Reaction Steps
2-(2-acetylphenyl)-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (Example 532, 77 mg, 0.17 mmol) was dissolved in dichloromethane (5 mL) and cooled to −78° C. Methylmagnesium bromide (0.056 mL, 3 M diethyl ether solution, 0.17 mmol, 1 equiv) was added dropwise and the mixture was stirred for 30 minutes at −78° C. Additional methylmagnesium bromide (0.057 mL, 3 M diethyl ether solution, 0.17 mmol, 1 equiv) was added and the mixture was stirred for an additional 30 minutes at −78° C. The mixture was treated with sodium bicarbonate (3 mL, aqueous saturated), warmed to ambient temperature, poured into water and extracted with dichloromethane (2×75 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified via silica gel gradient chromatography (100:0 to 0:100 hexanes:ethyl acetate containing 5% methanol), providing the titled compound: 1H-NMR (400 MHz, d6-DMSO) δ 9.12 (1H, s), 8.46 (1H, d, J=2.5 Hz), 8.15 (1H, dd, J=8.0, 1.1 Hz), 7.90 (1H, dd, J=7.9, 1.3 Hz), 7.84 (2H, d, J=8.7 Hz), 7.78 (1H, d, J=8.6 Hz), 7.73 (1H, d, J=1.4 Hz), 7.64-7.60 (1H, m), 7.53 (1H, t, J=7.6 Hz), 7.48 (2H, d, J=8.7 Hz), 7.46-7.43 (1H, m), 7.35 (1H, td, J=7.5, 1.3 Hz), 7.17 (1H, dd, J=7.5, 1.1 Hz), 6.53 (1H, dd, J=2.3, 1.9 Hz), 5.77 (2H, s), 5.28 (1H, s), 1.37 (6H, s) ppm; high resolution mass spectrometry (ES+) m/z 476.2069 [(M+H)+; calculated for C29H26N5O2: 476.2081].
