Reaction Steps
5-[(6-Chloropyridin-3-yl)methyl]-2-(2,3-dimethylphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one [(Example 4), 47 mg, 0.11 mmol], cesium carbonate (92 mg, 0.28 mmol, 2.5 equiv), copper(I) chloride (11 mg, 0.11 mmol, 1 equiv), 2-methyl-5-pyridinylboronic acid (39 mg, 0.28 mmol, 2.5 equiv) and bis(tri-tert-butylphosphine)palladium(0) (11 mg, 0.023 mmol, 0.2 equiv) were combined in tetrahydrofuran (4 mL) and placed into a preheated oil bath at 70° C. After 45 minutes, water (1 mL) was added and after 45 minutes, the mixture was poured into sodium bicarbonate (50 mL) and extracted with ethyl acetate (2×50 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 containing 5% methanol), providing the titled compound as a deep red solid: 1H-NMR (400 MHz, CDCl3) δ 9.04 (1H, d, J=1.4 Hz), 8.89 (1H, d, J=2.3 Hz), 8.79 (1H, dd, J=4,6, 1.7 Hz), 8.55 (1H, dd, J=8.0, 1.8 Hz), 8.18 (1H, dd, J=8.1, 2.3 Hz), 8.03 (1H, dd, J=8.2, 2.2 Hz), 7.70 (1H, d, J=8.2 Hz), 7.52 (1H, dd, J=8.0, 4.6 Hz), 7.27-7.25 (1H, m), 7.24-7.22 (3H, m), 6.02 (2H, s), 2.61 (3H, s), 2.36 (3H, s), 2.16 (3H, s) ppm; high resolution mass spectrometry (ES+) m/z 474.2043 [(M+H)+; calculated for C28H24N7O: 474.2037].
