反应详情

A slurry of 7-chloro-5-(2-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine-2-methanamine-4-oxide oxalate salt (VIII, EXAMPLE 6, 35 g, 85 mmol) and triethylorthoacetate (23.5 ml, 128 mmol) in acetonitrile (175 ml) is stirred at reflux for 2 hr during which time the 7-chloro-5-(2-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine-2-methanamine-4-oxide (VIII) dissolves and ethanol/acetonitrile (about 75 ml) is removed by distillation under ordinary pressure. TLC and HPLC analysis shows the reaction is complete. The temperature is adjusted to 40° and methyl t-butyl ether (175 ml) is added dropwise over about 1 hr. The resulting slurry is cooled to 5°, stirred 1 hr, the solids are collected and are washed with t-butyl ether. The product is dried in the vacuum oven at 35° to give the title compound as the oxalate salt, mp=178°-180°; TLC (methylene chloride/methanol/ammonium hydroxide, 90/10/1) Rf =0.28.

1. dissolutiondissolves
2. customethanol/acetonitrile (about 75 ml) is removed by distillation under ordinary pressure
3. customis adjusted to 40°
4. additionmethyl t-butyl ether (175 ml) is added dropwise over about 1 hr
5. temperatureThe resulting slurry is cooled to 5°
6. customthe solids are collected
7. washare washed with t-butyl ether
8. customThe product is dried in the vacuum oven at 35°