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

Tetrabutylammonium fluoride (1M in THF) (1.515 mL, 1.51 mmol) was added to (2S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-methylpyridin-2-yl)propanamide (Intermediate AD7) (0.9 g, 1.51 mmol) in THF (10 mL) under nitrogen. The resulting mixture was stirred at ambient temperature for 2.5 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% MeOH in EtOAc to afford the product (0.313 g, 43.1%, 98% ee). 1H NMR (400 MHz, CDCl3) δ 2.29 (3H, s), 2.50-2.78 (1H, m), 3.15-3.31 (4H, m), 3.79-3.89 (2H, m), 4.47-4.55 (1H, m), 5.91 (1H, t), 7.42-7.56 (4H, m), 7.59-7.65 (1H, m), 8.08-8.14 (2H, m), 8.37 (1H, s), 8.59 (1H, s), 9.53 (1H, s); m/z (ES+) (M+H)+=480.41; HPLC tR=1.19 min.