反应详情

温度

100 °C

Ethyl 5-[1-(4-cyanophenyl)-1H-pyrazol-5-yl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxylate (Intermediate A) (200 mg, 0.41 mmol) and 2-pyrrolidin-1-ylethanamine (928 mg, 8.12 mmol, 20 eq) were dissolved in MeOH (2.5 mL) and heated to 100° C. in a sealed vial by a microwave oven for 40 min The solvent was evaporated and EtOH (3 mL) was added and heated to 50° C. for two hours and then water (3 mL) was added and the mixture was stirred at room temperature over night. The precipitate was centrifuged (4000 rpm, 3 min) and washed three times with EtOH/H2O 1:1 (5 mL) and dried over night. The residue was dissolved in acetonitrile and purified by HPLC (30-95% MeOH in H2O+0.1% TFA), the pure fractions were freeze-dried, dissolved in acetonitrile and desalted with Na2CO3 (solid phase) and evaporated to afford 5-[1-(4-cyanophenyl)-1H-pyrazol-5-yl]-6-methyl-2-oxo-N-(2-pyrrolidin-1-ylethyl)-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamide as a white solid (156 mg, 65%); 1H NMR (500 MHz, DMSO): δ 1.67-1.59 (4H, m), 1.72 (3H, s), 2.43-2.37 (4H, m), 2.49-2.47 (2H, m), 3.38-3.33 (2H, m), 6.72 (1H, d), 7.67-7.63 (2H, m), 7.71 (1H, d), 7.88-7.82 (2H, m), 7.96-7.89 (4H, m), 8.07 (1H, s), 9.35 (1H, t);

1. customwas evaporated
2. additionEtOH (3 mL) was added
3. temperatureheated to 50° C. for two hours
4. additionwater (3 mL) was added
5. custom(4000 rpm, 3 min)
6. washwashed three times with EtOH/H2O 1:1 (5 mL)
7. customdried over night
8. dissolutionThe residue was dissolved in acetonitrile
9. custompurified by HPLC (30-95% MeOH in H2O+0.1% TFA)
10. customthe pure fractions were freeze-dried
11. dissolutiondissolved in acetonitrile
12. customevaporated