7-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-iodothieno[3,2-b]pyridine-6-carbonitrile → 7-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-[5-(1,3-dioxolan-2-yl)thien-3-yl]thieno[3,2-b]pyridine-6-carbonitrile

HRID 1178664Notes

Reaction equation

HRID 1178664 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([Sn](CCCC)(CCCC)[C:29]1[CH:33]=[C:32]([CH:34]2[O:38][CH2:37][CH2:36][O:35]2)[S:31][CH:30]=1)CCC>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[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:29]3[CH:33]=[C:32]([CH:34]4[O:38][CH2:37][CH2:36][O:35]4)[S:31][CH:30]=3)[S:22][C:13]=12

Participants

5

Reactant 2

HCID 103902087-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-iodothieno[3,2-b]pyridine-6-carbonitrileHCID 22256614Tributyl-(5-[1,3]dioxolan-2-yl-thiophen-3-yl)-stannane

Product 1

HCID 222566327-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-[5-(1,3-dioxolan-2-yl)thien-3-yl]thieno[3,2-b]pyridine-6-carbonitrileYield 75.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalyst3×HCID 312751,4-DioxaneSolvent2×

Procedure

A mixture of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-iodothieno[3,2-b]pyridine-6-carbonitrile (564 mg, 1.18 mmol), tributyl-(5-[1,3]dioxolan-2-yl-thiophen-3-yl)-stannane (680 mg, 1.52 mmol) and a pinch of bis(triphenylphosphine)palladium(II) chloride in 15 mL of dioxane is heated at reflux for 5 hours. Additional bis(triphenylphosphine)palladium(II) chloride is added and the reaction is heated at reflux overnight. Additional bis(triphenylphosphine)palladium(II) chloride and 10 mL of dioxane are added and the reaction is heated at reflux for 5 hours. The reaction mixture is concentrated in vacuo and partitioned between water and chloroform. The organic layer is dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with 1:1 hexane:ethyl acetate. The fractions containing product are combined and concentrated in vacuo to provide 447 mg of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-[5-(1,3-dioxolan-2-yl)thien-3-yl]thieno[3,2-b]pyridine-6-carbonitrile as white crystals, mp 219–221° C.; 1H NMR (DMSO-d6) δ 3.85 (s, 3H), 3.92–4.10 (m, 4H), 6.08 (s, 1H), 7.36 (s, 1H), 7.63 (s, 1H), 7.75 (s, 1H), 7.80 (s, 1H), 7.97 (s, 1H), 8.60 (s, 1H), 9.69 (s, 1H); MS 502.1 (M−H)−.

Workup

  1. temperatureat reflux for 5 hours
  2. temperaturethe reaction is heated
  3. temperatureat reflux overnight
  4. temperaturethe reaction is heated
  5. temperatureat reflux for 5 hours
  6. concentrationThe reaction mixture is concentrated in vacuo
  7. custompartitioned between water and chloroform
  8. dry with materialThe organic layer is dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue is purified by flash column chromatography
  12. washeluting with 1:1 hexane
  13. additionThe fractions containing product
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6dac570b77a445c1b612d6f3d2614f00
Source dataset
uspto-grants-2007_10
Patent number
US07276519B2

Reaction notes

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