1,3-Benzenedicarboxylic acid, 5-bromo-, 1,3-dimethyl ester → HCID 86607854, compound

HRID 646778Notes

Reaction equation

HRID 646778 reaction equation
[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:13]=[C:12](Br)[CH:11]=[C:6]([C:7]([O:9][CH3:10])=[O:8])[CH:5]=1.C([O-])(=O)C.[K+].[NH2:21][C:22]1[C:23]([C:29]([O:31][CH3:32])=[O:30])=[N:24][C:25](Br)=[CH:26][N:27]=1.C(=O)(O)[O-].[Na+]>O1CCOCC1.O.C(OCC)(=O)C>[NH2:21][C:22]1[N:27]=[CH:26][C:25]([C:12]2[CH:11]=[C:6]([C:7]([O:9][CH3:10])=[O:8])[CH:5]=[C:4]([C:3]([O:2][CH3:1])=[O:15])[CH:13]=2)=[N:24][C:23]=1[C:29]([O:31][CH3:32])=[O:30]

Participants

8

Reactant 4

HCID 1039541,3-Benzenedicarboxylic acid, 5-bromo-, 1,3-dimethyl esterHCID 227251Methyl 3-Amino-6-bromopyrazine-2-carboxylateHCID 516892Sodium BicarbonateHCID 517044Potassium Acetate

Product 1

HCID 86607854HCID 86607854, compoundYield 12%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture containing 5-bromoisophthalic acid dimethyl ester (0.20 g, 0.73 mmol), bispinacolatodiboron (0.21 g, 0.80 mmol), 1,1′-bis(diphenylphosphine)ferrocene palladium dichloride (0.029 g, 0.035 mmol), and potassium acetate (0.26 g, 2.3 mmol) in dioxane (5 mL) was heated at 80° C. for 1 h. The reaction mixture was cooled to room temperature and methyl 3-amino-6-bromo-pyrazine-2-carboxylate (0.17 mg, 0.70 mmol), 1,1′-bis(diphenylphosphine)ferrocene palladium dichloride (0.035 g, 0.042 mmol), sodium bicarbonate (320 mg, 3.8 mmol), and water (1 mL) were added. The mixture was heated at 80° C. for 12 h, after which time, the mixture was diluted with water and ethyl acetate. The layers were separated and the organic layer was extracted with 1 N hydrochloric acid (2×) and dried over sodium sulfate. Filtration, concentration, and silica gel chromatography gave the product as a yellow solid (23 mg, 12% yield). 1H NMR (400 MHz, d6-DMSO): δ 9.04 (s, 1H), 8.74 (d, 2H), 8.44 (t, 1H), 7.62 (s, 2H), 3.32 (s, 3H), 2.49 (s, 3H), 2.48 (s, 3H). MS (EI) for C16H15N3O6: 346 (MH+).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. temperatureThe mixture was heated at 80° C. for 12 h
  3. customThe layers were separated
  4. extractionthe organic layer was extracted with 1 N hydrochloric acid (2×)
  5. dry with materialdried over sodium sulfate
  6. filtrationFiltration, concentration, and silica gel chromatography

Sources & evidence

ORD record
ord-7685ce800bad4510b29c681755c3da5b
Source dataset
uspto-grants-2010_04
Patent number
US07704995B2

Reaction notes

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