Phenyl (3-fluoro-4-(hydroxymethyl)phenyl)carbamate → 1-((1-(2,3-dichlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(3-fluoro-4-(hydroxymethyl)phenyl)urea

HRID 1842887Notes

Reaction equation

HRID 1842887 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:10][C:11](=[O:19])OC2C=CC=CC=2)[CH:5]=[CH:6][C:7]=1[CH2:8][OH:9].Cl.[Cl:21][C:22]1[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:23]=1[N:29]1[C:33]([CH2:34][NH2:35])=[CH:32][C:31]([C:36]([F:39])([F:38])[F:37])=[N:30]1>C(Cl)Cl.O>[Cl:21][C:22]1[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:23]=1[N:29]1[C:33]([CH2:34][NH:35][C:11]([NH:10][C:4]2[CH:5]=[CH:6][C:7]([CH2:8][OH:9])=[C:2]([F:1])[CH:3]=2)=[O:19])=[CH:32][C:31]([C:36]([F:38])([F:39])[F:37])=[N:30]1

Participants

5

Reactant 2

HCID 86672140Phenyl (3-fluoro-4-(hydroxymethyl)phenyl)carbamateHCID 86672141(1-(2,3-dichlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochloride

Product 1

HCID 866721421-((1-(2,3-dichlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(3-fluoro-4-(hydroxymethyl)phenyl)ureaYield 23.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of phenyl 3-fluoro-4-(hydroxymethyl)phenylcarbamate (0.175 g, 0.63 mmol, 1.0 eq) in DCM (5 mL) was added TEA (0.25 mL, 1.9 mmol, 3.0 eq.) followed by compound (1-(2,3-dichlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochloride (0.218 mg, 0.63 mmol, 1.0 eq.) at RT and stirred for 16 h at RT. The reaction mixture was diluted with water (10 mL) and extracted into DCM (25 mL). The organic layer was washed with brine (10 mL), dried over (Na2SO4) and the solvent evaporated under vacuum. The resulting residue was purified by CC using EtOAc/PE (1:1) as eluent to get 1-((1-(2,3-dichlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(3-fluoro-4-(hydroxymethyl)phenyl)urea (70 mg; 23%) as white solid (TLC system: EtOAc, Rf: 0.55).

Workup

  1. extractionextracted into DCM (25 mL)
  2. washThe organic layer was washed with brine (10 mL)
  3. dry with materialdried over (Na2SO4)
  4. customthe solvent evaporated under vacuum
  5. customThe resulting residue was purified by CC

Sources & evidence

ORD record
ord-119c80bf81314a18af2a6f537d491d08
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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