Dimethylformamide → 3-Chloro-6-[(2,2-dimethyl-3-sulfamoylpropyl)oxy]imidazo[1,2-b]pyridazine

HRID 465946Notes

Reaction equation

HRID 465946 reaction equation
[OH:1][CH2:2][C:3]([CH3:10])([CH3:9])[CH2:4][S:5]([NH2:8])(=[O:7])=[O:6].[H-].[Na+].[Cl:13][C:14]1[CH:15]=[CH:16][C:17]2[N:18](C=CN=2)[N:19]=1.C[N:24]([CH:26]=O)[CH3:25]>>[Cl:13][C:14]1[N:19]2[N:18]=[C:17]([O:1][CH2:2][C:3]([CH3:10])([CH3:9])[CH2:4][S:5](=[O:7])(=[O:6])[NH2:8])[CH:16]=[CH:15][C:25]2=[N:24][CH:26]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 138828Imidazo(1,2-b)pyridazine, 6-chloro-HCID 103296873-Hydroxy-2,2-dimethylpropane-1-sulfonamide

Product 1

HCID 108294073-Chloro-6-[(2,2-dimethyl-3-sulfamoylpropyl)oxy]imidazo[1,2-b]pyridazine

Conditions

Temperature
70 °C

Procedure

To a solution of 1.67 g of 3-hydroxy-2,2-dimethyl-1-propanesulfonamide in 30 ml of DMF was added 0.8 g of sodium hydride, followed by heating at 70° C. for an hour. The mixture to which 1.88 g of 6-chloroimidazo [1,2-b]pyridazine was added was heated for 4.5 hours. The reaction mixture was distilled to remove the solvent under reduced pressure and 50 ml of ice-water was added to the residue. The mixture was adjusted to pH 6.0 with 1N-hydrochloric acid and then extracted with tetrahydrofuran and ethyl acetate (1:1). The extract was dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent. The residue was subjected to a silica gel column chromatography, eluting with chloroform and methanol (20:1). The corresponding combined fractions were concentrated to obtain 1.56 g of the title compound.

Workup

  1. temperaturewas heated for 4.5 hours
  2. distillationThe reaction mixture was distilled
  3. customto remove the solvent under reduced pressure and 50 ml of ice-water
  4. additionwas added to the residue
  5. extractionextracted with tetrahydrofuran and ethyl acetate (1:1)
  6. dry with materialThe extract was dried over anhydrous magnesium sulfate
  7. distillationdistilled under reduced pressure
  8. customto remove the solvent
  9. washeluting with chloroform and methanol (20:1)
  10. concentrationThe corresponding combined fractions were concentrated

Sources & evidence

ORD record
ord-239318e44645457da53e21c864e72c8e
Source dataset
uspto-grants-1992_10
Patent number
US05155108

Reaction notes

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