丁烯苯酞中两个潜在杂质的合成与解析

Synthesis and Resolution of Two Potential Impurities in Butene-phenylpeptides

丁苯酞是治疗缺血性脑卒中的重要药物。进行其合成工艺研究时发现在第一步以苯酐(7)和戊酸酐(6)为起始物料,戊酸钠(5)为催化剂经过缩合反应过程中,易产生两个较大杂质,文章通过对中间体(4)的水解、开环处理和柱层析分离得到比较纯的两个杂质,经过^(13)C-NMR、^(1)H-NMR、DEPT、COSY、HSQC、HMBC进行结构确认分别是杂质3-丁基-2-异丙基-1H-吲哚酮(双侧链1)和杂质3-(丁烯-1基)异苯并呋喃-1(3H)-酮(双键异位2)。

Butylphthalein is an important drug in the treatment of ischemic stroke.In the study of its synthesis process,it was found that in the first step,phthalic anhydride(7)and valerate anhydride(6)were used as starting materials,and sodium valerate(5)was used as catalyst during the condensation reaction process,two large impurities were easily produced.In this paper,two relatively pure impurities were obtained through hydrolysis,ring-opening treatment and column chromatography separation of the intermediate(4).The structure was confirmed by ^(13)C-NMR,^(1)H-NMR,DEPT,COSY,HSQC,and HMBC as impurity 3-butyl-2-propyl-1H-inden-1-one(bilateral-chain 1)and impurity 3-butyl-2-propyl-1H-inden-1-one(double bond ectopic 2),respectively.