目的 對阿哌沙班的合成工藝進(jìn)行改進(jìn)研究。方法 以4，5，6，7-四氫-1-（4-甲氧基苯基）-6-（4-硝基苯基）-7-氧代-1H-吡唑并[3，4-C]吡啶-3-羧酸乙酯為起始原料，通過還原、取代、環(huán)合、胺化反應(yīng)得到阿哌沙班。結(jié)果 合成了目標(biāo)化合物阿哌沙班，經(jīng)MS、¹H-NMR確證了結(jié)構(gòu)，質(zhì)量分?jǐn)?shù)為99.2%，本合成工藝的總收率為76.4%。結(jié)論 該合成工藝改進(jìn)后操作簡單、安全，適合工業(yè)化生產(chǎn)。

Objective To study the improved method for synthesis of apixaban. Methods 4,5,6,7-Tetrahydro-1-(4-methoxyphenyl)-6-(4-nitrophenyl)-7-oxo-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester was used as starting material to synthesize apixaban by reduction reaction, substitution reaction, cyclization reaction, and amination reaction. Results The target compound apixaban was synthesized and characterized by MS and ¹H-NMR. And the purity was 99.2%, and the total yield of this route was 76.4%. Conclusion The synthetic process has the advantages of simple operation, security, and suitable for industrial production.