反应详情

温度

70 °C

Ethyl 1-[(6-methyl-2,3′-bipyridin-5-yl)methyl]-4-thioxo-1,4-dihydropyrido[2,3-c]pyridazine-3-carboxylate [(Example 6, Step 2), 47 mg, 0.11 mmol], (±)-trans-2-hydrazinocyclohexanol (44 mg, 0.34 mmol, 3 equiv), potassium carbonate (0.16 g, 1.1 mmol, 10 equiv) and mercury(II) chloride (31 mg, 0.11 mmol, 1 equiv) were combined in ethanol (10 mL) at ambient temperature and after 5 minutes, the mixture was warmed to 70° C. for 3 h. The mixture was cooled to ambient temperature, poured into sodium bicarbonate (100 mL, aqueous saturated) and extracted with ethyl acetate (3×75 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by preparative TLC (eluting with ethyl acetate containing 10% methanol), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 9.02 (1H, d, J=2.1 Hz), 8.93 (1H, d, J=2.0 Hz), 8.75 (1H, dd, J=4.6, 1.8 Hz), 8.52 (1H, dd, J=8.1, 1.8 Hz), 8.16 (1H, dd, J=8.2, 2.4 Hz), 7.97 (1H, dd, J=8.3, 2.3 Hz), 7.66 (1H, dd, J=8.2, 0.6 Hz), 7.50 (1H, dd, J=8.0, 4.6 Hz), 7.23 (1H, d, J=8.0 Hz), 6.0 (1H, d, J=14.3 Hz), 5.96 (1H, d, J=14.3 Hz), 4.30 (1H, ddd, J=11.7, 9.8, 4.1 Hz), 4.07-4.01 (1H, m,), 2.60 (3H, s), 2.20 (1H, br d, J=10.3 Hz), 2.01 (1H, br d, J=11.9 Hz), 1.89-1.79 (2H, m), 1.72-1.53 (2H, m), 1.50-1.39 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 468.2142 [(M+H)+; calculated for C26H26N7O2: 468.2143].

1. temperatureThe mixture was cooled to ambient temperature
2. extractionextracted with ethyl acetate (3×75 mL)
3. dry with materialThe combined organic extracts were dried with sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe residue was purified by preparative TLC (eluting with ethyl acetate containing 10% methanol)