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Bromide ion → 4'-[[2,3,4,5-Tetrahydro-3(R)-[[3-methyl-1-oxo-3-[[(benzyloxy)carbonyl]amino] butyl]amino]-2-oxo-1H-1-benzazepin-1-yl]methyl]-[1,1'-biphenyl]-2-carboxylic acid 1,1-dimethylethyl ester

HRID 1033415
ノート
印刷プレビュー

反応式

HRID 1033415 の反応式
[CH2:1]([O:8][C:9]([NH:11][C:12]([CH3:30])([CH3:29])[CH2:13][C:14]([NH:16][C@@H:17]1[CH2:23][CH2:22][C:21]2[CH:24]=[CH:25][CH:26]=[CH:27][C:20]=2[NH:19][C:18]1=[O:28])=[O:15])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]2[C:42]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])=[CH:43][CH:44]=[CH:45][CH:46]=2)=[CH:37][CH:36]=1.[Br-]>CN(C)C=O>[CH3:53][C:50]([O:49][C:47]([C:42]1[C:41]([C:38]2[CH:37]=[CH:36][C:35]([CH2:34][N:19]3[C:20]4[CH:27]=[CH:26][CH:25]=[CH:24][C:21]=4[CH2:22][CH2:23][C@@H:17]([NH:16][C:14](=[O:15])[CH2:13][C:12]([CH3:30])([NH:11][C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[O:10])[CH3:29])[C:18]3=[O:28])=[CH:40][CH:39]=2)=[CH:46][CH:45]=[CH:44][CH:43]=1)=[O:48])([CH3:51])[CH3:52]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 259Bromide ionHCID 24758Sodium hydrideHCID 9906257tert-Butyl 4'-(bromomethyl)biphenyl-2-carboxylateHCID 105735633-Benzyloxycarbonylamino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1H-benzazepin-3(R)-yl]butanamide

生成物 1

HCID 228551634'-[[2,3,4,5-Tetrahydro-3(R)-[[3-methyl-1-oxo-3-[[(benzyloxy)carbonyl]amino] butyl]amino]-2-oxo-1H-1-benzazepin-1-yl]methyl]-[1,1'-biphenyl]-2-carboxylic acid 1,1-dimethylethyl ester
収率 96%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

To a solution of 1.22 g (3.0 mmol) of 3-benzyloxycarbonylamino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]-butanamide (Example 1, Step F) in 10 mL of dry dimethylformamide under nitrogen was added 131.6 mg (3.92 mmol) of 60% sodium hydride in oil. After stirring for 20 minutes, a solution of 1.14 g (3.29 mmol) of t-butyl 4'-bromomethyl-1,1'-biphenyl-2-carboxylate (prepared according to the procedure of D. J. Carini, et. al. EPO publication 324.377) in 2.5 mL of dimethylformamide was added by cannula. The flask which originally contained the bromide was rinsed with 2.5 mL dimethylformamide which was added to the reaction mixture. After stirring at room temperature for 2 hours, the reaction has diluted with 400 mL of ethyl acetate, washed with 100 mL of water and 100 mL of brine. The organic layer was dried over magnesium sulfate, filtered and the solvent removed under vacuum. The residue was purified by flash chromatography on silica gel eluting with ethyl acetate/hexane (55:45) to afford 1.74 g (96%) of the product as a white foam. 1H NMR (200MHz,CDCl3): 1.15 (s,9H), 1.45 (s,3H), 1.48 (s,3H), 1.76 (m,1H), 2.35-2.62 (m,5H), 4.48 (m,1H), 4.79 (d,14Hz,1H), 5.04 (t,12Hz,2H), 5.35 (d, 14Hz,1H), 6.70 (d,6Hz,1H), 7.10-7.45 (m,17H), 7.72 (m,1H). FAB-MS: calculated for C41H45N3O6 675; found 683 (M+Li).

後処理

  1. washwas rinsed with 2.5 mL dimethylformamide which
  2. additionwas added to the reaction mixture
  3. stirringAfter stirring at room temperature for 2 hours
  4. additionthe reaction has diluted with 400 mL of ethyl acetate
  5. washwashed with 100 mL of water and 100 mL of brine
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. filtrationfiltered
  8. customthe solvent removed under vacuum
  9. customThe residue was purified by flash chromatography on silica gel eluting with ethyl acetate/hexane (55:45)

出典と根拠

ORDレコード
ord-57ab064fbeb241bf959cc23874f097c8
出典データセット
uspto-grants-1994_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US05310737

反応ノート

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