Potassium Sodium Tartrate → HCID 57504443, compound

Participants

Reaction Conditions

Reaction Steps

Sodium hydride (116 mg, 2.90 mmol) was added to (S)-3-(azetidin-1-yl)-2-hydroxy-N-(pyridin-2-yl)propanamide (Intermediate BC1) (232 mg, 1.05 mmol) in anhydrous THF (50 mL) at 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes and then a solution of 3-chloro-2-(4-chloro-1H-pyrazolo[3,4-d]pyrimidin-1-yl)benzonitrile (Intermediate AH6) (280 mg, 0.97 mmol) in anhydrous THF (20 mL) was added dropwise over 1 minute. The mixture was stirred at 0° C. for 10 minutes and then allowed to warm to ambient temperature for 2 hours. It was then cooled to 0° C., 20% Rochelle salt (20 mL) added and the mixture stirred for 10 minutes. It was extracted with EtOAc (50 mL), the organic phase was washed with water (10 mL) and brine (20 mL), dried (MgSO4), filtered and evaporated. The residue was triturated with EtOAc (10 mL), filtered and the filtrates evaporated. The residue was purified by flash silica chromatography, elution gradient 0 to 20% MeOH in EtOAc and further purified by preparative HPLC (Phenomenex Luna C18 100A column, 5μ silica, 21 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 1% formic acid) and MeCN as eluents to afford the product (100 mg, 22%).

Provenance & Evidence