| 摘要: |
| 目的 改进阿哌沙班的合成工艺。方法 以3-吗啡啉-1-（4-硝基苯基）-5，6-二氢吡啶-2（1H）-酮（2）为起始原料，经缩合，氨化和"一锅法"还原和环合反应，得到阿哌沙班（1）。结果 中间体和目标化合物的结构经1H-NMR、13C-NMR、高分辨质谱确证，3步合成总收率为50.2%。结论 改进后的工艺适合工业化生产。 |
| 关键词: 阿哌沙班 合成 优化 |
| DOI：10.13748/j.cnki.issn1007-7693.2019.14.011 |
| 分类号:R914.5 |
| 基金项目: |
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| Improvement on Synthesis Process of Apixaban |
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WANG Peng, LIN Lihong
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Zhejiang Huahai Pharmaceutical Co., Ltd., Taizhou 317016, China
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| Abstract: |
| OBJECTIVE To improve the synthesis process of apixaban. METHODS Apixaban(1) was synthesized by using 3-morpholino-1-(4-nitrophenyl)-5,6-dihydropyridin-2(1H)-one(2) as the starting material, via condensation, aminolysis and "one-pot" reaction inculding reduction and cyclization. RESULTS The structures of intermediates and target molecule were confirmed by 1H-NMR, 13C-NMR and HRMS. The overall yield was 50.2% over 3 steps. CONCLUSION The improved process is suitable for industrial scaling-up. |
| Key words: apixaban synthesis optimization |
