反应详情

Tetrabutylammonium fluoride (1M in THF) (0.203 mL, 0.20 mmol) was added to (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(1-(2-chloro-6-cyanophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-methylpyridin-2-yl)propanamide (Intermediate AH9) (149 mg, 0.20 mmol) in THF (5 mL) under nitrogen. The resulting mixture was stirred at ambient temperature for 1 hour. The reaction mixture was quenched with saturated NH4Cl (2 mL), diluted with DCM (25 mL) and poured onto a phase separator. The organic phase was reduced to give a gum. 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 to afford the product (45.0 mg, 44.8%, 58% ee). 1H NMR (400 MHz, CDCl3) d 2.23 (3H, s), 3.77-3.62 (4H, m), 4.20-4.04 (2H, m), 6.01 (1H, m), 7.51-7.46 (1H, m), 7.55 (1H, t), 7.72 (1H, dd), 7.84-7.76 (1H, m), 8.03 (2H, d), 8.46 (1H, d), 8.55 (1H, d), 9.19-8.96 (1H, m) OH not observed. m/z (ES+) (M+H)+=494; HPLC tR=1.82 min.

1. customThe reaction mixture was quenched with saturated NH4Cl (2 mL)
2. additiondiluted with DCM (25 mL)
3. additionpoured onto a phase separator
4. customto give a gum
5. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length)
6. customto afford the product (45.0 mg, 44.8%, 58% ee)