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

HRID 495616Notes

Reaction equation

HRID 495616 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]2[C:13]([C:19]([F:22])([F:21])[F:20])=[CH:14][C:15]([C:17]#[N:18])=[CH:16][C:11]=2[NH:10][C:9]1=[O:23].[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][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]2[C:13]([C:19]([F:20])([F:21])[F:22])=[CH:14][C:15]([C:17]([NH2:18])=[O:36])=[CH:16][C:11]=2[N:10]([CH2:26][CH2:27][N:28]([CH2:31][CH3:32])[CH2:29][CH3:30])[C:9]1=[O:23]

Participants

7

Reactant 4

HCID 133631-Chloro-2-(diethylamine)ethane hydrochlorideHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 223273971-(2-chlorophenyl)-2-oxo-7-(trifluoromethyl)-2,3-dihydro-1H-benzimidazole-5-carbonitrile

Product 1

HCID 223273931-(2-chlorophenyl)-3-[2-(diethylamino)ethyl]-2-oxo-7-(trifluoromethyl)-2,3-dihydro-1H-benzimidazole-5-carboxamide trifluoroacetateYield 6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolvent

Procedure

1-(2-Chlorophenyl)-2-oxo-7-(trifluoromethyl)-2,3-dihydro-1H-benzimidazole-5-carbonitrile (17.6 mg) was dissolved in N,N-dimethylformamide (1.5 ml), and to the solution was added sodium hydride (2.7 mg). The mixture was stirred at room temperature for 20 minutes. A solution of 2-chlorotriethylamine hydrochloride (11.7 mg) in N,N-dimethylformamide (2 ml) and triethylamine (0.011 ml) were added, 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 water, dried over anhydrous sodium sulfate, and concentrated in vacuo. The resultant residue was dissolved in 2-methyl-2-propanol (1 ml) and heated at 50° C. To the solution was added powdered potassium hydroxide (73.1 mg), and the mixture was stirred for 1 hour. After allowing to cool, to the reaction mixture was added water, and the mixture was extracted 4 times 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 (6.2 mg, 6%).

Workup

  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 water
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. dissolutionThe resultant residue was dissolved in 2-methyl-2-propanol (1 ml)
  8. temperatureheated at 50° C
  9. additionTo the solution was added powdered potassium hydroxide (73.1 mg)
  10. stirringthe mixture was stirred for 1 hour
  11. temperatureto cool, to the reaction mixture
  12. additionwas added water
  13. extractionthe mixture was extracted 4 times 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

Sources & evidence

ORD record
ord-61c1ea60d38d4fecbde8ec5839c9a874
Source dataset
uspto-grants-2005_09
Patent number
US06939887B2

Reaction notes

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