4-Methylmorpholine → ethyl 6-chloro-2-({2,2,2-trifluoro-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-indole-5-carboxylate

HRID 514244Notes

Reaction equation

HRID 514244 reaction equation
[F:1][C:2]([F:17])([F:16])[CH:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]([C:12]([F:15])([F:14])[F:13])[CH:6]=1)[NH2:4].[Cl:18][C:19]1[CH:27]=[C:26]2[C:22]([CH:23]=[C:24]([C:28](O)=[O:29])[NH:25]2)=[CH:21][C:20]=1[C:31]([O:33][CH2:34][CH3:35])=[O:32].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.O>[Cl:18][C:19]1[CH:27]=[C:26]2[C:22]([CH:23]=[C:24]([C:28](=[O:29])[NH:4][CH:3]([C:5]3[CH:10]=[CH:9][C:8]([F:11])=[C:7]([C:12]([F:13])([F:14])[F:15])[CH:6]=3)[C:2]([F:1])([F:16])[F:17])[NH:25]2)=[CH:21][C:20]=1[C:31]([O:33][CH2:34][CH3:35])=[O:32]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 582479336-Chloro-5-(ethoxycarbonyl)-1H-indole-2-carboxylic acidHCID 771284572,2,2-Trifluoro-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethanamine

Product 1

HCID 86713969ethyl 6-chloro-2-({2,2,2-trifluoro-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-indole-5-carboxylateYield 82.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2,2,2-Trifluoro-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethanamine (0.82 g, 3.05 mmol) was dissolved in N,N-dimethylformamide (6 ml), and 6-chloro-5-(ethoxycarbonyl)-1H-indole-2-carboxylic acid (0.82 g, 3.05 mmol), N-[(1H-benzotriazol-1-yloxy)(dimethylamino)methylene]-N-methylmethanaminium hexafluorophosphate (1.16 g, 3.05 mmol) and 4-methylmorpholine (0.92 g, 9.10 mmol) were added. The reaction mixture was stirred at room temperature for 16 h and then water was added. The aqueous phase was extracted three times with ethyl acetate, dried over sodium sulphate, adsorbed on silica gel and chromatographed with cyclohexane/ethyl acetate (4/1). 1.29 g (65% of theory) of ethyl 6-chloro-2-({2,2,2-trifluoro-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-indole-5-carboxylate were obtained.

Workup

  1. extractionThe aqueous phase was extracted three times with ethyl acetate
  2. dry with materialdried over sodium sulphate
  3. customchromatographed with cyclohexane/ethyl acetate (4/1)

Sources & evidence

ORD record
ord-7c2d1a38270247eaa1993c543b502613
Source dataset
uspto-grants-2015_08
Patent number
US09107411B2

Reaction notes

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