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

HRID 1178682Notes

Reaction equation

HRID 1178682 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:10]=[C:9]([Cl:11])[C:8]([O:12][CH3:13])=[CH:7][C:5]=1[NH2:6].[Br:14][C:15]1[C:19]2=[N:20][CH:21]=[C:22]([C:25]#[N:26])[C:23](Cl)=[C:18]2[S:17][CH:16]=1.BrC1C2=NC=C(C#N)C(Br)=C2SC=1.[Cl-].[Na+]>O1CCCC1>[Br:14][C:15]1[C:19]2=[N:20][CH:21]=[C:22]([C:25]#[N:26])[C:23]([NH:6][C:5]3[CH:7]=[C:8]([O:12][CH3:13])[C:9]([Cl:11])=[CH:10][C:4]=3[Cl:3])=[C:18]2[S:17][CH:16]=1

Participants

7

Reactant 5

HCID 5234Sodium ChlorideHCID 24758Sodium hydrideHCID 14766362,4-Dichloro-5-methoxyanilineHCID 112671073,7-Dibromothieno[3,2-b]pyridine-6-carbonitrileHCID 114146423-Bromo-7-chlorothieno[3,2-b]pyridine-6-carbonitrile

Product 1

HCID 113962683-Bromo-7-[(2,4-dichloro-5-methoxyphenyl)amino]thieno[3,2-b]pyridine-6-carbonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of sodium hydride (438 mg of a 60% dispersion in mineral oil, 10.96 mmol) in 60 mL of tetrahydrofuran is added 2,4-dichloro-5-methoxyaniline (2.10 g, 10.96 mmol). The mixture is heated at reflux for 1 hour and then cooled to room temperature and 1.50 g of a 1 to 2.4 mixture of 3-bromo-7-chlorothieno[3,2-b]pyridine-6-carbonitrile and 3,7-dibromothieno[3,2-b]pyridine-6-carbonitrile is added. The reaction mixture is heated at reflux for 2 hours then cooled to room temperature and treated with saturated aqueous sodium chloride. The organic layer is separated and the aqueous layer is extracted with ethyl acetate. The combined organic layers are washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with a gradient of ethyl acetate in hexane to provide 1.78 g of 3-bromo-7-[(2,4-dichloro-5-methoxyphenyl)amino]thieno[3,2-b]pyridine-6-carbonitrile as a tan solid, mp 265–266° C.; 1H NMR (DMSO-d6) δ 3.85 (s, 3H), 7.44 (s, 1H), 7.79 (s, 1H), 8.31 (s, 1H), 8.72 (s, 1H), 9.93 (s, 1H); MS 427.9, 429.9, 431.8 (M+H)+.

Workup

  1. temperatureThe mixture is heated
  2. temperatureat reflux for 1 hour
  3. additionis added
  4. temperatureThe reaction mixture is heated
  5. temperatureat reflux for 2 hours
  6. temperaturethen cooled to room temperature
  7. customThe organic layer is separated
  8. extractionthe aqueous layer is extracted with ethyl acetate
  9. washThe combined organic layers are washed with brine
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe residue is purified by flash column chromatography
  14. washeluting with a gradient of ethyl acetate in hexane

Sources & evidence

ORD record
ord-c1648a7cba2b461bbd9ad09456c7b87f
Source dataset
uspto-grants-2007_10
Patent number
US07276519B2

Reaction notes

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