匹莫苯丹的合成工艺研究进展

Progress in Synthesis of Pimobendane

匹莫苯丹是国家二类新兽药。但由于该药的原料药成本较高,不易合成,反应步骤多而限制了该药物的临床普遍应用。因此,进行了对匹莫苯丹合成工艺的调查,概述了近年来国内外关于匹莫苯丹的10个合成方法。主要包括以氯苯、乙酰苯胺、对氯苯甲醛、3-(4-乙酰胺基苯甲酰基)-丁腈、邻苯二乙酸二铵和5-(2-溴代丙酰基)-1,3-2H-苯丙[d]咪唑-2-酮为起始原料合成制备匹莫苯丹,并分析了这些合成方法中存在的问题,还考察了匹莫苯丹副产物的产生和解决办法,为其工业化合成研究提供参考。

Pimobendane is the country′s new class two veterinary drugs.However,due to the high cost of the drug′s API,the difficulty in synthesis,and the large number of reaction steps,the widespread clinical application of the drug is limited.In this paper,the synthesis process of pimobendan was investigated,10 methods of pimobendan synthesis were summarized.It mainly includes chlorobenzene,acetanilide,p-chlorobenzaldehyde,3-(4-acetylaminobenzoyl)-butyronitrile,diammonium phthalate and 5-(2-bromopropionyl)-1,3-2h-phenylpropyl[D]imidazol-2-one was used as the starting material to synthesize pimobendan,and the problems in these synthesis methods were analyzed.The production and solution of the by-products of pimobendan were also investigated,providing reference for its industrial synthesis.