贝曲西班的合成工艺  

Synthetic process of betrixaban

作　　者：赵华[1] 褚倩倩[1] 王辉[1] 尚振华[1] 

机构地区：[1]河北科技大学,石家庄050018

出　　处：《中国新药杂志》2014年第24期2902-2904,2911,共4页Chinese Journal of New Drugs

摘　　要：目的:对目前贝曲西班的合成路线进行优化,以获得可用于工业生产的工艺路线。方法:以5-甲氧基-2-硝基苯甲酸和2-氨基-5-氯吡啶为起始原料制得N-(5-氯-2-吡啶基)-5-甲氧基-2-硝基苯甲酰胺,依次经过硝基还原,酰化,加成反应制得亚氨酸酯,再与二甲胺进行取代反应得到贝曲西班盐酸盐,碱解后成盐得到贝曲西班马来酸盐。结果:所得贝曲西班经HPLC检测纯度达到99.50%以上,总收率为19.63%。结论:该合成路线操作简单,收率较高,产品纯度高,适合工业化生产。Objective： To optimize the current synthesis routes in order to develop a new synthetic route applied in betrixaban production. Methods： 5-Methoxy-2-nitro benzoic acid and 2-amino-5-chlorine pyridine were used as the starting materials to get N-（5-chloro-2-pyridinyl）-5-methoxy-2-nitrobenzamide. Imidoate was synthesized through some procedures such as nitro reduction,acylation reaction and addition reaction. The synthezed imidoate reacted with dimethylamine to get betrixaban hydrochloride,which was salified by alkaline hydrolysis to obtain the betrixaban maleate. Results： Betrixaban was synthesized with a total yield of 19. 63%,and the purity was 99. 50% determined by HPLC. Conclusion： The synthetic process is not only easy to operate with achieving high yield and purity,but also suitable for industrial production.

关 键 词：贝曲西班 5-甲氧基-2-硝基苯甲酸 抗凝血药 合成 

分 类 号：R914.5[医药卫生—药物化学]