Cesium carbonate → 2-(1-((4-benzylmorpholin-2-yl)methyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246504

반응식

HRID 246504 반응식
[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH:27]([F:29])[F:28])[CH:24]=4)[NH:19][N:18]=3)[N:15]=2)[N:10]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:38]([N:45]1[CH2:50][CH2:49][O:48][CH:47]([CH2:51]Cl)[CH2:46]1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[CH2:38]([N:45]1[CH2:50][CH2:49][O:48][CH:47]([CH2:51][N:19]2[C:20]3[C:25](=[CH:24][C:23]([O:26][CH:27]([F:28])[F:29])=[CH:22][CH:21]=3)[C:17]([C:14]3[N:15]=[C:16]4[C:8]([C:6]([NH:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[CH:9][N:10]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:11]4=[N:12][CH:13]=3)=[N:18]2)[CH2:46]1)[C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1

참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 28015624-Benzyl-2-(chloromethyl)morpholineHCID 712795662-(5-difluoromethoxy-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

생성물 1

HCID 712796062-(1-((4-benzylmorpholin-2-yl)methyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide수율 49.5%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

N-tert-Butyl-2-(5-(difluoromethoxy)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (100 mg, 188 μmol), 4-benzyl-2-(chloromethyl)morpholine (51.0 mg, 226 μmol) and cesium carbonate (184 mg, 565 mmol) in dimethylformamide (1.4 mL) were heated in a microwave at 100° C. for 45 min. The mixture was cooled, partitioned between ethyl acetate and water, and the organic phases combined and washed with water 3 times. The organic phase was dried and concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 0-40% ethyl acetate in hexanes) gave 2-(1-((4-benzylmorpholin-2-yl)methyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (67 mg, 49%).

후처리

  1. temperatureThe mixture was cooled
  2. custompartitioned between ethyl acetate and water
  3. washwashed with water 3 times
  4. customThe organic phase was dried
  5. concentrationconcentrated in vacuo
  6. customPurification by chromatography (silica, 24 g Analogix column, 0-40% ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-5df6dca1f2074b71a7dcab9c8a2ff4ee
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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