Dimethylformamide → ethyl 2-(5-acetamido-3-phenyl-4-(phenylethynyl)-1H-pyrazol-1-yl)acetate

HRID 1615729Notes

Reaction equation

HRID 1615729 reaction equation
[C:1]([NH:4][C:5]1[N:9]([CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[N:8]=[C:7]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:6]=1I)(=[O:3])[CH3:2].[C:23]1([C:29]#[CH:30])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(N(CC)CC)C.CN(C=O)C>C(OCC)(=O)C.O.[Cu](I)I.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>[C:1]([NH:4][C:5]1[N:9]([CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[N:8]=[C:7]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:6]=1[C:30]#[C:29][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)(=[O:3])[CH3:2]

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 10821PhenylacetyleneHCID 86717317ethyl 2-(5-acetamido-4-iodo-3-phenyl-1H-pyrazol-1-yl)acetate

Product 1

HCID 70983078ethyl 2-(5-acetamido-3-phenyl-4-(phenylethynyl)-1H-pyrazol-1-yl)acetateYield 74.6%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
90 °C

Procedure

Nitrogen was bubbled through a mixture of ethyl 2-(5-acetamido-4-iodo-3-phenyl-pyrazol-1-yl)acetate (18.6 g, 45 mmol), phenyl acetylene (9.2 g, 90 mmol), copper iodide (860 mg, 4.5 mmol), triethylamine (200 mL) and DMF (75 mL) for 15 min. Bis(triphenylphosphine)palladium(II) dichloride (1.6 g, 2.25 mmol) was added and the reaction mixture was stirred at 90° C. under nitrogen for 4.5 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate and water. The organic phase was washed with water and brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was partially purified by column chromatography (silica gel, CH2Cl2, then isohexane/ethyl acetate 1:1 followed by CH2Cl2/ethyl acetate 9:1 to 8:2), then triturated with diethyl ether to provide the title compound as a solid (13 g).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washThe organic phase was washed with water and brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was partially purified by column chromatography (silica gel, CH2Cl2
  7. customthen triturated with diethyl ether

Sources & evidence

ORD record
ord-31e214990123434b8a86c609628fcf8f
Source dataset
uspto-grants-2014_07
Patent number
US08765762B2

Reaction notes

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