Sodium Carbonate → tert-butyl 1-(5-(5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate

HRID 1529350노트

반응식

HRID 1529350 반응식
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[C:16]([F:17])=[CH:15][CH:14]=[CH:13][C:12]=3[F:18])[CH:9]=2)[N:4]([CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)[N:3]=1.CC1(C)C(C)(C)OB([C:33]2[CH:34]=[C:35]([N:39]3[CH2:44][CH2:43][CH:42]([NH:45][C:46](=[O:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49])[CH2:41][CH2:40]3)[CH:36]=[N:37][CH:38]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.[Pd+2].ClC1C=C[C-](P(C2C=CC=CC=2)C2C=CC=CC=2)C=1Cl.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[F:18][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]([F:17])[C:11]=1[C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[N:4]([CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1)[N:3]=[C:2]2[C:33]1[CH:34]=[C:35]([N:39]2[CH2:40][CH2:41][CH:42]([NH:45][C:46](=[O:52])[O:47][C:48]([CH3:50])([CH3:49])[CH3:51])[CH2:43][CH2:44]2)[CH:36]=[N:37][CH:38]=1

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 679597623-bromo-5-(2,6-difluoro-phenyl)-1-(tetrahydro-pyran-2-yl)-1H-indazoleHCID 67959870Tert-butyl 1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)piperidin-4-ylcarbamate

생성물 1

HCID 67960050tert-butyl 1-(5-(5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate수율 89%

시약·촉매·용매 2

HCID 178478230HCID 178478230, 화합물촉매HCID 312751,4-Dioxane용매

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온도
135 °C

실험 절차

A mixture of 3-bromo-5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (90 mg, 0.229 mmol), tert-butyl 1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)piperidin-4-ylcarbamate (115 mg, 0.286 mmol), Na2CO3, 2.0 M (0.229 mL, 0.458 mmol) and dichloro 1,1′-bis(diphenylphosphino) ferrocene palladium (II) (18.69 mg, 0.023 mmol, Strem) in dioxane (3 mL) was capped, degassed and backfilled with argon. The reaction was heated to 135° C. in a microwave for 45 min. The reaction mixture was diluted with EtOAc (50 mL) and washed with brine (50 mL), dried over MgSO4, concentrated in vacuo and purified by silica gel chromatography (eluent: 0-3% MeOH/DCM), affording tert-butyl 1-(5-(5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate (120 mg, 89%). MS (ESI, pos. ion) m/z: 590.3 (M+1).

후처리

  1. customwas capped
  2. customdegassed
  3. additionThe reaction mixture was diluted with EtOAc (50 mL)
  4. washwashed with brine (50 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. custompurified by silica gel chromatography (eluent: 0-3% MeOH/DCM)

출처 및 근거

ORD 기록
ord-206cca678a2d45ff80490bbf37155eee
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09090593B2

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