乌拉地尔的合成改进  

Improvement of the Synthesis of Urapidil

作　　者：李雯[1] 吴桂英[1] 马晓青[1] 杜孟洪[1] 王盼盼[1] 张文亚[1] 陈水库 

机构地区：[1]郑州大学化工与能源学院,河南郑州450001 [2]河南辅仁医药科技开发有限公司,河南郑州450002

出　　处：《高校化学工程学报》2013年第1期131-135,共5页Journal of Chemical Engineering of Chinese Universities

基　　金：河南省高等学校青年骨干教师资助计划(2010GGJS-005)资助;郑州大学研究生教育支持基金(2011)资助;郑州大学化工与能源学院普润研究生科研基金(2011)资助

摘　　要：乌拉地尔是一种新型的多靶点降压药物,现对其已有的合成方法进行改进。讨论了相转移催化条件和逆向相转移催化条件下,以6-（3-氯丙基）氨基-1,3-二甲基尿嘧啶和1-（2-甲氧基苯基）哌嗪盐酸盐为原料,进行乌拉地尔合成的反应结果。逆向相转移催化条件下所获收率高于相转移催化条件。当选择β-CD为逆向相转移催化剂,水为溶剂,反应温度为95℃,在1500 r min 1转速下经2~3 h反应,可以大于80%的收率获得含量为96.6%~98.0%乌拉地尔粗品。乌拉地尔粗品精制采用反溶剂重结晶法,其适宜条件是7℃时,二氯甲烷为溶剂,丙酮为反溶剂,所获得乌拉地尔成品含量〉98.5%,收率〉95%。乌拉地尔结构经1H-NMR、MS、IR和元素分析确证。与已有工艺比较,改进的合成方法具有显著缩短反应时间,产物分离简单易行,合成工艺简单、易于工业化生产等优点。Urapidil is a new class antihypertensive drug with multiple targeted activities.An improved synthetic method of it was described.The reaction results of the synthesis of Urapidil under phase-transfer catalysis and inverse phase-transfer catalysis were discussed when 6-[（3-chloropropyl） amino]-1,3-dimethyluracil and 1-（2-methoxy phenyl） piperazine was chosen as the raw materials.The yields of inverse phase-transfer catalysis are higher than that of phase-transfer catalysis.When β-Cyclodextrin was used as an inverse phase-transfer catalyst,over 80% isolated yield of Urapidil with 96.6%~98.0% purity was obtained after 2~3 h reaction in aqueous media at 95℃ with an agitation rate of 1500 r.min.1.Urapidil was purified by anti-solvent precipitation.Under the appropriate condition which dichloromethane was used as the solvent and acetone was used as the anti-solvent at 7℃,Urapidil was got with 98.5% purity and 95% yield.The structure of objective product was confirmed by 1H-NMR,IR,MS and elemental analysis.Comparing with the current technology,this described synthetic method has the merits of the greatly shorten the reaction time,the easy purification of the products,and its synthetic technology is simple and convenient to be used for industrial application.

关 键 词：乌拉地尔 逆向相转移催化反应 反溶剂重结晶 合成 

分 类 号：R978.15[医药卫生—药品] R972.4[医药卫生—药学]