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

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Reaction Steps

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

Provenance & Evidence