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[1]古双喜,乔恒,段婷,等.HIV1抑制剂依曲韦林的合成[J].武汉工程大学学报,2014,(06):10-13.[doi:103969/jissn16742869201406003]
　GU Shuang xi,QIAO Heng,DUAN Ting,et al.Synthesis of HIV1 inhibitor etravirine[J].Journal of Wuhan Institute of Technology,2014,(06):10-13.[doi:103969/jissn16742869201406003]
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HIV1抑制剂依曲韦林的合成(/HTML)
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《武汉工程大学学报》[ISSN:1674-2869/CN:42-1779/TQ]

卷:
期数:
2014年06期
页码:
10-13
栏目:
化学与化学工程
出版日期:
2014-06-30

文章信息/Info

Title:
Synthesis of HIV1 inhibitor etravirine
文章编号:
16742869(2014)060001004
作者:
古双喜1; 2; 乔恒1; 2; 段婷1; 2; 朱园园3; 陈金芳1; 2; 巨修练1; 2*
1.武汉工程大学化工与制药学院，湖北 武汉 430074；2.绿色化工过程教育部重点实验室(武汉工程大学) ，湖北 武汉 430074；3.武汉工程大学化学与环境工程学院，湖北 武汉 430074
Author(s):
GU Shuangxi1; 2; QIAO Heng1; 2; DUAN Ting1; 2; ZHU Yuanyuan3; CHEN Jinfang1; 2; JU Xiulian1; 2
1.School of Chemical Engineering and Pharmacy,Wuhan Institute of Technology,Wuhan 430074,China;2.Key Laboratory of Green Chemical Process(Wuhan Institute of Technology),Ministry of Education,Wuhan 430074,China;3.School of Chemistry and Environmental Engineering,Wuhan Institute of Technology,Wuhan 430074,China
关键词:
依曲韦林; HIV1抑制剂; 艾滋病; 二芳基嘧啶类化合物
Keywords:
etravirine;  HIV1 inhibitors;  AIDS;  diarylpyrimidines
分类号:
O626.41
DOI:
103969/jissn16742869201406003
文献标志码:
A
摘要:
为了解决依曲韦林（Ⅰ）目前合成工艺中普遍存在的成本高问题，采用JoshiMaikap合成策略以更佳的工艺条件合成得到Ⅰ：原料2,4,6三氯嘧啶（Ⅱ）和3,5二甲基4羟基苯腈（Ⅲ）在N,N二异丙基乙胺作用下于1,4二氧六环中发生嘧啶环C4亲核取代反应得到中间体Ⅳ，收率为82.3%；Ⅳ与对氨基苯腈于N甲基吡咯烷酮中发生嘧啶环C2亲核取代反应得到中间体Ⅴ，收率为61.7%；Ⅴ与氨水于1,4二氧六环中发生嘧啶环C6亲核取代反应得到中间体Ⅵ，收率为84.5%；Ⅵ与液溴于二氯甲烷中发生溴代反应得到Ⅰ，收率为81.3%.四步反应的总收率由文献报道的30.4%提高到34.9%.中间体和产品的熔点、质谱和核磁数据均与文献报道数据吻合.
Abstract:
To overcome the highcost problem in the present synthetic process of etravirine (Ⅰ),JoshiMaikap synthetic strategy was adopted to prepare Ⅰ according to optimized process as follows: raw materials 2,4,6Trichloropyrimidine (Ⅱ) and 3,5,dimethyl4hydroxybenzonitrile (Ⅲ) were subject to nucleophilic substitution at C4 position on pyrimidine ring to get intermediate Ⅳ in the presence of N,Ndiisopropylethylamine and 1,4dioxane in a yield of 82.3%.Then Ⅳ and 4aminobenzonitrile reacted at C2 position on pyrimidine ring to afford intermediate Ⅴ in a yield of 61.7%,followed by aminolysis of Ⅴ in the presence of ammonia and 1,4dioxane to get C6 nucleophilic substituted intermediate Ⅵ in a yield of 84.5%.Finally,Ⅵ was brominated in dichloromethane to get Ⅰ in a yield of 81.3%.And the fourstep total yield was raised to 34.9% from the reported 30.4%.The data of melting point,mass spectrometry and 1H NMR are in accordance with that in literature.

参考文献/References:

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备注/Memo

备注/Memo:
收稿日期：20140506基金项目：湖北省教育厅科学技术研究计划青年人才项目（Q20141505）作者简介：古双喜（1979），男，湖北黄冈人，讲师，博士，硕士研究生导师.研究方向：药物合成工艺，药物化学，有机合成.*通信联系人
更新日期/Last Update: 2014-07-29