Sodium Carbonate → Methyl 3-amino-6-(4-(dimethylcarbamoyl)phenyl)pyrazine-2-carboxylate

HRID 78587Notes

Reaction equation

HRID 78587 reaction equation
[NH2:1][C:2]1[C:3]([C:9]([O:11][CH3:12])=[O:10])=[N:4][C:5](Br)=[CH:6][N:7]=1.[CH3:13][N:14]([CH3:26])[C:15]([C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1)=[O:16].C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(#N)C.O.CCOC(C)=O.[Pd]>[NH2:1][C:2]1[C:3]([C:9]([O:11][CH3:12])=[O:10])=[N:4][C:5]([C:20]2[CH:21]=[CH:22][C:17]([C:15](=[O:16])[N:14]([CH3:13])[CH3:26])=[CH:18][CH:19]=2)=[CH:6][N:7]=1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 227251Methyl 3-Amino-6-bromopyrazine-2-carboxylateHCID 35037674-(Dimethylcarbamoyl)phenylboronic Acid

Product 1

HCID 59471801Methyl 3-amino-6-(4-(dimethylcarbamoyl)phenyl)pyrazine-2-carboxylateYield 46.4%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

Methyl 3-amino-6-bromo-pyrazine-2-carboxylate (625.1 mg, 2.694 mmol), [4-(dimethylcarbamoyl)phenyl]boronic acid (520 mg, 2.694 mmol), sodium carbonate (571.1 mg, 5.388 mmol) and palladium; triphenylphosphane (311.3 mg, 0.2694 mmol) in a mixture of acetonitrile (3 mL) and water (3 mL) was heated at 110° C. in the microwave for 30 minutes. The reaction was diluted with EtOAc and water and the layers separated. The aqueous later was extracted further with EtOAc (2×) and the combined organics dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion™, 40 g column, 0-100% EtOAc/Petroleum ether) to give the desired product as a yellow solid (375 mg, 46% Yield). 1H NMR (400.0 MHz, DMSO) d 3.02 (3H, s), 3.15 (3H, s), 4.04 (3H, s), 7.54 (2H, m), 7.97 (2H, m), 8.71 (1H, s) ppm; MS (ES+) 301.13

Workup

  1. customthe layers separated
  2. extractionThe aqueous later was extracted further with EtOAc (2×)
  3. dry with materialthe combined organics dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (ISCO Companion™, 40 g column, 0-100% EtOAc/Petroleum ether)

Sources & evidence

ORD record
ord-39189b435e4f4578aa88a11e381f4c4c
Source dataset
uspto-grants-2014_09
Patent number
US08841308B2

Reaction notes

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