Carbon Dioxide → (S)-8-chloro-7-fluoro-12,12a-dihydro-1-[5-(dimethylaminomethyl)-1,2,4-oxadiazol-3-yl]-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one

Participants

Reaction Steps

1.24 g (12 mmol) of N,N-dimethylglycine were dissolved in 20 ml of N,N-dimethylformamide and treated portionwise with 2.43 g (15 mmol) of 1,1'-carbonyldiimidazole. After completion of the CO2 evolution the solution was stirred at 70° for 30'. Then, 3.35 g (10 mmol) of (S)-8-chloro-7-fluoro-12,12a-dihydro-9-oxo-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxamidoxime were added and the mixture was stirred at 90° for 3.5 hours. By evaporation of the solution, chromatography of the residue on 300 g of silica gel while eluting with ethyl acetate/methanol 9/1 and crystallization from ethyl acetate and hexane there was obtained 0.98 g (24%) of (S)-8-chloro-7-fluoro-12,12a-dihydro-1-[5-(dimethylaminomethyl)-1,2,4-oxadiazol-3-yl]-9H,11H- azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one of m.p. 166°-169°, which was converted into the hydrochloride of m.p. 223°-227°.

Provenance & Evidence