反应详情

温度

110 °C

5-Fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (5.12 g, 18.46 mmol), 4-(4-bromo-3-fluorobenzyl)morpholine (5.06 g, 18.46 mmol), (1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) (0.152 g, 0.18 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.107 g, 0.18 mmol) and sodium tert-pentoxide (4.07 g, 36.92 mmol) in toluene (70 mL) were mixed and degassed. The mixture was stirred at 110° C. under nitrogen atmosphere overnight. The mixture was concentrated. Dichloromethane and water were added and the phases were separated. The organic phase was concentrated and the crude was purified by preparative HPLC. The pooled fractions were concentrated to about half volume. The residue was extracted with EtOAc (×2). The combined organic phases were concentrated and the residue was dried in vacuo at 40° C. for 24 h to give the title compound (5.34 g, 61%) as a solid.

1. customdegassed
2. concentrationThe mixture was concentrated
3. additionDichloromethane and water were added
4. customthe phases were separated
5. concentrationThe organic phase was concentrated
6. customthe crude was purified by preparative HPLC
7. concentrationThe pooled fractions were concentrated to about half volume
8. extractionThe residue was extracted with EtOAc (×2)
9. concentrationThe combined organic phases were concentrated
10. customthe residue was dried in vacuo at 40° C. for 24 h