(1-(3-ethoxy-5-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochloride → 1-((1-(3-ethoxy-5-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(3-fluoro-4-((2-hydroxyethoxy)methyl)phenyl)urea

HRID 1842950Notes

Reaction equation

HRID 1842950 reaction equation
Cl.[CH2:2]([O:4][C:5]1[CH:6]=[C:7]([N:12]2[C:16]([CH2:17][NH2:18])=[CH:15][C:14]([C:19]([F:22])([F:21])[F:20])=[N:13]2)[CH:8]=[C:9]([CH3:11])[CH:10]=1)[CH3:3].[F:23][C:24]1[CH:25]=[C:26]([NH:35][C:36](=O)[O:37]C2C=CC=CC=2)[CH:27]=[CH:28][C:29]=1[CH2:30][O:31][CH2:32][CH2:33][OH:34]>C(#N)C>[CH2:2]([O:4][C:5]1[CH:6]=[C:7]([N:12]2[C:16]([CH2:17][NH:18][C:36]([NH:35][C:26]3[CH:27]=[CH:28][C:29]([CH2:30][O:31][CH2:32][CH2:33][OH:34])=[C:24]([F:23])[CH:25]=3)=[O:37])=[CH:15][C:14]([C:19]([F:20])([F:21])[F:22])=[N:13]2)[CH:8]=[C:9]([CH3:11])[CH:10]=1)[CH3:3]

Participants

4

Reactant 2

HCID 70816994(1-(3-ethoxy-5-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochlorideHCID 86672156Phenyl 3-fluoro-4-((2-hydroxyethoxy)methyl)-phenylcarbamate

Product 1

HCID 708162481-((1-(3-ethoxy-5-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(3-fluoro-4-((2-hydroxyethoxy)methyl)phenyl)ureaYield 39.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of (1-(3-ethoxy-5-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochloride (100 mg, 0.300 mmol, 1.0 eq) in acetonitrile (7 mL) was added TEA (0.166 mL, 1.20 mmol, 4.0 eq) followed by phenyl 3-fluoro-4-((2-hydroxyethoxy)methyl)-phenylcarbamate (93 mg, 0.306 mmol, 1.02 eq) and stirred at reflux for 16 h. The solvent of the reaction mixture was evaporated and the residue was purified by column chromatography (EtOAc/cyclohexane (1:1)) to get 1-((1-(3-ethoxy-5-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(3-fluoro-4-((2-hydroxyethoxy)methyl)phenyl)urea (60 mg, 39%).

Workup

  1. temperatureat reflux for 16 h
  2. customThe solvent of the reaction mixture was evaporated
  3. customthe residue was purified by column chromatography (EtOAc/cyclohexane (1:1))

Sources & evidence

ORD record
ord-dcad5138a4824165b88bb716fc6b7f0e
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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