米力农的合成新工艺  

A Novel Synthetic Process for Milrinone

作　　者：鲍广龙 张乃华 相阳光 费凡 张贵民 BAO Guanglong;ZHANG Naihua;XIANG Yangguang;FEI Fan;ZHANG Guimin(International Pharmaceutical Engineering Lab.of Shandong Province,Lunan Pharmaceutical Group Co.,Ltd.,Linyi 273400)

机构地区：[1]鲁南制药集团股份有限公司,山东省药物国际化工程实验室,山东临沂273400

出　　处：《中国医药工业杂志》2021年第1期59-62,共4页Chinese Journal of Pharmaceuticals

摘　　要：本研究报道了米力农(1)的合成新工艺。以4-甲基吡啶(2)为起始原料,与乙酰氯反应后,经乙酸酐处理制得关键中间体1-乙酰基-4-(乙酰基亚甲基)-1,4-二氢吡啶(3),α-氰基乙酰胺(4)与原甲酸三乙酯反应合成2-氰基-3-乙氧基丙烯酰胺(5),最后3与5环合制得目标产品1,纯度99.96%,收率74%(以2计)。其中由3和5制备1的方法未见文献报道,本工艺已经过中试验证,适合工业化生产。A novel synthetic process of milrinone(1)was reported in this paper.4-Methylpyridine(2)was reacted with acetyl chloride,followed by treatment with acetic anhydride,to afford 1-acetyl-4-(acetylmethylidene)-1,4-dihydropyridine(3),and 2-cyano-3-ethoxyacrylamide(5)was prepared fromα-cyanoacetamide(4)via condensation with triethylorthoformate.Finally,the target compound 1 was obtained through cyclization of 3 and 5 with an overall yield of 74%(based on 2)and a purity of 99.96%.The synthetic method for 1 from 3 and 5 has not been found in literature.The new route has been tested in pilot scale,which is suitable for industrial production.

关 键 词：米力农 强心药 合成工艺 

分 类 号：R972.1[医药卫生—药品] R914[医药卫生—药学]