氯氮平有关物质的合成

Synthesis of the Related Substances of Clozapine

为控制氯氮平的质量,本研究基于其合成工艺,合成了6个有关物质,分别为8-氯-5,10-二氢-11H-二苯并[b,e]-[1,4]二氮杂?-11-酮(有关物质A)、11,11'-(1,4-哌嗪二基)双(8-氯-5H-二苯并[b,e][1,4]二氮杂?)(有关物质B)、8-氯-11-(1-哌嗪基)-5H-二苯并[b,e][1,4]二氮杂?(有关物质C)、2-(2-氨基-4-氯苯基)氨基苯基-1-(4-甲基哌嗪基)-甲酮(有关物质D)、8-氯-11-(4-甲基哌嗪基)-5H-二苯并[b,e][1,4]二氮杂?·氮氧化物(有关物质E)和11-(4-甲基哌嗪基)-5H-二苯并[b,e][1,4]二氮杂?(有关物质F)。其中,该有关物质F的合成方法尚未见文献报道。上述有关物质的结构均经ESI-HRMS和~1H NMR确证。

In order to control the quality of clozapine,six related substances,namely 8-chloro-5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-one(related substance A),11,11’-(piperazin-1,4-diyl)bis(8-chloro-5H-dibenzo[b,e][1,4]-diazepine)(related substance B),8-chloro-11-(piperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepine(related substance C),[2-[(2-amino-4-chlorophenyl)amino]phenyl](4-methylpiperazin-1-yl)methanone(related substance D),8-chloro-11-(4-methylpiperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepine-1-oxide(related substance E)and 11-(4-methylpiperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepine(related substance F),were synthesized based on the synthetic process of clozapine.Among them,the synthetic method of related substance F has not been found in literature.The structures of the above related substances were confirmed by ESI-HRMS and^1H NMR.