Formamidine acetate → 6-(2-Furyl)-5-pyrimidin-4-ylpyrazin-2-amine

HRID 1710695Notes

Reaction equation

HRID 1710695 reaction equation
[NH2:1][C:2]1[N:3]=[C:4]([C:11]2[O:12][CH:13]=[CH:14][CH:15]=2)[C:5]([C:8](=O)[CH3:9])=[N:6][CH:7]=1.[C:16](O)(=O)C.[CH:20]([NH2:22])=[NH:21]>COC(OC)N(C)C.C(O)C.C1(C)C=CC=CC=1>[O:12]1[CH:13]=[CH:14][CH:15]=[C:11]1[C:4]1[N:3]=[C:2]([NH2:1])[CH:7]=[N:6][C:5]=1[C:8]1[CH:9]=[CH:16][N:22]=[CH:20][N:21]=1

Participants

6

Reactant 2

HCID 160693Formamidine acetateHCID 594576321-[5-Amino-3-(2-furyl)pyrazin-2-yl]ethanone

Product 1

HCID 160716606-(2-Furyl)-5-pyrimidin-4-ylpyrazin-2-amineYield 30%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 1140TolueneSolventHCID 78373Dimethylformamide dimethyl acetalSolvent

Conditions

Temperature
115 °C

Procedure

A solution of 1-[5-amino-3-(2-furyl)pyrazin-2-yl]ethanone (Preparation 4, 388 mg, 1.91 mmol) in N,N-dimethylformamide dimethyl acetal (1.3 mL) was heated to 100° C. After 9 h, the mixture was concentrated under reduced pressure to yield brown oil. Formamidine acetate (795 mg, 7.64 mmol) was added to this oily residue previously dissolved in ethanol (6.4 mL) and toluene (0.96 mL). Molecular sieves (4 Å) were added to the solution and the whole reaction mixture was heated to 115° C. in a sealed tube and stirred for 20 h. The crude reaction was filtered and concentrated to dryness. The residue was partitioned between ethyl acetate and water, the organic layer was washed with brine, dried (Na2SO4) and evaporated. The residue was purified by silica gel flash chromatography (100% ethyl acetate). Concentration in vacuo of the product-rich fractions provided the titled compound as a pale-yellow solid (137 mg, 30%).

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. customto yield brown oil
  3. additionMolecular sieves (4 Å) were added to the solution
  4. customthe whole reaction mixture
  5. customThe crude reaction
  6. filtrationwas filtered
  7. concentrationconcentrated to dryness
  8. customThe residue was partitioned between ethyl acetate and water
  9. washthe organic layer was washed with brine
  10. dry with materialdried (Na2SO4)
  11. customevaporated
  12. customThe residue was purified by silica gel flash chromatography (100% ethyl acetate)
  13. concentrationConcentration in vacuo of the product-rich fractions

Sources & evidence

ORD record
ord-cc24f7a7a0c34c5bb06864d75bded878
Source dataset
uspto-grants-2010_09
Patent number
US07790728B2

Reaction notes

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