奈韦拉平的合成工艺

目的研究奈韦拉平的合成工艺。方法以2-氯-3-氨基-4-甲基吡啶为原料,依次与2-氯烟酰氯缩合成化合物3、再与环丙胺高压氨解、最后发生分子内亲核取代反应,成功合成了奈韦拉平。结果合成的奈韦拉平经1H-NMR和ESI-MS确证结构,总收率质量分数为56.8%。结论缩合反应以二氯甲烷替代易燃、有毒的环己烷/二氧六环混和溶剂为溶剂,以吡啶替代N,N-二甲基苯胺或碳酸钾为缚酸剂,操作安全、简捷,且收率有所提高。取代反应以叔丁醇钾替代了比较危险的氢钠(NaH)或昂贵的六甲基二硅基胺基钠(NaHMDS)。

Preparation of nevirapine

Objective To get an improved synthesis of nevirapine. Methods Compound 3 was got via the formation of the amide from 2-chloro-3-amino-4-methyl pyridine and 2-chloronicotinoyl chloride, and then nevirapine was acquired by the aminolysis of 3 with cyclopropylamine in an autoclave, followed by the intramolecular nucleophilic substitution. Results The target compound was synthesized via 3 steps with a total yield of 56.8%(w) and its structure was identified by ¹H-NMR and ESI-MS. Conclusions Dichloromethane was used as the solvent in the amidation to replace the dangerous and toxic mixture of cyclohexane-dioxane used in literatures, and pyridine was employed as the base instead of N,N-dimethylaniline or potassium carbonate. This easily operated and much safe process could also improve the yield of the reaction. Moreover, potassium t-butoxide was employed for the substitution reaction to replace the dangerous NaH or expensive NaHMDS.