反应详情

To a stirred solution of (2-methyl-2H-1,2,4-triazol-3-yl)methanol (0.2206 g, 1.95 mmol) in anhydrous DMF (6 ml) under nitrogen was added sodium hydride (60% dispersion in oil, 77.7 mg, 1.94 mmol) and the mixture was stirred at room temperature for 20 min. The mixture was then cooled in an ice-water bath and a solution of 6-chloro-3-(2-fluorophenyl)-7-(1-hydroxycyclobutyl)-1,2,4-triazolo[4,3-b]pyridazine (0.2573 g, 0.807 mmol) in anhydrous DMF (5 ml) was added dropwise over min. The mixture was stirred for 20 min under nitrogen, then poured into saturated aqueous NH4Cl (50 ml), saturated aqueous NaCl (25 ml), and dichloromethane (75 ml). The aqueous layer was further extracted with dichloromethane (2×50 ml), and the combined organic extracts were dried (Na2SO4) and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, 3-5% MeOH/CH2Cl2) to afford 0.2793 g of 3-(2-fluorophenyl)-7-(1-hydroxycyclobutyl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo[4,3-b]pyridazine (containing approximately 20% of (2-methyl-2H-1,2,4-triazol-3-yl)methanol starting material) as a colourless solid; 1H NMR (360 MHz, CDCl3) δ1.74 (1H, m), 2.17 (1H, m), 2.43 (2H, m), 2.60 (2H, m), 3.82 (3H, s), 5.58 (2H, s), 7.27 (1H, t, J=9.6 Hz), 7.36 (1H, t, J=7.5 Hz), 7.58 (1H, m), 7.82 (1H, m), 7.85 (1H, s), 8.01 (1H, s); MS (ES+) m/e 396 [MH]+, 114.

1. temperatureThe mixture was then cooled in an ice-water bath
2. stirringThe mixture was stirred for 20 min under nitrogen
3. extractionThe aqueous layer was further extracted with dichloromethane (2×50 ml)
4. dry with materialthe combined organic extracts were dried (Na2SO4)
5. customevaporated in vacuo
6. customThe residue was purified by flash chromatography (silica gel, 3-5% MeOH/CH2Cl2)