Sodium hydride → 6-(2,2-Dimethyl-3-sulfamoyl-1-propoxy)-7-methylimidazo[1,2-b]pyridazine

HRID 2395960Notes

Reaction equation

HRID 2395960 reaction equation
[H-].[Na+].[OH:3][CH2:4][C:5]([CH3:12])([CH3:11])[CH2:6][S:7]([NH2:10])(=[O:9])=[O:8].Cl[C:14]1[C:15]([CH3:23])=[CH:16][C:17]2[N:18]([CH:20]=[CH:21][N:22]=2)[N:19]=1>CN(C)C=O>[CH3:11][C:5]([CH3:12])([CH2:6][S:7](=[O:9])(=[O:8])[NH2:10])[CH2:4][O:3][C:14]1[C:15]([CH3:23])=[CH:16][C:17]2[N:18]([CH:20]=[CH:21][N:22]=2)[N:19]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 103296873-Hydroxy-2,2-dimethylpropane-1-sulfonamideHCID 122483366-Chloro-7-methylimidazo[1,2-b]pyridazine

Product 1

HCID 108040336-(2,2-Dimethyl-3-sulfamoyl-1-propoxy)-7-methylimidazo[1,2-b]pyridazine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1.12 g of 60% oily sodium hydride was suspended in 25 ml of dimethylformamide. To this suspension, 1.51 g of 3-hydroxy-2,2-dimethyl-1-propanesulfonamide was added, followed by stirring at room temperature (15° to 20° C.) under reduced pressure for i hour. To this mixture was added 1.51 g of 6-chloro-7-methylimidazo[1,2-b]pyridazine, followed by stirring at 60° C. for 2 hours. After dimethylformamide was distilled off underreduced pressure, ice water was added to the residue, which was subsequently adjusted to pH 6 by the addition of 5 N hydrochloric acid andthen extracted with tetrahydrofuran. The extract was washed with 20 ml of saturated saline and then dried over magnesium sulfate. After the solvent was distilled off under reduced pressure, the residue was subjected to silica gel column chromatography and eluted with dichloromethane-ethyl acetate-methanol (5:5:1). The fraction containing the desired product was concentrated and recrystallized by the addition of ethyl ether-ethyl acetate (5:1). The resulting crystal was collected by filtration, to yield0.522 g of the title compound.

Workup

  1. stirringby stirring at 60° C. for 2 hours
  2. distillationAfter dimethylformamide was distilled off underreduced pressure, ice water
  3. additionwas added to the residue, which
  4. additionwas subsequently adjusted to pH 6 by the addition of 5 N hydrochloric acid
  5. extractionandthen extracted with tetrahydrofuran
  6. washThe extract was washed with 20 ml of saturated saline
  7. dry with materialdried over magnesium sulfate
  8. distillationAfter the solvent was distilled off under reduced pressure
  9. washeluted with dichloromethane-ethyl acetate-methanol (5:5:1)
  10. additionThe fraction containing the desired product
  11. concentrationwas concentrated
  12. customrecrystallized by the addition of ethyl ether-ethyl acetate (5:1)
  13. filtrationThe resulting crystal was collected by filtration, to yield0.522 g of the title compound

Sources & evidence

ORD record
ord-eb08811c08d745f79940679278d8dba4
Source dataset
uspto-grants-1996_02
Patent number
US05491145

Reaction notes

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