Boron tribromide → HCID 178424336, compound

Participants

Reaction Conditions

Reaction Steps

9-(Methyloxy)-2-(2-methylphenyl)-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (Example 723, 37 mg, 0.80 mmol) was dissolved in dichloromethane (5 mL) and cooled to −78° C. Boron tribromide (0.24 mL, 1 M dichloromethane solution, 0.24 mmol, 3 equiv) was added and the mixture was stirred for 3 hours at −78° C. The mixture was then warmed to −40° C. and stirred for an additional 30 minutes. The acetonitrile/dry ice bath was removed, the mixture was warmed to ambient temperature and stirred for 30 minutes. Additional boron tribromide (0.24 mL, 1 M dichloromethane solution, 0.24 mmol, 3 equiv) was added and the mixture was stirred for an additional 45 minutes at ambient temperature. The mixture was treated with sodium bicarbonate (6 mL, aqueous saturated) slowly over 5 minutes, stirred for 30 minutes at ambient temperature and then poured into sodium bicarbonate (50 mL, aqueous saturated). The aqueous layer was extracted with dichloromethane (3×100 mL) and the combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatograph (100:0 to 90:10 dichloromethane:methanol), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 9.71 (1H, s), 8.51 (1H, s), 7.91 (1H, d, J=1.9 Hz), 7.74-7.72 (3H, m), 7.47-7.45 (1H, m), 7.39 (1H, t, J=8.5 Hz), 7.36-7.30 (5H, m), 7.01 (1H, d, J=8.3 Hz), 6.94 (1H, d, J=8.6 Hz), 6.48 (1H, m), 5.46 (2H, s), 2.35 (3H, s) ppm; high resolution mass spectrometry (ES+) m/z 448.1785 [(M+H)+; calculated for C27H22N5O2: 448.1768].

Provenance & Evidence