2,4-Dimethoxybenzenesulfonyl chloride → HCID 67160335, compound

HRID 2408816Notes

Reaction equation

HRID 2408816 reaction equation
[NH2:1][C:2]1([C:14]2[C:15]([O:20][CH2:21][CH3:22])=[N:16][CH:17]=[CH:18][CH:19]=2)[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[NH:4][C:3]1=[O:13].CC(C)([O-])C.[K+].[CH3:29][O:30][C:31]1[CH:36]=[C:35]([O:37][CH3:38])[CH:34]=[CH:33][C:32]=1[S:39](Cl)(=[O:41])=[O:40].ClCCl.CO>CN(C)C=O>[NH2:1][C:2]1([C:14]2[C:15]([O:20][CH2:21][CH3:22])=[N:16][CH:17]=[CH:18][CH:19]=2)[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[N:4]([S:39]([C:32]2[CH:33]=[CH:34][C:35]([O:37][CH3:38])=[CH:36][C:31]=2[O:30][CH3:29])(=[O:41])=[O:40])[C:3]1=[O:13]

Participants

6

Reactant 4

HCID 27346262,4-Dimethoxybenzenesulfonyl chlorideHCID 21226129Dichloromethane methanolHCID 23665647Potassium tert-butoxideHCID 67160856HCID 67160856, compound

Product 1

HCID 67160335HCID 67160335, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

3.54 g (12.03 mmol) of 3-amino-3-(2-ethoxypyridin-3-yl)-2-oxoindoline-5-carbonitrile were dissolved in 80 ml of anhydrous dimethylformamide (dried over molecular sieve). Under an atmosphere of nitrogen and with cooling using an ice-bath, 1.49 g (13.23 mmol) of potassium tert-butoxide were added a little at a time. The colour of the reaction mixture changed, and the brown solution was stirred at 0° C. for another hour to ensure that the deprotonation proceeded to completion. At low temperature, 3.16 g (13.23 mmol) 2,4-dimethoxybenzenesulphonyl chloride were added, and the mixture was stirred at 0° C. for another two hours. The course of the reaction was monitored by TLC (silica gel, dichloromethane/methanol in a ratio of 9:1). The reaction mixture was poured into ice-water and then extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride solution and dried over magnesium sulphate, and the solvent was evaporated. The residue was suspended in diethyl ether and stirred until the product precipitated as a solid and could be removed by filtration. After removal of the solvent, the mother liquor was once more treated with diethyl ether (2×) until finally, after drying, 4.67 g (9.44 mmol, 79%) of the desired 3-amino-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-ethoxypyridin-3-yl)-2-oxoindoline-5-carbonitrile were obtained as a solid substance.

Workup

  1. temperatureUnder an atmosphere of nitrogen and with cooling
  2. stirringthe mixture was stirred at 0° C. for another two hours
  3. extractionextracted with ethyl acetate
  4. washThe organic phase was washed with saturated sodium chloride solution
  5. dry with materialdried over magnesium sulphate
  6. customthe solvent was evaporated
  7. stirringstirred until the product
  8. customprecipitated as a solid
  9. customcould be removed by filtration
  10. customAfter removal of the solvent
  11. additionthe mother liquor was once more treated with diethyl ether (2×) until finally,
  12. customafter drying

Sources & evidence

ORD record
ord-4026338884e7442294c4ac3edd94ea5c
Source dataset
uspto-grants-2014_08
Patent number
US08815868B2

Reaction notes

Loading…