Reaction Steps
To a solution of 17a (30 mg, 39 μmol) in EtOH (5.0 mL) was added a 1:1 mixture of EtOH/concentrated HCl (10 mL) and Pd(OH)2/C (20%, 30 mg). The mixture was charged with H2 under the pressure of 500 psi. The reaction mixture was allowed to stir at room temperature for 40 h. The catalyst was removed by filtration through Celite, and the resulting Celite cake was washed with EtOH (4×3 mL) and 2 N HCl (3 mL). The combined filtrates were concentrated to yield inhibitor 2a, a yellow solid, as a hydrochloride salt (15 mg, 85%): 1H NMR (500 MHz, D2O) δ 2.08 (s, 3H), 2.60-2.63 (m, 2H), 2.70-2.80 (m, 1H), 2.97-3.03 (m, 1H), 3.13-3.16 (m, 1H), 3.17-3.37 (m, 3H), 3.38-3.50 (m, 3H), 3.54 (br s, 1H), 3.73 (br s, 1H), 4.05 (br s, 1H), 4.17 (br s, 2H), 6.33 (s, 1H), 6.44 (s, 1H), 6.50-6.55 (br s, 1H), 6.58-6.70 (m, 3H), 7.06-7.08 (m, 1H); 13C NMR (125 MHz, D2O) δ 21.3, 29.4, 41.7, 46.6, 47.0, 47.3, 49.5, 63.0, 64.0, 78.6, 108.4, 108.6, 108.7, 110.4, 110.5, 114.3, 130.9, 131.0, 145.8, 154.0, 158.3, 158.7, 158.8, 162.4, 164.4; LCQ-MS (M+H+) calcd for C21H30FN4O2 389. found 389; LC-TOF (M+H+) calcd for C21H30FN4O2 389.23473. found 389.23444.
