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

HRID 2283902Notes

Reaction equation

HRID 2283902 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-701aed197d134067b6412498c0335e0c
Source dataset
uspto-grants-2015_09
Patent number
US09145410B2

Reaction notes

Loading…