Potassium Phosphate, Tribasic → 2-(2-fluoro-3-methylpyridin-4-yl)-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

Participants

Reaction Steps

5-{[4-(1H-Pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one (25 mg, 0.073 mmol), copper(I)iodide (14 mg, 0.073 mmol, 1 equiv), tribasic potassium phosphate (93 mg, 0.44 mmol, 6.0 equiv), (±)-trans-N,N′-bismethyl-1,2-cyclohexanediamine (31 mg, 3.0 equiv) and 2-fluoro-4-iodo-3-picoline (52 mg, 0.22 mmol, 3.0 equiv) were combined in degassed N,N-dimethylformamide (3 mL) and the mixture was placed into an oil bath preheated to 110° C. for 1 hour. The mixture was cooled to ambient temperature, poured into sodium bicarbonate (25 mL, aqueous saturated) and extracted with ethyl acetate (3×50 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), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.32 (1H, d, J=8.1 Hz), 8.15 (1H, d, J=5.3 Hz), 7.91 (1H, d, J=2.5 Hz), 7.72 (2H, d, J=8.5 Hz), 7.72 (1H, m), 7.67-7.59 (3H, m), 7.46 (1H, m), 7.43 (2H, d, J=8.3 Hz), 6.47 (1H, m), 5.89 (2H, s), 2.37 (3H, s) ppm; high resolution mass spectrometry (ES+) m/z 452.1623 [(M+H)+; calculated for C25H19FN7O: 452.1630].

Provenance & Evidence