反应详情

(±)-5-[(4-Iodophenyl)methyl]-2-(tetrahydro-2H-pyran-3-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one (50 mg, 0.10 mmol), pyrazole (11 mg, 0.17 mmol, 1.7 equiv), potassium phosphate (71 mg, 0.41 mmol, 4 equiv), (±)-trans-N,N′-dimethylcyclohexane-1,2-diamine (44 mg, 0.31 mmol, 3 equiv) and copper(I) iodide (20 mg, 0.10 mmol, 1 equiv) were combined in degassed N,N-dimethylformamide (2 mL) and placed into a preheated oil bath at 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 95:5 dichloromethane:methanol), providing the titled compound as a red solid: 1H-NMR (400 MHz, CDCl3) δ 8.74 (1H, dd, J=4.5, 1.7 Hz), 8.51 (1H, dd, J=8.0, 1.8 Hz), 8.78 (1H, d, J=2.5 Hz), 7.69 (1H, d, J=1.7 Hz), 7.64-7.62 (4H, m), 7.49 (1H, dd, J=8.0, 4.6 Hz), 6.44 (1H, dd, J=2.5, 1.6 Hz), 5.95 (2H, br s), 4.71-4.63 (1H, m), 4.01-3.95 (2H, m), 3.74 (1H, ap t, J=10.5 Hz), 3.47 (1H, td, J=11.1, 3.6 Hz), 2.22-2.06 (2H, m), 1.92-1.79 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 428.1837 [(M+H)+; calculated for C23H22N7O2:428.1829].

1. extractionextracted with ethyl acetate (3×50 mL)
2. dry with materialThe combined organic extracts were dried with sodium sulfate
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. customThe residue was purified by silica gel gradient chromatography (100:0 to 95:5 dichloromethane:methanol)