Benzo[b]furan-2-boronic acid → 2-(1-Benzofuran-2-yl)-7-[(2,4-dichloro-5-methoxyphenyl)amino]thieno[3,2-b]pyridine-6-carbonitrile

HRID 1611524

Reaction equation

HRID 1611524 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.[O:24]1[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[CH:26]=[C:25]1B(O)O>COCCOC.C(=O)(O)[O-].[Na+].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>[O:24]1[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[CH:26]=[C:25]1[C:21]1[S:22][C:13]2[C:14](=[N:15][CH:16]=[C:17]([C:18]#[N:19])[C:12]=2[NH:11][C:3]2[CH:4]=[C:5]([O:9][CH3:10])[C:6]([Cl:8])=[CH:7][C:2]=2[Cl:1])[CH:20]=1

Participants

6

Reactant 2

HCID 2776266Benzo[b]furan-2-boronic acidHCID 103902087-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-iodothieno[3,2-b]pyridine-6-carbonitrile

Product 1

HCID 100960622-(1-Benzofuran-2-yl)-7-[(2,4-dichloro-5-methoxyphenyl)amino]thieno[3,2-b]pyridine-6-carbonitrileYield 32.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 80711,2-DimethoxyethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-iodothieno[3,2-b]pyridine-6-carbonitrile (500 mg, 1.05 mmol), 2-benzofuranboronic acid (340 mg, 2.10 mmol) and 65 mg of tetrakis(triphenylphosphine)palladium(0) in 70 mL of ethylene glycol dimethyl ether and 40 mL of saturated aqueous sodium bicarbonate is heated at reflux for 2.5 hours. An additional 50 mg of tetrakis(triphenylphosphine)palladium(0) is added and the reaction is heated at reflux for 1 hour. The reaction mixture is cooled to room temperature and partitioned between water and ethyl acetate. The organic layer is washed with water, dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with 2:1 hexane:ethyl acetate. The fractions containing product are combined and concentrated in vacuo. The residue is washed with diethyl ether to provide 160 mg of 2-(1-benzofuran-2-yl)-7-[(2,4-dichloro-5-methoxyphenyl)amino]thieno[3,2-b]pyridine-6-carbonitrile as yellow crystals, mp 281-282° C.; 1H NMR (DMSO-d6) δ 3.87 (s, 3H), 7.29-7.45 (m, 3H), 7.61 (s, 1H), 7.69-7.73 (m, 2H), 7.81 (s, 1H), 8.02 (s, 1H), 8.65 (s, 1H), 9.82 (s, 1H); MS 464.2, 465.9 (M−H)−.

Workup

  1. temperatureis heated
  2. temperatureat reflux for 2.5 hours
  3. temperaturethe reaction is heated
  4. temperatureat reflux for 1 hour
  5. custompartitioned between water and ethyl acetate
  6. washThe organic layer is washed with water
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue is purified by flash column chromatography
  11. washeluting with 2:1 hexane
  12. additionThe fractions containing product
  13. concentrationconcentrated in vacuo
  14. washThe residue is washed with diethyl ether

Sources & evidence

ORD record
ord-67f9e6e4a33140138f079cd8c5743728
Source dataset
uspto-grants-2006_01
Patent number
US06987116B2

Linked notes

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