Potassium Phosphate, Tribasic → HCID 136160557, compound

HRID 1930136Notes

Reaction equation

HRID 1930136 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([NH2:10])=[O:9])[C:5]([CH3:11])=[N:4][C:3]=1[CH3:12].CC1(C)C(C)(C)OB([C:21]2[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.CO.O.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[OH:27][C:24]1[CH:25]=[CH:26][C:21]([C:2]2[N:7]=[C:6]([C:8]([NH2:10])=[O:9])[C:5]([CH3:11])=[N:4][C:3]=2[CH3:12])=[CH:22][CH:23]=1

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27346244-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 57992034HCID 57992034, compound2×

Product 1

HCID 136160557HCID 136160557, compoundYield 83.2%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 6-chloro-3,5-dimethylpyrazine-2-carboxamide (Intermediate A) (20.17 g, 108.67 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (26.3 g, 119.53 mmol) and tripotassium phosphate (34.6 g, 163.00 mmol) in DME (500 mL), MeOH (250 mL) and water (125 mL) was degassed before addition of (1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) (DCM adduct) (4.47 g, 5.43 mmol). The reaction mixture was heated to 80° C., under nitrogen, and left to stir for 1 hour. The reaction mixture was allowed to cool to room temperature and then evaporated. The residue was partitioned between water (1 L), 2M HCl aq. (1 L) and EtOAc (1 L). The aqueous was re-extracted with EtOAc (2 L) and the combined organics washed with brine (1 L), dried (MgSO4) and evaporated to give crude product. The aqueous was filtered and the solid was washed with water (2 L) to give pure product. The crude product from the organic layer was purified by flash silica chromatography, elution gradient 20 to 80% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford 6-(4-hydroxyphenyl)-3,5-dimethylpyrazine-2-carboxamide (22.00 g, 83%) as a cream solid.

Workup

  1. waitleft
  2. temperatureto cool to room temperature
  3. customevaporated
  4. customThe residue was partitioned between water (1 L), 2M HCl aq. (1 L) and EtOAc (1 L)
  5. extractionThe aqueous was re-extracted with EtOAc (2 L)
  6. washthe combined organics washed with brine (1 L)
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customto give crude product
  10. filtrationThe aqueous was filtered
  11. washthe solid was washed with water (2 L)
  12. customto give pure product
  13. customThe crude product from the organic layer was purified by flash silica chromatography, elution gradient 20 to 80% EtOAc in isohexane
  14. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-9bf53e4199e14cf995284b71c48d8dd3
Source dataset
uspto-grants-2012_05
Patent number
US08188092B2

Reaction notes

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