Ammonium Chloride → 2-(2-Methylphenyl)-5-[(5-methylpyridin-2-yl)methyl]-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one

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Reaction Conditions

Reaction Steps

5-[(5-Bromopyridin-2-yl)methyl]-2-(2-methylphenyl)-2,5-dihydro-3/1-pyrazolo[4,3-c]quinolin-3-one (Example 743, 40 mg, 0.090 mmol) was dissolved in tetrahydrofuran (2 mL), and the mixture was sparged under an atmosphere of nitrogen. Dimethyl zinc (0.49 mL, 2.0 Min toluene, 0.90 mmol, 10 equiv) and tetrakis(triphenylphosphine) palladium (0) (1.0 mg, 0.01 mmol, 0.1 equiv) were added and the mixture was placed into an oil bath preheated to 60° C. for 4 hours. Additional dimethyl zinc (0.49 mL, 2.0 M in toluene, 0.90 mmol, 10 equiv) and tetrakis(triphenylphosphine) palladium (0) (1.0 mg, 0.01 mmol, 0.1 equiv) were added and the mixture was heated at 70° C. for an additional 3 hours. The mixture was cooled to ambient temperature, treated with ammonium chloride (0.2 mL, aqueous saturated), and concentrated in vacuo. The residue was purified by preparative reverse phase HPLC (90:10 to 5:95; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid), providing the titled compound: 1H-NMR (400 MHz, CD3OD) δ 8.98 (1H, s), 8.39 (1H, s), 8.35-8.32 (1H, m), 7.78 (1H, d, J=8.5 Hz), 7.73 (1H, d, J=6.2 Hz), 7.66-7.56 (2H, m), 7.42-7.35 (5H, m), 5.86 (2H, s), 234 (3H, s), 2.28 (3H, s), ppm; low resolution mass spectrometry (ES+) m/z 381.0 (M+H)+; calculated for C24H20N4O: 381.2].

Provenance & Evidence