Sodium hydride → 4-[(2,4-Dichloro-5-methoxyphenyl)amino]thieno[2,3-b]pyridine-5-carbonitrile

HRID 1178632

Reaction equation

HRID 1178632 reaction equation
[Cl:1][C:2]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:3]=1[NH2:4].[H-].[Na+].Cl[C:15]1[C:20]([C:21]#[N:22])=[CH:19][N:18]=[C:17]2[S:23][CH:24]=[CH:25][C:16]=12>O1CCCC1>[Cl:1][C:2]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:3]=1[NH:4][C:15]1[C:20]([C:21]#[N:22])=[CH:19][N:18]=[C:17]2[S:23][CH:24]=[CH:25][C:16]=12

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 14766362,4-Dichloro-5-methoxyanilineHCID 114129074-Chlorothieno[2,3-b]pyridine-5-carbonitrile

Product 1

HCID 100434474-[(2,4-Dichloro-5-methoxyphenyl)amino]thieno[2,3-b]pyridine-5-carbonitrileYield 21.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2,4-dichloro-5-methoxyaniline (300 mg, 1.57 mmol) and 60% sodium hydride (70 mg, 1.75 mmol) in 10 mL of tetrahydrofuran is heated at reflux for 30 minutes The solution is cooled and 4-chlorothieno[2,3-b]pyridine-5-carbonitrile (150 mg, 0.8 mmol) [Khan, M. A.; Guarconi, A. E., J. Heterocyclic Chem., 14, 807 (1977)] is added. The reaction mixture is heated at reflux for 3.5 hours. The resultant black solution is partitioned between ethyl acetate and water. The organic layer is washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with 2:3 ethyl acetate:hexane. The fractions containing product are combined and concentrated. Diethyl ether is added and the insoluble material is collected by filtration to provide 60 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]thieno[2,3-b]pyridine-5-carbonitrile as a tan solid, mp 197–199° C.; 1H NMR (DMSO-d6) δ 3.85 (s, 3H), 7.38 (s, 1H), 7.68 (d, J=5.7 Hz, 1H), 7.76 (s, 1H), 7.81 (d, J=5.7 Hz, 1H), 8.43 (s, 1H), 9.80 (s, 1); MS 348.2 (M−H)−.

Workup

  1. temperatureis heated
  2. temperatureat reflux for 30 minutes The solution
  3. temperatureis cooled
  4. addition, 14, 807 (1977)] is added
  5. temperatureThe reaction mixture is heated
  6. temperatureat reflux for 3.5 hours
  7. customThe resultant black solution is partitioned between ethyl acetate and water
  8. washThe organic layer is washed with water
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue is purified by flash column chromatography
  13. washeluting with 2:3 ethyl acetate
  14. additionThe fractions containing product
  15. concentrationconcentrated
  16. additionDiethyl ether is added
  17. filtrationthe insoluble material is collected by filtration

Sources & evidence

ORD record
ord-db26b062a1db483b815409c04922b21d
Source dataset
uspto-grants-2007_10
Patent number
US07276519B2

Linked notes

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