Continuous-Flow Multistep Synthesis of Cinnarizine, Cyclizine, and a Buclizine Derivative from Bulk Alcohols
作者:Svetlana Borukhova、Timothy Noël、Volker Hessel
DOI:10.1002/cssc.201501367
日期:2016.1
Cinnarizine, cyclizine, buclizine, and meclizine belong to a family of antihistamines that resemble each other in terms of a 1‐diphenylmethylpiperazine moiety. We present the development of a four‐step continuous process to generate the final antihistamines from bulk alcohols as the starting compounds. HCl is used to synthesize the intermediate chlorides in a short reaction time and excellent yields
肉桂利嗪,环利嗪,丁克利嗪和甲氯嗪属于抗组胺药家族,它们在1-二苯基甲基哌嗪部分上彼此相似。我们提出了一个四步连续过程的开发过程,该过程从大量的醇类作为起始化合物生成最终的抗组胺药。HCl用于在短的反应时间内合成中间氯化物,并具有优异的收率。该方法学提供了合成用于药物合成的中间体的绝佳方法。在线分离允许在以下步骤中收集纯净的产品并立即消费它们。肉桂利嗪,环齐嗪和丁克利嗪衍生物的总分离产率分别为82%,94%和87%。这四个步骤的总停留时间为90分钟,生产率为2 mmol h -1。