Dichloromethane → Tert-butyl 3-{7-(bis{[2-(trimethylsilyl)ethoxy]methyl}amino)-3-[6-(2,6-difluorophenyl)pyridin-3-yl]pyrazolo[1,5-a]pyrimidin-5-yl}-8-azabicyclo[3.2.1]octane-8-carboxylate

Participants

Reaction Conditions

Reaction Steps

tert-Butyl 3-[7-(bis{[2-(trimethylsilyl)ethoxy]methyl}amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl]-8-azabicyclo[3.2.1]octane-8-carboxylate (1.26 g, 1.73 mmol), 2-(2,6-difluorophenyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.88 g, 2.1 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II)complex with dichloromethane (1:1) (141 mg, 0.173 mmol), and potassium carbonate (0.716 g, 5.18 mmol) were placed in a 100-mL round bottom flask equipped with a reflux condenser and rubber septa. Then, the reaction vessel was evacuated and back filled with nitrogen 3 times before adding 1,4-dioxane (3.50 mL) and water (0.933 mL). Then, the reaction was sparged with nitrogen for 8 minutes, then maintained under nitrogen with a balloon and heated at 95° C. for 6 hr. The reaction mixture was then cooled to ambient temperature, diluted with dichloromethane (100 mL), filtered through a plug of Magnesol (ca. 60 mL). and the filtrate was concentrated. The crude product was purified by flash chromatography, (0 to 10% ethylacetate/dichloromethane) to afford the title compound (690 mg, 50%) as an ivory foam.

Provenance & Evidence