摘要
目的 优化盐酸决奈达隆的合成工艺.方法 以5-硝基水杨醛为起始原料,经醚化、水解、环合、傅克酰化、脱甲基反应得到关键中间体2-丁基-3-(4-羟基苯甲酰基)-5-硝基苯并呋喃,再经醚化、还原、甲磺酰化和成盐反应得到目标化合物盐酸决奈达隆.结果 与结论 目标化合物及关键中间体的结构均经1H-NMR谱确证,目标化合物总收率为44.7％,纯度为99.9％,产品质量符合《欧洲药典》标准.优化后的工艺简化了实验操作,产品质量易于控制,更有利于实现工业化生产.
Abstract
Dronedarone hydrochloride is an approved drug for the treatment of arrhythmia.A new route to dronedarone hydrochloride was optimized on the base of references and laboratory verification.Using 5-nitrosalicylaldehyde as the starting material,the target compound was afforded by etherification,hydrolysis,cyclization,Friedel-Crafts acylation,demethylation,etherification,reduction,methane sulfonylation and salt formation,with a total yield of 44.7％and purity of 99.9％(HPLC).The improved synthetic process has the advantages of simple operation,mild reaction conditions,lower technology costs,high yield and purity,which is more suitable for industrial production.
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