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

HRID 1695433Notes

Reaction equation

HRID 1695433 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]([OH:23])=O)[N:18]([CH3:20])[N:19]=3)=[C:11]([CH2:24][OH:25])[O:10][N:9]=2)=[CH:4][CH:3]=1.C(N1C=CN=C1)([N:28]1C=CN=C1)=O.[OH-].[NH4+].[Cl-].[Na+]>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:12]([CH2:13][O:14][C:15]3[CH:16]=[C:17]([C:21]([NH2:28])=[O:23])[N:18]([CH3:20])[N:19]=3)=[C:11]([CH2:24][OH:25])[O:10][N:9]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 5234Sodium ChlorideHCID 14923Ammonium HydroxideHCID 682631,1'-CarbonyldiimidazoleHCID 666438625-[3-(4-fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-2-methyl-2H-pyrazole-3-carboxylic acid

Product 1

HCID 595684185-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-2-methyl-2H-pyrazole-3-car-boxylic acid amideYield 85%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 5-[3-(4-fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-2-methyl-2H-pyrazole-3-carboxylic acid (200 mg, 0.58 mmol) in DMF (16.7 mL) was added 1,1′-carbonyldiimidazole (116 mg, 0.69 mmol). The resulting reaction mixture was stirred for 1 h at 60° C. and then treated with an ammonium hydroxide solution (887 μL, 5.8 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=98:2 to 9:1) afforded the title compound (170 mg, 85%) as a white solid. MS: m/e=345.0 [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=98:2 to 9:1)

Sources & evidence

ORD record
ord-a8a5199143014878814e01c2d6530666
Source dataset
uspto-grants-2012_04
Patent number
US08163728B2

Reaction notes

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