1-Chloro-2-(diethylamine)ethane hydrochloride → 1-(4-chlorophenyl)-3-[2-(diethylamino)ethyl]-2-oxo-7-(trifluoromethyl)-2,3-dihydro-1H-benzimidazole-5-carboxamide trifluoroacetate

HRID 495646ノート

反応式

HRID 495646 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[C:13]([C:19]([F:22])([F:21])[F:20])=[CH:14][C:15]([C:17]#[N:18])=[CH:16][C:11]=3[NH:10][C:9]2=[O:23])=[CH:4][CH:3]=1.[H-].[Na+].[CH3:26][CH2:27][N:28]([CH2:31][CH2:32]Cl)[CH2:29][CH3:30].Cl.[C:35](=[O:38])(O)[O-:36].[Na+]>CN(C)C=O.C(N(CC)CC)C>[F:20][C:19]([F:22])([F:21])[C:35]([OH:36])=[O:38].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[C:13]([C:19]([F:21])([F:20])[F:22])=[CH:14][C:15]([C:17]([NH2:18])=[O:36])=[CH:16][C:11]=3[N:10]([CH2:26][CH2:27][N:28]([CH2:31][CH3:32])[CH2:29][CH3:30])[C:9]2=[O:23])=[CH:4][CH:3]=1

参加物

7

反応物 4

HCID 133631-Chloro-2-(diethylamine)ethane hydrochlorideHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 223273651-(4-chlorophenyl)-2-oxo-7-(trifluoromethyl)-2,3-dihydro-1H-benzimidazole-5-carbonitrile

生成物 1

HCID 98080931-(4-chlorophenyl)-3-[2-(diethylamino)ethyl]-2-oxo-7-(trifluoromethyl)-2,3-dihydro-1H-benzimidazole-5-carboxamide trifluoroacetate収率 30%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8471Triethylamine溶媒

実験手順

1-(4-Chlorophenyl)-2-oxo-7-(trifluoromethyl)-2,3-dihydro-1H-benzimidazole-5-carbonitrile (0.1767 g) was dissolved in N,N-dimethylformamide (5 ml), and to the solution was added sodium hydride (27.2 mg). The mixture was stirred at room temperature for 5 minutes. To the mixture were added 2-chlorotriethylamine hydrochloride (117.1 mg) and triethylamine (0.109 ml), and the mixture was stirred at 60-70° C. for 1 hour. After allowing to cool, to the reaction mixture was added saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The resultant residue was dissolved in 2-methyl-2-propanol (15 ml) and heated at 50° C. To the solution was added powdered potassium hydroxide (0.7340 g), and the mixture was stirred for 1 hour. After allowing to cool, to the reaction mixture was added saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The resultant residue was purified by HPLC using condition 1 to give the title compound (90.4 mg, 30%).

後処理

  1. stirringthe mixture was stirred at 60-70° C. for 1 hour
  2. temperatureto cool, to the reaction mixture
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. dissolutionThe resultant residue was dissolved in 2-methyl-2-propanol (15 ml)
  8. temperatureheated at 50° C
  9. additionTo the solution was added powdered potassium hydroxide (0.7340 g)
  10. stirringthe mixture was stirred for 1 hour
  11. temperatureto cool, to the reaction mixture
  12. additionwas added saturated aqueous sodium bicarbonate solution
  13. extractionthe mixture was extracted with ethyl acetate
  14. washThe organic layer was washed with saturated brine
  15. dry with materialdried over anhydrous sodium sulfate
  16. concentrationconcentrated in vacuo
  17. customThe resultant residue was purified by HPLC

出典と根拠

ORDレコード
ord-23b03dd0d7a4489fa197cf057623e477
出典データセット
uspto-grants-2005_09
特許番号
US06939887B2

反応ノート

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