Methanol → 7-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-(pyridin-3-ylethynyl)thieno[3,2-b]pyridine-6-carbonitrile

HRID 1611536Notes

Reaction equation

HRID 1611536 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:9][CH3:10])=[CH:4][C:3]=1[NH:11][C:12]1[C:17]([C:18]#[N:19])=[CH:16][N:15]=[C:14]2[CH:20]=[C:21](I)[S:22][C:13]=12.[C:24]([C:26]1[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=1)#[CH:25].CO>C(N(CC)CC)C.C1C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:9][CH3:10])=[CH:4][C:3]=1[NH:11][C:12]1[C:17]([C:18]#[N:19])=[CH:16][N:15]=[C:14]2[CH:20]=[C:21]([C:25]#[C:24][C:26]3[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=3)[S:22][C:13]=12

Participants

8

Reactant 3

HCID 887MethanolHCID 1860033-EthynylpyridineHCID 103902087-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-iodothieno[3,2-b]pyridine-6-carbonitrile

Product 1

HCID 222566427-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-(pyridin-3-ylethynyl)thieno[3,2-b]pyridine-6-carbonitrileYield 66.5%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 241BenzeneSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-iodothieno[3,2-b]pyridine-6-carbonitrile (160 mg, 0.33 mmol), 3-ethynylpyridine (45 mg, 0.43 mmol), 5 mg of tetrakis(triphenylphosphine)palladium(0) and 20 mg of copper(I) iodide in 2 mL of triethylamine and 7 mL of benzene is heated at reflux overnight. The mixture is cooled to room temperature and 5 mL of methanol is added. The solvents are removed in vacuo and the residue is treated with 50 mL of chloroform. The insoluble material is removed by filtration, washing with chloroform. The filtrate is washed with water. The residue is suspended in acetone, combined with the chloroform phase and concentrated in vacuo. The residue is purified by flash column chromatography eluting with a gradient of 5% methanol in dichloromethane to 10% methanol and 1% ammonium hydroxide in dichloromethane. The fractions containing product are combined and concentrated to provide 99 mg of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-(pyridin-3-ylethynyl)thieno[3,2-b]pyridine-6-carbonitrile as light brown crystals, mp 249-250° C.; MS 451.0 (M+H)+.

Workup

  1. temperatureis heated
  2. temperatureat reflux overnight
  3. customThe solvents are removed in vacuo
  4. additionthe residue is treated with 50 mL of chloroform
  5. customThe insoluble material is removed by filtration
  6. washwashing with chloroform
  7. washThe filtrate is washed with water
  8. concentrationconcentrated in vacuo
  9. customThe residue is purified by flash column chromatography
  10. washeluting with a gradient of 5% methanol in dichloromethane to 10% methanol and 1% ammonium hydroxide in dichloromethane
  11. additionThe fractions containing product
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-1073b8ee2d02411abc4fdc5d7e40bd0e
Source dataset
uspto-grants-2006_01
Patent number
US06987116B2

Reaction notes

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