科研之友
微信
新浪微博
Facebook
分享链接
摘要
Dronedarone hydrochloride (1), a potent blocker of multiple ion, was approved for atrial fibrillation by Food and Drug Administration (FDA) in 2009. It' s a modified synthetic analogue of amiodarone, which decreases lipophilicity and results in a shorter lifetime and lower tissue accumulation. Here a new process for compound 1 was achieved with 33% overall yield starting from commercial p-aminophenol(2). N-(4-oxocyclohexa-2,5-dien-1-yl)-methanesulfonamide (4) which was obtained by mesylation and oxidization from compound 2 reacted with methyl 3-oxoheptanoate followed by cyclization to afford N-[2-butyl-3-methoxy-carbonyl-5-benzofuranyl] -methanesulfonamide(6). The inversion of compound 6 into the desired compound 1 was realized by hydrolyzation and chlorination followed by Friedel-Crafts reaction with N-butyl-N-(3-phenoxypropyl)-1-butanamine hydrochloride. This process is characterized by cheap and readily available materials, shorter procedures, mild reaction conditions and convenient work-up, making it practical in industry.
- 出版日期2013-4-10
- 单位浙江大学; 浙江大学宁波理工学院; 南昌大学
