Reaction #324418

Reaction equation

3-benzyl-5-(4-methoxyphenyl)pyrazin-2-amine

2-(4-methoxyphenyl)propanoyl chloride

water

→

Compound 11w

N-[3-Benzyl-5-(4-methoxyphenyl)pyrazin-2-yl]-2-(4-methoxyphenyl)propanamide

Solvents

pyridine

Conditions

Workup

1. 1
   Otherprepared above at room temperature
2. 2
   Temperaturethe mixture was heated
3. 3
   TemperatureAfter cooling to room temperature, to the mixture
4. 4
   Extractionthe product was extracted with dichloromethane (×3)
5. 5
   ExtractionThe combined organic extract
6. 6
   Dryingwas dried over anhydrous sodium sulfate
7. 7
   Filtrationfiltered
8. 8
   Concentrationconcentrated under reduced pressure
9. 9
   OtherThe residual pyridine was azeotropically removed with toluene (×3)
10. 10
    OtherThe residue was purified twice by column chromatography (silica gel 50 g, dichloromethane/ethyl acetate=9/1, and silica gel 50 g, n-hexane/ethyl acetate=9/1→6/1)

Procedure

Under an argon atmosphere, to a solution of 3-benzyl-5-(4-methoxyphenyl)pyrazin-2-amine (12) (synthesized by the process of M. Adamczyk, et al., Org. Prep. Proced. Int, 33, 477-485 (2001)) (500 mg, 1.72 mmol) in pyridine (8 mL) were successively added 4-(dimethylamino)pyridine (21.0 mg, 172 μmol) and 2-(4-methoxyphenyl)propanoyl chloride (16) prepared above at room temperature, and the mixture was heated with stirring at 55° C. for 14 hours. After cooling to room temperature, to the mixture was added water and the product was extracted with dichloromethane (×3). The combined organic extract was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residual pyridine was azeotropically removed with toluene (×3). The residue was purified twice by column chromatography (silica gel 50 g, dichloromethane/ethyl acetate=9/1, and silica gel 50 g, n-hexane/ethyl acetate=9/1→6/1) to give Compound 11w (942 mg, <quant.) as a colorless foamy solid containing some impurities.

Source