Hydrochloric Acid → 1-[5-Amino-3-(2-furyl)pyrazin-2-yl]ethanone

HRID 1710678Notes

Reaction equation

HRID 1710678 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]([NH2:13])=[N:6][C:7]=1[C:8]1[O:9][CH:10]=[CH:11][CH:12]=1.[CH:14]([O:16]CCCC)=[CH2:15].C([O-])(=O)C.[K+].C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:13][C:5]1[N:6]=[C:7]([C:8]2[O:9][CH:10]=[CH:11][CH:12]=2)[C:2]([C:14](=[O:16])[CH3:15])=[N:3][CH:4]=1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 8108Butyl vinyl etherHCID 11430Potassium CarbonateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 517044Potassium AcetateHCID 594576565-Bromo-6-(2-furyl)pyrazin-2-amine

Product 1

HCID 594576321-[5-Amino-3-(2-furyl)pyrazin-2-yl]ethanoneYield 60.1%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
122 °C

Procedure

To a stirred solution of 5-bromo-6-(2-furyl)pyrazin-2-amine (Preparation 2, 1.5 g, 6.3 mmol) in a mixture of DMF (16 mL) and water (4 mL) was added butyl vinyl ether (4.10 mL, 31.5 mmol), potassium acetate (3.80 mL, 7.56 mmol), 1,3-bis-(diphenylphosphino)propane (0.172 g, 0.416 mmol) and palladium(II) acetate (42.0 mg, 0.189 mmol)1. The mixture was subjected to three cycles of evacuation-backfilling with argon and heated at 122° C. under microwave irradiation. After 4 h, the mixture was cooled to room temperature and hydrolyzed by adding of HCl 2N (30 mL) for 30 min. The mixture was then neutralized with a saturated solution of potassium carbonate and diluted with dichloromethane. The organic layer was separated, dried (Na2SO4) and evaporated. The residue was purified by silica gel flash chromatography (2% methanol in dichloromethane). Concentration in vacuo of the product-rich fractions provided the titled compound as a pale-yellow solid (0.77 g, 60%). 1K. S. A. Vallin, M. Larhed, A. Hallberg, J. Org. Chem., 2001, 66, 4340.

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. customevaporated
  5. customThe residue was purified by silica gel flash chromatography (2% methanol in dichloromethane)
  6. concentrationConcentration in vacuo of the product-rich fractions

Sources & evidence

ORD record
ord-9938d9d19b3a4c62bf14d79fa9254749
Source dataset
uspto-grants-2010_09
Patent number
US07790728B2

Reaction notes

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