Water → N-[3-Benzyl-5-(4-methoxyphenyl)pyrazin-2-yl]-6-methoxy-N-(6-methoxy-1-naphthoyl)-1-naphthamide

HRID 237240

Reaction equation

HRID 237240 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:26]=[C:27]2[C:32](=[CH:33][CH:34]=1)[C:31]([C:35](Cl)=[O:36])=[CH:30][CH:29]=[CH:28]2.[OH2:38]>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[CH2:1]([C:8]1[C:9]([N:22]([C:35]([C:31]2[C:32]3[C:27](=[CH:26][C:25]([O:24][CH3:23])=[CH:34][CH:33]=3)[CH:28]=[CH:29][CH:30]=2)=[O:38])[C:35]([C:31]2[C:32]3[C:27](=[CH:26][C:25]([O:24][CH3:23])=[CH:34][CH:33]=3)[CH:28]=[CH:29][CH:30]=2)=[O:36])=[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 575166936-Methoxy-1-naphthoyl chloride

Product 1

HCID 67432726N-[3-Benzyl-5-(4-methoxyphenyl)pyrazin-2-yl]-6-methoxy-N-(6-methoxy-1-naphthoyl)-1-naphthamideYield 68.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Conditions

Temperature
50 °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 (5 mL) were successively added 4-(dimethylamino)pyridine (21.0 mg, 172 μmol) and 6-methoxy-1-naphthoyl chloride (22) prepared above at room temperature, and the mixture was heated with stirring at 50° C. 18 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 successively purified twice by column chromatography (silica gel 50 g, dichloromethane/ethyl acetate=9/1, and silica gel 50 g, n-hexane/ethyl acetate=2/1) to give Compound 11z (775 mg, 1.17 mmol, <68.3%) as a brown foamy solid containing some impurities. Rf=0.21 (n-hexane/ethyl acetate=2/1); 1H NMR (400 MHz, DMSO-d6) δ 3.82 (s, 3H), 3.83 (s, 6H), 4.39 (s, 2H), 7.04-7.09 (AA′BB′, 2H), 7.15-7.23 (m, 6H), 7.26-7.31 (m, 1H), 7.34-7.41 (m, 4H), 7.63-7.69 (m, 2H), 7.75-7.80 (AA′BB′, 2H), 8.02-8.08 (m, 4H), 9.07 (s, 1H).

Workup

  1. customprepared above at room temperature
  2. temperaturethe mixture was heated
  3. custom18 hours
  4. temperatureAfter cooling to room temperature, to the mixture
  5. extractionthe product was extracted with dichloromethane (×3)
  6. extractionThe combined organic extract
  7. dry with materialwas dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residual pyridine was azeotropically removed with toluene (×3)
  11. customThe residue was successively purified twice by column chromatography (silica gel 50 g, dichloromethane/ethyl acetate=9/1, and silica gel 50 g, n-hexane/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-e9c27d4cdf8b4f5a93e9c89c04b2235e
Source dataset
uspto-grants-2014_02
Patent number
US08642281B2

Linked notes

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