Potassium Carbonate → 6-(2,4-Difluorophenoxy)-3-iodo-4-methyl-1,4-dihydro-pyrazolo[4,3-b]pyridin-5-one

HRID 230177Notes

Reaction equation

HRID 230177 reaction equation
[F:1][C:2]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:3]=1[O:4][C:5]1[C:10](=[O:11])[N:9]([CH3:12])[C:8]2[CH:13]=[N:14][N:15](COCC[Si](C)(C)C)[C:7]=2[CH:6]=1.[I:29]Cl.C(=O)([O-])[O-].[K+].[K+]>C(Cl)(Cl)Cl.ClCCl>[F:1][C:2]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:3]=1[O:4][C:5]1[C:10](=[O:11])[N:9]([CH3:12])[C:8]2[C:13]([I:29])=[N:14][NH:15][C:7]=2[CH:6]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 24640Iodine chloride2×HCID 598128336-(2,4-Difluorophenoxy)-4-methyl-1-(2-trimethylsilanyl-ethoxymethyl)-1,4-dihydro-pyrazolo[4,3-b]pyridin-5-one

Product 1

HCID 1784815796-(2,4-Difluorophenoxy)-3-iodo-4-methyl-1,4-dihydro-pyrazolo[4,3-b]pyridin-5-oneYield 10.3%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-(2,4-difluorophenoxy)-4-methyl-1-(2-trimethylsilanyl-ethoxymethyl)-1,4-dihydro-pyrazolo[4,3-b]pyridin-5-one (118 mg, 0.289 mmol) in chloroform (25 mL) was added iodine monochloride (141 mg, 3 eq) followed by potassium carbonate (200 mg, 5 eq) and the resulting mixture was heated under reflux with stirring (in the dark) for 24 hours. Additional iodine monochloride (large excess) was added and the resulting solution was stirred under reflux for another 16 hours. The reaction mixture was cooled to room temperature and diluted with dichloromethane, and washed 2× with an aqueous solution of Na2S2O3(aq) followed by brine. The organic layer was dried over magnesium sulfate, filtered and concentrated to give the crude product as an oil (97 mg). Purification by Preparative Thin Layer Chromatography eluting with 60% ethyl acetate in hexanes gave the title compound as an off-white powder (12 mg, (M+H)+=462).

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureunder reflux
  3. stirringthe resulting solution was stirred
  4. temperatureunder reflux for another 16 hours
  5. washwashed 2× with an aqueous solution of Na2S2O3(aq)
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give the crude product as an oil (97 mg)
  10. customPurification by Preparative Thin Layer Chromatography
  11. washeluting with 60% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-9615a29d9bc2417ab686a5280253955a
Source dataset
uspto-grants-2009_07
Patent number
US07566708B2

Reaction notes

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