吉莫斯特的合成  

Studies on the synthesis of gimeracil

作　　者：郝玲花[1] 周洁[1] 孙延龙[1] 王友奇[1] 曾昭钧[1] 

机构地区：[1]沈阳药科大学制药工程学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2005年第6期420-421,433,共3页Journal of Shenyang Pharmaceutical University

摘　　要：目的合成二氢嘧啶脱氢酶抑制剂吉莫斯特。方法以丙二腈、原乙酸三甲酯和1,1二甲氧基三甲胺为起始原料制备1,1二氰基2甲氧基4(N,N二甲基氨基)1,3丁二烯,经体积分数为80%的冰醋酸环合得3氰基4甲氧基2(1H)吡啶酮,再经NCS氯代形成5氯3氰基4甲氧基2(1H)吡啶酮,经质量分数为48%的HBr水解得吉莫斯特。结果合成了吉莫斯特,总收率达65.6%,各步中间体结构由MS1、H NMR确证,目标产物经MS、1H NMR以及元素分析确证。结论该工艺路线成本较低,反应条件温和,操作简便,容易实现工业化生产。Objective To synthesize gimeracil, which is a potent dihydropyrimidine dehydrogenase inhibitor. Methods Gimeracil was synthesized by four steps from malononitrile, trimethyl orthoacetate and 1, 1- dimethoxy-trimethylamine via condensation, cyclization, chlorination and hydrolysis reactions. Results Gimeracil was synthesized in overall yield of 65.6 %, its structure was confirmed by MS, 1H-NMR as well as elemental analysis. Intermediate compounds were confirmed by MS and 1H-NMR. Conclusions The improved process has advantages of lower cost, mild reaction conditions, convenient work-up. It is suitable for industrial production.

关 键 词：吉莫斯特 抗癌药物 药物合成 

分 类 号：R914[医药卫生—药物化学] R979.1[医药卫生—药学]