Acetonitrile → 1-ethyl-5-(2-hydroxy-2-methylpropyl)-4-(3-trimethylsilylprop-1-ynyl) 1H-pyrazole-3-carbonitrile

HRID 1360579Notes

Reaction equation

HRID 1360579 reaction equation
[CH2:1]([N:3]1[C:7]([CH2:8][C:9]([OH:12])([CH3:11])[CH3:10])=[C:6](I)[C:5]([C:14]#[N:15])=[N:4]1)[CH3:2].[CH2:16]([Si:19]([CH3:22])([CH3:21])[CH3:20])[C:17]#[CH:18].C(N(CC)CC)C.C(#N)C>C(OCC)(=O)C.[Cu]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>[CH2:1]([N:3]1[C:7]([CH2:8][C:9]([OH:12])([CH3:11])[CH3:10])=[C:6]([C:18]#[C:17][CH2:16][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:5]([C:14]#[N:15])=[N:4]1)[CH3:2]

Participants

8

Reactant 4

HCID 6342AcetonitrileHCID 8471TriethylamineHCID 83378Trimethyl-2-propynylsilaneHCID 669585891-ethyl-5-(2-hydroxy-2-methylpropyl)4-iodo-1H-pyrazole-3-carbonitrile

Product 1

HCID 669587061-ethyl-5-(2-hydroxy-2-methylpropyl)-4-(3-trimethylsilylprop-1-ynyl) 1H-pyrazole-3-carbonitrile

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolvent

Procedure

Under a nitrogen atmosphere, 1-ethyl-5-(2-hydroxy-2-methylpropyl)-4-iodo-1H-pyrazole-3-carbonitrile (900 mg, 2.81 mmol), propargyltrimethylsilane (0.8 mL, 5.6 mmol), copper(I) iodide (107 mg, 0.562 mmol), dichlorobis(triphenylphosphine)palladium(II) (197 mg, 0.281 mmol), triethylamine (1.2 mL, 8.4 mmol) and acetonitrile (14 mL) were combined and then heated at reflux for five hours. The reaction mixture was cooled to ambient temperature, diluted with ethyl acetate, and then filtered through a layer of silica gel. The filtrate was concentrated under reduced pressure. The residue was purified by chromatography on a HORIZON HPFC system (40+M cartridge, eluting with a gradient of 0 to 80% ethyl acetate in hexanes) to provide 1-ethyl-5-(2-hydroxy-2-methylpropyl)-4-(3-trimethylsilylprop-1-ynyl)-1H-pyrazole-3-carbonitrile as a yellow oil.

Workup

  1. temperatureheated
  2. temperatureat reflux for five hours
  3. filtrationfiltered through a layer of silica gel
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by chromatography on a HORIZON HPFC system (40+M cartridge
  6. washeluting with a gradient of 0 to 80% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-a7dd70288c204cbfb8889a1f637a5308
Source dataset
uspto-grants-2011_02
Patent number
US07879849B2

Reaction notes

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