Hydrochloric Acid → 6-Chloro-2-(trifluoromethyl)imidazo[1,2-b]pyridazine-3-sulfonamide

6-Chloro-2-trifluoromethylimidazo[1,2-b]pyridazine (6.00 g, 27.1 mmol) was dissolved in 1,1,2,2-tetrachloroethane (60.0 ml), and chlorosulfonic acid (97%, 2.80 ml, 40.7 mmol) was added to the solution with stirring at room temperature. The mixture was heated for 8 hours under reflux and then cooled to room temperature, and triethylamine (4.39 g, 43.4 mmol) and phosphorus oxychloride (7.47 g, 48.7 mmol) were added dropwise thereto. The reaction mixture was heated at 120° C. for 3 hours with stirring and then cooled to 50° C., and water (150 ml) was added thereto. After the reaction solution was partitioned, the aqueous layer was extracted twice with chloroform, and the organic layers were combined, washed twice with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residues were dissolved in acetonitrile (100 ml) and stirred at room temperature, during which ammonia water (14 M, 9.00 ml, 126 mmol) was added thereto. The reaction solution was stirred at room temperature for 2 hours, poured into ice-water (400 ml) and adjusted to pH 2 with conc. hydrochloric acid, to precipitate crystals which were then filtered and washed with water. The crystals were dried and then purified by silica gel chromatography (ethyl acetate:chloroform=1:9→1:4→1:2), to give the title compound as colorless crystals. The yield was 3.80 g (46.6%).

1. temperatureThe mixture was heated for 8 hours
2. temperatureunder reflux
3. temperaturecooled to room temperature
4. temperatureThe reaction mixture was heated at 120° C. for 3 hours
5. stirringwith stirring
6. temperaturecooled to 50° C.
7. customAfter the reaction solution was partitioned
8. extractionthe aqueous layer was extracted twice with chloroform
9. washwashed twice with water
10. dry with materialdried over anhydrous magnesium sulfate
11. concentrationconcentrated under reduced pressure
12. dissolutionThe residues were dissolved in acetonitrile (100 ml)
13. additionwas added
14. stirringThe reaction solution was stirred at room temperature for 2 hours
15. customto precipitate crystals which
16. filtrationwere then filtered
17. washwashed with water
18. customThe crystals were dried
19. custompurified by silica gel chromatography (ethyl acetate:chloroform=1:9→1:4→1:2)

ORD-Eintrag

ord-2b0089b043b542b9ae85147edfa0ad8c

Quelldatensatz

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07816526B2