Ethanol → 2-Amino-3-benzyl-5-phenylpyrazine

HRID 1970801Notes

Reaction equation

HRID 1970801 reaction equation
[NH2:1][C:2]1[C:7]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:6][C:5](Br)=[CH:4][N:3]=1.C(O)C.C(=O)([O-])[O-].[Na+].[Na+].[C:25]1(B(O)O)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>COCCOC.[Cl-].[Na+].O.C(OCC)(=O)C>[NH2:1][C:2]1[C:7]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:6][C:5]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:4][N:3]=1

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 27625493-Benzyl-5-bromopyrazin-2-amine

Product 1

HCID 102146592-Amino-3-benzyl-5-phenylpyrazineYield 59.9%

Reagents, catalysts & solvents 3

HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Under an argon atmosphere, 2-amino-3-benzyl-5-bromopyrazine (c-10) (1.66 g, 6.27 mmol) was dissolved in 1,2-dimethoxyethane (17 mL) and ethanol (13 mL) and to this were sequentially added 2 M aqueous solution of sodium carbonate (31.4 mL, 62.8 mmol), dichlorobis(triphenylphosphine) palladium(II) (221 mg, 315 μmol), and phenyl boronic acid (996 mg, 8.16 mmol) while stirring at room temperature and then stirred at 90° C. for 2.5 h. After cooling to room temperature, to this were added saturated brine and ethyl acetate to stop the reaction. The organic layer was washed with saturated brine and then dried over anhydrous sodium sulfate. After removing anhydrous sodium sulfate by filtration, the filtrate was concentrated under reduced pressure with a rotary evaporator. After purifying the residue by column chromatography (50 g, n-hexane/ethyl acetate=3/2→1/1), the obtained solid was recrystallized twice from ethyl acetate to give 2-amino-3-benzyl-5-phenylpyrazine (c-41) as a yellow solid (982 mg, 59.9%). Rf=0.30 (n-hexane/ethyl acetate=3/2). 1H NMR (400 MHz, DMSO-d6) δ 4.07 (s, 2H), 6.41 (s, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.24-7.31 (m, 3H), 7.34 (d, J=7.3 Hz, 2H), 7.40 (t, J=7.5 Hz, 2H), 7.90 (d, J=7.8 Hz, 2H), 8.41 (s, 1H). IR (KBr, cm−1) 596, 664, 694, 716, 733, 754, 773, 908, 937, 1070, 1152, 1217, 1233, 1396, 1427, 1450, 1462, 1493, 1543, 1636, 3024, 3125, 3291, 3487. HRMS (EI+) m/z 261.1269 (M, C17H15N3 requires 261.1266).

Workup

  1. stirringstirred at 90° C. for 2.5 h
  2. temperatureAfter cooling to room temperature
  3. customthe reaction
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customAfter removing anhydrous sodium sulfate
  7. filtrationby filtration
  8. concentrationthe filtrate was concentrated under reduced pressure with a rotary evaporator
  9. customAfter purifying the residue by column chromatography (50 g, n-hexane/ethyl acetate=3/2→1/1)
  10. customthe obtained solid was recrystallized twice from ethyl acetate

Sources & evidence

ORD record
ord-b5ba0c5833634401954d0021b0a7b83f
Source dataset
uspto-grants-2013_04
Patent number
US08431525B2

Reaction notes

Loading…