Dimethylacetamide → N-{6-Chloro-2-[5-(hydroxymethyl)-1,3-thiazol-2-yl]-1H-indol-7-yl}thiophene-2-sulfonamide

HRID 1851614Notes

Reaction equation

HRID 1851614 reaction equation
[Cl:1][C:2]1[C:10]([NH:11][S:12]([C:15]2[S:16][CH:17]=[CH:18][CH:19]=2)(=[O:14])=[O:13])=[C:9]2[C:5]([CH:6]=[C:7]([C:20](=[S:22])[NH2:21])[NH:8]2)=[CH:4][CH:3]=1.Br[CH:24]([CH:27]=O)[CH:25]=[O:26].CN(C)C(=O)C>O>[Cl:1][C:2]1[C:10]([NH:11][S:12]([C:15]2[S:16][CH:17]=[CH:18][CH:19]=2)(=[O:14])=[O:13])=[C:9]2[C:5]([CH:6]=[C:7]([C:20]3[S:22][C:24]([CH2:25][OH:26])=[CH:27][N:21]=3)[NH:8]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 31374DimethylacetamideHCID 749452-BromopropanedialHCID 574760296-chloro-7-[(2-thienylsulfonyl)amino]-1H-indole-2-carbothioamide

Product 1

HCID 57901643N-{6-Chloro-2-[5-(hydroxymethyl)-1,3-thiazol-2-yl]-1H-indol-7-yl}thiophene-2-sulfonamideYield 55%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 6-chloro-7-[(2-thienylsulfonyl)amino]-1H-indole-2-carbothioamide (0.75 g), bromomalonaldehyde (0.45 g) and N,N-dimethylacetamide (10 mL) was stirred at 90° C. for 3 hr. Water was added to the reaction mixture, and the obtained crystals were filtrated, washed with water and dried. To a mixture of the obtained crystals, tetrahydrofuran (10 mL) and methanol (5 mL) was added sodium borohydride (84 mg) at 0° C., and the mixture was stirred at the same temperature for 30 min. To the reaction mixture was added 10% aqueous citric acid solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography and the title compound (0.46 g, yield 55%) was obtained as pale-yellow crystals from a fraction eluted with tetrahydrofuran-hexane (3:1, volume ratio). melting point 197-199° C.

Workup

  1. filtrationthe obtained crystals were filtrated
  2. washwashed with water
  3. customdried
  4. additionTo a mixture of the obtained crystals, tetrahydrofuran (10 mL) and methanol (5 mL)
  5. additionwas added sodium borohydride (84 mg) at 0° C.
  6. stirringthe mixture was stirred at the same temperature for 30 min
  7. additionTo the reaction mixture was added 10% aqueous citric acid solution
  8. extractionthe mixture was extracted with ethyl acetate
  9. washThe ethyl acetate layer was washed with saturated brine
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-22c87ae0b01947deaf7e96af3f802e44
Source dataset
uspto-grants-2015_02
Patent number
US08957070B2

Reaction notes

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