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富马酸阿米福韦酯的合成改进

Improved synthesis of almifovir fumarate
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摘要 目的:改进富马酸阿米福韦酯的合成工艺,提高合成收率。方法:以2-氨基-6-氯嘌呤与对甲氧基苯硫酚缩合、与2-氯乙氧基甲基膦酸二乙酯(II)缩合、水解、与氯甲基异丙基碳酸酯缩合得阿米福韦酯,再和富马酸成盐制得新型抗乙肝药物富马酸阿米福韦酯。结果:总收率从8.9%提高到15.6%(以2-氨基-6-氯嘌呤计)。结论:通过对富马酸阿米福韦酯的合成的改进,减少了反应步骤,提高了收率,降低了成本。产物经元素分析、1H-NMR、13C-NMR、MS结构确证。 Objective ： To improve the synthesis process of almifovir fumarate and its yield. Methods ： Almifovir was synthesized from 2-amino-6-chloropurine with methoxy thiophenol condensation, 2-chloroethoxy-methylphosphonic acid diethyl ester （II） alkylation condensation, hydrolysis, and chloromethyl isopropyl carbonate condensation. Almifovir was then salified with fumaric acid to get the new anti-HBV drug almifovir fumarate. Results： The structure of the product was confirmed by elemental analysis, 1H-NMR, 13C-NMR and MS. The total yield was increased from 8.9% to 15.6% when calculated from 2-amino-6-chloropurine. Conclusion：The improved method for the synthesis of almifovir fumarate can reduce the reaction steps and manufacturing eosts.
作者 艾海马 徐明波 张晓峰 李亚军 白福英 范新风 李振雷
机构地区 北京双鹭药业股份有限公司 北京嘉林药业股份有限公司
出处 《中国新药杂志》 CAS CSCD 北大核心 2014年第21期2495-2497,2520,共4页 Chinese Journal of New Drugs
基金 国家"重大新药创制"科技重大专项(2014ZX09102001008)
关键词 富马酸阿米福韦酯 阿米福韦 抗乙肝 碳酸酯前药 合成 almifovir fumarate alamifovir anti-HBV carbonate prodrug synthesis
分类号 R914.5 [医药卫生—药物化学]
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参考文献10

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二级参考文献10

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中国新药杂志
2014年 第21期

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