2-Amino-5-chloropyridine → (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-chloropyridin-2-yl)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide

Participants

Reaction Conditions

Reaction Steps

Trimethylaluminium (2M in hexane) (0.455 mL, 0.91 mmol) was added to 5-chloropyridin-2-amine (112 mg, 0.87 mmol) in toluene (10 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 20 minutes. (2S)-methyl 3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanoate (Intermediate AB2) (500 mg, 0.79 mmol) in toluene (2 mL) was added and the reaction was heated to reflux for 24 hours. The reaction mixture was concentrated in vacuo and neutralised with citric acid (1M, aq) and then diluted with water (10 ml) and DCM (10 mL). The mixture was poured onto a phase separator and the organic layer collected and evaporated. The crude material was used without purification.

Provenance & Evidence