反应详情

A suspension of CeCl3 (0.37 g, 2.22 mmol) in THF (10 mL) is stirred at RT for 2 h. It is then cooled to 0° C., and treated with 3.0 M CH3MgBr (0.74 mL, 2.22 mmol). The mixture is stirred at 0° C. for 2 h. A solution of 1-{3-[8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazin-3-yl]-2-methyl-imidazo[1,2-a]pyridin-8-yl}-ethanone (0.57 g, 1.48 mmol) in THF (5 mL) is added to the mixture at 0° C. The reaction is stirred at 0° C. for 30 min and at RT for 2 h. It is finally quenched with sat. NH4Cl (10 mL), diluted with H2O (50 mL); extracted with EtOAc (3×100 mL). The combined organic layers is dried with Na2SO4, filtered and concentrated. Purification of the crude material by silica gel chromatography gives the title compound (0.36 g, 0.90 mmol, 61%). 1H NMR (CDCl3): δ 0.92 (t, J=7.5 Hz, 3H), 0.93 (t, J=7.5 Hz, 3H), 1.80 (s, 6H), 1.80-1.95 (m, 4H), 2.41 (s, 3H), 2.42 (s, 3H), 2.45 (s, 3H), 3.31-3.41 (m, 1H), 6.67-6.74 (m, 1H), 6.73 (s, 1H), 6.92 (bs, 1H), 7.09 (bs, 1H), 7.41 (d, J=5.6 Hz, 1H) ppm. ES-MS (m/z): calcd for C24H31N5O (M+H)+: 406.6. found: 406.3.

1. temperatureIt is then cooled to 0° C.
2. stirringThe mixture is stirred at 0° C. for 2 h
3. stirringThe reaction is stirred at 0° C. for 30 min and at RT for 2 h
4. customIt is finally quenched with sat. NH4Cl (10 mL)
5. additiondiluted with H2O (50 mL)
6. extractionextracted with EtOAc (3×100 mL)
7. dry with materialThe combined organic layers is dried with Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customPurification of the crude material by silica gel chromatography