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

HRID 1851618ノート

反応式

HRID 1851618 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
90 °C

実験手順

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 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 (70 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 (0.38 g, yield 45%) was obtained as pale-yellow crystals from a fraction eluted with tetrahydrofuran-hexane (2:1, volume ratio). melting point 214-215° C.

後処理

  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 (70 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

出典と根拠

ORDレコード
ord-0267f16d87be435a8275cc0577aff988
出典データセット
uspto-grants-2015_02
特許番号
US08957070B2

反応ノート

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