坎地沙坦酯的合成工艺改进

Synthesis of candesartan cilexetil

目的研究坎地沙坦酯的合成新方法,并对其工艺路线进行优化。方法以3-硝基邻苯二甲酸为原料,经过酯化、氯化、Curtius重排、脱Boc保护、还原、环合、水解、酯化、烃化、脱保护10步反应得到坎地沙坦酯。结果与结论该路线反应条件温和,原料廉价易得,同时避免了剧毒化合物烷基锡的使用,成本较低,总收率12.3%,适合工业化生产。

Candesartan cilexetil,as new non-peptide angiotensin Ⅱ receptor antagonist,was used for antihypertensive,with the characterstics of long-lasting（1 time/day）,good tolerance and high receptor selectivity.It was developed by TAKEDA company and listed in Sweden in 1997 at first.The synthetic routes,taking 3-nitrophthalic acid as staring material,candesartan cilexetil was obtained successfully via ten-step routes of esterification,chlorination,Curtius rearrangement et al with overall yield of 12.3% much higher than that of reported routes.The structure of candesartan cilexetil was confirmed by 1H-NMR,13C-NMR,HRMS,HPLC.