反应详情

温度

-78 °C

To a −78° C. solution of 3-(5-bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.60 g, 1.53 mmol) and THF (10 mL) is added 1.56 M n-Bu-Li (1.03 mL, 1.61 mmol). After 30 minutes tetrahydro-pyran-4-one (0.21 mL, 2.29 mmol) is added over 5 minutes. The solution is stirred at −78° C. for 2 hours, warmed to ambient temperature, diluted with EtOAc (50 mL), washed with sat. NH4Cl (50 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO column chromatography (20%-100% EtOAc/hexane gradient) furnish the title compound (0.38 g, 0.92 mmol, 60%). 1H NMR (CDCl3), δ 0.88 (t, J=7.5 Hz, 6H), 1.74-1.91 (m, 4H), 1.91-2.00 (m, 2H), 2.11 (s, 3H), 2.20-2.30 (m, 2H), 2.46 (s, 3H), 2.51 (s, 3H), 3.30-3.39 (m, 1H), 3.83-3.98 (m, 5H), 6.66 (s, 1H), 6.93 (s, 1H). LC/MS (m/z): calcd. for C23H31N3O2S (M+H)+: 414.3; found: 414.2.

1. temperaturewarmed to ambient temperature
2. washwashed with sat. NH4Cl (50 mL)
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated
6. customThe residue is purified by ISCO column chromatography (20%-100% EtOAc/hexane gradient)