A solution of tetrabutylammonium fluoride (1M in THF) (1.504 mL, 1.50 mmol) was added dropwise to a stirred solution of (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-chloropyridin-2-yl)-2-(1-(3-fluoro-2-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide (Intermediate AF3) (600 mg, 0.83 mmol) in THF (15 mL) over a period of 1 minute and the resulting solution stirred at ambient temperature for 3 hours. Saturated ammonium chloride (20 mL) was added to the reaction mixture which was then diluted with EtOAc (25 mL), and washed sequentially with water (25 mL) and saturated brine (25 mL). The organic layer was dried (MgSO4), filtered and evaporated in vacuo. The crude product was purified by flash silica chromatography, elution gradient 60 to 100% EtOAc in isohexane then by chiral HPLC to afford the product (252 mg, 62%). 1H NMR (400 MHz, DMSO) δ 2.07 (3H, s), 3.53-3.62 (2H, m), 3.65-3.72 (2H, m), 4.06-4.22 (2H, m), 4.61-4.71 (1H, m), 5.96-6.05 (1H, m), 7.36-7.42 (1H, m), 7.44-7.55 (2H, m), 7.92-7.96 (1H, m), 8.08 (1H, d), 8.45 (1H, dd), 8.60 (1H, s), 8.71 (1H, s), 11.18 (1H, s); m/z (ESI−) (M−H)−=485; HPLC tR=2.29 min.
