反应详情

A solution of 2-{[2-(1H-benzimidazol-2-ylsulfanylmethyl)-3-chloropyridin-4-yl]-methylamino}-ethanol (7.5 g, 21.5 mmol) in dimethylformamide (75 ml) is treated with sodium hydride (1.4 g 80% strength suspension) and stirred for 1 h at room temperature. Then 6-chloro-3-nitro-imidazo[1,2-b]pyridazine (4.3 g, 21.5 mmol) in tetrahydrofurane (50 ml) is added dropwise over a period of 20 min and stirring is continued for another 2 h. The solution is treated with water (750 ml) and extracted extensively with ethyl acetate. The combined organic extracts are washed with water, dried over magnesium sulfate and evaporated in vacuo. The residue is chromatographed (silica, toluene/dioxane/ammonia 2:1:0.1) and crystallized from ethyl acetate. The crude product is dissolved in boiling 2-pronanol (250 ml) and treated with charcoal. After filtration and cooling to 35° C., a saturated solution of hydrogen chloride in diethyl ether (1.5 ml) is added and the mixture is cooled to 4° C. The precipitate is filtered, washed with 2-propanol and dried in vacuo to give the title compound as a faintly yellow solid, 3.6 g (31%). M.p. 211-2° C.

1. stirringstirring
2. waitis continued for another 2 h
3. extractionextracted extensively with ethyl acetate
4. washThe combined organic extracts are washed with water
5. dry with materialdried over magnesium sulfate
6. customevaporated in vacuo
7. customThe residue is chromatographed (silica, toluene/dioxane/ammonia 2:1:0.1)
8. customcrystallized from ethyl acetate
9. dissolutionThe crude product is dissolved
10. additiontreated with charcoal
11. filtrationAfter filtration
12. temperaturecooling to 35° C.
13. additiona saturated solution of hydrogen chloride in diethyl ether (1.5 ml) is added
14. temperaturethe mixture is cooled to 4° C
15. filtrationThe precipitate is filtered
16. washwashed with 2-propanol
17. customdried in vacuo