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

HRID 514260

Reaction equation

HRID 514260 reaction equation
[F:1][C:2]([F:16])([F:15])[CH:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]([F:14])([F:13])[F:12])[CH:6]=1)[NH2:4].[Cl:17][C:18]1[C:19]([C:30](=[O:35])[NH:31][CH:32]2[CH2:34][CH2:33]2)=[CH:20][C:21]2[N:25]=[C:24]([C:26](O)=[O:27])[NH:23][C:22]=2[CH:29]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C)C=O.C(OCC)(=O)C>[Cl:17][C:18]1[C:19]([C:30]([NH:31][CH:32]2[CH2:34][CH2:33]2)=[O:35])=[CH:20][C:21]2[N:25]=[C:24]([C:26]([NH:4][CH:3]([C:5]3[CH:10]=[CH:9][CH:8]=[C:7]([C:11]([F:12])([F:13])[F:14])[CH:6]=3)[C:2]([F:15])([F:16])[F:1])=[O:27])[NH:23][C:22]=2[CH:29]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 438251722,2,2-Trifluoro-1-(3-(trifluoromethyl)phenyl)ethanamineHCID 682930886-chloro-5-(cyclopropylcarbamoyl)-1H-benzimidazole-2-carboxylic acid

Product 1

HCID 867139816-chloro-N5-cyclopropyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-benzimidazole-2,5-dicarboxamideYield 58%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2,2,2-Trifluoro-1-[3-(trifluoromethyl)phenyl]ethanamine (0.23 g, 0.82 mmol) was dissolved in N,N-dimethylformamide (4 ml), and 6-chloro-5-(cyclopropylcarbamoyl)-1H-benzimidazole-2-carboxylic acid (0.23 g, 0.82 mmol), N-[(1H-benzotriazol-1-yloxy)(dimethylamino)methylene]-N-methylmethanaminium hexafluorophosphate (0.31 g, 0.82 mmol) and 4-methylmorpholine (0.25 g, 2.47 mmol) were added. The reaction mixture was stirred at room temperature for 16 h and then ethyl acetate was added. The organic phase was washed with saturated sodium hydrogencarbonate solution and saturated sodium chloride solution and dried over sodium sulphate, and the solvent was removed under reduced pressure. The residue was chromatographed with cyclohexane/ethyl acetate (1/1) and gave 0.24 g (57% of theory) of 6-chloro-N5-cyclopropyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-benzimidazole-2,5-dicarboxamide.

Workup

  1. washThe organic phase was washed with saturated sodium hydrogencarbonate solution and saturated sodium chloride solution
  2. dry with materialdried over sodium sulphate
  3. customthe solvent was removed under reduced pressure
  4. customThe residue was chromatographed with cyclohexane/ethyl acetate (1/1)

Sources & evidence

ORD record
ord-fa81a40ed8874750b358d164afa61467
Source dataset
uspto-grants-2015_08
Patent number
US09107411B2

Linked notes

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