Triethylamine → 2-Amino-3-cyano-5-[(4-trifluoromethylphenyl)ethynyl]pyrazine

HRID 1734159Notes

Reaction equation

HRID 1734159 reaction equation
[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[N:6][C:5]([C:10]#[CH:11])=[CH:4][N:3]=1.[F:12][C:13]([F:22])([F:21])[C:14]1[CH:19]=[CH:18][C:17](I)=[CH:16][CH:15]=1.C(N(CC)CC)C>C(#N)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu](I)I>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[N:6][C:5]([C:10]#[C:11][C:17]2[CH:18]=[CH:19][C:14]([C:13]([F:22])([F:21])[F:12])=[CH:15][CH:16]=2)=[CH:4][N:3]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 67993Benzene, 1-iodo-4-(trifluoromethyl)-HCID 153352732-Amino-3-cyano-5-ethynylpyrazine

Product 1

HCID 153352742-Amino-3-cyano-5-[(4-trifluoromethylphenyl)ethynyl]pyrazine

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

A solution of 3.2 grams (0.022 mole) of 2-amino-3-cyano-5-ethynylpyrazine, 8.4 grams (0.031 mole) of 4-trifluoromethylphenyl iodide, 10.7 grams (0.077 mole) of triethylamine, 0.5 gram (catalyst) of bis(triphenylphosphine)palladium(II) chloride, and 0.5 gram (catalyst) of copper iodide in 100 mL of acetonitrile is stirred at ambient temperature for about 18 hours. After this time the reaction mixture is concentrated under reduced pressure to a residue. The residue is partitioned between ethyl acetate and aqueous 1N hydrochloric acid. The two-layered mixture is filtered to remove a solid. The aqueous layer and the organic layer are separated, and the aqueous layer is washed with ethyl acetate. The ethyl acetate wash is combined with the organic layer, and the combination is washed with an aqueous solution of 10% lithium chloride. The organic layer is dried with magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure to a residue. The residue is triturated with methylene chloride and filtered. The filtrate is subjected to column chromatography on silica gel. Elution is accomplished using methanol/methylene chloride combinations. The product-containing fractions are combined and concentrated under reduced pressure, yielding 2-amino-3-cyano-5-[(4-trifluoromethylphenyl)ethynyl]pyrazine.

Workup

  1. concentrationAfter this time the reaction mixture is concentrated under reduced pressure to a residue
  2. customThe residue is partitioned between ethyl acetate and aqueous 1N hydrochloric acid
  3. filtrationThe two-layered mixture is filtered
  4. customto remove a solid
  5. customThe aqueous layer and the organic layer are separated
  6. washthe aqueous layer is washed with ethyl acetate
  7. washThe ethyl acetate wash
  8. washthe combination is washed with an aqueous solution of 10% lithium chloride
  9. dry with materialThe organic layer is dried with magnesium sulfate
  10. filtrationfiltered
  11. concentrationThe filtrate is concentrated under reduced pressure to a residue
  12. customThe residue is triturated with methylene chloride
  13. filtrationfiltered
  14. washElution
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d21fb125e33d4b5c9d7d67d561300fd0
Source dataset
uspto-grants-1996_07
Patent number
US05532367

Reaction notes

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