Potassium Phosphate, Tribasic → Methyl 3-amino-6-methylpyrazine-2-carboxylate

HRID 1512071Notes

Reaction equation

HRID 1512071 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:10]([NH2:11])=[N:9][CH:8]=[C:7](Br)[N:6]=1)=[O:4].[CH:13]1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.CB(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O.Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[C:10]([NH2:11])=[N:9][CH:8]=[C:7]([CH3:13])[N:6]=1)=[O:4]

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 139377Methylboronic AcidHCID 227251Methyl 3-Amino-6-bromopyrazine-2-carboxylateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl

Product 1

HCID 58840780Methyl 3-amino-6-methylpyrazine-2-carboxylate

Reagents, catalysts & solvents 4

HCID 962WaterCatalystHCID 167845palladium(II) acetateCatalystHCID 313Hydrochloric AcidSolventHCID 1140TolueneSolvent

Procedure

3-Amino-6-bromo-pyrazine-2-carboxylic acid methyl ester (1.0 g) (made according to J. Org. Chem. (1988), 59(9), 2052-5), palladium(II) acetate (0.101 g), and 2′-dicyclohexylphosphino-2,6-dimethoxy-1,1′-biphenyl (“S-Phos”) were placed in a flask with toluene (15 ml) and water (3 drops). Methyl boronic acid (0.394 g) and potassium phosphate (1.71 g) were added and the reaction mixture was heated to reflux for 24 hours. After allowing the reaction mixture to cool to ambient temperature, the mixture was diluted with aqueous hydrochloric acid (1M) and extracted with ethyl acetate. The combined organic extracts were concentrated and the residue was purified by column chromatography on silica gel (eluent: diethyl ether) to give 3-amino-6-methyl-pyrazine-2-carboxylic acid methyl ester as a yellow solid (0.114 g). 1H-NMR (400 MHz, CDCl3): 2.40 (s, 3H), 3.92 (s, 3H), 6.21 (bs, 2H), 8.03 (s, 1H) ppm.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for 24 hours
  3. extractionextracted with ethyl acetate
  4. concentrationThe combined organic extracts were concentrated
  5. customthe residue was purified by column chromatography on silica gel (eluent: diethyl ether)

Sources & evidence

ORD record
ord-12b1f36f0cda4d249d74aba3679142a3
Source dataset
uspto-grants-2012_07
Patent number
US08217055B2

Reaction notes

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