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Sodium hydride → 3-Benzyloxycarbonylamino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1-[[2'-[(t-butoxycarbonylamino)methyl][1,1'-biphenyl]-4-yl]methyl]-1H-1-benzazepin-3(R)-yl]-butanamide

HRID 1080745
Notes
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Reaction equation

HRID 1080745 reaction equation
[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+].[C:33]([O:37][C:38]([NH:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=1[C:48]1[CH:53]=[CH:52][C:51]([CH2:54]O)=[CH:50][CH:49]=1)=[O:39])([CH3:36])([CH3:35])[CH3:34]>CN(C)C=O>[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[N:19]([CH2:54][C:51]2[CH:50]=[CH:49][C:48]([C:43]3[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=3[CH2:41][NH:40][C:38]([O:37][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:39])=[CH:53][CH:52]=2)[C:18]1=[O:28])=[O:15])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 105735633-Benzyloxycarbonylamino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1H-benzazepin-3(R)-yl]butanamideHCID 220084722'-[(t-Butoxycarbonylamino)methyl]-1,1-biphenyl-4-methanol

Product 1

HCID 228551563-Benzyloxycarbonylamino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1-[[2'-[(t-butoxycarbonylamino)methyl][1,1'-biphenyl]-4-yl]methyl]-1H-1-benzazepin-3(R)-yl]-butanamideYield 96%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 60 mg (0.15 mmol) of 3-benzyloxycarbonylamino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]butanamide (Step D) in 0.5 mL of dry dimethylformamide under nitrogen was added 6.4 mg (0.16 mmol) of 60% sodium hydride/oil dispersion. After stirring for 15 minutes, a solution of 60 mg (0.15 mmol) of 2'-[(t-butoxycarbonylamino)methyl]-1,1'-biphenyl-4-methanol, methanesulfonate ester (Step I) in 0.5 mL of dimethylformamide was aded by cannula. The flask which originally contained the methanesulfonate ester was rinsed with 0.5 mL of dimethylformamide which was added to the reaction mixture. After stirring at room temperature for two hours, the reaction mixture was diluted with 75 mL of ethyl acetate, washed with 20 mL of water and 20 mL of saturated aqueous sodium chloride. 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 (60:40) to afford 89 mg (96%) of the product as a white foam. FAB-MS: calculated for C42H48N4O6 704; found 705 (M+H). 1H NMR (200 MHz, CDCl3); 1.31 (s, 3H), 1.32 (s, 3H), 1.37 (s, 9H), 1.76 (s, 1H), 2.30-2.62 (m, 5H), 4.15 (d, 5 Hz, 2H), 4.40-4.60 (m, 2H), 4.85 (d, 14 Hz, 1H), 4.95 (d, 10 Hz, 1H), 5.04 (d, 10 Hz, 1H), 5.18 (d, 14 Hz, 1H), 5.65 (s, 1H), 6.70 (d, 6 Hz, 1H), 7.10-7.42 (m, 17H).

Workup

  1. washwas rinsed with 0.5 mL of dimethylformamide which
  2. additionwas added to the reaction mixture
  3. stirringAfter stirring at room temperature for two hours
  4. additionthe reaction mixture was diluted with 75 mL of ethyl acetate
  5. washwashed with 20 mL of water and 20 mL of saturated aqueous sodium chloride
  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 (60:40)

Sources & evidence

ORD record
ord-4242180809cd4b0b98b71003707d7fd9
Source dataset
uspto-grants-1996_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05583130

Reaction notes

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