Tetrabutylammonium Fluoride → (2S)-2-[1-(2,6-dichlorophenyl)pyrazolo[4,5-e]pyrimidin-4-yl]oxy-N-(5-fluoro-2-pyridyl)-3-(2-hydroxyethoxy)propanamide

Participants

Reaction Steps

Tetrabutylammonium fluoride (1M in THF) (0.838 mL, 0.84 mmol) was added dropwise to (S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(1-(2,6-dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-fluoropyridin-2-yl)propanamide (Intermediate BA1) (0.625 g, 0.84 mmol) in THF (10.34 mL) at ambient temperature under nitrogen. The resulting solution was stirred at ambient temperature for 1 hour. The reaction mixture was quenched with saturated NH4Cl (10 mL), and diluted with water (20 mL) and EtOAc (70 mL). The organic layer was separated and the aqueous layer extracted with EtOAc (70 mL). The combined organics were dried (MgSO4), filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 25 to 100% EtOAc in isohexane to afford the product (0.307 g, 72.1%). 1H NMR (400 MHz, CDCl3) δ 2.60 (1H, t), 3.71-3.81 (4H, m), 4.16-4.25 (2H, m), 6.10 (1H, t), 7.43-7.49 (2H, m), 7.53-7.55 (2H, m), 8.14 (1H, d), 8.22-8.25 (1H, m), 8.48 (1H, s), 8.60 (1H, s), 9.00 (1H, s); m/z (ES−) (M+H)+=507.31; HPLC tR=2.67 min.

Provenance & Evidence