Pyrrolidine → Sunitinib

HRID 50005ノート

反応式

HRID 50005 の反応式
[CH2:1]([N:3]([CH2:18][CH3:19])[CH2:4][CH2:5][NH:6][C:7]([C:9]1[C:13]([CH3:14])=[C:12]([CH:15]=O)[NH:11][C:10]=1[CH3:17])=[O:8])[CH3:2].[F:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[NH:26][C:25](=[O:30])[CH2:24]2.N1CCCC1>C(O)C>[CH2:1]([N:3]([CH2:18][CH3:19])[CH2:4][CH2:5][NH:6][C:7]([C:9]1[C:13]([CH3:14])=[C:12](/[CH:15]=[C:24]2\[C:25](=[O:30])[NH:26][C:27]3[C:23]\2=[CH:22][C:21]([F:20])=[CH:29][CH:28]=3)[NH:11][C:10]=1[CH3:17])=[O:8])[CH3:2]

参加物

5

反応物 3

HCID 31268PyrrolidineHCID 37310125-fluoro-1,3-dihydro-2H-indol-2-oneHCID 20761785N-(2-(diethylamino)ethyl)-5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxamide

生成物 1

HCID 5329102Sunitinib収率 88%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

5-Formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)-amide (809 g), 5-fluoro-1,3-dihydro-indol-2-one (438 g), ethanol (8000 mL) and pyrrolidine (13 mL) were heated at 78° C. for 3 hours. The mixture was cooled to room temperature and the solids collected by vacuum filtration and washed with ethanol. The solids were stirred with ethanol (5900 mL) at 72° C. for 30 minutes. The mixture was cooled to room temperature. The solids were collected by vacuum filtration, washed with ethanol and dried under vacuum at 54° C. for 130 hours to give 5-[5-fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylamino-ethyl)-amide (1013 g, 88% yield) as an orange solid. 1H-NMR (dimethylsulfoxide-d6) δ0.98 (t, 6H, 2×CH3), 2.43, 2.44 (2×s, 6H, 2×CH3), 2.50 (m, 6H, 3×CH2), 3.28 (q, 2H, CH2), 6.84, 6.92, 7.42, 7.71, 7.50 (5×m, 5H, aromatic, vinyl, CONH), 10.88 (s, 1H, CONH), 13.68 (s, 1H, pyrrole NH). MS m/z 397 [M−1].

後処理

  1. filtrationthe solids collected by vacuum filtration
  2. washwashed with ethanol
  3. temperatureThe mixture was cooled to room temperature
  4. filtrationThe solids were collected by vacuum filtration
  5. washwashed with ethanol
  6. customdried under vacuum at 54° C. for 130 hours

出典と根拠

ORDレコード
ord-fe021e7d960e41e1be11ef5b844d1b97
出典データセット
uspto-grants-2004_03
特許番号
US06710067B2

反応ノート

読み込み中…