Triethylamine → 4-(2,2-Dimethyl-propylamino)-5-ethynyl-pyrimidine-2-carbonitrile

HRID 1163017Notes

Reaction equation

HRID 1163017 reaction equation
Br[C:2]1[C:3]([NH:10][CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[N:4][C:5]([C:8]#[N:9])=[N:6][CH:7]=1.[C:16]([Si](C)(C)C)#[CH:17].C(N(CC)CC)C.[F-].[Cs+]>CN(C=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.CCOC(C)=O.CCCCCC>[CH3:13][C:12]([CH3:15])([CH3:14])[CH2:11][NH:10][C:3]1[C:2]([C:16]#[CH:17])=[CH:7][N:6]=[C:5]([C:8]#[N:9])[N:4]=1

Participants

10

Reactant 4

HCID 8471TriethylamineHCID 25953Cesium fluorideHCID 66111TrimethylsilylacetyleneHCID 179681615-Bromo-4-(2,2-dimethylpropylamino)pyrimidine-2-carbonitrile

Product 1

HCID 577141354-(2,2-Dimethyl-propylamino)-5-ethynyl-pyrimidine-2-carbonitrileYield 76%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-Bromo-4-(2,2-dimethyl-propylamino)-pyrimidine-2-carbonitrile (7.58 mmol) and ethynyl-trimethyl-silane (22.74 mmol) in DMF (20 ml) are treated with triethylamine (38.0 mmol), copper (I) iodide (0.76 mmol), and dichlorobis(triphenylphosphine)palladium(II) (0.38 mmol) at room temperature. The mixture is stirred for 1.5 h at room temperature, poured into an ice water and extracted with AcOEt. The organic layer is washed with brine, dried over magnesium sulfate and concentrated. The crude product is dissolved in methanol (60 ml) water (10 ml) and cesium fluoride (4.2 mmol) is added at room temperature and the mixture is stirred at room temperature for 5 min. The reaction mixture is evaporated, then water and CH2Cl2 are added. The organic layer is washed with brine, dried over magnesium sulfate and concentrated. The crude product is purified by silica gel column chromatography to give the product in 76% yield. Rf=0.67 (n-hexane:AcOEt=2:1)

Workup

  1. extractionextracted with AcOEt
  2. washThe organic layer is washed with brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. dissolutionThe crude product is dissolved in methanol (60 ml) water (10 ml)
  6. stirringthe mixture is stirred at room temperature for 5 min
  7. customThe reaction mixture is evaporated
  8. additionwater and CH2Cl2 are added
  9. washThe organic layer is washed with brine
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated
  12. customThe crude product is purified by silica gel column chromatography
  13. customto give the product in 76% yield

Sources & evidence

ORD record
ord-f693ddb91e8d4a51b8b5f6d34c8f14fa
Source dataset
uspto-grants-2010_10
Patent number
US07820818B2

Reaction notes

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