Pyridinium chloride → 4-[(3-chloro-4-[(1-methyl-1H-imidazol-2-yl)thio]phenyl)amino]thieno[2,3-b]pyridine-5-carbonitrile

HRID 1178633

Reaction equation

HRID 1178633 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[S:9][C:10]1[N:11]([CH3:15])[CH:12]=[CH:13][N:14]=1)[NH2:5].Cl.N1C=CC=CC=1.Cl[C:24]1[C:29]([C:30]#[N:31])=[CH:28][N:27]=[C:26]2[S:32][CH:33]=[CH:34][C:25]=12>C(OCCO)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:24]2[C:29]([C:30]#[N:31])=[CH:28][N:27]=[C:26]3[S:32][CH:33]=[CH:34][C:25]=23)[CH:6]=[CH:7][C:8]=1[S:9][C:10]1[N:11]([CH3:15])[CH:12]=[CH:13][N:14]=1

Participants

5

Reactant 3

HCID 10176127Pyridinium chlorideHCID 114129074-Chlorothieno[2,3-b]pyridine-5-carbonitrileHCID 114590883-chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)phenylamine

Product 1

HCID 117415504-[(3-chloro-4-[(1-methyl-1H-imidazol-2-yl)thio]phenyl)amino]thieno[2,3-b]pyridine-5-carbonitrileYield 26.6%

Reagents, catalysts & solvents 1

HCID 8076Glycol monoethyl etherSolvent

Procedure

A mixture of (3-chloro-4-[(1-methyl-1H-imidazol-2-yl)sulfanyl]aniline (135 mg, 0.57 mmol), pyridine hydrochloride (66 mg, 0.57 mmol) and 4-chlorothieno[2,3-b]pyridine-5-carbonitrile (0.1 g, 0.52 mmol) in 4 mL of 2-ethoxyethanol is heated at reflux for 24 hours. The solution is cooled and the solvent is evaporated. The resultant residue is treated with a minimum amount of methanol and the product is purified by flash column chromatography eluting with 3% methanol in dichloromethane. The fractions containing product are combined and concentrated. Ethyl acetate is added and the insoluble material collected by filtration to provide 55 mg of 4-[(3-chloro-4-[(1-methyl-1H-imidazol-2-yl)thio]phenyl)amino]thieno[2,3-b]pyridine-5-carbonitrile as a tan solid, mp>240° C.; 1H NMR (DMSO-d6) δ 3.61 (s, 3H), 6.53 (d, J=9 Hz, 1H), 7.15 (m, 1H), 7.17 (s, 1H), 7.44 (m, 1H), 7.52 (s, 1H), 7.54 (s, 1H), 7.81 (d, J=6 Hz, 1H), 8.53 (s, 1H), 9.76 (s, 1H); MS 396.2 (M−H)−.

Workup

  1. temperatureis heated
  2. temperatureat reflux for 24 hours
  3. temperatureThe solution is cooled
  4. customthe solvent is evaporated
  5. additionThe resultant residue is treated with a minimum amount of methanol
  6. customthe product is purified by flash column chromatography
  7. washeluting with 3% methanol in dichloromethane
  8. additionThe fractions containing product
  9. concentrationconcentrated
  10. additionEthyl acetate is added
  11. filtrationthe insoluble material collected by filtration

Sources & evidence

ORD record
ord-d2fc971d491549a488fa423a93f6e543
Source dataset
uspto-grants-2007_10
Patent number
US07276519B2

Linked notes

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