[F:1][CH:2]([F:5])[CH2:3][NH2:4].C[Al](C)C.ClC1[CH:19]=[C:18]2[C:14]([CH:15]=[C:16]([C:22](=[O:40])[NH:23][CH:24]([C:29]3[CH:34]=[CH:33][C:32]([F:35])=[C:31]([C:36]([F:39])([F:38])[F:37])[CH:30]=3)[C:25]([F:28])([F:27])[F:26])[N:17]2[CH2:20][CH3:21])=[CH:13][C:12]=1[C:41]([O:43]CC)=O.O.Cl[CH2:48][Cl:49]>>[Cl:49][C:48]1[CH:19]=[C:18]2[C:14]([CH:15]=[C:16]([C:22]([NH:23][CH:24]([C:29]3[CH:34]=[CH:33][C:32]([F:35])=[C:31]([C:36]([F:37])([F:38])[F:39])[CH:30]=3)[C:25]([F:28])([F:26])[F:27])=[O:40])[N:17]2[CH2:20][CH3:21])=[CH:13][C:12]=1[C:41]([NH:4][CH2:3][CH:2]([F:5])[F:1])=[O:43]2,2-Difluoroethanamine (0.12 g, 1.42 mmol) was dissolved under argon in dichloromethane (2 ml). At room temperature, a solution of trimethylaluminium in dichloromethane (0.71 ml, 1.42 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 30 min and then a solution of ethyl 6-chloro-1-ethyl-2-({2,2,2-trifluoro-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-indole-5-carboxylate (0.078 g, 0.14 mmol) in dichloromethane (2 ml) was added dropwise. The reaction mixture was heated under reflux for 16 h and, after cooling, water was added. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulphate and the solvent was removed under reduced pressure. The residue was chromatographed with cyclohexane/ethyl acetate (4/1) and gave 0.065 g (81% of theory) of 6-chloro-N5-(2,2-difluoroethyl)-1-ethyl-N2-{2,2,2-trifluoro-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide.
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