Triethylamine → 2-(4-(Isopropylsulfonyl)phenyl)-6-((trimethylsilyl)ethynyl)pyrazine

HRID 522530Notes

Reaction equation

HRID 522530 reaction equation
Cl[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH:17]([CH3:19])[CH3:18])(=[O:16])=[O:15])=[CH:10][CH:9]=2)[N:3]=1.CCN(CC)CC.[Si:27]([C:31]#[CH:32])([CH3:30])([CH3:29])[CH3:28]>C1(C)C=CC=CC=1.CCOC(C)=O.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>[CH:17]([S:14]([C:11]1[CH:12]=[CH:13][C:8]([C:4]2[CH:5]=[N:6][CH:7]=[C:2]([C:32]#[C:31][Si:27]([CH3:30])([CH3:29])[CH3:28])[N:3]=2)=[CH:9][CH:10]=1)(=[O:16])=[O:15])([CH3:19])[CH3:18]

Participants

9

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 866651482-Chloro-6-(4-(isopropylsulfonyl)phenyl)pyrazine

Product 1

HCID 674806192-(4-(Isopropylsulfonyl)phenyl)-6-((trimethylsilyl)ethynyl)pyrazineYield 50%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-chloro-6-(4-isopropylsulfonylphenyl)pyrazine (320 mg, 1.078 mmol) in anhydrous toluene (5 mL) was degassed and placed under an atmosphere of nitrogen. Pd(PPh3)2Cl2 (60.53 mg, 0.08624 mmol) and CuI (16.42 mg, 0.08624 mmol) were added and the reaction was again degassed under nitrogen. Et3N (109.1 mg, 150.3 μL, 1.078 mmol) as added followed by the quick addition of TMS-acetylene (116.5 mg, 167.6 μL, 1.186 mmol). After an initial exotherm the reaction was stirred at ambient temperature for 16 hours. The reaction was diluted with EtOAc and water and the layers separated. The aqueous layer was extracted with EtOAc (×2) and the combined organic extracts were washed with water, brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion™, 40 g column, eluting with 0 to 20% EtOAc/Petroleum Ether) to give the sub-title product as an off-white solid (192 mg, 50% Yield). 1H NMR (400.0 MHz, DMSO) δ 9.21 (s, 1H), 8.67 (s, 1H), 8.25 (d, 2H), 7.86 (d, 2H), 3.35 (sept, 1H), 1.03 (d, 6H) and 0.15 (s, 9H) ppm; MS (ES+) 359.1

Workup

  1. customthe reaction was again degassed under nitrogen
  2. customthe layers separated
  3. extractionThe aqueous layer was extracted with EtOAc (×2)
  4. washthe combined organic extracts were washed with water, brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (ISCO Companion™, 40 g column, eluting with 0 to 20% EtOAc/Petroleum Ether)

Sources & evidence

ORD record
ord-fd703ba60f1b445480acb015455eb6fd
Source dataset
uspto-grants-2016_05
Patent number
US09334244B2

Reaction notes

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