Diethyl Oxalate → 1-(6-methoxy-3-pyridyl)-5-(1H-pyrrol-2-yl)-1H-pyrazole-3-carboxylic acid

HRID 1437284Notes

Reaction equation

HRID 1437284 reaction equation
[C:1](OCC)(=O)[C:2]([O:4]CC)=[O:3].C1(S([N:20]2[CH:24]=[CH:23][CH:22]=[C:21]2[C:25](=O)[CH3:26])(=O)=O)C=CC=CC=1.[O-]CC.[Na+].Cl.[NH:33]([C:35]1[CH:36]=[CH:37][C:38]([O:41][CH3:42])=[N:39][CH:40]=1)[NH2:34]>C(O)C>[CH3:42][O:41][C:38]1[N:39]=[CH:40][C:35]([N:33]2[C:25]([C:21]3[NH:20][CH:24]=[CH:23][CH:22]=3)=[CH:26][C:1]([C:2]([OH:4])=[O:3])=[N:34]2)=[CH:36][CH:37]=1

Participants

6

Reactant 4

HCID 7268Diethyl OxalateHCID 7064062-Acetyl-1-(phenylsulfonyl)pyrroleHCID 2723922Sodium ethoxideHCID 230902035-Hydrazinyl-2-methoxypyridine hydrochloride

Product 1

HCID 1356217831-(6-methoxy-3-pyridyl)-5-(1H-pyrrol-2-yl)-1H-pyrazole-3-carboxylic acidYield 68%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

Under cooling with ice, diethyl oxalate (3.10 mL) and 1-[1-(phenylsulfonyl)pyrrol-2-yl]-1-ethanone (2.49 g) were added to sodium ethoxide (1.63 g) in ethanol (20 mL), followed by stirring at room temperature for 5 hours. To the reaction mixture, 5-hydrazino-2-methoxypyridine hydrochloride (2.52 g) obtained from Referential Example 1 and ethanol (20 mL) were added, and the resultant mixture was refluxed under heat for 14.5 hours, and then cooled in air. The reaction solvent was removed under reduced pressure, and the residue was partitioned by use of ethyl acetate and saturated aqueous sodium hydrogencarbonate. The aqueous layer was extracted again with ethyl acetate. The organic layers were combined, and then dried over sodium sulfate anhydrate, followed by filtration. The solvent was removed under reduced pressure, the residue was purified through silica gel column chromatography (ethyl acetate-hexane), to thereby give 1-(6-methoxy-3-pyridyl)-5-[1-(phenylsulfonyl)pyrrol-2-yl] pyrazole-3-carboxylic acid ethyl ester as an oily product (3.28 g, 72%). To the thus-obtained ethyl ester (3.28 g) in ethanol (22 mL), aqueous 1N sodium hydroxide (22 mL) was added, followed by stirring at room temperature for 2 days. Aqueous 1N hydrochloric acid was added to the reaction mixture, and the precipitated solid was recovered by filtration, to thereby give the title compound as a solid (1.40 g, 68%).

Workup

  1. additionwere added
  2. temperatureunder heat for 14.5 hours
  3. temperaturecooled in air
  4. customThe reaction solvent was removed under reduced pressure
  5. customthe residue was partitioned by use of ethyl acetate and saturated aqueous sodium hydrogencarbonate
  6. extractionThe aqueous layer was extracted again with ethyl acetate
  7. dry with materialdried over sodium sulfate anhydrate
  8. filtrationfollowed by filtration
  9. customThe solvent was removed under reduced pressure
  10. customthe residue was purified through silica gel column chromatography (ethyl acetate-hexane)
  11. additionTo the thus-obtained ethyl ester (3.28 g) in ethanol (22 mL), aqueous 1N sodium hydroxide (22 mL) was added
  12. stirringby stirring at room temperature for 2 days
  13. additionAqueous 1N hydrochloric acid was added to the reaction mixture
  14. filtrationthe precipitated solid was recovered by filtration

Sources & evidence

ORD record
ord-a12b454fa82443ff89b8b90938e6b84f
Source dataset
uspto-grants-2009_11
Patent number
US07622471B2

Reaction notes

Loading…