2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → N-(4-(((3S,5S)-3,5-Dimethylmorpholino)methyl)-2,5-difluorophenyl)-5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine

Participants

Reaction Conditions

Reaction Steps

(3S,5S)-4-(4-Chloro-2,5-difluorobenzyl)-3,5-dimethylmorpholine (0.118 g, 0.43 mmol), 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (0.142 g, 0.51 mmol) and potassium tert-butoxide (0.058 g, 0.51 mmol) were mixed in dioxane (2 mL) and DMF (0.5 mL). Argon was bubbled through the mixture for 2 minutes. Pd2(dba)3 (0.047 g, 0.05 mmol) and X-Phos (0.049 g, 0.10 mmol) were added and the reaction mixture was heated in a microwave reactor at 120° C. for 40 minutes. The mixture was diluted with dichloromethane and was filtered though a plug of diatomaceous earth. The filter plug was washed with dichloromethane and methanol. The filtrate was concentrated and purified by preparative HPLC. The fractions containing product were pooled. NaHCO3 (aq) was added and the mixture was extracted with dichloromethane (×3). The combined organic phases were dried (MgSO4) and evaporated to give the title compound as a solid (16 mg, 7.2%).

Provenance & Evidence