反应详情

温度

70 °C

A solution of 3-[(benzyloxycarbonyl)amino]-5-phenyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one (7.00 g, 18.2 mmol) in glacial acetic acid (200 mL), prepared as in Intermediate 6, is saturated with HBr gas. The reaction is warmed to 70° C. and held for 20 min. The temperature is raised to 80° C. and maintained for an additional 20 min. The resulting slurry is cooled to ambient temperature, diluted with anhydrous diethyl ether (200 ml), agitated for 0.5 hrs., filtered and washed with diethyl ether. The hydrobromide salt is dried at 60° C. under vacuum to provide the dihydrobromide salt (6.836 g, 16.5 mmol) of the title compound. The free base is obtained by partitioning the dihydrobromide (6.100 g, 14.3 mmol) between aqueous potassium carbonate (5% w/v, 50 mL) and a mixture of ethyl acetate, isopropanol and DCM. After separating the phases, the organic layer is dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to a solid. The product is dried under high vacuum to provide the title compound as a crystalline solid (3.69 g, 14.3 mmol). 1H NMR (300 MHz, d6-DMSO) δ=4.21 (s, 1H); 7.15-7.60 (m, 9H); 10.66 (s, 1H). TLC: Rf =0.33 (95:5 chloroform: methanol).

1. temperatureThe temperature is raised to 80° C.
2. temperaturemaintained for an additional 20 min
3. temperatureThe resulting slurry is cooled to ambient temperature
4. filtration, filtered
5. washwashed with diethyl ether
6. dry with materialThe hydrobromide salt is dried at 60° C. under vacuum