瑞替加滨的合成工艺改进

Improved synthesis of retigabine

目的:改进抗癫痫药物瑞替加滨的合成工艺。方法:以间氟苯胺为起始原料,经乙酰化、硝化制得N-(5-氟-2-硝基苯基)乙酰胺(3),3与对氟苄胺反应得到N-{5-[(4-氟苄基)胺]-2-硝基苯基}乙酰胺(4),4经过去乙酰化、还原、酰化即得目标产物瑞替加滨。结果:目标化合物的结构经熔点(mp)、核磁共振氢谱、碳谱(1H-NMR,13C-NMR)和质谱(MS)确证,总收率为39.6%。结论:该合成工艺操作简便,适合工业化生产。

Objective：To improve the synthesis process of retigabine.Methods：The target compound was synthesized from 3-fluoroaniline by acetylation and nitrification to give N-（5-fluoro-2-nitrophenyl） acetamide（2）,which was subjected to condensation with（4-fluorophenyl） methanamine to afford N-（5-（（4-fluorobenzyl） amino）-2-nitrophenyl） acetamide（3）,followed by deacetylation,reduction,and acylation.Results：The structure of retigabine was confirmed by1H-NMR and MS.The overall yield was 39.6%.Conclusion：This synthetic process is easy to scale up for its convenient operation.