反应详情

To a suspension of 7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5(6H)-one (Preparation I; 9.60 g, 44.6 mmol) in dry DCM (90 mL) was added DIEA and the suspension stirred at ambient temperature for 5 minutes. The mixture was cooled to 0° C. and POCl3 (12.3 mL, 134 mmol) was added over 5 minutes. The mixture was allowed to reach ambient temperature and the resulting thick slurry was treated with dry DCM (50 mL). The mixture was vigorously stirred at ambient temperature for 23 hours. The resulting light tan suspension was diluted with hexanes (90 mL) and collected by vacuum filtration. The collected solid was washed with Et2O and dried in vacuum to give the crude product salt. The salt was suspended in 5:20:75 MeOH/DIEA/EtOAc (200 mL) and stirred for 30 minutes at ambient temperature. The mixture was filtered through a SiO2 plug capped with a Celite layer eluting with 5% MeOH/EtOAc. The filtrate was concentrated and the residual solid dried in vacuum to provide the title compound (5.65 g, 54% yield) as a light cream colored solid. MS (apci) m/z=234.2 (M+H).

1. temperatureThe mixture was cooled to 0° C.
2. customto reach ambient temperature
3. stirringThe mixture was vigorously stirred at ambient temperature for 23 hours
4. filtrationcollected by vacuum filtration
5. washThe collected solid was washed with Et2O
6. customdried in vacuum
7. customto give the crude product salt
8. stirringstirred for 30 minutes at ambient temperature
9. filtrationThe mixture was filtered through a SiO2 plug
10. customcapped with a Celite layer
11. washeluting with 5% MeOH/EtOAc
12. concentrationThe filtrate was concentrated
13. customthe residual solid dried in vacuum