N-methyl-2-pyrrolidone → HCID 46938169, compound

Participants

Reaction Conditions

Reaction Steps

Tris(dibenzylideneacetone)dipalladium(0) (0.261 g, 0.29 mmol) was added in one portion to a de-gassed mixture of (2S)-2-(1-(2-bromo-6-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-methylpyrazin-2-yl)-3-((R)-1-(triisopropylsilyloxy)propan-2-yloxy)propanamide (Intermediate BO1) (4.1 g, 5.70 mmol), zinc cyanide (0.335 g, 2.85 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.330 g, 0.57 mmol) in N-methylpyrrolidone (41 mL) at 20° C. under nitrogen. The resulting suspension was degassed under vacuum with inlet of nitrogen four times and then heated to 110° C. (internal temperature) for 1 hour. The mixture was cooled, poured into water (100 mL) and extracted with ethyl acetate (2×50 mL). The organic layers were combined and washed with water (4×50 mL) and brine (50 mL), dried over MgSO4, filtered and evaporated. The crude product was purified by flash silica chromatography, elution gradient 30 to 100% EtOAc in isohexane to afford the product (3.0 g, 79%).

Provenance & Evidence