Methyl 3-Amino-6-bromopyrazine-2-carboxylate → Methyl 6-bromo-3-oxo-3,4-dihydropyrazine-2-carboxylate

HRID 1089683Notes

Reaction equation

HRID 1089683 reaction equation
N([O-])=[O:2].[Na+].N[C:6]1[C:11]([C:12]([O:14][CH3:15])=[O:13])=[N:10][C:9]([Br:16])=[CH:8][N:7]=1>S(=O)(=O)(O)O>[CH3:15][O:14][C:12]([C:11]1[C:6](=[O:2])[NH:7][CH:8]=[C:9]([Br:16])[N:10]=1)=[O:13]

Participants

4

Reactant 2

HCID 227251Methyl 3-Amino-6-bromopyrazine-2-carboxylateHCID 23668193Sodium Nitrite

Product 1

HCID 12134013Methyl 6-bromo-3-oxo-3,4-dihydropyrazine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent2×

Conditions

Temperature
3.5 °C

Procedure

Concentrated sulphuric acid (5 ml) was stirred and cooled to 2-5° C. and sodium nitrite (0.7 g) added batchwise such that the reaction exotherm did not exceed 10° C. The reaction mixture was allowed to reach room temperature and then warmed to 40° for 2-3 minutes to give a homogeneous solution. The stirred reaction mixture was then cooled to 2°-5° C. and a cooled (2°-5° C.) solution of 2-amino-3-methoxycarbonyl-5-bromopyrazine (JACS, 1949, 71, 2798; 2.32 g) in concentrated sulphuric acid added dropwise so that the reaction temperature did not exceed 5° C. After the addition was complete, the reaction mixture was allowed to warm to 15° C. over three hours and then added dropwise to crushed ice (200 g). The resulting mixture was extracted with ethyl acetate. The organic phase washed with brine, dried with sodium sulphate and evaporated under reduced pressure to give the crude product as a yellow solid. The crude product was used in further experiments without further purification. A portion of the crude product was recrystallised from acetonepetroleum ether (boiling range 60°-80° C.) to give 3-methoxycarbonyl-5-bromopyrazine-2-one as a yellow solid:

Workup

  1. customexotherm did not exceed 10° C
  2. customto reach room temperature
  3. temperaturewarmed to 40° for 2-3 minutes
  4. customto give a homogeneous solution
  5. customThe stirred reaction mixture
  6. temperaturewas then cooled to 2°-5° C.
  7. additionadded dropwise so that the reaction temperature
  8. customdid not exceed 5° C
  9. additionAfter the addition
  10. temperatureto warm to 15° C. over three hours
  11. additionadded dropwise
  12. extractionThe resulting mixture was extracted with ethyl acetate
  13. washThe organic phase washed with brine
  14. dry with materialdried with sodium sulphate
  15. customevaporated under reduced pressure
  16. customto give the crude product as a yellow solid
  17. customThe crude product was used in further experiments without further purification
  18. customA portion of the crude product was recrystallised from acetonepetroleum ether (boiling range 60°-80° C.)

Sources & evidence

ORD record
ord-6f718d072b1f4cb29d5e679a04b31c3d
Source dataset
uspto-grants-1992_01
Patent number
US05079251

Reaction notes

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