Cesium carbonate → 4-[4-(azetidine-1-carbonyl)-3-fluorophenoxy]-2,2-dimethyl-N-(1-methylpyrazol-3-yl)-3H-1-benzofuran-6-carboxamide

HRID 1177093노트

반응식

HRID 1177093 반응식
[CH3:1][N:2]1[CH:6]=[CH:5][C:4]([NH:7][C:8]([C:10]2[CH:20]=[C:19]([OH:21])[C:13]3[CH2:14][C:15]([CH3:18])([CH3:17])[O:16][C:12]=3[CH:11]=2)=[O:9])=[N:3]1.C([O-])([O-])=O.[Cs+].[Cs+].[N:28]1([C:32]([C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][C:35]=2[F:41])=[O:33])[CH2:31][CH2:30][CH2:29]1>>[CH3:1][N:2]1[CH:6]=[CH:5][C:4]([NH:7][C:8]([C:10]2[CH:20]=[C:19]([O:21][C:37]3[CH:38]=[CH:39][C:34]([C:32]([N:28]4[CH2:31][CH2:30][CH2:29]4)=[O:33])=[C:35]([F:41])[CH:36]=3)[C:13]3[CH2:14][C:15]([CH3:18])([CH3:17])[O:16][C:12]=3[CH:11]=2)=[O:9])=[N:3]1.[CH3:1][N:2]1[CH:6]=[CH:5][C:4]([NH:7][C:8]([C:10]2[CH:20]=[C:19]([O:21][C:35]3[CH:36]=[C:37]([F:40])[CH:38]=[CH:39][C:34]=3[C:32]([N:28]3[CH2:31][CH2:30][CH2:29]3)=[O:33])[C:13]3[CH2:14][C:15]([CH3:18])([CH3:17])[O:16][C:12]=3[CH:11]=2)=[O:9])=[N:3]1

참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 595600842,3-Dihydro-4-hydroxy-2,2-dimethyl-N-(1-methyl-1H-pyrazol-3-yl)-6-benzofurancarboxamideHCID 59560289Azetidin-1-yl-(2,4-difluorophenyl)methanone

생성물 2

HCID 247680194-[4-(azetidine-1-carbonyl)-3-fluorophenoxy]-2,2-dimethyl-N-(1-methylpyrazol-3-yl)-3H-1-benzofuran-6-carboxamide수율 46%HCID 595602224-[2-(azetidine-1-carbonyl)-5-fluoro-phenoxy]-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide수율 5%

반응 조건

온도
160 °C

실험 절차

4-Hydroxy-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide (31a) (421 mg, 1.47 mmol) and Cs2CO3 (965 mg, 2.96 mmol) was added to a solution of azetidin-1-yl(2,4-difluorophenyl)methanone (33a) (292 mg, 1.48 mmol). The reaction mixture was heated to 160° C. for 2 hr in a microwave. The mixture was filtered and concentrated, The residue was purified by SFC chromatography to give 4-[4-(azetidine-1-carbonyl)-3-fluoro-phenoxy]-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide (315 mg, 46% yield) and 4-[2-(azetidine-1-carbonyl)-5-fluoro-phenoxy]-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide (34 mg, 5% yield) as white solid.

후처리

  1. filtrationThe mixture was filtered
  2. concentrationconcentrated
  3. customThe residue was purified by SFC chromatography

출처 및 근거

ORD 기록
ord-18d88d1a3941477b828f4e6be071e3f0
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07842713B2

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