A suspension of 11.83 g (50 mmol) of (S)-5-chloro-1,10a-dihydro-azeto[2,1-c][1,4]benzodiazepine-4,10-(2H,9H)-dione in 35 ml of dry N,N-dimethylformamide is treated at -30° to -20° with 2.18 g (50 mmol) of sodium hydride (55 percent oil dispersion), the mixture is stirred at the above temperature for a further 35 minutes, and then at -70° there is added dropwise a solution of 13.43 g (50 mmol) of phosphoric acid diphenyl ester chloride in 8 ml of dry N,N-dimethylformamide. After stirring for 20 minutes in an acetone/dry-ice bath there is added dropwise at -70° a solution of 7.58 g (50 mmol) of 3-chlorobenzyl isocyanide in 4 ml of dry N,N-dimethylformamide, and subsequently at -65° to -40° there is added dropwise a solution of 5.61 g (50 mmol) of potassium t-butylate in 9 ml of dry N,N-dimethylformamide. The mixture is left to warm to room temperature and neutralized by the addition of 2.5 ml of glacial acetic acid. The mixture is poured into 300 ml of water and extracted five times with methylene chloride. The combined organic extracts are washed three times with water, dried over magnesium sulfate, and concentrated. The residue is chromatographed on silica gel while eluting with ethyl acetate and recrystallized twice from ethyl acetate. There is obtained (S)-8-chloro-1-(m-chlorophenyl)-12,12a-dihydro-9H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one having a melting point of 221°-223°.
