Hydrochloric Acid → 1-Butanesulfonamide, 2-ethyl-2-(((7-methyl(1,2,4)triazolo(1,5-b)pyridazin-6-yl)oxy)methyl)-

HRID 274268

Reaction equation

HRID 274268 reaction equation
[H-].[Na+].[OH:3][CH2:4][C:5]([CH2:13][CH3:14])([CH2:11][CH3:12])[CH2:6][S:7]([NH2:10])(=[O:9])=[O:8].Cl[C:16]1[C:17]([CH3:25])=[CH:18][C:19]2[N:20]([N:22]=[CH:23][N:24]=2)[N:21]=1.Cl>CN(C)C=O.O>[CH2:11]([C:5]([CH2:13][CH3:14])([CH2:6][S:7](=[O:8])(=[O:9])[NH2:10])[CH2:4][O:3][C:16]1[C:17]([CH3:25])=[CH:18][C:19]2[N:20]([N:22]=[CH:23][N:24]=2)[N:21]=1)[CH3:12]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 105597653-Hydroxy-2,2-diethyl-1-propanesulfonamideHCID 118051586-Chloro-7-methyl-[1,2,4]triazolo[1,5-b]pyridazine

Product 1

HCID 30737861-Butanesulfonamide, 2-ethyl-2-(((7-methyl(1,2,4)triazolo(1,5-b)pyridazin-6-yl)oxy)methyl)-Yield 30.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

In 20 ml of dimethylformamide was suspended 0.672 g of 60% sodium hydride in oil, followed by addition of 1.72 g of 3-hydroxy-2,2-diethyl-1-propanesulfonamide and the mixture was stirred under reduced pressure at room temperature for 1 hour. To this was added 1.35 g of 6-chloro-7-methyl[1,2,4]triazolo[1,5-b]pyridazine and the mixture was stirred under a nitrogen atmosphere at room temperature for 2 hours. Following addition of 70 ml of iced water, the reaction mixture was adjusted to pH 6 with 5N-hydrochloric acid and extracted with 3 portions of ethyl acetate-tetrahydrofuran (2:1). The extract was washed with saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure and the residue was subjected to silica gel column chromatography, elution being carried out with dichloromethane-ethyl acetate-methanol (10:10:1). The fractions containing the object product were pooled and concentrated, and 50 ml of 5N-hydrochloric acid was added to the residue. The mixture was refluxed for 30 minutes. After cooling, the mixture was concentrated under reduced pressure and the residue was diluted with water and aqueous solution of sodium hydrogen carbonate and extracted with 3 portions of ethyl acetate-tetrahydrofuran (1:1). The extract was washed with saturated aqueous solution of sodium chloride once, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from hot ethanol to provide 0.79 g of the title compound. m.p. 189°-192° C.

Workup

  1. stirringthe mixture was stirred under a nitrogen atmosphere at room temperature for 2 hours
  2. extractionextracted with 3 portions of ethyl acetate-tetrahydrofuran (2:1)
  3. washThe extract was washed with saturated aqueous solution of sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationThe solvent was then distilled off under reduced pressure
  6. washthe residue was subjected to silica gel column chromatography, elution
  7. additionThe fractions containing the object product
  8. concentrationconcentrated
  9. addition50 ml of 5N-hydrochloric acid was added to the residue
  10. temperatureThe mixture was refluxed for 30 minutes
  11. temperatureAfter cooling
  12. concentrationthe mixture was concentrated under reduced pressure
  13. additionthe residue was diluted with water and aqueous solution of sodium hydrogen carbonate
  14. extractionextracted with 3 portions of ethyl acetate-tetrahydrofuran (1:1)
  15. washThe extract was washed with saturated aqueous solution of sodium chloride once
  16. dry with materialdried over anhydrous magnesium sulfate
  17. concentrationconcentrated under reduced pressure
  18. customThe residue was recrystallized from hot ethanol

Sources & evidence

ORD record
ord-a7d37d205d4f41209bc47db64fd1e963
Source dataset
uspto-grants-1995_02
Patent number
US05389633

Linked notes

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