Ethanol → Methyl 5-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-2-chlorobenzoate

HRID 646691Notes

Reaction equation

HRID 646691 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][C:9](B2OC(C)(C)C(C)(C)O2)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[NH2:21][C:22]1[C:23]([C:29]([NH:31][CH3:32])=[O:30])=[N:24][C:25](Br)=[CH:26][N:27]=1.C(O)C.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[NH2:21][C:22]1[N:27]=[CH:26][C:25]([C:9]2[CH:10]=[CH:11][C:2]([Cl:1])=[C:3]([CH:8]=2)[C:4]([O:6][CH3:7])=[O:5])=[N:24][C:23]=1[C:29]([NH:31][CH3:32])=[O:30]

Participants

7

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 151481213-Amino-6-bromo-N-methylpyrazine-2-carboxamideHCID 56972886Benzoic acid, 2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-, methyl ester

Product 1

HCID 68651344Methyl 5-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-2-chlorobenzoateYield 56%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of methyl 2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (0.16 g, 0.55 mmol) in toluene (2 mL)) were added 3-amino-6-bromo-N-methyl-2-pyrazincarboxamide (0.13 g, 0.58 mmol), tetralds(triphenylphosphin)palladium(0) (64 mg, 0.06 mmol), ethanol (2 mL), and 2.0 N sodium carbonate (0.42 g, 4.00 mmol). The solution was degassed with nitrogen gas for 3-5 min and heated at 90-100° C. for 2 h. Reaction cooled to room temperature and diluted with ethyl acetate (200 mL). The organic layer was washed water (50 mL) and saturated aqueous sodium chloride (40 mL), dried over magnesium sulfate, filtered, and concentrated to afford crude product. Trituration with methanol (1 mL), filtration and drying gave methyl 5-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}-2-chlorobenzoate (96 mg, 56% yield) as yellow solid. 1H NMR (400 MHz, CDCl3): 8.62 (br s, 1H), 8.28 (d, 1H), 7.92 (dd, 2H), 7.52 (d, 1H), 4.02 (s, 3H), 3.02 (s, 3H); MS (EI) for C14H13N4O2Cl: 321 (MH+).

Workup

  1. customThe solution was degassed with nitrogen gas for 3-5 min
  2. customReaction
  3. temperaturecooled to room temperature
  4. washThe organic layer was washed water (50 mL) and saturated aqueous sodium chloride (40 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford crude product
  9. filtrationTrituration with methanol (1 mL), filtration
  10. customdrying

Sources & evidence

ORD record
ord-90e8afa896e94634811693ac113e40c4
Source dataset
uspto-grants-2010_04
Patent number
US07704995B2

Reaction notes

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