Methanol → HCID 22256640, compound

HRID 1611522Notes

Reaction equation

HRID 1611522 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:31]=[CH:30][CH:29]=[CH:28][N:27]=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:31]=[CH:30][CH:29]=[CH:28][N:27]=3)[S:22][C:13]=12

Participants

8

Reactant 3

HCID 887MethanolHCID 137268EthynylpyridineHCID 103902087-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-iodothieno[3,2-b]pyridine-6-carbonitrile

Product 1

HCID 22256640HCID 22256640, compoundYield 32.4%

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 (300 mg, 0.63 mmol), 2-ethynylpyridine (90 μL, 0.82 mmol), 7.3 mg of tetrakis(triphenylphosphine)palladium(0) and 3 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 are added. The solvents are removed in vacuo and the residue is treated with 10 mL of ethyl acetate. The insoluble material is removed by filtration, washing with ethyl acetate. The filtrate is washed with 10% aqueous hydrochloric acid, water, and saturated aqueous sodium chloride. The combined aqueous layers are extracted with dichloromethane. The organic layer is washed with saturated aqueous sodium chloride, dried over magnesium sulfate, filtered and concentrated in vacuo. The aqueous layer is adjusted to pH 6 and extracted with chloroform. The organic layer is washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo. The residues are combined and purified by flash column chromatography eluting with 5% methanol in dichloromethane. The fractions containing product are combined and concentrated. The resultant solid is recrystallized from ethyl acetate and hexane to provide 92 mg of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-(pyridin-2-ylethynyl)thieno[3,2-b]pyridine-6-carbonitrile as light brown crystals, mp 237-239° C.; 1H NMR (DMSO-d6) δ 3.86 (s, 3H), 7.35-7.52 (m, 2H), 7.73 (d, J=8 Hz, 1H), 7.80 (s, 1H), 7.83-7.92 (m, 2H), 8.60-8.72 (m, 2H), 9.89 (s, 1H); MS 449.1, 450.9 (M−H)−.

Workup

  1. temperatureis heated
  2. temperatureat reflux overnight
  3. customThe solvents are removed in vacuo
  4. additionthe residue is treated with 10 mL of ethyl acetate
  5. customThe insoluble material is removed by filtration
  6. washwashing with ethyl acetate
  7. washThe filtrate is washed with 10% aqueous hydrochloric acid, water, and saturated aqueous sodium chloride
  8. extractionThe combined aqueous layers are extracted with dichloromethane
  9. washThe organic layer is washed with saturated aqueous sodium chloride
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. extractionextracted with chloroform
  14. washThe organic layer is washed with water
  15. dry with materialdried over magnesium sulfate
  16. filtrationfiltered
  17. concentrationconcentrated in vacuo
  18. custompurified by flash column chromatography
  19. washeluting with 5% methanol in dichloromethane
  20. additionThe fractions containing product
  21. concentrationconcentrated
  22. customThe resultant solid is recrystallized from ethyl acetate and hexane

Sources & evidence

ORD record
ord-f0fa2c0715124db2964d28ed474f2876
Source dataset
uspto-grants-2006_01
Patent number
US06987116B2

Reaction notes

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