反应详情

温度

80 °C

Sodium hydride (60% dispersion in oil, 62 mg, 1.54 mmol) was added to a stirred solution of 3-(2-fluorophenyl)-7-(3-oxocyclobutyl)-1,2,4-triazolo[4,3-b]pyridazin-6-one (0.23 g, 0.7 mmol) in anhydrous N,N-dimethylformamide (5 ml), and heated to 80° C. under an atmosphere of nitrogen for 0.5 hours. The solution was allowed to cool before addition of 5-chloromethyl-1-methyl-1H-1,2,4-triazole monohydrochloride (prepared using the conditions described in EP-A-170073) (0.14 g, 0.85 mmol). The reaction was then heated to 80° C., under an atmosphere of nitrogen, for 18 hours. The solution was allowed to cool, concentrated and the residue was purified by chromatography on silica using 0-5% methanol/dichloromethane as eluent to give the required product as a white solid. Data for the title compound: 1H NMR (360 MHz, CDCl3) δ3.29-3.38 (2H, m), 3.45-3.56 (2H, m), 3.73-3.82 (4H, m), 5.52 (2H, s), 7.26-7.31 (1H, m), 7.35-7.39 (1H, m), 7.56-7.60 (1H, m), 7.81-7.85 (1H, m), 7.88 (1H, s), 7.98 (1H, s); MS (ES+) m/e 394 [MH]+.

1. customprepared
2. temperatureThe reaction was then heated to 80° C., under an atmosphere of nitrogen, for 18 hours
3. temperatureto cool
4. concentrationconcentrated
5. customthe residue was purified by chromatography on silica using 0-5% methanol/dichloromethane as eluent