The synthesis process optimization of 1(- 4-aminophenyl)-5, 6-dihydro-3- (4-morpholinyl)-2(1H)-pyridinone, an important intermediate for the apixaban synthesis / 国际药学研究杂志

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.