Sodium hydride → N-Isopropyl-2-{2-oxo-5-phenyl-3-[(benzyloxycarbonyl)amino]-2,3-dihydro-benzo[e][1,4]diazepin-1-yl}-N-phenyl acetamide

HRID 482342ノート

反応式

HRID 482342 の反応式
[H-].[Na+].[CH2:3]([O:10][C:11]([NH:13][CH:14]1[C:20](=[O:21])[NH:19][C:18]2[CH:22]=[CH:23][CH:24]=[CH:25][C:17]=2[C:16]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[N:15]1)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Br[CH2:33][C:34]([N:36]([CH:43]([CH3:45])[CH3:44])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:35].C1([C@H](OC(N[C@H]2C(=O)NC3C=CC=CC=3C(C3C=CC=CC=3)=N2)=O)C)C=CC=CC=1>CN(C=O)C.O>[CH:43]([N:36]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C:34](=[O:35])[CH2:33][N:19]1[C:18]2[CH:22]=[CH:23][CH:24]=[CH:25][C:17]=2[C:16]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[N:15][CH:14]([NH:13][C:11]([O:10][CH2:3][C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=2)=[O:12])[C:20]1=[O:21])([CH3:45])[CH3:44]

参加物

7

反応物 4

HCID 24758Sodium hydrideHCID 2756242Benzyl (2-oxo-5-phenyl-2,3-dihydro-1h-benzo[e][1,4]diazepin-3-yl)carbamateHCID 100464723(R)-{[(R)-1-phenyl-ethoxycarbonyl]amino}-5-phenyl-1,3-dihydro-benzo[e][1,4]diazepin-2-oneHCID 152160012-bromo-N-isopropyl-N-phenyl-acetamide

生成物 1

HCID 86753034N-Isopropyl-2-{2-oxo-5-phenyl-3-[(benzyloxycarbonyl)amino]-2,3-dihydro-benzo[e][1,4]diazepin-1-yl}-N-phenyl acetamide収率 101%

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 6228Dimethylformamide溶媒2 回

実験手順

Sodium hydride (60% dispersion in mineral oil, 428 mg, 10.7 mmol) is added to a suspension of 3-[(benzyloxycarbonyl)amino]-5-phenyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one (3.924 g, 10.19 mmol), prepared as in Intermediate 6, in anhydrous DMF under nitrogen at 0°-5° C. After stirring for 1 hr., 2-Bromo-N-isopropyl-N-phenyl-acetamide (2.739 g, 10.70 mmol), prepared as in Intermediate 3, in anhydrous DMF (5 mL) is added and the mixture is allowed to stir at ambient temperature overnight. The reaction is added via pipette to water (200 mL) with vigorous agitation. The resulting slurry is diluted with water (50 mL) and then cooled to 0°-5° C. with a ice-water bath. After stirring for 30 min., the cold slurry is filtered, washed with water and then dried overnight under high vacuum to provide the title compound as a white solid (5.765 g, 10.29 mmol) of sufficient purity for the next step. 1H NMR (300 MHz, CDCl3) δ=1.09 (d, J=6.8 Hz, 6H); 3.92 (d, J=16.5 Hz, 1H); 4.28 (d, J=16.5 Hz, 1H); 4.97-5.08 (m, 1H); 5.08-5.19 (m, 2H); 5.39 (d, J=8.2 Hz, 1H); 6.70 (d, J=8.1 Hz, 1H); 7.11-7.62 (m, 19H). MS (FAB): [M+H]+ =561

後処理

  1. stirringto stir at ambient temperature overnight
  2. temperaturecooled to 0°-5° C. with a ice-water bath
  3. stirringAfter stirring for 30 min.
  4. filtrationthe cold slurry is filtered
  5. washwashed with water
  6. customdried overnight under high vacuum

出典と根拠

ORDレコード
ord-8a12230f7c5146528f623cd07494493f
出典データセット
uspto-grants-1998_08
特許番号
US05795887

反応ノート

読み込み中…