2,4-Dichloroaniline → 7-[(2,4-Dichlorophenyl)amino]thieno[3,2-b]pyridine-6-carbonitrile

HRID 1178637Notes

Reaction equation

HRID 1178637 reaction equation
[Cl:1][C:2]1[CH:8]=[C:7]([Cl:9])[CH:6]=[CH:5][C:3]=1[NH2:4].[H-].[Na+].Cl[C:13]1[C:18]([C:19]#[N:20])=[CH:17][N:16]=[C:15]2[CH:21]=[CH:22][S:23][C:14]=12>O1CCCC1>[Cl:1][C:2]1[CH:8]=[C:7]([Cl:9])[CH:6]=[CH:5][C:3]=1[NH:4][C:13]1[C:18]([C:19]#[N:20])=[CH:17][N:16]=[C:15]2[CH:21]=[CH:22][S:23][C:14]=12

Participants

5

Reactant 3

HCID 111232,4-DichloroanilineHCID 24758Sodium hydrideHCID 118164017-Chlorothieno[3,2-b]pyridine-6-carbonitrile

Product 1

HCID 100416617-[(2,4-Dichlorophenyl)amino]thieno[3,2-b]pyridine-6-carbonitrileYield 52.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2,4-dichloroaniline (333.8 mg, 2.06 mmol) and 60% sodium hydride (82.4 mg, 2.06 mmol) in 10 mL of tetrahydrofuran is heated at reflux for 1 hour. The solution is cooled and 7-chlorothieno[3.2-b]pyridine-6-carbonitrile (200 mg, 1.03 mmol) is added. The resulting reaction mixture is heated at reflux for 7 hours, cooled to room temperature, and concentrated in vacuo. The residue is treated with water for 1 hour. The precipitate is filtered, washed with water, and air dried. The resultant solid is purified by flash column chromatography eluting with a gradient of 1% ethyl acetate in hexane to 8% ethyl acetate in hexane to provide 173.1 mg of 7-[(2,4-dichlorophenyl)amino]thieno[3,2-b]pyridine-6-carbonitrile as a white solid, mp 198–200° C.; 1H NMR (DMSO-d6) δ 7.47 (d, J=4 Hz, 1H), 7.54 (dd, J=6, 2 Hz, 1H), 7.59 (d, J=6 Hz, 1H), 7.81 (d, J=2 Hz, 1H), 8.12 (d, J=4 Hz, 1H), 8.61 (s, 1H), 9.67 (s, 1H); MS 318.1, 320.2 (M+H)+.

Workup

  1. temperatureis heated
  2. temperatureat reflux for 1 hour
  3. temperatureThe solution is cooled
  4. customThe resulting reaction mixture
  5. temperatureis heated
  6. temperatureat reflux for 7 hours
  7. concentrationconcentrated in vacuo
  8. additionThe residue is treated with water for 1 hour
  9. filtrationThe precipitate is filtered
  10. washwashed with water, and air
  11. customdried
  12. customThe resultant solid is purified by flash column chromatography
  13. washeluting with a gradient of 1% ethyl acetate in hexane to 8% ethyl acetate in hexane

Sources & evidence

ORD record
ord-aefdf16e557a41a68bdd0a09ceea1ded
Source dataset
uspto-grants-2007_10
Patent number
US07276519B2

Reaction notes

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