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

HRID 853975ノート

反応式

HRID 853975 の反応式
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C@H:12]([NH2:18])[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].C[O:20][C:21](=O)[C:22]1[C:27]([NH:28][C:29]([CH:31]2[CH2:33][CH2:32]2)=[O:30])=[CH:26][CH:25]=[C:24]([Br:34])[C:23]=1[CH2:35]Br.C(N(CC)CC)C>CN(C=O)C>[Br:34][C:24]1[CH:25]=[CH:26][C:27]([NH:28][C:29]([CH:31]2[CH2:32][CH2:33]2)=[O:30])=[C:22]2[C:23]=1[CH2:35][N:18]([C@@H:12]([C:6]1[CH:7]=[CH:8][C:9]([O:10][CH3:11])=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=1)[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[C:21]2=[O:20]

参加物

5

反応物 3

HCID 8471TriethylamineHCID 11282264(1S)-1-(3-Ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethylamineHCID 686904882-Bromomethyl-3-bromo-6-(cyclopropanecarbonyl-amino)-benzoic acid methyl ester

生成物 1

HCID 10099083(1S)-cyclopropanecarboxylic acid {7-bromo-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-3-oxo-2,3-dihydro-1h-isoindol-4-yl}-amide収率 74.2%

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 (1S)-1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl ethylamine (0.35 g, 1.2 mmol) in DMF (10 ml) was added 2-bromomethyl-3-bromo-6-(cyclopropanecarbonyl-amino)-benzoic acid methyl ester (0.45 g, 1.1 mmol) and triethyl amine (0.5 ml, 3.3 mmol). The mixture was heated at 90° C. overnight. The solvent was removed in vacuo. The resulted oil was extracted with ethyl acetate (50 ml) and water (30 ml). The organic layer was washed with water (30 ml×2), brine (30 ml) and dried over magnesium sulfate. The solvent was removed in vacuo and the resulted oil was purified by silica gel column to give (1S)-cyclopropanecarboxylic acid {7-bromo-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide as a white solid (450 mg, 74%): mp, 219-221° C.; 1H NMR (CDCl3) δ 0.89-0.93 (m, 2H, c-CH2), 1.08-1.14 (m, 2H, c-CH2), 1.47 (t, J=7.0 Hz, 3H, OCH2CH3), 1.65-1.70 (m, 1H, c-CH), 2.98 (s, 3H, CH3SO2), 3.70 (dd, J=5, 15 Hz, 1H, CHH), 3.87(s, 3H, OCH3), 4.06-4.14 (m, 3H, NCHH+OCH2CH3), 4.19 (dd, J=10, 15 Hz, 1H, CHH), 4.55 (d, J=17 Hz, 1H, CH), 5.75-5.81 (m, 1H, CHN), 6.86-6.96 (m, 3H, Ar), 7.53 (d, J=9 Hz, 1H, Ar), 8.40(d, J=9 Hz, 1H, Ar), 10.38 (s, 1H, NHCO). 3CNMR (CDCl3): δ 9.1, 9.2, 15.4, 16.9, 42.2, 49.1, 52.0, 56.1, 56.7, 65.3, 110.1, 112.3, 112.8, 119.5, 119.9, 120.7, 129.7, 136.8, 138.1, 142.0, 149.6, 150.5, 170.0, 173.3; Anal Calcd for C24H27BrN2O6S: C, 52.27; H, 4.94; N, 5.08. Found: C, 52.57; H, 4.68; N, 4.95.

後処理

  1. customThe solvent was removed in vacuo
  2. extractionThe resulted oil was extracted with ethyl acetate (50 ml) and water (30 ml)
  3. washThe organic layer was washed with water (30 ml×2), brine (30 ml)
  4. dry with materialdried over magnesium sulfate
  5. customThe solvent was removed in vacuo
  6. customthe resulted oil was purified by silica gel column

出典と根拠

ORDレコード
ord-ebf288564bfa417aa920cf39fb463d68
出典データセット
uspto-grants-2007_08
特許番号
US07256210B2

反応ノート

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