反应详情

A THF solution (6 mL) of 5-fluoro-3-methyl-benzofuran (187.0 mg, 1.25 mmol) is cooled to −78° C. under N2 then treated with nBuLi (1.6 M in hexane, 1.0 mL, 1.6 mmol). After 10 min at −78° C., ZnCl2 (Aldrich, 0.5 M in THF, 3.0 mL, 1.5 mmol) is added. 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 (212.4 mg, 0.62 mmol) and PdCl2(dppf)-CH2Cl2 complex (Aldrich, 60 mg, 0.073 mmol). The mixture is heated to 65° C. for 18 hours, then poured into H2O, acidified with 1 N HCl then extracted with ethyl acetate. The organic extract is ished 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 give the title compound as a solid (121.7 mg, 54% yield).

1. temperatureThe mixture is heated to 65° C. for 18 hours
2. extractionthen extracted with ethyl acetate
3. extractionThe organic extract
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe crude product is purified by chromatography