奥氮平的合成工艺改进  

The improved synthesis of olanzapine

作　　者：杨先金[1] 袁文蛟[1] 吴范宏[1] 

机构地区：[1]华东理工大学结构可控先进材料教育部重点实验室精细化学研究所化学与分子工程学院,上海200237

出　　处：《中国新药杂志》2007年第22期1891-1892,共2页Chinese Journal of New Drugs

摘　　要：目的:合成奥氮平工艺改进。方法:以硫、丙醛、丙二腈为起始原料,缩合得到2-氨基-5-甲基噻吩-3-腈,在相转移催化剂下与邻氟硝基苯反应制得2-(2-硝基苯氨基)-5-甲基噻吩-3-腈,再经过还原、环合和缩合得到纯度99%以上的奥氮平。结果:目标化合物经核磁共振等确证其化学结构,总收率达到33.8%。结论:改进后的工艺路线反应条件温和,产率较高,操作简单,更适合工业化生产。Objective： To improve the synthetic process of olanzapine. Methods： Starting from sulphur, propioaldehyde and malononitrile, 2-（2-nitroanilino）-5-methylthionphene-3-carbonitrile was ob- tained via the condensation of 2-amino-5-methyl-thionphene-3-carbonitrile with 2-fluoronitrobenzene in the present of PTC, and then oalanzapine was obtained via subsequent reduction, cyclization and condensation. Results： The HPLC purity of the target compound was more than 99%. The structure of olanzapine was confirmed by MS and 1H-NMR. The overall yield of olanzapine was up to 33.8%. Conclusion： The improved synthetic process with mild reactive condition and good yield is applicable to pilot manufacture.

关 键 词：奥氮平 抗精神病药 药物合成 

分 类 号：R971.4[医药卫生—药品] R749[医药卫生—药学]