Sodium hydride → 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-(pyridin-4-yloxy)-3-quinolinecarbonitrile

HRID 1837362Notes

Reaction equation

HRID 1837362 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:9]=[CH:8][N:7]=[CH:6][CH:5]=1.[Cl:10][C:11]1[CH:16]=[C:15]([Cl:17])[C:14]([O:18][CH3:19])=[CH:13][C:12]=1[NH:20][C:21]1[C:30]2[C:25](=[CH:26][C:27](F)=[C:28]([O:31][CH3:32])[CH:29]=2)[N:24]=[CH:23][C:22]=1[C:34]#[N:35]>CN(C=O)C>[Cl:10][C:11]1[CH:16]=[C:15]([Cl:17])[C:14]([O:18][CH3:19])=[CH:13][C:12]=1[NH:20][C:21]1[C:30]2[C:25](=[CH:26][C:27]([O:3][C:4]3[CH:9]=[CH:8][N:7]=[CH:6][CH:5]=3)=[C:28]([O:31][CH3:32])[CH:29]=2)[N:24]=[CH:23][C:22]=1[C:34]#[N:35]

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 114861534-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrileHCID 178418642HCID 178418642, compound

Product 1

HCID 234980894-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-(pyridin-4-yloxy)-3-quinolinecarbonitrileYield 54.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of sodium hydride (128 mg, 3.2 mmol) and 4-hydroxypyridine (750 mg, 7.89 mmol) in 5 mL of N, N′-dimethylformamide is heated at 100° C. for 1 hour. 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (200 mg, 0.51 mmol) is added and the reaction mixture is heated at 130° C. for 2 hours. An additional 21 mg of sodium hydride is added and the reaction mixture is heated at 130° C. for an additional 30 minutes. 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 heating with methanol and dichloromethane to provide 130 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-(pyridin-4-yloxy)-3-quinolinecarbonitrile, mp 267-269° C.

Workup

  1. temperaturethe reaction mixture is heated at 130° C. for 2 hours
  2. temperaturethe reaction mixture is heated at 130° C. for an additional 30 minutes
  3. customThe reaction mixture is partitioned between ethyl acetate and water
  4. dry with materialThe organic layer is dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified
  8. temperatureby heating with methanol and dichloromethane

Sources & evidence

ORD record
ord-f902decce26446459da72492d0992e13
Source dataset
uspto-grants-2004_08
Patent number
US06780996B2

Reaction notes

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