Water → 6-chloro-N5-cyclopropyl-1-ethyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-benzimidazole-2,5-dicarboxamide

HRID 514261Notes

Reaction equation

HRID 514261 reaction equation
[Cl:1][C:2]1[C:3]([C:29]([NH:31][CH:32]2[CH2:34][CH2:33]2)=[O:30])=[CH:4][C:5]2[N:9]=[C:8]([C:10]([NH:12][CH:13]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=3)[C:14]([F:17])([F:16])[F:15])=[O:11])[NH:7][C:6]=2[CH:28]=1.[H-].[Na+].I[CH2:38][CH3:39].O>CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[C:3]([C:29]([NH:31][CH:32]2[CH2:34][CH2:33]2)=[O:30])=[CH:4][C:5]2[N:9]([CH2:38][CH3:39])[C:8]([C:10]([NH:12][CH:13]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:25])([F:27])[F:26])[CH:19]=3)[C:14]([F:15])([F:16])[F:17])=[O:11])=[N:7][C:6]=2[CH:28]=1.[Cl:1][C:2]1[C:3]([C:29]([NH:31][CH:32]2[CH2:34][CH2:33]2)=[O:30])=[CH:4][C:5]2[N:9]=[C:8]([C:10]([NH:12][CH:13]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:25])([F:27])[F:26])[CH:19]=3)[C:14]([F:15])([F:16])[F:17])=[O:11])[N:7]([CH2:38][CH3:39])[C:6]=2[CH:28]=1

Participants

8

Reactant 4

HCID 962WaterHCID 6340IodoethaneHCID 24758Sodium hydrideHCID 867139816-chloro-N5-cyclopropyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-benzimidazole-2,5-dicarboxamide

Product 2

HCID 867139825-chloro-N6-cyclopropyl-1-ethyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-benzimidazole-2,6-dicarboxamideYield 12%HCID 867139836-chloro-N5-cyclopropyl-1-ethyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-benzimidazole-2,5-dicarboxamideYield 18%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

6-Chloro-N5-cyclopropyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-benzimidazole-2,5-dicarboxamide (0.1 g, 0.22 mmol) was dissolved under argon at 0° C. in N,N-dimethylformamide (2 ml). Sodium hydride (60%; 0.0082 g, 0.22 mmol) was added and the mixture was stirred while cooling with ice for 1 h. Subsequently, iodoethane (0.034 g, 0.22 mmol) was added dropwise. The reaction mixture was thawed while stirring within 16 h. Water and ethyl acetate were added and the phases were separated. The organic phase was washed with saturated sodium chloride solution and dried over magnesium sulphate, and the solvent was removed under reduced pressure. The residue was chromatographed with cyclohexane/ethyl acetate (4/1) and gave 0.012 g (12% of theory) of 5-chloro-N6-cyclopropyl-1-ethyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-benzimidazole-2,6-dicarboxamide and 0.018 g (18% of theory) of 6-chloro-N5-cyclopropyl-1-ethyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-benzimidazole-2,5-dicarboxamide.

Workup

  1. temperaturewhile cooling with ice for 1 h
  2. stirringwhile stirring within 16 h
  3. customthe phases were separated
  4. washThe organic phase was washed with saturated sodium chloride solution
  5. dry with materialdried over magnesium sulphate
  6. customthe solvent was removed under reduced pressure
  7. customThe residue was chromatographed with cyclohexane/ethyl acetate (4/1)

Sources & evidence

ORD record
ord-0667cc94e98f4682800072af02b38372
Source dataset
uspto-grants-2015_08
Patent number
US09107411B2

Reaction notes

Loading…