Triethylamine → {4-[6-(3-Propyl[1,2,4]oxadiazol-5-YL)pyridazin-3-YL]piperazin-1-YL}-(2-trifluoromethylphenyl)methanone

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To a suspension of 6-[4-(2-trifluoromethylbenzoyl)piperazin-1-yl]pyridazine-3-carboxylic acid (0.500 g, 1.314 mmol) in chloroform, one drop of DMF was added followed by the addition of thionyl chloride (0.5 mL). The mixture was heated at reflux overnight. The clear solution was evaporated to dryness under vacuum to get a pale yellow syrup. This syrup was then dissolved in anhydrous dichloromethane (1 mL) and transferred to a solution containing N-hydroxybutyramidine (0.134 g, 1.314 mmol) and triethylamine (0.5 mL) in dichloromethane (5 mL) at 0° C. The mixture was warmed up to room temperature and stirred for another 30 minutes. The solvent was removed in vacuo. The crude mixture was suspended in 1,4-dioxane-water (1:1, 9 mL) containing cesium carbonate (0.3 g) and heated at reflux overnight, cooled, concentrated and diluted with water (10 mL), extracted with ethyl acetate. The organic phase was dried over anhydrous Na2SO4 and concentrated. The residue was purified by column chromatography and recrystallization from ethyl acetate-hexanes. The title compound was obtained as a white solid in 39% yield (0.228 g). m.p. 226° C. 1H NMR (300 MHz, CDCl3) 7.98 (d, J=9.6 Hz, 1H), 7.71 (d, J=7.7 Hz, 1H), 7.65-7.50 (m, 2H), 7.34 (d, J=7.4 Hz, 1H), 6.97 (d, J=9.6 Hz, 1H), 4.11-3.98 (m, 1H), 3.96-3.70 (m, 5H), 3.34 (t, J=5.1 Hz, 2H), 2.77 (t, J=7.4 Hz, 2H), 1.90-1.75 (m, 2H), 0.99 (t, J=7.3 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 172.6, 171.1, 167.7, 159.2, 139.7, 134.1, 132.4, 129.5, 127.8, 127.2, 126.9, 126.8, 111.3, 46.3, 44.5, 44.1, 41.2, 27.9, 20.4, 13.7. MS (ES+) m/z 447.0 (M+1).

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