3,5-Dichloro-2-cyanopyridine → HCID 66874911, compound

HRID 1259243Notes

Reaction equation

HRID 1259243 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9](=[O:11])[CH3:10])=[CH:5][CH:4]=1)#[CH:2].[Cl:12][C:13]1[C:14]([C:20]#[N:21])=[N:15][CH:16]=[C:17](Cl)[CH:18]=1.CN(C=O)C.C(N(CC)CC)C>C(OCC)(=O)C.C(=O)(O)[O-].[Na+].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>[C:9]([C:6]1[CH:7]=[CH:8][C:3]([C:1]#[C:2][C:17]2[CH:18]=[C:13]([Cl:12])[C:14]([C:20]#[N:21])=[N:15][CH:16]=2)=[CH:4][CH:5]=1)(=[O:11])[CH3:10]

Participants

8

Reactant 3

HCID 27696993,5-Dichloro-2-cyanopyridineHCID 51236261-(4-Ethynylphenyl)ethan-1-oneHCID 22056947triethylamine N,N-dimethylformamide

Product 1

HCID 66874911HCID 66874911, compound

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 1-(4-ethynylphenyl)ethanone (commercially available) (1 eq) 3,5-dichloropicolinonitrile (1 eq), dichlorobis(triphenylphosphine)-palladium (II) (20 mol %), copper iodide (10 mol %) and DMF: Triethylamine (10:1) (0.13 M) was stirred at ambient temperature overnight. The reaction mixture was then diluted with ethyl acetate and sodium bi-carbonate solution. The two phases were separated, and the aqueous phase was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated en vaccuo. The crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-100% ethyl acetate in hexane and 5-((4-acetylphenyl)ethynyl)-3-chloropicolinonitrile was isolated as a yellow solid

Workup

  1. customThe two phases were separated
  2. extractionthe aqueous phase was extracted twice with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated en vaccuo
  6. customThe crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO)
  7. customwas isolated as a yellow solid

Sources & evidence

ORD record
ord-5721af2c721b467785e05c058ef338f0
Source dataset
uspto-grants-2013_06
Patent number
US08466167B2

Reaction notes

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