Water → (+/-)-5-[4-(1H-pyrazol-1-yl)benzyl]-2-(tetrahydro-2H-pyran-3-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

Participants

Reaction Steps

Ethyl 1-[4-(1H-pyrazol-1-yl)benzyl]-4-thioxo-1,4-dihydrocinnoline-3-carboxylate (200 mg, 0.510 mmol) and (±)-tetrahydro-2H-pyran-3-ylhydrazine hydrochloride (172 mg, 1.13 mmol, 2.2 equiv) were dissolved in N,N-dimethylformamide (10 mL) and acetonitrile (10 mL). The solution was sparged under nitrogen, treated with potassium carbonate (708 mg, 5.12 mmol, 10 equiv) and mercury(II)chloride (139 mg, 0.51 mmol, 1 equiv) and stirred at ambient temperature for 14 hours. The mixture was poured into water and extracted with ethyl acetate (3×70 mL) and 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) to provide the titled compound as a dark red solid: 1H-NMR (400 MHz, CDCl3) δ 8.33-8.29 (1H, m), 7.88 (1H, d, J=2.5 Hz), 7.74 (1H, d, J=1.8 Hz), 7.66 (2H, d, J=8.7 Hz), 7.61-7.56 (3H, m), 7.40 (2H, d, J=8.6 Hz), 6.47 (1H, dd, J=2.4, 1.9 Hz), 5.85 (2H, s), 4.77-4.69 (1H, m), 4.06 (1H, ddd, J=10.8, 4.4, 1.6 Hz), 4.00 (1H, d, J=11.0 Hz), 3.84 (1H, ap t, J=10.6 Hz), 3.55-3.48 (1H, m), 2.31-2.19 (1H, m), 2.17-2.10 (1H, m), 1.92-1.83 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 427.1872 [(M+H)+; calculated for C24H22N6O2: 427.1877].

Provenance & Evidence