Hexamethyldisilazane → 5-(5-(4-Bromo-3-fluorophenyl)-4-ethyl-3-trifluoromethyl-1H-pyrazol-1-yl)-2-pyridinesulfonamide

To a stirred solution of hexamethyldisilazane (2.5 ml, 11.75 mmol) in tetrahydrofuran (25 ml) was added n-butyllithium (7.5 ml, 11.75 mmol) dropwise at 0° C. under nitrogen. The reaction mixture was stirred at room temperature for 30 min. Then cooled to −78° C., to the mixture was added a solution of 1-(4-bromo-3-fluorophenyl)-1-butanone (2.4 g, 9.79 mmol) in tetrahydrofuran (12 ml) dropwise and stirred at rt for 1 h. Then 1-trifluoroacetylimidazole (1.3 ml, 11.75 mmol) was added to the mixture at same temperature, the mixture was stirred at rt for 5 h. This was quenched by water and the pH was adjusted to pH 4-5, extracted with ethyl acetate. The extracts was dried (MgSO4) and concentrated. This was purified on silica gel eluting with ethyl acetate/hexane (1:20/1:15) to afford 2.7 g (80.9%) as a yellow oil. A mixture of 1-(4-bromo-3-fluorophenyl)-2-ethyl-4,4,4-trifluoro-1,3-butanedione (1.5 g, 4.40 mmol) and 5-hydrazino-2-pyridinesulfonamide hydrochloride (1.28 g, 5.72 mmol) in ethanol (60 ml) was stirred at reflux for 3 h. After cooling, the solvent was removed and the residue was diluted with ethyl acetate, washed with water. The extracts was dried (MgSO4) and concentrated. This was purified on silica gel eluting with ethyl acetate/hexane (1:10/1:5/1:4) to afford 1.64 g (75.6%) of the titled compound as a white amorphous.

1. temperatureThen cooled to −78° C., to the mixture
2. stirringstirred at rt for 1 h
3. stirringthe mixture was stirred at rt for 5 h
4. customThis was quenched by water
5. extractionextracted with ethyl acetate
6. dry with materialThe extracts was dried (MgSO4)
7. concentrationconcentrated
8. customThis was purified on silica gel eluting with ethyl acetate/hexane (1:20/1:15)
9. customto afford 2.7 g (80.9%) as a yellow oil
10. stirringwas stirred
11. temperatureat reflux for 3 h
12. temperatureAfter cooling
13. customthe solvent was removed
14. additionthe residue was diluted with ethyl acetate
15. washwashed with water
16. dry with materialThe extracts was dried (MgSO4)
17. concentrationconcentrated
18. customThis was purified on silica gel eluting with ethyl acetate/hexane (1:10/1:5/1:4)

ORD-Eintrag

ord-30d6cd41fc3e4a6aa0cc345b18bb3208

Quelldatensatz

uspto-grants-2003_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06603008B1