Sodium hydride → 1-{4'-[3-Methyl-4-(3-phenyl-pyrazol-1-ylmethyl)-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid

HRID 1624377Notes

Reaction equation

HRID 1624377 reaction equation
C([O:3][C:4]([C:6]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[CH2:27]Br)=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:8][CH2:7]1)=[O:5])C.[C:29]1([C:35]2[CH:39]=[CH:38][NH:37][N:36]=2)[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.[H-].[Na+]>CN(C=O)C.CCOC(C)=O.Cl>[CH3:26][C:23]1[C:22]([CH2:27][N:37]2[CH:38]=[CH:39][C:35]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[N:36]2)=[C:21]([C:18]2[CH:19]=[CH:20][C:15]([C:12]3[CH:11]=[CH:10][C:9]([C:6]4([C:4]([OH:3])=[O:5])[CH2:7][CH2:8]4)=[CH:14][CH:13]=3)=[CH:16][CH:17]=2)[O:25][N:24]=1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 665771991-[4'-(4-Bromomethyl-3-methyl-isoxazol-5-yl)-biphenyl-4-yl]-cyclopropanecarboxylic acid ethyl esterHCID 178420101HCID 178420101, compound

Product 1

HCID 513475671-{4'-[3-Methyl-4-(3-phenyl-pyrazol-1-ylmethyl)-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-[4′-(4-Bromomethyl-3-methyl-isoxazol-5-yl)-biphenyl-4-yl]-cyclopropanecarboxylic acid ethyl ester (0.132 g, 0.3 mmol) and 3-phenyl-1H-pyrazole (0.043 g, 0.3 mmol) were combined in DMF. Sodium hydride (60% in mineral oil; 0.014 g, 0.35 mmol) was added, and the reaction was stirred at room temperature for 1.5 hours. Once no starting material was seen by analytical LCMS, the mixture was diluted with EtOAc and 1N aqueous HCl. The aqueous layer was extracted with EtOAc, and the combined organic layers were washed with H2O and brine, and then dried over Na2SO4, filtered, and concentrated. The residue was purified by preparative HPLC to give the title compound.

Workup

  1. extractionThe aqueous layer was extracted with EtOAc
  2. washthe combined organic layers were washed with H2O and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-4c26ac55c2de4d7f90aa1c2bac2f096f
Source dataset
uspto-grants-2014_07
Patent number
US08778983B2

Reaction notes

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