The synthesis process optimization of 1(- 4-aminophenyl)-5, 6-dihydro-3- (4-morpholinyl)-2(1H)-pyridinone, an important intermediate for the apixaban synthesis
10.13220/j.cnki.jipr.2020.08.015
- VernacularTitle: 阿哌沙班合成重要中间体1-(4-氨苯基)-3-吗啉-5, 6-二氢吡啶-2(1H)-酮的合成工艺优化
- Author:
Hui-Hong ZHANG
1
Author Information
1. School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology
- Publication Type:Journal Article
- Keywords:
Apixaban;
P-nitroaniline;
Systhesis
- From:
Journal of International Pharmaceutical Research
2020;47(8):671-676
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To optimize the synthesis process of 1-(4-aminophenyl)-5, 6-dihydro-3-(4-orpholinyl)-2(1H)-pyridinone.Methods: Using p-nitroaniline as the raw material, the target compound was obtained by amidation, cyclization, chlorination, nitration and reduction reactions. The sodium hydride catalyst for cyclization was taken out in the reaction, the reaction acid binding agent was improved, the reaction temperature of intermediate was reduced, the optimal ratio and reaction ratio condition were investigated, and the post-processing conditions were optimized for each reaction. Results: The target compound was confirmed by 1H NMR and 13C NMR data, and the total yield was 65.4%. Conclusion: The optimized process is simple to operate, mild and controllable, and the solvent is easy to recycle, low-polluting and more conducive to industrial production.
