反应详情

To a −78° C. solution of 3-(5-bromo-3,4-dimethyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.10 g, 0.25 mmol) and THF (1 mL) is added 1.6 M n-BuLi (0.16 mL). The solution is stirred for 45 minutes and 0.5 M ZnCl2 in THF (0.52 mL, 0.26 mmol) is added. The solution is warmed to ambient temperature and stirred for 30 minutes. 2-Bromo-thiazole (0.044 mL, 0.49 mmol), and PdCl2(dppf) (0.009 g, 0.012 mmol) are added and the solution heated at 65° C. overnight, diluted with EtOAc (25 mL), washed with sat. NH4Cl (20 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO column chromatography (15%-20% EtOAc/hexane gradient), furnish the title compound (6.1 mg, 0.015 mmol, 6%). 1H NMR (CDCl3), δ 0.87 (t, J=7.5 Hz, 6H), 1.74-1.92 (m, 4H), 2.07 (s, 3H), 2.49 (s, 3H), 2.51 (s, 3H), 2.53 (s, 3H), 3.29-3.39 (m, 1H), 6.68 (s, 1H), 7.35 (d, J=3.1 Hz, 1H), 7.86 (d, J=3.1 Hz, 1H). LC/MS (m/z): calcd. for C22H26N4S2 (M+H)+: 411.6; found: 411.2.

1. stirringstirred for 30 minutes
2. temperaturethe solution heated at 65° C. overnight
3. washwashed with sat. NH4Cl (20 mL)
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue is purified by ISCO column chromatography (15%-20% EtOAc/hexane gradient)