Potassium Iodide → 4-(3-Chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-1-(morpholinoacetyl)pyrrolidin-2-yl]methoxy}quinazoline
反応式
[Cl:1][C:2]1[C:3]([F:32])=[C:4]([CH:29]=[CH:30][CH:31]=1)[NH:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:27][CH3:28])=[C:13]([O:16][CH2:17][C@@H:18]3[CH2:22][CH2:21][CH2:20][N:19]3[C:23](=[O:26])[CH2:24]Cl)[CH:14]=2)[N:9]=[CH:8][N:7]=1.[I-].[K+].[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>>[Cl:1][C:2]1[C:3]([F:32])=[C:4]([CH:29]=[CH:30][CH:31]=1)[NH:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:27][CH3:28])=[C:13]([O:16][CH2:17][C@@H:18]3[CH2:22][CH2:21][CH2:20][N:19]3[C:23](=[O:26])[CH2:24][N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)[CH:14]=2)[N:9]=[CH:8][N:7]=1参加物
実験手順
4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-1-(chloroacetyl)pyrrolidin-2-yl]methoxy}quinazoline (0.45 g, 0.94 mmole) was dissolved in morpholine (7.5 ml) and stirred at ambient temperature overnight in the presence of potassium iodide (10 mg). The solvent was evaporated and the residue purified by column chromatography eluting with methylene chloride/methanol (saturated with ammonia) (98/2). The fractions containing the expected product were combined and evaporated under vacuum to give the title product as a foam (0.22 g, 44%); 1H NMR Spectrum: (CDCl3) 1.91-2.01 (m, 1H); 2.06-2.14 (m, 2H); 2.19-2.27 (m, 1H); 2.48-2.53 (m, 2H); 2.62-2.68 (m, 2H); 3.18 (q, 2H); 3.41-3.52 (m, 1H); 3.56-3.72 (m, 5H); 4.01-4.08 (m, 4H); 4.53 (d, 1H); 4.72 (t, 1H); 7.11-7.28 (m, 3H); 7.96 (m, 1H); 8.36 (s, 1H); 8.60 (s, 1H); 8.63 (s, 1H); Mass Spectrum: (M−H)− 528.
後処理
- customThe solvent was evaporated
- customthe residue purified by column chromatography
- washeluting with methylene chloride/methanol (saturated with ammonia) (98/2)
- additionThe fractions containing the expected product
- customevaporated under vacuum
出典と根拠
- ORDレコード
- ord-891f6ef095f14def90ff6a40fe7a4295
- 出典データセット
- uspto-grants-2013_03
- 特許番号
- US08399667B2
反応ノート
読み込み中…