高质量盐酸多奈哌齐的制备方法  

Preparation Method of High Quality Donepezil hydrochloride

作　　者：冯建鹏[1] 祝传宝[1] 胡丽娜[1] 王伟[1] 

机构地区：[1]扬子江药业集团江苏海慈生物药业有限公司研发部,江苏泰州225321

出　　处：《河北化工》2012年第9期12-13,16,共3页Hebei Chemical Industry

基　　金：国家"十二五"重大新药创制项目(2012ZX09201101-003)

摘　　要：提供了一条较为简洁的盐酸多奈哌齐合成路线,即以5,6-二甲氧基-2-(4-哌啶基甲基)-2,3-二氢-1H-茚酮为起始原料,PtO2催化氢化将吡啶还原为哌啶衍生物,以刘卡特-瓦拉赫反应为关键反应将胺基苄基取代制得盐酸多奈哌齐。再经过成盐和精制,以四步反应,69%的总收率得到了高质量的药用盐酸多奈哌齐。To provide a concise synthetic route of donepezil hydrochloride.Firstly,to choose 5,6-dimethoxy-2-（4-piperidinyl methylene）-2,3-dihydro-1H-inden-1-one as the starting material,to reduce pyridine to piperidine derivative,by PtO2 hydrogenization.Secondly to prepare donepezil hydrochloride,by the key Leuckart-Wallach reaction.Finally,by salification and refination,to obtain the high quality pharmaceutical grade donepezil hydrochloride by four step reaction with a overall yield of 69%.

关 键 词：盐酸多奈哌齐 阿尔茨海默病 刘卡特-瓦拉赫反应 精制 

分 类 号：R971[医药卫生—药品]