盐酸曲美他嗪的合成工艺改进  

Improvement of Synthetic Process of Trimetazidine Dihydrochloride

作　　者：陈敏 陈多鹏 刘祈星 刘义稳 周海峰 CHEN Min;CHEN Duopeng;LIU Qixing;LIU Yiwen;ZHOU Haifeng(Hubei Key Lab.of Natural Products Research&Development,College of Biological&Pharmaceutical Sciences,China Three Gorges University,Yichang 443002;Wufeng Chicheng Biotech Co.,Ltd.,Yichang 443003)

机构地区：[1]三峡大学生物与制药学院,天然产物研究与利用湖北省重点实验室,湖北宜昌443002 [2]五峰赤诚生物科技股份有限公司,湖北宜昌443003

出　　处：《中国医药工业杂志》2025年第2期187-189,238,共4页Chinese Journal of Pharmaceuticals

基　　金：国家自然科学基金面上项目(22278244)。

摘　　要：文章对盐酸曲美他嗪(1)的合成工艺进行改进。以廉价、易得的2,3,4-三甲氧基苯甲醛(2)和无水哌嗪(3)为起始原料,商业可得的吡啶酰胺铱络合物(4)为催化剂,甲酸为氢源,通过还原胺化和水解反应制备曲美他嗪(5),再与氯化氢成盐得到1,纯度达99.8%,总收率为75.5%(以2计)。该合成工艺反应条件温和,催化剂用量少(物质的量分数为0.01%),收率高,3和甲酸的用量少、成本较低。The synthesis process of trimetazidine hydrochloride(1) was improved in this study.Trimetazidine(5) was prepared from inexpensive and widely available 2,3,4-trimethoxybenzaldehyde(2) and anhydrous piperazine(3) via reductive amination and hydrolysis with formic acid as hydrogen source and commercially available pyridinamide iridium complex(4) as catalyst,which was further treated with hydrogen chloride to provide trimetazidine dihydrochloride(1) with 99.8% purity and 75.5% total yield (based on 2).This improved process has the advantages of mild reaction conditions,low catalyst loading(0.01% of mole fraction),high yield,less consumption of 3 and formic acid and low cost.

关 键 词：曲美他嗪 活性药物成分 抗心绞痛药 工艺改进 

分 类 号：R914.5[医药卫生—药物化学] TQ460.6[医药卫生—药学]