Reaction Steps
Methyl [2-(3-oxo-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-3,5-dihydro-2H-pyrazolo[4,3-c]quinolin-2-yl)phenyl]acetate (Example 533, 0.10 g, 0.21 mmol) was suspended in diethyl ether (6 mL) and dichloromethane (9 mL), cooled to 0° C. and treated with lithium borohydride (4.9 mg, 0.23 mmol, 1.1 equiv) and then methanol (9.2 μL, 0.23 mmol, 1.1 equiv). The mixture was stirred at 0° C. for 15 minutes and then warmed to ambient temperature. After 20 minutes, the mixture was treated with additional lithium borohydride (10 mg, 0.46 mmol, 2.2 equiv) and methanol (20 μL, 0.46 mmol, 2.2 equiv) and stirred for an additional 1 hour at ambient temperature. The mixture was treated with ammonium chloride (3 mL, aqueous saturated) and stirred at ambient temperature for 15 minutes. The mixture was poured into water (20 mL) and extracted with dichloromethane (3×50 mL). The combined organic extracts were treated with dichloro-5,6-dicyanobenzoquinone (DDQ, 52 mg, 0.46 mmol, 2.2 equiv) and stirred for 45 minutes at ambient temperature. The mixture was treated with sodium bicarbonate (50 mL, aqueous saturated) and vigorously stirred for 30 minutes, partitioned and the aqueous layer was further extracted with dichloromethane (1×50 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by 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 9.13 (1H, s), 8.46 (1H, d, J=2.5 Hz), 8.19 (1H, d, J=7.6 Hz), 7.84 (2H, d, J=8.5 Hz), 7.77 (1H, d, J=8.5 Hz), 7.73 (1H, d, J=1.4 Hz), 7.64-7.59 (1H, m), 7.53 (1H, t, J=7.2 Hz), 7.48 (2H, d, J=8.5 Hz), 7.43 (1H, br d, J=6.9 Hz), 7.39-7.33 (3H, m), 6.53 (1H, m), 5.77 (2H, s), 4.61 (1H, t, J=5.2 Hz), 3.58-3.53 (2H, m), 2.77 (2H, t, J=7.4 Hz) ppm; high resolution mass spectrometry (ES+) m/z 462.1912 [(M+H)+; calculated for C28H24N5O2: 462.1925].
