Reaction Steps
(±)-5-(4-Iodobenzyl)-2-(tetrahydro-2H-pyran-3-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one [(Example 45), 25 mg, 0.051 mmol] was dissolved in degassed dimethylsulfoxide (1 mL) and water (0.2 mL), which was treated with copper (I) iodide (3.9 mg, 0.021 mmol, 0.4 equiv), 1,2,3-triazole (4.3 mg, 0.062 mmol, 1.2 equiv), (±)-trans-N,N′-dimethylcyclohexane-1,2-diamine (1.5 mg, 0.0010 mmol, 0.2 equiv) and potassium phosphate (27 mg, 0.15 mmol, 3 equiv). The vessel was sparged under nitrogen, sealed and placed into an oil bath preheated at 100° C. for 5 hours. The mixture was cooled to ambient temperature, poured into sodium bicarbonate (15 mL, aqueous saturated) and extracted with ethyl acetate (3×20 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (100:0 to 90:10; dichloromethane:methanol), providing the titled compound as a red solid: 1H-NMR (400 MHz, CDCl3) δ 8.30-8.28 (1H, m), 7.96 (1H, d, J=0.9 Hz), 7.84 (1H, d, J=0.9 Hz), 7.76 (2H, m), 7.74 (2H, d, J=8.6 Hz), 7.58-7.55 (1H, m), 7.46 (2H, d, J=8.4 Hz), 5.87 (2H, s), 4.75-4.67 (1H, m), 4.04 (1H, dd, J=10.7, 1.4 Hz), 3.99 (1H, d, J=11.1 Hz), 3.82 (1H, ap t, J=10.7 Hz), 3.51 (1H, td, J=11.0, 3.3 Hz), 2.29-2.18 (2H, m), 2.12 (1H, br d, J=12.4 Hz), 1.94-1.83 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 428.1849 [(M+H)+; calculated for C23H22N7O2: 428.1829].
