一种新的贝达喹啉消旋体合成工艺研究

A new synthetic process of bedaquiline racemate

目的一种新的贝达喹啉消旋体(1)的合成工艺。方法依次以3-溴苄基-6-溴-2-甲氧基喹啉(2),1-萘醛(3)和N,N-二甲氨基乙基溴化镁(6)为起始原料,经格氏试剂与羰基加成、Swern-氧化和再次格氏试剂与羰基加成的3步反应制得贝达喹啉消旋体(1)。结果经过LC-MS、核磁共振谱等进行结构表征,证实得到了目标产物1,其HPLC纯度达到98%,总收率为61%(以2计)。结论改进后的工艺路线短,反应条件简单易行,杂质容易控制,可用于大规模生产。

Objective A new synthesis process of bedaquiline racemate(I).Methods The bedaquiline racemate(1)was prepared by a three-step route from 3-bromobenzyl-6-bromo-2-methoxyq-uinoline(2),1-naphthaldehyde(3),and N,N-dimethylaminoethylmagnesium bromide(6).The synthetic route started via the addition reaction of Grignard reagent with carbonyl,then via the reaction of Swern Oxidation,followed by the addition reaction of Grignard reagent with carbonyl again.Results After structural characterization by LC-MS and nuclear magnetic resonance spectroscopy,it was confi rmed that the target product 1 was obtained,its HPLC purity reached 98%,and the total yield was 61%(calculated as 2).Conclusions The improved process route is short,the reaction conditions are simple and easy to operate,and the impurities are easy to control,which can be used for largescale production.