贝达喹啉中间体3-苄基-6-溴-2-甲氧基喹啉的合成工艺优化
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摘要
贝达喹啉是本世纪初开发上市的新型二芳基喹啉类药物,而3-苄基-6-溴-2-甲氧基喹啉是合成贝达喹啉的重要中间体。本文针对此中间体合成时间长,收率低的问题,通过探讨不同的反应时间、温度、溶剂等因素对其影响,寻找到较优的反应条件,提高了反应收率,缩短了反应时间,便于工业化生产。
Beidaquiline is a novel diaryl quinoline drug developed and marketed at the beginning of this century,and 3-benzyl-6-bromo-2-methoxyquinoline is an important intermediate for the synthesis of bedaquiline. This article aimed at the problem of long synthesis time and low yield of this intermediate. Through the discussion of different reaction time,temperature,solvent and other factors,it found better reaction conditions,improved the reaction yield and shortened the reaction time.This condition facilitated industrial production.
Beidaquiline is a novel diaryl quinoline drug developed and marketed at the beginning of this century,and 3-benzyl-6-bromo-2-methoxyquinoline is an important intermediate for the synthesis of bedaquiline. This article aimed at the problem of long synthesis time and low yield of this intermediate. Through the discussion of different reaction time,temperature,solvent and other factors,it found better reaction conditions,improved the reaction yield and shortened the reaction time.This condition facilitated industrial production.
引文
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[9]鲁振浩,李文军,陈世强,等. 2-(5-氨基-1,3,4-噻二唑)基乙酸乙酯的合成及优化[J].化学研究与应用,2014,26(8):1 356-1 359.
[2]杨臻峥.抗结核药Bedaquiline[J].药学进展,2013,37(1):50-51.
[3]谭初兵,时丽丽,王士伟,等.2012年美国FDA批准新药介绍和分析[J].现代药物与临床,2013,28(3):415-420.
[4]应苗法,朱剑萍,马珂,等.新型抗结核药物贝达喹啉的作用及其研究进展[J].中国新药与临床杂志,2014,33(5):325-329.
[5]Stehr M,A Elamin A,Singh M. Filling the pipeline-new drugs for an old disease[J].Curr Top Med Chem,2014,14(1):110-129.
[6]Guillemont,Emile,Georges,et al.Quinoline derivatives and their use as mycobacterial inhibitors[P]. America:WO:2004011436,2004-02-05.
[7]顾红蕾,吴泰志,张福利.富马酸贝达喹啉合成路线图解[J].中国医药工业杂志,2014,45(10):990-993.
[8]侯玲,侯旭,王志明,等.新型抗结核药物贝达喹啉的合成[J].广西大学学报(自然科学版),2016,41(6):2067-2 070.
[9]鲁振浩,李文军,陈世强,等. 2-(5-氨基-1,3,4-噻二唑)基乙酸乙酯的合成及优化[J].化学研究与应用,2014,26(8):1 356-1 359.