Ethanethiol → 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-ethylsulfanyl-6-methoxy-3-quinolinecarbonitrile

HRID 1837357Notes

Reaction equation

HRID 1837357 reaction equation
[H-].[Na+].[CH2:3]([SH:5])[CH3:4].[Cl:6][C:7]1[CH:12]=[C:11]([Cl:13])[C:10]([O:14][CH3:15])=[CH:9][C:8]=1[NH:16][C:17]1[C:26]2[C:21](=[CH:22][C:23](F)=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][C:18]=1[C:30]#[N:31]>O1CCCC1>[Cl:6][C:7]1[CH:12]=[C:11]([Cl:13])[C:10]([O:14][CH3:15])=[CH:9][C:8]=1[NH:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([S:5][CH2:3][CH3:4])=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][C:18]=1[C:30]#[N:31]

Participants

5

Reactant 3

HCID 6343EthanethiolHCID 24758Sodium hydrideHCID 114861534-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile

Product 1

HCID 104780234-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-ethylsulfanyl-6-methoxy-3-quinolinecarbonitrileYield 69.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a mixture of sodium hydride (82 mg, 2.04 mmol) in 6 mL of tetrahydrofuran is added ethanethiol (77 mg, 1.12 mmol) in 6 mL of tetrahydrofuran. The reaction mixture is stirred at room temperature for 2 hours. A solution of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (200 mg, 0.51 mmol) in 7 mL of tetrahydrofuran is added via syringe and the reaction mixture is heated at 70° C. for 5 hours, then cooled to room temperature. The reaction volume is reduced by concentration in vacuo and then partitioned between ethyl acetate and water. The aqueous layer is extracted with additional ethyl acetate and the organic layers are combined and washed with water. The organic layer is dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with a gradient of 10% to 30% ethyl acetate in hexane to provide 154 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-ethylsulfanyl-6-methoxy-3-quinolinecarbonitrile, mp 212-214° C.

Workup

  1. temperaturethe reaction mixture is heated at 70° C. for 5 hours
  2. temperaturecooled to room temperature
  3. concentrationThe reaction volume is reduced by concentration in vacuo
  4. custompartitioned between ethyl acetate and water
  5. extractionThe aqueous layer is extracted with additional ethyl acetate
  6. washwashed with water
  7. dry with materialThe organic layer is dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue is purified by flash column chromatography
  11. washeluting with a gradient of 10% to 30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-8880af4a04cb456aaa9768b8afc8306d
Source dataset
uspto-grants-2004_08
Patent number
US06780996B2

Reaction notes

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