2-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl → HCID 67458930, compound

Participants

Reaction Steps

To a flask charged with 7-(4-bromophenyl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine (Preparation L; 0.250 g, 0.531 mmol), 8-oxa-3-azabicyclo[3.2.1]octane (0.430 g, 3.80 mmol), and potassium 2-methylpropan-2-olate (0.119 g, 1.06 mmol) was added 6 mL of THF at ambient temperature with stirring. Argon was bubbled through the reaction for 10 minutes before dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (0.0436 g, 0.106 mmol) and tris(dibenzylideneacetone)dipalladium (0.0487 g, 0.0531 mmol) were added. Argon was bubbled through the reaction for 15 minutes before the reaction was sealed and allowed to proceed at 40° C. for 4 hours. The reaction was charged with more tris(dibenzylideneacetone)dipalladium (0.0487 g, 0.0531 mmol) and purged with argon for 5 minutes before it was sealed and allowed to proceed at 40° C. for 7 hours. The reaction mixture was diluted with DCM and aqueous saturated sodium bicarbonate (2 mL) and stirred for 30 minutes. The layers were separated and the organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography eluting with 1% methanol in DCM to afford 3-(4-(5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-7-yl)phenyl)-8-oxa-3-azabicyclo[3.2.1]octane (0.133 g, 0.265 mmol, 49.0% yield). MS (apci) m/z=503.2 (M+H).

Provenance & Evidence