Potassium Carbonate → 2-(2-Fluorophenyl)-5-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one

Participants

Reaction Steps

(4-{[2-(2-Fluorophenyl)-3-oxo-2,3-dihydro-5H-pyrazolo[4,3-c]quinolin-5-yl]methyl}phenyl)boronic acid (Example 370, 60 mg, 0.14 mmol) was dissolved in degassed dimethylsulfoxide (1 mL), treated with 2-dicyclohexylphosphino-2′,4′,6′-tri-iso-propyl-1,1′-biphenyl (10 mg, 0.022 mmol, 0.15 equiv), 4-iodo-1-methyl-1H-pyrazole (33 mg, 0.16 mmol, 1.1 equiv), an aqueous solution (0.2 mL) of potassium carbonate (50 mg, 0.36 mmol, 2.5 equiv) and palladium(II) acetate (1.6 mg, 0.0073 mmol, 0.05 equiv) and placed into a preheated oil bath at 80° C. for 1 hour. The mixture was cooled to ambient temperature, poured into water (25 mL) and extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed once with water (10 mL) and brine (10 mL), dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (100:0 to 95:5; chloroform:methanol), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.45 (1H, s), 8.42 (1H, br d, 7.1 Hz), 7.74 (1H, s), 7.65 (1H, td, J=7.7, 2.0 Hz), 7.60 (1H, s), 7.54-7.46 (5H, m), 7.38-7.33 (1H, m), 7.29-7.23 (2H, m), 7.20 (2H, d, J=8.2 Hz), 5.46 (2H, s), 3.94 (3H, s) ppm; high resolution mass spectrometry (ES+) m/z 450.1739 [(M+H)+; calculated for C27H21FN5O: 450.1725].

Provenance & Evidence