Hydrochloric Acid → 8-(1-Ethyl-propyl)-2,6-dimethyl-3-(3-methyl-benzofuran-2-yl)-imidazo[1,2-b]pyridazine

Participants

Reaction Conditions

Reaction Steps

A THF solution (6 mL) of 3-methyl-benzofuran (200 mg, 1.51 mmol) is cooled to −78° C. under N2 then treated with nBuLi (1.6 M in hexane, 1.0 mL, 1.6 mmol). After 5 min at −78° C., the solution is warmed to 0° C. for 10 minutes, then to room temperature for 10 min. The mixture is then cooled to −78° C. and treated with ZnCl2 (Aldrich, 0.5 M in THF, 3.2 mL, 1.6 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 (235.3 mg, 0.69 mmol) and PdCl2(dppf)-CH2Cl2 complex (Aldrich, 64 mg, 0.078 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 organic extract is washed with aq. brine, dried over Na2SO4, filtered, and concentrated. The crude product is purified by chromatography using hexane-ethyl acetate gradient (100% hexane to 20% ethyl acetate in hexane) to elute the product. Obtained is 8-(1-ethyl-propyl)-2,6-dimethyl-3-(3-methyl-benzofuran-2-yl)-imidazo[1,2-b]pyridazine as a solid (143.8 mg, 60% yield). ES-MS (m/z): calc'd for C22H25N3O: 347.20. found 348.5 (M+H)+1H NMR (400 mHz, CDCl3): δ 7.65 (d, J=8.4 Hz, 1H), 7.57 (d, J=7.9 Hz, 1H), 7.41-7.31 (m, 2H), 6.76 (br s, 1H), 3.38 (br s, 1H), 2.56 (s, 6H), 2.32 (s, 3H), 1.94-1.81 (m, 4H), 0.91 (t, J=7.5 Hz, 6H) ppm.

Provenance & Evidence