2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 5-Amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazine-2-carbonitrile

HRID 1749673Notes

Reaction equation

HRID 1749673 reaction equation
Br[C:2]1[N:3]=[C:4]([C:9]2[O:10][C:11]([C:14]([CH3:17])([CH3:16])[CH3:15])=[N:12][N:13]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[C:52]([Zn]C#N)#[N:53]>CC(N(C)C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[Zn]>[NH2:8][C:5]1[N:6]=[CH:7][C:2]([C:52]#[N:53])=[N:3][C:4]=1[C:9]1[O:10][C:11]([C:14]([CH3:17])([CH3:16])[CH3:15])=[N:12][N:13]=1

Participants

7

Reactant 3

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 867276555-Bromo-3-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-amineHCID 178514179HCID 178514179, compound

Product 1

HCID 867276605-Amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazine-2-carbonitrileYield 158.5%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

A stream of nitrogen gas was passed through a solution of 5-bromo-3-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-amine (89.35 g, 239.75 mmol) in DMA (1.2 L) for 20 minutes. Dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (11.43 g, 23.98 mmol), tris(dibenzylideneacetone)dipalladium(0) (5.49 g, 5.99 mmol), zinc (1.568 g, 23.98 mmol) and dicyanozinc (16.89 g, 143.85 mmol) were added sequentially to the stirred mixture. The mixture was heated to 100° C. and stirred for 1 hour. The mixture was cooled and partitioned between DCM (3 L) and water (1 L). The black mixture was filtered through celite and the organic layer was separated. The solution was washed with water then brine. The solution was dried with magnesium sulfate and concentrated under reduced pressure. The residue was triturated with MTBE and isolated by filtration, washing with MTBE. The filter cake was dried in vacuo to afford 5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazine-2-carbonitrile (55.7 g, 95%) as a pale orange solid: 1H NMR Spectrum: (DMSO-d6) 1.46 (9H, s), 6.02 (1H, s), 8.38 (2H, s); Mass Spectrum [M−H]−=242.

Workup

  1. temperatureThe mixture was cooled
  2. custompartitioned between DCM (3 L) and water (1 L)
  3. filtrationThe black mixture was filtered through celite
  4. customthe organic layer was separated
  5. washThe solution was washed with water
  6. dry with materialThe solution was dried with magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was triturated with MTBE
  9. customisolated by filtration
  10. washwashing with MTBE
  11. customThe filter cake was dried in vacuo

Sources & evidence

ORD record
ord-a2b05b1da02f46419255d5a8824c39e8
Source dataset
uspto-grants-2015_10
Patent number
US09156831B2

Reaction notes

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