摘要
目的改进盐酸普拉克索的合成工艺。方法以1,4-环己二酮单乙二醇缩酮为原料,采用“一锅法”对重要中间体2-氨基-6-羟基4,5,6,7-四氢苯并噻唑的合成进行改进,该中间体经进一步叠氮化、还原、拆分、烷基化及成盐反应得到目标化合物盐酸普拉克索。结果与结论合成过程中所有中间体及最终产物的结构均经1H-NMR、13C-NMR确证,总收率为17.4%(以1,4-环己二酮单乙二醇缩酮计),纯度大于99.0%。改进后的工艺为盐酸普拉克索的后续生产和应用研究提供了实验基础。
A"one-pot"method was used to optimize on the synthesis of 2-amino-6-hydroxyM,5,6,7-tetrahydrobenzothiazole(2)with 1,4-cyclohexanedione monoethyleneacetal(1)as the raw material.Compound 2 was a key intermediate in the preparation of pramipexole dihydrochloride.The method has the advantage of simple operation without separation and purification.Pramipexole dihydrochloride was obtained by optimizing the reaction conditions of the azidation,reduction,resolution,alkylation and salt formation with compound 2 as starting material,with the yield of 17.4%.All the intermediates and final products were confirmed by 1H-NMR and 13C-NMR.The results will provide a solid experimental basis for the future production and application of pramipexole dihydrochloride.
作者
陈昊天
孙兰天
辛红兴
闫红
CHEN Hao-tian;SUN Lan-tian;XIN Hong-xing;YAN Hong(College of Life Science and Bioengineering,Beijing University of Technology,Beijing 100124,China;Jumpcan Pharmaceutical Co.,Ltd.,Taizhou 225441,China)
出处
《中国药物化学杂志》
CAS
CSCD
北大核心
2019年第2期118-121,共4页
Chinese Journal of Medicinal Chemistry
关键词
普拉克索
抗帕金森症
合成工艺优化
一锅法
pramipexole
anti-Parkinsons drugs
synthesis process optimization
one-pot
