反应详情

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)-2-(1-(3-fluoro-2-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-methylpyridin-2-yl)propanamide (Intermediate AF2) (430 mg, 0.61 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 to afford crude product which was purified by flash silica chromatography, elution gradient 60 to 100% EtOAc in isohexane then by chiral HPLC to afford the product (160 mg, 56%). 1H NMR (400 MHz, DMSO) δ 1.99 (3H, d), 2.24 (3H, s), 3.50-3.56 (2H, m), 3.58-3.68 (2H, m), 4.00-4.05 (1H, m), 4.08-4.13 (1H, m), 4.61 (1H, t), 5.91-5.96 (1H, m), 7.30-7.33 (1H, m), 7.40-7.51 (2H, m), 7.57-7.60 (1H, m), 7.85-7.88 (1H, m), 8.17-8.18 (1H, m), 8.54 (1H, s), 8.61 (1H, s), 10.85 (1H, s); m/z (ESI+) (M+H)+=467; HPLC tR=1.98 min.

1. washwashed sequentially with water (25 mL) and saturated brine (25 mL)
2. dry with materialThe organic layer was dried (MgSO4)
3. filtrationfiltered
4. customevaporated
5. customto afford crude product which
6. customwas purified by flash silica chromatography, elution gradient 60 to 100% EtOAc in isohexane