反应详情

温度

0 °C

To a cooled (0° C.) solution of 3-[5-bromo-4-[(2,4-difluorobenzyl)oxy]-6-oxopyrimidin-1(6H)-yl]-4-methylbenzoic acid (from Step 1) (0.80 g, 1.77 mmol) in DMA (3.2 mL) was added isobutyl chloroformate (0.28 mL, 2.13 mmol) and 4-methylmorpholine (0.25 mL, 2.30 mmol). Stirred at 0° C. for 5 min, ambient temperature for 30 min. Added (S)-(+)-2-amino-1-propanol (0.21 mL, 2.66 mmol) and DMAP (0.02 g, 0.18 mmol). Stirred at ambient temperature overnight. Purified crude product by preparatory HPLC using a 10–90% CH3CN/H2O (30 min) gradient containing 0.5% TFA at a flow rate of 80 mL/min. Appropriate fractions (M+H m/z=509) were combined and concentrated to approximately 20 mL under reduced pressure. Added 5% NaHCO3 (20 mL) and extracted with DCM (3×15 mL). The organic extracts were dried over Na2SO4, filtered, concentrated under reduced pressure, and dried in vacuo to give the desired product as a pale yellow foam (0.61 g, 67%).

1. stirringStirred at ambient temperature overnight
2. customPurified crude product by preparatory HPLC
3. customa 10–90% CH3CN/H2O (30 min) gradient
4. additioncontaining 0.5% TFA at a flow rate of 80 mL/min
5. concentrationconcentrated to approximately 20 mL under reduced pressure
6. additionAdded 5% NaHCO3 (20 mL)
7. extractionextracted with DCM (3×15 mL)
8. dry with materialThe organic extracts were dried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customdried in vacuo