Triethylamine → N-(4-((5-chloro-6-cyanopyridin-3-yl)ethynyl)phenyl)acetamide

HRID 1259194Notes

Reaction equation

HRID 1259194 reaction equation
[Cl:1][C:2]1[C:3]([C:9]#[N:10])=[N:4][CH:5]=[C:6](Cl)[CH:7]=1.[C:11]([C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:22])[CH3:21])=[CH:15][CH:14]=1)#[CH:12].C(N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C.O.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>[Cl:1][C:2]1[CH:7]=[C:6]([C:12]#[C:11][C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:22])[CH3:21])=[CH:15][CH:14]=2)[CH:5]=[N:4][C:3]=1[C:9]#[N:10]

Participants

9

Reactant 3

HCID 8471TriethylamineHCID 27696993,5-Dichloro-2-cyanopyridineHCID 11412536N-(4-ethynylphenyl)acetamide

Product 1

HCID 66875230N-(4-((5-chloro-6-cyanopyridin-3-yl)ethynyl)phenyl)acetamide

Reagents, catalysts & solvents 5

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3,5-dichloropicolinonitrile (1.0 eq.), N-(4-ethynylphenyl)acetamide (from the previous step) (1.0 eq.), bis(triphenyl-phosphine)palladium chloride (10 mol %), copper iodide (10 mol %), and triethylamine (5.0 eq.) in DMF (0.04 M) was stirred at 60° C. for 4 hours. After cooling to ambient temperature, the reaction mixture was diluted with ethyl acetate and water. The two phases were separated. The organic layer was washed twice with water, dried over anhydrous MgSO4, and concentrated en vaccuo. The crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-80% ethyl acetate in hexane to give N-(4-((5-chloro-6-cyanopyridin-3-yl)ethynyl)phenyl)acetamide as a white solid.

Workup

  1. customThe two phases were separated
  2. washThe organic layer was washed twice with water
  3. dry with materialdried over anhydrous MgSO4
  4. concentrationconcentrated en vaccuo
  5. customThe crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO)

Sources & evidence

ORD record
ord-7b3a1e8c42d44b67888a3bafa8f05cc6
Source dataset
uspto-grants-2013_06
Patent number
US08466167B2

Reaction notes

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