Hydrochloric Acid → Pyridazine

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A THF solution (5 mL) of 3-methylfuran (Acros, 232 mg, 2.83 mmol) is cooled to −78° C. under N2 then treated with nBuLi (1.6 M in hexane, 1.8 mL, 2.9 mmol). After addition of the nBuLi, the solution is warmed to 0° C. for 15 minutes, then to room temperature for an additional 5 minutes. The reaction mixture is then cooled to −78° C. and treated with ZnCl2 (Aldrich, 0.5 M in THF, 5.8 mL, 2.9 mmol). The resulting mixture is warmed to room temperature and treated with 8-(1-ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazine (400 mg, 1.17 mmol) and PdCl2(dppf)-CH2Cl2 complex (Aldrich, 95 mg, 0.12 mmol). The mixture is heated to 60° C. for 4 hours, then poured into 1 N HCl (60 mL) and extracted with ethyl acetate (2×60 mL). The combined organic extracts are washed with aq. brine, dried over Na2SO4, filtered, and concentrated. The crude residue is purified by chromatography using hexane-ethyl acetate gradient (100% hexane to 20% ethyl acetate in hexane) to elute the title compound as an oil pyridazine (149 mg, 43% yield). ES-MS (m/z): calc'd for C18H23N3O: 297.2; found: 298.5 (M+H); 1H NMR (400 mHz, CDCl3): δ 7.59 (d, J=1.8 Hz, 1H), 6.71 (s, 1H), 6.47 (d, J=1.8 Hz, 1H), 3.36 (m, 1H), 2.55 (s, 3H), 2.50 (s, 3H), 2.10 (s, 3H), 1.92-1.79 (m, 4H), 0.90 (t, J=7.5 Hz, 6H).

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