5-Amino-2-(trifluoromethyl)pyridine → 2-(2,6-dichlorophenyl)-1H-indole-6-carboxylic acid (6-trifluoromethylpyridin-3-yl)-amide

Participants

Reaction Conditions

Reaction Steps

To 4 mL of ice-cold toluene was added 0.28 mL of 2 M trimethylaluminum in toluene then 6-trifluoromethyl-pyridin-3-ylamine (84 mg, 0.5 mmol) was added in one portion and the yellow solution was stirred for 30 min. To this was added a solution of methyl 2-(2,6-dichlorophenyl)-1H-indole-6-carboxylate (150 mg, 0.47 mmol) in toluene (5 mL) dropwise and the resulting solution was heated at 100° C. for 18 h. A second aliquot of trimethylaluminum was added and the mixture heated another 18 h, after which it was cooled to ambient temperature, quenched with 1N HCl. Water was added and the mixture was extracted with EtOAc (2×). The combined organic layers were dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was chromatographed using methylene chloride then 20% EtOAc/methylene chloride as eluent to give 2-(2,6-dichlorophenyl)-1H-indole-6-carboxylic acid (6-trifluoromethylpyridin-3-yl)-amide as a purple glass. MS (m/z) 449.9 (M+1); retention time=1.63 min (Method 10).

Provenance & Evidence