Sodium Chloride → 5-[3-(4-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-2-methyl-2H-pyrazole-3-carboxylic acid amide

HRID 1695394Notes

Reaction equation

HRID 1695394 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([CH2:13][O:14][C:15]3[CH:16]=[C:17]([C:21](O)=[O:22])[N:18]([CH3:20])[N:19]=3)=[C:11]([CH3:24])[O:10][N:9]=2)=[CH:4][CH:3]=1.C(N1C=CN=C1)([N:27]1C=CN=C1)=O.[OH-].[NH4+].[Cl-].[Na+]>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([CH2:13][O:14][C:15]3[CH:16]=[C:17]([C:21]([NH2:27])=[O:22])[N:18]([CH3:20])[N:19]=3)=[C:11]([CH3:24])[O:10][N:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 5234Sodium ChlorideHCID 14923Ammonium HydroxideHCID 682631,1'-CarbonyldiimidazoleHCID 66643617HCID 66643617, compound

Product 1

HCID 595684665-[3-(4-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-2-methyl-2H-pyrazole-3-carboxylic acid amideYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 5-[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-2-methyl-2H-pyrazole-3-carboxylic acid (100 mg, 0.36 mmol) in DMF (8.3 mL) was added 1,1′-carbonyldiimidazole (60.6 mg, 0.36 mmol). The resulting reaction mixture was stirred for 1 h at 60° C. and then treated with an ammonium hydroxide solution (465 μL, 3.0 mmol) and stirred overnight at room temperature. The reaction mixture was then poured into aqueous sodium chloride (saturated) and the mixture was extracted with ethyl acetate. The combined organic layers were then washed with water and saturated sodium hydrogen carbonate solution and then dried over sodium sulfate, filtered and evaporated. Concentration and purification by chromatography (silica, dichloromethane:methanol=99:1 to 95:5) afforded the title compound (79 mg, 79%) as a white solid. MS: m/e=331.2 [M+H]+.

Workup

  1. customThe resulting reaction mixture
  2. stirringstirred overnight at room temperature
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe combined organic layers were then washed with water and saturated sodium hydrogen carbonate solution
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. concentrationConcentration and purification by chromatography (silica, dichloromethane:methanol=99:1 to 95:5)

Sources & evidence

ORD record
ord-56eef6e8504a40e9a1124dd828438597
Source dataset
uspto-grants-2012_04
Patent number
US08163728B2

Reaction notes

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