′ (trifluoromethyl) benz amido) phenyl) 1— (tetrahydro-2 ^ Pyran— 2-yl) indazole-3-carboxylic acid (0.0625 mmol) and DMF (1.0 niL), followed by 4 ᅳ aminopyridine (0.125 mniol),
2-( 1/ 7-아자벤조트리아졸— 1-일 )-1,1,3, 3—테트라메틸 유로니움 2- (1 / 7-azabenzotriazole— 1-yl) -1,1,3, 3—tetramethyl uronium
핵사플루오로포스페이트 메탄암모늄 (0.125 i皿 ol), 디이소프로필에틸아민 (DIPEA; 0.188画101)을 넣고 상온에서 3시간동안 교반하였다. 반응 진행 후 에틸아세테이트와 염화나트륨 수용액으로 추출하고, 무수 황산나트륨으로 건조하고, 컬럼크로마토그래피 (실리카겔, 메탄을：메틸렌클로라이드 =1:9)로 정제하여 Nuxafluorophosphate methane ammonium (0.125 i 皿 ol) and diisopropylethylamine (DIPEA; 0.188 x 101) were added thereto and stirred at room temperature for 3 hours. After the reaction proceeded, the mixture was extracted with ethyl acetate and aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and purified by column chromatography (silica gel, methane: methylene chloride = 1: 9).
6— (4-플루오로 -2ᅩ메틸 -5-(3-(4-메틸피페라진 -1—일 )-5- (트리플루오로메틸 )벤즈 아미도)페닐 )-Λ 피리딘— 4—일 )— 1_ (테트라하이드로 -2^피란 -2-일 인다졸 -3- 카복시아마이드 12 nig을 얻었다. 6— (4-fluoro-2 ᅩ methyl-5- (3- (4-methylpiperazin-1-yl) -5- (trifluoromethyl) benz amido) phenyl) -Λ pyridin— 4—yl 12 nig of tetrahydro-2 ^ pyran-2-yl indazole-3-carboxamide.
50 niL 플라스크에 In a 50 niL flask
6-(4—플루오로 -2-메틸 -5-(3-(4—메틸피페라진— 1-일) -5- (트리플루오로메틸)벤즈 아미도)페닐 ) -Λ 피리딘—4—일 )-1-(테트라하이드로 피란 -2-일 )-1^인다졸一 3- 카복스아미드 (0.014 ᅵ誦 ol)을 메틸렌클로라이드에 녹이고 TFA (0.5 iiiL)을 넣고 상온에서 12시간 교반하였다. 반응이 모두 진행되면 탄산나트륨을 넣어 반웅을 중단시킨 후， 메틸렌클로라이드와 물을 넣고 추출하고, 무수  6- (4—Fluoro-2-methyl-5- (3- (4—methylpiperazin— 1-yl) -5- (trifluoromethyl) benz amido) phenyl) -Λ pyridin—4—yl ) -1- (tetrahydro pyran-2-yl) -1 ^ indazol-I 3-carboxamide (0.014 誦 ol) was dissolved in methylene chloride and TFA (0.5 iiiL) was added thereto, followed by stirring at room temperature for 12 hours. When the reaction proceeded, add reaction with sodium carbonate to stop reaction, add methylene chloride and water, and extract.
황산나트륨으로 건조시키고 농축시켰다. 결과물을 컬럼크로마토그래피 (실리카겔, 메탄을：메틸렌클로라이드 =1:9)로 정제하여 Dried over sodium sulfate and concentrated. The resulting product was purified by column chromatography (silica gel, methane: methylene chloride = 1: 9)
6-(4-플루오로 -2-메틸 -5— (3— (4-메틸피페라진— 1-일 )-5ᅳ (트리플루오로메틸)벤즈 아미도)페닐) -Λ 피리딘—4—일) -1^인다졸 -3—카복스아미드 3 mg를 얻었다. 6- (4-fluoro-2-methyl-5— (3— (4-methylpiperazin— 1-yl) -5 ᅳ (trifluoromethyl) benz amido) phenyl) -Λ pyridin—4—yl 3 mg of) -1 ^ indazole-3-carboxamide were obtained.
i NMR (300 MHzᅳ DMSO-^) δ 3.97 (s, 1H), 9.86 (s, 1H), 9.38 (s,lH), 8.65 (s, 2H), 8.45-8.34 (in, 1H), 8.31-8.20 (m, 1H), 8.08—7.95 (m, 2H), 7.95—7.86 (m, 1H), 7.53-7.63 (m, 2H), 7.43 (t, J= 9.7 Hz, 2H), 7.15-7.33 (m, 3H), 2.21 (s, 3H). 실시예 176.  i NMR (300 MHz ᅳ DMSO- ^) δ 3.97 (s, 1H), 9.86 (s, 1H), 9.38 (s, lH), 8.65 (s, 2H), 8.45-8.34 (in, 1H), 8.31- 8.20 (m, 1H), 8.08—7.95 (m, 2H), 7.95—7.86 (m, 1H), 7.53-7.63 (m, 2H), 7.43 (t, J = 9.7 Hz, 2H), 7.15-7.33 ( m, 3H), 2.21 (s, 3H). Example 176.
싸이클로프로필 -6— (4—플루오로 -2-메틸 -5-(3-(4—메틸피페라진 -1—일) -5— (트리 플루오로메틸)벤즈아미도)페닐 )-1 인다졸— 3-카복스아미드의 제조  Cyclopropyl-6- (4-fluoro-2-methyl-5- (3- (4-methylpiperazin-1-yl) -5) (trifluoromethyl) benzamido) phenyl) -1 indazole — Preparation of 3-carboxamides
Figure imgf000105_0001
Figure imgf000105_0001
상기 실시예 175와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾ NMR (300 MHz, DMSO-o!;) δ 10.35 (s, 1H), 8.43 (d, J= 4.5 Hz, 1H)， 8.22 (d, J = 8.4 Hz, 1H), 7.81 (s, 1H), 7.74 (s, 1H), 7.52-7.40 (m, 3H), 7.31 (d, J = 8.4 Hz, 1H), 7.22 (d, J= 8.4 Hz, 1H), 4.10 (bs, 4H) , 3.17 (bs, 4H), 2.88 (s, 4H), 2.27 (s, 3H), 0.72-0.66 (m, 4H) 실시예 177. The title compound was obtained in the same manner as the Example 175. ¾ NMR (300 MHz, DMSO-o !;) δ 10.35 (s, 1H), 8.43 (d, J = 4.5 Hz, 1H), 8.22 (d, J = 8.4 Hz, 1H), 7.81 (s, 1H) , 7.74 (s, 1H), 7.52-7.40 (m, 3H), 7.31 (d, J = 8.4 Hz, 1H), 7.22 (d, J = 8.4 Hz, 1H), 4.10 (bs, 4H), 3.17 ( bs, 4H), 2.88 (s, 4H), 2.27 (s, 3H), 0.72-0.66 (m, 4H) Example 177.
6-(4-플루오로 -2-메틸— 5-(3-(4—메틸피페라진 -1-일 )-5— (트리플루오로메틸 )페닐) 벤즈아미도)페닐) 인다졸 -3-카복스아미드의 제조  6- (4-fluoro-2-methyl— 5- (3- (4—methylpiperazin-1-yl) -5— (trifluoromethyl) phenyl) benzamido) phenyl) indazol-3- Preparation of Carboxamide
Figure imgf000106_0001
Figure imgf000106_0001
상기 실시예 175와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. 'Η NMR (300 MHz , DMS0-i¾) δ 10.32 (s, 1H), 8.12 (d, J= 8.4 Hz, IH), 7.79 (s, 1H), 7.74 (s, IH), 7.54-7.47 (m, 3H), 7.32 (d, J 11.4 Hz, IH), 7.24 (d, J = 8.4 Hz, IH), 4.1-4.06 (m, 2H), 3.53 (bs, 2H) , 3.14 (bs, 4H), 2.87 (s, 3H), 2.26 (s, 3H) 실시예 178.  The title compound was obtained in the same manner as the Example 175. 'Η NMR (300 MHz, DMS0-i¾) δ 10.32 (s, 1H), 8.12 (d, J = 8.4 Hz, IH), 7.79 (s, 1H), 7.74 (s, IH), 7.54-7.47 (m , 3H), 7.32 (d, J 11.4 Hz, IH), 7.24 (d, J = 8.4 Hz, IH), 4.1-4.06 (m, 2H), 3.53 (bs, 2H), 3.14 (bs, 4H), 2.87 (s, 3 H), 2.26 (s, 3 H) Example 178.
6- (4-플루오로— 2-메틸— 5- (3- (4-메틸피페라진 -1-일 )-5— (트리플루오로메틸)페닐) 벤즈아미도)페닐)—N , 디메틸 - 1 / 인다졸 -3-카복스아미드의 제조  6- (4-fluoro— 2-methyl— 5- (3- (4-methylpiperazin-1-yl) -5— (trifluoromethyl) phenyl) benzamido) phenyl) —N, dimethyl- Preparation of 1 / indazole-3-carboxamide
Figure imgf000106_0002
Figure imgf000106_0002
상기 실시예 175와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. lH NMR (300 MHz, α)30Ι)- ) δ 8.03 (d, /= 8.4 Hz, 1Η)' 7.76 (s, IH), 7.45—7.53 (m, 2H), 7.38 (s, IH), 7.30 (d, J 11.5 Hz, IH), 7.19 (del, J = 8.3, 1.0 Hz, IH), 3.37-3.45 (m, 3H), 3.03—3.13 (m, 3H), 2.43-2.48 (in, 2H), 2.27 (s, 3H), 2.24 (s, 3H) 실시예 179. The title compound was obtained in the same manner as the Example 175. l H NMR (300 MHz, α) 3 0Ι)-) δ 8.03 (d, / = 8.4 Hz, 1Η) ' 7.76 (s, IH), 7.45—7.53 (m, 2H), 7.38 (s, IH), 7.30 (d, J 11.5 Hz, IH), 7.19 (del, J = 8.3, 1.0 Hz, IH), 3.37-3.45 (m, 3H), 3.03—3.13 (m, 3H), 2.43-2.48 (in, 2H ), 2.27 (s, 3H), 2.24 (s, 3H) Example 179.
Λ 2-플루오로 -4-메틸 -5-(3- (피페라진 -1-카보닐) 인다졸 -6—일)페닐) -3-(4- 메틸피페라진 - 1-일 )-5- (트리플루오로메틸)벤즈아미드의 제조  Λ 2-fluoro-4-methyl-5- (3- (piperazin-1-carbonyl) indazol-6-yl) phenyl) -3- (4-methylpiperazin-1-yl) -5- Preparation of (trifluoromethyl) benzamide
Figure imgf000106_0003
Figure imgf000106_0003
상기 실시예 175와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. \{ NMR (300 MHz, (¾0Ε)-β ) δ 7.95 (d, J= 8.3 Hz, IH), 7.39 (s, IH), 7.23-7.28 (m, 2H), 7.08 (s, IH), 7.00 (d, J= 8.0 Hz, IH), 6.91 (d, J= 12.3 Hz, IH), 6.70 (d, J= 9.6 Hz, IH), 3.25-3.33 (m, 12H), 2.45-2.50 (m, 4H), 2.23 (s, 3H), 실시예 180. The title compound was obtained in the same manner as the Example 175. \ {NMR (300 MHz, (¾0Ε ) -β) δ 7.95 (d, J = 8.3 Hz, IH), 7.39 (s, IH), 7.23-7.28 (m, 2H), 7.08 (s, IH), 7.00 (d, J = 8.0 Hz, IH), 6.91 (d, J = 12.3 Hz, IH), 6.70 (d, J = 9.6 Hz, IH), 3.25-3.33 (m, 12H), 2.45-2.50 (m, 4H), 2.23 (s, 3H), Example 180.
Λ 2-플루오로 -4-메틸 -5- (3- (4—메틸피페라진— 1-카보닐 )-1^인다졸 -6-일)페닐 ) - 3一 (4-메틸피페라진—1-일) -5— (트리플루오로메틸)벤즈아미드의 제조  Λ 2-Fluoro-4-methyl-5- (3- (4—methylpiperazin— 1-carbonyl) -1 ^ indazol-6-yl) phenyl) -3 一 (4-methylpiperazin—1 -Yl) -5—Preparation of (trifluoromethyl) benzamide
Figure imgf000107_0001
Figure imgf000107_0001
상기 실시예 175와 동일한 방법으로 수행하여 상기 표체화합물을 얻었다. :H NMR (300 MHz, CD::i0D-f/4) δ 7.99 (cl, /= 8.4 Hz, 1H), 7.75 (s, 1H), 7.62 (s, 1H), 7.50 (s, 1H), 7.47 (d, J = 8.0 Hz, 1H), 7.36 (s, 1H), 7.29 (d, J= 11.6 Hz, 1H), 7.17 (dd, /= 8.5, 1.2 Hz, 1H), 3.19—3.41 (m, 8H), 2.41-2.48 (in, 2H), 2.33-2.43 (i , 4H), 2.26 (s, 3H), 2.23 (s, 3HJ, 2.21 (s, 3H) 실시예 181. The title compound was obtained in the same manner as in Example 175. : H NMR (300 MHz, CD :: i 0D-f / 4 ) δ 7.99 (cl, / = 8.4 Hz, 1H), 7.75 (s, 1H), 7.62 (s, 1H), 7.50 (s, 1H) , 7.47 (d, J = 8.0 Hz, 1H), 7.36 (s, 1H), 7.29 (d, J = 11.6 Hz, 1H), 7.17 (dd, / = 8.5, 1.2 Hz, 1H), 3.19—3.41 ( m, 8H), 2.41-2.48 (in, 2H), 2.33-2.43 (i, 4H), 2.26 (s, 3H), 2.23 (s, 3HJ, 2.21 (s, 3H) Example 181.
6一 (4-플루오로 -2-메틸— 5— (3-(4-메틸피페라진 -1—일 )-5- (트리플루오로메틸)페닐) 벤즈아미도)페닐 )-Λ 피페리딘—4-일 )—1/ 인다졸 -3-카복스아미드의 제조  6- (4-Fluoro-2-methyl— 5— (3- (4-methylpiperazin-1-yl) -5- (trifluoromethyl) phenyl) benzamido) phenyl) -Λ piperidine —4-yl) —1 / Preparation of indazole-3-carboxamide
Figure imgf000107_0002
Figure imgf000107_0002
상기 실시예 175와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. NMR (300 MHz, DMS으 ) δ 10.33 (s, 1H), 8.20 (d, /= 8.2 Hz, 1H), 8.19 (cl, J= 8.4 Hz, 1H), 7.75 (s, 1H), 7.62 (s, 1H), 7.51 (s, 1H), 7.47 (cl, J = 7.9 Hz, 1H), 7.39 (s, 1H), 7.32 (d, J = 11.6 Hz, 1H), 7.22 (dd, J= 8.4, 1.3 Hz, The title compound was obtained in the same manner as the Example 175. NMR (300 MHz, DMS) δ 10.33 (s, 1H), 8.20 (d, / = 8.2 Hz, 1H), 8.19 (cl, J = 8.4 Hz, 1H), 7.75 (s, 1H), 7.62 (s , 1H), 7.51 (s, 1H), 7.47 (cl, J = 7.9 Hz, 1H), 7.39 (s, 1H), 7.32 (d, J = 11.6 Hz, 1H), 7.22 (dd, J = 8.4, 1.3 Hz,
1H), 3.80-4.00 (m, 2H), 3.10—3.35 (m, 4H), 2.87—3.03 (m, 3H) , 2.40-2.50 (m, 4H), 2.26 (s, 3H), 2.23 (s, 3H), 1.68-1.80 (m, 2H), 1.45—1.60 (ᅵ 11， 2H) 실시예 182. 1H), 3.80-4.00 (m, 2H), 3.10—3.35 (m, 4H), 2.87—3.03 (m, 3H), 2.40-2.50 (m, 4H), 2.26 (s, 3H), 2.23 (s, 3H), 1.68-1.80 (m, 2H), 1.45-1.60 (11, 2H) Example 182.
6-(4—플루오로— 2ᅩ메틸— 5-(3-(4-메틸피페라진 -1—일 )-5— (트리플루오로메틸)페닐) 벤즈아미도)페닐 )-yH 1—메틸피페리딘 -4—일 )—1^인다졸 -3—카복스아미드의 제조 상기 실시예 175와 방법으로 수행하여 싱-기 표제화합물을 얻었다. ]H NMR (300 MHz, DMS으^) δ 8.15 (d, J = 8.0 Hz, 1H), 8.04 (s, 1H), 7.75 (s, 1H), 7.62 (s, 1H), 7.45—7.55 (m, 2H), 7.37 (s, 3H), 7.28 (d, J= 11.7 Hz, 3H) , 7.14 (del , J= 8.4， 1.0 Hz, 3H), 4.02—4.12 (m,lH), 3.75-3.85 (m, 1H), 3.13-3.23 (m, 4H), 2.70-2.83 (m, 3H), 2.43-2.48 (m, 4H), 2.26 (s, 3H), 2.23 (s,3H), 2.17 (s, 3H), 1.93-2.03 (m, 2H), 1.65—1.77 (m, 2H) 실시예 183. 6- (4—fluoro— 2 ᅩ methyl— 5- (3- (4-methylpiperazin-1—yl) -5— (trifluoromethyl) phenyl) benzamido) phenyl) -yH 1—methyl Preparation of Piperidine-4-yl) -1 ^ indazol-3 Carboxamide Performed in the same manner as in Example 175, to obtain a single-group title compound. ] H NMR (300 MHz, DMS) δ 8.15 (d, J = 8.0 Hz, 1H), 8.04 (s, 1H), 7.75 (s, 1H), 7.62 (s, 1H), 7.45—7.55 (m , 2H), 7.37 (s, 3H), 7.28 (d, J = 11.7 Hz, 3H), 7.14 (del, J = 8.4, 1.0 Hz, 3H), 4.02—4.12 (m, lH), 3.75-3.85 ( m, 1H), 3.13-3.23 (m, 4H), 2.70-2.83 (m, 3H), 2.43-2.48 (m, 4H), 2.26 (s, 3H), 2.23 (s, 3H), 2.17 (s, 3H), 1.93-2.03 (m, 2H), 1.65-1.77 (m, 2H) Example 183.
6一 (4-플루오로— 2-메틸 -5-(3— (4-메틸피페라진 -1-일 )—5- (트리플루오로메틸 )페닐) 벤즈아미도)페닐) -Λ 4-메틸피페리딘— 1—일)— 1 / 인다졸—3—카복스아미드의 제조  6- (4-Fluoro— 2-methyl-5- (3— (4-methylpiperazin-1-yl) —5- (trifluoromethyl) phenyl) benzamido) phenyl) -Λ 4-methyl Piperidine— 1—yl) — 1 / indazole—3—carboxamide preparation
Figure imgf000108_0001
Figure imgf000108_0001
상기 실시예 175와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. Ή NMR (300 MHz, DMS( ) δ 9.19 (s, 1H), 8.13 (d, J = 8.6 Hz, 1H), 7.75 (s, 1H) , 7.63 (s, 1H), 7.45-7.53 (m, 2H), 7.37 (s, 1H), 7.29 (d, /= 11.5 Hz, 1H) , 7.15 (del, J 8.2， 1.1 Hz, 1H), 4.00-4.15 (m, 2H), 3.15—3.23 (m,8H), 2.85-2.95 (in, 4H), 2.40-2.46 (m, 4H), 2.26 (s, 3H), 2.23 (s, 3H), 2.20 (s, 3H). 실시예 184.  The title compound was obtained in the same manner as the Example 175. MR NMR (300 MHz, DMS () δ 9.19 (s, 1H), 8.13 (d, J = 8.6 Hz, 1H), 7.75 (s, 1H), 7.63 (s, 1H), 7.45-7.53 (m, 2H ), 7.37 (s, 1H), 7.29 (d, / = 11.5 Hz, 1H), 7.15 (del, J 8.2, 1.1 Hz, 1H), 4.00-4.15 (m, 2H), 3.15—3.23 (m, 8H ), 2.85-2.95 (in, 4H), 2.40-2.46 (m, 4H), 2.26 (s, 3H), 2.23 (s, 3H), 2.20 (s, 3H) .Example 184.
^싸이클로핵실— 6-(4—플루오로 -2-메틸— 5— (3— (4—메틸피페라진—1—일 ) -5- (트리플 루오로메틸)벤즈아미도)페닐 )—1^인다졸 -3—카복스아미드의 제조  ^ Cyclonuclear chamber— 6- (4—fluoro-2-methyl— 5— (3— (4—methylpiperazin—1—yl) -5- (trifluoromethyl) benzamido) phenyl) —1 ^ Preparation of indazole-3—carboxamide
Figure imgf000108_0002
Figure imgf000108_0002
상기 실시예 175와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. :H NMR (300 MHz, DMSO— ) δ 10.34 (s, 1H), 8.21 (d, J= 8.4 Hz, 1H), 8.07 (d, J= 8.4 Hz, 1H), 7.81 (s, 1H), 7.74 (s, 1H), 7.52-7.47 (m, 3H), 7.31 (d, J = 8.4 Hz, 11-0, 7.21 (〔1， / = 8.4 \ , , 4.10 (bs, 2H), 3.5 (bs, 2H), 3.16 (bs, 4H), 2.88 (s, 3H), 2.26 (s, 3H), 1,85-1.72 (in, 4H), 1.44—1.30 (m, 5H) 실시예 '185. The title compound was obtained in the same manner as the Example 175. : H NMR (300 MHz, DMSO—) δ 10.34 (s, 1H), 8.21 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 8.4 Hz, 1H), 7.81 (s, 1H), 7.74 (s, 1H), 7.52-7.47 (m, 3H), 7.31 (d, J = 8.4 Hz, 11-0, 7.21 ([1 ， / = 8.4 \,, 4.10 (bs, 2H), 3.5 (bs, 2H), 3.16 (bs, 4H), 2.88 (s, 3H), 2.26 (s , 3H), 1,85-1.72 (in, 4H), 1.44—1.30 (m, 5H) Example ' 185.
6一 (4-플루오로 -2-메틸— 5-(3— (4-메틸피페라진 -1-일 ) -5- (트리플루오로메틸)페닐) 벤즈아미도)페닐) -Λ ίΙ]닐— 다졸 -3-카복스아미드의 제조 6一(4-fluoro-2-methyl-5- (3- (4-methylpiperazin-1-yl) -5- (trifluoromethyl) phenyl) benz amido) phenyl) -Λ ί Ι] Preparation of Nyl-dazole-3-carboxamide
Figure imgf000109_0001
Figure imgf000109_0001
상기 실시예 175와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ll\ NMR (300 MHz, DMS0— ) δ 10.34 (d, /= 3.9 Hz, 2H), 8.28 (d, J = 8.4 Hz 1H), 7.90 (d, /= 7.5 Hz, 2H), 7.81 (s, 1H), 7.74 (s, 1H), 7.58-7.50 (m, 3H) 7.38-7.26 (m, 4H), 7.12-7.05 (m, 1H), 4.09 (bs, 2H), 3.63 (bs, 4H), 3.16 (bs 2H), 2.87 (s, 3H), 2.28 (s, 3H) 실시예 186. The title compound was obtained in the same manner as the Example 175. l l \ NMR (300 MHz, DMS0—) δ 10.34 (d, / = 3.9 Hz, 2H), 8.28 (d, J = 8.4 Hz 1H), 7.90 (d, / = 7.5 Hz, 2H), 7.81 (s , 1H), 7.74 (s, 1H), 7.58-7.50 (m, 3H) 7.38-7.26 (m, 4H), 7.12-7.05 (m, 1H), 4.09 (bs, 2H), 3.63 (bs, 4H) , 3.16 (bs 2H), 2.87 (s, 3H), 2.28 (s, 3H) Example 186.
6-(4—플루오로 -2—메틸 -5— (3-(4-메틸피페라진— 1ᅳ일 )-5- (트리플루오로메틸 )페닐) 벤즈아미도)페닐 )— 피리딘 -2ᅳ일 인다졸— 3-카복스아미드의 제조  6- (4—Fluoro-2—methyl-5— (3- (4-methylpiperazin—1 ᅳ yl) -5- (trifluoromethyl) phenyl) benzamido) phenyl) —pyridine-2xyl Sol—Preparation of 3-Carboxamides
Figure imgf000109_0002
Figure imgf000109_0002
상기 실시예 175와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾ NMR (300 MHz, DMSO- ) δ 14.00 (s, 1H), 10.33 (s, 1H), 9.85 (s, 1H), 8.39 (s, 1H), 8.29 (s, 1H), 8.26 (s, 1H), 7.91 (s, 1H), 7.80 (s, 1H), 7.75 (s, 1H), 7.60 (s, 1H), 7.53 (s, 2H), 7.32 (s, 2H), 7.21 (s, 1H), 4.12 (s, 4H), 3.15 (s, 4H), 2.87 (s, 3H), 2.28 (s, 3H). 실시예 187.  The title compound was obtained in the same manner as the Example 175. ¾ NMR (300 MHz, DMSO-) δ 14.00 (s, 1H), 10.33 (s, 1H), 9.85 (s, 1H), 8.39 (s, 1H), 8.29 (s, 1H), 8.26 (s, 1H ), 7.91 (s, 1H), 7.80 (s, 1H), 7.75 (s, 1H), 7.60 (s, 1H), 7.53 (s, 2H), 7.32 (s, 2H), 7.21 (s, 1H) , 4.12 (s, 4H), 3.15 (s, 4H), 2.87 (s, 3H), 2.28 (s, 3H). Example 187.
6-(4—플루오로 -2-메틸 -5-(3— (4-메틸피페라진 -1-일) -5— (트리플루오로메틸)페닐) 벤즈아미도)페닐) 피리딘 -3—일)—1^인다졸 -3-카복스아미드의 제조  6- (4—fluoro-2-methyl-5- (3— (4-methylpiperazin-1-yl) -5— (trifluoromethyl) phenyl) benzamido) phenyl) pyridin-3-3-yl ) — Preparation of 1 ^ indazole-3-carboxamide
Figure imgf000109_0003
Figure imgf000109_0003
상기 실시예 175와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. Ί-Ι NMR (300 MHz , C¾0으 ) δ 9.08 (d, /= 2.3 Hz, 1H), 8.33 (dcld, J= 8.5, 2.5, 1.5 Hz, 1H), 8.26 (del, J= 4.6, 1.4 Hz, 1H), 8.18 (d, J = 8.1 Hz, 1H), 7.76 (s, 1H), 7.63 (s, 1H), 7.56 (s, 1H), 7.48 (d, J二 7.9 Hz, 1H), 7.33-7.40 ' (in, 2H), 7.29 (d, J = 11.3 Hz, 1H), 7.14 (d, J = 8.5 Hz, 1H), 3.33-3.40 (m, 6H), 2.42-2.47 (m, 2H), 2.29 (s, 3H), 2.23 (s, 3H) 실시예 188. The title compound was obtained in the same manner as the Example 175. Ί-Ι NMR (300 MHz, C¾0) δ 9.08 (d, / = 2.3 Hz, 1H), 8.33 (dcld, J = 8.5, 2.5, 1.5 Hz, 1H), 8.26 (del, J = 4.6, 1.4 Hz , 1H), 8.18 (d, J = 8.1 Hz, 1H), 7.76 (s, 1H), 7.63 (s, 1H), 7.56 (s, 1H), 7.48 (d, J 二 7.9 Hz, 1H), 7.33 -7.40 '(in, 2H), 7.29 (d, J = 11.3 Hz, 1H), 7.14 (d, J = 8.5 Hz, 1H), 3.33-3.40 (m, 6H), 2.42-2.47 (m, 2H) , 2.29 (s, 3H), 2.23 (s, 3H) Example 188.
6-(4—플루오로— 2—메틸 -5-(3-(4-메틸피페라진 -1-일 ) -5- (트리플루오로메틸)페닐) 벤즈아미도)페닐 인다졸—3-카복스아미드의 제조  6- (4—Fluoro— 2—methyl-5- (3- (4-methylpiperazin-1-yl) -5- (trifluoromethyl) phenyl) benzamido) phenyl indazole—3-car Preparation of Voxamide
Figure imgf000110_0001
Figure imgf000110_0001
상기 실시예 175와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. 醒 (300 MHz, DMSO— δ 10.32 (s, 1H), 8.17 (d, J二 8.4 Hz, 1H), 7.80 (s, 1H), 7.75 (s, 1H), 7.52-7.47 (m, 4H), 7.32 (d, J = 12.4 Hz, 1H), 7.21 (d, J = 8.4 Hz, 1H), 4.12-4.07 (m, 2H), 3.54 (bs, 2H) , 3.15 (bs, 4H), 2.88 (s, 3H), 2.27 (s, 3H) 실시예 189.  The title compound was obtained in the same manner as the Example 175. 300 (300 MHz, DMSO— δ 10.32 (s, 1H), 8.17 (d, J 2 8.4 Hz, 1H), 7.80 (s, 1H), 7.75 (s, 1H), 7.52-7.47 (m, 4H), 7.32 (d, J = 12.4 Hz, 1H), 7.21 (d, J = 8.4 Hz, 1H), 4.12-4.07 (m, 2H), 3.54 (bs, 2H), 3.15 (bs, 4H), 2.88 (s , 3H), 2.27 (s, 3H) Example 189.
6_(4-플루오로— 2ᅳ메틸 -5-(3-(4-메틸피페라진 1—일)— 5- (트리플루오로메틸)페닐) 벤즈아미도)페닐 )-Λ 6ᅳ플루오로피리딘 -3_일 )-1/ 인다졸ᅳ 3-카복스아미드  6_ (4-Fluoro— 2 ᅳ methyl-5- (3- (4-methylpiperazin 1-yl) — 5- (trifluoromethyl) phenyl) benzamido) phenyl) -Λ 6 ᅳ fluoropyridine -3_yl) -1 / indazol3-carboxamide
Figure imgf000110_0002
Figure imgf000110_0002
상기 실시예 175와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾ NMR (300 MHz, DMSO-οί;) δ 13.99 (s, 1H) , 10.82 (s, 1H), 10.36 (s, 1H) , 8.75 (s, 1H), 8.42-8.50 (m, 1H), 8.27 (d, J = 8.3 Hz, 1H), 7.80 (s, 1H), 7.75 (s, 1H), 7.59 (s, 1H), 7.54 (s, 1H), 7.53 (s, 1H), 7.51 (d, J= 8.3 Hz, 1H), 7.34 The title compound was obtained in the same manner as the Example 175. ¾ NMR (300 MHz, DMSO-οί;) δ 13.99 (s, 1H), 10.82 (s, 1H), 10.36 (s, 1H), 8.75 (s, 1H), 8.42-8.50 (m, 1H), 8.27 (d, J = 8.3 Hz, 1H), 7.80 (s, 1H), 7.75 (s, 1H), 7.59 (s, 1H), 7.54 (s, 1H), 7.53 (s, 1H), 7.51 (d, J = 8.3 Hz, 1H), 7.34
(d, J= 11.5 Hz, 1H), 7.29 (d, /= 8.4 Hz, 1H), 7.23 (dd, J = 8.7, 3.2 Hz, 1H), 4.05—4.17 (m, 2H), 3.50-3.65 (m, 2H), 3.05-3.22 (m, 4H), 2.87 (s, 3H), 2.28 (s, 3H). 실시예 190. (d, J = 11.5 Hz, 1H), 7.29 (d, / = 8.4 Hz, 1H), 7.23 (dd, J = 8.7, 3.2 Hz, 1H), 4.05—4.17 (m, 2H), 3.50-3.65 ( m, 2H), 3.05-3.22 (m, 4H), 2.87 (s, 3H), 2.28 (s, 3H). Example 190.
6-(4—플루오로 -2ᅳ메틸— 5-(3-(4-메틸피페라진 -1ᅳ일 )-5- (트리플루오로메틸)페닐) 벤즈아미도)페닐 )-Λ 6-메틸피리딘— 3-일 )-1//·인다졸— 3-카복스아 6- (4—Fluoro-2 ᅳ methyl— 5- (3- (4-methylpiperazin-1xyl) -5- (trifluoromethyl) phenyl) Benzamido) phenyl) -Λ 6-methylpyridine- 3-yl) -1 // · indazole- 3-carboxa
트리플루오로아서 J트산염의 제조 Preparation of Trifluoro Arthur J-Tate
Figure imgf000111_0001
Figure imgf000111_0001
상기 실시예 175와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. Ή NMR (300 MHz, DMSO—οί;) δ 14.07 (s, 1H), 10.98 (s, 1H), 10.37 (s, 1H), 9.15 (s, 1H), 8.49 (d, J = 8.6 Hz, 1H)， 8.28 (d, J = 8.5 Hz, 1H), 7.81 (s, 1H), 7.75 (s, 1H), 7.56—7.63 (m, 2H), 7.54 (s, 1H), 7.51 (d, /= 8.1 Hz, 1H), 7.35 (d, J 12.5 Hz, 1H), 7.29-7.33 (m, 4.05—4.15 (m, 2H) , 3.50-3.65 (m, 2H), 3.05-3.25 (m, 4H), 2.88 (s, 3H), 2.57 (s, 3H), 2.28 (s, 3H). 실시예 191.  The title compound was obtained in the same manner as the Example 175. MR NMR (300 MHz, DMSO—οί;) δ 14.07 (s, 1H), 10.98 (s, 1H), 10.37 (s, 1H), 9.15 (s, 1H), 8.49 (d, J = 8.6 Hz, 1H ), 8.28 (d, J = 8.5 Hz, 1H), 7.81 (s, 1H), 7.75 (s, 1H), 7.56—7.63 (m, 2H), 7.54 (s, 1H), 7.51 (d, / = 8.1 Hz, 1H), 7.35 (d, J 12.5 Hz, 1H), 7.29-7.33 (m, 4.05—4.15 (m, 2H), 3.50-3.65 (m, 2H), 3.05-3.25 (m, 4H), 2.88 (s, 3H), 2.57 (s, 3H), 2.28 (s, 3H) Example 191.
6-(4-플루오로— 2-메틸 -5-(3-(4-메틸피페라진 1-일) -5- (트리플루오로메틸)페닐) 벤즈아미도)페닐 )-Λ 4-메틸피리딘 -3—일 인다졸 -3—카복스아미드  6- (4-fluoro— 2-methyl-5- (3- (4-methylpiperazin 1-yl) -5- (trifluoromethyl) phenyl) benzamido) phenyl) -Λ 4-methylpyridine -3—yl indazole-3—carboxamide
트리플루오로아세트산염의 제조 Preparation of Trifluoroacetic Acid
Figure imgf000111_0002
Figure imgf000111_0002
상기 실시예 175와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. Ή NMR (300 MHz, DMS0-of:i) δ 14.00 (s, 1H), 10.36 (s, 1H), 10.30 (s, 1H), 8.85 (s, 1H), 8.46 (d, J= 5.2 Hz, 1H), 8.24 (cl, /= 8.3 Hz, 1H), 7.80 (s, 1H), 7.75 (s, 1H), 7.65-7.78 (m, 2H), 7.53 (s, 1H), 7.51 (d, J= 8.3 Hz, 1H), 7.35 (d, J= 11.6 Hz, 1H), 7.31-7.27 (m, 1H), 4.05-4.15 (m, 2H) , 3.47-3.65 (ra, 2H), 3.05-3.25 (111， 4H), 2.88 (s, 3H), 2.43 (s, 3H), 2.28 (s, 3H). 실시예 192. The title compound was obtained in the same manner as the Example 175. NMR (300 MHz, DMS0-of : i ) δ 14.00 (s, 1H), 10.36 (s, 1H), 10.30 (s, 1H), 8.85 (s, 1H), 8.46 (d, J = 5.2 Hz, 1H), 8.24 (cl, / = 8.3 Hz, 1H), 7.80 (s, 1H), 7.75 (s, 1H), 7.65-7.78 (m, 2H), 7.53 (s, 1H), 7.51 (d, J = 8.3 Hz, 1H), 7.35 (d, J = 11.6 Hz, 1H), 7.31-7.27 (m, 1H), 4.05-4.15 (m, 2H), 3.47-3.65 (ra, 2H), 3.05-3.25 ( 111, 4H), 2.88 (s, 3H), 2.43 (s, 3H), 2.28 (s, 3H). Example 192.
6_(4-플루오로 -2—메틸 -5-(3-(4-메틸피페라진— 1-일 )-5- (트리플루오로메틸)페닐) 벤즈아미도)페닐) -7H피리미딘— 5-일 )-1^인다졸 -3—카복스아미드  6_ (4-Fluoro-2—methyl-5- (3- (4-methylpiperazin— 1-yl) -5- (trifluoromethyl) phenyl) benzamido) phenyl) -7Hpyrimidine— 5 -Yl) -1 ^ indazole-3—carboxamide
트리플루오로아세트산염의 제조
Figure imgf000112_0001
Preparation of Trifluoroacetic Acid
Figure imgf000112_0001
상기 실시예 175와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. NMR (300 MHz, DMSO-flf;) δ 14.07 (s, 1H), 10.96 (s, 1H), 10.37 (s, 1H), 9.32 (s, 2H), 8.94 (s, 1H), 8.28 (d, J= 8.4 Hz, 1H), 7.80 (s, 1H), 7.75 (s, 1H), 7.61 (s, 1H) , 7.54 (s, 1H), 7.51. (d, J= 8.2 Hz, 1H), 7.35 (d, J = 12.6 Hz, 1H), 7.32-7.28 (m, 1H), 4.05-4.15 (m, 2H) , 3.53—3.63 (m, 2H), 3.05—3.25 (m, 4H), 2.87 (s, 3H), 2.29 (s, 3H). 실시예 193.  The title compound was obtained in the same manner as the Example 175. NMR (300 MHz, DMSO-flf;) δ 14.07 (s, 1H), 10.96 (s, 1H), 10.37 (s, 1H), 9.32 (s, 2H), 8.94 (s, 1H), 8.28 (d, J = 8.4 Hz, 1H), 7.80 (s, 1H), 7.75 (s, 1H), 7.61 (s, 1H), 7.54 (s, 1H), 7.51. (d, J = 8.2 Hz, 1H), 7.35 (d, J = 12.6 Hz, 1H), 7.32-7.28 (m, 1H), 4.05-4.15 (m, 2H), 3.53—3.63 (m, 2H), 3.05—3.25 (m, 4H), 2.87 (s, 3H), 2.29 (s, 3H). Example 193.
벤질 -6_(4—플루오로 -2—메틸 -5-(3-(4-메틸피페라진 -1-일)ᅳ 5- (트리플루오로메 틸)벤즈아미도)페닐)—1^인다졸 -3—카복스아미드의 제조  Benzyl-6_ (4—fluoro-2—methyl-5- (3- (4-methylpiperazin-1-yl) ᅳ 5- (trifluoromethyl) benzamido) phenyl) —1 ^ indazole- 3—Manufacture of Carboxamides
Figure imgf000112_0002
Figure imgf000112_0002
상기 실시예 175와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. l\\ NMR (300 MHz , DMSO^) δ 10.33 (s, 1H), 9.02—8.97 (m, 1H), 8.22 (d, J = 8.4 Hz, 1H), 7.80 (s, 1H), 7.74 (s, 1H), 7.52—7.47 (m, 3H), 7.38—7.25 (in, 6H), 4.51 (d, J = 6.3 Hz, 2H), 4.11—4.07 (in, 2H), 3.54 (bs, 2H), 3.15 (bs, 4H), 2.88 (s, 31-1)， 2.27 (s, 3H) 실시예 194. The title compound was obtained in the same manner as the Example 175. l \\ NMR (300 MHz, DMSO ^) δ 10.33 (s, 1H), 9.02—8.97 (m, 1H), 8.22 (d, J = 8.4 Hz, 1H), 7.80 (s, 1H), 7.74 (s , 1H), 7.52—7.47 (m, 3H), 7.38—7.25 (in, 6H), 4.51 (d, J = 6.3 Hz, 2H), 4.11—4.07 (in, 2H), 3.54 (bs, 2H), 3.15 (bs, 4H), 2.88 (s, 31-1), 2.27 (s, 3H) Example 194.
6_(4-플루오로 -2-메틸 -5— (3— (4—메틸피페라진 -1—일 )-5— (트리플루오로메틸)벤즈 아미도)페닐)ᅳ Λ 피리딘—2—일메틸 인다졸—3—카복스아미드의 제조  6_ (4-fluoro-2-methyl-5— (3— (4—methylpiperazin-1—yl) -5— (trifluoromethyl) benz amido) phenyl) ᅳ Λ pyridine—2—ylmethyl Indazole-3 Preparation of Carboxamide
Figure imgf000112_0003
Figure imgf000112_0003
상기 실시예 175와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾ NMR (300 MHz, DMS으^) δ 13.71 (s, 1H), 10.30 (s, 1H), 8.99 (t, J= 5.9 Hz, 1H), 8.53 (d, J 3.5 Hz, 1H), 8.22 (d, J= 8.3 Hz, 1H) , 7.77 (d, J= 8.1 Hz, 2H), 7.64 (s, 1H), 7.54 (s, 1H) , 7.49 (d, J= 7.9 Hz, 1H), 7.38 (s, 2H), 7.34 (d, J= 7.7 Hz, 1H), 7.31-7.19 (m, 2H), 4.64 (d, J= 5.8 Hz, 2H), 3.33 (s, 4H), 2.51 (s, 4H), 2.27 (s, 6H). 실시예 195. The title compound was obtained in the same manner as the Example 175. ¾ NMR (300 MHz, DMS) δ 13.71 (s, 1H), 10.30 (s, 1H), 8.99 (t, J = 5.9 Hz, 1H), 8.53 (d, J 3.5 Hz, 1H), 8.22 ( d, J = 8.3 Hz, 1H), 7.77 (d, J = 8.1 Hz, 2H), 7.64 (s, 1H), 7.54 (s, 1H), 7.49 (d, J = 7.9 Hz, 1H), 7.38 ( s, 2H), 7.34 (d, J = 7.7 Hz, 1H), 7.31-7.19 (m, 2H), 4.64 (d, J = 5.8 Hz, 2H), 3.33 (s, 4H), 2.51 (s, 4H ), 2.27 (s, 6 H). Example 195.
Λ (6—클로로피리딘 -3—일)메틸) -6-(4-플루오로 -2—메틸 -5— (3-(4—메틸피페라진一 1 ᅳ일 )一5- (트리플루오로메틸 )벤즈아미도)페닐 )-Λ 피리미딘 -5-일 )— I/ 인다졸 -3— 카복스아미드의 제조  Λ (6—Chloropyridin-3—yl) methyl) -6- (4-fluoro-2—methyl-5— (3- (4-methylpiperazin 一 1 kyl) 一 5- (trifluoromethyl) Preparation of benzamido) phenyl) -Λ pyrimidin-5-yl) —I / indazol-3—carboxamide
Figure imgf000113_0001
Figure imgf000113_0001
상기 실시예 175와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. NMR (300 MHz , DMS0— δ 13.71 (s, 1H), 10.29 (s, 1H), 9.13 (t, J = 6.2 Hz, 1H), 8.42 (d, J = 2.5 Hz, 1H) , 8.20 (d, J = 8.4 Hz, 1H), 7.85 (del, / = 8.2, 2.4 Hz, 1H), 7.75 (s, 1H), 7.62 (s, 1H), 7.52 (s, 1H), 7.48 (del, /= 8.1, 2.5 Hz, 2H), 7.38 (s, 1H), 7.31 (d, J 11.5 Hz, 1H), 7.23 (d, J 8.4 Hz, IH), 4.52 (d, J= 6.2 Hz, 2H), 3.31 (s, 4H), 2.45 (s, 4H), 2.26 (s, 3H), 2.23 (s, 3H). 실시예 196.  The title compound was obtained in the same manner as the Example 175. NMR (300 MHz, DMS0—δ 13.71 (s, 1H), 10.29 (s, 1H), 9.13 (t, J = 6.2 Hz, 1H), 8.42 (d, J = 2.5 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 7.85 (del, / = 8.2, 2.4 Hz, 1H), 7.75 (s, 1H), 7.62 (s, 1H), 7.52 (s, 1H), 7.48 (del, / = 8.1 , 2.5 Hz, 2H), 7.38 (s, 1H), 7.31 (d, J 11.5 Hz, 1H), 7.23 (d, J 8.4 Hz, IH), 4.52 (d, J = 6.2 Hz, 2H), 3.31 ( s, 4H), 2.45 (s, 4H), 2.26 (s, 3H), 2.23 (s, 3H) Example 196.
6_(4ᅳ플루오로— 2-메틸 -5ᅳ (3-(4—메틸피페라진— 1-일 )ᅳ5— (트리플루오로메틸 )벤즈 아미도)페닐) -Λ 피리미딘— 4—일메틸 인다졸 -3-카복스아미드의 제조  6_ (4 ᅳ fluoro— 2-methyl-5 ᅳ (3- (4—methylpiperazin— 1-yl) ᅳ 5— (trifluoromethyl) benz amido) phenyl) -Λ pyrimidin— 4—yl Preparation of Methyl Indazole-3-Carboxamide
Figure imgf000113_0002
Figure imgf000113_0002
상기 실시예 175와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ]H匪 R (300 MHz, DMSO-^;) δ 13.79 (s, 1H), 10.33 (s, 1H), 9.24 (t, J= 6.2 Hz, IH), 8.68 (d, J = 6.3 Hz, 2H) , 8.19 (d, / = 8.5 Hz, 1H), 7.80 (s, 1H), 7.75 (s, IH), 7.67 (s, IH), 7.65 (s, IH), 7.54 (d, J= 6.7 Hz, 2H), 7.49 (d, J = 7.9 Hz, IH), 7.33 (d, J = 11.6 Hz, IH), 7.23 (d, J= 8.4 Hz, IH), 4.66 (d, J = 6.2 Hz, 2H), 4.08 (s, 4H), 3.55 (s, 4H), 2.88 (s, 3H), 2.26 (s, 3H). 실시예 197. The title compound was obtained in the same manner as the Example 175. ] H 匪 R (300 MHz, DMSO- ^;) δ 13.79 (s, 1H), 10.33 (s, 1H), 9.24 (t, J = 6.2 Hz, IH), 8.68 (d, J = 6.3 Hz, 2H ), 8.19 (d, / = 8.5 Hz, 1H), 7.80 (s, 1H), 7.75 (s, IH), 7.67 (s, IH), 7.65 (s, IH), 7.54 (d, J = 6.7 Hz , 2H), 7.49 (d, J = 7.9 Hz, IH), 7.33 (d, J = 11.6 Hz, IH), 7.23 (d, J = 8.4 Hz, IH), 4.66 (d, J = 6.2 Hz, 2H ), 4.08 (s, 4H), 3.55 (s, 4H), 2.88 (s, 3H), 2.26 (s, 3H). Example 197.
6-(4-플루오로— 2-메틸 -5-(3-(4-메틸피페라진 -1—일) -5- (트리플루오로메틸)벤즈 아미도)페닐) -Λ 피리딘—3—일메틸)— I 인다졸-카복스아미드의 제조  6- (4-fluoro— 2-methyl-5- (3- (4-methylpiperazin-1-yl) -5- (trifluoromethyl) benz amido) phenyl) -Λ pyridin—3—yl Methyl) —I Preparation of Indazole-Carboxamide
Figure imgf000113_0003
Figure imgf000113_0003
상기 실시예 175와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ]ll NMR (300 MHz , DMSO-fi!:;) δ 13.77 (s, 1H), 10.34 (s, 1H), 9.19 (t, /= 6.2 Hz, 11-0, 8.72 (s, 1H), 8.60 (d, J = 5.1 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 8.07 (d, J 8.1 Hz, 111)， 7.80 (s, 1H), 7.74 (s, 1H), 7.62 (del, J = 7.8, 5.3 Hz, 1H), 7.53 (s, 2H), 7.49 (d, J 7.9 Hz, 1H), 7.32 (cl, J= 11.7 Hz, 1H), 7.23 (del, J 8.4, 1.3 Hz, 1H), 4.60 (cl, J = 6.2 Hz, 2H) , 4.06 (s, 4H), 3.15 (s, 4H), 2.88 (s, 3H), 2.26 (s, 3H). 실시예 198. The title compound was obtained in the same manner as the Example 175. ] Ll NMR (300 MHz, DMSO -fi:;!) Δ 13.77 (s, 1H), 10.34 (s, 1H), 9.19 (t, / = 6.2 Hz, 11-0, 8.72 (s, 1H), 8.60 (d, J = 5.1 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 8.07 (d, J 8.1 Hz, 111), 7.80 (s, 1H), 7.74 (s, 1H), 7.62 ( del, J = 7.8, 5.3 Hz, 1H), 7.53 (s, 2H), 7.49 (d, J 7.9 Hz, 1H), 7.32 (cl, J = 11.7 Hz, 1H), 7.23 (del, J 8.4, 1.3 Hz, 1H), 4.60 (cl, J = 6.2 Hz, 2H), 4.06 (s, 4H), 3.15 (s, 4H), 2.88 (s, 3H), 2.26 (s, 3H) Example 198.
6-(4-플루오로— 5-(3-(4-플루오로 -3— (트리플루오로메틸)페닐)우레이도)—2—메틸 페닐)— 피리딘 -2—일 )-1^인다졸 -3-카복스아미드의 제조  6- (4-fluoro— 5- (3- (4-fluoro-3— (trifluoromethyl) phenyl) ureido) —2—methyl phenyl) —pyridin-2-yl) -1 ^ indazole Preparation of 3-Carboxamide
Figure imgf000114_0001
단계 1. 에틸
Figure imgf000114_0001
Step 1. Ethyl
6-(4-플루오로 -5-(3-(4-플루오로 -3- (트리플루오로메틸)페닐)우레이도) -2-메틸 페닐) 인다졸 -3-카복실레이트의 제조  Preparation of 6- (4-fluoro-5- (3- (4-fluoro-3- (trifluoromethyl) phenyl) ureido) -2-methyl phenyl) indazole-3-carboxylate
상기 실시예 175의 단계 5와 동일한 방법으로 에틸 Ethyl in the same manner as in step 5 of Example 175
6-( 5-아미노 -4-플루오로 -2-메틸페닐 )—1- (테트라하이드로 -2/ 피란ᅳ 2-일 )-1그인 다졸 -3-카복실레이트를 반응시켜， 에틸  6- (5-amino-4-fluoro-2-methylphenyl) —1- (tetrahydro-2 / pyranjan 2-yl) -1 ginazole carboxylate to react, ethyl
6-(4-플루오로 -5-(3-(4-플루오로— 3- (트리플루오로메틸)페닐 )우레이도)— 2—메틸 페닐) 인다졸 -3—카복실레이트를 얻었다. MS m/z [M+H] 519 단계 2.  6- (4-Fluoro-5- (3- (4-fluoro- 3- (trifluoromethyl) phenyl) ureido) -2 -methyl phenyl) indazole-3-carboxylate was obtained. MS m / z [M + H] 519 step 2.
6一 (4-플루오로 -5— (3-(4-플루오로 -3- (트리플루오로메틸)페닐)우레이도) -2—메틸 페닐) -Λ 피리딘 -2—일 )-1그인다졸 -3-카복스아미드의 제조  6- (4-fluoro-5— (3- (4-fluoro-3- (trifluoromethyl) phenyl) ureido) -2—methyl phenyl) -Λ pyridin-2-2-yl) -1 Preparation of Sol-3-Carboxamide
상기 실시예 175의 단계 3, 단계 4 및 단계 5와 동일한 방법으로 에틸 Ethyl in the same manner as in Step 3, Step 4 and Step 5 of Example 175
6-(4—플루오로 -5-(3-(4—플루오로 -3- (트리플루오로메틸)페닐)우레이도)—2-메틸 페닐 인다졸— 3-카복실레이트를 반웅시켜 , 6- (4—Fluoro-5 (3- (4—fluoro-3- (trifluoromethyl) phenyl) ureido) —2-methyl Phenyl indazole — reacted with 3-carboxylate,
6- (4-플루오로— 5- (3— (4-플루오로— 3— (트리플루오로메틸)페닐)우레이도)—2—메틸 페닐 )— Λ 피리딘 -2-일 )-1/"인다졸 -3—카복스아미드를 얻었다.  6- (4-fluoro— 5- (3— (4-fluoro— 3— (trifluoromethyl) phenyl) ureido) —2—methyl phenyl) — Λ pyridin-2-yl) -1 / " Indazole-3—carboxamide was obtained.
Ή NMR (300 MHz, DMS0 i) δ 13.97 (s, 1H), 9.86 (s, 1H), 9.38 (s,lH), 8.65 (s, 2H), 8.45-8.34 (m, 1H), 8.31-8.20 (m, 1H), 8.08—7.95 (m, 2H), 7.95-7.86 (m, 1H), 7.53-7.63 (in, 2H), 7.43 (t, J= 9.7 Hz, 2H), 7.15—7.33 (m, 3H), 2.21 (s, 3H). 실시예 199. MR NMR (300 MHz, DMS0 i) δ 13.97 (s, 1H), 9.86 (s, 1H), 9.38 (s, lH), 8.65 (s, 2H), 8.45-8.34 (m, 1H), 8.31-8.20 (m, 1H), 8.08—7.95 (m, 2H), 7.95-7.86 (m, 1H), 7.53-7.63 (in, 2H), 7.43 (t, J = 9.7 Hz, 2H), 7.15—7.33 (m , 3H), 2.21 (s, 3H). Example 199.
6-(4—플루오로 -5-(3-(4- -3- (트리폴루오로메틸)페닐)우레이도)— 2-메틸 페닐) -Λ 피리딘—3—일)— 1^인다졸 -3ᅳ카복스아미드의 제조  6- (4—Fluoro-5 (3- (4--3- (tripololomethyl) phenyl) ureido) — 2-methyl phenyl) -Λ pyridin—3—yl) — 1 ^ indazole Preparation of -3 ᅳ carboxamide
Figure imgf000115_0001
Figure imgf000115_0001
상기 실시예 198과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. Ή NMR (300 MHz, DMS0— ) δ 13.93 (s, 3H), 10.70 (s, 3H), 9.39 (s, 4H), 9.08 (s, 4H), 8.67 (s, 4H), 8.30 (dd, J = 20.9, 8.2 Hz, 12H), 8.08-7.97 (m, 8H), 7.56 (s, 6H), 7.49-7.36 (in, 8H), 7.29 (s, 4H), 7.25 (d, J= 4.9 Hz, 4H), 2.21 (s, 12H) , 1.26 (d, / = 6.8 Hz, 5H), 1.12 (d, J = 6.7 Hz, 5H). 실시예 200.  The title compound was obtained in the same manner as the Example 198. NMR (300 MHz, DMS0—) δ 13.93 (s, 3H), 10.70 (s, 3H), 9.39 (s, 4H), 9.08 (s, 4H), 8.67 (s, 4H), 8.30 (dd, J = 20.9, 8.2 Hz, 12H), 8.08-7.97 (m, 8H), 7.56 (s, 6H), 7.49-7.36 (in, 8H), 7.29 (s, 4H), 7.25 (d, J = 4.9 Hz, 4H), 2.21 (s, 12H), 1.26 (d, / = 6.8 Hz, 5H), 1.12 (d, J = 6.7 Hz, 5H). Example 200.
6-(4ᅳ플루오로 -5-(3— (4—플루오로 -3— (트리플루오로메틸)페닐)우레이도) -2-메틸 페닐) -Λ 4-메틸피페라진—1—일 )ᅳ 1^인다졸 -3-카복스아미드의 제조  6- (4 ᅳ fluoro-5- (3— (4—fluoro-3— (trifluoromethyl) phenyl) ureido) -2-methyl phenyl) -Λ 4-methylpiperazine—1—yl) 제조 Preparation of 1 ^ indazole-3-carboxamide
Figure imgf000115_0002
Figure imgf000115_0002
상기 실시예 198과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. lW NMR (300 MHz, DMS0— ) δ 13.72 (s, 1Η), 9.92 (s, 1H), 9.43 (s, 1H), 8.70 (s, 1H), 8.16 (d, J= 8.4 Hz, 1H), 8.02 (d, /= 8.2 Hz, 2H) , 7.55 (s, 1H), 7.50 (s, 1H), 7.44 (t, J = 9.8 Hz, 1H), 7.24 (t, J 11.2 Hz, 2H), 3.44 (s, 3H), 3.20 (s, 5H), 2.83 (s, 3H), 2.19 (s, 3H). 실시예 201. The title compound was obtained in the same manner as the Example 198. l W NMR (300 MHz, DMS0- ) δ 13.72 (s, 1Η), 9.92 (s, 1H), 9.43 (s, 1H), 8.70 (s, 1H), 8.16 (d, J = 8.4 Hz, 1H) , 8.02 (d, / = 8.2 Hz, 2H), 7.55 (s, 1H), 7.50 (s, 1H), 7.44 (t, J = 9.8 Hz, 1H), 7.24 (t, J 11.2 Hz, 2H), 3.44 (s, 3H), 3.20 (s, 5H), 2.83 (s, 3H), 2.19 (s, 3H). Example 201.
6一 (4ᅳ플루오로 -5— (3-(4ᅳ플루오로— 3- (트리플루오로메틸)페닐)우레이도) -2ᅳ메틸 페닐) - ^이소프로필 -1^인다졸 -3-카복스아미드의 제조
Figure imgf000116_0001
6 one (4 ᅳ fluoro-5— (3- (4 ᅳ fluoro—3- (trifluoromethyl) phenyl) ureido) -2 ᅳ methyl phenyl)-^ isopropyl-1 ^ indazole-3- Preparation of Carboxamide
Figure imgf000116_0001
상기 실시예 198과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ]H NMR (300 MHz, DMS( ) δ 9.40 (s, 1Η), 8.65 (s, 1H) , 8.20 (d, J 8.4 Hz, 11-1), 8.08 (cl, J= 8.4 Hz, 1H) ,7.96-8.03 (m, 2H), 7.55—7.63 (m, 1H), 7.47 (s, IH), 7.38-7.47 (m, 1H), 7.24 (d, J = 12.3 Hz, 1H), 7.19 (del, J= 8.4, 1.1 Hz, 1H), 4.12-4.28 (m, 1H), 2.19 (s, 3H), 1.22 (d, / = 6.6 Hz, 6H). 실시예 202. The title compound was obtained in the same manner as the Example 198. ] H NMR (300 MHz, DMS () δ 9.40 (s, 1Η), 8.65 (s, 1H), 8.20 (d, J 8.4 Hz, 11-1), 8.08 (cl, J = 8.4 Hz, 1H), 7.96-8.03 (m, 2H), 7.55—7.63 (m, 1H), 7.47 (s, IH), 7.38-7.47 (m, 1H), 7.24 (d, J = 12.3 Hz, 1H), 7.19 (del, J = 8.4, 1.1 Hz, 1H), 4.12-4.28 (m, 1H), 2.19 (s, 3H), 1.22 (d, / = 6.6 Hz, 6H) Example 202.
Λ 이클로프로필ᅳ 6-(4-플루오로— 5— (3-(4—플루오로 -3— (트리- t루오로메틸)페닐) 우레이도)— 2-메틸페닐 )—1//·인다졸 -3-카복스아미드의 제조  Λ Iclopropyl ᅳ 6- (4-fluoro— 5— (3- (4—fluoro-3— (tri- t-fluoromethyl) phenyl) ureido) — 2-methylphenyl) —1 // Preparation of Sol-3-Carboxamide
Figure imgf000116_0002
Figure imgf000116_0002
상기 실시예 198과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ^ NMR (300 MHz, 画一 ) δ 13.56 (s, 1H), 9.36 (s, 1H) , 8.63 (d, J= 1.8 Hz, 1H), 8.42 (d, /= 4.6 Hz, 1H), 8.20 (d, J= 7.9 Hz, 1H), 7.96—8.05 (m, 2H), 7.52-7.66 (m, 1H), 7.37-7.47 (m, 2H), 7.24 (d, J = 12.6 Hz, IH), 7.20 (del, J = 8.4, 1.4 Hz, IH), 2.83-2.98 (m, IH), 2.20 (s, 3H), 0.63—0.78 (m, 4H). 실시예 203.  The title compound was obtained in the same manner as the Example 198. ^ NMR (300 MHz, 画 一) δ 13.56 (s, 1H), 9.36 (s, 1H), 8.63 (d, J = 1.8 Hz, 1H), 8.42 (d, / = 4.6 Hz, 1H), 8.20 ( d, J = 7.9 Hz, 1H), 7.96—8.05 (m, 2H), 7.52-7.66 (m, 1H), 7.37-7.47 (m, 2H), 7.24 (d, J = 12.6 Hz, IH), 7.20 (del, J = 8.4, 1.4 Hz, IH), 2.83-2.98 (m, IH), 2.20 (s, 3H), 0.63-0.78 (m, 4H). Example 203.
6一 (4—플루오로 -5-(3-(4-플루오로 -3- (트리플루오로메틸)페닐)우레이도) -2-메틸 페닐) 몰포린 -1 인다졸 -3—카복스아미드의 제조  6- (4—fluoro-5- (3- (4-fluoro-3- (trifluoromethyl) phenyl) ureido) -2-methyl phenyl) morpholine-1 indazole-3—carboxamide Manufacture
Figure imgf000116_0003
Figure imgf000116_0003
상기 실시예 198과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾ NMR (300 MHz, DMS오^) δ 9.50 (s, IH), 9.47 (s, IH) , 8.68 (d, J 1.6 Hz, IH), 8.16 (d, J= 8.4 Hz, IH), 7.95-8.04 (m, 2H), 7.54—7.65 (m, IH), 7.48 (s, IH), 7.37-7.47 (m, IH), 7.24 (d, J= 12.8 Hz, IH), 7.19 (d, J= 1.2 Hz, IH), 3.65-3.72 (m, 4H), 2.87-2.96 (m, 4H), 2.19 (s, 3H). 실시예 204.  The title compound was obtained in the same manner as the Example 198. ¾ NMR (300 MHz, DMS) δ 9.50 (s, IH), 9.47 (s, IH), 8.68 (d, J 1.6 Hz, IH), 8.16 (d, J = 8.4 Hz, IH), 7.95- 8.04 (m, 2H), 7.54–7.65 (m, IH), 7.48 (s, IH), 7.37-7.47 (m, IH), 7.24 (d, J = 12.8 Hz, IH), 7.19 (d, J = 1.2 Hz, IH), 3.65-3.72 (m, 4H), 2.87-2.96 (m, 4H), 2.19 (s, 3H). Example 204.
6-(4-플루오로 -5— (3-(4ᅳ플루오로 -3— (트리플루오로메틸)페닐)우레이도) -2-메틸 페닐) -/H피리딘— 2—일메틸 ) - l/ 인다졸— 3-카복스아미드의 제조 6- (4-fluoro-5— (3- (4 ᅳ fluoro-3— (trifluoromethyl) phenyl) ureido) -2-methyl Phenyl)-/ Hpyridine-2-ylmethyl)-l / indazole-Preparation of 3-carboxamide
Figure imgf000117_0001
Figure imgf000117_0001
상기 실시예 198과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾ NMR (300 MHz, DMS0一^) δ 13.70 (s, 1H), 9.37 (s, 1H), 9.08 (t, J= 5.9 Hz, 1H), 8.63 (d, /= 3.7 Hz, 2H), 8.19 (d, J = 8.6 Hz, 1H) ,7.95-8.05 (m, 2H), 7.55-7.63 (m, 2H), 7.38-7.54 (m, 3H), 7.25 (cl, / = 10.5 Hz, 1H), 7.19—7.23 (in, 1H), 4.71 (d, /= 5.9 Hz, 2H), 2.20 (s, 3H). 실시예 205.  The title compound was obtained in the same manner as the Example 198. ¾ NMR (300 MHz, DMS0 一 ^) δ 13.70 (s, 1H), 9.37 (s, 1H), 9.08 (t, J = 5.9 Hz, 1H), 8.63 (d, / = 3.7 Hz, 2H), 8.19 (d, J = 8.6 Hz, 1H), 7.95-8.05 (m, 2H), 7.55-7.63 (m, 2H), 7.38-7.54 (m, 3H), 7.25 (cl, / = 10.5 Hz, 1H), 7.19—7.23 (in, 1H), 4.71 (d, / = 5.9 Hz, 2H), 2.20 (s, 3H). Example 205.
6-(4—플루오로 -5— (3-(4ᅳ플루오로 -3- (트리플루오로메틸)페닐)우레이도) -2—메틸 페닐) -Λ 피리딘—3-일메틸 ) - 인다졸 -3ᅳ카복스아미드의 제조  6- (4—Fluoro-5— (3- (4 ᅳ fluoro-3- (trifluoromethyl) phenyl) ureido) -2—methyl phenyl) -Λ pyridin—3-ylmethyl) -indazole Preparation of -3 ᅳ carboxamide
Figure imgf000117_0002
Figure imgf000117_0002
상기 실시예 198과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. NMR (300 MHz, DMS0— ) δ 9.40 (s, IH), 9.21 (s, 1H), 8.78 (s, 1H), 8.67 (s, 2H), 8.26-8.10 (m, 2H) , 8.02 (s, 2H), 7.71 (s, IH), 7.61 (s, 1H), 7.53—7.40 (m, IH), 7.27 (d, J = 12.5 Hz, 2H), 4.63 (s, 3H), 2.16 (d, J 34.5 Hz, 3H) . 실시예 206.  The title compound was obtained in the same manner as the Example 198. NMR (300 MHz, DMS0—) δ 9.40 (s, IH), 9.21 (s, 1H), 8.78 (s, 1H), 8.67 (s, 2H), 8.26-8.10 (m, 2H), 8.02 (s, 2H), 7.71 (s, IH), 7.61 (s, 1H), 7.53—7.40 (m, IH), 7.27 (d, J = 12.5 Hz, 2H), 4.63 (s, 3H), 2.16 (d, J 34.5 Hz, 3H). Example 206.
6-(4-플루오로 -5— (3— (4—플루오로— 3— (트리플루오로메틸)페닐)우레이도) -2-메틸 페닐 (피리딘ᅳ 4-일메틸 )ᅳ1/ 인다졸 -3-카복스아미드의 제조  6- (4-fluoro-5— (3— (4—fluoro— 3— (trifluoromethyl) phenyl) ureido) -2-methyl phenyl (pyridin ᅳ 4-ylmethyl) ᅳ 1 / indazole Preparation of 3-Carboxamide
Figure imgf000117_0003
Figure imgf000117_0003
상기 실시예 198과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. NMR (300 MHz, DMSO-οί;) δ 9.40 (s, IH), 9.27 (s, IH), 8.76-8.63 (m, 3H), 8.20 (d, J= 8.7 Hz, IH), 8.04 (d, J = 8.3 Hz, 2H), 7.70 (d, J= 5.1 Hz, 2H), 7.59 (s, 1H)' 7.54 (s, IH), 7.50—7.39 (m, IH), 7.26 (t, J= 10.5 Hz, 2H), 4.68 (d, J = 6.2 Hz, 2H), 2.22 (s, 3H). 실시예 207.  The title compound was obtained in the same manner as the Example 198. NMR (300 MHz, DMSO-οί;) δ 9.40 (s, IH), 9.27 (s, IH), 8.76-8.63 (m, 3H), 8.20 (d, J = 8.7 Hz, IH), 8.04 (d, J = 8.3 Hz, 2H), 7.70 (d, J = 5.1 Hz, 2H), 7.59 (s, 1H) '7.54 (s, IH), 7.50—7.39 (m, IH), 7.26 (t, J = 10.5 Hz, 2H), 4.68 (d, J = 6.2 Hz, 2H), 2.22 (s, 3H). Example 207.
ΛΚ (6-클로로피리딘 -3-일)메틸 )-6-(4-플루오로 -5-(3-(4—플루오로 -3- (트리폴루 오로메틸)페닐 )우레이도)—2-메틸페닐)— 1/ 인다졸—3ᅳ카복스아미드의 제조 ΛΚ (6-chloropyridin-3-yl) methyl) -6- (4-fluoro-5- (3- (4—fluoro-3- (tripol) Preparation of oromethyl) phenyl) ureido) -2-methylphenyl) -1 / indazole-3 ᅳ carboxamide
Figure imgf000118_0001
Figure imgf000118_0001
상기 실시예 198과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ]H NMR (300 MHz, DMSO— (4) δ 13.71 (s, 1Η), 9.39 (s, 1H), 9.18 (cl, J = 5.9 Hz, 1H), 8.66 (s, 1H), 8.44 (s, 1H), 8.21 (d, J= 8.4 Hz, 1H), 8.04 (cl, J = 8.3 Hz, 2H), 7.93-7.79 (in, 1H), 7.59 (s, 1H), 7.49 (dt， J 19.7, 7.0 Hz, 3H), 7.25 (t, J= 10.8 Hz, 2H), 4.55 (d, J = 6.0 Hz, 2H), 2.16 (d, J= 34.5 Hz, 3H). 실시예 208. The title compound was obtained in the same manner as the Example 198. ] H NMR (300 MHz, DMSO— (4) δ 13.71 (s, 1Η), 9.39 (s, 1H), 9.18 (cl, J = 5.9 Hz, 1H), 8.66 (s, 1H), 8.44 (s, 1H), 8.21 (d, J = 8.4 Hz, 1H), 8.04 (cl, J = 8.3 Hz, 2H), 7.93-7.79 (in, 1H), 7.59 (s, 1H), 7.49 (dt, J 19.7, 7.0 Hz, 3H), 7.25 (t, J = 10.8 Hz, 2H), 4.55 (d, J = 6.0 Hz, 2H), 2.16 (d, J = 34.5 Hz, 3H) Example 208.
6-(4-플루오로 -5-(3-(4-플루오로 -3- (트리플루오로메틸)페닐)우레이도) -2—메틸 페닐 )-Λ 피리딘 -4—일 인다졸— 3ᅳ카복스아미드의 제조  6- (4-fluoro-5- (3- (4-fluoro-3- (trifluoromethyl) phenyl) ureido) -2-2-methylphenyl) -Λ pyridin-4-yl indazole—3doca Preparation of Voxamide
Figure imgf000118_0002
Figure imgf000118_0002
상기 실시예 198과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. NMR (300 MHz , DMSO— d;) δ 14.20 (s, 1H), 11.65 (s, 1H), 9.42 (s, 1H), 8.77-8.67 (in, 3H),.8.40 (cl, J= 6.8 Hz, 2H), 8.29 (d, J 8.4 Hz, 1H), 8.13-8.00 (m, 2H), 7.61 (d, J 16.8 Hz, 2H) , 7.50—7.40 (m, 1H), 7.37 (d, J= 9.6 Hz, 1H), 7.30 (cl, J = 12.4 Hz, 1H), 2.24 (s, 3H). 실시예 209. ¬에틸 -6ᅳ(4-플루오로— 5— (3— (4—플루오로 -3— (트리플루오로메틸)페닐 )우레이도)一 2ᅳ메틸페닐 인다졸 -3—카복스아미드의 제조  The title compound was obtained in the same manner as the Example 198. NMR (300 MHz, DMSO— d;) δ 14.20 (s, 1H), 11.65 (s, 1H), 9.42 (s, 1H), 8.77-8.67 (in, 3H), .8.40 (cl, J = 6.8 Hz , 2H), 8.29 (d, J 8.4 Hz, 1H), 8.13-8.00 (m, 2H), 7.61 (d, J 16.8 Hz, 2H), 7.50—7.40 (m, 1H), 7.37 (d, J = 9.6 Hz, 1H), 7.30 (cl, J = 12.4 Hz, 1H), 2.24 (s, 3H). Example 209. -Ethyl-6 '(4-Fluoro— 5— (3— (4—Fluoro-3— (trifluoromethyl) phenyl) ureido) 一 2 ᅳ methylphenyl indazole-3—carbox Preparation of Amides
Figure imgf000118_0003
Figure imgf000118_0003
상기 실시예 198과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾ NMR (300 MHz, DMSO-οί;) δ 13.60 (s, 1H), 9.39 (s, 1H)， 8.66 (s, 1H)， 8.45 (t, J= 5.9 Hz, 1H), 8.23 (d, J= 8.4 Hz, 1H), 8.02 (dd, J= 9.6, 5.6 Hz, 2H), 7.65—7.56 (m, 1H), 7.51-7.39 (m, 2H), 7.27 (d, J= 12.3 Hz, 1H), 7.22 (d, J = 8.4 Hz, 1H), 3.43-3.30 (m, 8H), 2.22 (s, 3H), 1.18 (t, J= 7.1 Hz, 3H). 실시예 210. The title compound was obtained in the same manner as the Example 198. ¾ NMR (300 MHz, DMSO-οί;) δ 13.60 (s, 1H), 9.39 (s, 1H), 8.66 (s, 1H), 8.45 (t, J = 5.9 Hz, 1H), 8.23 (d, J = 8.4 Hz, 1H), 8.02 (dd, J = 9.6, 5.6 Hz, 2H), 7.65—7.56 (m, 1H), 7.51-7.39 (m, 2H), 7.27 (d, J = 12.3 Hz, 1H) , 7.22 (d, J = 8.4 Hz, 1H), 3.43-3.30 (m, 8H), 2.22 (s, 3H), 1.18 (t, J = 7.1 Hz, 3H). Example 210.
이미다졸—2-일)메틸)—6— (4-플루오로— 5— (3— (4—플루오로 -3- (트리플루오로 메틸)페닐)우레이도)—2-메틸페닐 )-1/ 인다졸 -3—카복스아미드의 제조  Imidazole—2-yl) methyl) —6— (4-fluoro— 5— (3— (4—fluoro-3- (trifluoro methyl) phenyl) ureido) —2-methylphenyl) -1 / Preparation of indazole-3—carboxamide
Figure imgf000119_0001
Figure imgf000119_0001
상기 실시예 198과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. !Η NMR (300 MHz, DMS으^) δ 13.7 (bs, 1H), 11.8 (s, 1H) , 9.60 (s, 1H), 8.80 (s, 1H), 8.75 (t, 1H, J = 5.7 Hz), 8.23 (d, 1H, J 8.4 Hz), 8.01 (s, 1H), 7.98 (s, 1H), 7.62 (m, 1H), 7.49 (s, 1H), 7.46 (t, 1H, J = 9.9 Hz), 7.26 (d, 1H, J= 12.3 Hz), 7.23 (dd, 1H, /= 8.4， 1.2 Hz), 7.02 (s, 1H), 6.82 (s, 1H), 4.55 (d, 2H, / = 5.7 Hz), 2.19 (s, 3H). 실시예 211.  The title compound was obtained in the same manner as the Example 198. ! Η NMR (300 MHz, DMS) δ 13.7 (bs, 1H), 11.8 (s, 1H), 9.60 (s, 1H), 8.80 (s, 1H), 8.75 (t, 1H, J = 5.7 Hz ), 8.23 (d, 1H, J 8.4 Hz), 8.01 (s, 1H), 7.98 (s, 1H), 7.62 (m, 1H), 7.49 (s, 1H), 7.46 (t, 1H, J = 9.9 Hz), 7.26 (d, 1H, J = 12.3 Hz), 7.23 (dd, 1H, / = 8.4, 1.2 Hz), 7.02 (s, 1H), 6.82 (s, 1H), 4.55 (d, 2H, / = 5.7 Hz), 2.19 (s, 3 H). Example 211.
(R)— 6-(4ᅳ플루오로 -5— (3-(4-플루오로 -3- (트리플루오로메틸)페닐)우레이도)— 2- 메틸페닐)— K피롤리딘 -3—일) -1/ 인다졸— 3-카복스아미드의 제조  (R) — 6- (4 ᅳ Fluoro-5— (3- (4-fluoro-3- (trifluoromethyl) phenyl) ureido) — 2-methylphenyl) —Kpyrrolidin-3—yl ) -1 / indazole— Preparation of 3-carboxamide
Figure imgf000119_0002
Figure imgf000119_0002
상기 실시예 198과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾ NMR (300 MHz , DMSO- ) δ 13.79 (s, 1H), 9.50 (s, 1H), 8.94-8.72 (m, 4H), 8.22 (d, J= 8.4 Hz, 1H), 8.04 (cl, J = 8.5 Hz, 2H), 7.66—7.56 (in, 1H), 7.54 (s, 1H), 7.45 (t, J 9.8 Hz, 1H), 7.34-7.20 Cm, 2H), 4.70 (del, J= 12.1， 5.3 Hz, 1H), 3.35-3.17 (m, 2H), 2.27 (dd, J = 12.2, 6.3 Hz, 1H), 2.22 (s, 3H), 2.10 (tt, / = 13.4, 6.8 Hz, 1H). 실시예 212.  The title compound was obtained in the same manner as the Example 198. ¾ NMR (300 MHz, DMSO-) δ 13.79 (s, 1H), 9.50 (s, 1H), 8.94-8.72 (m, 4H), 8.22 (d, J = 8.4 Hz, 1H), 8.04 (cl, J = 8.5 Hz, 2H), 7.66—7.56 (in, 1H), 7.54 (s, 1H), 7.45 (t, J 9.8 Hz, 1H), 7.34-7.20 Cm, 2H), 4.70 (del, J = 12.1, 5.3 Hz, 1H), 3.35-3.17 (m, 2H), 2.27 (dd, J = 12.2, 6.3 Hz, 1H), 2.22 (s, 3H), 2.10 (tt, / = 13.4, 6.8 Hz, 1H). Example 212.
(S)-6— (4—플루오로— 5-(3— (4—플루오로 -3- (트리플루오로메틸)페닐)우레이도) -2- 메틸페닐) -Λ 피를리딘ᅳ 3—일 )—1^인다졸—3—카복스아미드의 제조  (S) -6— (4—Fluoro— 5- (3— (4—Fluoro-3- (trifluoromethyl) phenyl) ureido) -2-methylphenyl) -Λ pyridinyl 3-yl ) — Production of 1 ^ indazole—3—carboxamide
Figure imgf000119_0003
Figure imgf000119_0003
상기 실시예 198과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ^ NMR (300 MHz, DMSO—O δ 13.79 (s, 1H), 9.52 (s, 1H), 8.98—8.71 (m, 4H) 8.22 (d, J= 8.4 Hz, 1H)' 8.12-7.98 (m, 2H), 7.59 (dd, J 7.6, 4.3 Hz, 1H) 7.54 (s, 1H), 7.45 (t, /= 9.7 Hz, 1H), 7.34-7.19 (m, 2H) , 4.70 (dd, /= 12.3, 5.4 Hz, 1H), 3.48 (del, J= 11.8, 5.6 Hz, 2H), 3.37—3.20 (m, 2H), 2.27 (del, J = 13.2， 7.6 Hz, 1H), 2.22 (s, 3H)， 2.10 (tt, J = 13.1， 6.4 Hz, 1H). 실시예 213. The title compound was obtained in the same manner as the Example 198. ^ NMR (300 MHz, DMSO—O δ 13.79 (s, 1H), 9.52 (s, 1H), 8.98—8.71 (m, 4H) 8.22 (d, J = 8.4 Hz, 1H) '8.12-7.98 (m, 2H), 7.59 (dd, J 7.6, 4.3 Hz, 1H) 7.54 (s, 1H), 7.45 (t, / = 9.7 Hz, 1H), 7.34-7.19 (m, 2H), 4.70 (dd, / = 12.3, 5.4 Hz, 1H), 3.48 (del, J = 11.8, 5.6 Hz, 2H), 3.37—3.20 (m, 2H), 2.27 (del, J = 13.2, 7.6 Hz, 1H), 2.22 (s, 3H), 2.10 (tt, J = 13.1, 6.4 Hz, 1H). Example 213.
6-(4-플루오로— 5— (3-(4—플루오로 -3- (트리플루오로메틸)페닐)우레이도) -2—메틸 페닐 )_Λ 1-메틸 -1^이미다졸— 4-일 인다졸—3-카복스아미드의 제조  6- (4-fluoro— 5— (3- (4—fluoro-3- (trifluoromethyl) phenyl) ureido) -2—methyl phenyl) _Λ 1-methyl-1 ^ imidazole— 4- Preparation of yl indazole—3-carboxamide
Figure imgf000120_0001
Figure imgf000120_0001
상기 실시예 198과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾丽 R (300 MHz, DMSO-di) δ 2.21 (s, 3H), 3.83 (s, 3H), 7.24-7.28 (q, J= 12.3 Hz, 1H), 7.28-7.31 (dd, J 8.4 Hz, J 1.2 Hz, 1H), 7.40-7.46 (t, J 9.3 Hz, 1H), 7.55-7.62 (m, 3H), 7.99-8.05 (m, 2H) , 8.22-8.24 (d, /= 8.7 Hz, 1H) , 8.47 (s, 1H), 8.08-8.10 (d, = 1.8 Hz, 1H) , 9.55 (s, 1H), 8.43—8.45 (d, /= 1.2 Hz, 1H), 14.03 (s, 1H) 실시예 214.  The title compound was obtained in the same manner as the Example 198. ¾ 丽 R (300 MHz, DMSO-di) δ 2.21 (s, 3H), 3.83 (s, 3H), 7.24-7.28 (q, J = 12.3 Hz, 1H), 7.28-7.31 (dd, J 8.4 Hz, J 1.2 Hz, 1H), 7.40-7.46 (t, J 9.3 Hz, 1H), 7.55-7.62 (m, 3H), 7.99-8.05 (m, 2H), 8.22-8.24 (d, / = 8.7 Hz, 1H ), 8.47 (s, 1H), 8.08-8.10 (d, = 1.8 Hz, 1H), 9.55 (s, 1H), 8.43—8.45 (d, / = 1.2 Hz, 1H), 14.03 (s, 1H) Example 214.
6一 (4ᅳ플루오로— 5— (3-(4-플루오로 -3— (트리플루오로메틸)페닐)우레이도)—2—메틸 페닐 )-Λ ΐ ^이미다졸 -4-일) 인다졸 -3-카복스아미드의 제조  6 one (4 ᅳ fluoro— 5— (3- (4-fluoro-3— (trifluoromethyl) phenyl) ureido) —2—methyl phenyl) -Λ ΐ ^ imidazol-4-yl) Preparation of Sol-3-Carboxamide
Figure imgf000120_0002
Figure imgf000120_0002
상기 실시예 198과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 198.
匪 R (300 MHz , DMSO-oii) δ 2.21 (s, 3H), 7.25-7.29 (d, J= 12.6 Hz, 1H), 7.29-7.32 (dd, J = 7.2 Hz, J 1.2 Hz, 1H), 7.40—7.47 (t, J= 9.3 Hz, 1H), 7.54-7.58 (m, 3H), 7.99—8.05 (m, 2H), 8.22-8.25 (d, J= 8.1 Hz, 1H) , 8.59 (s, 1H), 8.68 (d, J = 1.5 Hz, 1H), 9.40 (s, 1H), 11.11 (s, 1H), 14.02 (s, 1H) 실시예 215.  匪 R (300 MHz, DMSO-oii) δ 2.21 (s, 3H), 7.25-7.29 (d, J = 12.6 Hz, 1H), 7.29-7.32 (dd, J = 7.2 Hz, J 1.2 Hz, 1H), 7.40—7.47 (t, J = 9.3 Hz, 1H), 7.54-7.58 (m, 3H), 7.99—8.05 (m, 2H), 8.22-8.25 (d, J = 8.1 Hz, 1H), 8.59 (s, 1H), 8.68 (d, J = 1.5 Hz, 1H), 9.40 (s, 1H), 11.11 (s, 1H), 14.02 (s, 1H) Example 215.
6一 (4ᅳ플루오로— 5— (3-(4ᅳ플루오로— 3- (트리플루오로메틸)페닐)우레이도)—2ᅳ메틸 페닐 )_Λ 피리미딘ᅳ 4—일 )— 인다졸 -3-카복스아미드의 제조  6 一 (4 ᅳ fluoro— 5— (3- (4 ᅳ fluoro— 3- (trifluoromethyl) phenyl) ureido) —2 ᅳ methyl phenyl) _Λ pyrimidin ᅳ 4—yl) — indazole- Preparation of 3-carboxamide
Figure imgf000120_0003
Figure imgf000120_0003
상기 실시예 198과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ]H隱 (300 MHz , DMSO-d. δ 14.10 (d, J= 13.7 Hz, 2H) , 10.28 (d, /= 24.9The title compound was obtained in the same manner as the Example 198. ] H 隱 (300 MHz, DMSO-d.δ 14.10 (d, J = 13.7 Hz, 2H), 10.28 (d, / = 24.9
Hz, IH), 9.40 (cl, J= 9.3 liz, 1H), 8.99 (s, 1H), 8.82-8.75 (m, 1H), 8.68 (d,Hz, IH), 9.40 (cl, J = 9.3 liz, 1H), 8.99 (s, 1H), 8.82-8.75 (m, 1H), 8.68 (d,
J = 12.8 Hz, IH), 8.33-8.21 (m, 2H), 8.06 (cl, J= 9.8 Hz, 2H), 7.61 (s, 2H), 7.46 (s, IH), 7.32 (dd, J = 16.8， 10.3. Hz, 2H),'2.23 (s, 3H) . 실시예 216. J = 12.8 Hz, IH), 8.33-8.21 (m, 2H), 8.06 (cl, J = 9.8 Hz, 2H), 7.61 (s, 2H), 7.46 (s, IH), 7.32 (dd, J = 16.8 , 10.3.Hz, 2H), ' 2.23 (s, 3H). Example 216.
6— (4—플루오로 -5-(3— (4—플루오로— 3- (트리플루오로메틸)페닐)우레이도) -2—메틸 페닐 )-/^(6—메틸피리딘— 3—일 ) -1/ 인다졸ᅳ 3—카복스아미드의 제조  6— (4—fluoro-5- (3— (4—fluoro— 3- (trifluoromethyl) phenyl) ureido) -2—methylphenyl)-/ ^ (6—methylpyridin— 3—yl ) -1 / indazolazole 3—carboxamide preparation
Figure imgf000121_0001
Figure imgf000121_0001
상기 실시예 198과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 198.
NMR (300 MHz , DMSO-^) δ δ 14.07 ( IH), 11.12 (s, 11)， 9.45 (s, IH), 9.23 (d, J 2.3 Hz, IH), 8.72 (d, J = 1.5 Hz, IH), 8.62 (del, ./ = 8.7, 2.3 Hz, IH), 8.26 (d, / = 8.4 Hz. IH), 7.97—8.07 (m, 2H), 7.72 (d, J 8.7 Hz, IH), 7.64-7.51 (m, 2H), 7.43 (t, J= 9.7 Hz, IH), 7.21—7.35 (m, 2H), 2.21 (s, 3H).  NMR (300 MHz, DMSO- ^) δ δ 14.07 (IH), 11.12 (s, 11), 9.45 (s, IH), 9.23 (d, J 2.3 Hz, IH), 8.72 (d, J = 1.5 Hz, IH), 8.62 (del, ./ = 8.7, 2.3 Hz, IH), 8.26 (d, / = 8.4 Hz.IH), 7.97—8.07 (m, 2H), 7.72 (d, J 8.7 Hz, IH), 7.64-7.51 (m, 2H), 7.43 (t, J = 9.7 Hz, IH), 7.21—7.35 (m, 2H), 2.21 (s, 3H).
Figure imgf000121_0002
Figure imgf000121_0002
상기 실시예 198과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. NMR (300 MHz, DMSOof 6 δ 14.00 (s, IH), 10.38 (s, IH), 9.44 (s, IH) 8.99 (s, IH), 8.72 (s, IH), 8.54 (d, J = 5.4 Hz, IH), 8.22 (cl, J = 8.3 Hz IH), 7.97-8.10 (m, 2H), 7.75 (d, /= 5.5 Hz, IH) , 7.53-7.63 (m, 2H), 7.43 (t J = 9.7 Hz, IH), 7.33-7.20 (m, 2H), 2.20 (s, 3H). 실시예 218.  The title compound was obtained in the same manner as the Example 198. NMR (300 MHz, DMSOof 6 δ 14.00 (s, IH), 10.38 (s, IH), 9.44 (s, IH) 8.99 (s, IH), 8.72 (s, IH), 8.54 (d, J = 5.4 Hz , IH), 8.22 (cl, J = 8.3 Hz IH), 7.97-8.10 (m, 2H), 7.75 (d, / = 5.5 Hz, IH), 7.53-7.63 (m, 2H), 7.43 (t J = 9.7 Hz, IH), 7.33-7.20 (m, 2H), 2.20 (s, 3H) Example 218.
6一 (4ᅳ플루오로 -5-(3— (4ᅳ플루오로 -3- (트리플루오로메틸)페닐)우레이도)— 2ᅳ메틸 페닐시(2—플루오로피리딘— 3-일 인다졸— 3-카복스아미드의 제조  6 one (4 ᅳ fluoro-5- (3— (4 ᅳ fluoro-3- (trifluoromethyl) phenyl) ureido) — 2 ᅳ methyl phenylcy (2—fluoropyridin— 3-yl indazole — Preparation of 3-carboxamides
Figure imgf000121_0003
상기 실시예 198과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.
Figure imgf000121_0003
The title compound was obtained in the same manner as the Example 198.
]H NMR (300 MHz, DMS으 ) δ 13.96 (s, 1H), 10.13 (s, 1H), 9.38 (s, 1H), 8.67 ] H NMR (300 MHz, with DMS) δ 13.96 (s, 1H), 10.13 (s, 1H), 9.38 (s, 1H), 8.67
(d, /= 1.5 Hz, 1H), 8.34-8.43 (m, 1H), 8.22 (cl, J 8.3 Hz, III), 8.09—7.97(d, / = 1.5 Hz, 1H), 8.34-8.43 (m, 1H), 8.22 (cl, J 8.3 Hz, III), 8.09—7.97
(in, 3H), 7.63-7.54 (m, 2H), 7.50-7.38 (m, '2H), 7.33-7.23 (m, 2H), 2.21 (s,(in, 3H), 7.63-7.54 (m, 2H), 7.50-7.38 (m, ' 2H), 7.33-7.23 (m, 2H), 2.21 (s,
3H). 실시예 219. 3H). Example 219.
6-(4-플루오로 -5-(3— (4-플루오로— 3- (트리플루오로메틸)페닐)우레이도) -2-메틸 페닐 )-ΛΚ5—플루오로피리딘— 3-일 )—1/ 인다졸ᅳ 3-카복스아미드의 제조  6- (4-fluoro-5- (3— (4-fluoro— 3- (trifluoromethyl) phenyl) ureido) -2-methyl phenyl) -ΛΚ5—fluoropyridin— 3-yl) — 1 / Preparation of indazolycol 3-carboxamide
Figure imgf000122_0001
Figure imgf000122_0001
상기 실시예 198과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 198.
]H NMR (300 MHz, DMS으^) δ 14.00 (s, 1Η), 10.98 (s, 1H), 9.39 (s, 1H), 9.00 (s, 1H), 8.67 (s, 1H), 8.30—8.40 (m, 2H), 8.26 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 8.5 Hz, 1H), 8.02-7.97 (m, 1H), 7.63—7.51 (m, 2H), 7.43 (t, = 9.8 Hz, 1H), 7.33-7.19 (m, 2H), 2.21 (s, 3H). 실시예 220. ] H NMR (300 MHz, DMS) δ 14.00 (s, 1Η), 10.98 (s, 1H), 9.39 (s, 1H), 9.00 (s, 1H), 8.67 (s, 1H), 8.30—8.40 (m, 2H), 8.26 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 8.5 Hz, 1H), 8.02-7.97 (m, 1H), 7.63—7.51 (m, 2H), 7.43 ( t, = 9.8 Hz, 1H), 7.33-7.19 (m, 2H), 2.21 (s, 3H). Example 220.
6-(4ᅳ플루오로 -5-(3— (4-플루오로— 3- (트리플루오로메틸)페닐)우레이도) -2—메틸 페닐 ) -Λ 6—플루오로피리딘 -3-일 인다졸 -3—카복스아미드의 제조  6- (4 ᅳ fluoro-5- (3— (4-fluoro- 3- (trifluoromethyl) phenyl) ureido) -2-methylphenyl) -Λ 6-fluoropyridin-3-yl Preparation of Sol-3—Carboxamides
Figure imgf000122_0002
Figure imgf000122_0002
상기 실시예 198과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. x\\ NMR (300 MHz, DMS0— ) δ 13.97 (s, 1Η), 10.85 (s, 1H), 9.41 (s, 1H), 8.77 (s, 1H), 8.69 (d, /= 1.5 Hz, 1H), 8.45—8.53 (m, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.06 (d, J= 8.5 Hz, 1H), 8.05-7.99 (m, 1H), 7.65—7.55 (m, 2H), 7.46 (t, J = 9.7 Hz, 1H), 7.34-7.21 (m, 3H), 2.24 (s, 3H). 실시예 221. The title compound was obtained in the same manner as the Example 198. x \\ NMR (300 MHz, DMS0—) δ 13.97 (s, 1Η), 10.85 (s, 1H), 9.41 (s, 1H), 8.77 (s, 1H), 8.69 (d, / = 1.5 Hz, 1H ), 8.45—8.53 (m, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.06 (d, J = 8.5 Hz, 1H), 8.05-7.99 (m, 1H), 7.65—7.55 (m, 2H), 7.46 (t, J = 9.7 Hz, 1H), 7.34-7.21 (m, 3H), 2.24 (s, 3H). Example 221.
6一 (5ᅳ( (3— ?r 부틸페닐)카바모일 )-4—1 루오로—2—메틸페닐 메틸— 1^인다졸- 3-카복스아미드의 제조 Preparation of 6- (5 ᅳ ((3—r butylphenyl) carbamoyl) -4—1 urouro—2—methylphenyl methyl—1 ^ indazole-3-carboxamide
Figure imgf000123_0001
Figure imgf000123_0001
단계 1. 메틸  Step 1. Methyl
2-플루오로 -4—메틸 -5-(3ᅳ메틸카바모일) -1- (테트라하이드로 -2^피란— 2-일) -l^ 인다졸-일 )벤조에이트의 제조  Preparation of 2-Fluoro-4-methyl-5- (3 ᅳ methylcarbamoyl) -1- (tetrahydro-2 ^ pyran— 2-yl) -l ^ indazol-yl) benzoate
상기 제조예 3의 단계 7과 동일한 방법으로 In the same manner as in Step 7 of Preparation Example 3
메틸— 1- (테트라하이드로— 2//·피란— 2-일) -6-(4, 4, 5， 5-테트라메틸 -1,3,2-다이옥 사보란 -2-일 )-1/·인다졸 -3—카복스아미드와 메틸  Methyl— 1- (tetrahydro— 2 // pyran— 2-yl) -6- (4, 4, 5, 5-tetramethyl-1,3,2-dioxane saboran-2-yl) -1 / Indazole-3—carboxamide and methyl
5ᅳ브로모ᅳ2-플루오로 -4—메틸벤조에이트를 반웅시켜， 메틸  5 로 Bromo ᅳ 2-fluoro-4—methylbenzoate was reacted to form methyl.
2ᅳ풀루오로 -4-메틸 -5-(3-메틸카바모일 )— 1— (테트라하이드로 -2/ 피란 -2—일) 인다졸 -일)벤조에이트를 얻었다. MS m/z [M+H] 426 단계 2.  2-Mn-Pluoro-4-methyl-5- (3-methylcarbamoyl)-1— (tetrahydro-2 / pyran-2-yl) indazol-yl) benzoate was obtained. MS m / z [M + H] 426 Step 2.
6ᅳ(5— ( (3— e^-부틸페닐)카바모일) -4-플루오로— 2-메틸페닐) 메틸ᅳ 인다졸- 3ᅳ카복스아미드의 제조  Preparation of 6 ′ (5— ((3—e ^ -butylphenyl) carbamoyl) -4-fluoro—2-methylphenyl) methyl ᅳ indazole-3′carboxamide
상기 실시예 43의 단계 1과 단계 2와 동일한 방법으로 수행하여 , In the same manner as in Step 1 and Step 2 of Example 43,
6一 (5-((3— er ᅩ부틸페닐)카바모일)— 4-플루오로 -2—메틸페닐)ᅳ 메틸— 인다졸- 3ᅳ카복스아미드를 얻었다. 6一(5 - ((3- er o-butylphenyl) carbamoyl) - 4-fluoro-2-methylphenyl) eu-methyl-indazole-3-carboxamide was obtained euka.
Ή NMR (400 MHz , CD30D-d,) δ 8.25 (d, J= 8.4 Hz, 1H), 7.73-7.72 (m, 1H), 7.62MR NMR (400 MHz, CD 3 0D-d,) δ 8.25 (d, J = 8.4 Hz, 1H), 7.73-7.72 (m, 1H), 7.62
(d, /= 8.4 Hz, lH), 7.54-7.51 (m, 1H), 7.47 (s, 1H), 7.28—7.15 (m, 4H), 2.98 (s, 3H), 2.79 (s, 1H), 2.28 (s, 3H), 1.30 (s, 9H) 실시예 222. (d, / = 8.4 Hz, lH), 7.54-7.51 (m, 1H), 7.47 (s, 1H), 7.28—7.15 (m, 4H), 2.98 (s, 3H), 2.79 (s, 1H), 2.28 (s, 3H), 1.30 (s, 9H) Example 222.
6ᅳ (4—플루오로— 2—메틸 -5— ( (3- (트리플루오로메틸)페닐)카바모일)페닐 ) - 메틸 -1 ^인다졸 -3—카복스아미드의 제조  Preparation of 6 ′ (4—fluoro— 2—methyl-5— ((3- (trifluoromethyl) phenyl) carbamoyl) phenyl) -methyl-1 ^ indazole-3—carboxamide
Figure imgf000123_0002
Figure imgf000123_0002
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 221.
¾ NMR (300 MHz , DMS으/6) δ 10.63 (s, 1H), 8.28 (q, J= 4.5 Hz' 1H), 8.16-8.05 (m, 2H), 7.85 (d, J 8.1 Hz, IH), 7.55-7.43 (m, 3H), 7.36 (d, J = 7.5 Hz, IH), 7.28 (d, J = 11.3 Hz, IH), 7.13 (del, /= 8.7, 1.1 Hz, IH), 2.27 (d, J = 4.6 Hz, IH), 2.22 (s, 3H) 실시예 223. ¾ NMR (300 MHz, DMS / 6 ) δ 10.63 (s, 1H), 8.28 (q, J = 4.5 Hz '1H), 8.16-8.05 (m, 2H), 7.85 (d, J 8.1 Hz, IH), 7.55-7.43 (m, 3H), 7.36 (d, J = 7.5 Hz, IH), 7.28 (d, J = 11.3 Hz, IH), 7.13 (del, / = 8.7, 1.1 Hz, IH), 2.27 (d, J = 4.6 Hz, IH), 2.22 (s, 3H) Example 223.
6-(4-플루오로 -5-( (4-플루오로ᅳ 3— (트리플루오로메틸)페닐)카바모일) -2-메틸페 닐)— ^메틸 -1/ 인다졸 -3-카복스아미드의 제조  6- (4-fluoro-5-((4-fluorophenyl 3— (trifluoromethyl) phenyl) carbamoyl) -2-methylphenyl) — ^ methyl-1 / indazole-3-carbox Preparation of Amides
Figure imgf000124_0001
Figure imgf000124_0001
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 221.
Ή NMR (300 MHz, CD,0D-rf,) δ 8.36-8.34 (m, IH), 8.23 (d, J= 8.4, IH), 7.98 (s, IH), 7.79 (s, IH), 7.60 (d, J = 4.5 Hz, IH), 7.55 (s, IH), 7.37 (d, J = 11.4 Hz, IH), 7.27 (d, J = 1.5 Hz, IH), 7.24 (d, J 1.5 Hz, IH), 2.83 (d, / = 4.8 Hz, 3H), 2.39 (s, 3H), 2.32 (s, 3H) 실시예 225. MR NMR (300 MHz, CD, 0D-rf,) δ 8.36-8.34 (m, IH), 8.23 (d, J = 8.4, IH), 7.98 (s, IH), 7.79 (s, IH), 7.60 ( d, J = 4.5 Hz, IH), 7.55 (s, IH), 7.37 (d, J = 11.4 Hz, IH), 7.27 (d, J = 1.5 Hz, IH), 7.24 (d, J 1.5 Hz, IH ), 2.83 (d, / = 4.8 Hz, 3H), 2.39 (s, 3H), 2.32 (s, 3H) Example 225.
6-(5— ( (4-클로로— 3- (트리플루오로메틸 )페닐 )카바모일 )—4-플루오로 -2-메틸페닐 ) 메틸 인다졸 -3-카복스아미드의 제조  Preparation of 6- (5— ((4-chloro— 3- (trifluoromethyl) phenyl) carbamoyl) —4-fluoro-2-methylphenyl) methyl indazole-3-carboxamide
Figure imgf000124_0002
Figure imgf000124_0002
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 221.
l NMR (300 MHz, CDgOD-cO δ 8.38-8.30 (m, 1Η)' 8.30 (d, J= 2.5 Hz, IH), 8.19 (d, J= 8.3 Hz, IH), 8.02 (dd, J= 8.7， 2.5 Hz, IH), 7.72 (d, J= 8.8 Hz, IH), 7.62 (d, /= 7.4 Hz, 1H), 7.56(s, 1H) , 7.38 (cl, / = 11.3 Hz, 1H), 7.21 (d /= 8.3, 1H), 2.82 (t, J = 4.6 Hz, 3H), 2.32 (s, 3H) 실시예 226. ᅳ NMR (300 MHz, CDgOD-cO δ 8.38-8.30 (m, 1Η) ' 8.30 (d, J = 2.5 Hz, IH), 8.19 (d, J = 8.3 Hz, IH), 8.02 (dd, J = 8.7 , 2.5 Hz, IH), 7.72 (d, J = 8.8 Hz, IH), 7.62 (d, / = 7.4 Hz, 1H), 7.56 (s, 1H), 7.38 (cl, / = 11.3 Hz, 1H), 7.21 (d / = 8.3, 1H), 2.82 (t, J = 4.6 Hz, 3H), 2.32 (s, 3H) Example 226.
6-(5— ((4— ((2- (디메틸아미노)에틸)아미노 )-3- (트리플루오로메틸)페닐)카바모일 )-4-플루오로 -2-메틸페닐 )ᅳ그메틸— 1/ 인다졸 -3-카복스아미드의 제조  6- (5— ((4— ((2- (dimethylamino) ethyl) amino) -3- (trifluoromethyl) phenyl) carbamoyl) -4-fluoro-2-methylphenyl) dogmethyl— 1 / Preparation of indazole-3-carboxamide
Figure imgf000125_0001
Figure imgf000125_0001
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 221.
!H NMR (300 MHz , DMS0— ) δ 8.21 (cl, J = 8.4 Hz, 1H), 8.08-8.05 (m, 1H), 7.88-7.83 (m, 1H), 7.62 (s, 1H), 7.5 1H), 7.29—7.23 (m, 2H), 6.73 (s, 1H) 3.37 (t, J 6.6 Hz, 2H), 2.99 (s, 3H), 2.65 (t, J = 6.6 Hz, 2H), 2.33 (s 6H) 실시예 227. ! H NMR (300 MHz, DMS0—) δ 8.21 (cl, J = 8.4 Hz, 1H), 8.08-8.05 (m, 1H), 7.88-7.83 (m, 1H), 7.62 (s, 1H), 7.5 1H ), 7.29—7.23 (m, 2H), 6.73 (s, 1H) 3.37 (t, J 6.6 Hz, 2H), 2.99 (s, 3H), 2.65 (t, J = 6.6 Hz, 2H), 2.33 (s 6H) Example 227.
6-(4—플루오로— 2—메틸— 5-((3-(4ᅳ메틸피페라진 -1—일)— 5— (트리플루오로메틸)페닐 )카바모일 )-2ᅳ메틸페닐 메틸 인다졸 -3—카복스아미드의 제조  6- (4—fluoro— 2—methyl— 5-((3- (4 ᅳ methylpiperazin-1—yl) — 5— (trifluoromethyl) phenyl) carbamoyl) -2 ᅳ methylphenyl methyl indazole -3—Manufacture of Carboxamides
Figure imgf000125_0002
Figure imgf000125_0002
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 221.
Ή NMR (300 MHz, CD30D-i4) δ 8.25 (d, J = 8.6 Hz, 1H), 7.64 (cl, J = 7.2 Hz, 1H), 7.53-7.50 (m, 3H), 7.23 (s, 1H), 7.19 (d, /= 3.9 Hz, 1H), 6.97 (s, 1H), 3.30-3.25 (m, 4H), 2.99 (s, 3H), 2.61-2.58 (m, 4H), 2.34 (s, 3H), 2.32 (s, 3H) 실시예 228. MR NMR (300 MHz, CD 3 0D-i 4 ) δ 8.25 (d, J = 8.6 Hz, 1H), 7.64 (cl, J = 7.2 Hz, 1H), 7.53-7.50 (m, 3H), 7.23 (s , 1H), 7.19 (d, / = 3.9 Hz, 1H), 6.97 (s, 1H), 3.30-3.25 (m, 4H), 2.99 (s, 3H), 2.61-2.58 (m, 4H), 2.34 ( s, 3H), 2.32 (s, 3H) Example 228.
6一 ( 4ᅳ플루오로 -2—메틸 -5- ( 4- ( 2- (피를리딘 - 1-일 )에톡시 ) -3- (트리플루오로메틸) 페닐 )카바모일)페닐 메틸 -1^인다졸 -3-카복스아미드의 제조  6- (4'fluoro-2-2-methyl-5- (4- (2- (pyridin-1-yl) ethoxy) -3- (trifluoromethyl) phenyl) carbamoyl) phenyl methyl-1 ^ Preparation of indazole-3-carboxamides
Figure imgf000125_0003
Figure imgf000125_0003
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. H NMR (300 MHz, CDsOD-rft) δ 8.27 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 2.7 Hz 1H), 7.85 (del, J = 8.4 and 2.7 Hz, 1H), 7.65 (cl, ./ = 7.5 Hz, 1H), 7.51 (s, 1H), 7.24-7.17 (m, 3H), 4.23 (t, J 5.4 Hz, 2H), 2.99 (s, 2H), 2.96-2.94 (111， 3H), 2.71-2.63 (111, 4H), 2.32 (s, 2H), 1.89-1.81 (m, 4H) 실시예 229. The title compound was obtained in the same manner as the Example 221. H NMR (300 MHz, CDsOD-rft) δ 8.27 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 2.7 Hz 1H), 7.85 (del, J = 8.4 and 2.7 Hz, 1H), 7.65 (cl, ./ = 7.5 Hz, 1H), 7.51 (s, 1H), 7.24-7.17 (m, 3H), 4.23 (t, J 5.4 Hz, 2H), 2.99 (s, 2H), 2.96-2.94 (111, 3H), 2.71-2.63 (111, 4H), 2.32 (s, 2H), 1.89-1.81 (m, 4H) Example 229 .
6-(5ᅳ((3-((2- (디메틸아미노)에틸)아미노 )— 5- (트리플루오로메틸)페닐)카바모일 )-4—플루오로 -2-메틸페닐 )— 메틸 -1^인다졸 -3—카복스아미드의 제조  6- (5 ᅳ ((3-((2- (dimethylamino) ethyl) amino) — 5- (trifluoromethyl) phenyl) carbamoyl) -4—fluoro-2-methylphenyl) — methyl -1 ^ Preparation of indazole-3—carboxamide
Figure imgf000126_0001
Figure imgf000126_0001
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. lW NMR (300 MHz , CD,OD-rf,) δ 8.26 (d, J = 8.6 Hz, 1H), 7.63 (d, J = 8.6 Hz, 1H), 7.50 (s, 1H), 7.28 (s, 1H), 7.24-7.19 (111, 3H), 6.65 (s, 1H), 3.26 (t, J - 6.6 Hz, 2H), 2.99 (s, 3H), 2.58 (t, J = 6.6 Hz, 2H), 2.32 (s, 3H), 2.30 (s, 6H) 실시예 230. The title compound was obtained in the same manner as the Example 221. l W NMR (300 MHz, CD , OD-rf,) δ 8.26 (d, J = 8.6 Hz, 1H), 7.63 (d, J = 8.6 Hz, 1H), 7.50 (s, 1H), 7.28 (s, 1H), 7.24-7.19 (111, 3H), 6.65 (s, 1H), 3.26 (t, J-6.6 Hz, 2H), 2.99 (s, 3H), 2.58 (t, J = 6.6 Hz, 2H), 2.32 (s, 3H), 2.30 (s, 6H) Example 230.
6一(4ᅳ플루오로 -2ᅳ메틸 -5ᅳ((2ᅳ몰포리노—5ᅳ (트리플루오로메틸)페닐)카바모일)페 닐) 메틸 인다졸ᅳ 3ᅳ카복스아미드의 제조  Preparation of 6- (4'fluoro-2'methyl-5 '((2'morpholino--5' (trifluoromethyl) phenyl) carbamoyl) phenyl) methyl indazole ᅳ 3'carboxamide
Figure imgf000126_0002
Figure imgf000126_0002
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. NMR (300 MHz, C¾0D— ο ) δ 8.83 (s, 1Η), 8.30 (d, J= 8.4 Hz, 1H), 8.01 (d, J = 8.4 Hz, 1H), 7.53—7.47 (m, 3H) , 7.36 (d, J 13.2 Hz, 1H), 7.25 (d, J = 8.4 Hz, 1H), 3.95-3.91 (m, 4H), 2.99-2.97 (m, 7H), 2.37 (s, 3H) 실시예 231.  The title compound was obtained in the same manner as the Example 221. NMR (300 MHz, C¾0D—ο) δ 8.83 (s, 1Η), 8.30 (d, J = 8.4 Hz, 1H), 8.01 (d, J = 8.4 Hz, 1H), 7.53—7.47 (m, 3H), 7.36 (d, J 13.2 Hz, 1H), 7.25 (d, J = 8.4 Hz, 1H), 3.95-3.91 (m, 4H), 2.99-2.97 (m, 7H), 2.37 (s, 3H) Example 231 .
6ᅳ (4-플루오로— 5-( (2ᅳ플루오로— 5ᅳ (트리플루오로메틸)페닐)카바모일 )2—메틸페닐 )ᅳ ^메틸 -1^인다졸—3-카복스아미드의 제조  Preparation of 6 ′ (4-fluoro— 5- ((2 ᅳ fluoro— 5 ′ (trifluoromethyl) phenyl) carbamoyl) 2—methylphenyl) ᅳ ^ methyl-1 ^ indazole—3-carboxamide
Figure imgf000126_0003
Figure imgf000126_0003
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. Ή NM (300 MHz , C OD— d,) δ 8.52 (d, /= 7.2 Hz, 1H)， 8.29 (cl, J= 8.4 Hz, 1H), 7.81 (cl, /= 8.4 Hz, IH), 7.53 (s, 2H), 7.45—7.38 (m, 2H), 7.29-7.22 (m, 3H), 2.99 (s, 3H), 2.35 (s, 3H) 실시예 232. The title compound was obtained in the same manner as the Example 221. Ή NM (300 MHz, C OD— d,) δ 8.52 (d, / = 7.2 Hz, 1H), 8.29 (cl, J = 8.4 Hz, 1H), 7.81 (cl, / = 8.4 Hz, IH), 7.53 (s, 2H), 7.45—7.38 (m, 2H), 7.29-7.22 (m, 3H), 2.99 (s, 3H), 2.35 (s, 3H) Example 232.
6-(4-플루오로— 2-메틸— 5-{3— [(메틸) (2-메틸아미노에틸)아미노]ᅳ 5-트리플루오로 메틸—페닐카바모일 }—페닐 인다졸—3-카복시산 메틸아미드의 제조  6- (4-fluoro— 2-methyl— 5- {3— [(methyl) (2-methylaminoethyl) amino] ᅳ 5-trifluoro methyl—phenylcarbamoyl} —phenyl indazole—3-carboxy Preparation of Acid Methylamide
Figure imgf000127_0001
Figure imgf000127_0001
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 221.
¾ NMR (300 MHz, CD?>0D— ί¾) δ 8.28 (d, /= 8.6 Hz, 1H), 7.64 (d, J= 7.2 Hz 1H), 7.51-7.50 (m, 1H), 7.26—7.22 (m, 3H), 6.75 (s, IH), 3.60—3.56 (m, 2H) 3.41-3.37 (m, 2H )， 2.99 (s, 3H), 2.95 (s, 6H) 실시예 233. ¾ NMR (300 MHz, CD ?> 0D— ί¾) δ 8.28 (d, / = 8.6 Hz, 1H), 7.64 (d, J = 7.2 Hz 1H), 7.51-7.50 (m, 1H), 7.26—7.22 ( m, 3H), 6.75 (s, IH), 3.60—3.56 (m, 2H) 3.41-3.37 (m, 2H), 2.99 (s, 3H), 2.95 (s, 6H) Example 233.
6-(5ᅳ ((2ᅳ ((2ᅳ (디메틸아미노)에틸)아미노 )-5- (트리플루오로메틸)페닐)카바모일 )-4-플루오로ᅳ 2-메틸페닐)— 메틸 - 1 / 인다졸 -3-카복스아미드의 제조  6- (5 '((2' ((2 '(dimethylamino) ethyl) amino) -5- (trifluoromethyl) phenyl) carbamoyl) -4-fluoro'2-methylphenyl) — methyl-1 / Preparation of indazole-3-carboxamide
Figure imgf000127_0002
Figure imgf000127_0002
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 221.
Ή匿 (300 MHz, C¾0D—rfi) δ 8.62 (d, J= 8.6 Hz, IH), 8.29 (cl, J 8.6 Hz, IH), 7.85 (s, IH), 7.55-7.43 (m, 4H), 7.26 (dd, J= 8.6, 1.2 Hz, IH), 3.52 (t, J = 6.6 Hz, IH), 3.19 (t, J= 6.6 Hz, IH), 2.99 (s, 3H), 2.90 (s, 3H), 2.73 (s, 3H), 2.37 (s, 3H) 실시예 234. 300 (300 MHz, C¾0D—rfi) δ 8.62 (d, J = 8.6 Hz, IH), 8.29 (cl, J 8.6 Hz, IH), 7.85 (s, IH), 7.55-7.43 (m, 4H), 7.26 (dd, J = 8.6, 1.2 Hz, IH), 3.52 (t, J = 6.6 Hz, IH), 3.19 (t, J = 6.6 Hz, IH), 2.99 (s, 3H), 2.90 (s, 3H ), 2.73 (s, 3H), 2.37 (s, 3H) Example 234.
6-(5-( (3-클로로 -4-메톡시페닐)카바모일 )ᅳ4—플루오로 -2ᅳ메틸페닐 메틸— 1^ 인다졸 -3-카복스아미드의 제조  Preparation of 6- (5- ((3-chloro-4-methoxyphenyl) carbamoyl) ᅳ 4—fluoro-2 ᅳ methylphenyl methyl—1 ^ indazole-3-carboxamide
Figure imgf000127_0003
Figure imgf000127_0003
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 221.
¾ NMR (300 MHz, CD30D-i¾) δ 8.36 (d, J= 4.5 Hz, IH), 8.23 (d, J= 3.9， IH) 7.88 (s, 1H), 7.61-7.55 (m, 3H), 7.35 (d, J 11.4 Hz, 1H), 7.25 (d, J 8.4 Hz, 1H), 7.14 (d, J 9.3 Hz, 2H), 3.83 (s, 3H), 2.83 (d, / = 4.5 Hz, 3H), 2.31 (s, 3H) 실시예 235. ¾ NMR (300 MHz, CD 3 0D-i¾) δ 8.36 (d, J = 4.5 Hz, IH), 8.23 (d, J = 3.9, IH) 7.88 (s, 1H), 7.61-7.55 (m, 3H), 7.35 (d, J 11.4 Hz, 1H), 7.25 (d, J 8.4 Hz, 1H), 7.14 (d, J 9.3 Hz, 2H), 3.83 (s, 3H), 2.83 (d, / = 4.5 Hz, 3H), 2.31 (s, 3H) Example 235.
6-(5-( (4—클로로— 3—메틸페닐)카바모일 )-4-플루오로 -2—메틸페닐 메틸— 1^인 다졸 -3—카복스아미드의 제조  Preparation of 6- (5- ((4—chloro-3 —methylphenyl) carbamoyl) -4-fluoro-2—methylphenyl methyl— 1 ^ indazole-3carboxamide
Figure imgf000128_0001
Figure imgf000128_0001
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 221.
]H NMR (300 MHz, C¾0D— οθ δ 8.36 (s, 1H), 8.22 (d, J= 8.4， 1H), 7.71 (s 1H), 7.58-7.53 (i , 3H), 7.39—7.34 (m, 3H), 7.23 (d, J = 8.4 Hz, 1H), 2.83 (d J = 4.8 Hz, 3H), 2.31 (s, 6H) 실시예 236. ] H NMR (300 MHz, C¾0D—οθ δ 8.36 (s, 1H), 8.22 (d, J = 8.4, 1H), 7.71 (s 1H), 7.58-7.53 (i, 3H), 7.39—7.34 (m, 3H), 7.23 (d, J = 8.4 Hz, 1H), 2.83 (d J = 4.8 Hz, 3H), 2.31 (s, 6H) Example 236.
6-(4-플루오로 -5-( (4_플루오로 -3-메틸페닐)카바모일 )-2-메틸페닐 ) - 메틸— 1/ 인다졸 -3-카복스아미드의 제조  Preparation of 6- (4-fluoro-5-((4_fluoro-3-methylphenyl) carbamoyl) -2-methylphenyl) -methyl- 1 / indazole-3-carboxamide
Figure imgf000128_0002
Figure imgf000128_0002
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 221.
¾ NMR (300 MHz, C¾0D一 ) δ 8.37-8.35 (m, 1H), 8.23 (d, J 8.1 Hz, 1H), 7.65-7.62 (m, 1H), 7.61—7.50 (m, 3H), 7.34 (d, J = 11.4 Hz, 1H) , 7.26 (d, J = 8.4 Hz, 1H), 7.13-7.07 (m, 1H), 2.83 (d, J= 4.8 Hz, 3H), 2.31 (s, 3H), 2.23 (d, J = 1.8 Hz, 3H) 실시예 237. ¾ NMR (300 MHz, C¾0D 一) δ 8.37-8.35 (m, 1H), 8.23 (d, J 8.1 Hz, 1H), 7.65-7.62 (m, 1H), 7.61—7.50 (m, 3H), 7.34 ( d, J = 11.4 Hz, 1H), 7.26 (d, J = 8.4 Hz, 1H), 7.13-7.07 (m, 1H), 2.83 (d, J = 4.8 Hz, 3H), 2.31 (s, 3H), 2.23 (d, J = 1.8 Hz, 3H) Example 237.
6一 (4-플루오로— 5- ( (4-이소프로필페닐)카바모일 )—2ᅳ메틸페닐) 메틸 -1^인다졸 -3-카복스아미드의 제조  Preparation of 6- (4-Fluoro— 5- ((4-isopropylphenyl) carbamoyl) —2′methylphenyl) methyl-1 ^ indazole-3-carboxamide
Figure imgf000128_0003
Figure imgf000128_0003
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 221.
匪 R (300 MHz, CD30D-(¾) δ 8.37—8.33 (m, 1H), 8.22 (d, J= 8.4 Hz, 1H), 7.63 (s, 1H), 7.60 (s, 1H), 7.56-7.53 (m, 2H), 7.34 (d, J= 11.4 Hz, 1H), 7.26-7.19 (iii, 3H), 2. 82-2.84 (m, IH) , 2.83 (d, J= 4.5 Hz, 3H), 2.3 (s, 3H), 1.18 (d ./ = 6.9 Hz, 6H) 실시예 238. 匪 R (300 MHz, CD 3 0D- (¾) δ 8.37—8.33 (m, 1H), 8.22 (d, J = 8.4 Hz, 1H), 7.63 (s, 1H), 7.60 (s, 1H), 7.56 -7.53 (m, 2H), 7.34 (d, J = 11.4 Hz, 1H), 7.26-7.19 (iii, 3H), 2. 82-2.84 (m, IH), 2.83 (d, J = 4.5 Hz, 3H), 2.3 (s, 3H), 1.18 (d./= 6.9 Hz, 6H) Example 238 .
6-(4-플루오로 -2-메틸— 5— (//;를일카바모일)페닐)—^메틸 -l^인다졸 -3—카복스아 미드의 제조  Preparation of 6- (4-fluoro-2-methyl— 5— (//; ylcarbamoyl) phenyl)-^ methyl-l ^ indazole-3-carboxamide
Figure imgf000129_0001
Figure imgf000129_0001
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. 'HNMR (300 MHz, C¾0D— ) δ 8.37-8.34 (m, 1H)， 8.23 (d, J= 8.4， IH) , 7.56—7.49 (111， 4H), 7.35 (cl, J= 11.4 Hz, IH), 7.26-7.19 (m, 2H), 6.92 (d, J = 7.5 Hz, IH), 2.84 (cl, J 4.8 Hz, 3H), 2.31 (s, 3H), 2.29 (s, 3H) 실시예 239. , The title compound was obtained in the same manner as the Example 221. 'HNMR (300 MHz, C¾0D—) δ 8.37-8.34 (m, 1H), 8.23 (d, J = 8.4, IH), 7.56—7.49 (111, 4H), 7.35 (cl, J = 11.4 Hz, IH) 7.26-7.19 (m, 2H), 6.92 (d, J = 7.5 Hz, IH), 2.84 (cl, J 4.8 Hz, 3H), 2.31 (s, 3H), 2.29 (s, 3H) Example 239. ,
6-(4-플루오로 -2-메틸 -5-( (4-메틸 -3- (트리플루오로메틸)페닐 )카바모일)페닐 ) 6- (4-fluoro-2-methyl-5-((4-methyl-3- (trifluoromethyl) phenyl) carbamoyl) phenyl)
-메틸 인다졸 -3-카복스아미드의 제조 Preparation of -methyl indazole-3-carboxamide
Figure imgf000129_0002
Figure imgf000129_0002
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. \\ NMR (300 MHz, CD^D-rf ) δ 8.35—8.34 (m, IH), 8.23 (d, /= 8.4 Hz, IH), 8.12 (cl, J= 1.5 Hz, IH), 7.86 (d, J 8.4 Hz, IH), 7.60 (d, /= 7.5 Hz, IH), 7.56 (s, IH), 7.41 (d, J = 8.4 Hz, IH), 7.36 (cl, J= 8.4 Hz, IH), 7.25 (d, J 8.4 Hz, IH), 2.83 (cl, J = 4.8 Hz, 3H), 2.40 (d, J= 1.2 Hz, 3H), 2.31 (s, 3H) 실시예 240. The title compound was obtained in the same manner as the Example 221. \\ NMR (300 MHz, CD ^ D-rf) δ 8.35—8.34 (m, IH), 8.23 (d, / = 8.4 Hz, IH), 8.12 (cl, J = 1.5 Hz, IH), 7.86 (d , J 8.4 Hz, IH), 7.60 (d, / = 7.5 Hz, IH), 7.56 (s, IH), 7.41 (d, J = 8.4 Hz, IH), 7.36 (cl, J = 8.4 Hz, IH) , 7.25 (d, J 8.4 Hz, IH), 2.83 (cl, J = 4.8 Hz, 3H), 2.40 (d, J = 1.2 Hz, 3H), 2.31 (s, 3H) Example 240.
6— (4-플루오로 -5-( (3-플루오로 -5- (트리플루오로메톡시 )페닐)카바모일 )—2—메틸 페닐 )— 메틸— 인다졸 -3—카복스아미드의 제조  6— Preparation of (4-fluoro-5-((3-fluoro-5- (trifluoromethoxy) phenyl) carbamoyl) —2—methyl phenyl) —methyl—indazole-3—carboxamide
Figure imgf000129_0003
Figure imgf000129_0003
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾ NMR (300 MHz, CD30D-i¾) δ 8.37-8.35 (m, IH), 8.23 (d, / = 8.4 Hz, IH), 7.68—7.60 (m, 3H), 7.55 (s, IH), 7.38 (d, J= 11.4 Hz, IH), 7.25 (d, J= 8.4 Hz, IH), 7.11, (d, J = 9.0 Hz, IH), 2.83 (d, J = 4.8 Hz, 3H), 2.32 (s, 3H) 실시예 241. The title compound was obtained in the same manner as the Example 221. ¾ NMR (300 MHz, CD 3 0D-i¾) δ 8.37-8.35 (m, IH), 8.23 (d, / = 8.4 Hz, IH), 7.68—7.60 (m, 3H), 7.55 (s, IH), 7.38 (d, J = 11.4 Hz, IH), 7.25 (d, J = 8.4 Hz, IH), 7.11, (d, J = 9.0 Hz, IH), 2.83 (d, J = 4.8 Hz, 3H), 2.32 (s, 3H) Example 241.
6-(5-((3-( ev기틸 )-1—페닐— I/ 피라졸ᅳ 5—일)카바모일 )-4ᅳ플루오로—2—메틸페 닐 메틸 인다졸 -3-카복스아미드의 제조  6- (5-((3- (evgityl) -1—phenyl—I / pyrazolyl 5-yl) carbamoyl) -4 ᅳ fluoro—2—methylphenyl methyl indazole-3-carboxamide Manufacture
Figure imgf000130_0001
Figure imgf000130_0001
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 221.
1删 R (300ΜΗζ 0Ι)- ) δ 8.37-8.35 (m, 1H), 8.22 (d, J= 8.4, 1H) , 7.57-7,43 (m, 6H), 7.37-7.31 (m, 2H), 7.21 (d, /= 8.4 Hz, 1H), 2.84 (d, J = 4.8 Hz, 3H), 2.29 (s, 3H), 1.30 (s, 9H) 실시예 242. 1 删 R (300ΜΗζ 0Ι)-) δ 8.37-8.35 (m, 1H), 8.22 (d, J = 8.4, 1H), 7.57-7,43 (m, 6H), 7.37-7.31 (m, 2H), 7.21 (d, / = 8.4 Hz, 1H), 2.84 (d, J = 4.8 Hz, 3H), 2.29 (s, 3H), 1.30 (s, 9H) Example 242.
6-(4-플루오로 -2—메틸— 5—( (1,2, 2, 6, 6-펜타메틸피페리딘 -4—일)카바모일)페닐) -Λ/ -메틸 인다졸 -3—카복스아미드의 제조  6- (4-fluoro-2—methyl— 5 — ((1,2, 2, 6, 6-pentamethylpiperidin-4—yl) carbamoyl) phenyl) -Λ / -methyl indazole-3 —Manufacture of Carboxamides
Figure imgf000130_0002
Figure imgf000130_0002
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. x\\ NMR (300 MHz , C¾0D— ) δ 8.26 (d, J 8.4 Hz, 1H), 7.57 (d, J = 7.5 Hz, 1H), 7.49 (s, 1H), 7.20 (s, 1H), 7.19 (d, /= 4.5 Hz, 1H), 2.99 (s, 3H), 2.87 (s, 3H), 2.31 (s, 3H), 2.28-2.23 (m, 1H) , 1.9—1.80 (m, 2H), 1.55 Cs, 6H), 1.51 (s, 6H) 실시예 243. The title compound was obtained in the same manner as the Example 221. x \\ NMR (300 MHz, C¾0D—) δ 8.26 (d, J 8.4 Hz, 1H), 7.57 (d, J = 7.5 Hz, 1H), 7.49 (s, 1H), 7.20 (s, 1H), 7.19 (d, / = 4.5 Hz, 1H), 2.99 (s, 3H), 2.87 (s, 3H), 2.31 (s, 3H), 2.28-2.23 (m, 1H), 1.9—1.80 (m, 2H), 1.55 Cs, 6H), 1.51 (s, 6H) Example 243.
6一 (4-플루오로 -2-메틸— 5— ( (2-( 1ᅳ메틸피롤리딘— 2-일 )에틸 )카바모일 )페닐 )-그메 틸— 1/ 인다졸 -3—카복스아미드의 제조  6- (4-Fluoro-2-methyl— 5— ((2- (1 ᅳ methylpyrrolidin— 2-yl) ethyl) carbamoyl) phenyl) -gmethyl— 1 / indazole-3—carbox Preparation of Amides
Figure imgf000130_0003
Figure imgf000130_0003
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾ NMR (300 MHz, CD30D-c¾) δ 8.29 (d, J= 8.4 Hz, 1H), 7.66 (d, J = 7.8 Hz, 1H), 7.49 (s, 1H), 7.24-7.19 (m, 2H), 3.52 (t, J= 6.6 Hz, 2H), 2.99 (s, 3H), 2.94 (s, 3H), 2.51-2.47 (m, 1H), 2.32 (s, 3H) , 2.13-2.07 (ra, 2H) , 1.85-1.82 (m, 2H), 1.29 (s, 3H) 실시예 244. The title compound was obtained in the same manner as the Example 221. ¾ NMR (300 MHz, CD 3 0D-c¾) δ 8.29 (d, J = 8.4 Hz, 1H), 7.66 (d, J = 7.8 Hz, 1H), 7.49 (s, 1H), 7.24-7.19 (m, 2H), 3.52 (t, J = 6.6 Hz, 2H), 2.99 (s, 3H), 2.94 (s, 3H), 2.51-2.47 (m, 1H), 2.32 (s, 3H), 2.13-2.07 (ra , 2H), 1.85-1.82 (m, 2H), 1.29 (s, 3H) Example 244.
6-(4—폴루오로— 5-(2-(3-플루오로페닐 )하0
Figure imgf000131_0001
6- (4—Polouro—5- (2- (3-fluorophenyl) ha0
Figure imgf000131_0001
/ 인다졸 -3-카복스아미드의 제조 / Preparation of indazole-3-carboxamide
Figure imgf000131_0002
Figure imgf000131_0002
상기 실시예 43의 단계 1과 단계 2와 동일한 방법으로 수행하여 , 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Step 1 and Step 2 of Example 43.
!H NMR (300 MHz , DMSO—οί;) δ 7.56 (d, J = 8.6 Hz, 1H), 6.94 (d, J= 7.2 1H), 6.78 (s, 1H), 6.56-6.42 (111， 3H), 5.99-5.94 (111, 1H), 5.90-5.86 (m, 5.80-5.70 (m, 1H), 2.27 (s, 3H), 1.62 (s, 3H) 실시예 245. ! H NMR (300 MHz, DMSO—οί;) δ 7.56 (d, J = 8.6 Hz, 1H), 6.94 (d, J = 7.2 1H), 6.78 (s, 1H), 6.56-6.42 (111, 3H), 5.99-5.94 (111, 1H), 5.90-5.86 (m, 5.80-5.70 (m, 1H), 2.27 (s, 3H), 1.62 (s, 3H) Example 245.
6-(4-플루오로 -2—메틸 -5—( (3-(4-메틸피페라진 -1—일 ) -5- (트리플루오로메틸)벤질 )카바모일 )페닐 )ᅳ 메틸 -1/·인다졸 -3-카복스아미드의 제조  6- (4-Fluoro-2—methyl-5 — ((3- (4-methylpiperazin-1—yl) -5- (trifluoromethyl) benzyl) carbamoyl) phenyl) ᅳ methyl-1 / Preparation of indazole-3-carboxamide
Figure imgf000131_0003
Figure imgf000131_0003
상기 실시예 43의 단계 1과 단계 2와 동일한 방법으로 수행하여， 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Step 1 and Step 2 of Example 43.
¾ NMR (300 MHz, DMS0- ) δ 8.24 (d, J= 8.6 Hz, 1H), 7.63 Cd, J = 8.6 Hz, 1H), 7.46 (s, 1H), 7.19—7.11 (m, 4H), 7.06 (s, 1H), 3.25-3.22 (m, 4H), 4.58 (s, 2H), 3.25-3.22 (m, 4H), 2.98 (s, 3H), 2.57—2.53 (4H), 2.30 (s, 6H), 2.27 (s, 3H) 실시예 246.  ¾ NMR (300 MHz, DMS0-) δ 8.24 (d, J = 8.6 Hz, 1H), 7.63 Cd, J = 8.6 Hz, 1H), 7.46 (s, 1H), 7.19—7.11 (m, 4H), 7.06 (s, 1H), 3.25-3.22 (m, 4H), 4.58 (s, 2H), 3.25-3.22 (m, 4H), 2.98 (s, 3H), 2.57—2.53 (4H), 2.30 (s, 6H ), 2.27 (s, 3 H) Example 246.
6-(4-플루오로— 2-메틸 -5— (2—페닐아세타미도)페닐；)ᅳ ^메틸— 1^인다졸—3-카복스 아미드의 제조  Preparation of 6- (4-fluoro—2-methyl-5— (2—phenylacetamido) phenyl;) ^ methyl—1 ^ indazole—3-carbox amide
Figure imgf000131_0004
Figure imgf000131_0004
상기 실시예 43의 단계 1과 단계 2와 동일한 방법으로 In the same manner as in Step 1 and Step 2 of Example 43
6- (5-아미노— 4-플루오로 -2-메틸페닐 메틸 -1- (테트라하이드로 -2^피란 -2—일 ) -1^인다졸 -3-카르보아미드를 반웅시켜， 6一 (4—플루오로 -2-메틸 -5ᅳ(2-페닐아세타미도)페닐 )— 메틸— 1/ 인다졸 -3ᅳ카복스 아미드를 얻었다. 6- (5-amino— 4-fluoro-2-methylphenyl methyl-1- (tetrahydro-2 ^ pyran-2-yl) -1 ^ indazole-3-carboamide 6- (4-Fluoro-2-methyl-5 '(2-phenylacetamido) phenyl) -methyl-1 / indazol-3'carboxamide was obtained.
Ή NMR (300 MHz , DMSO- ) δ 9.97 (s, 1H) , 8.36 (d, J= 4.8 Hz, 1H)， 8.17 (cl, /= 9.0 Hz, 1H), 7.78 (d, / = 8.1 Hz, 1H), 7.43 (s, 1H) , 7.32-7.21 (m, 7H), 7.15 (d. J 8.1 Hz, 1H), 3.71 (s, 2H), 2.82 (d, / = 4.8 Hz, 3H), 2.19 (s, 3H) 실시예 247.  NMR (300 MHz, DMSO-) δ 9.97 (s, 1H), 8.36 (d, J = 4.8 Hz, 1H), 8.17 (cl, / = 9.0 Hz, 1H), 7.78 (d, / = 8.1 Hz, 1H), 7.43 (s, 1H), 7.32-7.21 (m, 7H), 7.15 (d.J 8.1 Hz, 1H), 3.71 (s, 2H), 2.82 (d, / = 4.8 Hz, 3H), 2.19 (s, 3H) Example 247.
6-(5-(2— (4—클로로—3- (트리플루오로메틸)페닐)아세타미도) -4—플루오로ᅳ 2—메틸 페닐 )— 메틸— 1/ 인다졸ᅳ 3-카복스아미드의 제조  6- (5- (2— (4—Chloro—3- (trifluoromethyl) phenyl) acetamido) -4—fluoro ᅳ 2—methyl phenyl) — methyl— 1 / indazole ᅳ 3-carbox Preparation of Amides
Figure imgf000132_0001
Figure imgf000132_0001
상기 실시예 246과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 246.
NMR (300 MHz, DMSO—ii) δ 13.57 (s, 1H)， 10.08 (s, 1H), 8.37 (cl, / = 3.0 Hz, 1H), 8.18 (d, /= 9.0 Hz, 1H), 7.82-7.77 (m, 2H) , 7.69—7.61 (m, 2H). 7.44 (s, 1H), 7.25 (d, J= 12.0 Hz, 1H), 7.16 (d, J = 9.0 Hz, IH), 3.86 (s, 2H), 2.83 (d, J = 3.0 Hz, 3H), 2.20 (s, 3H) 실시예 248.  NMR (300 MHz, DMSO—ii) δ 13.57 (s, 1H), 10.08 (s, 1H), 8.37 (cl, / = 3.0 Hz, 1H), 8.18 (d, / = 9.0 Hz, 1H), 7.82- 7.77 (m, 2 H), 7.69—7.61 (m, 2 H). 7.44 (s, 1H), 7.25 (d, J = 12.0 Hz, 1H), 7.16 (d, J = 9.0 Hz, IH), 3.86 (s, 2H), 2.83 (d, J = 3.0 Hz, 3H), 2.20 (s, 3 H) Example 248.
6-(4-플루오로— 5— (2-(3-메톡시페닐)아세타미도) -2-메틸페닐)— 메틸 인다졸 -3—카복스아미드의 제조  Preparation of 6- (4-fluoro— 5— (2- (3-methoxyphenyl) acetamido) -2-methylphenyl) — methyl indazole-3—carboxamide
Figure imgf000132_0002
Figure imgf000132_0002
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾ NMR (300 MHz, DMSO- ) δ 9.96 (s, 1H), 8.37 (d, J 4.8 Hz, 1H), 8.17 (d' J 8.4 Hz, 1H), 7.78 (d, J = 8.4 Hz, IH), 7.44 (s, 1H), 7.26-7.14 (m, 3H), 6.92-6.88 (m, 2H)' 6.80 (d, J 7.2 Hz, IH), 3.73 (s, 3H), 3.68 (s, 2H), 2.82 (d, J = 4.5 Hz, 3H), 2.20 (s, 3H) 실시예 249. The title compound was obtained in the same manner as the Example 221. ¾ NMR (300 MHz, DMSO-) δ 9.96 (s, 1H), 8.37 (d, J 4.8 Hz, 1H), 8.17 (d 'J 8.4 Hz, 1H), 7.78 (d, J = 8.4 Hz, IH) , 7.44 (s, 1H), 7.26-7.14 (m, 3H), 6.92-6.88 (m, 2H) ' 6.80 (d, J 7.2 Hz, IH), 3.73 (s, 3H), 3.68 (s, 2H) , 2.82 (d, J = 4.5 Hz, 3H), 2.20 (s, 3H) Example 249.
6ᅳ(4-플루오로 -2—메틸— 5-(2— (/^를일)아세타미도)페닐) - 메틸 -l^인다졸— 3一카 복스아미드의 제조
Figure imgf000133_0001
6 '(4-Fluoro-2—methyl—5- (2 — (/ ^ ylyl) acetamido) phenyl) -methyl-l ^ indazole—a preparation of 3-carboxamide
Figure imgf000133_0001
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 221.
]\ NMR (300 MHz , DMSO-^f;) δ 9.98 (s, 1H), 8.40 (d, ./ = 4.8 Hz, 1H) , 8.21 (d, J= 8.4 Hz, 1H), 7.81 (d, J 8.4 Hz, III), 7.46 (s, 1H), 7.28-7.16 (m, 5H), 7.06 (d, /= 8.4 Hz, 1H) , 3.69 (s, 2H), 2.85 (cl, /= 4.5 Hz,3H), 2.30 (s, 3H), 2.22 (s, 3H) 실시예 250.  ] \ NMR (300 MHz, DMSO- ^ f;) δ 9.98 (s, 1H), 8.40 (d, ./ = 4.8 Hz, 1H), 8.21 (d, J = 8.4 Hz, 1H), 7.81 (d, J 8.4 Hz, III), 7.46 (s, 1H), 7.28-7.16 (m, 5H), 7.06 (d, / = 8.4 Hz, 1H), 3.69 (s, 2H), 2.85 (cl, / = 4.5 Hz , 3H), 2.30 (s, 3H), 2.22 (s, 3H) Example 250.
6-(4-플루오로 -5ᅳ(2-(4ᅳ플루오로페닐)아세타미도)ᅳ 2—메틸페닐) - ^메틸 -l^인다 졸 -3—카복스아미드의 제조  Preparation of 6- (4-Fluoro-5 '(2- (4'fluorophenyl) acetamido)' 2-methylphenyl)-^ methyl-l ^ indazol-3-carboxamide
Figure imgf000133_0002
Figure imgf000133_0002
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 221.
]H NMR (300 MHz, DMSO— ;) δ 9.98 (s, 1H), 8.36 (d, J 4.8 Hz, 1H), 8.17 (d, J = 8.4 Hz, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.43 (s, 1H), 7.35 (del, J= 8.4, 5.7 Hz, 1H), 7.23 (d, J 12.0 Hz, 1H), 7.17—7.09 (m, 3H), 3.69 (d, J = 6.6 Hz, 2H), 2.82 (d, J 4.8 Hz, 3H), 2.19 (s, 3H) 실시예 251. ] H NMR (300 MHz, DMSO— ; ) δ 9.98 (s, 1H), 8.36 (d, J 4.8 Hz, 1H), 8.17 (d, J = 8.4 Hz, 1H), 7.78 (d, J = 8.4 Hz , 1H), 7.43 (s, 1H), 7.35 (del, J = 8.4, 5.7 Hz, 1H), 7.23 (d, J 12.0 Hz, 1H), 7.17—7.09 (m, 3H), 3.69 (d, J = 6.6 Hz, 2H), 2.82 (d, J 4.8 Hz, 3H), 2.19 (s, 3H) Example 251.
6-(5-(2- (벤조 [d][l,3]디옥솔 -5-일)아세타미도)— 4ᅳ플루오로 -2-메틸페닐) -Λ^메  6- (5- (2- (benzo [d] [l, 3] dioxol-5-yl) acetamido) — 4'fluoro-2-methylphenyl) -Λ ^ meth
Figure imgf000133_0003
Figure imgf000133_0003
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다.  The title compound was obtained in the same manner as the Example 221.
¾ NMR (300 MHz, DMS0一 0 δ 9.90 (s, 1H)， 8.34 (d, /= 4.8 Hz, 1H), 8.18 (d, J 8.4 Hz, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.43 (s, 1H), 7.23 (d, J = 12.0 Hz, 1H), 7.15 (dd, J= 8.4, 1.2 Hz, 1H), 6.89—6.85 (m, 3H), 5.96 (s, 2H), 3.61 (s, 2H), 2.82 (d, J = 4.5 Hz, 3H), 2.19 (s, 3H) 실시예 252.  ¾ NMR (300 MHz, DMS0 0 0 δ 9.90 (s, 1H), 8.34 (d, / = 4.8 Hz, 1H), 8.18 (d, J 8.4 Hz, 1H), 7.77 (d, J = 8.4 Hz, 1H ), 7.43 (s, 1H), 7.23 (d, J = 12.0 Hz, 1H), 7.15 (dd, J = 8.4, 1.2 Hz, 1H), 6.89—6.85 (m, 3H), 5.96 (s, 2H) , 3.61 (s, 2H), 2.82 (d, J = 4.5 Hz, 3H), 2.19 (s, 3H) Example 252.
6-(5— (2-(3,4-디클로로페닐)아세타미도) -4-플루오로 -2-메틸페닐 )— 메틸— 1^인 다졸 -3-카복스아미드의 제조
Figure imgf000134_0001
Preparation of 6- (5— (2- (3,4-dichlorophenyl) acetamido) -4-fluoro-2-methylphenyl) —methyl—1 ^ dazole 3-carboxamide
Figure imgf000134_0001
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 221.
]H NMR (300 MHz , DMS0一 ) δ 13.57 (s, 1Η), 10.04 (s, 1H), 8.37 (d, J 4.8 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.79 (s, 1H), 7.76 (s, 1H), 7.44 (s, 1H), 7.33-7.23 (in, 2H), 7.16 (del, /= 8.4, 1.5 Hz, 1H) , 3.76 (s, 2H), 2.82 (d, J = 4.8 Hz, 3H), 2.20 (s, 3H) 실시예 253. ] H NMR (300 MHz, DMS0 一) δ 13.57 (s, 1Η), 10.04 (s, 1H), 8.37 (d, J 4.8 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 7.78 ( d, J = 8.4 Hz, 1H), 7.79 (s, 1H), 7.76 (s, 1H), 7.44 (s, 1H), 7.33-7.23 (in, 2H), 7.16 (del, / = 8.4, 1.5 Hz , 1H), 3.76 (s, 2H), 2.82 (d, J = 4.8 Hz, 3H), 2.20 (s, 3H) Example 253.
6—(4-플루오로 -5— (2— (2—메톡시페닐)아세타미도)—2—메틸페닐 메틸 인다졸 一 3-카복스아미드의 제조  Preparation of 6— (4-fluoro-5— (2— (2—methoxyphenyl) acetamido) —2—methylphenyl methyl indazole -1-3-carboxamide
Figure imgf000134_0002
Figure imgf000134_0002
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾刚 R (300 MHz, DMS0- ) δ 13.57 (s, 1H), 9.78 (s, 1H) , 8.38 (cl, J 4.8 Hz, 1H), 8.17 (d, J= 8.4 Hz, 1H), 7.79 (d, J= 8.4 Hz, 1H), 7.44 (s, 1H), 7.26—6.98 (m, 4H), 6.98 (d, J 8.4 Hz, 1H), 6.87 (d, /= 8.2 Hz, 1H), 3.77 (s, 3H), 3.69 (s, 2H), 2.83 (s, 3H), 2.20 (s, 3H) 실시예 254.  The title compound was obtained in the same manner as the Example 221. ¾ 刚 R (300 MHz, DMS0-) δ 13.57 (s, 1H), 9.78 (s, 1H), 8.38 (cl, J 4.8 Hz, 1H), 8.17 (d, J = 8.4 Hz, 1H), 7.79 ( d, J = 8.4 Hz, 1H), 7.44 (s, 1H), 7.26—6.98 (m, 4H), 6.98 (d, J 8.4 Hz, 1H), 6.87 (d, / = 8.2 Hz, 1H), 3.77 (s, 3H), 3.69 (s, 2H), 2.83 (s, 3H), 2.20 (s, 3H) Example 254.
6-(5— (2-(3,5—디메톡시페닐)아세타미도) -4-플루오로— 2—메틸페닐) 메틸 인 다졸 -3-카복스아미드의 제조  Preparation of 6- (5— (2- (3,5—dimethoxyphenyl) acetamido) -4-fluoro— 2—methylphenyl) methyl indazole-3-carboxamide
Figure imgf000134_0003
Figure imgf000134_0003
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 221.
丽 R (300 MHz, DMS0- ) δ 13.57 (s, 1H), 9.94 (s, 1H), 8.38 (d, J= 4.8 Hz, 1H), 8.17 (d, J= 8.4 Hz, 1H), 7.77 (d, J= 8.4 Hz, 1H), 7.44 (s, 1H), 7.24 (d, J= 11.7 Hz, 1H), 7.16 (d, J= 8.4 Hz, 1H), 6.51 (d, J= 1.8 Hz, 1H), 6.38 (d, J 1.8 Hz, 1H), 3.71 (s, 6H), 3.63 (s, 2H), 2.82 (d, J= 4.8 Hz, 3H) , 2.20 (s, 3H) 실시예 255. R R (300 MHz, DMS0-) δ 13.57 (s, 1H), 9.94 (s, 1H), 8.38 (d, J = 4.8 Hz, 1H), 8.17 (d, J = 8.4 Hz, 1H), 7.77 ( d, J = 8.4 Hz, 1H), 7.44 (s, 1H), 7.24 (d, J = 11.7 Hz, 1H), 7.16 (d, J = 8.4 Hz, 1H), 6.51 (d, J = 1.8 Hz, 1H), 6.38 (d, J 1.8 Hz, 1H), 3.71 (s, 6H), 3.63 (s, 2H), 2.82 (d, J = 4.8 Hz, 3H), 2.20 (s, 3H) Example 255.
6-(5-(2-(4-디메특시아미노페닐 )아세타미도) -4-플루오로 -2-메틸페닐 )ᅳ ^메틸 -1 인다졸—3-카복스아미드의 제조  Preparation of 6- (5- (2- (4-dimethoxyaminophenyl) acetamido) -4-fluoro-2-methylphenyl) ᅳ ^ methyl-1 indazole—3-carboxamide
Figure imgf000135_0001
Figure imgf000135_0001
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. NMR (300 MHz , DMSO- ) δ 13.57 (s, 1H), 9.89 (s, 1H), 8.38 (cl, J= 4.8 Hz, 1H), 8.17 (d, /= 8.4 Hz, 1H), 7.77 (d, 8.4 Hz, 1H), 7.43 (s, 1H), 7.26-7.16 (m, 4H), 7.15 (dd, J= 8.4, 1.2 Hz, 1H), 6.66 (bs, 1H), 3.61 (s, 2H) , 2.92 (s, 6H), 2.82 (d, J = 4.5 Hz, 3H), 2.20 (s, 3H) 실시예 256.  The title compound was obtained in the same manner as the Example 221. NMR (300 MHz, DMSO-) δ 13.57 (s, 1H), 9.89 (s, 1H), 8.38 (cl, J = 4.8 Hz, 1H), 8.17 (d, / = 8.4 Hz, 1H), 7.77 (d , 8.4 Hz, 1H), 7.43 (s, 1H), 7.26-7.16 (m, 4H), 7.15 (dd, J = 8.4, 1.2 Hz, 1H), 6.66 (bs, 1H), 3.61 (s, 2H) , 2.92 (s, 6H), 2.82 (d, J = 4.5 Hz, 3H), 2.20 (s, 3H) Example 256.
6-(4-플루오로 -2—메틸 -5-(2-(4-나이트로페닐)아세타미도)페닐) -y 메틸 -1 ^인다 졸 -3-카복스아미드의 제조  Preparation of 6- (4-fluoro-2—methyl-5 (2- (4-nitrophenyl) acetamido) phenyl) -y methyl-1 ^ indazol-3-carboxamide
Figure imgf000135_0002
Figure imgf000135_0002
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾ NMR (300 MHz, DMS0— (¾) δ 13.57 (s, 1H), 10.13 (s, 1H), 8.38 (cl, J 4.8 Hz, 1H), 8.21-8.16 (m, 3H) , 7.79 (d, J = 8.4 Hz, 1H), 7.60 (d, J = 8.4 Hz, 2H), 7.44 (s, 1H), 7.25 (d, J 12.0 Hz, 1H), 7.16 (dd, J 8.4， 1.2 Hz, 1H), 3.92 (s, 2H), 2.82 (d, J = 4.5 Hz, 3H), 2.20 (s, 3H) 실시예 257.  The title compound was obtained in the same manner as the Example 221. ¾ NMR (300 MHz, DMS0— (¾) δ 13.57 (s, 1H), 10.13 (s, 1H), 8.38 (cl, J 4.8 Hz, 1H), 8.21-8.16 (m, 3H), 7.79 (d, J = 8.4 Hz, 1H), 7.60 (d, J = 8.4 Hz, 2H), 7.44 (s, 1H), 7.25 (d, J 12.0 Hz, 1H), 7.16 (dd, J 8.4, 1.2 Hz, 1H) , 3.92 (s, 2H), 2.82 (d, J = 4.5 Hz, 3H), 2.20 (s, 3H) Example 257.
6_(5-(2-(4- (브로모메틸)페닐)아세타미도) 4—플루오로 -2—메틸페닐) - 메틸 인다졸 -3-카복스아미드의 제조  Preparation of 6_ (5- (2- (4- (bromomethyl) phenyl) acetamido) 4-fluoro-2-methylphenyl) -methyl indazole-3-carboxamide
Figure imgf000135_0003
Figure imgf000135_0003
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 221.
¾丽 R (300 MHz, DMS0-4) δ 13.57 (s, 1H), 10.01 (s, 1H), 8.78 (dd, J= 4.5, 1.2 Hz, 1H), 8.57 (dd, J= 4.5, 1.2 Hz, 1H), 8.38 (d, J= 4.5 Hz, 1H), 8.18 (d, J= 8.8 Hz, 1H), 7.78 (d, J= 8.8 Hz, 1H)， 7.56-7.51 (m, 2H), 7.43 (d, J = 7.8 Hz, 1H), 7.35 (d, J= 8.4 Hz, 1H), 7.24 (d, J= 12.0 Hz, 1H), 7.16 (d, J= 8.4 Hz, 1H), 5.62 (s, 2H), 3.74 (s, 2H), 2.82 (d, ./ = 2.4 Hz, 3H), 2.20 (s, 3H) 실시예 258. ' 6-(4-플루오로 -2-메틸 -5-(2-(3- (트리플루오로메틸)페닐)아세타미도)페닐) 메 틸ᅳ 1^인다졸 -3-카복스아미드의 제조 ¾ 丽 R (300 MHz, DMS0-4) δ 13.57 (s, 1H), 10.01 (s, 1H), 8.78 (dd, J = 4.5, 1.2 Hz, 1H), 8.57 (dd, J = 4.5, 1.2 Hz , 1H), 8.38 (d, J = 4.5 Hz, 1H), 8.18 (d, J = 8.8 Hz, 1H), 7.78 (d, J = 8.8 Hz, 1H), 7.56-7.51 (m, 2H), 7.43 (d, J = 7.8 Hz, 1H), 7.35 (d, J = 8.4 Hz, 1H), 7.24 (d, J = 12.0 Hz, 1H), 7.16 (d, J = 8.4 Hz, 1H), 5.62 (s, 2H), 3.74 (s, 2H), 2.82 (d, ./= 2.4 Hz, 3H), 2.20 (s, 3H) Example 258. ' 6 Preparation of-(4-fluoro-2-methyl-5- (2- (3- (trifluoromethyl) phenyl) acetamido) phenyl) methyl ᅳ 1 ^ indazole-3-carboxamide
Figure imgf000136_0001
Figure imgf000136_0001
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. lH NMR (300 MHz , DMSO— i) δ 13.56 (s, 1H), 10.07 (s, 1H), 8.18 (d, J = 2.4 Hz. 1H), 8.18 (d, J = 8.4 Hz, 1H), 7.62-7.50 (m, 4H), 7.43 (d, J = 7.8 Hz, 1H), 7.70 (s, 1H), 7.25 (d, J 8.4 Hz, 1H), 7.15 (d, J = 8.4 Hz, 1H), 3.86 (s, 2H), 2.82 (d, J 4.5 Hz, 1H), 2.2 (s, 1H) 실시예 259. The title compound was obtained in the same manner as the Example 221. l H NMR (300 MHz, DMSO- i) δ 13.56 (s, 1H), 10.07 (s, 1H), 8.18 (d, J = 2.4 Hz. 1H), 8.18 (d, J = 8.4 Hz, 1H), 7.62-7.50 (m, 4H), 7.43 (d, J = 7.8 Hz, 1H), 7.70 (s, 1H), 7.25 (d, J 8.4 Hz, 1H), 7.15 (d, J = 8.4 Hz, 1H) , 3.86 (s, 2H), 2.82 (d, J 4.5 Hz, 1H), 2.2 (s, 1H) Example 259.
6-(4—플루오로 -5-(2-(4-플루오로— 3- (트리플루오로메틸)페닐)아세타미도) -2-메 틸페닐 메틸— 1/ 인다졸 -3-카복스아미드의 제조  6- (4—Fluoro-5 (2- (4-fluoro—3- (trifluoromethyl) phenyl) acetamido) -2-methylphenyl methyl— 1 / indazole-3-carbox Preparation of Amides
Figure imgf000136_0002
Figure imgf000136_0002
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 221.
lll NMR (300 MHz, DMS0- ) δ 13.5 (s, 1H), 10.06 (s, 1H), 8.38 (d, /= 3.0 Hz, 1H), 8.18 (d, J= 9.0 Hz, 1H), 7.80-7.66 (in, 3H), 7.27-7.23 (m, 2H), 7.17—7.14 (m, 2H), 3.84 (s, 2H), 2.83 (d, J = 3.0 Hz, 3H), 2.20 (s, 3H) 실시예 260. lll NMR (300 MHz, DMS0-) δ 13.5 (s, 1H), 10.06 (s, 1H), 8.38 (d, / = 3.0 Hz, 1H), 8.18 (d, J = 9.0 Hz, 1H), 7.80- 7.66 (in, 3H), 7.27-7.23 (m, 2H), 7.17—7.14 (m, 2H), 3.84 (s, 2H), 2.83 (d, J = 3.0 Hz, 3H), 2.20 (s, 3H) Example 260.
6-(5—(2-(4-브로모-3-메틸페닐)아세타미도)—4-플루오로— 2-메틸페닐)— 메틸 —인다졸 -3—카복스아미드의 제조  Preparation of 6- (5— (2- (4-bromo-3-methylphenyl) acetamido) —4-fluoro- 2-methylphenyl) —methyl-indazole-3—carboxamide
Figure imgf000136_0003
Figure imgf000136_0003
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. ¾ NMR (300 MHz, DMS0_(¾) δ 13.57 (s, 1H), 10.00 (s, 1H), 8.39 (d, J 6.0 Hz, 1H), 8.18 (d, J= 9.0 Hz, 1H), 7.78 (d, J= 6.0 Hz, 1H), 7.56 (s, 1H), 7.44 (s, 1H), 7.22 (m, 4H), 3.71 (s, 2H), 2.83 (d, J= 6.0 Hz, 3H), 2.30 (s, 3H), 2.20 (s, 3H) 실시예 261. The title compound was obtained in the same manner as the Example 221. ¾ NMR (300 MHz, DMS0_ (¾) δ 13.57 (s, 1H), 10.00 (s, 1H), 8.39 (d, J 6.0 Hz, 1H), 8.18 (d, J = 9.0 Hz, 1H), 7.78 ( d, J = 6.0 Hz, 1H), 7.56 (s, 1H), 7.44 (s, 1H), 7.22 (m, 4H), 3.71 (s, 2H), 2.83 (d, J = 6.0 Hz, 3H), 2.30 (s, 3H), 2.20 (s, 3H) Example 261.
6一 (4—플루오로 -5-(2-(3-플루우로페닐)아세타미도) -2-메틸페닐)— 메틸 인다 졸 -3—카복스아미드의 제조  Preparation of 6- (4—Fluoro-5 (2- (3-fluorofluoro) acetamido) -2-methylphenyl) —methyl indazole-3—carboxamide
Figure imgf000137_0001
Figure imgf000137_0001
상기 실시예 221과 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 221.
¾ NMR (300 MHz , DMS0一 ) δ 13.60 (s, 1H), 10.05 (s, 1H), 8.41 (d, / = 6.0 Hz, 1H), 8.21 (d, /= 9.0 Hz, 1H) , 7.82 (cl, J 9.0 Hz, 1H), 7.47 (s, 1H), 7.36 (m, 1H), 7.27 (d, J 12.0 Hz, 1H) , 7.20 (s, 1H), 7.17 (s, 1H), 7.12-7.06 (m, 1H), 3.78 (s. 2H), 2.85 (d, J 6.0 Hz, 3H). 2.22 (s, 3H) 실시예 262. . ¾ NMR (300 MHz, DMS0 一) δ 13.60 (s, 1H), 10.05 (s, 1H), 8.41 (d, / = 6.0 Hz, 1H), 8.21 (d, / = 9.0 Hz, 1H), 7.82 ( cl, J 9.0 Hz, 1H), 7.47 (s, 1H), 7.36 (m, 1H), 7.27 (d, J 12.0 Hz, 1H), 7.20 (s, 1H), 7.17 (s, 1H), 7.12- 7.06 (m, 1 H), 3.78 (s. 2 H), 2.85 (d, J 6.0 Hz, 3 H). 2.22 (s, 3 H) Example 262.
6- (4—플루오로 -2-메틸— 5-(메틸설폰아미도)페닐 ) 메틸— 1/ 인다졸 -3—카복스아 미드의 제조  Preparation of 6- (4—fluoro-2-methyl— 5- (methylsulfonamido) phenyl) methyl— 1 / indazole-3—carboxamide
Figure imgf000137_0002
Figure imgf000137_0002
6-(5_아미노— 4-플루오로— 2-메틸페닐) 메틸— 1- (테트라하이드로 -2^피란 -2-일) -1//·인다졸—3-카르보아미드를 메틸렌클로라이드에 녹이고 메탄설포닐  6- (5_amino— 4-fluoro— 2-methylphenyl) methyl— 1- (tetrahydro-2 ^ pyran-2-yl) -1 // indazole-3-carboamide in methylene chloride Methanesulfonyl
클로라이드 (MsCl)와 트리에틸아민 (TEA)을 넣고 2시간 실온에서 교반하였다. 반응이 종결된 후에 감압 농축하였다. 그리고, 얻어진 잔사는 상기 실시예 43의 단계 2와 동일한 방법으로 반웅시켜 Chloride (MsCl) and triethylamine (TEA) were added and stirred at room temperature for 2 hours. After the reaction was completed, the mixture was concentrated under reduced pressure. The obtained residue was reacted in the same manner as in Step 2 of Example 43.
6-(4-플루오로 -2—메틸 -5- (메틸설폰아미도)페닐) 메틸 인다졸 -3—카복스아 미드를 얻었다. i NMR (300 MHz, DMSO-^) δ 13.62 (s, 1H), 9.58 (s, 1H) 8.40 (d, J = 4.8 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 7.49 (s, 1H), 7.29 (d J= 8.9 Hz, 1H), 7.26 (d, J = 5.7 Hz, 1H), 7.20 (dd, J = 8.4, 1.2 Hz, 1H). 3.03 (s, 3H), 2.83 (d, J = 4.7 Hz, 3H), 2.23 (s, 3H).  6- (4-Fluoro-2-methyl-5- (methylsulfonamido) phenyl) methyl indazole-3-carboxamide was obtained. i NMR (300 MHz, DMSO- ^) δ 13.62 (s, 1H), 9.58 (s, 1H) 8.40 (d, J = 4.8 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 7.49 ( s, 1H), 7.29 (d J = 8.9 Hz, 1H), 7.26 (d, J = 5.7 Hz, 1H), 7.20 (dd, J = 8.4, 1.2 Hz, 1H). 3.03 (s, 3H), 2.83 (d, J = 4.7 Hz, 3H), 2.23 (s, 3H).
실시예 263. Example 263.
6-(4ᅳ플루오로— 2-메틸 -5- (트리플루오로메틸설폰아미도)페닐 )— 메틸 -1그인다졸 -3-카복스아미드의 제조  Preparation of 6- (4'Fluoro- 2-methyl-5- (trifluoromethylsulfonamido) phenyl) -methyl-1gindazole-3-carboxamide
Figure imgf000137_0003
상기 실시예 262와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. Ή NMR (300 MHz, DMSCH ) δ 13.64 (s, 1H), 8.42 (cl, ./= 4.7 Hz, 1H), 8.22 (cl, J 8.4 Hz, 1H), 7.50 (s, 1H) , 7.37 (d, J 11.1 Hz, 1H) , 7.28 (d, J = 8.1 Hz, 1H), 7.22 (d, J = 8.4 Hz, 1H), 2.85 (d, J = 4.7 Hz, 3Η') , 2.27 (s, 3H). 실시예 264.
Figure imgf000137_0003
The title compound was obtained in the same manner as the Example 262. NMR (300 MHz, DMSCH) δ 13.64 (s, 1H), 8.42 (cl, ./= 4.7 Hz, 1H), 8.22 (cl, J 8.4 Hz, 1H), 7.50 (s, 1H), 7.37 (d , J 11.1 Hz, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.22 (d, J = 8.4 Hz, 1H), 2.85 (d, J = 4.7 Hz, 3Η ' ), 2.27 (s, 3H ). Example 264.
6-(5- (에틸설폰아미도) -4-플루오로 -2ᅳ메틸페닐) 메틸 인다졸 -3-카복스아 미드의 제조  Preparation of 6- (5- (ethylsulfonamido) -4-fluoro-2'methylphenyl) methyl indazole-3-carboxamide
Figure imgf000138_0001
Figure imgf000138_0001
상기 실시예 262와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. The title compound was obtained in the same manner as the Example 262.
]H NMR (300 MHz, DMSO ) δ 13.61 is, 1Η), 9.62 (s, 1H), 8.40 (cl, J= 4.8 Hz, 1H), 8.20 (d, J 8.4 Hz, 1H), 7.48 (s, 1H), 7.29 (cl, J 4.4 Hz, 1H), 7.25 (s, 1H), 7.20 (del, J = 8.4, 1.3 Hz, 1H), 3.10 (q, J = 7.3 Hz, 2H), 2.83 (d, J 4.7 Hz, 3H), 2.22 (s, 3H), 1.26 (t, J = 7.3 Hz, 3H). 실시예 265. ] H NMR (300 MHz, DMSO) δ 13.61 is, 1Η), 9.62 (s, 1H), 8.40 (cl, J = 4.8 Hz, 1H), 8.20 (d, J 8.4 Hz, 1H), 7.48 (s, 1H), 7.29 (cl, J 4.4 Hz, 1H), 7.25 (s, 1H), 7.20 (del, J = 8.4, 1.3 Hz, 1H), 3.10 (q, J = 7.3 Hz, 2H), 2.83 (d , J 4.7 Hz, 3H), 2.22 (s, 3H), 1.26 (t, J = 7.3 Hz, 3H). Example 265.
6_(4-폴루오로 -2-메틸 -5-( 1-메틸에틸설폰아미도)페닐 )-그메틸 -1/ 인다졸— 3-카 복스아미드의 제조  6_ (4-Polouro-2-methyl-5- (1-methylethylsulfonamido) phenyl) -gmethyl-1 / indazole— Preparation of 3-carboxamide
Figure imgf000138_0002
Figure imgf000138_0002
상기 실시예 262와 동일한 방법으로 수행하여 상기 표제화합물을 얻었다. Ή NMR (300 MHz, DMSO- ) δ 13.60 (s, 1H), 9.60 (s, 1H) , 8.38 (cl, J= 4.7 Hz, 1H), 8.20 (d, J= 8.4 Hz, 1H), 7.47 (s, 1H), 7.31-7.22 (m, 2H), 7.19 (d, J = 8.4 Hz, 1H), 3.30-3.15 (m, 1H), 2.83 (d, /= 4.3 Hz, 3H), 2.21 (s, 3H), 1.28 (d, J= 6.7 Hz, 6H). 실시예 266.  The title compound was obtained in the same manner as the Example 262. Ή NMR (300 MHz, DMSO-) δ 13.60 (s, 1H), 9.60 (s, 1H), 8.38 (cl, J = 4.7 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 7.47 ( s, 1H), 7.31-7.22 (m, 2H), 7.19 (d, J = 8.4 Hz, 1H), 3.30-3.15 (m, 1H), 2.83 (d, / = 4.3 Hz, 3H), 2.21 (s , 3H), 1.28 (d, J = 6.7 Hz, 6H). Example 266.
6一(5-(3-아미노 -5- (트리플루오로메틸)벤즈아미도)—2-메틸피리딘— 3-일 ) - 메틸- 1^인다졸 -3—카복스아미드의 제조 Preparation of 6- (5- (3-amino-5- (trifluoromethyl) benzamido) —2-methylpyridin— 3-yl) -methyl-1 ^ indazole-3—carboxamide
Figure imgf000139_0001
Figure imgf000139_0001
단계 1.  Step 1.
6一 (5—아미노 -2-메틸피리딘— 3-일 )-N-메틸 -1- (테트라하이드로 피란— 2—일 )-1//· 인다졸—3-카복스아미드의 제조  Preparation of 6 一 (5—amino-2-methylpyridin— 3-yl) -N-methyl-1- (tetrahydropyran— 2—yl) -1 // · indazole—3-carboxamide
상기 제조예 3의 단계 7과 동일한 방법으로  In the same manner as in Step 7 of Preparation Example 3
^메틸 -1— (테트라하이드로— 2/ 피란 -2-일 )-6-(4 , 4,5, 5-테트라메틸 -1 , 3 , 2—다이옥 사보란—2—일)— 1/ 인다졸 -3-카복스아미드와 5—브로모—6-메틸피리딘— 3-아민을 반응시켜,  ^ Methyl-1— (tetrahydro— 2 / pyran-2-yl) -6- (4, 4,5, 5-tetramethyl-1, 3, 2—dioxane saborane—2—day) — 1 / Reacting sol-3-carboxamide with 5—bromo—6-methylpyridine—3-amine,
6-(5-아미노 -2—메틸피리딘 -3—일 )— N—메틸 -1- (테트라하이드로— 2/"피란 -2—일 )— 1^ 인다졸—3-카복스아미드를 얻었다. MS m/z [M+H] 366 단계 2.  6- (5-Amino-2-2-methylpyridin-3-yl) -N-methyl-1- (tetrahydro-2 / "pyran-2-yl) -1 ^ indazole- 3-carboxamide was obtained. MS m / z [M + H] 366 Step 2.
6一 (5-(3-아미노 -5— (트리플루오로메틸 )벤즈아미도) -2-메틸피리딘— 3-일 메틸- 인다졸 -3—카복스아미드의 제조  Preparation of 6- (5- (3-amino-5— (trifluoromethyl) benzamido) -2-methylpyridine—3-yl methyl-indazole-3—carboxamide
상기 실시예 43의 단계 1과 단계 2와 동일한 방법으로 수행하여 ,  In the same manner as in Step 1 and Step 2 of Example 43,
6-(5-(3-아미노 -5- (트리플루오로메틸 )벤즈아미도) -2-메틸피리딘 -3-일 )— "메틸- 1^인다졸 -3—카복스아미드를 얻었다. NMR (300 MHz, DMSO-^) δ  6- (5- (3-amino-5- (trifluoromethyl) benzamido) -2-methylpyridin-3-yl) — “methyl-1 ^ indazole-3—carboxamide was obtained. NMR (300 MHz, DMSO- ^) δ
13.74-13.51 (m, 1H), 10.47 (s, 1H)， 8.87 (s, 1H), 8.34 (s, 1H), 8.25 (d, J = 8.4 Hz, 1H), 8.09 (s, 1H), 7.59 (s, 1H), 7.37 (s, 2H) , 7.27 (d, J= 8.3 Hz, 1H), 7.05 (s, 1H), 5.86 (s, 2H), 2.84 (d, J= 4.7 Hz, 3H), 2.43 (s, 3H). 실시예 267.  13.74-13.51 (m, 1H), 10.47 (s, 1H), 8.87 (s, 1H), 8.34 (s, 1H), 8.25 (d, J = 8.4 Hz, 1H), 8.09 (s, 1H), 7.59 (s, 1H), 7.37 (s, 2H), 7.27 (d, J = 8.3 Hz, 1H), 7.05 (s, 1H), 5.86 (s, 2H), 2.84 (d, J = 4.7 Hz, 3H) , 2.43 (s, 3 H). Example 267.
6- ( 5— ( 3— ( 4—플루오로— 3-메틸페닐)우레이도) -2-메틸피리딘 -3-일) 메틸— 인 다졸 -3—카복스아미드의 제조  Preparation of 6- (5— (3— (4—fluoro— 3-methylphenyl) ureido) -2-methylpyridin-3-yl) methyl- indazole-3—carboxamide
Figure imgf000139_0002
상기 실시예 134와 동일한 방법으로
Figure imgf000139_0002
In the same manner as in Example 134
6—(5—아미노 -2—메틸피리딘— 3-일 )— ^메틸 -1- (테트라하이드로 -2/ 피란— 2-일 인다졸 -3_카복스아미드를 반응시켜，  6— (5—amino-2—methylpyridin— 3-yl) — ^ methyl-1- (tetrahydro-2 / pyran— 2-yl indazole-3_carboxamide,
6— (5-(3-(4—플루오로ᅳ 3-메틸페닐)우레이도)— 2-메틸피리딘 -3—일) - 메틸— 1^인 다졸 -3-카복스아미드를 얻었다. NMR (300 MHz， DMSO— ;) δ 13.60 (s, 1H)，6- (5- (3- (4—Fluoro ᅳ 3-methylphenyl) ureido)-2-methylpyridin-3-yl) -methyl-1 ^ dazole 3-carboxamide was obtained. NMR (300 MHz, DMSO— ; ) δ 13.60 (s, 1H),
8.88 (s, 1H), 8.80 (s, 1H), 8.51-8.51 (cl, J = 2.5 Hz, 1H), 8.36-8.35 (d, J = 5.2 Hz, 1H), 8.25-8.22 (m, 1H), 7.88—7.88 (d, / = 2.5 Hz, 1H), 7.56—7.55 (t. J = 1.2 Hz, 1H), 7.39-7.35 (del, J 7.2, 2.6 Hz, 1H), 7.27-7.24 (dd, J = 8.3， 1.4 Hz, 2H), 7.06-7.00 (t, /= 9.2 Hz, 1H), 2.85-2.83 (cl, J 4.7 Hz, 3H), 2.38 (s, 3H), 2.20-2.20 (cl, J = 1.9 Hz, 3H). 한편， 본 발명에 따른 상기 화학식 1로 표시되는 신규 화합물은 목적에 따라 여러 형태로 제제화가 가능하다. 다음은 본 발명에 따른 상기 화학식8.88 (s, 1H), 8.80 (s, 1H), 8.51-8.51 (cl, J = 2.5 Hz, 1H), 8.36-8.35 (d, J = 5.2 Hz, 1H), 8.25-8.22 (m, 1H) , 7.88—7.88 (d, / = 2.5 Hz, 1H), 7.56—7.55 (t. J = 1.2 Hz, 1H), 7.39-7.35 (del, J 7.2, 2.6 Hz, 1H), 7.27-7.24 (dd, J = 8.3, 1.4 Hz, 2H), 7.06-7.00 (t, / = 9.2 Hz, 1H), 2.85-2.83 (cl, J 4.7 Hz, 3H), 2.38 (s, 3H), 2.20-2.20 (cl, J = 1.9 Hz, 3H). On the other hand, the novel compound represented by Formula 1 according to the present invention can be formulated in various forms according to the purpose. The following formula according to the present invention
1로 표시되는 화합물을 활성성분으로 함유시킨 몇몇 제제화 방법을 예시한 것으로 본 발명이 이에 한정되는 것은 아니다. Some formulation methods in which the compound represented by 1 is included as an active ingredient are illustrated, but the present invention is not limited thereto.
(제제예) (Example)
제제예 1. 정제 (직접 가압)  Formulation Example 1 Tablet (Direct Pressing)
활성성분 5.0 mg을 체로 친 후, 락토스 14.1 mg, 크로스포비돈 USNF 0.8 mg 및 마그네슘 스테아레이트 0.1 ing을 흔합하고 가압하여 정제로 만들었다. 제제예 2. 정게 (습식 조립)  After sifting 5.0 mg of active ingredient, 14.1 mg of lactose, 0.8 mg of crospovidone USNF and 0.1 ing of magnesium stearate were combined and pressed to form tablets. Formulation Example 2. Crab (wet granulation)
활성성분 5.0 nig을 체로 친 후, 락토스 16.0 mg괴- 녹말 4.0 mg을 섞었다.  Sieve 5.0 nig of active ingredient and mix 16.0 mg lactose-starch 4.0 mg.
폴리솔베이트 80 0.3 g을 순수한 물에 녹인 후 이 용액의 적당량을 첨가한 다음, 미립화하였다. 건조 후에 미립을 체질한 후 콜로이달 실리콘 디옥사이드 2.7 nig 및 마그네슘 스테아레이트 2.0 ᅵ ng과 섞었다. 미립을 가압하여 정제로 만들었다. 제제예 3. 분말과 캡슬제  0.3 g of polysorbate 80 was dissolved in pure water and then an appropriate amount of this solution was added and then atomized. After drying, the fine particles were sieved and mixed with 2.7 nig of colloidal silicon dioxide and 2.0 lng of magnesium stearate. The granules were pressed into tablets. Formulation Example 3 Powder and Capsule
활성성분 5.0 mg을 체로 친 후에， 락토스 14.8 mg, 폴리비닐 피를리돈 10.0 nig, 마그네슘 스테아레이트 0.2 mg와 함께 섞었다. 흔합물을 적당한 장치를 사용하여 단단한 No. 5 젤라틴 캡슐에 채웠다. 제제예 4. 주사제  After sifting 5.0 mg of the active ingredient, 14.8 mg of lactose, 10.0 nig of polyvinyl pyridone, and 0.2 mg of magnesium stearate were mixed together. No. solid using a suitable device for the mixture Filled in 5 gelatin capsules. Formulation Example 4 Injection
활성성분으로서 100 mg을 함유시키고, 그 밖에도 만니를 180 mg, Na2HP04.12H20 26 mg 및 증류수 2974 mg를 함유시켜 주사제를 제조하였다. ' Containing 100 mg as the active ingredient and, learn more about the manni 180 mg, Na 2 HP0 4 .12H 2 0 26 mg and 2974 mg of distilled water to contain an injection was prepared. '
(실험예) 실험예 1. A375P 세포주 (혹색종)에 대한 증식 억제 활성 측정 Experimental Example 1. Measurement of proliferation inhibitory activity against A375P cell line
ATCC에서 구입한 A375P 세포주를 DMEM 배양액 [10% FBS, 1% 페니실린 /스트렙토마이신 포함]으로 5% C¾ 존재 하에서 37 °C에서 배양하였다. 배양된 A375P 세포주를 0.05% 트립신 -0.02% EDTA로 취하여 한 개 웰 (well) 당 5 X 103개의 세포를 96-well 플레이트에 넣었다. A375P cell line purchased from ATCC was cultured in DMEM [10% FBS, 1%]. With penicillin / streptomycin] at 37 ° C. in the presence of 5% C¾. Cultured A375P cell lines were taken with 0.05% trypsin -0.02% EDTA and 5 × 10 3 cells per well were placed in a 96-well plate.
세포의 생존 능력을 측정하기 위해서 다음과 같이 MTT To measure cell viability, MTT
[3-(4,5-climethylthiazol-2-yl ) -2, 5-d i phenyl tetrazol ium bromide] 활성 검색법[3- (4,5-climethylthiazol-2-yl) -2,5-d i phenyl tetrazol ium bromide] activity screening method
(CellTiter 96 Assay, Promega)을 사용하였다. 한 개의 well 당 15 uL 염료를 넣고 2 시간 동안 배양한 다음에 스롭용액 (stop solution) 100 μ L를 처리하고 24 시간 뒤에 흡광도를 측정하였다. 플레이팅한 후 하루 뒤에 화합물을 처리하였다. 화합물 처리 시에는 ΙΟηιΜ의 원료용액을 준비하였으며, 디메틸설폭사이드 (DMS0)에 3분의 1로 멸균 회석하여 12 point로 실험용 화합물 플레이트를 준비하여 0.5 u L 첨가하였다 (최종농도 DMS00.5%). (CellTiter 96 Assay, Promega) was used. 15 uL dye per one well was incubated for 2 hours, and then treated with 100 μL of a stop solution and absorbance was measured after 24 hours. Compounds were treated one day after plating. When the compound was treated, a raw material solution of ΙΟηιΜ was prepared, and dimethyl sulfoxide (DMS0) was sterilized in one-third of sterile distilled to prepare a compound plate at 12 points, and 0.5 uL was added (final concentration DMS00.5%).
EnVision2103을 사용해 590 nm 파장에서 판독하였으며， GIai값은 GraphPad Prism 4.0 소프트웨어를 사용하여 계산하였다. Readings were made at 590 nm wavelength using EnVision2103 and GI ai values were calculated using GraphPad Prism 4.0 software.
본 발명에 따른 상기 화학식 1로 표시되는 화합물들은 B-Raf-V600E Compounds represented by Formula 1 according to the present invention are B-Raf-V600E
돌연변이종이 과발현된 인간흑색종 세포주인 A375P의 증식을 억제하는 활성을 나타내었으며 , Glr„, 범위는 0.G01 내지 10 μΜ 이었다. 본 발명에 따른 몇몇 대표 화합물들의 Α375Ρ의 증식 억제활성은 하기 표 3에 나타내었다. Mutant species showed activity inhibiting the proliferation of the overexpressed human melanoma cell line A375P, Glr ', range from 0.G01 to 10 μΜ. The proliferative inhibitory activity of A375Ρ of several representative compounds according to the present invention is shown in Table 3 below.
【표 3】  Table 3
Figure imgf000141_0001
Figure imgf000142_0001
실험예 2. HCT116 세포주 (대장암)에 대한 증식 억제 활성 측정
Figure imgf000141_0001
Figure imgf000142_0001
Experimental Example 2. Measurement of proliferation inhibitory activity against HCT116 cell line (colon cancer)
ATCC에서 구입한 HCT116 세포주를 DMEM 배양액 [10% FBS, 1%  HCT116 cell line purchased from ATCC was cultured in DMEM [10% FBS, 1%
페니실린 /스트렙토마이신 (penici l lin/streptomycin)포함]으로 5% C02 존재 하에서 37 °C에서 배양하였다. 배양된 HCT116 세포주를 0.0M trypsinPenicillin / streptomycin (including penici l lin / streptomycin)] was incubated at 37 ° C in the presence of 5% CO 2 . Trypsin 0.0M in cultured HCT116 cell line
-0.02% EDTA로 취하여 한 개 wel l 당 5 X 10:;개의 세포를 96-white wel l 플레이트에 넣었다. 화합물 처리 후, 세포의 생존 능력을 측정하기 위해서 활성 검색법 Cel lTiter 96 Assay(#G7572, Pr이 ega)을 사용하였다. 한 개의 wel l 당 동량의 염료를 넣고 10분 동안 반웅 시킨 후, 다표지 시료 ' 측정장치 (EnVision2103)을 사용하여 , luminescence 700 파장에서 측정하였다. 본 발명에 따른 몇몇 대표 화합물들의 HCT116의 증식 억제활성은 하기 표 4에 나타내었다. 5 × 10 per wel l taken with −0.02% EDTA :; Cells were placed in 96-white wel l plates. After compound treatment, the activity screening Cel lTiter 96 Assay (# G7572, Pr ega) was used to measure the viability of the cells. After the same amount of dye per wel l and reacted for 10 minutes, using a multi-label sample measuring device (EnVision2103), it was measured at luminescence 700 wavelength. The proliferative inhibitory activity of HCT116 of several representative compounds according to the invention is shown in Table 4 below.
【표 4】 Table 4
Figure imgf000142_0002
Figure imgf000143_0001
Figure imgf000144_0001
Figure imgf000145_0001
실험예 3. B-Raf 키나아제 효소활성 측정 : 단계적 어세이 (Kinase Cascade Assay) 마그네슘 /ATP 용액 (500 μΜ ATP, 75 niM 마그네슘 클로라이드)을 5 μ 1씩 분주하였다. 희석된 B-Raf -V600E 효소를 2 yL 씩 분주하고 (최종농도 20 ng) 비활성화된 MEK1을 2 μ L 처리하였다 (최종농도 0.13 μ g) .
Figure imgf000142_0002
Figure imgf000143_0001
Figure imgf000144_0001
Figure imgf000145_0001
Experimental Example 3 Determination of B-Raf Kinase Enzyme Activity: Kinase Cascade Assay Magnesium / ATP solution (500 μΜ ATP, 75 niM magnesium chloride) was dispensed by 5 μl. Diluted B-Raf-V600E enzyme was dispensed by 2 yL (final concentration 20 ng) and treated with 2 μL of inactivated MEK1 (final concentration 0.13 μg).
디메틸설폭사이드 (DMS0)에 녹인 시험 화합물 용액 (ΙΟ ηιΜ)을 순차적으로 희석하여 1 uL씩 처리한 후 (DMS05%) 30 °C에서 30분 동안 반응시켰다. The test compound solution (ΙΟ ηιΜ) dissolved in dimethyl sulfoxide (DMS0) was sequentially diluted and treated in 1 uL (DMS05%) and reacted at 30 ° C for 30 minutes.
반응이 끝난 후 Kinase Glo reagent (#V6711 , pr에 lega)를 동량 넣고 10분 동안 반응시킨 후, 다표지 시료 측정장치 (EnVision2103)을 사용하여 , luminescence 700 파장에서 측정하였다.  After the reaction, the same amount of Kinase Glo reagent (# V6711, lega in pr) was added and reacted for 10 minutes, and then measured using a multi-label sample measuring device (EnVision2103) at luminescence 700 wavelength.
본 발명에 따른 상기 화학식 1로 표시되는 화합물들은 B-Raf 키나아제 저해 활성을 나타내었으며, ICW,의 범위는 0.12 내지 20 μΜ 이었다. 본 발명에 따른 몇몇 대표 화합물들의 B-Raf 키나아제 저해 활성은 하기 표 5와 같다. 【표 5】 Compounds represented by the formula (1) according to the present invention showed a B-Raf kinase inhibitory activity, IC W , the range of 0.12 to 20 μΜ. The B-Raf kinase inhibitory activity of some representative compounds according to the invention is shown in Table 5 below. Table 5
Figure imgf000145_0002
Figure imgf000145_0002

Claims

【청구범위】 【청구항 1】 하기 화학식 1로 표시되는 3， 6ᅳ이치환된 인다졸 유도체， 약학적으로 허용되는 이의 염, 이의 수화물， 이의 용매화물 및 이의 이성질체로부터 선택된 화합물 ： Claims Claim 1 A compound selected from 3, 6-substituted indazole derivatives represented by the following formula (1), a pharmaceutically acceptable salt thereof, a hydrate thereof, a solvate thereof and an isomer thereof:
[화학식 1]  [Formula 1]
Figure imgf000146_0001
Figure imgf000146_0001
상기 화학식 1에서，  In Chemical Formula 1,
八^은 아릴렌기; 바이아릴렌기; 2가 해테로방향족고리기; 또는 2가  八 ^ is an arylene group; Biarylene group; Divalent heteroaromatic ring; Or 2
해테로지방족고리기를 나타내고,  Heterocyclic aliphatic ring,
Ar2는 단일결합선이거나; 아릴렌기; 바이아릴렌기; 2가 해테로방향족고리기; 또는 2가 해테로지방족고리기를 나타내고， Ar 2 is a single bond line; Arylene group; Biarylene group; Divalent heteroaromatic ring; Or 2 represents a heteroaliphatic ring,
X 및 L은 서로 같거나 다른 것으로서 단일결합선이거나; — C(O)ᅳ; ᅳ NR5-; X and L are the same or different from each other and are a single bond line; — C (O) ′; NR 5- ;
-NR5-C(0)-; -C(0)NR5-; -C(0)NR5NR6-; — C(0)NR5-(CH2)n— (n은 1 내지 10의 정수);-NR 5 -C (0)-; -C (0) NR 5- ; -C (0) NR 5 NR 6- ; — C (0) NR 5 — (CH 2 ) n — (n is an integer from 1 to 10);
-NR5-C(0)-NR6; -NR5-C(S)-NR6; 또는 -NR5-S(0)0- ； 를 나타내고， -NR 5 -C (0) -NR 6 ; -NR 5 -C (S) -NR 6 ; Or -NR 5 -S (0) 0- ;;
R1 및 R2는 서로 같거나 다른 것으로서 수소원자;— N¾; -OR4; -NR¾6; -NR5C(0)R8;R 1 and R 2 are the same as or different from each other and are a hydrogen atom; -OR 4 ; -NR¾ 6 ; -NR 5 C (0) R 8 ;
-C(0)R8; -C(0)0R4; -CN, -N02) -OR4, -NR5R6, -NR5C(0)R8, -C(0)R8, -C(0)0R4, 아릴， 해테로방향족고리, 및 헤테로지방족고리로 이루어진 군으로부터 선택된 치환체로 치환또는 비치환된 직쇄, 분지형 또는 환형의 d— C10알킬기 ; 아릴기 ; 헤테로방향족고리기; 또는 해테로지방족고리기; 를 나타내고， -C (0) R 8 ; -C (0) 0R 4 ; -CN, -N0 2) -OR 4 , -NR 5 R 6 , -NR 5 C (0) R 8 , -C (0) R 8 , -C (0) 0R 4 , aryl, heteroaromatic ring, And a straight chain, branched or cyclic d—C 10 alkyl group unsubstituted or substituted with a substituent selected from the group consisting of heteroaliphatic rings; Aryl group; Heteroaromatic ring groups; Or heteroaliphatic ring groups; ,
또한 상기 R1과 R2는 서로 결합하여 해테로방향족고리기; 또는 In addition, R 1 and R 2 are bonded to each other heteroaromatic ring group; or
해테로지방족고리기를 형성할 수 있으며，  Can form a heteroaliphatic ring,
R3은 수소원자; 할로겐원자; CN;一 N¾; -OR4; -SR4;— NR¾6; -NR5(C C10알킬렌 -OR4); — NR^d-do알킬렌ᅳ NR¾6)； -NR5 (해테로지방족고리 ) — NR5(해테로방향족고리 )； ᅳ NR5(dᅳ C10알킬렌ᅳ해테로지방족고리 )； — NR^d-do알킬렌-해테로방향족고리 )； -NR5(d-C10알킬렌ᅳ해테로방향족고리 )； — NR5C(0)ᅳ해테로지방족고리； R 3 is a hydrogen atom; Halogen atom; CN; 一 N¾; -OR 4 ; -SR 4 ; — NR¾ 6 ; -NR 5 (CC 10 alkylene-OR 4 ); — NR ^ d-doalkylene ᅳ NR¾ 6 ); -NR 5 (heteroaliphatic ring) — NR 5 (heteroaromatic ring); ᅳ NR 5 (d ᅳ C 10 alkylene ᅳ heteroaliphatic ring); NR ^ d-doalkylene-heteroaromatic ring) -NR 5 (dC 10 alkylene-heteroaromatic ring); — NR 5 C (0) heteroaliphatic ring;
-NR¾(0)-해테로방향족고리; — NR¾(0)R8; -NR¾(0)0R4, -NR5C(0)-(d-C10 알킬렌— NR¾6); -C(0)R8; -C(0)0R4; 할로겐， ᅳ CN, ᅳ N02, -OR4, -NR¾6, -NR5^— C10 알킬렌— NR¾6), =N(0H) , NR5C(0)0R4, -C(0)R8, — C(0)0R4로 이루어진 군으로부터 선택된 치환기로 치환체로 치환또는 비치환된 직쇄, 분지형 또는 환형의 Crdo알킬기; 할로겐원자가 1 내지 20개 치환된 직쇄 또는 분지형의 d— C10 할로알킬기; 아릴기; 해테로방향족고리기; 또는 해테로지방족고리기; 를 나타내고， -NR¾ (0) -heteroaromatic ring; — NR¾ (0) R 8 ; -NR¾ (0) 0R 4 , -NR 5 C (0)-(dC 10 alkylene—NRNR 6 ); -C (0) R 8 ; -C (0) 0R 4 ; Halogen, ᅳ CN, ᅳ N0 2 , -OR 4 , -NR¾ 6 , -NR 5 ^ — C 10 alkylene— NR¾ 6 ), = N (0H), NR 5 C (0) 0R 4 , -C (0 ) R 8 , — straight, branched or cyclic Crdoalkyl group unsubstituted or substituted with a substituent selected from the group consisting of C (0) 0R 4 ; Linear or branched d—C 10 haloalkyl group having 1 to 20 halogen atoms; Aryl group; Heteroaromatic ring groups; Or heteroaliphatic ring groups; ,
또한， 상기 치환기 정의에 사용된 아릴렌, 바이아릴렌， 아릴，  In addition, arylene, biarylene, aryl, used in the above substituent definition
해테로방향족고리， 또는 해테로지방족고리는 각각 독립적으로 수소원자;  The heteroaromatic ring or the heteroaliphatic ring are each independently a hydrogen atom;
할로겐원자; 직쇄， 분지형 또는 환형의 포화또는 불포화된 -(：6알킬기; Halogen atom; Straight chain, branched or cyclic saturated or unsaturated — (： 6 alkyl groups);
할로겐원자가 내지 10개 포함된 d-C6할로알킬기 ; 시아노기 ; 옥소 (=0); -N02; -OBoc; -OR4; -(CH2)„-OR4-0(CH2)nNR5R6; — NR¾6; -NR5C(0)R8;— NR (0)NR¾7; -C(0)R8; DC 6 haloalkyl group containing from 10 to 10 halogen atoms; Cyano group; Oxo (= 0); -N0 2 ; -OBoc; -OR 4 ; -(CH 2 ) „-OR 4 -0 (CH 2 ) n NR 5 R 6 ; — NR¾ 6 ; -NR 5 C (0) R 8 ; — NR (0) NR¾ 7 ; -C (0) R 8 ;
145  145
대체용지 (규칙 제 26조) -C(0)0R4; -C(0)NR¾6; -C(0)NH(CH2)nNR¾6; -S(0)R8; ᅳ S(0)2R8; — S(0)2NR¾6; 아릴기 ; 바이아릴기; 헤테로방향족고리기; 또는 해테로지방족고리기; 로 이루어진 군으로부터 선택된 1 내지 3개의 치환체로 치환또는 비치환되며， 이때 n은 1 내지 6의 정수이고， Alternative Site (Article 26) -C (0) 0R 4 ; -C (0) NR 3 6 ; -C (0) NH (CH 2 ) n NR¾ 6 ; -S (0) R 8 ; S (0) 2 R 8 ; — S (0) 2 NR¾ 6 ; Aryl group; Biaryl group; Heteroaromatic ring groups; Or heteroaliphatic ring groups; Is substituted or unsubstituted with 1 to 3 substituents selected from the group consisting of, where n is an integer of 1 to 6,
R4는 수소원자; 직쇄， 분지형 또는 환형의 포화 또는 불포화된 Crdo알킬기 ; 할로겐원자가 ： 내지 10개 포함된 <： (：6할로알킬기 ; d-C10알킬렌— O— ^—CK) 알킬); — ( — C10알킬렌) NR¾6; -(d"^알킬렌) -해테로지방족고리 ; -(d-C10 알킬렌)—헤테로방향족고리 ; 해테로지방족고리기; 또는 헤테로방향족고리기; 를 나타내고， R 4 is a hydrogen atom; Linear, branched or cyclic saturated or unsaturated Crdoalkyl groups; <: (: 6 haloalkyl group; dC 10 alkylene— O— ^ —CK ) alkyl containing from 10 to 10 halogen atoms); — (— C 10 alkylene) NR¾ 6 ; - (d "^ alkylene) - by interrogating an aliphatic ring;; by interrogating an aliphatic ring group, - (dC 10 alkylene) represents a heteroaromatic ring; group or a heteroaromatic ring
R5, R6, R7 및 R8은 서로 같거나 다른 것으로서 수소원자; 직쇄, 분지형 또는 환형의 포화또는 볼포화된 C— C10알킬기; 또는 아릴기; 를 나타내며， 상기 치환기 정의에 사용된 아릴 또는 아릴렌은 단일고리， 두고리 또는 세고리로 이루어지고， 핵원자수가 5 내지 15개인 방향족 탄화수소기를 R 5 , R 6 , R 7 and R 8 are the same as or different from each other and are a hydrogen atom; Straight chain, branched or cyclic saturated or ball-saturated C—C 10 alkyl groups; Or an aryl group; The aryl or arylene used in the above substituent definition consists of a single ring, a bicyclic ring or a three ring, and has an aromatic hydrocarbon group of 5 to 15 nuclear atoms.
나타내고;  Represent;
상기 치환기 정의에 사용된 헤테로방향족고리는 N, 0 및 S 증에서 선택된 헤테로원자가 1 내지 4개 포함되고， 단일고리， 두고리 또는 세고리로  The heteroaromatic ring used in the above substituent definition includes 1 to 4 heteroatoms selected from N, 0 and S, and may be selected from monocyclic, bicyclic or tricyclic.
이루어지고， 핵원자수가 5내지 15개인 방향족 헤테로탄화수소기를 나타내고; 상기 치환기 정의에 사용된 해테로지방족고리는 N, 0 및 S 중에서 선택된 해테로원자가 1 내지 4개 포함되고， 단일고리, 두고리 또는 세고리로  An aromatic heterohydrocarbon group having 5 to 15 nuclear atoms; The heteroaliphatic ring used in the above substituent definition includes 1 to 4 heteroatoms selected from N, 0, and S, monocyclic, bicyclic or tricyclic
이루어지고， 불포화 탄소사슬을 포함 또는 미포함할 수 있는 핵원자수가 5 내지 15개인 지방족 해테로탄화수소기를 나타낸다.  And an aliphatic heterohydrocarbon group having 5 to 15 nuclear atoms, which may or may not contain an unsaturated carbon chain.
【청구항 2】 [Claim 2]
청구항 1에 있어서，  The method according to claim 1,
상기 은 할로겐， d— C6알킬 및 d-Ce할로알킬로 이루어진 군으로부터 선택된 치환체가 1 내지 4개 치환또는 비치환된 핵원자수가 5내지 7인 아릴렌기를 나타내고, The silver represents an arylene group having 5 to 7 nuclear atoms having 1 to 4 substituted or unsubstituted substituents selected from the group consisting of halogen, d—C 6 alkyl and d-Ce haloalkyl,
상기 Ar2는 단일결합선이거나; 할로겐， C^Ce알킬 및 d— C6할로알킬로 이루어진 군으로부터 선택된 치환체가 1 내지 4개 치환또는 비치환된 핵원자수가 5 내지 8인 아릴렌기 ; 할로겐， — C6알킬 및 d-C6할로알킬로 이루어진 Ar 2 is a single bond line; An arylene group having 5 to 8 substituted or unsubstituted nuclear atoms having 1 to 4 substituents selected from the group consisting of halogen, C ^ Cealkyl and d—C 6 haloalkyl; Halogen, — consisting of C 6 alkyl and dC 6 haloalkyl
군으로부터 선택된 치환체가 1 내지 4개 치환또는 비치환된 핵원자수가 5 내지 8인 2가 해테로방향족고리기; 또는 할로겐， Cr i알킬 및 d- 할로알킬로 이루어진 군으로부터 선택된 치환체가 1 내지 4개 치환또는 비치환된 핵원자수가 5 내지 8인 2가 해테로지방족고리기; 를 나타내고，  A divalent heteroaromatic ring group having 5 to 8 substituted or unsubstituted nuclear atoms having 1 to 4 substituents selected from the group; Or a divalent heteroaliphatic ring having 5 to 8 substituted or unsubstituted nuclear atoms having 1 to 4 substituents selected from the group consisting of halogen, Cr ialkyl and d-haloalkyl; ,
상기 X 및 L은 서로 같거나 다른 것으로서 단일결합선이거나; — NH—； -N(C¾)-; X and L are the same as or different from each other and are a single bond line; —NH—; -N (C¾)-;
-NHC(O)一; -C(0)NH-; -C(0)NHNH-; -C(0)NHCH2-; — C(0)NHC¾CH2—； — NHC(0)NH_; -NHC(0)N(CH3)-; -NHC(S)NH-; 또는 — NHS02- 를 나타내고， -NHC (O) l; -C (0) NH-; -C (0) NHNH-; -C (0) NHCH 2- ; — C (0) NHC¾CH 2 —; — NHC (0) NH_; -NHC (0) N (CH 3 )-; -NHC (S) NH-; Or — NHS0 2- ;
상기 R1 및 R2는 서로 같거나 다른 것으로서 수소원자; — OH; C-Ce알킬기; R 1 and R 2 are the same as or different from each other as a hydrogen atom; — OH; C-Ce alkyl group;
-0-(C C6알킬); -d-C6하이드록시알킬기； -(C C6알킬렌)ᅳ해테로지방족고리； -(C C6알킬렌)—헤테로방향족고리； -(d— C6알킬렌) -아릴； 아릴기； -0- (CC 6 alkyl); -dC 6 hydroxyalkyl group;-(CC 6 alkylene) -heteroaliphatic ring;-(CC 6 alkylene) -heteroaromatic ring;-(d—C 6 alkylene) -aryl;
해테로방향족고리기； 또는 해테로지방족고리기를 나타내고， 또한상기 R1과 Heteroaromatic ring group; or a heteroaliphatic ring group, and R 1 and
R2는 서로 결합하여 해테로방향족고리기; 또는 해테로지방족고리기를 형성할수 있으며 , 이때 상기 아릴， 해테로방향족고리 , 및 해테로지방족고리는 각각 R 2 is a heteroaromatic ring group bonded to each other; Or a heteroaliphatic ring group, wherein the aryl, heteroaromatic ring, and heteroaliphatic ring, respectively
146  146
대체용지 (규칙 제 26조) 독립적으로 할로겐， d— C6알킬， 및 d— c6할로알킬로 이루어진 군으로부터 선택된 1 내지 3개의 치환체로 치환또는 비치환될 수 있고， Alternative Site (Article 26) Independently substituted or unsubstituted with 1 to 3 substituents selected from the group consisting of halogen, d—C 6 alkyl, and d—c 6 haloalkyl,
상기 R3은 수소원자; 할로겐원자; CN; -N02; -OH; -SH; -NH2; -NH(d— C10알킬)； -N(d-C10알킬 )2; Ci-do알킬기 ; d-C10할로알킬기; d一 C10시아노알킬기; d-C10 하이드록시알킬기； C2-C10알콕시알킬기； — (Xd-do알킬 )； — 0(d— C10할로알킬 )；R 3 is a hydrogen atom; Halogen atom; CN; -N0 2 ; -OH; -SH; -NH 2 ; -NH (d—C 10 alkyl);-N (dC 10 alkyl) 2 ; Ci-do alkyl group; dC 10 haloalkyl group; d one C 10 cyanoalkyl group; dC 10 hydroxyalkyl group; C 2 -C 10 alkoxyalkyl group; — (Xd-doalkyl); — 0 (d—C 10 haloalkyl);
-S(d— C10알킬)； -S(d— C10할로알킬); — (Crdo알킬렌)— N¾; -(d-C10 -S (d—C 10 alkyl);-S (d—C 10 haloalkyl); — (Crdoalkylene) — N¾; -(dC 10
알킬렌)— NKd-do알킬)； -(Cr C10알킬렌)— d-d。알킬 )2; -(C do Alkylene) — NKd-doalkyl)-(C r C 10 alkylene) — dd。 alkyl) 2 ; -(C do
알킬렌)— N d-do알킬렌)— N(d-C10알킬 )2]^— C10알킬]; -(d-C10 Alkylene) —N d-doalkylene) —N (dC 10 alkyl) 2] ^ — C 10 alkyl]; -(dC 10
알킬렌)— (하이드록시이미노); (Crdo알킬렌) -NH2; -O-Cd-do Alkylene) — (hydroxyimino); (Crdoalkylene) -NH 2 ; -O-Cd-do
알킬렌) -NH(d-C10알킬)； -0— (Crdo알킬렌 )— N ^-do알킬 )2; -0-(C C10 알킬렌) -해테로지방족고리； -0—해테로지방족고리； —NlKdᅳ C10알킬렌ᅳ NH2)； -NH[C C10알킬렌 -NH(d-C10알킬) ]； -NHtd-do알킬렌 -N(d-C10알킬 )2]； -N[C C10 알킬] [Crdo알킬렌 -NH(d— C10알킬)]； -N[C-C10알킬] [Crdo알킬렌—N C10 알킬 )2] -NH(d-C10하이드록시알킬); -N(d-C10알킬) (d-C10하이드록시알킬)； -NH(해테로지방족고리 )； — N(d-C10알킬 ) (해테로지방족고리 )； -NH(dᅳ C10 알킬렌-헤테로지방족고리); -N(d-C10알킬) (d-do알킬렌-해테로지방족고리); 一 NHC(O)-해테로지방족고리 ; -NKXOXd-do알킬); -NHC(0)0-(C C10알킬)， - HC(0)-(C C10알킬렌 -NR5R6);—C(0) (Crdo알킬 ); -C(0)0H; -C(O)O(d-C10알킬); 아릴기; 해테로방향족고리기; 또는 해테로지방족고리기; 를 나타내고， 이때 아릴， 해테로방향족고리， 또는 해테로지방족고리는 각각 독립적으로 할로겐，Alkylene) -NH (dC 10 alkyl); -0— (Crdoalkylene) —N ^ -doalkyl) 2 ; -0- (CC 10 alkylene) -heteroaliphatic ring; -0—heteroaliphatic ring; —NlKd ᅳ C 10 alkylene ᅳ NH 2 ); -NH [CC 10 alkylene -NH (dC 10 alkyl)] -NHtd-doalkylene -N (dC 10 alkyl) 2 ]; -N [CC 10 alkyl] [Crdoalkylene -NH (d—C 10 alkyl)]; -N [CC 10 alkyl] [Crdoalkylene —NC 10 alkyl) 2] —NH (dC 10 hydroxyalkyl); -N (dC 10 alkyl) (dC 10 hydroxyalkyl); -NH (heteroaliphatic ring); — N (dC 10 alkyl) (heteroaliphatic ring); -NH (d ᅳ C 10 alkylene-heteroaliphatic ring); -N (dC 10 alkyl) (d-doalkylene-heteroaliphatic ring); One NHC (O) -heteroaliphatic ring; -NKXOXd-doalkyl); -NHC (0) 0- (CC 10 alkyl),-HC (0)-(CC 10 alkylene -NR 5 R 6 ); — C (0) (Crdoalkyl); -C (0) 0H; -C (O) O (dC 10 alkyl); Aryl group; Heteroaromatic ring groups; Or heteroaliphatic ring groups; Wherein aryl, heteroaromatic ring, or heteroaliphatic ring are each independently halogen,
-OH, -CN, 옥소 (=0)， C C6알킬， C C6할로알킬， d-C6알콕시， C C6알킬렌 -(d-C6 알콕시), d— C6알킬렌 -C(0)ᅳ NH2; ( ;알킬렌 -(XW-NlKdᅳ C6알킬); C C6 알킬렌 -C(0)-N(CrC6알킬 )2; d-C6알킬렌— C(0)-아릴 ; -C(0)(d-C6알킬)， — C(0) (아릴) , -C(0) (해테로방향족고리)， — COOH, -CXOXXd- ;알킬)， -S(0)(C C6 알킬)， -5(0)2 ^ ；알킬)， -NH2, H(d— (：6알킬)， 및 N(d-C6알킬 )2로 이루어진 군으로부터 선택된 1 내지 3개의 치환체로 치환또는 비치환되며， -OH, -CN, oxo (= 0), CC 6 alkyl, CC 6 haloalkyl, dC 6 alkoxy, CC 6 alkylene-(dC 6 alkoxy), d—C 6 alkylene -C (0) ᅳ NH 2 ; (; Alkylene-(XW-NlKd ᅳ C 6 alkyl); CC 6 alkylene -C (0) -N (CrC 6 alkyl) 2 ; dC 6 alkylene— C (0) -aryl; -C (0) (dC 6 alkyl) ， — C (0) (aryl), —C (0) (heteroaromatic ring) ， — COOH, —CXOXXd-; alkyl) ，-S (0) (CC 6 alkyl) ，-5 (0) 2 ^; alkyl), -NH 2 , H (d— (: 6 alkyl), and N (dC 6 alkyl) 2 It is substituted or unsubstituted with 1 to 3 substituents selected from the group consisting of,
상기 치환기 정의에 사용된 아릴 또는 아릴렌은 단일고리， 두고리 또는 세고리로 이루어지고， 핵원자수가 5 내지 15개인 방향족 탄화수소기를 나타내고;  Aryl or arylene used in the above substituent definition consists of a monocyclic, bicyclic or tricyclic, and represents an aromatic hydrocarbon group having 5 to 15 nuclear atoms;
상기 치환기 정의에 사용된 해테로방향족고리는 N, 0및 S 중에서 선택된 해테로원자가 1 내지 4개 포함되고， 단일고리， 두고리 또는 세고리로  The heteroaromatic ring used in the substituent definition includes 1 to 4 heteroatoms selected from N, 0, and S, monocyclic, bicyclic or tricyclic
이루어지고, 핵원자수가 5 내지 15개인 방향족 해테로탄화수소기를 나타내고; 상기 치환기 정의에 사용된 해테로지방족고리는 N, 0 및 S중에서 선택된 해테로원자가 1 내지 4개 포함되고， 단일고리, 두고리 또는 세고리로  An aromatic heterohydrocarbon group having 5 to 15 nuclear atoms; The heteroaliphatic ring used in the substituent definition includes 1 to 4 heteroatoms selected from N, 0, and S, monocyclic, bicyclic or tricyclic
이루어지고, 블포화 탄소사술을 포함또는 미포함할 수 있는 핵원자수가 5 내지 15개인 지방족 해테로탄화수소기를 나타낸다.  And an aliphatic heterohydrocarbon group having 5 to 15 nuclear atoms, which may or may not include saturated carbon hex.
【청구항 3】 [Claim 3]
청구항 1에 있어서，  The method according to claim 1,
상기 Arr^ 클로로， 플루오로, 브로모， 메틸 및 트리플루오로메틸로 이루어진 군으로부터 선택된 치환체가 1 내지 2개 치환 또는 비치환된 페닐렌을  Arr ^ phenylene having 1 to 2 substituted or unsubstituted substituents selected from the group consisting of chloro, fluoro, bromo, methyl and trifluoromethyl
나타내고;  Represent;
상기 Ar2는 단일결합선이거나， 클로로， 플루오로， 브로모, 메틸 및 Ar 2 is a single bond, or chloro, fluoro, bromo, methyl and
147  147
대체용지 (규칙 제 26조) 트리플루오로메틸로 이루어진 군으로부터 선택된 치환체가 1 내지 2개 치환 또는 비치환된 페닐렌， 피리디닐렌， 피라지닐렌, 피라지닐렌， 이미다졸일렌， 이미다졸일렌， 피라졸일렌， 옥사졸일렌， 이소옥사졸일렌， 티아졸일렌， 퓨란일렌 피페리딘일렌， 피롤리딘일렌， 또는 벤조 [d][l,3]디옥솔 -5—일렌을 나타내는 것을 특징으로 하는 화합물. Alternative Site (Article 26) Phenylene, pyridinylene, pyrazinylene, pyrazinylene, imidazolylene, imidazolylene, pyrazolylene, oxazolylene having 1 to 2 substituents or unsubstituted substituents selected from the group consisting of trifluoromethyl Or isoxoxazolylene, thiazolylene, furanylene piperidinylene, pyrrolidinylene, or benzo [d] [l, 3] dioxol-5—ylene.
【청구항 4】 [Claim 4]
청구항 1에 있어서，  The method according to claim 1,
상기 X는 단일결합이거나， — NH―， 또는 -N(CH3)— 를 나타내는 것을 특징으로 하는 화합물. X is a single bond, or — NH —, or —N (CH 3 ).
【청구항 5】 [Claim 5]
청구항 1에 있어서，  The method according to claim 1,
상기 L은 - HC(O)-, -C(0)NH ―， -C(0)NHNH—， — C(0)NHC¾-, — C(0)NHCH2C¾— , — NHC(0)NH―， -NHC(0)N(CH3)- , -NHC(S)NH-, 또는 -NHS02— 를 나타내는 것을 특징으로 하는 화합물. L is-HC (O)-, -C (0) NH-, -C (0) NHNH—, — C (0) NHC¾-, — C (0) NHCH 2 C¾—, — NHC (0) NH -, -NHC (0) N (CH 3 )-, -NHC (S) NH-, or -NHS0 2 —.
【청구항 6】 [Claim 6]
청구항 1에 있어서，  The method according to claim 1,
상기 R1및 R2는 서로 같거나 다른 것으로서 수소원자, 하이드록시기， 메틸기, 에틸기， 프로필기， 이소프로필기， 싸이클로프로필기， 싸이클로핵실기, 하이드록시에틸기， 몰포리노기; 몰포리노에틸기， 피페리딘 -4—일기, R 1 and R 2 are the same as or different from each other and are a hydrogen atom, a hydroxy group, a methyl group, an ethyl group, a propyl group, isopropyl group, a cyclopropyl group, a cyclonuclear group, a hydroxyethyl group, and a morpholino group; Morpholinoethyl group, piperidine-4—diary,
1—메틸피페리딘 -4-일기， 피페라진 -1-일기， 4-메틸피페라진—1-일기, 페닐기, 벤질기， 피리딘ᅩ2-일기， 피리딘 -3-일기， 피리딘 -4-일기， (피리딘 -2-일)메틸기， (피리딘ᅳ 3—일)메틸기, (피리딘 -4-일)메틸기， (6-클로로피리딘—3-일)메틸기， 1—Methylpiperidin-4-yl, piperazine-1-yl, 4-methylpiperazin—1-yl, phenyl, benzyl, pyridin ᅩ 2-yl, pyridin-3-yl, pyridin-4-yl , (Pyridin-2-yl) methyl group, (pyridinyl 3-yl) methyl group, (pyridin-4-yl) methyl group, (6-chloropyridin- 3-yl) methyl group ，
2-플루오로피리딘— 3-일기， 5ᅳ플루오로피리딘 -3-일기， 6—플루오로피리딘 -3—일기， 4-메틸피리딘— 3—일기， 6-메틸피리딘 -3-일기， 피리미딘 -3-일기， 피리미딘 -4-일기， (피리미딘 -3ᅳ일)메틸기， (피리미딘 -4-일)메틸기， 피리미딘— 5—일기，  2-fluoropyridine- 3-yl group, 5 ᅳ fluoropyridin-3-yl group, 6-fluoropyridine-3-yl group, 4-methylpyridine- 3-yl group, 6-methylpyridin-3-yl group, pyrimidine -3-yl group, pyrimidin-4-yl group, (pyrimidin-3 yl) methyl group, (pyrimidin-4-yl) methyl group, pyrimidine— 5—yl group ，
이미다졸— 4-일기， 1-메틸이미다졸 -4—일기， (이미다졸 -2-일)메틸기， 또는 피롤리딘— 3-일기를 나타내고, 또는 상기 R1및 R2가 서로 결합하여 피페라지닐기， 또는 4-메틸피페라진 -1-일기를 형성할 수 있는 것을 특징으로 하는 화합물. Imidazole— 4-yl group, 1-methylimidazole-4—yl group, (imidazol-2-yl) methyl group, or pyrrolidin—3-yl group, or R 1 and R 2 are bonded to each other A compound characterized by being able to form a piperazinyl group or a 4-methylpiperazin-1-yl group.
【청구항 71 [Claim 71
청구항 1에 있어서,  The method according to claim 1,
상기 R3은 수소원자, 클로로원자， 폴루오로원자， 브로모원자， 시아노기， 니트로기, 하이드록시기， 아세틸기， 메틸기, 에틸기， 이소프로필기， ar/-부틸기， 브로모메틸기， 시아노프로필기， 디메틸아미노메틸기， R 3 represents a hydrogen atom, a chloro atom, a polo atom, a bromo atom, a cyano group, a nitro group, a hydroxyl group, an acetyl group, a methyl group, an ethyl group, an isopropyl group, ar / -butyl group, bromomethyl group, Cyanopropyl group, dimethylaminomethyl group,
( (2-디메틸아미노에틸) (메틸)아미노)메틸기， 1- (하이드록시이미노)에틸기， 트리플루오로메틸기， (트리플루오로메틸)싸이오기， 메록시기，  ((2-dimethylaminoethyl) (methyl) amino) methyl group, 1- (hydroxyimino) ethyl group, trifluoromethyl group, (trifluoromethyl) thio group, hydroxy group,
디플루오로메특시기， 트리플루오로메록시기, 2_ (디메틸아미노)에톡시기， 피페리딘 -4—일메록시기 , (1-메틸피페리딘 -4-일 )메톡시기，  Difluoromethoxy group, trifluoromethoxy group, 2_ (dimethylamino) ethoxy group, piperidine-4-ylmethoxy group, (1-methylpiperidin-4-yl) methoxy group,
2- (피롤리딘— 1—일)에록시기， 2-(1-메틸피롤리딘 -2-일)에록시기,  2- (pyrrolidin— 1—yl) ethoxy group, 2- (1-methylpyrrolidin-2-yl) ethoxy group,
2-아미노 -2-메틸프로폭시기， 1- (디메틸아미노)프로판 -2—일옥시기，  2-amino-2-methylpropoxy group, 1- (dimethylamino) propane-2-ylyl group,
148  148
대체용지 (규칙 제 26조) 2- (디메틸아미노) -2-메틸프로폭시기, 피페리딘 -4—일옥시기， (1-메틸피페리딘—4-일)옥시기， 아미노기, 메틸아미노기, 디메틸아미노기， (2-아미노에틸)아미노기 , (2-아미노—2-메틸프로필)아미노기， Alternative Site (Article 26) 2- (dimethylamino) -2-methylpropoxy group, piperidine-4-ylyl group, (1-methylpiperidin-4-yl) oxy group, amino group, methylamino group, dimethylamino group, (2-amino Ethyl) amino group, (2-amino-2-methylpropyl) amino group,
(2-디메틸아미노 -2-메틸프로필)아미노기， (2-하이드록시에틸 )아미노기 , (2-하이드록시프로필)아미노기， (3-하이드록시프로필)아미노기，  (2-dimethylamino-2-methylpropyl) amino group, (2-hydroxyethyl) amino group, (2-hydroxypropyl) amino group, (3-hydroxypropyl) amino group,
(2一하이드록시부틸)아미노기， (2-디메틸아미노에틸)아미노기，  (2 one hydroxybutyl) amino group, (2-dimethylaminoethyl) amino group,
(2-디메틸아미노에틸) (메틸 )아미노기， (2-하이드록시에틸) (메틸)아미노기， (2-하이드록시— 2-메틸프로필)아미노기，  (2-dimethylaminoethyl) (methyl) amino group, (2-hydroxyethyl) (methyl) amino group, (2-hydroxy- 2-methylpropyl) amino group,
(메틸 )((1-메틸ᅳ 1^피라졸 -4-일)메틸)아미노기, (피롤리딘 -1—일에틸)아미노기， (테트라하이드로— 2 피란— 4ᅳ일)아미노기,  (Methyl) ((1-methyl ᅳ 1 ^ pyrazol-4-yl) methyl) amino group, (pyrrolidin-1-ylethyl) amino group, (tetrahydro-2 pyran- 4 ᅳ yl) amino group,
(1,2,2,6,6-펜타메틸피페리딘 -4ᅳ일)아미노기， (1一메틸피페리딘 -4—일)아미노기, (1,2,2,6,6-pentamethylpiperidin-4xyl) amino group, (1 one methylpiperidin-4-yl) amino group,
1-아세틸피페리딘 -4-카복스아미도기, 2- (디메틸아미노)아세트아미도기, 페닐기 4-클로로페닐기， 4-플루오로페닐기， 4—메특시페닐기, 4-하이드록시페닐기, 피리딘—2-일기， 피리딘 -3-일기， 피리딘 -4-일기, 피페라진 -1ᅳ일기， 1-acetylpiperidine-4-carboxamido group, 2- (dimethylamino) acetamido group, phenyl group 4-chlorophenyl group, 4-fluorophenyl group, 4—methoxyphenyl group, 4-hydroxyphenyl group, pyridine— 2-yl, pyridine-3-yl, pyridine-4-yl, piperazine-1
4-메틸피페라진ᅳ1-일기， 4-에틸피페라진 -1-일기, 부틸피페라진 -1-일기， 4-methyl piperazine- 1-yl group, 4-ethyl piperazine-1-yl group, butyl piperazine-1-yl group,
3， 5ᅳ디메틸피페라진ᅳ 1-일기， 3， 4 , 5-트리메틸피페라진 -1-일기 , 3,5'dimethylpiperazin '1-yl group, 3, 4, 5-trimethylpiperazine-1-yl group,
4-(2-메록시에틸)피페라진 -1-일기 , 4- (메틸설포닐)피페라진ᅳ 1-일기，  4- (2-methoxyethyl) piperazine-1-yl group, 4- (methylsulfonyl) piperazine ᅳ 1-yl group,
4—아세틸피페라진 -1-일기， 4-니코티노일피페라진 -1-일기，  4-—acetylpiperazin-1-yl group, 4-nicotinoylpiperazin-1-yl group,
4一 (2- (디메틸아미노) -2-옥소에틸)피페라진—1-일기,  4 one (2- (dimethylamino) -2-oxoethyl) piperazine—1-yl group,
4— (2-옥소 -2- (페닐아미노)에틸)피페라진— 1-일기 ,  4— (2-oxo-2- (phenylamino) ethyl) piperazine— 1-yl group,
4- (이소프로필설포닐)피페라진— 1-일기， 4-벤조일피페라진 -1ᅳ일기， 이미다졸기， 4- (isopropylsulfonyl) piperazine— 1-yl, 4-benzoylpiperazine-1 -yl, imidazole,
2-메틸이미다졸기， 4-메틸이미다졸기， 2, 4-디메틸이미다졸기， 피롤리디닐기，2-methylimidazole group, 4-methylimidazole group, 2, 4-dimethylimidazole group, pyrrolidinyl group,
3-하이드록시피롤리딘—1—일기， 3- (디메틸아미노)피롤리딘— 1-일기， 3-hydroxypyrrolidine—1—yl, 3- (dimethylamino) pyrrolidine— 1-yl,
3- (디에틸아미노)피롤리딘 -1—일기, 4-메틸— 1，4-디아제판 -1-일기,  3- (diethylamino) pyrrolidine-1-yl group, 4-methyl- 1,4-diazepane-1-yl group,
핵사하이드로피를로 [1，2— a]피라진 -2(1^)-일기，  Nucleohydropyrrolo [1,2—a] pyrazine-2 (1 ^)-diary
1,4-디옥사 -8—아자스피로 [4,5]데칸— 8—일기， 몰포리노기, 피페리딘— 1—일기, 1,4-dioxa-8—azaspiro [4,5] decane—8—diary, morpholino group, piperidine— 1—diary,
4-옥소피페리딘—1-일기， 4一하이드록시피페리딘 -1-일기， 4-메틸피페리딘 -1-일기 4一이소프로필피페리딘 -1-일기， 4-메특시피페리딘 -1-일기， 4-oxopiperidine- 1-yl group, 4-one hydroxypiperidin-1-yl group, 4-methylpiperidine-1-yl group 4-one isopropyl piperidine-1-yl group, 4-methoxypiperi Dean -1- diary ，
4一 (메틸아미노)피페리딘 -1—일기， 또는 4ᅳ (디메틸아미노)피페리딘 -1-일기를 나타내는 것을 특징으로 하는 화합물.  A compound characterized by representing a 4-one (methylamino) piperidine-1-yl group or a 4 ′ (dimethylamino) piperidin-1-yl group.
【청구항 8] [Claim 8]
청구항 1에 있어서，  The method according to claim 1,
6— ( 5- ( 3- ( 2-시아노프로판—2-일)벤즈아미도 ) -2-메틸페닐아미노) -/V-메틸 - L -인다 졸 -3-카복스아미드 (실시예 1);  6— (5- (3- (2- cyanopropane- 2-yl) benzamido) -2-methylphenylamino)-/ V-methyl-L-indazol-3-carboxamide (Example 1) ;
6-(5-(3-(2ᅳ시아노프로판 -2ᅳ일 )벤즈아미도)ᅳ 2-메틸페닐아미노)—Λ 2-몰포리노 에틸) 인다졸 -3-카복스아미드 (실시예 2);  6- (5- (3- (2xyanopropane-2xyl) benzamido) -2-methylphenylamino) —Λ 2-morpholino ethyl) indazole-3-carboxamide (Example 2);
6- ( 5- ( 3— ( 2ᅳ시아노프로판 -2-일)벤즈아미도) -2-메틸페닐아미노)— Λ 2-히드록시 에틸) 인다졸 _3-카복스아미드 (실시예 3);  6- (5- (3— (2′cyanopropane-2-yl) benzamido) -2-methylphenylamino) — Λ 2-hydroxy ethyl) indazole — 3-carboxamide (Example 3);
6-(5-(3-(2-시아노프로판 -2ᅳ일 )벤즈아미도)ᅳ 2—메틸페닐아미노) -ΛΚ피리딘 -4-일 6- (5- (3- (2-cyanopropane-2xyl) benzamido) ᅳ 2—methylphenylamino) -ΛΚpyridin-4-yl
)-1 -인다졸 -3-카복스아미드 (실시예 4); ) -1 -indazole-3-carboxamide (Example 4);
6-(2-메틸— 5-(3ᅳ (트리플루오로메틸)벤즈아미도)페닐아미노)— Λ 피리딘 -4—일) -1 -인다졸— 3-카복스아미드 (실시예 5);  6- (2-methyl— 5- (3 ′ (trifluoromethyl) benzamido) phenylamino) —Λ pyridin-4-yl) -1-indazole—3-carboxamide (Example 5);
149  149
대체용지 (규칙 제 26조) -시클로프로필 -6ᅳ(2ᅳ메틸ᅳ5-(3ᅳ (트리플루오로메틸)벤즈아미도)페닐아미노)— -인다졸 -3-카복스아미드 (실시예 6);Alternative Site (Article 26) -Cyclopropyl-6 '(2'methyl ᅳ 5- (3' (trifluoromethyl) benzamido) phenylamino) —- indazole-3-carboxamide (Example 6);
V-(2—히드록시에틸 )-6-(2—메틸 -5-(3- (트리플루오로메틸)벤즈아미도)페닐아미노 )-1 -인다졸ᅳ 3-카복스아미드 (실시예 7); V- (2—hydroxyethyl) -6- (2—methyl-5 (3- (trifluoromethyl) benzamido) phenylamino) -1 -indazoljan 3-carboxamide (Example 7 );
6-(2-메틸 -5ᅳ(3- (트리플루오로메틸)벤즈아미도)페닐아미노) -/H2—몰포리노에틸6- (2-methyl-5 '(3- (trifluoromethyl) benzamido) phenylamino)-/ H2—morpholinoethyl
)一1 -인다졸ᅳ 3-카복스아미드 (실시예 8); ) I1-indazolazole 3-carboxamide (Example 8);
/V—메틸ᅳ 6-((2-메틸 -5ᅳ (3-(4—메틸피페라진— 1ᅳ일) -5- (트리플루오로메틸)벤즈아미 도)페닐)아미노 )-1 -인다졸 -3-카복스아미드 (실시예 9);  / V—methyl ᅳ 6-((2-methyl-5-(3- (4—methylpiperazin— 1 ᅳ yl) -5- (trifluoromethyl) benzamido) phenyl) amino) -1 -indazole -3-carboxamide (Example 9);
6-((5-(4— (4-폴루오로페닐 )— 2ᅳ (트리플루오로메틸 )— 1 ᅳ이미다졸— 5-카복스아미도 )-2-메틸페닐)아미노) - -메틸 인다졸— 3-카복스아미드 (실시예 10);  6-((5- (4— (4-polourophenyl) —2 ′ (trifluoromethyl) —1 thiimidazole—5-carboxamido) -2-methylphenyl) amino)-methyl Indazole—3-carboxamide (Example 10);
一메틸ᅳ 6- (메틸 (2—메틸 -5— (3—몰포리노 -5- (트리플루오로메틸)벤즈아미도)페닐) 아미노 )-1 "인다졸 -3-카복스아미드 (실시예 11);  Imethyl ᅳ 6- (methyl (2—methyl-5— (3—morpholino-5 (trifluoromethyl) benzamido) phenyl) amino) -1 ”indazole-3-carboxamide (Example 11);
메틸— 6— (메틸 (4- ( 3ᅳ (트리플루오로메틸)벤즈아미도)페닐)아미노)ᅳ 1 -인다졸 -3 Methyl— 6— (methyl (4- (3 ′ (trifluoromethyl) benzamido) phenyl) amino) ᅳ 1-indazole-3
-카복스아미드 (실시예 12); Carboxamide (Example 12);
6ᅳ ( (4— (3—브로모페닐설폰아미도)페닐) (메틸)아미노) 메틸 - 1 ᅳ인다졸— 3-카복 스아미드 (실시예 13)； 6 ′ ((4— (3—bromophenylsulfonamido) phenyl) (methyl) amino) methyl-1 quindazol—3-carboxamide (Example 13);
6ᅳ((5— (3-(1 씨미다졸 -1-일) -5- (트리플루오로메틸)벤즈아미도) -2ᅳ메틸페닐 )( 메틸)아미노세메틸 -1 —인다졸 -3-카복스아미드 (실시예 14);  6 '((5— (3- (1 Cimidazol-1-yl) -5- (trifluoromethyl) benzamido) -2 ᅳ methylphenyl) (methyl) aminocemethyl-1 —indazol-3 -Carboxamide (Example 14);
메틸ᅳ 6— (메틸 (2-메틸— 5-(3-(4-메틸피페라진 _1—일) -5- (트리물루오로메틸)벤즈 아미도)페닐)아미노) 인다졸 -3—카복스아미드 (실시예 15);  Methyl ᅳ 6— (methyl (2-methyl— 5- (3- (4-methylpiperazin _1—yl) -5- (trimulomethyl) benz amido) phenyl) amino) indazole-3—carbox Amides (Example 15);
6-((5_(3-(4-히드록시피페리딘— 1ᅳ일)— 5- (트리물루오로메틸)벤즈아미도) -2-메틸 페닐) (메틸)아미노 )— /V-메틸 인다졸 -3—카복스아미드 (실시예 16); 6-((5_ (3- (4-hydroxypiperidin—1hexyl) — 5- (trimulomethyl) benzamido) -2-methyl phenyl) (methyl) amino) — / V-methyl Sol-3—carboxamide (Example 16);
-메틸 -6- (메틸 (2-메틸— 5-(3— (4—메틸 이미다졸 -1ᅳ일)— 5- (트리풀루오로메틸) 벤즈아미도)페닐)아미노 인다졸 _3ᅳ카복스아미드 (실시예 17);  -Methyl-6- (methyl (2-methyl- 5- (3— (4—methyl imidazole -1) yl)-5- (trifulomethyl) benzamido) phenyl) amino indazole _3carboxamide (Example 17);
/Vᅳ메틸 -6— (메될 (2-메틸— 5-(3-(2—메틸 미다졸— 1-일) -5— (트리플루오로메틸) 벤즈아미도)페닐)아미노 )-1 "인다졸 -3-카복스마이드 (실시예 18); / V ᅳ methyl-6— (methyl (2-methyl— 5- (3- (2—methyl midazol— 1-yl) -5— (trifluoromethyl) benzamido) phenyl) amino) -1 " Indazole-3-carboxamide (Example 18);
6ᅳ ( (5-(3-(2，4—디메틸— 1 ᅭ이미다졸 -1-일) -5— (트리플루오로메틸)벤즈아미도) -2- 메틸페닐) (메틸)아미노 )ᅳ -메틸 -1 -인다졸— 3-카복스아미드 (실시예 19); 6-((5- (3- (2,4—dimethyl— 1 ᅭ imidazol-1-yl) -5— (trifluoromethyl) benzamido) -2-methylphenyl) (methyl) amino) ᅳ- Methyl-1 -indazole— 3-carboxamide (Example 19);
(S)-6— ((5ᅳ (3-(3— (디메틸아미노)피롤리딘 -1—일) -5— (트리플루오로메틸)벤즈아미 도) -2—메틸페닐) (메틸)아미노) -yV—메틸 -1 -인다졸— 3-카복스아미드 (실시예 20); 一메틸 -6- (메틸 ( 2-메틸—5— ( 4- (4—메틸피페라진— 1-일 )— 3ᅳ (트리플루오로메틸)벤즈 아미도)페닐)아미노 )—1 ᅳ인다졸 -3_카복스아미드 (실시예 21); (S) -6— ((5 ′ (3- (3— (dimethylamino) pyrrolidin-1—yl) -5— (trifluoromethyl) benzamido) -2—methylphenyl) (methyl) amino ) -yV—methyl-1-indazole— 3-carboxamide (Example 20); 1-methyl-6- (methyl (2-methyl—5— (4- (4—methylpiperazin— 1-yl) — 3 ′ (trifluoromethyl) benz amido) phenyl) amino) —1 quinazole -3_carboxamide (Example 21);
6ᅳ( (5— (3— (2-시아노프로판 -2-일 )벤즈아미도)—2—메틸페닐) (메틸)아미노) - -메틸 一 1 ᅩ인다졸— 3-카복스아미드 (실시예 22); 6-((5— (3— (2-cyanopropan-2-yl) benzamido) —2-methylphenyl) (methyl) amino)--methyl one 1 ᅩ indazole— 3-carboxamide (implemented Example 22);
ᅳ메틸 -6- (메틸 (2—메틸 -5— (3- (트리풀루오로메틸)벤즈아미도)페닐)아미노 인다졸 -3—카복스아미드 (실시예 23);  ᅳ methyl-6- (methyl (2—methyl-5— (3- (trifuluromethyl) benzamido) phenyl) amino indazole-3—carboxamide (Example 23);
6-((5— (1-(4-메특시페닐) -5ᅳ (트리플루오로메틸 )— 1 -피라졸 -4-카복스아미도 )— 2- 메틸페닐) (메틸)아미노 HV-메틸 -1 -인다졸 -3-카복스아미드 (실시예 24);  6-((5— (1- (4-Methoxyphenyl) -5 ′ (trifluoromethyl) — 1-pyrazole-4-carboxamido) — 2-methylphenyl) (methyl) amino HV-methyl -1 -indazole-3-carboxamide (Example 24);
5- (4ᅳ클로로페닐)— yV— (4—메틸— 3_ (메틸 (3— (메틸카바모일 )ᅳ1 —인다졸 -6_일 )아미노 )페닐)이소옥사졸— 3-카복스아미드 (실시예 25);  5- (4 ᅳ chlorophenyl) — yV— (4—methyl— 3_ (methyl (3— (methylcarbamoyl) ᅳ 1 —indazol-6_yl) amino) phenyl) isoxazole— 3-carboxamide (Example 25);
6- ( (5— ( 5- (4—메특시페닐)퓨란— 2—카복스아미도)— 2—메틸페닐) (메틸)아미노) - -메 틸 -1 ―인다졸ᅳ 3—카복스아미드 (실시예 26);  6- ((5— (5- (4—Methoxyphenyl) furan— 2—carboxamido) — 2—methylphenyl) (methyl) amino)--methyl -1-indazole ᅳ 3-carboxamide (Example 26);
一 (4ᅳ메틸— 3- (메틸 (3- (메틸카바모일 )-1 —인다졸—6ᅳ일)아미노)페닐) -2- (피리딘- 一 (4 ᅳ methyl— 3- (methyl (3- (methylcarbamoyl) -1 —indazol—6 ᅳ yl) amino) phenyl) -2- (pyridine-
150 150
대체용지 (규칙 제 26조) 4-일)티아졸 -5-카복스아미드 (실시예 27)；Alternative Site (Article 26) 4-yl) thiazole-5-carboxamide (Example 27);
V-메틸 -6- (메틸 (4— (3-몰포리노ᅳ 5- (트리폴루오로메틸)벤즈아미도)페닐)아미노)ᅳ 1 -인다졸— 3-카복스아미드 (실시예 28); V-Methyl-6- (methyl (4— (3-morpholino ᅳ 5- (trifluoromethyl) benzamido) phenyl) amino) ᅳ 1-indazole— 3-carboxamide (Example 28) ;
6一 ((4ᅳ(3-(1 ᅵ미다졸— 1-일) -5— (트리플루오로메틸)벤즈아미도)페닐) (메틸)아 미노) -/V—메틸 -1 -인다졸 -3-카복스아미드 (실시예 29); 6 一 ((4 ᅳ (3- (1 ᅵ midazol— 1-yl) -5) (trifluoromethyl) benzamido) phenyl) (methyl) amino)-/ V-methyl-1 -indazole -3-carboxamide (Example 29);
-메틸 -6- (메틸 (4-(3-(4-메틸피페라진— 1-일) -5ᅳ (트리플루오로메틸)벤즈아미도) 페닐)아미노) 인다졸 -3—카복스아미드 (실시예 30);  -Methyl-6- (methyl (4- (3- (4-methylpiperazin— 1-yl) -5) (trifluoromethyl) benzamido) phenyl) amino) indazol-3—carboxamide ( Example 30);
6-((4-(3-(4—히드록시피페리딘 -1ᅳ일)— 5ᅳ (트리플루오로메틸)벤즈아미도)페닐 )( 메틸)아미노)ᅳV-메틸 -1 —인다졸—3—카복스아미드 (실시예 31);  6-((4- (3- (4—hydroxypiperidin-1xyl) — 5 ′ (trifluoromethyl) benzamido) phenyl) (methyl) amino) ᅳ V-methyl-1 —indazole —3—carboxamide (Example 31);
yV-메틸ᅳ 6— (메틸 (4— (3-(4-메틸 이미다졸— 1ᅳ일) -5— (트리플루오로메틸)벤즈아 미도)페닐)아미노 )-1#ᅳ인다졸 -3-카복스아미드 (실시예 32); yV-methyl ᅳ 6— (methyl (4— (3- (4-methyl imidazole— 1 ᅳ yl) -5— (trifluoromethyl) benzamido) phenyl) amino) -1 # binindazol-3- Carboxamide (Example 32);
(S)-6— ((4-(3-(3- (디메틸아미노)피를리딘— 1-일) -5- (트리플루오로메틸)벤즈아미 도)페닐) (메틸)아미노 HV—메틸— 1 ^인다졸ᅳ 3-카복스아미드 (실시예 33);  (S) -6— ((4- (3- (3- (dimethylamino) pyridin— 1-yl) -5- (trifluoromethyl) benzamido) phenyl) (methyl) amino HV—methyl — 1 ^ indazoljan 3-carboxamide (Example 33);
一메틸 -6- (메틸 (4— (4-(4ᅳ메틸피페라진 -1-일)— 3— (트리플루오로메틸)벤즈아미도) 페닐)아미노 )-1 ᅳ인다졸ᅳ 3-카복스아미드 (실시예 34);  One-Methyl-6- (Methyl (4— (4- (4 ᅳ methylpiperazin-1-yl) -3) (trifluoromethyl) benzamido) phenyl) amino) -1 Voxamide (Example 34);
6一 ( (4— (3-(2—시아노프로판— 2-일 )벤즈아미도)페닐) (메틸)아미노；卜 메틸 -1 "인 다졸ᅳ 3-카복스아미드 (실시예 35);  6zol ((4— (3- (2—cyanopropane- 2-yl) benzamido) phenyl) (methyl) amino; 다 methyl-1 ”dazol ᅳ 3-carboxamide (Example 35);
5-메틸— /V— (4— (메틸 (3- (메틸카바모일 )—1 -인다졸— 6—일)아미노)페닐 )이소옥사졸- 3ᅳ카복스아미드 (실시예 36);  5-methyl— / V— (4— (methyl (3- (methylcarbamoyl) —1-indazol— 6—yl) amino) phenyl) isoxazole-3′carboxamide (Example 36);
Λ 4ᅳ (메틸 (3- (메틸카바모일)ᅳ 1 ᅳ인다졸ᅳ 6—일)아미노)페닐 )티아졸ᅳ 4ᅳ카복스아 미드 (실시예 37); Λ 4 ′ (methyl (3- (methylcarbamoyl) ′ 1 indaindazol 6-yl) amino) phenyl) thiazol 4′carboxamide (Example 37);
그메틸 -6- (메틸 (4— (5-메틸피라진ᅳ 2ᅳ카복스아미도)페닐)아미노) -1^인다졸 -3-카 복스아미드 (실시예 38);Methylmethyl-6- (methyl (4— (5-methylpyrazine ᅳ 2′carboxamido) phenyl) amino) -1 ^ indazole-3-carboxamide (Example 38);
-메틸ᅳ 6- (메틸 (4-(3-(3- (트리풀루오로메틸)페닐)우레이도)페닐)아미노) -1 ^인 다졸—3ᅳ카복스아미드 (실시예 39);  -Methyl VI 6- (methyl (4- (3- (3- (tripulouromethyl) phenyl) ureido) phenyl) amino) -1 ^ indazole- 3'carboxamide (Example 39);
6- (( 5— ( 3- ( 4ᅳ클로로 -3ᅩ플루오로페닐)우레이도)— 2ᅳ메틸페닐) (메틸)아미노)ᅳ그메 틸— 1 -인다졸— 3-카복스아미드 (실시예 40); 6- ((5— (3- (4 ᅳ chloro-3 ᅩ fluorophenyl) ureido) — 2 ᅳ methylphenyl) (methyl) amino) dogmethyl— 1-indazole— 3-carboxamide (Example 40);
6-( (5— (3— (4ᅳ클로로페닐)우레이도 )ᅳ2ᅳ메틸페닐) (메틸)아미노사메틸— 1 -인다 졸 -3—카복스아미드 (실시예 41);  6- ((5— (3— (4 ᅳ chlorophenyl) ureido) ᅳ 2 ᅳ methylphenyl) (methyl) aminosamethyl— 1-indazol-3—carboxamide (Example 41);
6ᅳ(2-메틸 -5ᅳ (4ᅳ몰포리노페닐카바모일)페닐아미노)ᅳ Λ 4ᅳ몰포리노페닐)— 1 -인 다졸 -3-카복스아미드 (실시예 42); 6 ′ (2-Methyl-5 ′ (4′morpholinophenylcarbamoyl) phenylamino) ᅳ 4′morpholinophenyl) — 1-ynedazole-3-carboxamide (Example 42);
6ᅳ(4-플루오로— 5— (3—플루오로 -5ᅳ (트리풀루오로메틸)벤즈아미도 )-2_메틸페닐) —메틸 -1^인다졸—3-카복스아미드 (실시예 43);  6 ′ (4-Fluoro— 5— (3—Fluoro-5 ′ (tripulouromethyl) benzamido) -2_methylphenyl) —methyl-1 ^ indazole—3-carboxamide (Example 43);
6一 (4-풀루오로ᅳ 2—메틸— 5— (3—메틸 -5— (트리풀루오로메틸)벤즈아미도)페닐) - 메 틸— 1^인다졸—3—카복스아미드 (실시예 44);  6 一 (4-Pluorouro 2-methyl- 5— (3—methyl-5— (trifulomethyl) benzamido) phenyl) -methyl— 1 ^ indazole—3—carboxamide ( Example 44);
6-(4-풀루오로ᅳ 5-(3-플루오로 -5-메틸벤즈아미도)— 2ᅳ메틸페닐)ᅳ^메틸 -1^인다 졸 -3—카복스아미드 (실시예 45);  6- (4-Pluorolotyl 5- (3-fluoro-5-methylbenzamido) —2′methylphenyl) ᅳ ^ methyl-1 ^ indada sol-3—carboxamide (Example 45);
6-(4—폴루오로 -2-메틸— 5-(4—메틸— 3— (트리플루오로메틸 )벤즈아미도)페닐)ᅳ 메 틸 -1^인다졸—3—카복스아미드 (실시예 46);  6- (4—Polouro-2-methyl— 5- (4—methyl— 3— (trifluoromethyl) benzamido) phenyl) ᅳ methyl-1 ^ indazole—3—carboxamide (implemented Example 46);
6-(5-(4-클로로— 3- (트리플루오로메틸)벤즈아미도)— 4—플루오로 -2ᅳ메틸페닐)— 메틸— 인다졸ᅳ3ᅳ카복스아미드 (실시예 47); 6- (5- (4-chloro- 3- (trifluoromethyl) benzamido)-4-fluoro-2 "methylphenyl)-methyl- indazole" 3 "carboxamide (Example 47);
6-(4ᅳ풀루오로 -2-메틸— 5— (3— (트리풀루오로메틸)벤즈아미도)페닐)—^메틸 -L 인 다졸 -3-카복스아미드 (실시예 48);  6- (4'Pluorouro-2-methyl- 5— (3— (trifuluromethyl) benzamido) phenyl)-^ methyl-L phosphorusazole 3-carboxamide (Example 48);
151  151
대체용지 (규칙 제 26조) 6-(4-플루오로 -5— (4-플루오로 -3- (트리플루오로메틸)벤즈아미도 )_2ᅩ메틸페닐) -메틸 -1^인다졸 -3-카복스아미드 (실시예 49); Alternative Site (Article 26) 6- (4-Fluoro-5— (4-fluoro-3- (trifluoromethyl) benzamido) _2'methylphenyl ) -methyl-1 ^ indazole-3-carboxamide (Example 49) ;
6-(4—풀루오로ᅳ 5-(2-풀루오로 -5- (트리플루오로메틸)벤즈아미도) -2ᅳ메틸페닐) -메틸 인다졸 -3-카복스아미드 (실시예 50);  6- (4—Pluorofluoro 5- (2-Pluoro-5- (trifluoromethyl) benzamido) -2′methylphenyl) -methyl indazole-3-carboxamide (Example 50) ;
6-(4-플루오로ᅳ 5-(4-플루오로 -2- (트리플루오로메틸 )벤즈아미도) -2-메틸페닐 )- 一메틸 -1^인다졸—3-카복스아미드 (실시예 51); 6- (4-Fluoro ᅳ 5- (4-fluoro-2- (trifluoromethyl) benzamido) -2-methylphenyl) -onemethyl-1 ^ indazole—3-carboxamide (Example 51);
6-(4-플루오로ᅳ 2-메틸 -5ᅳ (4- (트리플루오로메톡시 )벤즈아미도)페닐) - 메틸ᅳ 1^ 인다졸 -3-카복스아미드 (실시예 52);  6- (4-fluoro ᅳ 2-methyl-5 ′ (4- (trifluoromethoxy) benzamido) phenyl) -methyl ᅳ 1 ^ indazole-3-carboxamide (Example 52);
6-(4-플루오로ᅳ 5-(2-메록시 -3- (트리플루오로메틸 )벤즈아미도) -2—메틸페닐)ᅳ^ 메틸 -1^인다졸 -3—카복스아미드 (실시예 53); 6- (4-fluoro ᅳ 5- (2-methoxy-3- (trifluoromethyl) benzamido) -2—methylphenyl) 페닐 ^ methyl-1 ^ indazole-3—carboxamide (Example 53);
6— (4-플루오로— 5— (2—메특시—5- (트리풀루오로메틸)벤즈아미도) -2-메틸페닐)ᅳ^ 메틸 -1^인다졸 -3—카복스아미드 (실시예 54);  6— (4-Fluoro— 5— (2—Mesophilic—5- (Tripulouromethyl) benzamido) -2-methylphenyl) ᅳ ^ methyl-1 ^ indazole-3—carboxamide (implemented Example 54);
6一 (4-플루오로 -5— (3-메특시—5— (트리플루오로메틸)벤즈아미도) -2-메틸페닐)ᅳ^ 메틸 -1^인다졸 -3-카복스아미드 (실시예 55);  6- (4-Fluoro-5— (3-methoxy--5— (trifluoromethyl) benzamido) -2-methylphenyl) ᅳ ^ methyl-1 ^ indazole-3-carboxamide (Example 55);
6-(4-플루오로— 5-(2-하이드록시 -5— (트리플루오로메틸 )벤즈아미도) -2-메틸페닐) 메틸— l 다졸 -3-카복스아미드 (실시예 56);  6- (4-fluoro— 5- (2-hydroxy-5— (trifluoromethyl) benzamido) -2-methylphenyl) methyl—ldazole-3-carboxamide (Example 56);
6-(4-풀루오로 -5-(4-하이드록시 -3_ (트리플루오로메틸 )벤즈아미도 )— 2_메틸페닐) 메틸 인다졸ᅳ 3-카복스아미드 (실시에 57); 6- (4-Pluoro-5- (4-hydroxy-3_ (trifluoromethyl) benzamido) — 2_methylphenyl) methyl indazol-3-carboxamide (Example 57);
6-(4-플루오로— 2—메틸 -5— (3— (트리풀루오로메특시)벤즈아미도)페닐) - ^메틸ᅳ 1^ 인다졸ᅳ 3-카복스아미드 (실시예 58); 6- (4-Fluoro— 2—methyl-5— (3— (tripulolomome) benzamido) phenyl)-^ methyl ᅳ 1 ^ indazole ᅳ 3-carboxamide (Example 58) ;
6-(5-(4-아미노 -3- (트리플루오로메틸)벤즈아미도) -4-플루오로 -2-메틸페닐) 메틸— 1^인다졸—3-카복스아미드 (실시예 59);  6- (5- (4-amino-3- (trifluoromethyl) benzamido) -4-fluoro-2-methylphenyl) methyl-l ^ indazole-3-carboxamide (Example 59);
6-(5-(4-아미노 -3- (트리플루오로메톡시)벤즈아미도)—4-플루오로 -2—메틸페닐) -메틸 인다졸 -3ᅳ카복스아미드 (실시예 60);  6- (5- (4-amino-3- (trifluoromethoxy) benzamido) —4-fluoro-2—methylphenyl) -methyl indazole-3′carboxamide (Example 60);
6-(4_플루오로— 5-(4-플루오로 -3- (트리플루오로메록시)벤즈아미도 )_2—메틸페닐) 一 ^메틸 -1^인다졸 -3-카복스아미드 (실시예 61);  6- (4_fluoro— 5- (4-fluoro-3- (trifluoromethoxy) benzamido) _2—methylphenyl) one ^ methyl-1 ^ indazole-3-carboxamide (Example 61 );
6-(4-풀루오로 -2-메틸— 5ᅳ (6- (트리풀루오로메틸)니코티아미도)페닐) 메틸— 1^ 인다졸ᅳ3—카복스아미드 (실시예 62);  6- (4-Pluoro-2-methyl—5 ′ (6- (trifuluromethyl) nicothiamido) phenyl) methyl-1 ^ indazole ᅳ 3—carboxamide (Example 62);
6-(4-풀루오로 -2—메틸 -5ᅳ (2- (트리풀루오로메틸 )이소니코틴아미도)페닐)— ^메틸6- (4-Pluoro-2-2-methyl-5 ᅳ (2- (trifuluromethyl) isonicotinamido) phenyl) — ^ methyl
-1^인다졸—3-카복스아미드 (실시예 63); · -1 ^ indazole-3-carboxamide (Example 63); ·
6- ( 5- ( 6- (디메틸아미노) -5-메틸니코틴아미도) -4—플루오로— 2—메틸페닐)— ^메틸- 1^인다졸 -3—카복스아미드 (실시예 64); 6- (5- (6- (dimethylamino)-5-methylnicotinamido) -4-fluoro-2-methylphenyl)--methyl- 1-indazole-3-carboxamide (Example 64);
6一 (5-(4-클로로ᅳ 3-(2-시아노프로판— 2—일)벤즈아미도 )-4ᅳ플로로—2-메틸페닐) 메틸 -1^인다졸 -3—카복스아미드 (실시예 65);  6- (5- (4-chloro ᅳ 3- (2-cyanopropane- 2--yl) benzamido) -4 fluoro-2-methylphenyl) methyl-1 ^ indazole-3-carboxamide ( Example 65);
6-(5-(3-(2-시아노프로판 -2-일)— 5- (트리플투오로메틸 )벤즈아미도) -4-플로로 -2- 메틸페닐)— ^메틸 -1^인다졸 -3-카복스아미드 (실시예 66);  6- (5- (3- (2-cyanopropane-2-yl) — 5- (tripletomethyl) benzamido) -4-fluoro-2-methylphenyl) — ^ methyl-1 ^ indazole -3-carboxamide (Example 66);
6-(5— (3— (2ᅳ시아노프로판 -2ᅳ일) -5—풀루오로벤즈아미도)ᅳ 4—플로로 _2ᅳ메틸페닐) - 메틸 -1^인다졸—3-카복스아미드 (실시예 67);  6- (5— (3— (2 ᅳ cyanopropane-2) yl) -5—Pluorobenzamido) 4—fluoro _2 ᅳ methylphenyl) -methyl-1 ^ indazole—3-carboxamide (Example 67);
6— (5-(3ᅳ아미노 -5— (트리플루오로메틸)벤즈아미도) -4—플루오로— 2ᅳ메틸페닐) 메틸 -1^인다졸ᅳ 3-카복스아미드 (실시예 68); 6— (5- (3′amino-5— (trifluoromethyl) benzamido) -4—fluoro—2′methylphenyl) methyl-1 ^ indazol-3-carboxamide (Example 68);
6-(5-(3- (디메틸아미노) -5— (트리풀루오로메틸)벤즈아미도) -4—플루오로 -2—메틸 페닐) 메틸— 인다졸ᅳ 3-카복스아미드 (실시예 69);  6- (5- (3- (dimethylamino) -5— (trifuluromethyl) benzamido) -4—fluoro-2-2-methyl phenyl) methyl-indazolox 3-carboxamide (Example 69);
152  152
대체용지 (규칙 제 26조) 6-(5-(3- ((디메틸아미노)에틸)아미노 )-5- (트리플루오로메틸)벤즈아미도)ᅳ 4一플 루오로 -2—메틸페닐 )-/^메틸 -L 인다졸—3-카복스아미드 (실시예 70); Alternative Site (Article 26) 6- (5- (3- ((dimethylamino) ethyl) amino) -5- (trifluoromethyl) benzamido) ᅳ 4 fluoro -2 -methylphenyl)-/ ^ methyl -L indazole— 3-carboxamide (Example 70);
6-(5-(3_ ((디메틸아미노)에틸) (메틸)아미노)ᅳ 5- (트리플루오로메틸)벤즈아미도) -4ᅳ플루오로ᅳ 2—메틸페닐) - ^메틸 -1^인다졸 -3-카복스아미드 (실시예 71); 6_(4-플루오로 -2ᅳ메틸 -5-(3-몰포리노 -5- (트리플루오로메틸)벤즈아미도)페닐)6- (5- (3 _ ((dimethylamino) ethyl) (methyl) amino) ᅳ 5- (trifluoromethyl) benzamido) -4 ᅳ fluoro ᅳ 2—methylphenyl)-^ methyl-1 ^ indazole -3-carboxamide (Example 71); 6_ (4-Fluoro-2 ᅳ methyl-5- (3-morpholino-5- (trifluoromethyl) benzamido) phenyl)
-메틸 -1^인다졸 -3-카복스아미드 (실시예 72); -Methyl-l-indazole-3-carboxamide (Example 72);
6-(4-플루오로— 2ᅳ메틸 -5-(3- (메틸아미노) -5- (트리플투오로메틸)벤즈아미도)페 닐)— ^메틸—1^인다졸 -3_카복스아미드 (실시예 73);  6- (4-fluoro—2—methyl-5 (3- (methylamino) -5- (trifluoromethyl) benzamido) phenyl) — ^ methyl—1 ^ indazole-3_carbox Amides (Example 73);
6-(5-(2- (디메틸아미노) -5ᅳ (트리풀루오로메틸)벤즈아미도) -4—풀루오로 -2ᅳ메틸 페닐)— ^메틸 다졸 -3ᅳ카복스아미드 (실시예 74);  6- (5- (2- (dimethylamino) -5 ′ (tripulouromethyl) benzamido) -4—pulrouro-2′methyl phenyl) —methyldiazole-3′carboxamide (Example 74);
6-(4—풀루오로 -2—메틸 -5-(2-(4-메틸피페라진 -1-일) -5- (트리플루오로메틸)벤즈 아미도)페닐)—Λ^메틸— 1^인다졸 -3—카복스아미드 (실시예 75);  6- (4—Pluoro-2-2-methyl-5- (2- (4-methylpiperazin-1-yl) -5- (trifluoromethyl) benz amido) phenyl) —Λ ^ methyl— 1 ^ Indazole-3—carboxamide (Example 75);
6-{4-플루오로 -2-메틸 -5-[3-(2— (피롤리딘 -1-일—에틸아미노)— 5-트리풀루오로메 틸-벤조일아미노]페닐 인다졸—3-카복시산 메틸아미드 (실시예 76);  6- {4-fluoro-2-methyl-5 [3- (2— (pyrrolidin-1-yl—ethylamino) — 5-trifuluromethyl-benzoylamino] phenyl indazole—3- Carboxylic acid methylamide (Example 76);
6- (4-플루오로 -2-메틸 -5— (3— ( (테트라하이드로 -2^피란ᅳ4-일 )아미노 )ᅳ5- (트리플 루오로메틸)벤즈아미도)페닐)― 메틸 -1^인다졸 -3-카복스아미드 (실시예 77);6- (4-Fluoro-2-methyl-5— (3— ((tetrahydro-2 ^ pyran ᅳ 4-yl) amino) ᅳ 5- (trifluoromethyl) benzamido) phenyl)-methyl- 1 ^ indazole-3-carboxamide (Example 77);
6-(4—플루오로 -2-메틸 -5-(3- (피페라진 -1ᅳ일)ᅳ 5- (트리플루오로메틸)벤즈아미도) 페닐) - 메틸 -1^인다졸—3ᅳ카복스아미드 (실시예 78); 6- (4—Fluoro-2-methyl-5- (3- (piperazin-1xyl) ᅳ 5- (trifluoromethyl) benzamido) phenyl) -methyl-1 ^ indazole—3 ᅳ carbox Amides (Example 78);
6-(4-플루오로 -2—메틸— 5_(3-(4-메틸피페라진— 1—일) -5- (트리플루오로메틸)벤즈 아미도)페닐) - 메틸— 1^인다졸 -3-카복스아미드 (실시예 79);  6- (4-Fluoro-2—methyl— 5_ (3- (4-methylpiperazin— 1—yl) -5 (trifluoromethyl) benz amido) phenyl) -methyl- 1 ^ indazole- 3-carboxamide (Example 79);
6-(5-(3-(4-에틸피레라진 -1-일) -5- (트리플루오로메틸 )벤즈아미도)—4-플루오로- 2-메틸페닐)ᅳ/^메틸 -1^인다졸—3—카복스아미드 (실시예 80);  6- (5- (3- (4-ethylpyrazin-1-yl) -5- (trifluoromethyl) benzamido) —4-fluoro-2-methylphenyl) ᅳ / ^ methyl-1 ^ is Sol—3—carboxamide (Example 80);
(R)-6_(5-(3ᅳ (3— (디메틸아미노)피롤리딘ᅳ 1—일) -5- (트리플루오로메틸)벤즈아미 도) -4-풀루오로 -2-메틸페닐) 메틸ᅳ 1^인다졸 -3—카복스아미드 (실시예 81); 6— (4—플루오로 -2-메틸 -5-(3_(4_메틸ᅳ 1,4ᅳ디아제판 -1—일)— 5— (트리플루오로메틸) 벤즈아미도)페닐) - ^메틸 -1^인다졸ᅳ3-카복스아미드 (실시예 82); (R) -6_ (5- (3 ′ (3— (dimethylamino) pyrrolidinyl 1-yl) -5- (trifluoromethyl) benzamido) -4-pululo-2-methylphenyl) Methyl ᅳ 1 ^ indazole-3—carboxamide (Example 81); 6— (4—Fluoro-2-methyl-5- (3_ (4_methyl ᅳ 1,4 diazepane-1-1)) — 5— (trifluoromethyl) benzamido) phenyl)-^ methyl -1 ^ indazole ᅳ 3-carboxamide (Example 82);
6-(4-폴루오로— 5-(3- (핵사하이드로피롤로 [1,2— a]피라진— 2(1H)_일 )-5ᅳ (트리풀루 오로메틸 )벤즈아미도) -2-메틸페닐) - ^메틸 -1^인다졸 _3-카복스아미드 (실시예 83)； 6- (4-Polouro— 5- (3- (Nucleohydropyrrolo [1,2—a] pyrazine— 2 (1H) _yl) -5 ᅳ (tripulouromethyl) benzamido) -2 -Methylphenyl)-^ methyl-1 ^ indazole _3-carboxamide (Example 83);
6-(4-플루오로— 5-(3-(((2—하이드록시에틸) (메틸)아미노 )-5- (트리플루오로메틸) 벤즈아미도) -2-메틸페닐) - 메틸— 1^인다졸—3-카복스아미드 (실시예 84); (S)— 6_(5— (3ᅳ(3- (디메틸아미노)피롤리딘 -1-일) -5— (트리폴루오로메틸)벤즈아미 도) -4-플루오로— 2-메틸페닐) 메틸— 1^인다졸—3-카복스아미드 (실시예 85); 6-(4—플루오로— 2-메틸ᅳ 5-(3-(4-메틸설포닐)피페라진 -1-일) -5— (트리풀루오로메 틸)벤즈아미도)페닐) 메틸 -1 ^인다졸 -3—카복스아미드 (실시예 86); 6- (4-fluoro— 5- (3-(((2—hydroxyethyl) (methyl) amino) -5- (trifluoromethyl) benzamido) -2-methylphenyl) -methyl— 1 ^ Indazole—3-carboxamide (Example 84); (S) — 6_ (5— (3 ′ (3- (dimethylamino) pyrrolidin-1-yl) -5— (tripololomethyl) Benzamido) -4-fluoro—2-methylphenyl) methyl—1 ^ indazole—3-carboxamide (Example 85); 6- (4—fluoro—2-methyl ᅳ 5- (3- ( 4-methylsulfonyl) piperazin-1-yl) -5— (trifuluromethyl) benzamido) phenyl) methyl-1 ^ indazole-3—carboxamide (Example 86);
6-(5-(3ᅳ (4—아세틸피페라진 -1-일) -5ᅳ (트리플루오로메틸)벤즈아미도 )ᅳ4-플루오 로 -2-메틸페닐) - ^메틸 -1^인다졸 _3ᅳ카복스아미드 (실시예 87);  6- (5- (3 ′ (4—acetylpiperazin-1-yl) -5 ′ (trifluoromethyl) benzamido) ᅳ 4-fluoro-2-methylphenyl)-^ methyl-1 ^ indazole _3 ᅳ carboxamide (Example 87);
6一 (4-플루오로— 2-메틸— 5-(3-(4-니코티노일피페라진—1-일) -5- (트리플루오로메틸 )벤즈아미도)페닐) - 메틸 -i^인다졸 _3-카복스아미드 (실시예 88); 6- (4-Fluoro— 2-methyl- 5- (3- (4-nicotinoylpiperazin-1-yl) -5- (trifluoromethyl) benzamido) phenyl) -methyl-i ^ Indazole_3-carboxamide (Example 88);
6-(5-(3ᅳ (4-(2— (디메틸아미노) -2-옥소에틸)피페라진 -1ᅳ일) -5— (트리풀루오로메 틸 )벤즈아미도)—4-플루오로 _2—메틸페닐)— ^메틸 -1^인다졸 -3—카복스아미드 (실시예 89)； 6- (5- (3 ′ (4- (2— (dimethylamino) -2-oxoethyl) piperazin-1xyl) -5— (trifuluromethyl) benzamido) —4-fluoro _2 —Methylphenyl) — ^ methyl-1 ^ indazole-3—carboxamide (Example 89);
6一(4-플루오로 -2—메틸ᅳ 5-(3-(4-(2-옥소— 2- (페닐아미노)에틸)피페라진 -1—일)一 5ᅳ  6- (4-Fluoro-2-methyl ᅳ 5- (3- (4- (2-oxo- 2- (phenylamino) ethyl) piperazine-1-yl) 一 5 ᅳ
153  153
대체용지 (규칙 제 26조) (트리풀루오로메틸 )벤즈아미도)페닐) 메틸 -1/^인다졸 -3-카복스아미드 (실시예 90)； Alternative Site (Article 26) (Trifulomethyl) benzamido) phenyl) methyl-1 / ^ indazole-3-carboxamide (Example 90);
6-(4-폴루오로 -5ᅳ(3— (4- (이소프로필설포닐)피페라진 -1—일)— 5- (트리플루오로메 틸)벤즈아미도)—2—메틸페닐 )-^데틸 -1^인다졸—3—카복스아미드 (실시예 91); 6ᅳ (5— (3-(4-벤조일피페라진 -1—일) -5— (트리플루오로메틸)벤즈아미도)—4—풀루오 로 -2-메틸페닐) - 메틸— ly 인다졸—3-카복스아미드 (실시예 92);  6- (4-Polouro-5 ′ (3— (4- (isopropylsulfonyl) piperazin-1—yl) — 5- (trifluoromethyl) benzamido) —2—methylphenyl)-^ Decyl-1-indazole-3 carboxamide (Example 91); 6 '(5— (3- (4-benzoylpiperazin-1-yl) -5) (trifluoromethyl) benzamido) -4 4-puloloro-2-methylphenyl) -methyl- ly indazole 3-carboxamide (Example 92);
6ᅳ ( 5— ( 3- ( 1-아세틸피페리딘 -4-카복스아미도 )—5- (트리플루오로메틸)벤즈아미도) —4-플루오로 -2-메틸페닐) 메틸— 1^인다졸 -3-카복스아미드 (실시예 93); 6-(5— (3— (2- (디메틸아미노)아세트아미도 )—5— (트리풀루오로메틸)벤즈아미도) -4一 플루오로ᅳ 2ᅳ메틸페닐) - ^메틸 -1^인다졸 -3-카복스아미드 (실시예 94); 6 ᅳ (5— (3- (1-acetylpiperidine-4-carboxamido) —5- (trifluoromethyl) benzamido) —4-fluoro-2-methylphenyl) methyl— 1 ^ Indazole-3-carboxamide (Example 93); 6- (5— (3— (2- (dimethylamino) acetamido) —5— (trifuluromethyl) benzamido) -4 one fluoro ᅳ 2 ᅳ methylphenyl)-^ methyl -1 ^ Sol-3-carboxamide (Example 94);
6-(4-풀루오로— 5ᅳ (3-(4-(2—메특시에틸)피페라진 -1-일)— 5- (트리플루오로메틸)벤 즈아미도 )—2_메틸페닐)— ^메틸 -1^인다졸 -3—카복스아미드 (실시예 95);  6- (4-Pluoro— 5 ᅳ (3- (4- (2—Methoxyethyl) piperazin-1-yl) — 5- (trifluoromethyl) benzamido) —2_methylphenyl) — ^ Methyl-1 ^ indazole-3—carboxamide (Example 95);
6ᅳ(4—풀루오로 -2ᅳ메틸 -5ᅳ(3-(4— (1—메틸피페라진 -4—일) -5- (트리플루오로메틸)벤 즈아미도)페닐) 메틸— 1^인다졸 -3-카복스아미드 (실시예 96); 6 '(4—Pluoro-2-2-methyl-5' (3- (4— (1—methylpiperazin-4-yl) -5- (trifluoromethyl) benzamido) phenyl) methyl— 1 ^ indazole-3-carboxamide (Example 96);
6-(4-플루오로 -2ᅳ메틸ᅳ 5ᅳ(3-((1，2,2，6，6-펜타메틸피페리딘— 4-일)아미노 )-5ᅳ (트 리풀루오로메틸 )벤즈아미도)페닐) - ^메틸 -1^인다졸ᅳ 3-카복스아미드 (실시예 97)； 6- (4-fluoro-2'methyl ᅳ 5 ᅳ (3-((1,2,2,6,6-pentamethylpiperidin- 4-yl) amino) -5 '(tripooluromethyl ) Benzamido) phenyl)-^ methyl-1 ^ indazolazole 3-carboxamide (Example 97);
6— (4-플루오로ᅳ 2ᅳ메틸ᅳ 5ᅳ (3— (4—옥소피페리딘ᅳ 1-일) -5- (트리플투오로메틸)벤즈 아미도)페닐) - ^메틸 -L 인다졸—3—카복스아미드 (실시예 98);  6— (4-fluoro ᅳ 2 ᅳ methyl ᅳ 5 ᅳ (3— (4—oxopiperidin ᅳ 1-yl) -5- (triple toomethyl) benz amido) phenyl)-^ methyl-L Sol—3—carboxamide (Example 98);
6ᅳ (4—플루오로 -2-메틸ᅳ 5-(3-(4-메특시피페리딘 -1—일) -5- (트리플투오로메틸)벤 즈아미도)페닐)—^메틸— 1^인다졸 -3—카복스아미드 (실시예 99); 6 '(4—fluoro-2-methyl 5- (3- (4-methoxypiperidin-1-yl) -5- (triple toomethyl) benzamido) phenyl) — ^ methyl— 1 ^ Indazole-3—carboxamide (Example 99);
6ᅳ (4—플루오로 -2-메틸ᅳ 5-(3-(3-하이드록시피롤리딘—1-일) -5- (트리플루오로메틸 6 ′ (4—fluoro-2-methyl ᅳ 5- (3- (3-hydroxypyrrolidin—1-yl) -5- (trifluoromethyl
)벤즈아미도)페닐) 메틸— 인다졸 -3-카복스아미드 (실시예 100); ) Benzamido) phenyl) methyl-indazole-3-carboxamide (Example 100);
6- ( 5- ( 3- ( 1 , 4-디옥사ᅳ 8-아자스피로 [ 4， 5 ]데칸— 8—일)— 5— (트리플루오로메틸)벤즈 아미도 )-4-플루오로 -2ᅳ메틸페닐)—^메틸 -1^인다졸 -3-카복스아미드 (실시예 6- (5- (3- (1 (4- Dioxan) 8-azaspiro [4, 5] decane — 8—yl) — 5— (trifluoromethyl) benz amido) -4-fluoro- 2 ᅳ methylphenyl)-^ methyl-1 ^ indazole-3-carboxamide (Example
101)； 101);
6-(4-플루오로ᅳ 2-메틸ᅳ 5-(3-(4— (메틸아미노)피페리딘— 1-일) -5- (트리플루오로메 틸)벤즈아미도)페닐) 메틸— 1^인다졸 -3-카복스아미드 (실시예 102);  6- (4-fluoro ᅳ 2-methyl ᅳ 5- (3- (4— (methylamino) piperidin— 1-yl) -5 (trifluoromethyl) benzamido) phenyl) methyl— 1 ^ Indazole-3-carboxamide (Example 102);
6一 (4—플루오로ᅳ 2—메틸— 5-(3ᅳ (4- (디메틸아미노)피페리딘 -1ᅳ일 )—5- (트리플루오로 메틸)벤즈아미도)페닐) - 메틸 -1^인다졸—3-카복스아미드 (실시예 103);  6 一 (4—Fluoro ᅳ 2—methyl— 5- (3 ᅳ (4- (dimethylamino) piperidin-1xyl) —5- (trifluoromethyl) benzamido) phenyl) -methyl-1 ^ Indazole—3-carboxamide (Example 103);
6ᅳ (4—플루오로— 5— (3-(4ᅳ하이드록시피페리딘— 1-일)ᅳ 5— (트리플루오로메틸)벤즈아 미도) 2ᅳ메틸페닐) - 메틸 -1^인다졸 -3-카복스아미드 (실시예 104);  6 '(4—Fluoro— 5— (3- (4'hydroxypiperidin— 1-yl) ᅳ 5— (trifluoromethyl) benzamido) 2' methylphenyl) -methyl-1 ^ indazole -3-carboxamide (Example 104);
6-(4-풀루오로 -2-메틸 -5-(3ᅳ((1—메틸피페리딘— 4-일)아미노 )— 5- (트리플루오로메 틸)벤즈아미도)페닐) 메틸— 1^인다졸 -3-카복스아미드 (실시예 105); 6- (4-Pluoro-2-methyl-5- (3 ′ ((1—methylpiperidin- 4-yl) amino) — 5- (trifluoromethyl) benzamido) phenyl) methyl— 1 ^ indazole-3-carboxamide (Example 105);
6-(4—플루오로ᅳ 2-메틸 -5-(3-피페리딘 -4—일옥시)ᅳ 5ᅳ (트리플루오로메틸)벤즈아미 도)페닐)—^메틸— 1^인다졸ᅳ 3-카복스아미드 (실시예 106); 6- (4—Fluoro ᅳ 2-methyl-5- (3-piperidine-4-yloxy) ᅳ 5 ᅳ (trifluoromethyl) benzamido) phenyl) — ^ methyl— 1 ^ indazol ᅳ 3-carboxamide (Example 106);
6-(4—플루오로ᅳ2—메틸 -5— (3-( 1-메틸피페리딘 -4-일)옥시)— 5— (트리플루오로메틸) 벤즈아미도)페닐) - ^메틸 -L 인다졸—3-카복스아미드 (실시예 107); 6- (4—Fluoro ᅳ 2—methyl-5— (3- (1-methylpiperidin-4-yl) oxy) — 5— (trifluoromethyl) benzamido) phenyl)-^ methyl- L indazole—3-carboxamide (Example 107);
6ᅳ (4ᅳ풀루오로 -2-메틸— 5-(3—( ( 1—메틸피페리딘 -4ᅳ일)메록시 )-5- (트리플루오로메 틸 )벤즈아미도)페닐 )— 메틸 -l 인다졸 -3—카복스아미드 6 '(4'Pluoro-2-methyl— 5- (3— ((1—methylpiperidin-4 ᅳ yl) methoxy) -5- (trifluoromethyl) benzamido) phenyl) —methyl- indazole-3—carboxamide
트리플루오로아세트산염 (실시예 108); Trifluoroacetic acid salt (Example 108);
6-(4ᅳ풀루오로— 2-메틸 -5-(3ᅳ (피페리딘 -4ᅳ일메록시) -5— (트리플루오로메틸)벤즈 아미도)페닐) 메틸— 1^인다졸 -3-카복스아미드 트리풀루오로아세트산염  6- (4'Pluorouro- 2-methyl-5- (3 '(piperidin-4xylylmethoxy) -5- (trifluoromethyl) benz amido) phenyl) methyl- 1 ^ indazole-3 Carboxamide Trifluuroacetic Acid
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대체용지 (규칙 제 26조) (실시예 109)； Alternative Site (Article 26) (Example 109);
6-(4-플루오로 -5-(3_(4-이소프로필피페리딘 -1—일 )—5- (트리플루오로메틸 )벤즈아 미도)—2—메틸페닐) - 메틸 -1^인다졸 -3ᅳ카복스아미드 (실시예 110);  6- (4-fluoro-5- (3_ (4-isopropylpiperidin-1-yl) -5- (trifluoromethyl) benzamido) -2-methylphenyl) -methyl-1 ^ indazole -3′carboxamide (Example 110);
6-(4-풀루오로 -2-메틸 -5-(3— (4-메틸 -1,4-디아제판— 1-일) -5— (트리플루오로메틸) 벤즈아미도)페닐)—^메틸ᅳ 1^인다졸 -3-카복스아미드 (실시예 111); 6- (4-Pluoro-2-methyl-5- (3— (4-methyl-1,4-diazepan— 1-yl) -5— (trifluoromethyl) benzamido) phenyl) — ^ Methyl # 1 ^ indazole-3-carboxamide (Example 111);
6-(5— (3-(4ᅳ^기ᅭ부틸)—피페라진 _1-일) -5— (트리플루오로메틸)벤즈아미도)— 4-플 루오로ᅳ 2-메틸페닐) 메틸 -1^인다졸 -3-카복스아미드 (실시예 112); 6- (5- (3- (4-eu Receive yo-butyl) -piperazine-_1- yl) -5- (trifluoromethyl) benz amido) - eu 4-fluorine-2-methylphenyl) methyl-1 ^ Indazole-3-carboxamide (Example 112);
6-(5-(3-(3ᅳ (디에틸아미노)피롤리딘— 1-일)— 5- (트리플루오로메필)벤즈아미도) -4 -플루오로 -2-메틸페닐) - 메틸 -1^인다졸 -3-카복스아미드 (실시예 113); 6- (5- (3- (3 ᅳ (Diethylamino) pyrrolidin— 1-yl) — 5- (trifluoromephil) benzamido) -4-fluoro-2-methylphenyl) -methyl- 1 ^ indazole-3-carboxamide (Example 113);
6— (4—플투오로 -2-메틸 -5-(3— (4-메틸—피페리딘 _1—일 )— 5_ (트리플루오로메틸)벤즈 아미도)페닐) - ^메틸 -1^인다졸—3-카복스아미드 (실시예 114); 6— (4—Plutouro-2-methyl-5- (3— (4-methyl-piperidin _1—yl) — 5_ (trifluoromethyl) benz amido) phenyl)-^ methyl-1 ^ Sol—3-carboxamide (Example 114);
6-(5—(3-(3，5—디메틸피페라진 -1—일) -5- (트리플루오로메틸)벤즈아미도)— 4—플루 오로— 2-메틸페닐) - ^메틸ᅳ1^인다졸 -3-카복스아미드 트리플루오로아세트산염 (실시예 115)； 6- (5— (3- (3,5—Dimethylpiperazin-1-yl) -5- (trifluoromethyl) benzamido) — 4—fluoro- 2-methylphenyl)-^ methyl ᅳ 1 ^ Indazole-3-carboxamide trifluoroacetic acid salt (Example 115);
6-(4-플루오로 -2-메틸 -5-(3— (트리플루오로메틸 )-5-(3，4，5-트라이메틸피페라진-6- (4-Fluoro-2-methyl-5- (3— (trifluoromethyl) -5- (3,4,5-trimethylpiperazine-
1-일 )벤즈아미도)페닐)— ^메틸一 W— 1다졸 -3-카복스아미드 1-yl) benzamido) phenyl) — ^ methyl 一 W— 1dazole-3-carboxamide
트리플루오로아세트산염 (실시예 116); Trifluoroacetic acid salt (Example 116);
6一(4-플루오로 -2—메틸— 5-(3-( (4—메틸피페라진 -1—일)— 5-트리플루오로메틸)벤즈 아미도)페닐) 메틸ᅳ 1^인다졸—3-카복스아미드 (실시예 117);  6 一 (4-Fluoro-2—methyl— 5- (3- ((4—methylpiperazin-1-yl) — 5-trifluoromethyl) benz amido) phenyl) methyl ᅳ 1 ^ indazole— 3-carboxamide (Example 117);
6-(5— (3-(((2—디메틸아미노)에틸 (메틸)아미노)메틸)— 5— (트리플루오로메틸)벤즈 아미도 )-4—풀루오로 -2-메틸페닐) _ 메틸— 1^인다졸 -3-카복스아미드 (실시예 118)； 6- (5— (3-(((2—dimethylamino) ethyl (methyl) amino) methyl) — 5— (trifluoromethyl) benz amido) -4—pululouro-2-methylphenyl) _methyl — 1 ^ indazole-3-carboxamide (Example 118);
6-(5-(3-( (2—아미노에틸 )아미노 )-5ᅳ (트리플루오로메틸 )벤즈아미도 )-4_플루오로 6- (5- (3- ((2—aminoethyl) amino) -5 ′ (trifluoromethyl) benzamido) -4_fluoro
-2—메틸페닐)— 메틸ᅳ 1^인다졸 -3-카복스아미드 (실시예 119); -2—methylphenyl) —methyl ᅳ 1 ^ indazole-3-carboxamide (Example 119);
6-(5-(3-((2—아미노— 2-메틸프로필)아미노 )-5- (트리플루오로메틸)벤즈아미도)ᅳ 46- (5- (3-((2—amino— 2-methylpropyl) amino) -5- (trifluoromethyl) benzamido) ᅳ 4
-플루오로 -2-메틸페닐) - 메틸 -1^인다졸—3—카복스아미드 (실시예 120); -Fluoro-2-methylphenyl) -methyl-1 ^ indazole—3—carboxamide (Example 120);
6一 (5_(3-((2-디메틸아미노—2-메틸프로필)아미노)ᅳ 5- (트리플루오로메틸)벤즈아 미도) -4-플루오로— 2-메틸페닐)—^메틸— 1^인다졸 -3—카복스아미드  6 一 (5_ (3-((2-dimethylamino—2-methylpropyl) amino) ᅳ 5- (trifluoromethyl) benzamido) -4-fluoro— 2-methylphenyl) — ^ methyl— 1 ^ Indazole-3—carboxamide
트리플루오로아세트산염 (실시예 121); Trifluoroacetic acid salt (Example 121);
6-(4—풀루오로— 5ᅳ (3-((2-하이드록시부틸)아미노)ᅳ 5- (트리플루오로메틸)벤즈아 미도)—2-메틸페닐) 메틸— 인다졸 -3—카복스아미드 (실시예 122); 6- (4—Pluoro— 5 ′ (3-((2-hydroxybutyl) amino) ᅳ 5- (trifluoromethyl) benzamido) —2-methylphenyl) methyl— indazole-3—car Voxamide (Example 122);
6-(4-풀루오로— 5ᅳ(3-( (3—하이드록시프로필 )아미노 )-5- (트리플루오로메틸 )벤즈 아미도 )-2-메틸페닐)ᅳ 메틸 인다졸 -3-카복스아미드 (실시예 123);  6- (4-Pluoro— 5 ′ (3- ((3—hydroxypropyl) amino) -5- (trifluoromethyl) benz amido) -2-methylphenyl) ᅳ methyl indazole-3-car Voxamide (Example 123);
6-(4—플루오로 -5ᅳ (3-( (2—하이드록시에틸 )아미노 )ᅳ5- (트리풀루오로메틸 )벤즈아 미도)—2-메틸페닐)— ^메틸 인다졸—3-카복스아미드 (실시예 124);  6- (4—Fluoro-5 ′ (3- ((2—hydroxyethyl) amino) ᅳ 5- (trifuluromethyl) benzamido) —2-methylphenyl) — ^ methyl indazole—3- Carboxamide (Example 124);
6— (4—플루오로— 5— (3-( (2—하이드록시프로필)아미노 )-5- (트리플루오로메틸)벤즈 아미도 )-2-메틸페닐)ᅳ^메틸 -1^인다졸 -3-카복스아미드 (실시예 125);  6— (4—fluoro— 5— (3- ((2—hydroxypropyl) amino) -5- (trifluoromethyl) benz amido) -2-methylphenyl) ᅳ ^ methyl-1 ^ indazole- 3-carboxamide (Example 125);
6-(4-풀루오로 -5ᅳ(3— ( (2—하이드록시—2—메틸프로필 )아미노 )-5— (트리플루오로메 틸)벤즈아미도 )-2_메틸페닐) - 메틸— 인다졸—3ᅳ카복스아미드 (실시예 126); 6— (4-풀루오로 -2-메틸 -5-(3- (메틸) ( ( 1-메틸—1^피라졸 -4—일 )메틸)아미노) -5-( 트리플루오로메틸 )벤즈아미도)페닐 )—^메틸 -1^인다졸—3-카복스아미드 (실시예 6- (4-Pluoro-5 ′ (3— ((2—hydroxy—2—methylpropyl) amino) -5— (trifluoromethyl) benzamido) -2_methylphenyl) -methyl- Sol—3′carboxamide (Example 126); 6— (4-Pluoro-2-methyl-5- (3- (methyl) ((1-methyl-l ^ pyrazol-4-yl) methyl) amino) -5- (trifluoromethyl) benz Amido) phenyl) — ^ methyl-1 ^ indazole—3-carboxamide (Example
127)； 127);
6-(5-(3-(2-디메틸아미노)에록시 )-5— (트리풀루오로메틸)벤즈아미도) -4—풀루오  6- (5- (3- (2-dimethylamino) ethoxy) -5— (trifuluromethyl) benzamido) -4—pulluo
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대체용지 (규칙 제 26조) 로 -2ᅳ메틸페닐)—^메틸— 인다졸—3ᅳ카복스아미드 (실시예 128); Alternative Site (Article 26) Rho-2′methylphenyl) — ^ methyl—indazole—3′carboxamide (Example 128);
6-(4ᅳ플루오로— 2—메틸 -5— (3ᅳ(2-(1-메틸피롤린 -2—일)에특시 )— 5- (트리플루오로메 틸)벤즈아미도)페닐) 메틸— 1^인다졸—3ᅳ카복스아미드 (실시예 129);  6- (4 ᅳ fluoro— 2—methyl-5— (specific to 3 ᅳ (2- (1-methylpyrroline-2—yl)) — 5- (trifluoromethyl) benzamido) phenyl) methyl — 1 ^ indazole—3′carboxamide (Example 129);
6一(5ᅳ (3— (2- (디메틸아미노)— 2-메틸프로폭시 )-5ᅳ (트리플루오로메틸)벤즈아미도) 6 ((5 ᅳ (3— (2- (dimethylamino) — 2-methylpropoxy) -5 ᅳ (trifluoromethyl) benzamido)
-4一플루오로 -2—메틸페닐) - 메틸 - 1^인다졸—3-카복스아미드 -4 fluoro -2 -methylphenyl) -methyl -1 ^ indazole- 3-carboxamide
트리플투오로아세트산염 (실시예 130); Triple toroacetic acid salt (Example 130);
6-(5ᅳ (3-(2—아미노 -2-메틸프로폭시 )ᅳ5- (트리플루오로메틸 )벤즈아미도)—4ᅳ플루 오로ᅳ 2—메틸페닐)— ^메틸 -1^인다졸ᅳ 3-카복스아미드 (실시예 131);  6- (5 ′ (3- (2—amino-2-methylpropoxy) ᅳ 5- (trifluoromethyl) benzamido) —4′fluoropent 2—methylphenyl) — ^ methyl-1 ^ indazole (Iii) 3-carboxamide (Example 131);
6-(5ᅳ(3-((1— (디메틸아미노)프로판 _2-일)옥시)— 5— (트리플루오로메틸)벤즈아미 도)— 4-풀루오로— 2—메틸페닐) -yV "메틸 인다졸—3-카복스아미드 6- (5 ᅳ (3-((1— (dimethylamino) propane _2-yl) oxy) — 5— (trifluoromethyl) benzamido) — 4-pululo— 2—methylphenyl) -yV " Methyl Indazole—3-Carboxamide
트리플루오로아세트산염 (실시예 132); Trifluoroacetic acid salt (Example 132);
6-(5-(3ᅳ (피를리딘 -1—일에특시) -5- (트리플루오로메틸)벤즈아미도) -4-풀루오로ᅳ 2一메틸페닐)—^메틸 -1^인다졸 -3—카복스아미드 (실시예 133);  6- (5- (3 '(Pyridin-1-yl)-5- (trifluoromethyl) benzamido) -4-puloloro-2-one methylphenyl)-^ methyl -1 ^ Indazole-3—carboxamide (Example 133);
6-(4-플루오로— 5-(3— (4—풀루오로 -3-메틸페닐)우레이도) -2-메틸페닐)— ^메틸 -인다졸 -3-카복스아미드 (실시예 134); 6- (4-fluoro— 5- (3— (4—Pluoro-3-methylphenyl) ureido) -2-methylphenyl) — ^ methyl-indazole-3-carboxamide (Example 134);
(£)-6— (4—풀루오로 -5-(3-(3— (1ᅳ (하이드록시이미노)에틸)페닐)우레이도)— 2—메틸 페닐) - ^메틸 -1^인다졸—3-카복스아미드 (실시예 135); (£ ) -6— (4—Pluoro-5- (3- (3— (1 ᅳ (hydroxyimino) ethyl) phenyl) ureido) — 2—methyl phenyl)-^ methyl-1 ^ indazole —3-carboxamide (Example 135);
6- ( 4-플루오로— 2ᅳ메틸ᅳ5— ( 3— ( 3ᅳ (트리플투오로메틸)페닐)우레이도)페닐)—Λ1 "메틸 -1^인다졸 -3ᅳ카복스아미드 (실시예 136); 6- (4-fluoro— 2—methyl ᅳ 5— (3— (3 ᅳ (tripletomethyl) phenyl) ureido) phenyl) —Λ 1 "methyl-1 ^ indazole-3 -carboxamide (implemented Example 136);
6一 (4—플루오로 -2—메틸 -5— (3— (4-메틸 -3— (트리플루오로메틸)페닐)우레이도)페닐) - 메틸 -1^인다졸 -3-카복스아미 (실시예 137);  6 一 (4—Fluoro-2—methyl-5— (3— (4-methyl-3— (trifluoromethyl) phenyl) ureido) phenyl) -methyl-1 ^ indazole-3-carboxami (Example 137);
6-(5-(3ᅳ (4-클로로 _3- (트리플루오로메틸)페닐)우레이도)— 4ᅳ폴루오로ᅳ 2ᅳ메틸페 닐)ᅳ^메틸ᅳ 1^인다졸 -3-카복스아미드 (실시예 138);  6- (5- (3 '(4-Chloro_3- (trifluoromethyl) phenyl) ureido) —4'polouro'2'methylphenyl)' ^ methyl'1 ^ indazole-3-carbox Amides (Example 138);
6一 (5-(3-(3, 5-비스 (트리풀루오로메틸)페닐)우레이도)ᅳ 4—플루오로— 2ᅳ메틸페닐) - ^메틸—1^인다졸 -3ᅳ카복스아미드 (실시예 139);  6- (5- (3- (3,5-bis (tripulouromethyl) phenyl) ureido) ᅳ 4—fluoro—2 ᅳ methylphenyl)-^ methyl-1 ^ indazole-3 ᅳ carboxamide ( Example 139);
6— (5-(3ᅩ(3，4—디메틸페닐)우레이도)—4—플루오로 -2-메틸페닐)— ^메틸— 1^인다졸 -3-카복스아미드 (실시예 140)； 6— (5- (3 ᅩ (3,4 dimethylphenyl) ureido) —4—fluoro-2-methylphenyl) — ^ methyl—1 ^ indazole-3-carboxamide (Example 140);
6-(4-풀루오로 -5ᅳ(3ᅳ (3—풀루오로 -5— (트리폴루오로메틸)페닐)우레이도)ᅳ 2-메틸 페닐) 메틸— 1^인다졸—3-카복스아미드 (실시예 141);  6- (4-Pluoro-5 (3) (3—Pluoro-5— (trifluoromethyl) phenyl) ureido) ᅳ 2-methylphenyl) methyl—1 ^ indazole—3- Carboxamide (Example 141);
6一 (4-풀루오로 -5ᅳ (3-(3-풀루오로 -4-메틸페닐)우레이도) -2-메틸페닐)— 메틸 -인다졸 -3-카복스아미드 (실시예 142); 6- (4-Pluoro-5 ′ (3- (3-Pluoro-4-methylphenyl) ureido) -2-methylphenyl) —methyl-indazole-3-carboxamide (Example 142);
6-(5-(3-(3ᅳ클로로 -4—플루오로페닐 )우레이도) -4—플루오로— 2—메틸페닐)ᅳ^메틸ᅳ 1^인다졸 -3-카복스아미드 (실시예 143);  6- (5- (3- (3 ᅳ Chloro-4—fluorophenyl) ureido) -4—fluoro- 2—methylphenyl) ᅳ ^ methyl ᅳ 1 ^ indazole-3-carboxamide (Example 143 );
6-(5— (3— ᅳ부틸)페닐)우레이도) -4—플루오로ᅳ 2-메틸페닐) 메틸 -1^인 다졸— 3-카복스아미드 (실시예 144);  6- (5— (3—butylbutyl) phenyl) ureido) -4—fluorophenyl 2-methylphenyl) methyl-1 ^ dazole—3-carboxamide (Example 144);
6-(5— (3— (4ᅳ ( erᅳ부틸)페닐)우레이도)— 4-플루오로 -2—메틸페닐) 메틸 -1^인 다졸 -3-카복스아미드 (실시예 145)；  6- (5— (3— (4 ′ (er ᅳ butyl) phenyl) ureido) —4-fluoro-2-2-methylphenyl) dazole-3-carboxamide which is methyl-1 ^ (Example 145);
6-(5— (3-(4ᅩ클로로페닐)우레이도) -4-플루오로ᅳ 2-메틸페닐) - ^메틸 -1^인다졸 -3 -카복스아미드 (실시예 146)； 6- (5— (3- ( 4'Chlorophenyl ) ureido) -4-fluoro'2-methylphenyl)-^ methyl-l-indazole-3-carboxamide (Example 146);
6一 (5— (3-(3，4—디플로오로페닐)우레이도)— 4—플루오로— 2—메틸페닐)ᅳ 메틸 -1^인 다졸— 3—카복스아미드 (실시예 147);  6- (5 -— (3- (3,4—difluorophenyl) ureido) —4—fluoro—2—methylphenyl) ᅳ methyl-1 ^ dazole- 3—carboxamide (Example 147);
6-(4-플루오로 -5ᅳ (3-(4ᅳ플루오로페닐)우레이도) -2-메틸페닐) - ^메틸 - 인다졸 ᅳ 3-카복스아미드 (실시예 148)；  6- (4-fluoro-5 '(3- (4'fluorophenyl) ureido) -2-methylphenyl)-^ methyl-indazole ᅳ 3-carboxamide (Example 148);
156  156
대체용지 (규칙 제 26조) 6-(4-폴루오로ᅳ 5— (3— (4ᅳ플루오로— 3- (트리풀루오로메틸)페닐)우레이도)ᅳ 2-메틸 페닐) -/ "메틸— 1^인다졸—3-카복스아미드 (실시예 149); Alternative Site (Article 26) 6- (4-Polourosulf-5— (3— (4 ᅳ fluoro— 3- (tripulouromethyl) phenyl) ureido) ᅳ 2-methyl phenyl)-/ "methyl— 1 ^ indazole— 3-carboxamide (Example 149);
6一 ( 5— ( 3- ( 3-시아노페닐)우레이도) -4—풀루오로 -2-메틸페닐)— ^메틸ᅳ 1^인다졸 -3 -카복스아미드 (실시예 150);  6 one (5— (3- (3-cyanophenyl) ureido) -4—pululouro-2-methylphenyl) — ^ methyl ᅳ 1 ^ indazole-3-carboxamide (Example 150);
6— (5— (3-(3—아세틸페닐)우레이도) -4-플루오로 -2-메틸페닐)ᅳ^메틸 -1^인다졸 -3 -카복스아미드 (실시예 151);  6— (5— (3- (3—acetylphenyl) ureido) -4-fluoro-2-methylphenyl) ᅳ ^ methyl-1 ^ indazole-3 -carboxamide (Example 151);
6-(4-플루오로ᅳ 2-메틸 -5-(3-(3- (트리플루오로메록시)페닐)우레이도)페닐)—^메 틸ᅳ 1 y다졸 -3_카복스아미드 (실시예 152);  6- (4-fluoro ᅳ 2-methyl-5- (3- (3- (trifluoromethoxy) phenyl) ureido) phenyl) — ^ methyl ᅳ 1 ydazole-3_carboxamide (Example 152);
6-(4—폴루오로 -5-(3-(4-플루오로 -3-나이트로페닐)우레이도) -2—메틸페닐) - ^메 틸ᅳ 1^인다졸 -3-카복스아미드 (실시예 153);  6- (4—Polouro-5- (3- (4-fluoro-3-nitrophenyl) ureido) -2-methylphenyl)-^ methyl 메 1 ^ indazole-3-carboxamide ( Example 153);
6一 (4—플루오로ᅳ 2-메틸 -5-(3—(4ᅳ메틸 -3-니트로페닐)우레이도)페닐) - 메틸— 인다졸 -3—카복스아미드 (실시예 154)；  6- (4—Fluoro ᅳ 2-methyl-5- (3— (4 ᅳ methyl-3-nitrophenyl) ureido) phenyl) -methyl-indazole-3—carboxamide (Example 154);
6-(4-폴루오로ᅳ5-(3-(3-이소프로필페닐)우레이도)—2-메틸페닐) 메틸 -L 인다 졸 -3-카복스아미드 (실시예 155)；  6- (4-fluorouro5-5- (3- (3-isopropylphenyl) ureido) —2-methylphenyl) methyl-L indazole-3-carboxamide (Example 155);
6-(5-(3- (벤조 [d][l,3]디옥솔 -5—일)우레이도 )_4—플루오로 -2-메틸페닐) - ^메틸- 1^인다졸 -3-카복스아미드 (실시예 156)；  6- (5- (3- (benzo [d] [l, 3] dioxol-5—yl) ureido) _4—fluoro-2-methylphenyl)-^ methyl-1 ^ indazole-3-carbox Amide (Example 156);
6- ( 5— ( 3- ( 3- ( 2-시아노프로판 -2-일)페닐)우레이도)—4-플투오로 -2—메틸페닐 H 메틸 -1^인다졸—3-카복스아미드 (실시예 157);  6- (5— (3- (3- (2- (2-cyanopropane-2-yl) phenyl) ureido)-4- pluturo-2-methylphenyl H methyl-1 ^ indazole-3-carboxamide ( Example 157);
6-(5-(3-(3-(2-시아노프로판 -2ᅳ일)ᅳ 4-폴루오로페닐)우레이도) -4-플루오로— 2-메 틸페닐)ᅳ^메틸 -1^인다졸 -3-카복스아미드 (실시예 158);  6- (5- (3- (3- (2-cyanopropane-2xyl) ᅳ 4-fluorofluoro) ureido) -4-fluoro— 2-methylphenyl) ᅳ ^ methyl -1 ^ Indazole-3-carboxamide (Example 158);
6一 ( 5- (3- (3- ((디메틸아미노)메틸) -4-플루오로페닐)우레이도)—4-플루오로— 2-메 틸페닐)— ^메틸—L 인다졸 -3-카복스아미드 (실시예 159);  6 一 (5- (3- (3- ((dimethylamino) methyl) -4-fluorophenyl) ureido) —4-fluoro— 2-methylphenyl) — ^ methyl—L indazole-3- Carboxamide (Example 159);
6-(4-플루오로— 5ᅳ(3— (4—플루오로 -3ᅳ (트리플루오로메특시)페닐)우레이도)— 2ᅳ메 틸페닐) 메틸 -1^인다졸 -3—카복스아미드 (실시예 160);  6- (4-fluoro—5 ′ (3— (4—fluoro-3 ′ (trifluoromepoxy) phenyl) ureido) —2′methylphenyl) methyl-1 ^ indazole-3—carbox Amide (Example 160);
6-(4—폴루오로 -5-(3— (3ᅳ ((트리플루오로메틸)싸이오)페닐)우레이도)페닐) - ^메 틸 -1^인다졸 -3-카복스아미드 (실시예 161);  6- (4—Polouro-5- (3— (3 ᅳ ((trifluoromethyl) thio) phenyl) ureido) phenyl)-^ methyl-1 ^ indazole-3-carboxamide ( Example 161;
6-(4-플루오로 -5-(3— (3—풀루오로페닐)우레이도) -2—메틸페닐)— ^메틸 -1 ^인다졸 -3-카복스아미드 (실시예 162)；  6- (4-fluoro-5- (3— (3—Pluorophenyl) ureido) -2—methylphenyl) — ^ methyl-1 ^ indazole-3-carboxamide (Example 162);
6— ( 5- ( 3ᅳ ( 3ᅳ (디플루오로메톡시)페닐)우레이도 ) -4_플루오로 -2—메틸페닐) - ^메틸 -1 ^인다졸 -3-카복스아미드 (실시예 163);  6— (5- (3 ′ (3 ′ (difluoromethoxy) phenyl) ureido) -4_fluoro-2—methylphenyl)-^ methyl-1 ^ indazole-3-carboxamide (Example 163 );
6一 (5-(3-(2ᅳ클로로— 3- (트리플루오로메틸)페닐)우레이도)—4-플루오로 -2-메틸페 닐)— 메틸 -1 "인다졸 -3—카복스아미드 (실시예 164);  6- (5- (3- (2 ᅳ chloro— 3- (trifluoromethyl) phenyl) ureido) —4-fluoro-2-methylphenyl) —methyl-1 “indazol-3—carbox Amide (Example 164);
6— (5-(3-(2-클로로—5— (트리플루오로메틸)페닐)우레이도)— 4—플루오로 -2-메틸페 닐) - ^메틸 -L 인다졸—3-카복스아미드 (실시예 165);  6— (5- (3- (2-chloro—5— (trifluoromethyl) phenyl) ureido) — 4—fluoro-2-methylphenyl)-^ methyl-L indazole—3-carbox Amide (Example 165);
6一(4-풀루오로 -2-메틸 -5— (3-(3— (4-메틸피페라진 -1-일 )-5— (트리플루오로메틸 )페 닐)우레이도)페닐) - ^메틸 -1^인다졸 -3ᅳ카복스아미드 (실시예 166);  6 一 (4-Pluoro-2-methyl-5— (3- (3— (4-methylpiperazin-1-yl) -5— (trifluoromethyl) phenyl) ureido) phenyl)- ^ Methyl-1 ^ indazole-3 -carboxamide (Example 166);
6-(4—플루오로 -2—메틸 -5-(3ᅳ (2-몰포리노 -5- (트리플투오로메틸)페닐)우레이도) 페닐) -/V·메틸— 1 "인다졸 -3_카복스아미드 (실시예 167); 6- (4—Fluoro-2-methyl-5- (3 ′ (2-morpholino-5- (triplefluoromethyl) phenyl) ureido) phenyl)-/ V-methyl— 1 "indazol-3 _Carboxamide (Example 167);
6-(4-플루오로 -2-메틸 -5-(3ᅳ(4-(2- (피롤리딘— 1-일)에록시 )-3- (트리플루오로메 틸)페닐)우레이도)페닐) 메틸 -1 ^인다졸—3—카복스아미드 (실시예 168); 6-(4-플루오로 -2-메틸ᅳ 5-(3-(3— (4-메틸피페라진ᅳ1-일)페닐)우레이도)페닐) 메틸— 1^인다졸 -3—카복스아미드 (실시예 169);  6- (4-fluoro-2-methyl-5- (3 ′ (4- (2- (pyrrolidin— 1-yl) ethoxy) -3- (trifluoromethyl) phenyl) ureido) phenyl ) Methyl-1 ^ indazole-3 and carboxamide (Example 168); 6- (4-fluoro-2-methyl 5- (3- (3— (4-methylpiperazin ᅳ 1-yl) phenyl) ureido) phenyl) methyl— 1 ^ indazole-3—carboxamide (Example 169);
6-(4—플루오로 -2-메틸— 5— (3ᅩ(4— (4-메틸피페라진— 1-일)— 3- (트리플루오로메틸)페 6- (4—fluoro-2-methyl— 5— (3 ᅩ (4— (4-methylpiperazin— 1-yl) — 3- (trifluoromethyl) phenyl
157  157
대체용지 (규칙 제 26조) 닐)우레이도)페닐)—^메틸 -1^인다졸 -3-카복스아미드 트리플루오로아세트산염 (실시예 170)； Alternative Site (Article 26) Nil) ureido) phenyl) — ^ methyl-1 ^ indazole-3-carboxamide trifluoroacetic acid salt (Example 170);
6- ( 4-플루오로 -5- ( 3- ( 4_플루오로 -3-메틸페닐)싸이오우레이도)— 2-메틸페닐) 메틸— 1^인다졸 -3-카복스아미드 (실시예 171);  6- (4-Fluoro-5- (3- (4_fluoro-3-methylphenyl) thioureido) — 2-methylphenyl) methyl- 1 ^ indazol-3-carboxamide (Example 171) ;
6-(5-(3-(4-클로로ᅳ 3— (트리플루오로메틸)페닐)싸이오우레이도) -4-플루오로 2一메 틸페닐) ^메틸 -1^인다졸 -3—카복스아미드 (실시예 172); 6- (5- (3- (4-chloro ᅳ 3— (trifluoromethyl) phenyl) thioureido) -4-fluoro 2 butylphenyl) ^ methyl-1 ^ indazole-3—car Voxamide (Example 172);
6-(4-플루오로 -5_(3— (4-플루오로 -3ᅳ (트리플루오로메틸)페닐)—3-메틸우레이도) - 6- (4-Fluoro-5_ (3— (4-fluoro-3 ′ (trifluoromethyl) phenyl) —3-methylureido)-
2-메틸페닐) 메틸— 1^인다졸ᅳ3-카복스아미드 (실시예 173); 2-methylphenyl) methyl — ^^ indazole ᅳ 3-carboxamide (Example 173);
6-(4-플루오로 -5-(3-(4-플루오로— 3ᅳ (트리플루오로메틸)페닐) -1-메틸우레이도) - 2-메틸페닐) - ^메틸 -1^인다졸 3-카복스아미드 (실시예 174);  6- (4-Fluoro-5- (3- (4-fluoro- 3 '(trifluoromethyl) phenyl) -1-methylureido)-2-methylphenyl)-^ methyl-1 ^ indazole 3 Carboxamide (Example 174);
6-(4-폴루오로 -2-메틸 -5-(3-(4ᅳ메틸피페라진 -1ᅳ일) 5- (트리폴루오로메틸)페닐) 벤즈아미도)페닐) -Λ 피리딘—4-일 인다졸 -3-카복스아미드 (실시예 175); 6- (4-Polouro-2-methyl-5- (3- (4 ᅳ methylpiperazin-1xyl) 5- (trifluoromethyl) phenyl) benzamido) phenyl) -Λ pyridine—4 -Yl indazole-3-carboxamide (Example 175);
Λ 사이클로프로필 _6-(4-플루오로 -2ᅳ메틸 -5-(3-(4_메틸피페라진 -1—일) -5— (트리 플루오로메틸)벤즈아미도)페닐)—L 인다졸 -3-카복스아미드 (실시예 176); 6-(4—풀루오로 -2-메틸— 5-(3-(4ᅳ메틸피페라진 -1ᅳ일) -5- (트리플루오로메틸)페닐) 벤즈아미도)페닐) -1^인다졸—3-카복스아미드 (실시예 177); Λ cyclopropyl _6- (4-fluoro-2 ᅳ methyl-5- (3- (4_methylpiperazin-1-yl) -5— (trifluoromethyl) benzamido) phenyl) —L indazole -3-carboxamide (Example 176); 6- (4—Pluoro-2-methyl— 5- (3- (4 ᅳ methylpiperazin-1xyl) -5 (trifluoromethyl) phenyl) benzamido) phenyl) -1 ^ indazole —3-carboxamide (Example 177);
6-(4—풀루오로 -2-메틸 -5— (3-(4ᅳ메틸피페라진 1-일) -5- (트리플루오로메틸)페닐) 벤즈아미도)페닐) 디메틸 -1^인다졸—3-카복스아미드 (실시예 178);  6- (4—Pluoro-2-methyl-5— (3- (4 ᅳ methylpiperazin 1-yl) -5 (trifluoromethyl) phenyl) benzamido) phenyl) dimethyl-1 ^ is Sol—3-carboxamide (Example 178);
Λ 2-플루오로 -4-메틸— 5-(3- (피페라진 -1-카보닐 )— 1 "인다졸 -6-일)페닐) 3-(4- 메틸피페라진 -1-일)— 5- (트리플루오로메틸)벤즈아미드 (실시예 179);  Λ 2-Fluoro-4-methyl— 5- (3- (piperazin-1-carbonyl) — 1 "indazol-6-yl) phenyl) 3- (4-methylpiperazin-1-yl) — 5- (trifluoromethyl) benzamide (Example 179);
2-풀루오로 -4-메틸 -5— ( 3- (4—메틸피페라진 1-카보닐 ) 1^인다졸 -6-일)페닐) - 2-Pluoro-4-methyl-5— (3- (4—methylpiperazin 1-carbonyl) 1 ^ indazol-6-yl) phenyl)-
3 (4-메틸피페라진 -1-일) -5— (트리플루오로메틸)벤즈아미드 (실시예 180);3 (4-methylpiperazin-1-yl) -5— (trifluoromethyl) benzamide (Example 180);
6— (4-플루오로— 2—메틸 -5_(3_(4—메틸피페라진 1-일)ᅳ 5— (트리플루오로메틸)페닐) 벤즈아미도)페닐) - 피페리딘 -4-일)— 1^인다졸—3-카복스아미드 (실시예 181); 6-(4-플루오로 -2—메틸— 5-(3-(4-메틸피페라진 -1ᅳ일) -5- (트리플루오로메틸)페닐) 벤즈아미도)페닐) -Λ 1ᅳ메틸피페리딘 -4-일) - 1^인다졸 _3—카복스아미드 (실시예6— (4-fluoro— 2—methyl-5_ (3_ (4—methylpiperazin 1-yl) ᅳ 5— (trifluoromethyl) phenyl) benzamido) phenyl) -piperidin-4-yl ) —1 ^ indazole—3-carboxamide (Example 181); 6- (4-fluoro-2—methyl— 5- (3- (4-methylpiperazin-1xyl) -5- (trifluoromethyl) phenyl) benzamido) phenyl) -Λ 1 ᅳ methylpi Ferridin-4-yl) -1 ^ indazole _3—carboxamide (Example
182)； 182);
6 (4-플루오로 -2-메틸— 5-(3-(4-메틸피페라진 -1ᅳ일 )ᅳ5- (트리플루오로메틸)페닐 ) 벤즈아미도)페닐)—Λ 4-메틸피페리딘 -1-일) -1^인다졸 -3-카복스아미드 (실시예 183)；  6 (4-fluoro-2-methyl— 5- (3- (4-methylpiperazin-1xyl) ᅳ 5- (trifluoromethyl) phenyl) benzamido) phenyl) —Λ 4-methylpiperi Din-1-yl) -1 ^ indazole-3-carboxamide (Example 183);
^싸이클로핵실— 6-(4-풀루오로 _2—메틸 -5-(3 (4-메틸피페라진 1ᅳ일)ᅳ 5— (트리플 투오로메틸)벤즈아미도)페닐)—1^인다졸 _3—카복스아미드 (실시예 184);  ^ Cyclonuclear chamber— 6- (4-Pluoro _2—methyl-5- (3 (4-methylpiperazin 1 ᅳ yl) ᅳ 5— (triple touromethyl) benzamido) phenyl) —1 ^ indazole _3 —Carboxamide (Example 184);
6-(4—플루오로 -2-메틸 -5-(3ᅳ (4-메틸피페라진 1-일)— 5- (트리플루오로메틸)페닐) 벤즈아미도)페닐)― 페닐— 1^인다졸 -3-카복스아미드 (실시예 185); 6- (4—Fluoro-2-methyl-5- (3 ′ (4-methylpiperazin 1-yl) — 5- (trifluoromethyl) phenyl) benzamido) phenyl) -phenyl—1 ^ Sol-3-carboxamide (Example 185);
6-(4-풀루오로— 2—메틸— 5— (3ᅳ (4-메틸피페라진 -1-일 )ᅳ5— (트리플루오로메틸)페닐) 벤즈아미도)페닐) -Λ 피리딘—2-일) -1^인다졸—3—카복스아미드 (실시예 186); 6-(4-플루오로 -2-메틸 -5_(3ᅳ(4-메틸피페라진 1-일)ᅳ 5- (트리플루오로메틸)페닐) 벤즈아미도)페닐) 피리딘 -3—일) -1^인다졸 -3—카복스아미드 (실시예 187); 6-(4—플루오로— 2-메틸 -5-(3ᅳ (4-메틸피페라진— 1-일)— 5- (트리플루오로메틸)페닐) 벤즈아미도)페닐)— 하이드록시 -1^인다졸 -3—카복스아미드 (실시예 188);6- (4-Pluoro— 2—methyl— 5— (3 ′ (4-methylpiperazin-1-yl) ᅳ 5— (trifluoromethyl) phenyl) benzamido) phenyl) -Λ pyridine— 2-yl) -1 ^ indazole—3—carboxamide (Example 186); 6- (4-Fluoro-2-methyl-5_ (3 ′ (4-methylpiperazin 1-yl) ᅳ 5- (trifluoromethyl) phenyl) benzamido) phenyl) pyridin-3—yl)- 1 ^ indazole-3—carboxamide (Example 187); 6- (4—Fluoro— 2-methyl-5- (3 ′ (4-methylpiperazin— 1-yl) — 5- (trifluoromethyl) phenyl) benzamido) phenyl) —hydroxy-1 ^ Indazole-3—carboxamide (Example 188);
6 (4-풀루오로— 2—메틸 -5— (3ᅳ (4-메틸피페라진—1-일 )-5- (트리풀루오로메틸)페닐) 벤즈아미도)페닐)— 6-플루오로피리딘ᅳ 3—일) -1^인다졸—3-카복스아미드 트리플루오로아세트산염 (실시예 189); 6 (4-Pluoro— 2—methyl-5— (3 ′ (4-methylpiperazin—1-yl) -5- (trifuluromethyl) phenyl) benzamido) phenyl) — 6-fluoro Ropyridinyl 3-yl) -1 ^ indazole-3-carboxamide trifluoroacetate (Example 189);
158  158
대체용지 (규칙 제 26조) 6ᅳ(4-플루오로 -2—메틸— 5-(3ᅳ (4-메틸피페라진 -1-일)ᅳ 5- (트리풀루오로메틸)페닐) 벤즈아미도)페닐) -Λ 6—메틸피리딘— 3-일)ᅳ ΙΛί"인다졸 -3-카복스아미드 Alternative Site (Article 26) 6 '(4-Fluoro-2—methyl— 5- (3' (4-methylpiperazin-1-yl) ᅳ 5- (trifulomethyl) phenyl) benzamido) phenyl) -Λ 6— methylpyridin-3- yl) eu ΙΛ ί "indazole-3-carboxamide
트리폴루오로아세트산염 (실시예 190); Tripolouroacetic acid salt (Example 190);
6- ( 4-플루오로 -2-메틸— 5- ( 3- ( 4—메틸피페라진 - 1-일) -5- (트리플투오로메틸)페닐) 벤즈아미도)페닐)— 메틸피리딘— 3—일 )—1^인다졸 -3-카복스아미드  6- (4-fluoro-2-methyl— 5- (3- (4—methylpiperazin-1-yl) -5- (triplopuromethyl) phenyl) benzamido) phenyl) — methylpyridine— 3 —Yl) —1 ^ indazole-3-carboxamide
트리플루오로아세트산염 (실시예 191); Trifluoroacetic acid salt (Example 191);
6-(4ᅳ플루오로 -2-메틸 -5— (3-(4-메틸피페라진— 1-일) -5- (트리플루오로메틸)페닐) 벤즈아미도)페닐) -Λ 피리미딘ᅳ5-일) -1^인다졸—3—카복스아미드  6- (4 ᅳ fluoro-2-methyl-5— (3- (4-methylpiperazin— 1-yl) -5 (trifluoromethyl) phenyl) benzamido) phenyl) -Λ pyrimidine ᅳ 5-day) -1 ^ indazole—3—carboxamide
트리플루오로아세트산염 (실시예 192); Trifluoroacetic acid salt (Example 192);
^벤질 -6-(4—플루오로ᅳ 2—메틸 -5-(3-(4-메틸피페라진— 1-일)— 5— (트리플루오로메 틸)벤즈아미도)페닐) -1^인다졸 -3—카복스아미드 (실시예 193); ^ Benzyl-6- (4—fluoro ᅳ 2—methyl-5- (3- (4-methylpiperazin— 1-yl) — 5— (trifluoromethyl) benzamido) phenyl) -1 ^ Sol-3—carboxamide (Example 193);
6一 (4ᅳ플루오로—2ᅳ메틸ᅳ 5-(3ᅳ (4-메틸피페라진 -1—일) -5- (트리풀루오로메틸)벤즈 아미도)페닐)ᅳ 피리딘—2_일메틸)— I 인다졸—3-카복스아미드 (실시예 194); 6- (4'fluoro-2'methyl ᅳ 5- (3 '(4-methylpiperazin-1-yl) -5- (trifuluromethyl) benz amido) phenyl) ᅳ pyridin—2_yl Methyl) —I indazole—3-carboxamide (Example 194);
Λ (6-클로로피리딘 -3ᅳ일 )메틸) -6-(4-플루오로 -2-메틸— 5— (3— (4—메틸피페라진一 1 -일 )ᅳ5— (트리풀루오로메틸)벤즈아미도)페닐)ᅳ Λ 피리미딘— 5-일 )ᅳ1^인다졸 -3- 카복스아미드 (실시예 195)； Λ (6-Chloropyridin-3 ᅳ yl) methyl) -6- (4-fluoro-2-methyl— 5— (3— (4—methylpiperazin 1 1-yl) ᅳ 5— (tripulouromethyl ) Benzamido) phenyl) ᅳ Λ pyrimidine- 5-yl) ᅳ 1 ^ indazole-3-carboxamide (Example 195);
6-(4-플루오로— 2-메틸ᅳ 5-(3-(4-메틸피페라진 -1-일) -5- (트리플루오로메틸)벤즈 아미도)페닐)—Λ 피리미딘— 4-일메틸 )-1^인다졸 -3ᅳ카복스아미드 (실시예 196); 6— (4ᅳ플루오로 -2-메틸ᅳ 5-(3-(4-메틸피페라진ᅳ 1-일)— 5ᅳ (트리풀루오로메틸)벤즈 아미도)페닐) -Λ 피리미딘— 3—일메틸 )-L 인다졸-카복스아미드 (실시예 197); 6- (4-fluoro— 2-methyl 2- 5- (3- (4-methylpiperazin-1-yl) -5- (trifluoromethyl) benz amido) phenyl) —Λ pyrimidine— 4- Ylmethyl) -1 ^ indazole-3 ᅳ carboxamide (Example 196); 6— (4 ᅳ fluoro-2-methyl ᅳ 5- (3- (4-methylpiperazin 페 1-yl) — 5 ᅳ (trifulomethyl) benz amido) phenyl) -Λ pyrimidine— 3 —Ylmethyl) -L indazole-carboxamide (Example 197);
6- (4-플루오로 _5— (3— (4-플루오로 _3— (트리플루오로메틸)페닐)우레이도)— 2-메틸 페닐) - 피리딘ᅳ2—일) -1^인다졸 -3-카복스아미드 (실시예 198); 6- (4-Fluoro_5— (3— (4-fluoro _3— (trifluoromethyl) phenyl) ureido) — 2-methyl phenyl) -pyridin ᅳ 2-yl) -1 ^ indazole-3 -Carboxamide (Example 198);
6-(4—폴루오로 -5-(3— (4-폴루오로 -3— (트리풀루오로메틸)페닐)우레이도) -2-메틸 페닐) -Λ 피리딘 -3-일)— 1^인다졸 -3-카복스아미드 (실시예 199); 6- (4—Polouro-5- (3— (4-Polouro-3— (Trifluorouromethyl) phenyl) ureido) -2-methyl phenyl) -Λ pyridin-3-yl) — 1 ^ indazole-3-carboxamide (Example 199);
6-(4-플루오로 -5ᅳ (3-(4—플루오로 -3- (트리플루오로메틸)페닐 )우레이도) -2ᅳ메틸 페닐) -Λ 4—메틸피페라진 -1-일) -1^인다졸—3-카복스아미드 (실시예 200); 6- (4-fluoro-5 '(3- (4—fluoro-3- (trifluoromethyl) phenyl) ureido) -2'methyl phenyl) -Λ 4-methylpiperazin-1-yl) -1 ^ indazole-3-carboxamide (Example 200);
6一 (4-플루오로— 5-(3-(4-플루오로— 3- (트리풀루오로메틸)페닐)우레이도) -2-메틸 페닐) - ^이소프로필 -1^인다졸ᅳ 3-카복스아미드 (실시예 201); 6- (4-Fluoro— 5- (3- (4-Fluoro— 3- (tripulouromethyl) phenyl) ureido) -2-methyl phenyl)-^ isopropyl-1 ^ indazol ᅳ 3 Carboxamide (Example 201);
^싸이클로프로필— 6-(4—풀루오로— 5-(3-(4-플루오로 _3ᅳ (트리플루오로메틸)페닐) 우레이도) -2—메틸페닐 )-L 인다졸ᅳ 3-카복스아미드 (실시예 202); ^ Cyclopropyl— 6- (4—Pluoro— 5- (3- (4-fluoro_3 ᅳ (trifluoromethyl) phenyl) ureido) -2—methylphenyl) -L indazole ᅳ 3-carbox Amides (Example 202);
6— (4-플투오로 -5ᅳ(3-(4-풀루오로— 3- (트리플루오로메틸)페닐 )우레이도) -2-메틸 페닐) - 몰포린 -1^인다졸 -3-카복스아미드 (실시예 203); 6— (4-Plutouro-5 ′ (3- (4-Pluoro— 3- (trifluoromethyl) phenyl) ureido) -2-methyl phenyl) -morpholine-1 ^ indazole-3- Carboxamide (Example 203);
6-(4—풀루오로— 5-(3-(4—풀루오로 -3— (트리플루오로메틸)페닐)우레이도)ᅳ 2-메틸 페닐) -Λ 피리딘 -2—일메틸 )-1^인다졸 -3-카복스아미드 (실시예 204); 6- (4—Pluoro— 5- (3- (4—Pluuro-3— (trifluoromethyl) phenyl) ureido) ᅳ 2-methyl phenyl) -Λ pyridine-2—ylmethyl)- 1 ^ indazole-3-carboxamide (Example 204);
6-(4-플루오로— 5ᅳ(3-(4-플루오로 -3- (트리풀루오로메틸)페닐)우레이도) -2-메틸 페닐) -Λ 피리딘ᅳ3-일메틸 )-L 인다졸 -3-카복스아미드 (실시예 205);  6- (4-Fluoro— 5 ᅳ (3- (4-fluoro-3- (trifuluromethyl) phenyl) ureido) -2-methyl phenyl) -Λ pyridin ᅳ 3-ylmethyl) -L Indazole-3-carboxamide (Example 205);
6- (4-플루오로— 5ᅳ( 3ᅳ (4—플루오로— 3— (트리플루오로메틸)페닐)우레이도)ᅳ 2-메틸 페닐)ᅳ 피리딘ᅳ4—일메틸 )—1^인다졸—3-카복스아미드 (실시예 206); 6- (4-Fluoro— 5 ᅳ (3 ᅳ (4—Fluoro— 3— (trifluoromethyl) phenyl) ureido) ᅳ 2-methyl phenyl) ᅳ pyridin ᅳ 4—ylmethyl) —1 ^ Sol—3-carboxamide (Example 206);
Λ (6-클로로피리딘ᅳ 3-일)메틸 )-6ᅳ(4-플루오로 -5-(3— (4—폴루오로 -3— (트리플루 오로메틸)페닐)우레이도 )ᅳ2-메틸페닐)— 1^인다졸 -3-카복스아미드 (실시예 207)； Λ (6-Chloropyridin- 3-yl) methyl) -6 ᅳ (4-fluoro-5- (3— (4—polouro-3— (trifluoromethyl) phenyl) ureido) ᅳ 2- Methylphenyl) -1 ^ indazole-3-carboxamide (Example 207);
6-(4_플루오로 -5-(3-(4—플루오로 -3— (트리풀루오로메틸)페닐)우레이도) -2-메틸  6- (4_fluoro-5- (3- (4—fluoro-3— (trifuluromethyl) phenyl) ureido) -2-methyl
159  159
대체용지 (규칙 제 26조) 페닐) -Λ 피리딘ᅳ 4-일 )-L^인다졸 -3—카복스아미드 (실시예 208); ¬에틸 -6-(4—풀루오로 -5ᅳ (3-(4-풀루오로 -3— (트리풀루오로메틸)페닐)우레이도)— Alternative Site (Article 26) Phenyl) -Λ pyridinyl 4-yl) -L ^ indazol-3—carboxamide (Example 208); ¬Ethyl-6- (4—Pluoro-5) (3- (4-Pluoro-3) (trifuluromethyl) phenyl) ureido)
2ᅳ메틸페닐)— 인다졸 -3-카복스아미드 (실시예 209);  2'methylphenyl) —indazole-3-carboxamide (Example 209);
Λ ( 1^이미다졸 -2—일 )메틸)— 6-(4-풀루오로— 5— (3— (4ᅳ플루오로 -3- (트리풀루오로 메틸)페닐)우레이도) -2—메틸페닐) -1^인다졸ᅳ 3ᅳ카복스아미드 (실시예 210);  Λ (1 ^ imidazol-2—yl) methyl) — 6- (4-pulluoro— 5— (3— (4 ᅳ fluoro-3- (tripulouro methyl) phenyl) ureido) -2 —Methylphenyl) -1 ^ indazole ᅳ 3′carboxamide (Example 210);
(R)-6-(4ᅳ플루오로 -5— (3-(4-플루오로 -3- (트리플루오로메틸)페닐)우레이도)ᅳ 2- 메틸페닐) -Λ 피롤리딘 -3-일)ᅳ 1^인다졸 -3—카복스아미드 (실시예 211);  (R) -6- (4 ᅳ fluoro-5) (3- (4-fluoro-3- (trifluoromethyl) phenyl) ureido) 도 2-methylphenyl) -Λ pyrrolidin-3-yl ) ᅳ 1 ^ indazole-3—carboxamide (Example 211);
(S)-6-(4-플루오로 -5-(3ᅳ (4-풀루오로ᅳ 3- (트리플루오로메틸)페닐)우레이도)一 2- 메틸페닐) -Λ 피롤리딘— 3-일) -1^인다졸 -3-카복스아미드 (실시예 212);  (S) -6- (4-Fluoro-5- (3 ′ (4-Pluorofluoro 3- (trifluoromethyl) phenyl) ureido) 一 2-methylphenyl) -Λ pyrrolidine— 3- (I) -1 ^ indazole-3-carboxamide (Example 212);
6ᅳ (4-풀루오로 -5-(3-(4_플루오로 -3- (트리풀루오로메틸)페닐)우레이도) -2ᅳ메틸 6 '(4-Pluoro-5- (3- (4_fluoro-3- (trifuluromethyl) phenyl) ureido) -2'methyl
페닐) -Λ 1-메틸 -1^이미다졸— 4-일) 다졸ᅳ 3—카복스아미드 (실시예 213); Phenyl) -Λ 1 -methyl-1 ^ imidazol—4-yl) dazolazole 3—carboxamide (Example 213);
6-(4-플루오로ᅳ 5ᅳ (3_(4—플루오로 -3- (트리풀루오로메틸)페닐)우레이도) -2-메틸  6- (4-fluoro ᅳ 5 ′ (3_ (4—fluoro-3- (trifuluromethyl) phenyl) ureido) -2-methyl
페닐) -Λ Ι^이미다졸ᅳ 4-일) -1^인다졸—3—카복스아미드 (실시예 214); Phenyl) -Λ Ι ^ imidazol ᅳ 4-yl) -1 ^ indazole—3—carboxamide (Example 214);
6ᅳ(4—풀루오로ᅳ 5— (3— (4—플루오로 -3- (트리풀루오로메틸)페닐 )우레이도)—2-메틸  6 '(4—Pluorouromethyl 5— (3— (4—Fluoro-3- (trifuluromethyl) phenyl) ureido) —2-methyl
페닐) -Λ 피리미딘 -4-일)— 1^인다졸 -3-카복스아미드 (실시예 215); Phenyl) -Λ pyrimidin-4-yl) —1 ^ indazole-3-carboxamide (Example 215);
6-(4-풀루오로 -5-(3ᅩ(4—플루오로— 3- (트리플루오로메틸)페닐)우레이도) -2-메틸 6- (4- Pluoro -5- (3 ᅩ (4—fluoro— 3- (trifluoromethyl) phenyl) ureido) -2-methyl
페닐)— Λ 6-메틸피리딘 -3-일 )ᅳ1^인다졸 -3ᅳ카복스아미드 (실시예 216); Phenyl) —Λ 6-methylpyridin-3-yl) ᅳ 1 ^ indazole-3 ᅳ carboxamide (Example 216);
6ᅳ (4-풀루오로ᅳ 5ᅳ (3— (4-플루오로 -3- (트리플루오로메틸)페닐)우레이도) -2ᅳ메틸  6 '(4-Pluorouro ᅳ 5' (3— (4-fluoro-3- (trifluoromethyl) phenyl) ureido) -2'methyl
페닐) -Λ 4—메틸피리딘 -3—일)ᅳ 1^인다졸—3ᅳ카복스아미드 (실시예 217); Phenyl) -Λ 4 -methylpyridin-3 -yl) ᅳ 1 ^ indazole—3′carboxamide (Example 217);
6-(4—풀루오로 -5-(3ᅳ(4-풀루오로— 3ᅳ (트리풀루오로메틸)페닐)우레이도)ᅳ 2ᅳ메틸 6- (4—Pluoro-5- (3 ′ (4-Pluoro— 3 ′ (trifuluromethyl) phenyl) ureido) ᅳ 2 ᅳ methyl
페닐)ᅳ (2_플루오로피리딘 -3—일) -1^인다졸ᅳ 3—카복스아미드 (실시예 218); Phenyl) '(2_fluoropyridin-3-yl) -1 ^ indazole ᅳ 3—carboxamide (Example 218);
6ᅳ(4-풀루오로ᅳ 5-(3ᅳ(4-풀루오로 -3- (트리풀루오로메틸)페닐)우레이도 )ᅳ2ᅳ메틸  6 '(4-Pluorouromethyl 5- (3' (4-Pluoro-3- (trifuluromethyl) phenyl) ureido) ᅳ 2'methyl
페닐)—Λ 5—플루오로피리딘 -3-일)— 1^인다졸 -3—카복스아미드 (실시예 219); Phenyl) —Λ 5—fluoropyridin-3-yl) —1 ^ indazole-3—carboxamide (Example 219);
6ᅳ(4—플루오로ᅳ 5-(3-(4—플루오로 -3ᅳ (트리플루오로메틸)페닐)우레이도) -2ᅳ메틸  6 '(4—Fluoro ᅳ 5- (3- (4—fluoro-3' (trifluoromethyl) phenyl) ureido) -2 ᅳ methyl
페닐)—Λ 6—플루오로피리딘ᅳ 3ᅳ일 )-1^인다졸 -3—카복스아미드 (실시예 220); Phenyl) —Λ 6—fluoropyridinyl 3xyl) -1 ^ indazole-3—carboxamide (Example 220);
6-(5-( (3- ieriᅳ부틸페닐)카바모일)ᅳ 4-플루오로— 2-메틸페닐) 메틸— 1^인다졸- 6- (5- ((3- ieri ᅳ butylphenyl) carbamoyl) ᅳ 4-fluoro- 2-methylphenyl) methyl- 1 ^ indazole-
3-카복스아미드 (실시예 221)； 3-carboxamide (Example 221);
6— (4-풀루오로ᅳ 2-메틸 -5-( (3- (트리플루오로메틸)페닐)카바모일)페닐) 메틸 -1  6— (4-Pluorohydro 2-methyl-5-((3- (trifluoromethyl) phenyl) carbamoyl) phenyl) methyl-1
^인다졸 -3-카복스아미드 (실시예 222); ^ Indazole-3-carboxamide (Example 222);
6— (4-플루오로 -5-((4-플루오로 -3ᅳ (트리풀루오로메틸)페닐)카바모일) -2—메틸페 6— (4-fluoro-5-((4-fluoro-3 ′ (trifuluromethyl) phenyl) carbamoyl) -2—methylfe
닐)— ^메틸 인다졸—3—카복스아미드 (실시예 223); Nil) — ^ methyl indazole—3—carboxamide (Example 223);
6-(4-플루오로 -2—메틸 -5_( (3-메틸 -5- (트리플루오로메틸)페닐)카바모일)페닐)一^ —메틸 -1^인다졸 _3—카복스아미드 (실시예 224);  6- (4-fluoro-2—methyl-5 _ ((3-methyl-5- (trifluoromethyl) phenyl) carbamoyl) phenyl) 一 ^ -methyl-1 ^ indazole _3—carboxamide (implemented Example 224);
6— (5ᅳ ( (4-클로로—3— (트리플루오로메틸)페닐)카바모일)— 4—플루오로 -2-메틸페닐)  6— (5 ᅳ ((4-chloro—3— (trifluoromethyl) phenyl) carbamoyl) — 4—fluoro-2-methylphenyl)
메틸— 인다졸 -3—카복스아미드 (실시예 225);  Methyl-indazole-3-carboxamide (Example 225);
6-(5ᅳ((4-((2— (디메틸아미노)에틸)아미노 )ᅳ3— (트리폴루오로메틸)페닐)카바모일  6- (5 ᅳ ((4-((2— (dimethylamino) ethyl) amino) ᅳ 3— (trifluoromethyl) phenyl) carbamoyl
)-4—플루오로 -2-메틸페닐) 메틸— 다졸 -3—카복스아미드 (실시예 226); ) -4—fluoro-2-methylphenyl) methyl-dazole-3—carboxamide (Example 226);
6-(4-플루오로 -2-메틸 -5— ((3-(4-메틸피페라진— 1ᅳ일) -5— (트리플루오로메틸)페닐 6- (4-fluoro-2-methyl-5 — ((3- (4-methylpiperazin— 1 ᅳ yl) -5— (trifluoromethyl) phenyl
)카바모일 )—2-메틸페닐)— ^메틸 -L 인다졸—3-카복스아미드 (실시예 227); ) Carbamoyl) —2-methylphenyl) — ^ methyl-L indazole—3-carboxamide (Example 227);
6-(4ᅳ풀루오로 -2-메틸 -5-(4ᅳ(2— (피롤리딘 -1—일)에록시 )-3- (트리플루오로메틸) 페닐)카바모일)페닐)— ^메틸 -1^인다졸 -3-카복스아미드 (실시예 228); 6- (4'Pluoro-2-methyl-5- (4 '(2— (pyrrolidin-1-yl) ethoxy) -3- (trifluoromethyl) phenyl) carbamoyl) phenyl) — ^ Methyl-1 ^ indazole-3-carboxamide (Example 228);
6-(5-((3-((2— (디메틸아미노)에틸)아미노 )— 5— (트리플루오로메틸)페닐)카바모일 6- (5-((3-((2— (dimethylamino) ethyl) amino) — 5— (trifluoromethyl) phenyl) carbamoyl
)-4-플루오로 -2-메틸페닐) - ^메틸 -1^인다졸 -3-카복스아미드 (실시예 229); ) -4-fluoro-2-methylphenyl)-^ methyl-1 ^ indazole-3-carboxamide (Example 229);
160  160
대체용지 (규칙 제 26조) 6一 (4-풀루오로 -2-메틸— 5— ((2-몰포리노 -5- (트리플루오로메틸)페닐)카바모일)페 닐)— 메틸 -1^인다졸—3-카복스아미드 (실시예 230); Alternative Site (Article 26) 6 一 (4-Pluoro-2-methyl— 5— ((2-morpholino-5- (trifluoromethyl) phenyl) carbamoyl) phenyl) —methyl-1 ^ indazole—3-carbox Amide (Example 230);
6- (4—풀루오로ᅳ 5- ( (2-플루오로ᅳ 5— (트리플루오로메틸 )페닐)카바모일 )2-메틸페닐 )- ^메틸— 1^인다졸 _3-카복스아미드 (실시예 231);  6- (4—Pluorolot 5- ((2-fluoro 플루오 5— (trifluoromethyl) phenyl) carbamoyl) 2-methylphenyl)-^ methyl- 1 ^ indazole _3-carboxamide (implemented Example 231);
6— (5-((3-((2- (디메틸아미노)에틸)아미노)ᅳ 5— (트리플루오로메틸)페닐)카바모일6— (5-((3-((2- (dimethylamino) ethyl) amino) ᅳ 5— (trifluoromethyl) phenyl) carbamoyl
)一4-플루오로— 2—메틸페닐)ᅳ ^메틸 -1^인다졸—3-카복스아미드 (실시예 232); 6-(5-((2— ((2- (디메틸아미노)에틸)아미노)ᅳ 5- (트리플루오로메틸)페닐)카바모일 )—4-플루오로— 2-메틸페닐) 메틸 -1^인다졸 -3ᅳ카복스아미드 (실시예 233); 6-(5-( (3-클로로 -4ᅳ메톡시페닐 )카바모일 )-4-플루오로— 2-메틸페닐) 메틸— 1^ 인다졸 -3—카복스아미드 (실시예 234); ) 1-4-fluoro-2-methylphenyl) ^ methyl-1 ^ indazole-3-carboxamide (Example 232); 6- (5-((2— ((2- (dimethylamino) ethyl) amino) ᅳ 5- (trifluoromethyl) phenyl) carbamoyl) —4-fluoro—2-methylphenyl) methyl-1 ^ is Sol-3′carboxamide (Example 233); 6- (5- ((3-chloro-4 ᅳ methoxyphenyl) carbamoyl) -4-fluoro—2-methylphenyl) methyl-1 ^ indazole-3—carboxamide (Example 234);
6一 (5-( (4-클로로—3ᅳ메틸페닐)카바모일) -4-폴루오로— 2—메틸페닐)— ^메틸 -1^인 다졸— 3-카복스아미드 (실시예 235); 6- (5- ((4-chloro- 3'methylphenyl) carbamoyl) -4-polouro-2-methylphenyl)-^ methyl-1 ^ dazole- 3-carboxamide (Example 235);
6-(4-플루오로ᅳ 5-( (4-플루오로ᅳ 3-메틸페닐)카바모일) -2-메틸페닐)— ^메틸— 1^ 인다졸 -3-카복스아미드 (실시예 236);  6- (4-fluoro ᅳ 5- ((4-fluoro4- 3-methylphenyl) carbamoyl) -2-methylphenyl) — ^ methyl-1 ^ indazole-3-carboxamide (Example 236);
6-(4-플루오로ᅳ 5-( (4-이소프로필페닐)카바모일 )-2_메틸페닐)—^메틸 -1^인다졸 -3ᅳ카복스아미드 (실시예 237)；  6- (4-fluoro ᅳ 5-((4-isopropylphenyl) carbamoyl) -2_methylphenyl) — ^ methyl-1 ^ indazole-3′carboxamide (Example 237);
6— (4-플루오로 -2-메틸 -5—0»ᅭ를일카바모일)페닐) - 메틸— 1^인다졸 -3_카복스아 미드 (실시예 238)； 6- (4-fluoro-2-methyl -5-0 »yo reulil carbamoyl) phenyl) methyl-1-indazole ^ -3_ carboxaldehyde O-carboxamide (Example 238);
6-(4—풀루오로 -2—메틸— 5-( (4—메틸— 3— (트리플루오로메틸 )페닐)카바모일 )페닐)一/ V -메틸 -1^인다졸 _3ᅳ카복스아미드 (실시예 239);  6- (4—Pluoro-2—methyl— 5- ((4—methyl— 3— (trifluoromethyl) phenyl) carbamoyl) phenyl) 一 / V-methyl-1 ^ indazole _3 ᅳ carboxamide (Example 239);
6— (4-플루오로 -5— ( (3—플루오로 -5— (트리풀루오로메특시 )페닐)카바모일) -2-메틸 페닐)― 메틸 -1^인다졸 -3—카복스아미드 (실시예 240);  6— (4-Fluoro-5— ((3—Fluoro-5— (Trifluorolumespecial) phenyl) carbamoyl) -2-methyl phenyl) -methyl-1 ^ indazole-3—carbox Amide (Example 240);
6— (5— ( (3— ( ^ᅳ부틸 )-1-페닐 -1^피라졸 -5-일 )카바모일 )—4-플루오로 -2-메틸페 닐)—^메틸 -1^인다졸 -3-카복스아미드 (실시예 241);  6— (5— ((3— (^ ᅳ butyl) -1-phenyl-1 ^ pyrazol-5-yl) carbamoyl) —4-fluoro-2-methylphenyl) — ^ methyl-1 ^ is Sol-3-carboxamide (Example 241);
6— ( 4-플루오로 -2-메틸 -5- (( 1， 2 , 2， 6 , 6_펜타메틸피페리딘 -4-일)카바모일)페닐) -메틸—1^인다졸 -3ᅳ카복스아미드 (실시예 242);  6— (4-fluoro-2-methyl-5-((1,2,2,6,6_pentamethylpiperidin-4-yl) carbamoyl) phenyl) -methyl--1 ^ indazole-3 Shock carboxamide (Example 242);
6-(4-풀루오로— 2—메틸— 5— ((2-(1 메틸피롤리딘 -2-일)에틸)카바모일)페닐) 메 틸一 1^인다졸 -3-카복스아미드 (실시예 243);  6- (4-Pluoro— 2—methyl— 5— ((2- (1 methylpyrrolidin-2-yl) ethyl) carbamoyl) phenyl) methyl 一 1 ^ indazole-3-carboxamide (Example 243);
6-(4—풀루오로 -5— (2— (3-플루오로페닐)하이드라진카보닐)—2-메틸페닐) - ^메틸一 1 ^인다졸 -3-카복스아미드 (실시예 244);  6- (4—Pluoro-5— (2— (3-fluorophenyl) hydrazinecarbonyl) —2-methylphenyl)-^ methyll 1 ^ indazole-3-carboxamide (Example 244);
6-(4-플루오로 -2—메틸 -5-((3— (4—메틸피페라진— 1_일) -5- (트리플루오로메틸)벤질 )카바모일)페닐) 메틸 -1^인다졸 -3-카복스아미드 (실시예 245);  6- (4-fluoro-2—methyl-5-((3— (4—methylpiperazin—1_yl) -5 (trifluoromethyl) benzyl) carbamoyl) phenyl) methyl-1 ^ Sol-3-carboxamide (Example 245);
6- (4—풀루오로 -2-메틸 -5_(2-페닐아세타미도)페닐)— 메틸 -1^인다졸 -3-카복스 아미드 (실시예 246)； 6- (4—Pluoro-2-methyl-5_ (2-phenylacetamido) phenyl)-methyl-1 ^ indazole-3-carboxamide (Example 246);
6一(5-(2— (4ᅳ클로로 -3— (트리풀루오로메틸)페닐)아세타미도 )-4-플루오로 -2-메틸 페닐) 메틸 -1^인다졸 _3-카복스아미드 (실시예 247);  6- (5- (2— (4 ᅳ chloro-3— (tripulouromethyl) phenyl) acetamido) -4-fluoro-2-methylphenyl) methyl-1 ^ indazole _3-carboxamide (Example 247);
6一(4-플루오로 -5-(2_(3ᅳ메특시페닐 )아세타미도 )-2—메틸페닐) - 메틸 -1^인다졸 -3-카복스아미드 (실시예 248)；  6- (4-Fluoro-5- (2_ (3'methoxyphenyl) acetamido) -2-methylphenyl) -methyl-1 ^ indazole-3-carboxamide (Example 248);
6-(4-풀루오로 -2-메틸 -5-(2ᅳ에일 )아세타미도)페닐) 메틸 -1^인다졸 -3-카 복스아미드 (실시예 249)；  6- (4-Pluoro-2-methyl-5- (2′yl) acetamido) phenyl) methyl-1 ^ indazole-3-carboxamide (Example 249);
6-(4-풀루오로— 5-(2-(4-폴루오로페닐)아세타미도)ᅳ 2-메틸페닐)— ^메틸 -1^인다 졸 -3-카복스아미드 (실시예 250)；  6- (4-Pluoro— 5- (2- (4-polourophenyl) acetamido) ᅳ 2-methylphenyl) — ^ methyl-1 ^ indazol-3-carboxamide (Example 250) ;
161  161
대체용지 (규칙 제 26조) 6- ( 5- ( 2- (벤조 [ d ][ 1， 3 ]디옥솔 -5-일)아세타미도)—4—플루오로— 2-메틸페닐) - ^메 틸 -1^인다졸 -3-카복스아미드 (실시예 251); Alternative Site (Article 26) 6- (5- (2- (benzo [d] [1, 3] diosol-5-yl) acetamido) —4—fluoro— 2-methylphenyl)-^ methyl-1 ^ indazole-3 -Carboxamide (Example 251);
6-(5-(2— (3,4-디클로로페닐)아세타미도 )ᅳ4-플루오로— 2ᅳ메틸페닐) - ^메틸 -1^인 다졸 -3-카복스아미드 (실시예 252);  Dazol-3-carboxamide that is 6- (5- (2— (3,4-dichlorophenyl) acetamido) ᅳ 4-fluoro—2 ᅳ methylphenyl)-^ methyl-1 ^ (Example 252);
6-(4—플루오로ᅳ 5— (2-(2-메톡시페닐)아세타미도)ᅳ 2—메틸페닐) - ^메틸ᅳ1^인다졸 一 3—카복스아미드 (실시예 253)；  6- (4—Fluoro ᅳ 5— (2- (2-methoxyphenyl) acetamido) ᅳ 2—methylphenyl)-^ methyl ᅳ 1 ^ indazole Ⅰ 3—carboxamide (Example 253);
6-(5-(2— (3,5—디메특시페닐)아세타미도) -4-플루오로— 2—메틸페닐)ᅳ 메틸 -L 인 다졸 -3-카복스아미드 (실시예 254);  6- (5- (2— (3,5—dimethoxyphenyl) acetamido) -4-fluoro—2—methylphenyl) ᅳ methyl-L indazole-3-carboxamide (Example 254);
6-(5— (2-(4—디메특시아미노페닐)아세타미도)— 4-폴루오로ᅳ 2-메틸페닐)— ^메틸— 1 ^인다졸 -3-카복스아미드 (실시예 255);  6- (5— (2- (4—dimethoaminoaminophenyl) acetamido) — 4-fluorouro 2-methylphenyl) — ^ methyl— 1 ^ indazole-3-carboxamide (Example 255 );
6-(4-풀루오로— 2ᅳ메틸 -5-(2-(4-나이트로페닐 )아세타미도)페닐) - ^메틸ᅳ1^인다 졸 -3—카복스아미드 (실시예 256);  6- (4-Pluoro—2'methyl-5- (2- (4-nitrophenyl) acetamido) phenyl)-^ methyl ᅳ 1 ^ indazol-3—carboxamide (Example 256) ;
6-(5_(2-(4- (브로모메틸)페닐)아세타미도) -4ᅳ플루오로— 2-메틸페닐)ᅳ ^메틸— 1^ 인다졸—3-카복스아미드 (실시예 257);  6- (5_ (2- (4- (bromomethyl) phenyl) acetamido) -4 ᅳ fluoro—2-methylphenyl) ᅳ ^ methyl—1 ^ indazole—3-carboxamide (Example 257) ;
6ᅳ (4-플루오로— 2-메틸 -5- (2- (3- (트리플루오로메틸)페닐)아세타미도)페닐)— ^메 틸 -L 인다졸—3-카복스아미드 (실시예 258);  6- (4-Fluoro— 2-methyl-5- (2- (3- (trifluoromethyl) phenyl) acetamido) phenyl) — ^ methyl-L indazole—3-carboxamide (implemented Example 258);
6— (4—플루오로 -5ᅳ (2ᅳ (4—풀루오로 -3— (트리플루오로메틸)페닐)아세타미도) -2ᅳ메 틸페닐) - ^메틸 -1^인다졸 -3-카복스아미드 (실시예 259);  6— (4—Fluoro-5 ᅳ (2 ᅳ (4—Pluoro-3— (trifluoromethyl) phenyl) acetamido) -2 ᅳ methylphenyl)-^ methyl-1 ^ indazole-3 Carboxamide (Example 259);
6-(5-(2-(4-브로모ᅳ 3-메틸페닐)아세타미도) -4-플루오로 -2-메틸페닐) - ^메틸— -인다졸ᅳ 3-카복스아미드 (실시예 260);  6- (5- (2- (4-Bromoq 3-methylphenyl) acetamido) -4-fluoro-2-methylphenyl)-^ methyl--indazoljan 3-carboxamide (Example 260) ;
6-(4-풀루오로 -5— (2— (3-플루우로페닐)아세타미도)ᅳ 2ᅳ메틸페닐)ᅳ^메틸 -1^인다 졸ᅳ 3ᅳ카복스아미드 (실시예 261);  6- (4-Pluoro-5— (2— (3-fluurophenyl) acetamido) ᅳ 2 ᅳ methylphenyl) ᅳ ^ methyl-1 ^ indazol 3 ᅳ carboxamide (Example 261);
6— (4ᅳ플루오로— 2ᅳ메틸 -5ᅳ (메틸설폰아미도)페닐) - ^메틸 -1^인다졸 -3—카복스아 미드 (실시예 262)；  6— (4'fluoro—2'methyl-5 '(methylsulfonamido) phenyl)-^ methyl-1 ^ indazole-3—carboxamide (Example 262);
6ᅳ(4ᅳ폴루오로— 2—메필 -5ᅳ (트리풀루오로메틸설폰아미도)페닐) - ^메틸 -1^인다졸 6 '(4'Polouro— 2—mephil-5' (tripulouromethylsulfonamido) phenyl)-^ methyl-1 ^ indazole
-3-카복스아미드 (실시예 263)； -3-carboxamide (Example 263);
6-(5ᅳ (에틸설폰아미도) -4-플루오로 -2-메틸페닐) - ^메틸 -L 인다졸—3-카복스아 미드 (실시예 264)； 및  6- (5 ′ (ethylsulfonamido) -4-fluoro-2-methylphenyl)-^ methyl-L indazole—3-carboxamide (Example 264); and
6ᅳ (4ᅳ플루오로— 2ᅳ메틸ᅳ 5-(1—메틸에틸설폰아미도)페닐)ᅳ^메틸— 1^인다졸 -3-카 복스아미드 (실시예 265);  6 ′ (4′fluoro—2 ᅳ methyl ᅳ 5- (1—methylethylsulfonamido) phenyl) ᅳ methyl-1 ^ indazole-3-carboxamide (Example 265);
로 이루어진 군으로부터 선택된 화합물.  Compound selected from the group consisting of.
【청구항 91 [Claim 91]
상기 청구항 1 내지 8항증에서 선택된 어느 한항의 화합물이 유효성분으로 함유된 것을특징으로 하는 암질환의 예방 및 치료용 약학적 조성물.  A pharmaceutical composition for the prevention and treatment of cancer diseases, characterized in that the compound of any one selected from claim 1 to 8 as an active ingredient.
【청구항 10】 [Claim 10]
청구항 9에 있어서，  The method according to claim 9,
단백질 키나아제의 저해 기전을 통해 비정상 세포 성장으로 유발되는 질환의 예방 및 치료에 사용되는 약학적 조성물.  A pharmaceutical composition used for the prevention and treatment of diseases caused by abnormal cell growth through the mechanism of inhibition of protein kinases.
【청구항 11】 [Claim 11]
청구항 9에 있어서,  The method according to claim 9,
162 162
정정용지 (규칙 제 91조) ISA/KR 위암， 폐암， 간암， 대장암, 소장암, 췌장암， 피부암, 유방암 , 자궁암， 갑상선암， 부갑상선암 , 신장암， 전립선암， 방광암, 혈액암， 림프종인 것을 특징으로 하는 암질환의 예방 및 치료용 약학적 조성물 . Correction Sheet (Rule 91) ISA / KR Pharmacy for the prevention and treatment of cancer diseases characterized in that the stomach cancer, lung cancer, liver cancer, colon cancer, small intestine cancer, pancreatic cancer, skin cancer, breast cancer, uterine cancer, thyroid cancer, parathyroid cancer, kidney cancer, prostate cancer, bladder cancer, blood cancer, lymphoma Composition.
【청구항 12】 [Claim 12]
상기 청구항 1 내지 8항 증에서 선택된 어느 한 항의 화합물이 유효성분으로 함유된 것을 특징으로 하는 종양 예방 및 치료제 .  Claim 1 to 8 of any one of the compounds selected from the prevention of tumors, characterized in that the active ingredient contained as an active ingredient.
163 163
정 정 용지 (규칙 제 91조) ISA/KR  Correction Paper (Rule 91) ISA / KR
PCT/KR2012/011655 2011-12-29 2012-12-28 3,6-disubstituted indazole derivative having protein kinase inhibiting activity WO2013100672A1 (en)

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