阿哌沙班的合成改进

Improved Synthetic Process of Apixaban

对硝基苯胺与?-戊内酯进行酰胺化、环化、双氯取代和消除反应得到3-(吗啉-4-基)-1-(4-硝基苯基)-5,6-二氢-1H-吡啶-2-酮,与[(4-甲氧基苯基)肼基]氯乙酸乙酯经1,3-偶极环加成反应、消除、还原、酰胺化、环化反应得到阿哌沙班,总收率为47.8%(以对硝基苯胺计),纯度为99.9%。

Apixaban was synthesized from 4-nitroaniline and 5-valerolactone by amidation, cyclization, dichlorination and elimination to give 3-（4-morpholinyl）- 1-（4-nitrophenyl）-5,6-dihydropyridin-2 （1 H）-one, which was subjected to 1,3-dipolar cycloaddition with ethyl （2Z）-2-chloro-2-[ （4-methoxyphenyl）hydrazinylidene] acetate, elimination, reduction, amidation and cyclization with an overall yield of 47.8 % （based on 4-nitroaniline） and HPLC purity of 99.9 %.