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 482342Notes

Reaction equation

HRID 482342 reaction equation
[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]

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent2×

Procedure

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

Workup

  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

Sources & evidence

ORD record
ord-8a12230f7c5146528f623cd07494493f
Source dataset
uspto-grants-1998_08
Patent number
US05795887

Reaction notes

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