盐酸川丁特罗的合成工艺研究  

Study on the synthesis of tradinterol hydrochloride

作　　者：刘丹[1] 潘莉[1] 李晓强[1] 金盛飞[1] 程卯生[1] 

机构地区：[1]沈阳药科大学基于靶点的药物设计与研究教育部重点实验室,辽宁沈阳110016

出　　处：《中国药物化学杂志》2012年第4期282-285,共4页Chinese Journal of Medicinal Chemistry

基　　金："重大新药创制"科技重大专项(2009ZX09102-018)

摘　　要：目的合成抗哮喘药盐酸川丁特罗。方法以2-三氟甲基苯胺为起始原料,经碘代、酰化、取代、Stephen还原、水解、氯代、Wittig反应、环氧化、胺化和成盐10步反应制得盐酸川丁特罗。结果与结论目标化合物的总收率为5.71%,其结构经质谱、1H-NMR谱确证。改进后的合成工艺缩短了步骤、简化了操作、降低了合成成本,适合工业化生产。Tradinterol hydrochloride is a kind of long-acting β2-adrenoceptor agonist for the treatment of asthma.The target compound was synthesized from 2-trifluoromethyl-aniline via eleven reactions with an overall yield of 1.2% in the literature.Due to the low yield,a new route of tradinterol hydrochloride was designed,and it was synthesized from 2-trifluoromethyl-aniline via ten reactions of iodination,N-acetylation,substitution,Stephen reduction,hydrolysis,chlorination on benzene ring,Wittig reaction,epoxidation,amination and salt formation with an overall yield of 5.71%.The structure of tradinterol hydrochloride and its key intermediates were identified by 1H-NMR and MS.Compared with the synthetic process reported in the literature,the improved synthetic process is suitable for industrialized production owing to the simple operation and high yield. tradinterol hydrochloride

关 键 词：川丁特罗 哮喘 Β2肾上腺素受体激动剂 合成工艺 

分 类 号：TQ463.2[化学工程—制药化工]