N-methyl-2-pyrrolidone → 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-phenylsulfanyl-3-quinolinecarbonitrile

HRID 1837358Notes

Reaction equation

HRID 1837358 reaction equation
[S-:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Na+].[Cl:9][C:10]1[CH:15]=[C:14]([Cl:16])[C:13]([O:17][CH3:18])=[CH:12][C:11]=1[NH:19][C:20]1[C:29]2[C:24](=[CH:25][C:26](F)=[C:27]([O:30][CH3:31])[CH:28]=2)[N:23]=[CH:22][C:21]=1[C:33]#[N:34].CN1CCCC1=O.C1(S)C=CC=CC=1.[Na]>O1CCCC1>[Cl:9][C:10]1[CH:15]=[C:14]([Cl:16])[C:13]([O:17][CH3:18])=[CH:12][C:11]=1[NH:19][C:20]1[C:29]2[C:24](=[CH:25][C:26]([S:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[C:27]([O:30][CH3:31])[CH:28]=2)[N:23]=[CH:22][C:21]=1[C:33]#[N:34]

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 4110039Sodium benzenethiolateHCID 114861534-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrileHCID 66586497Sodium benzenethiol

Product 1

HCID 103904984-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-phenylsulfanyl-3-quinolinecarbonitrileYield 27.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of sodium thiophenoxide (181 mg, 1.37 mmol) and 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (100 mg, 0.27 mmol) in 3 mL of tetrahydrofuran is heated at reflux overnight. N-methylpyrrolidone (2 mL) is added and the reaction mixture is heated at 120° C. for 1 hour then at 140° C. for for 45 min. An additional 100 mg of sodium thiophenol is added and the reaction mixture is heated at 140° C. for 3 hours. The reaction mixture is partitioned between ethyl acetate and water. The organic layer is dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with a 1:4 ethyl acetate:hexane to provide 36 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-phenylsulfanyl-3-quinolinecarbonitrile, mp 220-222° C.

Workup

  1. temperatureis heated
  2. temperatureat reflux overnight
  3. customat 140° C.
  4. customfor for 45 min
  5. temperaturethe reaction mixture is heated at 140° C. for 3 hours
  6. customThe reaction mixture is partitioned between ethyl acetate and water
  7. dry with materialThe organic layer is dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue is purified by flash column chromatography
  11. washeluting with a 1:4 ethyl acetate

Sources & evidence

ORD record
ord-a51b2b9092b2486a83e9bdd41e5a5753
Source dataset
uspto-grants-2004_08
Patent number
US06780996B2

Reaction notes

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