Imidazole → N-[3-cyano-4-(4-hydroxypiperidin-1-yl)phenyl]-N-methylbenzo[b]thiophene-2-carboxamide

HRID 2216410ノート

反応式

HRID 2216410 の反応式
[C:1]([C:3]1[CH:4]=[C:5]([NH:16][C:17]([C:19]2[S:23][C:22]3[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=3[CH:20]=2)=[O:18])[CH:6]=[CH:7][C:8]=1[N:9]1[CH2:14][CH2:13][CH:12]([OH:15])[CH2:11][CH2:10]1)#[N:2].[C:28]([Si](Cl)(C)C)(C)(C)C.N1C=CN=C1.CN(C)C=O>O>[C:1]([C:3]1[CH:4]=[C:5]([N:16]([CH3:28])[C:17]([C:19]2[S:23][C:22]3[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=3[CH:20]=2)=[O:18])[CH:6]=[CH:7][C:8]=1[N:9]1[CH2:14][CH2:13][CH:12]([OH:15])[CH2:11][CH2:10]1)#[N:2]

参加物

6

反応物 4

HCID 795ImidazoleHCID 6228DimethylformamideHCID 28928tert-Butyldimethylsilyl chlorideHCID 21942334HCID 21942334、化合物

生成物 1

HCID 21942376N-[3-cyano-4-(4-hydroxypiperidin-1-yl)phenyl]-N-methylbenzo[b]thiophene-2-carboxamide収率 38.6%

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

N-[3-Cyano-4-(4-hydroxypiperidin-1-yl)phenyl]benzo[b]thiophene-2-carboxamide (2.0 g) obtained in Example 12, tertiary butyldimethylsilyl chloride (0.9 g) and imidazole (0.4 g) were added to dimethylformamide (20 ml) and the mixture was stirred at room temperature for 12 hr. Then the reaction mixture was treated with water and the organic layer was extracted with ethyl acetate. The extract was washed with aqueous sodium hydrogencarbonate solution and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was dissolved in dimethylformamide. Under ice-cooling, sodium hydride (60% contained, 0.2 g) (was added and the mixture was stirred for 1 hr and methyl iodide (0.6 g) was added. The mixture was further stirred for 1 hr. The reaction mixture was treated with water and the organic layer was extracted with toluene. The extract was washed with water and the solvent was evaporated under reduced pressure. To the residue were added tetrabutylammonium fluoride (0.93 g) and tetrahydrofuran(15 ml) and the mixture was stirred at 60° C. for 4.5 hr. Then the solvent was evaporated and the residue was separated and purified by silica gel column chromatography (mobile phase: chloroform) to give the title compound (0.8 g). melting point: 211-212° C.

後処理

  1. extractionthe organic layer was extracted with ethyl acetate
  2. washThe extract was washed with aqueous sodium hydrogencarbonate solution
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. dissolutionthe obtained residue was dissolved in dimethylformamide
  6. temperatureUnder ice-cooling
  7. additionsodium hydride (60% contained, 0.2 g) (was added
  8. stirringthe mixture was stirred for 1 hr
  9. additionmethyl iodide (0.6 g) was added
  10. stirringThe mixture was further stirred for 1 hr
  11. additionThe reaction mixture was treated with water
  12. extractionthe organic layer was extracted with toluene
  13. washThe extract was washed with water
  14. customthe solvent was evaporated under reduced pressure
  15. additionTo the residue were added tetrabutylammonium fluoride (0.93 g) and tetrahydrofuran(15 ml)
  16. stirringthe mixture was stirred at 60° C. for 4.5 hr
  17. customThen the solvent was evaporated
  18. customthe residue was separated
  19. custompurified by silica gel column chromatography (mobile phase: chloroform)

出典と根拠

ORDレコード
ord-3c92f8f32ce9492faa8c210ff6be8030
出典データセット
uspto-grants-2006_09
特許番号
US07112594B2

反応ノート

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