马来酸氟吡汀中杂质D14461及其氟吡汀二聚物的合成研究

目的研究马来酸氟吡汀中杂质D14461及其氟吡汀二聚物的合成研究。方法以对氟苄胺和2-氨基-3-硝基-6-氯吡啶为起始原料,通过亲核取代反应得到2-氨基-3-硝基-6对氟苄氨基吡啶(ANFP),随后经氢化还原,光照聚合一锅法反应生成两个目标化合物,经制备液相分离纯化得到纯品。结果制备了马来酸氟吡汀中的杂质D14461及其氟吡汀二聚物,利用MS、~1H-NMR和~(13)C-NMR确证了结构,质量分数分别为99.92%、99.95%,并推测了其可能的生成机制。结论杂质D14461和氟吡汀二聚物的合成和纯化为马来酸氟吡汀的杂质研究提供了理论依据。

Synthesis of impurities D14461 and the polymer of flupirtine in flupirtine maleate

Objective To study the synthesis of impurities D14461 and the polymer of flupirtine.Methods 4-Fluorobenzylamine and 2-amino-6-chloro-3-nitropyridine were used as starting materials to synthesize 2-amino-3-nitro-6-p-fluorobenzylamino-pyridine (ANFP) by nucleophilic substitution reactions. The two target compounds were synthesized by hydrogenation reduction and photopolymerization in one-pot, and they were purified by preparative chromatography. Results The impurities D14461 and the polymer of flupirtine in flupirtine maleate were synthesized and characterized by MS, ¹H-NMR, and ¹³C-NMR method. And the purity detected were 99.92% and 99.95%, respectively. Formation mechanism of impurities D14461 and the polymer of flupirtine were presumed. Conclusion The synthesis and purification of impurities D14461 and the polymer of flupirtine provide the theoretical basis for the study of impurities in flupirtine maleate.