Reaction Steps
To a solution of 21b (70 mg, 0.10 mmol) in MeOH (2 mL) was added 6 N HCl (4 mL) at room temperature. The mixture was stirred for 12 h and then concentrated. The crude product was purified by recrystallization (EtOH/H2O) to give inhibitor 10 (38 mg, 97%): 1H NMR (500 MHz, CDCl3) δ 2.26 (s, 1H), 2.55-2.65 (m, 1H), 2.78-2.85 (dd, J=7.0, 15.0 Hz, 1H), 2.88-2.95 (dd, J=8.0, 15.0 Hz, 1H), 3.02-3.07 (dd, J=15.5, 16.0 Hz, 1H), 3.25-3.33 (m, 2H), 3.39-3.43 (m, 3H), 3.71-3.74 (t, J=6.5 Hz, 2H), 3.89-3.96 (t, J=15.0 Hz, 2H), 4.29 (s, 1H), 6.68 (s, 1H), 6.72 (s, 1H), 7.50-7.53 (dd, J=5.0, 7.5 Hz, 1H), 7.70-7.73 (d, J=8.0 Hz, 1H), 7.92-7.96 (ddd, J=2.0, 8.0, 8.0 Hz, 1H), 8.45-8.55 (d, J=5.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 21.3, 29.1, 37.8, 42.0, 46.4, 46.9, 50.4, 50.6, 50.8, 53.3, 69.4, 108.0, 114.8, 115.1, 116.7, 118.7, 120.9, 121.0, 126.9, 139.1, 147.4, 149.2, 149.4, 149.6, 149.8, 152.5, 159.3; LC-TOF (M+H+) calcd for C20H28F2N5O 392.2262, found 392.2265.
