奥氮平的合成工艺改进

The improved synthesis of olanzapine

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.