Potassium Carbonate → 5-{[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethyl]-amino}-2-methyl-2H-pyrazole-3-carboxylic acid methyl ester

HRID 1695488Notes

Reaction equation

HRID 1695488 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([CH:13]=O)=[C:11]([CH3:15])[O:10][N:9]=2)=[CH:4][CH:3]=1.Cl.[CH3:17][O:18][C:19]([C:21]1[N:22]([CH3:27])[N:23]=[C:24]([NH2:26])[CH:25]=1)=[O:20].C(=O)([O-])[O-].[K+].[K+].[BH4-].[Na+]>CO.Cl>[CH3:17][O:18][C:19]([C:21]1[N:22]([CH3:27])[N:23]=[C:24]([NH:26][CH2:13][C:12]2[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)=[N:9][O:10][C:11]=2[CH3:15])[CH:25]=1)=[O:20]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 4311764Sodium borohydrideHCID 167282913-(4-Fluorophenyl)-5-methylisoxazole-4-carboxaldehydeHCID 66643934methyl 3-amino-1-methyl-1H-pyrazole-5-carboxylate hydrochloride

Product 1

HCID 666437125-{[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethyl]-amino}-2-methyl-2H-pyrazole-3-carboxylic acid methyl esterYield 27%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 887MethanolSolvent

Procedure

To a solution of 3-(4-fluoro-phenyl)-5-methyl-isoxazole-4-carbaldehyde (1.32 g, 6.44 mmol) and the 5-amino-2-methyl-2H-pyrazole-3-carboxylic acid methyl ester hydrochloride (1.0 g, 6.44 mmol) in methanol (30 mL) at room temperature was added potassium carbonate (890 mg, 6.44 mmol) and then the reaction mixture was heated under reflux for 2 h. After cooling to room temperature sodium borohydride (487 mg, 12.9 mmol) was added and then the mixture heated under reflux for 12 h. The mixture was then cooled and treated with hydrochloric acid (1 N, 10 drops) and evaporated. Water was then added and the mixture extracted with ethyl acetate. The aqueous layer was acidified with hydrochloric acid (2 N) and then extracted with ethyl acetate. The combined organic extracts were then dried over sodium sulfate, filtered and evaporated to afford 5-{[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethyl]-amino}-2-methyl-2H-pyrazole-3-carboxylic acid methyl ester (27%) which was obtained as a white solid.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureunder reflux for 2 h
  3. additionwas added
  4. temperaturethe mixture heated
  5. temperatureunder reflux for 12 h
  6. temperatureThe mixture was then cooled
  7. customevaporated
  8. additionWater was then added
  9. extractionthe mixture extracted with ethyl acetate
  10. extractionextracted with ethyl acetate
  11. dry with materialThe combined organic extracts were then dried over sodium sulfate
  12. filtrationfiltered
  13. customevaporated

Sources & evidence

ORD record
ord-ec0337d3de284c189b7a8d8d00f939c6
Source dataset
uspto-grants-2012_04
Patent number
US08163728B2

Reaction notes

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