Example 15
To a mixture of 6-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-4-(prop-1-en-2-yl)isoquinolin-1(2H)-one (200 mg, 0.6 mmol) in DMF (6 mL) was added 2-methylphenyl boronic acid (304 mg, 2.2 mmol), Et3N (227 mg, 2.2 mmol) and Cu(OAc)2 (102 mg, 0.6 mmol), respectively. The reaction mixture was stirred under O2 (15 Psi) at room temperature for 72 h. The reaction was quenched by the addition of saturated aqueous NH4Cl solution. The mixture was extracted with EtOAc. The organic layer was separated, washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by preparative reversed phase HPLC (Stationary phase: Phenomenex Gemini-NX, 5 μm, 150×30 mm; Mobile phase: water (0.04% NH3.H2O+10 mM NH4HCO3) (A) -MeCN (B), gradient elution: 42-72% B in A over 8 min, flow rate: 25 mL/min) to give the title compound as a yellow solid (28 mg, yield: 12%). ESI-MS: mass calcd. for C24H24N4O3, 416.2; m/z found, 417.3 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 8.39 (d, J=1.71 Hz, 1H), 8.35 (d, J=8.80 Hz, 1H), 8.10 (dd, J=1.71, 8.80 Hz, 1H), 7.27-7.42 (m, 4H), 7.16 (s, 1H), 5.79 (t, J=5.87 Hz, 1H), 5.35 (s, 1H), 5.11 (s, 1H), 4.49 (d, J=5.87 Hz, 2H), 3.77 (q, J=7.09 Hz, 2H), 2.09 (s, 3H), 2.05 (s, 3H), 1.25 (t, J=7.09 Hz, 3H) ppm.