盐酸决奈达隆合成新工艺

设计了一条全新的盐酸决奈达隆(1)的合成路线, 该路线以价廉易得的对氨基苯酚(2)为起始原料, 经N-甲磺酰化、 氧化得到对甲磺酰亚氨基苯醌(4)后, 再与3-氧代庚酸甲酯缩合、 环化制得关键中间体2-丁基-5-甲磺酰胺基苯并呋喃-3-甲酸甲酯(6), 然后经水解、 酰氯化, 继而与1-苯氧基-3-二正丁胺基丙烷盐酸盐进行傅-克酰基化反应, 成盐后即得化合物1, 总收率达33%.

New Process for Preparation of Dronedarone Hydrochloride

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--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.