反应详情

温度

50 °C

To a flask of 4-iodo-3,5-dimethyl-isoxazole (0.34 g, 1.53 mmol) is added a solution of Rieke® zinc 5 g/100 mL in THF (3 mL, 2.29 mmol). The slurry is heated at a reflux for 4 hours, the zinc is allowed to settle and the solution transferred to a flask of 3-(5-bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.30 g, 0.76 mmol) and PdCl2(dppf) (0.028 g, 0.038 mmol). The solution is heated at 50° C. overnight, diluted with EtOAc (20 mL), washed with 0.1 M HCl (15 mL), water (15 mL), brine (15 mL) dried over MgSO4, filtered and concentrated. The residue is purified by ISCO column chromatography (15%-30% EtOAc/hexane gradient) furnish the title compound (0.22 g, 0.54 mmol, 71%). 1H NMR (CDCl3), δ 0.92 (t, J=7.5 Hz, 6H), 1.78-1.96 (m, 4H), 2.21 (s, 3H), 2.47 (s, 3H), 2.53 (s, 3H), 2.56 (s, 3H), 2.61 (s, 3H), 3.33-3.42 (m, 1H), 6.72 (s, 1H), 6.98 (s, 1H). LC/MS (m/z): calcd. for C23H28N4OS (M+H)+: 409.3; found: 409.2.

1. temperatureThe slurry is heated at
2. temperaturea reflux for 4 hours
3. washwashed with 0.1 M HCl (15 mL), water (15 mL), brine (15 mL)
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue is purified by ISCO column chromatography (15%-30% EtOAc/hexane gradient)