Tetrabutylammonium Fluoride → (2S)-2-(1-(2-chloro-6-cyanophenyl)-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) (0.203 mL, 0.20 mmol) was added to (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(1-(2-chloro-6-cyanophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-methylpyridin-2-yl)propanamide (Intermediate AH9) (149 mg, 0.20 mmol) in THF (5 mL) under nitrogen. The resulting mixture was stirred at ambient temperature for 1 hour. The reaction mixture was quenched with saturated NH4Cl (2 mL), diluted with DCM (25 mL) and poured onto a phase separator. The organic phase was reduced to give a gum. The crude product 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 0.1% formic acid) and MeCN as eluents to afford the product (45.0 mg, 44.8%, 58% ee). 1H NMR (400 MHz, CDCl3) d 2.23 (3H, s), 3.77-3.62 (4H, m), 4.20-4.04 (2H, m), 6.01 (1H, m), 7.51-7.46 (1H, m), 7.55 (1H, t), 7.72 (1H, dd), 7.84-7.76 (1H, m), 8.03 (2H, d), 8.46 (1H, d), 8.55 (1H, d), 9.19-8.96 (1H, m) OH not observed. m/z (ES+) (M+H)+=494; HPLC tR=1.82 min.

Provenance & Evidence