Triethylamine → cyclopropanecarboxylic acid {7-chloro-2-[2-cyano-1-(3-ethoxy-4-methoxy-phenyl)-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide

HRID 853977ノート

反応式

HRID 853977 の反応式
[NH2:1][CH:2]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][CH2:15][CH3:16])[CH:7]=1)[CH2:3][C:4]#[N:5].CCN(CC)CC.C[O:25][C:26](=O)[C:27]1[C:32]([NH:33][C:34]([CH:36]2[CH2:38][CH2:37]2)=[O:35])=[CH:31][CH:30]=[C:29]([Cl:39])[C:28]=1[CH2:40]Br>CN(C=O)C>[Cl:39][C:29]1[CH:30]=[CH:31][C:32]([NH:33][C:34]([CH:36]2[CH2:37][CH2:38]2)=[O:35])=[C:27]2[C:28]=1[CH2:40][N:1]([CH:2]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][CH2:15][CH3:16])[CH:7]=1)[CH2:3][C:4]#[N:5])[C:26]2=[O:25]

参加物

5

反応物 3

HCID 8471TriethylamineHCID 221771543-Amino-3-(3-ethoxy-4-methoxyphenyl)propanenitrileHCID 669200082-Bromomethyl-3-chloro-6-(cyclopropanecarbonyl-amino)-benzoic acid methyl ester

生成物 1

HCID 9981379cyclopropanecarboxylic acid {7-chloro-2-[2-cyano-1-(3-ethoxy-4-methoxy-phenyl)-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide収率 80%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

To the DMF solution (20 ml) of 3-Amino-3-(3-ethoxy-4-methoxy-phenyl)-propionitrile (1.55 g, 7 mmol) was added Et3N (1.6 ml, 12 mmol) followed by 2-bromomethyl-3-chloro-6-(cyclopropanecarbonyl-amino)-benzoic acid methyl ester (2.42 g, 7 mmol). The mixture was heated at 90° C. for 12 hrs then cooled to room temperature. The mixture was extracted with EtOAc (50 ml) and water (50 ml). The organic layer was washed with water (50 ml) and brine (50 ml), dried over Na2SO4 and concentrated in vacuo. The resulted oil was purified by silica gel chromatography to give cyclopropanecarboxylic acid {7-chloro-2-[2-cyano-1-(3-ethoxy-4-methoxy-phenyl)-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide as white solid (2.4 g, 80%): mp 200-202° C.; 1H NMR (CDCl3)δ 0.90-0.94 (m, 2H, c-CH2), 1.09-1.14 (m, 2H, c-CH2), 1.45 (t, J=7.0 Hz, 3H, CH3), 1.64-1.70(m, 1H, c-CH), 3.12-3.32(m, 2H; CH2CN), 3.89(s, 3H), 3.99-4.12 (m, 3H, OCH2CH3+CHHN), 4.37 (d, J=18 Hz, 1H. CHHN), 5.62-5.68 (m, 1H, NCH), 6.87-6.98 (m, 3H, Ar), 7.40 (d, J=9 Hz, 1H, Ar), 8.47 (t, J=9 Hz, 1H, Ar), 10.34 (s, 1H, NH); 3C NMR (CDCl3) δ 8.5, 14.7, 16.2, 21.2, 46.4, 51.8, 56.0, 64.7, 111.7, 112.2, 116.9, 118.4, 119.1, 119.8, 121.9, 127.9, 133.3, 136.9, 138.9, 149.9, 150.0, 169.0, 172.7; Anal Calcd for C24H24ClN3O4: C, 63.50; H, 5.33; N, 9.26. Found: C, 63.43; H, 5.31; N, 9.01

後処理

  1. temperaturethen cooled to room temperature
  2. extractionThe mixture was extracted with EtOAc (50 ml) and water (50 ml)
  3. washThe organic layer was washed with water (50 ml) and brine (50 ml)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe resulted oil was purified by silica gel chromatography

出典と根拠

ORDレコード
ord-d1fc3d78f7d8433db8fcad028bea3024
出典データセット
uspto-grants-2007_08
特許番号
US07256210B2

反応ノート

読み込み中…