【摘要】 目的:确定并优化赛乐西帕的合成工艺。方法:以联苯甲酰和甘氨酰胺盐酸盐为原料,依次经环合、氯代、取代得到中间体I,中间体I与N-(2-氯乙酰基)-甲磺酰胺经Williamson反应得到赛乐西帕。结果:所得赛乐西帕经HPLC检测纯度99.9%以上,总收率为14.2%(以联苯甲酰为基准计算)。结论:该合成工艺操作简便,适合工业化生产。更多还原

【Abstract】 Objective: To optimize the synthetic process of selexipag. Methods: Benzil and glycinamide hydrochloride were used as starting materials and they were subjected to the reactions of cyclization,chlorination and nucleophilic substitution to generate intermediate I. Then intermediate I was reacted with N-( 2-chloracetyl)methanesulfonamide to produce selexipag by Williamson reaction. Results: Selexipag was synthesized with a total yield of 14. 2%( calculate as benzil),and the purity was > 99. 9% determined by HPLC. Conclusion: The synthetic process is easy to scale up for its convenient operation.更多还原