反应详情

温度

0 °C

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.

1. waitto room temperature for 10 min
2. temperatureThe mixture is then cooled to −78° C.
3. temperatureThe resulting mixture is warmed to room temperature
4. temperatureThe mixture is heated to 60° C. for 4 hours
5. extractionextracted with ethyl acetate (2×60 mL)
6. extractionThe organic extract
7. washis washed with aq. brine
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. customThe crude product is purified by chromatography
12. washto elute the product
13. customObtained