Glycol monoethyl ether → 4-(4-Chloro-5-methoxy-2-methylphenylamino)-8-nitrobenzo[4,5]thieno[3,2-b]pyridine-3-carbonitrile

HRID 989324Notes

Reaction equation

HRID 989324 reaction equation
Cl[C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]2[C:10]3[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[CH:14]=[CH:13][C:11]=3[S:12][C:3]=12.C(OCCO)C.[Cl:26][C:27]1[C:33]([O:34][CH3:35])=[CH:32][C:30]([NH2:31])=[C:29]([CH3:36])[CH:28]=1.Cl.N1C=CC=CC=1>>[Cl:26][C:27]1[C:33]([O:34][CH3:35])=[CH:32][C:30]([NH:31][C:2]2[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]3[C:10]4[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[CH:14]=[CH:13][C:11]=4[S:12][C:3]=23)=[C:29]([CH3:36])[CH:28]=1

Participants

5

Reactant 4

HCID 8076Glycol monoethyl etherHCID 10176127Pyridinium chlorideHCID 109571994-Chloro-8-nitrobenzo[4,5]thieno[3,2-b]pyridine-3-carbonitrileHCID 123258794-Chloro-5-methoxy-2-methylaniline2×

Product 1

HCID 219564974-(4-Chloro-5-methoxy-2-methylphenylamino)-8-nitrobenzo[4,5]thieno[3,2-b]pyridine-3-carbonitrileYield 26%

Procedure

A solution of 286 mg (0.99 mmol) of 4-chloro-8-nitrobenzo[4,5]thieno[3,2-b]pyridine-3-carbonitrile in 10 mL of 2-ethoxyethanol containing 131 mg (1.42 mmol) of 4-chloro-5-methoxy-2-methylaniline (WO 8501939A1) and 131 mg of pyridine hydrochloride is heated at reflux temperature overnight. The reaction mixture is cooled slightly and an additional 100 mg (0.58 mmol) of 4-chloro-5-methoxy-2-methylaniline is added and the reaction mixture is heated at reflux temperature overnight. The mixture is cooled to room temperature and the solid is collected by filtration, then suspended in methanol. Aqueous ammonium hydroxide is added and the mixture is partitioned between ethyl acetate and water. The organic layer is washed with water, then dried over magnesium sulfate, filtered and concentrated in vacuo. Diethyl ether is added to the residue and the resultant solid is collected by filtration, and washed with diethyl ether to give 110 mg (26%) of a tan solid, mp>305° C.

Workup

  1. temperatureat reflux temperature overnight
  2. temperatureThe reaction mixture is cooled slightly
  3. temperaturethe reaction mixture is heated
  4. temperatureat reflux temperature overnight
  5. filtrationthe solid is collected by filtration
  6. additionAqueous ammonium hydroxide is added
  7. customthe mixture is partitioned between ethyl acetate and water
  8. washThe organic layer is washed with water
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. additionDiethyl ether is added to the residue
  13. filtrationthe resultant solid is collected by filtration
  14. washwashed with diethyl ether

Sources & evidence

ORD record
ord-f54c6fac356245d4ad13c4ec0097e45f
Source dataset
uspto-grants-2003_10
Patent number
US06638929B2

Reaction notes

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