Triethylamine → (1S)-cyclopropanecarboxylic acid {2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-7-fluoro-3-oxo-2,3-dihydro-1h-isoindol-4-yl}-amide

HRID 1787976ノート

反応式

HRID 1787976 の反応式
CO[C:3](=[O:19])[C:4]1[C:9]([NH:10][C:11]([CH:13]2[CH2:15][CH2:14]2)=[O:12])=[CH:8][CH:7]=[C:6]([F:16])[C:5]=1[CH2:17]Br.CCN(CC)CC.[CH2:27]([O:29][C:30]1[CH:31]=[C:32]([C@H:38]([NH2:44])[CH2:39][S:40]([CH3:43])(=[O:42])=[O:41])[CH:33]=[CH:34][C:35]=1[O:36][CH3:37])[CH3:28]>CN(C=O)C>[CH2:27]([O:29][C:30]1[CH:31]=[C:32]([C@H:38]([N:44]2[C:3](=[O:19])[C:4]3[C:5](=[C:6]([F:16])[CH:7]=[CH:8][C:9]=3[NH:10][C:11]([CH:13]3[CH2:14][CH2:15]3)=[O:12])[CH2:17]2)[CH2:39][S:40]([CH3:43])(=[O:42])=[O:41])[CH:33]=[CH:34][C:35]=1[O:36][CH3:37])[CH3:28]

参加物

5

反応物 3

HCID 8471TriethylamineHCID 11282264(1S)-1-(3-Ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethylamineHCID 686893502-Bromomethyl-6-(cyclopropanecarbonyl-amino)-3-fluoro benzoic acid methyl ester

生成物 1

HCID 10368301(1S)-cyclopropanecarboxylic acid {2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-7-fluoro-3-oxo-2,3-dihydro-1h-isoindol-4-yl}-amide収率 55%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

To a solution of 2-bromomethyl-6-(cyclopropanecarbonyl-amino)-3-fluoro benzoic acid methyl ester (1 g, 3 mmol) and Et3N (1.25 ml, 9 mmol) in DMF (10 ml) was added (1S)-1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethylamine (870 mg, 3.2 mmol). The mixture was heated at 90° C. for 20 hrs. The reaction mixture was cooled to room temperature and extracted with water (50 ml) and EtOAc (50 ml). The organic layer washed with water (50 ml), brine (25 ml), dried over Na2SO4 and concentrated. The resulted oil was purified by chromatography to give (1S)-cyclopropanecarboxylic acid {2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-7-fluoro-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide as a white solid (800 mg, 55% yield): mp, 176-178° C.; 1H NMR (CDCl3) δ 0.88-0.92 (m, 2H, c-propylCH2), 1.09-1.12 (m, 2H, c-propylCH2), 1.47 (t, J=7.0 Hz, 3H, OCH2CH3), 1.64-1.68 (m, 1H, c-propylCH), 2.98 (s, 3H, CH3), 3.63-3.73 (m, 1H, CHHSO2), 3.87 (s, 3H, CH3), 4.05-4.28 (m, 4H, CHHSO2+CNHH+OCH2CH3), 4.49 (d, J=18 Hz, 1H, C), 6.85-6.92 (m, 1H, NCH), 6.86-6.93 (m, 3H, Ar), 7.04 (t, J=8 Hz, 1H, Ar), 8.45-8.55 (m, 1H, Ar), 10.32 (s, 1H, NHCO); 13C NMR (CDCl3) δ 8.26, 8.27, 14.67, 16.04, 41.50, 44.67, 51.30, 55.39, 55.96, 64.65, 111.63, 112.21, 118.95, 119.26, 119.68, 119.92, 126.43, 126.74, 128.99, 134.48, 134.53, 148.98, 149.88, 150.31, 154.22, 168.89, 172.39. Anal Calcd for C24H27FN2O6S: C, 58.76; H, 5.55; N, 5.71. Found: C, 58.60; H, 5.33; N, 5.65.

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with water (50 ml) and EtOAc (50 ml)
  3. washThe organic layer washed with water (50 ml), brine (25 ml)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe resulted oil was purified by chromatography

出典と根拠

ORDレコード
ord-cf3ec6d5cbfa414cad6175c0d48601e2
出典データセット
uspto-grants-2009_03
特許番号
US07511072B2

反応ノート

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