Dimethyl malonate → Methyl 8-hydroxy-6-oxo-5,6-dihydropyrido[2,3-b]pyrazine-7-carboxylate

HRID 241778Notes

Reaction equation

HRID 241778 reaction equation
C[O-].[Na+].[C:4]([O:11]C)(=O)[CH2:5][C:6]([O:8][CH3:9])=[O:7].[NH2:13][C:14]1[C:15]([C:20](OC)=[O:21])=[N:16][CH:17]=[CH:18][N:19]=1>CO>[CH3:9][O:8][C:6]([C:5]1[C:4](=[O:11])[NH:13][C:14]2=[N:19][CH:18]=[CH:17][N:16]=[C:15]2[C:20]=1[OH:21])=[O:7]

Participants

5

Reactant 3

HCID 7943Dimethyl malonateHCID 72669Methyl 3-aminopyrazinecarboxylateHCID 10942334Sodium Methoxide

Product 1

HCID 57998840Methyl 8-hydroxy-6-oxo-5,6-dihydropyrido[2,3-b]pyrazine-7-carboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Sodium methoxide (6.5 ml) (30% by weight in methanol) was dissolved in methanol (75 ml) at room temperature. Dimethyl malonate (3.7 ml) was added dropwise at ambient temperature over a period of 20 minutes and the reaction stirred at ambient temperature for 1 hour. Methyl 3-aminopyrazine-2-carboxylate (5.0 g) was added in portions at ambient temperature over a period of 40 minutes. The reaction mixture was heated to reflux for 3 days, and then allowed to cool. The solvent was concentrated. The residue was dissolved in water and acidified with concentrated hydrochloric acid (36% by weight in water). The precipitate was isolated, washed with water, methanol and ethyl acetate, and dried under high vacuum to give 8-hydroxy-6-oxo-5,6-dihydro-pyrido[2,3-b]pyrazine-7-carboxylic acid methyl ester as a beige solid (4.16 g). 1H-NMR (d6-DMSO): 3.80 (s, 3H), 8.59 (s, 1H), 8.70 (s, 1H) ppm.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 3 days
  3. temperatureto cool
  4. concentrationThe solvent was concentrated
  5. dissolutionThe residue was dissolved in water
  6. customThe precipitate was isolated
  7. washwashed with water, methanol and ethyl acetate
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-db2d6f18e753432d8721d7f13f98cb9c
Source dataset
uspto-grants-2014_02
Patent number
US08653078B2

Reaction notes

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