Sodium hydride → 6-(2,2-Dimethyl-3-sulfamoyl-1-propoxy)-7,8,9,10-tetrahydroimidazo[2,1-a]phthalazine

HRID 2395962Notes

Reaction equation

HRID 2395962 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:23]2[CH2:22][CH2:21][CH2:20][CH2:19][C:18]=2[C:17]2=[N:24][CH:25]=[CH:26][N:16]2[N:15]=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:23]2[CH2:22][CH2:21][CH2:20][CH2:19][C:18]=2[C:17]2=[N:24][CH:25]=[CH:26][N:16]2[N:15]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 103296873-Hydroxy-2,2-dimethylpropane-1-sulfonamideHCID 131789756-Chloro-7,8,9,10-tetrahydroimidazo[2,1-a]phthalazine

Product 1

HCID 108069496-(2,2-Dimethyl-3-sulfamoyl-1-propoxy)-7,8,9,10-tetrahydroimidazo[2,1-a]phthalazineYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.59 g of 60% oily sodium hydride was suspended in 20 ml of dimethylformamide. To this suspension, 1.18 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 30 minutes. To this mixture was added 1.35 g of 6-chloro-7,8,9,10-tetrahydroimidazo[2,1-a]phthalazine, followed by stirring at 60° C. for 1.5 hours. After dimethylformamide was distilled off under reduced pressure, ice water was added to the residue, which was subsequently adjusted to pH 6 by the addition of 5 N hydrochloric acid and then extracted with ethyl acetate-tetrahydrofuran (2:1). 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 (20:20:1). The fraction containing the desired product was concentrated, and ethyl ether was added to separate a crystal, which was collected by filtration, to yield 0.66 g of the title compound.

Workup

  1. stirringby stirring at 60° C. for 1.5 hours
  2. distillationAfter dimethylformamide was distilled off under reduced 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. extractionextracted with ethyl acetate-tetrahydrofuran (2:1)
  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 (20:20:1)
  10. additionThe fraction containing the desired product
  11. concentrationwas concentrated
  12. additionethyl ether was added
  13. customto separate a crystal, which
  14. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-a33ac3ffa4204888ba6dd273f478077d
Source dataset
uspto-grants-1996_02
Patent number
US05491145

Reaction notes

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