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

HRID 2238906Notes

Reaction equation

HRID 2238906 reaction equation
[Cl:1][C:2]1[C:10]([N:11]([CH3:20])[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:21](=[S:23])[NH2:22])[NH:8]2)=[CH:4][CH:3]=1.Br[CH:25]([CH:28]=O)[CH:26]=[O:27].CN(C)C(=O)C>O>[Cl:1][C:2]1[C:10]([N:11]([CH3:20])[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:21]3[S:23][C:25]([CH2:26][OH:27])=[CH:28][N:22]=3)[NH:8]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 31374DimethylacetamideHCID 749452-BromopropanedialHCID 574760336-chloro-7-[methyl(2-thienylsulfonyl)amino]-1H-indole-2-carbothioamide

Product 1

HCID 57503208N-{6-chloro-2-[5-(hydroxymethyl)-1,3-thiazol-2-yl]-1H-indol-7-yl}-N-methylthiophene-2-sulfonamideYield 55.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 6-chloro-7-[methyl(2-thienylsulfonyl)amino]-1H-indole-2-carbothioamide (0.60 g), bromomalonaldehyde (0.38 g) and N,N-dimethylacetamide (10 ml) was stirred at 90° C. for 3 hr. Water was added to the reaction mixture, and the resulting crystals were collected by filtration, washed with water, and dried. To a mixture of the obtained crystals, tetrahydrofuran (10 ml) and methanol (5 ml) was added sodium borohydride (70 mg) at 0° C., and the mixture was stirred at the same temperature for 30 min. 10% Aqueous citric acid solution was added to the reaction mixture, 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 to give the title compound (0.38 g, yield 54%) as pale-yellow crystals from a fraction eluted with tetrahydrofuran-hexane (2:1, volume ratio). melting point 214-215° C.

Workup

  1. filtrationthe resulting crystals were collected by filtration
  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 (70 mg) at 0° C.
  6. stirringthe mixture was stirred at the same temperature for 30 min
  7. addition10% Aqueous citric acid solution was added to the reaction mixture
  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-36e572af561d4843ae9523d82c92939f
Source dataset
uspto-grants-2010_05
Patent number
US07718798B2

Reaction notes

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