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

Participants

Reaction Steps

A solution of tetrabutylammonium fluoride (1M in THF) (7.14 mL, 7.14 mmol) was added in one portion to a stirred solution of (2S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-fluoropyridin-2-yl)propanamide (Intermediate AX1) (4.27 g, 7.14 mmol) in tetrahydrofuran (100 mL). The resulting solution was stirred at ambient temperature for 30 minutes. The reaction mixture was quenched with saturated NH4Cl (30 mL), concentrated to approximately 50 mL and then diluted with water (50 mL) and EtOAc (100 mL). The organic layer was separated and the aqueous layer extracted with EtOAc (100 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 0 to 10% MeOH in EtOAc to afford the product (2.54 g, 73.6%). 1H NMR (400 MHz, CDCl3) δ 2.35 (1H, s), 3.15-3.21 (3H, m), 3.27-3.31 (1H, m), 3.84-3.91 (2H, m), 4.50-4.57 (1H, m), 5.90-5.93 (1H, m), 7.41-7.54 (4H, m), 7.61-7.63 (1H, m), 8.14 (1H, d), 8.23-8.26 (1H, m), 8.37 (1H, s), 8.59 (1H, s), 9.74 (1H, s); m/z (ES+) (M+H)+=484.17; HPLC tR=1.65 min.

Provenance & Evidence