p-Toluenesulfonic acid → (S)-8-chloro-12,12a-dihydro-1-[5-(pyrrolidin-1-ylmethyl)-1,2,4-oxadiazol-3-yl]-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one

Participants

Reaction Steps

2.55 g (13.5 mmol) of 1-pyrrolidine-acetic acid were dissolved in 20 ml of N,N-dimethylformamide and treated portionwise with 2.6 g (15.9 mmol) of 1,1'-carbonyldiimidazole. After stirring for 45 minutes 3.9 g (12.3 mmol) of (S)-8-chloro-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° overnight. 0.2 g of p-toluenesulphonic acid was added and the mixture was stirred at 90° for a further 4 hours. The reaction mixture was concentrated. By chromatography of the residue on silica gel while eluting with methylene chloride/methanol 19/1 and recrystallization from ethyl acetate and hexane there were obtained 1.6 g (32%) of (S)-8-chloro-12,12a-dihydro-1-[5-(pyrrolidin-1-ylmethyl)-1,2,4-oxadiazol-3-yl]-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one of m.p. 117°-120°, which was converted into the hydrochloride.

Provenance & Evidence