Phenol → HCID 54597086, compound

HRID 1853148Notes

Reaction equation

HRID 1853148 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[NH2:10][C:11]1[C:12]([C:18]([NH:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:19])=[N:13][C:14](Br)=[CH:15][N:16]=1>CN(C=O)C>[NH2:10][C:11]1[C:12]([C:18]([NH:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)=[O:19])=[N:13][C:14]([O:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:15][N:16]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 529371483-amino-6-bromo-N-phenylpyrazine-2-carboxamide

Product 1

HCID 54597086HCID 54597086, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Phenol (62.60 mg, 59.06 μL, 0.6652 mmol) was added slowly to a suspension of sodium hydride (60% dispersion in mineral oil) (15.96 mg, 17.73 μL, 0.6652 mmol) in anhydrous DMF (1.3 mL) at 0° C. The reaction mixture was stirred until the evolution of H2 ceased. 3-Amino-6-bromo-N-phenyl-pyrazine-2-carboxamide (130 mg, 0.4435 mmol) was added followed by Cu2O (15.87 mg, 0.1109 mmol) and reaction mixture heated to 100° C. overnight. The reaction mixture was cooled to ambient temperature and quenched with crushed ice. The aqueous layer was extracted with EtOAc (×3) and the combined organic extracts washed with ammonium hydroxide (×1), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected, passed through a sodium bicarbonate cartridge and freeze-dried to give the title compound as a yellow solid (16 mg, 12% Yield). 1H NMR (400.0 MHz, DMSO) δ 7.15-7.17 (m, 4H), 7.34-7.47 (m, 6H), 7.66-7.68 (m, 2H), 8.24 (s, 1H) and 9.92 (s, 1H) ppm; MS (ES+) 306.99.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customquenched with crushed ice
  3. extractionThe aqueous layer was extracted with EtOAc (×3)
  4. washthe combined organic extracts washed with ammonium hydroxide (×1)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  9. customThe fractions were collected
  10. customfreeze-dried

Sources & evidence

ORD record
ord-521d237cb4154c2580a36a45a8129cba
Source dataset
uspto-grants-2015_02
Patent number
US08962631B2

Reaction notes

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