反应详情

温度

0 °C

To a suspension of 3-Bromo-4-[(2,4-difluorobenzyl)oxy]-1-{[5-(hydroxymethyl)pyrazin-2-yl]methyl}-6-methylpyridin-2(1H)-one (0.21 g, 0.00055 mol) in THF (5.0 mL) and DMF (2.0 mL), was added 4-nitrophenylchloroformate (0.1 g, 0.0005 mol) and cooled to 0° C. Triethylamine (0.052 g, 0.0005 mol) was then added, stirred at room temperature for 1 h, and at 65° C. for an additional 1 h. It was cooled in an ice bath and added 2M ammonia in propanol (1.0 mL) and stirred at room temperature for 2 h. After the removal of the solvents under reduced pressure, the residue was partitioned between 5% sod. bicarbonate, and EtOAc (25 mL). The organic phase was washed with 5% sod. bicarbonate, (3×25 mL), water (3×25 mL), dried (Na2SO4) and concentrated under reduced pressure. The resulting substance was purified by isolated by reverse-phase HPLC using 10-90% CH3CN/Water (30 min gradient) at a flow rate of 100 mL/min. The appropriate fractions (m/z=495 M+H) were combined and freeze-dried, and the residue was partitioned between 5% sod. bicarbonate (20 mL) and EtOAc (25 mL). The organic phase was washed with water, dried (Na2SO4) and concentrated to dryness under reduced pressure, to afford the title compound as a white powder (0.065 g):

1. waitat 65° C. for an additional 1 h
2. temperatureIt was cooled in an ice bath
3. stirringstirred at room temperature for 2 h
4. customAfter the removal of the solvents under reduced pressure
5. customthe residue was partitioned between 5% sod
6. washThe organic phase was washed with 5% sod
7. dry with materialbicarbonate, (3×25 mL), water (3×25 mL), dried (Na2SO4)
8. concentrationconcentrated under reduced pressure
9. customThe resulting substance was purified
10. customby isolated by reverse-phase
11. customfreeze-dried
12. customthe residue was partitioned between 5% sod
13. washThe organic phase was washed with water
14. dry with materialdried (Na2SO4)
15. concentrationconcentrated to dryness under reduced pressure