Trifluoroacetic acid → N-[1-[1-(6-Chloro-3-pyridyl)ethyl]-2-pyridylidene]-2,2,2-trifluoroacetamide

HRID 2199245Notes

Reaction equation

HRID 2199245 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[F:8][C:9]([F:14])([F:13])[C:10](O)=[O:11].S(Cl)(Cl)=O.C(=O)([O-])[O-].[K+].[K+].[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32]Cl)=[CH:28][N:27]=1>C1(C)C=CC=CC=1.O.CN(C)C=O>[Cl:25][C:26]1[N:27]=[CH:28][C:29]([CH2:32][N:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]2=[N:1][C:10](=[O:11])[C:9]([F:14])([F:13])[F:8])=[CH:30][CH:31]=1

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 104392-AminopyridineHCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 1554792-Chloro-5-(chloromethyl)pyridine

Product 1

HCID 14127920N-[1-[1-(6-Chloro-3-pyridyl)ethyl]-2-pyridylidene]-2,2,2-trifluoroacetamideYield 64.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
5 °C

Procedure

In 100 ml of toluene, 10.0 g (0.106 mol) of 2-aminopyridine was dissolved. After the solution was cooled to 5° C., 11.8 ml (0.159 mol) of trifluoroacetic acid and subsequently 7.76 ml (0.106 mol) of thionyl chloride were added thereto portionwise, followed by stirring at room temperature overnight. Then, 50 ml of toluene was distilled off under reduced pressure. To the reaction liquid, 50 ml of toluene was added. Then, 50 ml of dimethylformamide, 22.03 g (0.16 mol) of potassium carbonate powder, and 17.56 g (0.108 mol) of 2-chloro-5-chloromethylpyridine were added thereto under ice-cooling. Then, distillation was conducted under reduced pressure (90 to 36 hPa) at 60° C. for 1.5 hours. To the reaction liquid, 30 ml of methanol and 20 ml of water were added. The reaction liquid was added to 300 ml of water of 50° C., while the vessel was also washed. The mixture was stirred at room temperature for 30 minutes, and then the crystals were filtered, and washed with 50 ml of water and 30 ml of toluene. The obtained crystals were dried under reduced pressure at 60° C. Thus, 21.45 g of the target compound was obtained (64.1%).

Workup

  1. distillationThen, 50 ml of toluene was distilled off under reduced pressure
  2. customTo the reaction liquid, 50 ml of toluene
  3. additionwas added
  4. temperatureunder ice-cooling
  5. distillationThen, distillation
  6. waitwas conducted under reduced pressure (90 to 36 hPa) at 60° C. for 1.5 hours
  7. customTo the reaction liquid, 30 ml of methanol and 20 ml of water
  8. additionwere added
  9. customThe reaction liquid
  10. washwas also washed
  11. stirringThe mixture was stirred at room temperature for 30 minutes
  12. filtrationthe crystals were filtered
  13. washwashed with 50 ml of water and 30 ml of toluene
  14. customThe obtained crystals were dried under reduced pressure at 60° C

Sources & evidence

ORD record
ord-0de79ead7a9c4cdf8237b20a7609c37d
Source dataset
uspto-grants-2016_06
Patent number
US09357776B2

Reaction notes

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