Preparation method of alprazolam and impurity LAP thereof

• Main Authors: ZOU ZONGJI, LU JUN, PAN YUELONG, FAN SONG, ZHU LIQIANG, LIU YINQIANG, MENG LINGHUA, XU QINLIANG, LI ZHUOHUA, LYU JIA, WANG YUEHENG
• Format: Patent
• Language: Chinese; English
• Published: 21.11.2023
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

The invention discloses a preparation method of alprazolam and its impurity LAP, the method takes 7-chloro-5-phenylbenzodiazepinone as a starting material, the 7-chloro-5-phenylbenzodiazepinone and acetyl chloride are subjected to an acylation reaction, and then the product and hydrazine hydrate are subjected to a cyclization reaction to obtain the alprazolam finished product, the method can avoid the impurity LAP generation, and the purity of the alprazolam is improved. Meanwhile, the use of phosphorus pentasulfide and the risk of poisoning caused by hydrogen sulfide generated in the reaction process are avoided, and the safety of the process is greatly improved. According to the invention, 7-chloro-5-phenylbenzodiazepinone is taken as a starting material, the 7-chloro-5-phenylbenzodiazepinone reacts with chloroacetic acid, then the 7-chloro-5-phenylbenzodiazepinone and hydrazine hydrate are subjected to a cyclization reaction under the catalysis of a condensing agent N, N '-carbonyl di (1, 2, 4-triazole) to