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

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Reaction Conditions

Reaction Steps

(±)-2-(2,3-Dihydroxypropyl)-5-[4-(1H-pyrazol-1-yl)benzyl]-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one [(Example 11), 0.10 g, 0.24 mmol] was dissolved in degassed N,N-dimethylformamide (5 mL), cooled to 0° C. and sparged under nitrogen. The mixture was treated with sodium hydride (21 mg, 0.53 mmol, 2.2 equiv) and after minutes, treated with iodomethane (37 μL, 0.60 mmol, 2.5 equiv). After stirring for 1 hour, the mixture was treated with methanol (2 mL), poured into water (25 mL) 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 via silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate containing 10% methanol), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.29-8.26 (1H, m), 7.89 (1H, d, J=2.5 Hz), 7.71 (1H, d, J=1.7 Hz), 7.68 (2H, d, J=8.6 Hz), 7.56-7.51 (3H, m), 7.39 (2H, d, J=8.6 Hz), 6.46 (1H, dd, J=2.4, 1.9 Hz), 5.83 (2H, s), 4.21 (2H, d, J=5.8 Hz), 3.92-3.86 (1H, m), 3.64 (1H, dd, J=10.4, 3.7 Hz), 3.55 (1H, dd, J=10.4, 6.0 Hz), 3.52 (3H, s), 3.42 (3H, s) ppm; high resolution mass spectrometry (ES+) m/z 445.1976 [(M+H)+; calculated for C24H24N6O3: 445.1983].

Provenance & Evidence