Dichloromethane → 3-amino-6-(3-aminophenyl)-N-methylpyrazine-2-carboxamide

HRID 646687Notes

Reaction equation

HRID 646687 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[C:10]([NH2:11])=[N:9][CH:8]=[C:7](Br)[N:6]=1)=[O:4].ClCCl.O.[NH2:17][C:18]1[CH:19]=[C:20](B(O)O)[CH:21]=[CH:22][CH:23]=1.C(N(CC)CC)C>CN(C)C=O.CCOC(C)=O>[NH2:11][C:10]1[C:5]([C:3]([NH:2][CH3:1])=[O:4])=[N:6][C:7]([C:22]2[CH:21]=[CH:20][CH:19]=[C:18]([NH2:17])[CH:23]=2)=[CH:8][N:9]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 143894233-Aminophenylboronic acid monohydrateHCID 151481213-Amino-6-bromo-N-methylpyrazine-2-carboxamide

Product 1

HCID 100374223-amino-6-(3-aminophenyl)-N-methylpyrazine-2-carboxamideYield 54%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
87.5 °C

Procedure

To a solution of 3-amino-6-bromo-pyrazine-2-carboxylic acid methylamide (1.234 g, 5.30 mmol, 1.00 equiv.) in N,N-dimethylformamide (DMF, 30 mL) was added [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with dichloromethane (1:1), (Aldrich Chemical Company, 433 mg, 0.530 mmol, 0.100 equiv.), 3-aminophenylboronic acid monohydrate (Aldrich Chemical Company, 1.149 g, 7.41 mmol, 1.40 equiv.), and triethylamine (TEA, 1.073 g, 10.6 mmol, 2.00 equiv.). Nitrogen was passed through the solution for 3-5 min. The reaction mixture was heated at 85-90° C. for 15 h with stirring. The reaction was allowed to cool to room temperature and diluted with 400 mL of EtOAc. The mixture was washed with saturated aqueous NaHCO3 (2×50.0 mL), saturated aqueous NaCl (1×50.0 mL), dried over magnesium sulfate (MgSO4), and filtered. The filtrate was concentrated on a rotary evaporator under reduced pressure. To the crude product was added 30 mL of a 4.0M solution of anhydrous HCl in dioxane. The resulting solid was filtered and rinsed with 20% methanol in diethyl ether to remove impurities. The solid was dissolved in methanol and neutralized with sufficient AG 1-X8 Resin (hydroxide form) that the pH of the solution became basic. The mixture was filtered, and the filtrate was concentrated on a rotary evaporator at reduced pressure to afford the title compound (0.695 g, 54% yield).

Workup

  1. temperatureto cool to room temperature
  2. washThe mixture was washed with saturated aqueous NaHCO3 (2×50.0 mL), saturated aqueous NaCl (1×50.0 mL)
  3. dry with materialdried over magnesium sulfate (MgSO4)
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated on a rotary evaporator under reduced pressure
  6. additionTo the crude product was added 30 mL of a 4.0M solution of anhydrous HCl in dioxane
  7. filtrationThe resulting solid was filtered
  8. washrinsed with 20% methanol in diethyl ether
  9. customto remove impurities
  10. dissolutionThe solid was dissolved in methanol and neutralized with sufficient AG 1-X8 Resin (hydroxide form) that the pH of the solution
  11. filtrationThe mixture was filtered
  12. concentrationthe filtrate was concentrated on a rotary evaporator at reduced pressure

Sources & evidence

ORD record
ord-8ceedd6e34614a8a97256343475c0b0f
Source dataset
uspto-grants-2010_04
Patent number
US07704995B2

Reaction notes

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