Tetrabutylammonium Fluoride → (2S)-2-(1-(3-cyano-2-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-(2-hydroxyethoxy)-N-(5-methylpyridin-2-yl)propanamide

Participants

Reaction Steps

Tetrabutylammonium fluoride (1M in THF) (0.440 mL, 0.44 mmol) was added to (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(1-(3-cyano-2-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-methylpyridin-2-yl)propanamide (Intermediate AT6) (313 mg, 0.44 mmol) in THF (2 mL) under nitrogen. The resulting mixture was stirred at ambient temperature for 2 hours. The reaction mixture was quenched with saturated NH4Cl, diluted with DCM and poured onto a phase separator. The organic layer was evaporated to a gum. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% methanol in ethyl acetate to afford the product (59.0 mg, 28.3%, 84% ee). 1H NMR (400 MHz, CDCl3) δ 2.30 (3H, s), 2.40 (3H, s), 3.02 (1H, s), 3.72-3.83 (4H, m), 4.13-4.26 (2H, m), 6.09 (1H, t), 7.45-7.57 (2H, m), 7.63-7.68 (1H, m), 7.76-7.81 (1H, m), 8.03-8.12 (2H, m), 8.43 (1H, s), 8.58 (1H, s), 8.95 (1H, s); m/z (ES+) (M+H)+=474.49; HPLC tR=1.83 min.

Provenance & Evidence