反应详情

10.9 g of sodium hydride (80% strength suspension) are suspended in 350 ml of tetrahydrofuran under a nitrogen atmosphere. A solution of 73 g (0.31 mol) of [4-(3-mercaptopropylsulfanyl)-3-methylpyridin-2-yl]methanol in tetrahydrofuran (350 ml) is then added dropwise with vigorous stirring at room temperature during the course of 2 h. The suspension is then stirred at room temperature for a further 2.5 h. A solution of 51.6 g (0.26 mol) of 6-chloro-3-nitroimidazo[1,2-b]pyridazine in tetrahydrofuran (1000 ml) is then added dropwise during the course of 3.5 h and the mixture is stirred at room temperature for a further 18 h. The mixture is then cooled to 0° C. and cautiously treated with water (500 ml) with vigorous stirring. The organic solvent is then distilled off. The aqueous residue is diluted with a further 500 ml of water and cooled to 0° C. The beige precipitate is filtered off, washed with water and dried in a high vacuum at 40° C. The crude product is then dissolved in hot toluene (1.2 l) and clarified with activated carbon (25 g) and kieselguhr (15 g). After filtration at boiling heat, the solution is concentrated to 750 ml and treated with diisopropyl ether (1.2 l). For complete precipitation, the suspension is cooled to 0° C. with stirring. The precipitate is filtered off and then dried in vacuo at 40° C. For further purification, the product is suspended in hot methanol (1.2 l) and treated again with diisopropyl ether (500 ml) after cooling to room temperature. After filtration and drying in vacuo, 82 g (80%) of the title compound of m.p. 127-129° C. are isolated.

1. stirringThe suspension is then stirred at room temperature for a further 2.5 h
2. stirringthe mixture is stirred at room temperature for a further 18 h
3. temperatureThe mixture is then cooled to 0° C.
4. distillationThe organic solvent is then distilled off
5. additionThe aqueous residue is diluted with a further 500 ml of water
6. temperaturecooled to 0° C
7. filtrationThe beige precipitate is filtered off
8. washwashed with water
9. customdried in a high vacuum at 40° C
10. dissolutionThe crude product is then dissolved in hot toluene (1.2 l)
11. filtrationAfter filtration
12. temperatureat boiling heat
13. concentrationthe solution is concentrated to 750 ml
14. additiontreated with diisopropyl ether (1.2 l)
15. customFor complete precipitation
16. temperaturethe suspension is cooled to 0° C.
17. stirringwith stirring
18. filtrationThe precipitate is filtered off
19. customdried in vacuo at 40° C
20. customFor further purification
21. additiontreated again with diisopropyl ether (500 ml)
22. temperatureafter cooling to room temperature
23. filtrationAfter filtration
24. dry with materialdrying in vacuo, 82 g (80%) of the title compound of m.p. 127-129° C.
25. customare isolated