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

HRID 1695495Notes

Reaction equation

HRID 1695495 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[NH:22][N:23]=[C:24]([NH2:26])[CH:25]=1)=[O:20].C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[CH3:17][O:18][C:19]([C:21]1[NH:22][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

6

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 167282913-(4-Fluorophenyl)-5-methylisoxazole-4-carboxaldehydeHCID 50998527Methyl 3-Amino-1H-pyrazole-5-carboxylate hydrochloride

Product 1

HCID 666437475-{[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethyl]-amino}-2H-pyrazole-3-carboxylic acid methyl esterYield 44%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 3-(4-fluoro-phenyl)-5-methyl-isoxazole-4-carbaldehyde (1.75 g, 8.53 mmol) and the 5-amino-2H-pyrazole-3-carboxylic acid methyl ester hydrochloride (1.2 g, 8.53 mmol) in methanol (70 mL) at room temperature was added molecular sieves (2.5 g) and then after 1 h, acetic acid (6.8 mL, 119.4 mmol) was added. Then sodium cyanoborohydride (1.07 g, 17.1 mmol) was added portionwise and the mixture stirred at room temperature overnight. After evaporation, dichloromethane was added and the mixture washed with sodium hydrogen carbonate (saturated solution). The organic layer was then dried over sodium sulfate, filtered and evaporated. Purification by chromatography (silica, heptane:ethyl acetate 7:3 to 6:4) afforded 5-{[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethyl]-amino}-2H-pyrazole-3-carboxylic acid methyl ester (1.2 g, 44%).

Workup

  1. customAfter evaporation, dichloromethane
  2. additionwas added
  3. washthe mixture washed with sodium hydrogen carbonate (saturated solution)
  4. dry with materialThe organic layer was then dried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customPurification by chromatography (silica, heptane:ethyl acetate 7:3 to 6:4)

Sources & evidence

ORD record
ord-6594fc062f1b4b8c8c7a10c930299972
Source dataset
uspto-grants-2012_04
Patent number
US08163728B2

Reaction notes

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