Dronedarone hydrochloride, SR-33589B

决奈达隆Chemical Name: 2-Butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5-(methylsulfonamido)benzofuran hydrochloride
CAS No. 141626-36-0 (free base)
项目整合开发状态: Phase III
项目研究机构: Sanofi-Aventis (Originator)
合成路线:Treatment of 2-hydroxy-5-nitrobenzyl bromide (I) with triphenylphosphine in refluxing chloroform provides phosphonium bromide derivative (II),which is converted into 2-butyl-5-nitro benzofuran (IV) by first reaction with pentanoyl chloride (III) in refluxing chloroform in the presence of pyridine,followed by treatment with Et3N in refluxing toluene.Acylation of (IV) with anisoyl chloride (V) by means of tin tetrachloride in dichloroethane furnishes 2-butyl-3-(4-methoxy benzoyl)-5-nitro benzofuran (VI),whose methoxy group is then converted into an hydroxy group by treatment with aluminum chloride in refluxing dichloroethane,yielding hydroxy benzoyl derivative (VII).Condensation of (VII) with N,N-dibutyl-N-(3-chloropropyl)amine (VIII) by means of K2CO3 in refluxing butanone affords compound (IX),which is then hydrogenated over PtO2 in EtOH to give amino derivative (X).Finally,the target product is obtained by reaction of (X) with methanesulfonyl chloride and Et3N in dichloroethane and hydrochloride salt formation with HCl in AcOEt/ethyl ether.