Pentafluorophenol → 4-({2-[5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4-methyl-1H-pyrazol-3-ylmethoxy]-2-methyl-propionylamino}-methyl)-benzoic acid

HRID 526708Notes

Reaction equation

HRID 526708 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=3[Cl:20])[N:11]=[C:10]([CH2:21][O:22][C:23]([CH3:28])([CH3:27])[C:24](O)=[O:25])[C:9]=2[CH3:29])=[CH:4][CH:3]=1.Cl.CN(C)CCCN=C=NCC.FC1C(O)=C(F)C(F)=C(F)C=1F.[NH2:54][CH2:55][C:56]1[CH:64]=[CH:63][C:59]([C:60]([OH:62])=[O:61])=[CH:58][CH:57]=1>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=3[Cl:20])[N:11]=[C:10]([CH2:21][O:22][C:23]([CH3:27])([CH3:28])[C:24]([NH:54][CH2:55][C:56]3[CH:57]=[CH:58][C:59]([C:60]([OH:62])=[O:61])=[CH:63][CH:64]=3)=[O:25])[C:9]=2[CH3:29])=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 13041PentafluorophenolHCID 655264-(Aminomethyl)Benzoic AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 899079182-[5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4-methyl-1H-pyrazol-3-ylmethoxy]-2-methyl-propionic acid

Product 1

HCID 721652204-({2-[5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4-methyl-1H-pyrazol-3-ylmethoxy]-2-methyl-propionylamino}-methyl)-benzoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 710 mg of 2-[5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4-methyl-1H-pyrazol-3-ylmethoxy]-2-methyl-propionic acid in 5 ml of DMF, 360 mg of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC), 345 mg of pentafluorophenol and 392 mg of NEM were added and the reaction mixture was stirred for 3 h at room temperature. Then, 353 mg of 4-Aminomethyl-benzoic acid and 540 mg of NEM in 5 ml of DMF were added. After 16 h the reaction mixture was diluted with water and filtered through a chem Elut® cartridge by eluting with ethyl acetate. The solvents were removed under reduced pressure and the residue was purified by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to yield a white solid. Yield: 288 mg.

Workup

  1. filtrationfiltered through a chem Elut® cartridge
  2. washby eluting with ethyl acetate
  3. customThe solvents were removed under reduced pressure
  4. customthe residue was purified by preparative HPLC (
  5. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)
  6. additionThe fractions containing the product
  7. customwere evaporated
  8. customto yield a white solid

Sources & evidence

ORD record
ord-54c4f0e411ed49bb9faabba3d6c41b7b
Source dataset
uspto-grants-2016_05
Patent number
US09346762B2

Reaction notes

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