Water → N-[3-benzyl-5-(4-methoxyphenyl)pyrazin-2-yl]-3-methoxybenzamide

HRID 237238Notes

Reaction equation

HRID 237238 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.[C:23](Cl)(=[O:32])[C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([O:30][CH3:31])[CH:25]=1.O.[K+].[Br-]>N1C=CC=CC=1.CN(C)C1C=CN=CC=1.ClCCl.C(OCC)(=O)C>[CH2:1]([C:8]1[C:9]([NH:22][C:23](=[O:32])[C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([O:30][CH3:31])[CH:25]=2)=[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

8

Reactant 4

HCID 962WaterHCID 74374m-Anisoyl chlorideHCID 253877Potassium BromideHCID 113007862-Amino-3-benzyl-5-(4-methoxyphenyl)pyrazine

Product 1

HCID 57516691N-[3-benzyl-5-(4-methoxyphenyl)pyrazin-2-yl]-3-methoxybenzamide

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolventHCID 21226138Dichloromethane ethylacetateSolvent

Conditions

Temperature
50 °C

Procedure

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)) (800 mg, 2.75 mmol) in pyridine (10 mL) were successively added 4-(dimethylamino)pyridine (33.6 mg, 275 μmol) and m-anisoyl chloride (18) (773 μL, 5.50 mmol) at room temperature, and the mixture was heated with stirring at 50° C. for 22 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. After filtration and concentration under reduced pressure, the residual pyridine was azeotropically removed with toluene (×3). The residue was purified by column chromatography (silica gel 100 g, dichloromethane/ethyl acetate=9/1). The residue was recrystallized from ethyl acetate to give Compound fly (967 mg, 2.27 mmol, 82.5%) as a colorless solid. Rf=0.63 (dichloromethane/ethyl acetate=9/1); 1H NMR (400 MHz, DMSO-d6) δ 3.83 (s, 6H), 4.19 (s, 2H), 7.05-7.12 (AA′BB′, 2H), 7.14-7.28 (m, 6H), 7.42-7.49 (m, 2H), 7.53 (d, 1H, J=7.5 Hz), 8.06-8.12 (AA′BB′, 2H), 8.98 (s, 1H), 10.77 (s, 1H); 13C NMR (67.8 MHz, CDCl3) δ 41.5, 55.3, 55.4, 112.5, 114.3 (2C), 118.6, 119.3, 126.7 (2C), 128.1, 128.55, 128.61 (2C), 128.5 (2C), 129.6, 135.0, 136.8, 137.7, 143.3, 149.2, 149.9, 159.8, 160.9, 165.7; IR (KBr, cm−1) 700, 746, 833, 1022, 1040, 1117, 1179, 1254, 1300, 1325, 1373, 1416, 1441, 1501, 1607, 1655, 2936, 3265; Anal. Calcd. For C26H23N3O3: C, 73.39; H, 5.45; N, 9.88. Found: C, 73.55; H, 5.36; N, 9.86.

Workup

  1. customat 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. filtrationAfter filtration and concentration under reduced pressure
  8. customthe residual pyridine was azeotropically removed with toluene (×3)
  9. customThe residue was purified by column chromatography (silica gel 100 g, dichloromethane/ethyl acetate=9/1)
  10. customThe residue was recrystallized from ethyl acetate
  11. customto give Compound fly (967 mg, 2.27 mmol, 82.5%) as a colorless solid

Sources & evidence

ORD record
ord-6d5bb17e955143c4a344e6c161a45de2
Source dataset
uspto-grants-2014_02
Patent number
US08642281B2

Reaction notes

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