Water → HCID 67432957, compound

HRID 333628Notes

Reaction equation

HRID 333628 reaction equation
[CH2:1]([C:8]1[C:9]([NH2:22])=[N:10][CH:11]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[N:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([CH:31]([CH3:35])[C:32](Cl)=[O:33])=[CH:27][CH:26]=1.O>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[CH2:1]([C:8]1[C:9]([NH:22][C:32](=[O:33])[CH:31]([C:28]2[CH:29]=[CH:30][C:25]([O:24][CH3:23])=[CH:26][CH:27]=2)[CH3:35])=[N:10][CH:11]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[N:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 962WaterHCID 113007862-Amino-3-benzyl-5-(4-methoxyphenyl)pyrazineHCID 14946077HCID 14946077, compound

Product 1

HCID 67432957HCID 67432957, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Conditions

Temperature
55 °C

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.

Workup

  1. customprepared above at room temperature
  2. temperaturethe mixture was heated
  3. temperatureAfter cooling to room temperature, to the mixture
  4. extractionthe product was extracted with dichloromethane (×3)
  5. extractionThe combined organic extract
  6. dry with materialwas dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residual pyridine was azeotropically removed with toluene (×3)
  10. customThe 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)

Sources & evidence

ORD record
ord-c8b0c487bf334e168c20dfb08548ff1d
Source dataset
uspto-grants-2014_11
Patent number
US08883432B2

Reaction notes

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