Ammonia → 1-Benzenesulfonyl-5-methythioindole-2-carboxamide

HRID 1432207Notes

Reaction equation

HRID 1432207 reaction equation
C1(S([N:10]2C3C(=CC(SC)=CC=3)C=C2)(=O)=O)C=CC=CC=1.C(=O)=O.Cl.[C:25]1([S:31]([N:34]2[C:42]3[C:37](=[CH:38][C:39]([CH3:43])=[CH:40][CH:41]=3)[CH:36]=[C:35]2[C:44](O)=[S:45])(=[O:33])=[O:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(Cl)(=O)OCC.N>O1CCCC1.C([Li])CCC.C(OCC)(=O)C.C(N(CC)CC)C.CN(C)P(=O)(N(C)C)N(C)C>[C:25]1([S:31]([N:34]2[C:42]3[C:37](=[CH:38][C:39]([CH3:43])=[CH:40][CH:41]=3)[CH:36]=[C:35]2[C:44]([NH2:10])=[S:45])(=[O:33])=[O:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

12

Reactant 6

HCID 222AmmoniaHCID 280Carbon DioxideHCID 313Hydrochloric AcidHCID 10928Ethyl chloroformateHCID 225044271-Benzenesulfonyl-5-methylthioindoleHCID 178422521HCID 178422521, compound

Product 1

HCID 874593601-Benzenesulfonyl-5-methythioindole-2-carboxamideYield 49.6%

Reagents, catalysts & solvents 5

HCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolventHCID 12679HexamethylphosphoramideSolventHCID 178418339ButyllithiumSolvent

Procedure

To a solution of 1-benzenesulfonyl-5-methylthioindole (2 g) in tetrahydrofuran (70 ml), n-butyl lithium (5 ml, 1.59M) was added dropwise at −78° C. under nitrogen atmosphere, the mixture was stirred at the same temperature for 30 minutes, followed by drwopise addition of hexamethylphosphoric triamide (2.3 ml), and the mixture was stirred at the same temperature for 10 minutes. The stirred reaction mixture was heated to 15 to 30° C. over 30 minutes while carbon dioxide gas was blown therein at −78° C. To the reaction mixture was added 1N hydrochloric acid and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with water and dried. The solvent was distilled off under reduced pressure. The resulting residue was separated using silica gel column chromatography (dichloromethane methanol:acetic acid=100:5:1) to obtain a crude product (4 g). To absolution of the resulting crude 1-benzenesulfonyl-5-methylthioindole-2-carboxylic acid (4 g) in tetrahydrofuran (70 ml) was added triethylamine (1.84 ml) and ethyl chlorocarbonate (1 ml) under ice-cooling, the mixture was stirred at the same temperature for 30 minutes, followed by addition of aqueous ammonia (2 ml) at the same temperature. The mixture was stirred for 15 minutes. The reaction mixture was diluted with ethyl acetate, washed with water and dried. The solvent was distilled off under reduced pressure. The resulting residue was recrystallized (hexane/ethyl acetate) to obtain 1.08 g of the desired product as a white powder.

Workup

  1. stirringthe mixture was stirred at the same temperature for 10 minutes
  2. customThe stirred reaction mixture
  3. customat −78° C
  4. extractionthe resulting mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with water
  6. customdried
  7. distillationThe solvent was distilled off under reduced pressure
  8. customThe resulting residue was separated
  9. customto obtain a crude product (4 g)
  10. temperaturecooling
  11. stirringthe mixture was stirred at the same temperature for 30 minutes
  12. stirringThe mixture was stirred for 15 minutes
  13. washwashed with water
  14. customdried
  15. distillationThe solvent was distilled off under reduced pressure
  16. customThe resulting residue was recrystallized (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-5a03c0b9608b48e6a4503db02395df69
Source dataset
uspto-grants-2009_11
Patent number
US07612070B2

Reaction notes

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