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 (0.876 g, 3.16 mmol), 4-(4-bromo-2,5-difluorobenzyl)morpholine (0.923 g, 3.16 mmol), Sodium tert-pentoxide (0.696 g, 6.32 mmol, (1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) (0.026 g, 0.03 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.018 g, 0.03 mmol) in toluene (10 mL) were mixed and degassed. The mixture was stirred at 110° C. under a nitrogen atmosphere overnight. The mixture was concentrated. Dichloromethane and water was added and the phases were separated. The organic phase was concentrated and the crude was purified by prep HPLC. The pooled fractions were concentrated to about half volume and the residue was extracted with EtOAc (×2). The organic phases were concentrated and the residue was dried under vacuum at 40° C. over a weekend to give the title compound (0.992 g, 64%) as a solid.

1. customdegassed
2. concentrationThe mixture was concentrated
3. additionDichloromethane and water was added
4. customthe phases were separated
5. concentrationThe organic phase was concentrated
6. customthe crude was purified by prep HPLC
7. concentrationThe pooled fractions were concentrated to about half volume
8. extractionthe residue was extracted with EtOAc (×2)
9. concentrationThe organic phases were concentrated
10. customthe residue was dried under vacuum at 40° C. over a weekend