Bromide ion → 3-[[1-[[2'-Cyano-[1,1'-biphenyl]-4-yl]methyl]-2,3,4,5-tetrahydro-2-oxo-1H-benzazepin-3(R)-yl]amino]-1,1-dimethyl-3-oxopropylcarbamic acid, 1,1-dimethylethyl ester

HRID 1591470

반응식

HRID 1591470 반응식
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:27])([CH3:26])[CH2:10][C:11]([NH:13][C@@H:14]1[CH2:20][CH2:19][C:18]2[CH:21]=[CH:22][CH:23]=[CH:24][C:17]=2[NH:16][C:15]1=[O:25])=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2[C:39]([C:44]#[N:45])=[CH:40][CH:41]=[CH:42][CH:43]=2)=[CH:34][CH:33]=1.[Br-]>CN(C)C=O>[C:44]([C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=1[C:35]1[CH:34]=[CH:33][C:32]([CH2:31][N:16]2[C:17]3[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=3[CH2:19][CH2:20][C@@H:14]([NH:13][C:11](=[O:12])[CH2:10][C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])([CH3:27])[CH3:26])[C:15]2=[O:25])=[CH:37][CH:36]=1)#[N:45]

참가 물질

6

반응물 4

HCID 259Bromide ionHCID 24758Sodium hydride2회HCID 15019124'-(Bromomethyl)-2-cyanobiphenylHCID 104746043-t-butoxycarbonylamino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1H-benzazepin-3(R)-yl]butanamide

생성물 1

HCID 571704893-[[1-[[2'-Cyano-[1,1'-biphenyl]-4-yl]methyl]-2,3,4,5-tetrahydro-2-oxo-1H-benzazepin-3(R)-yl]amino]-1,1-dimethyl-3-oxopropylcarbamic acid, 1,1-dimethylethyl ester수율 90.2%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

To a solution of 0.83 g (2.21 mmol) of 3-t-butoxycarbonylamino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]-butanamide (Example 57, Step A) in 6 mL of dry dimethylformamide at room temperature under nitrogen was added 97 mg of 60% sodium hydride dispersion in oil (58 mg NaH, 2.43 mmol, 1.1 eq). After stirring for 1 hour, a solution of 780 mg (2.88 mmol, 1.3 eq) of 4'-bromomethyl-1,1'-biphenyl-2-nitrile (Step C) in 2.0 mL of dimethylformamide was added via cannula. The flask which originally contained the bromide was washed with 1 mL of dry dimethylformamide which was then added to the reaction mixture via cannula. After stirring at room temperature for 3 hours, the reaction was diluted with 200 mL of ethyl acetate, washed with 50 mL of water and 50 mL of brine. The organic layer was separated, 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 (6:4), to afford 1.13 g (90%) of the product as a white foam. 1H NMR (200 MHz,CDCl3): 1.32 (s,3H), 1.40 (s,12H), 1.85 (m,1H), 2.35-2.70 (m,5H), 4.52 (m,1H), 4.90 (d,12 Hz,1H), 5.21 (d,12 Hz,1H), 6.70 (d,5 Hz,1H), 7.10-7.65 (m,12H), 7.72 (d,6 Hz,1H). FAB-MS: calculated for C34H38N4O4 566; found 567 (M+H).

후처리

  1. washwas washed with 1 mL of dry dimethylformamide which
  2. additionwas then added to the reaction mixture via cannula
  3. stirringAfter stirring at room temperature for 3 hours
  4. additionthe reaction was diluted with 200 mL of ethyl acetate
  5. washwashed with 50 mL of water and 50 mL of brine
  6. customThe organic layer was separated
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customthe solvent removed under vacuum
  10. customThe residue was purified by flash chromatography on silica gel
  11. washeluting with ethyl acetate/hexane (6:4)

출처 및 근거

ORD 기록
ord-a186ee16567e410c8bf862a9fcbe60c9
출처 데이터셋
uspto-grants-1993_04
특허 번호
US05206235

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