反应详情

To a stirred solution of (3-{7-[(4-methylphenyl)sulfonyl]-4-[(3S)-3-methylpiperidin-1-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}phenyl)methanol (C16) from the previous step (<0.50 mmol) in 2-propanol (20 mL) was added lithium hydroxide monohydrate (0.42 g, 10 mmol) and water (3 mL) and the reaction mixture was stirred at room temperature for 18 hours. After concentration in vacuo, the residue was purified by preparative HPLC (Column: Waters XBridge; Mobile phase A: 0.1% ammonia in water; Mobile phase B: acetonitrile; Gradient: 44% to 60% B) to provide the product as a white solid. Yield: 130 mg, 0.403 mmol, 80% over two steps. LCMS m/z 323.4 [M+H+]. 1H NMR (400 MHz, CD3OD) δ 8.24 (s, 1H), 7.46 (br s, 1H), 7.35-7.43 (m, 2H), 7.30 (br d, J=6 Hz, 1H), 7.23 (s, 1H), 4.67 (s, 2H), 3.89 (br d, J=13 Hz, 1H), 3.79 (br d, J=12 Hz, 1H), 2.58-2.69 (m, 1H), 2.27 (dd, J=12.0, 11.0 Hz, 1H), 1.62-1.71 (m, 1H), 1.30-1.52 (m, 3H), 0.87-1.01 (m, 1H), 0.60 (d, J=6.5 Hz, 3H).

1. concentrationAfter concentration in vacuo
2. customthe residue was purified by preparative HPLC (Column: Waters XBridge; Mobile phase A: 0.1% ammonia in water; Mobile phase B: acetonitrile; Gradient: 44% to 60% B)