Water → 2-Amino-3-benzyl-5-(4-methoxy-2-vinylphenyl)-6-vinylpyrazine

HRID 1620415Notes

Reaction equation

HRID 1620415 reaction equation
[CH2:1]([Li])CCC.[NH2:6][C:7]1[N:8]=[C:9]([CH:30]=[CH2:31])[C:10]([C:20]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:21]=2[CH:22]=O)=[N:11][C:12]=1[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.O>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[NH2:6][C:7]1[C:12]([CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[N:11][C:10]([C:20]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:21]=2[CH:22]=[CH2:1])=[C:9]([CH:30]=[CH2:31])[N:8]=1

Participants

6

Reactant 3

HCID 962WaterHCID 866706782-(5-Amino-6-benzyl-3-vinylpyrazin-2-yl)-5-methoxybenzaldehydeHCID 178418339Butyllithium

Product 1

HCID 706628152-Amino-3-benzyl-5-(4-methoxy-2-vinylphenyl)-6-vinylpyrazineYield 65.9%

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Under an argon atmosphere, to a suspension of methyltriphenylphosphonium bromide (1.29 g, 3.61 mmol) in anhydrous THF (5 mL) was gradually dropwise added n-butyl lithium (1.65 M in n-hexane) (1.70 mL, 2.81 mmol) at 0° C. The mixture was stirred at 0° C. for 15 minutes as it was. To the mixture was added 2-(5-amino-6-benzyl-3-vinylpyrazin-2-yl)-5-methoxybenzaldehyde (8) (871 mg, 2.52 mmol) at 0° C. After elevating to room temperature, stirring was continued for 1.5 hours. After to this was added water, the product was extracted with ethyl acetate (×3). The combined organic extract was washed successively with water (×1) and brine (×1), followed by drying over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue was purified by silica gel flash column chromatography (n-hexane/ethyl acetate=3/1) to give 2-amino-3-benzyl-5-(4-methoxy-2-vinylphenyl)-6-vinylpyrazine (9) (570 mg, 1.66 mmol, 65.8%) as a white solid. TLC Rf=0.37 (n-hexane/ethyl acetate=3/1); 1H NMR (500 MHz, CDCl3) δ 3.88 (s, 3H), 4.16 (s, 2H), 4.39 (s, 2H), 5.18 (dd, 1H, J=1.0, 10.5 Hz), 5.30 (dd, 1H, J=2.0, 10.5 Hz), 5.67 (dd, 1H, J=1.0, 17.5 Hz), 6.25 (dd, 1H, J=2.0, 17.5 Hz), 6.47 (dd, 1H, J=10.5, 17.5 Hz), 6.50 (dd, 1H, J=10.5, 17.5 Hz), 6.90 (dd, 1H, J=2.5, 8.0 Hz), 7.20-7.26 (m, 5H), 7.29-7.35 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 41.2, 55.6, 110.5, 113.8, 115.4, 119.3, 127.2, 128.7 (2C), 129.2 (2C), 129.8, 132.1, 133.0, 135.1, 137.0, 138.3, 140.3, 141.9, 144.8, 151.4, 159.8.

Workup

  1. customat 0° C
  2. customAfter elevating to room temperature
  3. stirringstirring
  4. waitwas continued for 1.5 hours
  5. extractionthe product was extracted with ethyl acetate (×3)
  6. extractionThe combined organic extract
  7. washwas washed successively with water (×1) and brine (×1)
  8. dry with materialby drying over anhydrous sodium sulfate
  9. filtrationAfter filtration and concentration under reduced pressure
  10. customthe residue was purified by silica gel flash column chromatography (n-hexane/ethyl acetate=3/1)

Sources & evidence

ORD record
ord-016902e0197c401d8d31955769edc7c0
Source dataset
uspto-grants-2014_07
Patent number
US08772484B2

Reaction notes

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