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

HRID 504624Notes

Reaction equation

HRID 504624 reaction equation
[CH3:1][N:2]([S:15]([C:18]1[S:19][CH:20]=[CH:21][CH:22]=1)(=[O:17])=[O:16])[C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12](=[S:14])[NH2:13])=[CH:8]2.Br[CH:24]([CH:27]=O)[CH:25]=[O:26].CN(C)C(=O)C>O>[OH:26][CH2:25][C:24]1[S:14][C:12]([C:9]2[NH:10][C:11]3[C:7]([CH:8]=2)=[CH:6][CH:5]=[CH:4][C:3]=3[N:2]([CH3:1])[S:15]([C:18]2[S:19][CH:20]=[CH:21][CH:22]=2)(=[O:17])=[O:16])=[N:13][CH:27]=1

Participants

5

Reactant 3

HCID 31374DimethylacetamideHCID 749452-BromopropanedialHCID 574759607-[methyl(2-thienylsulfonyl)amino]-1H-indole-2-carbothioamide

Product 1

HCID 57475965N-{2-[5-(hydroxymethyl)-1,3-thiazol-2-yl]-1H-indol-7-yl}-N-methylthiophene-2-sulfonamideYield 39%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 7-[methyl(2-thienylsulfonyl)amino]-1H-indole-2-carbothioamide (1.00 g), bromomalonaldehyde (0.86 g) and N,N-dimethylacetamide (8 ml) was stirred at 80° C. for 3 hr. Water was added to the reaction mixture, and the resulting crystals were collected by filtration, washed with water, and dried. The obtained crystals were dissolved in tetrahydrofuran (8 ml) and methanol (8 ml), sodium borohydride (63 mg) was added at 0° C., and the mixture was stirred at 0° C. for 1 hr. The reaction mixture was concentrated, 10% aqueous citric acid solution was added, and the resulting crystals were collected by filtration, washed with water, and dried. The crystals were subjected to silica gel column chromatography to give the title compound (0.43 g, yield 39%) as colorless crystals from a fraction eluted with ethyl acetate-hexane (3:1, volume ratio). melting point 201-202° C.

Workup

  1. filtrationthe resulting crystals were collected by filtration
  2. washwashed with water
  3. customdried
  4. dissolutionThe obtained crystals were dissolved in tetrahydrofuran (8 ml)
  5. additionmethanol (8 ml), sodium borohydride (63 mg) was added at 0° C.
  6. stirringthe mixture was stirred at 0° C. for 1 hr
  7. concentrationThe reaction mixture was concentrated
  8. addition10% aqueous citric acid solution was added
  9. filtrationthe resulting crystals were collected by filtration
  10. washwashed with water
  11. customdried

Sources & evidence

ORD record
ord-f7ad2e9df6f3458db89d493033e02be4
Source dataset
uspto-grants-2010_08
Patent number
US07777047B2

Reaction notes

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