Water → N-(3-Benzyl-5-(4-methoxy-2-vinylphenyl)-6-vinylpyrazin-2-yl)acetamide

HRID 526786Notes

Reaction equation

HRID 526786 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]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=2[CH:23]=[CH2:24])=[C:4]([CH:25]=[CH2:26])[N:3]=1.[C:27](Cl)(=[O:29])[CH3:28].O>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[CH2:8]([C:7]1[C:2]([NH:1][C:27](=[O:29])[CH3:28])=[N:3][C:4]([CH:25]=[CH2:26])=[C:5]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=2[CH:23]=[CH2:24])[N:6]=1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 3

HCID 962WaterHCID 6367Acetyl chlorideHCID 706628152-Amino-3-benzyl-5-(4-methoxy-2-vinylphenyl)-6-vinylpyrazine

Product 1

HCID 70662797N-(3-Benzyl-5-(4-methoxy-2-vinylphenyl)-6-vinylpyrazin-2-yl)acetamideYield 79.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Conditions

Temperature
60 °C

Procedure

Under an argon atmosphere, to a solution of 2-amino-3-benzyl-5-(4-methoxy-2-vinylphenyl)-6-vinylpyrazine (9) (100 mg, 292 μmol) in anhydrous pyridine (20 mL) were successively added 4-(dimethylamino)pyridine (DMAP)(3.0 mg, 25 μmol) and acetyl chloride (65.0 μL, 911 μmol) at room temperature. The mixture was heated at 60° C. and stirred for an hour. After cooling to room temperature, to the mixture was added water and 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 N-(3-benzyl-5-(4-methoxy-2-vinylphenyl)-6-vinylpyrazin-2-yl)acetamide (10) (89.5 mg, 232 μmol, 79.7%) as a yellow solid. TLC Rf=0.17 (n-hexane/ethyl acetate=3/1); 1H NMR (400 MHz, CDCl3) δ 2.33 (s, 3H), 3.89 (s, 3H), 4.28 (s, 2H), 5.19 (dd, 1H, J=1.0, 10.8 Hz), 5.39 (dd, 1H, J=2.0, 10.8 Hz), 5.66 (dd, 1H, J=1.0, 17.2 Hz), 6.30 (dd, 1H, J=2.0, 17.2 Hz), 6.45 (dd, 1H, J=10.8, 17.2 Hz), 6.52 (dd, 1H, J=10.8, 17.2 Hz), 6.94 (dd, 1H, J=2.6, 8.4 Hz), 7.19-7.24 (m, 5H), 7.27-7.32 (m, 2H).

Workup

  1. customat room temperature
  2. temperatureAfter cooling to room temperature, to the mixture
  3. extractionthe product was extracted with ethyl acetate (×3)
  4. extractionThe combined organic extract
  5. washwas washed successively with water (×1) and brine (×1)
  6. dry with materialby drying over anhydrous sodium sulfate
  7. filtrationAfter filtration and concentration under reduced pressure
  8. customthe residue was purified by silica gel flash column chromatography (n-hexane/ethyl acetate=3/1)

Sources & evidence

ORD record
ord-a2a4b7ab87724dba85d2cda5065a1fdb
Source dataset
uspto-grants-2016_05
Patent number
US09346767B2

Reaction notes

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