Nitrogen → 1-(2-Hydroxy-2-methylpropyl)-N-(4-(5-isoquinolinyl)-3-methylphenyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

Participants

Reaction Steps

A sealable tube was charged with PdCl2(dppf)-CH2Cl2 adduct (0.013 g, 0.016 mmol), isoquinolin-5-ylboronic acid (0.057 g, 0.33 mmol), N-(4-bromo-3-methylphenyl)-1-(2-hydroxy-2-methylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (0.150 g, 0.33 mmol) and 4 mL dioxane. To this mixture, NaHCO3 solution (0.49 ml, 0.98 mmol) was added and the reaction mixture blanket with N2. The vessel was sealed and heated at 80 C for 19 h. The mixture was allowed to cool to rt, filtered through a pad of celite using ethyl acetate as the eluent and the organic layer washed with water, brine, dried over Na2SO4, filtered and evaporated. The mixture was purified via flash chromatography using a mixture of MeOH in EtOAc as the eluent. The title compound was isolated as an off-white solid (80 mg). MS (ESI pos. ion) m/z=507 (MH+). Calc'd mass for C31H30FN4O3: 506.60. 1H NMR (400 MHz, dmso-d6) δ 10.86 (s, 1H), 9.39 (s, 1H), 8.45 (d, J=5.9 Hz, 1H), 8.17 (d, J=8.1 Hz, 1H), 7.74-7.80 (m, 1H), 7.56-7.85 (m, 5H), 7.44-7.50 (m, 1H), 7.37 (d, J=7.7 Hz, 2H), 7.25 (d, J=5.8 Hz, 1H), 7.17 (d, J=8.1 Hz, 1H), 3.31 (s, 2H), 2.82 (s, 3H), 1.95 (s, 3H), 0.98 (s, 6H).

Provenance & Evidence