替格瑞洛的合成工艺研究  

Synthesis Process of Ticagrelor

作　　者：陈全会 吕新宇[1] 邱滔[1] CHE Quanhui;LV Xinyu;QIU Tao(School of Petrochemical Engineering,Changzhou University,Changzhou 213164,China)

机构地区：[1]常州大学石油化工学院,江苏常州213164

出　　处：《化学反应工程与工艺》2023年第2期159-165,共7页Chemical Reaction Engineering and Technology

摘　　要：以2-正丙硫基-4,6-二氯-5-氨基嘧啶为起始原料,经芳香亲核取代、重氮化、芳香亲核取代和脱亚异丙基保护四步反应制得抗凝血药替格瑞洛。结果表明:在第一步芳香亲核取代反应中,以三乙胺和N,N-二异丙基乙胺体系作为溶剂和缚酸剂,大幅缩短了反应时间,提高了转化率和收率;在第三步芳香亲核取代反应中,以碳酸钾为缚酸剂,简化了后处理过程,减少了对环境的污染。所用合成方法操作简单、易于纯化,为工业化放大生产提供了可能性。The 2-n-propylthio-4,6-dichloro-5-aminopyrimidine was used as raw material to synthesis the anticoagulant ticagrelor through a four-step reaction,including aromatic nucleophilic substitution,diazotization,aromatic nucleophilic substitution and deisopropylidene protection.In the first step of the aromatic nucleophilic substitution reaction,triethylamine and N,N-diisopropylethylamine system were used as the solvent and acid binding agent.The reaction time was greatly shortened,the conversion rate and yield were improved.In the third step of the aromatic nucleophilic substitution reaction,potassium carbonate was used as an acid binding agent,which simplified the post-processing and reduced environmental pollution.The synthetic method is simple to operate and easy to purify,and provides the possibility for industrial scale-up production.

关 键 词：替格瑞洛 芳香亲核取代 缚酸剂 

分 类 号：O626.4[理学—有机化学] O623.7[理学—化学]