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

HRID 1611508Notes

Reaction equation

HRID 1611508 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][C:24]([CH3:26])=[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][C:24]([CH3:26])=[CH:25][C:16]=12

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 14766362,4-Dichloro-5-methoxyanilineHCID 222566394-Chloro-2-methylthieno[2,3-b]pyridine-5-carbonitrile

Product 1

HCID 102481854-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-methylthieno[2,3-b]pyridine-5-carbonitrileYield 74.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2,4-dichloro-5-methoxyaniline (0.15 g, 0.73 mmol) and 60% sodium hydride (50 mg, 1.25 mmol) in 15 mL of tetrahydrofuran is heated at reflux for 1 hour. The solution is cooled and 4-chloro-2-methylthieno[2,3-b]pyridine-5-carbonitrile (0.06 g, 0.29 mmol) is added. The reaction mixture is heated at reflux for 3 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 3:7 ethyl acetate:hexane The fractions containing product are combined and concentrated. Diethyl ether is added and the insoluble material collected by filtration to provide 79 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-2-methylthieno[2,3-b]pyridine-5-carbonitrile as a tan solid, mp 179-181° C.; 1H NMR (DMSO-d6) δ 2.57 (s, 3H), 3.85 (s, 3H), 7.32 (s, 1H), 7.39 (s, 1H), 7.74 (s, 1H), 8.35 (s, 1H), 9.61 (s, 1H); MS 362.1 (M−H)−.

Workup

  1. temperatureis heated
  2. temperatureat reflux for 1 hour
  3. temperatureThe solution is cooled
  4. temperatureThe reaction mixture is heated
  5. temperatureat reflux for 3 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 3:7 ethyl acetate
  13. additionhexane The fractions containing product
  14. concentrationconcentrated
  15. additionDiethyl ether is added
  16. filtrationthe insoluble material collected by filtration

Sources & evidence

ORD record
ord-8631368c13ed4480ab5fc86a8cfe749b
Source dataset
uspto-grants-2006_01
Patent number
US06987116B2

Reaction notes

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