反应详情

温度

0 °C

To a mixture of (R)—N-(3-fluoro-4-(7-methoxyquinolin-4-yloxy)phenyl-1-(2-hydr-oxypropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (2.0 g, 3.68 mmol), (S)—N-Cbz-alanine (1.647 g, 7.36 mmol, Shanghai Hanhong Chemical CO., LTD.) and DMAP (0.90 g, 7.36 mmol, Aladdin) in CH2Cl2 (30 mL) was added EDC solid (2.116 g, 11.04 mmol, Aladdin) in portions at 0° C. After stirring at 0° C. for 2 hrs, the reaction mixture was warmed up to room temperature and continued to stir at rt for 20 hrs. The mixture was diluted with 180 mL of CH2Cl2. The resulted mixture was washed with 30 mL of 0.1 N HCl, followed by 50 mL of saturated NaHCO3 solution. The aqueous phase was extracted with EtOAc (50 mL×3), and the combined organic phases were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by a silica gel column chromatography (EtOAc) to give the desired compound as a pale yellow solid (2.1 g, 73.1%).

1. temperaturethe reaction mixture was warmed up to room temperature
2. stirringto stir at rt for 20 hrs
3. washThe resulted mixture was washed with 30 mL of 0.1 N HCl
4. extractionThe aqueous phase was extracted with EtOAc (50 mL×3)
5. dry with materialthe combined organic phases were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by a silica gel column chromatography (EtOAc)