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

Participants

Reaction Steps

Tetrabutylammonium fluoride (1M in THF) (0.790 mL, 0.79 mmol) was added to (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 (Intermediate AB4) (576 mg, 0.79 mmol) in THF (2 mL) under nitrogen. The resulting mixture was stirred at ambient temperature for 1 hour. The reaction mixture was quenched with saturated NH4Cl (1 mL), diluted with DCM (10 ml) and poured onto a phase separator. The organic layer was collected and evaporated. The residue was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. The resulting product decomposed to an extent during evaporation and so was re-purified by flash silica chromatography, eluting with 0 to 10% MeOH in ethyl acetate to afford the product (82 mg, 21%). 1H NMR (400 MHz, CDCl3) δ 2.49-2.56 (1H, m), 3.69-3.85 (4H, m), 4.14-4.25 (2H, m), 6.08 (1H, t), 7.45-7.50 (1H, m), 7.67-7.72 (1H, m), 7.98-8.04 (1H, m), 8.15-8.28 (2H, m), 8.47 (1H, s), 8.58-8.65 (2H, m), 8.99 (1H, s); m/z (ES+) (M+H)+=490.35; HPLC tR=1.82 min.

Provenance & Evidence