Hydrochloric Acid → Methyl 6-amino-3-methoxy-2-pyrazinecarboxylate

HRID 392303Notes

Reaction equation

HRID 392303 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[C:5]([O:12][CH3:13])=[N:4][CH:3]=1.C(=[NH:27])(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+].Cl.[OH-].[Na+]>C1(C)C=CC=CC=1.O1CCCC1.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].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.C(Cl)(Cl)Cl>[NH2:27][C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[C:5]([O:12][CH3:13])=[N:4][CH:3]=1

Participants

12

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 136809Benzophenone imineHCID 22248028Methyl 6-bromo-3-methoxypyrazine-2-carboxylateHCID 23676156Sodium t-butoxide

Product 1

HCID 22662843Methyl 6-amino-3-methoxy-2-pyrazinecarboxylateYield 43.1%

Reagents, catalysts & solvents 6

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

In an atmosphere of nitrogen gas, 11.4 g of methyl 6-bromo-3-methoxy-2-pyrazinecarboxylate was dissolved in 227 mL of toluene, and 10.3 g of benzophenoneimine, 0.42 g of tris(dibenzylideneacetone)dipalladium, 0.86 g of (s)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl and 6.20 g of sodium tert-butoxide were successively added. The mixture thus obtained was stirred at 80° C. for one hour. After cooling the reaction mixture, it was filtered. The filtrate was purified by column chromatography [eluent: toluene:ethyl acetate=20:1]. The oily product thus obtained was dissolved in 140 mL of tetrahydrofuran, 7 mL of 2 mol/L hydrochloric acid was added, and the mixture thus obtained was stirred at room temperature for 15 minutes. A mixture of 200 mL of chloroform and 50 mL of water was added to the reaction mixture and then 1 mol/L sodium hydroxide was added to alkalinize the mixture, and the organic layer was separated. The organic layer thus obtained was washed with a saturated aqueous solution of sodium chloride and dried on anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography [eluent: toluene:ethyl acetate=1:1] to obtain 3.64 g of methyl 6-amino-3-methoxy-2-pyrazinecarboxylate as a yellow-colored oily product.

Workup

  1. customThe mixture thus obtained
  2. temperatureAfter cooling the reaction mixture, it
  3. filtrationwas filtered
  4. customThe filtrate was purified by column chromatography [eluent: toluene:ethyl acetate=20:1]
  5. customThe oily product thus obtained
  6. customthe mixture thus obtained
  7. stirringwas stirred at room temperature for 15 minutes
  8. additionwas added to the reaction mixture
  9. customthe organic layer was separated
  10. customThe organic layer thus obtained
  11. washwas washed with a saturated aqueous solution of sodium chloride
  12. dry with materialdried on anhydrous magnesium sulfate
  13. customthe solvent was removed under reduced pressure
  14. customThe residue was purified by column chromatography [eluent: toluene:ethyl acetate=1:1]

Sources & evidence

ORD record
ord-7e7108b74e394c45b2c42c878649cca9
Source dataset
uspto-grants-2004_10
Patent number
US06800629B2

Reaction notes

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