反应详情

温度

60 °C

A THF slurry (5 mL) of 3-(5-bromo-1-methyl-1H-pyrrol-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (143 mg, 0.38 mmol) and PdCl2(dppf)-CH2Cl2 complex (Aldrich, 19 mg, 0.023 mmol) is treated with 3-methyl-2-thienyl zinc bromide (Aldrich, 0.5 M in THF, 3.8 mL, 1.9 mmol) then heated to 60° C. for 1 hr. The resulting mixture is poured into sat'd NH4Cl (25 mL) and extracted with diethyl ether (35 mL). The organic extract is washed with aq. NaCl, dried over Na2SO4, filtered, and concentrated. The crude product is purified by chromatography using hexane-ethyl acetate gradient (100% hexane to 15% ethyl acetate in hexane) to elute the product. The material is purified a second time by flash chromatography using hexane-ethyl acetate gradient (100% hexane to 12% ethyl acetate in hexane) to elute the product. Only the fractions containing pure desired product, as judged by MS analysis, are collected and give the title compound (82.6 mg, 55% yield) as an oil. ES-MS (m/z): calc'd for C23H28N4S: 392.20. found 393.1 (M+H)+. 1H NMR (400 mHz, CDCl3): δ 7.28 (d, J=5.3 Hz, 1H), 6.96 (d, J=4.8 Hz, 1H), 6.67 (br s, 1H), 6.39 (d, J=3.5 Hz, 1H), 6.37 (d, J=4.0 Hz, 1H), 3.35 (br s, 1H), 3.33, (s, 3H), 2.52 (s, 3H), 2.51 (s, 3H), 2.26 (s, 3H), 1.89-1.76 (m, 4H), 0.87 (t, J=7.5 Hz, 6H).

1. extractionextracted with diethyl ether (35 mL)
2. extractionThe organic extract
3. washis washed with aq. NaCl
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe crude product is purified by chromatography
8. washto elute the product
9. customThe material is purified a second time by flash chromatography
10. washto elute the product
11. additionOnly the fractions containing pure desired product
12. customare collected