Sodium hydride → 7-[(2,4-Dichloro-5-methoxyphenyl)amino]thieno[3,2-b]pyridine-6-carbonitrile

HRID 1178627

Reaction equation

HRID 1178627 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[CH:23]=[CH:24][S: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[CH:23]=[CH:24][S:25][C:16]=12

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 14766362,4-Dichloro-5-methoxyanilineHCID 118164017-Chlorothieno[3,2-b]pyridine-6-carbonitrile

Product 1

HCID 53304087-[(2,4-Dichloro-5-methoxyphenyl)amino]thieno[3,2-b]pyridine-6-carbonitrileYield 36.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2,4-dichloro-5-methoxyaniline (336 mg, 1.75 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 7-chlorothieno[3,2-b]pyridine-6-carbonitrile (200 mg, 1.02 mmol) is added. The reaction mixture is heated at reflux for 3.5 hours then allowed to stir at room temperature overnight. 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 1:1 ethyl acetate:hexane. The fractions containing product are combined and concentrated. Diethyl ether is added and the insoluble material collected by filtration to provide 131 mg of 7-[(2,4-dichloro-5-methoxyphenyl)amino]thieno[3,2-b]pyridine-6-carbonitrile as a tan solid, mp 216–220° C.; 1 H NMR (DMSO-d6) δ 3.85 (s, 3H), 7.40 (3, 1H), 7.46 (d, J=5 Hz, 1H), 7.76 (s, 1H), 8.11 (d, J=5 Hz, 1H), 8.61 (s, 1H), 9.71 (s, 1H); MS 350.2 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-b634967879864f8597e515e834b734a0
Source dataset
uspto-grants-2007_10
Patent number
US07276519B2

Linked notes

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