反应详情

A solution of tetrabutylammonium fluoride (1M in THF) (0.701 mL, 0.70 mmol) was added dropwise to a stirred solution of (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-cyanopyridin-2-yl)-2-(1-(2,3-dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide (440 mg, 0.58 mmol) in THF (15 mL) over a period of 1 minute. The resulting solution was 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. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 0.1% formic acid) and MeCN as eluents. Fractions containing the desired compound were concentrated to remove most of the MeCN and then EtOAc was added. The organic phase was washed sequentially with saturated NaHCO3 and water the organic layer was evaporated to dryness to afford the product (240 mg, 80%). 1H NMR (400 MHz, CDCl3) δ 2.37 (1H, s), 3.81-3.62 (4H, m), 4.14 (2H, m), 6.00 (1H, t), 7.44-7.28 (2H, m), 7.60 (1H, dd), 7.90 (1H, dd), 8.29 (1H, dd), 8.36 (1H, s), 8.49 (1H, dd), 8.52 (1H, s), 9.26 (1H, s); m/z (ES+) (M+H)+=514; HPLC tR=2.13 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
6. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length)
7. additionFractions containing the desired compound
8. concentrationwere concentrated
9. customto remove most of the MeCN
10. additionEtOAc was added
11. washThe organic phase was washed sequentially with saturated NaHCO3 and water the organic layer
12. customwas evaporated to dryness