Sodium Chloride → 3-(2-fluorophenyl)-7-(1-hydroxycyclobutyl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo[4,3-b]pyridazine

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Reaction Steps

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 5 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) δ 1.74 (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.

Provenance & Evidence