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

HRID 1514943Notes

Reaction equation

HRID 1514943 reaction equation
C[Al](C)C.[F:5][C:6]([F:15])([F:14])[C:7]1[N:12]=[CH:11][C:10]([NH2:13])=[CH:9][CH:8]=1.[Cl:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=1[C:24]1[NH:25][C:26]2[C:31]([CH:32]=1)=[CH:30][CH:29]=[C:28]([C:33](OC)=[O:34])[CH:27]=2>C1(C)C=CC=CC=1>[F:15][C:6]([F:5])([F:14])[C:7]1[N:12]=[CH:11][C:10]([NH:13][C:33]([C:28]2[CH:27]=[C:26]3[C:31]([CH:32]=[C:24]([C:18]4[C:19]([Cl:23])=[CH:20][CH:21]=[CH:22][C:17]=4[Cl:16])[NH:25]3)=[CH:30][CH:29]=2)=[O:34])=[CH:9][CH:8]=1

Participants

5

Reactant 3

HCID 27377445-Amino-2-(trifluoromethyl)pyridineHCID 16682925Trimethylaluminum2×HCID 66965661methyl 2-(2,6-dichlorophenyl)-1H-indole-6-carboxylate

Product 1

HCID 669652792-(2,6-dichlorophenyl)-1H-indole-6-carboxylic acid (6-trifluoromethylpyridin-3-yl)-amide

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
100 °C

Procedure

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).

Workup

  1. temperaturethe mixture heated another 18 h
  2. temperatureafter which it was cooled to ambient temperature
  3. customquenched with 1N HCl
  4. additionWater was added
  5. extractionthe mixture was extracted with EtOAc (2×)
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. customthe solvent was removed under reduced pressure
  9. customThe residue was chromatographed

Sources & evidence

ORD record
ord-0afafe587539482c9f7963328fd5b1c0
Source dataset
uspto-grants-2012_07
Patent number
US08222248B2

Reaction notes

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