Citric Acid → (S)-2-(1-benzyl-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-methylpyridin-2-yl)propanamide

Participants

Reaction Conditions

Reaction Steps

Sodium hydride (90 mg, 2.25 mmol) was added to (S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-hydroxy-N-(5-methylpyridin-2-yl)propanamide (538 mg, 1.12 mmol) (Intermediate AU2) in anhydrous THF (20 mL) at 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes and then 1-benzyl-4-chloro-1H-pyrazolo[3,4-d]pyrimidine (Intermediate AL2) (250 mg, 1.02 mmol) was added. The reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was neutralised with 1M citric acid, diluted with water (20 mL) and EtOAc (50 mL). The organic layer was separated and the aqueous layer re-extracted with EtOAc (2×50 mL). The combined organics were washed with saturated brine (75 mL), dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by flash silica chromatography, elution gradient 30 to 50% EtOAc in isohexane to afford the product (540 mg, 77%). m/z (ES+) (M+H)+=687; HPLC tR=3.89 min.

Provenance & Evidence