Potassium Phosphate, Tribasic → (R)-4-((R)-1-(3-methyl-6-(pyrazolo[1,5-a]pyridin-3-yl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one

Participants

Reaction Steps

Under Ar, (R)-4-((R)-1-(6-chloro-3-methyl-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one 2.06 (21.7 mg, 0.074 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolo[1,5-a]pyridine (40 mg, 0.16 mmol), K3PO4 (57 mg, 0.27 mmol) and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (3.3 mg, 0.0047 mmol) were taken up in dioxane (0.65 mL) and water (0.07 mL). The stirred mixture was heated to 100° C. for 70 min, at which time additional boronic ester (28 mg, 0.12 mmol), K3PO4 (45 mg, 0.21 mmol) and precatalyst (3.3 mg, 0.0047 mmol) were added. The mixture was stirred for an additional 15 h and was then cooled to r.t. and diluted with EtOAc (20 mL), water (10 mL) and brine (10 mL). The phases were separated, and the aqueous phase was extracted with EtOAc (20 mL). The combined organic phase was dried over Na2SO4, filtered, and concentrated directly onto silica gel. Purification by silica gel chromatography (0% to 15% MeOH in CH2Cl2) provided (R)-4-((R)-1-(3-methyl-6-(pyrazolo[1,5-a]pyridin-3-yl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one 3.20.

Provenance & Evidence