(1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochloride → 1-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(3-fluoro-4-(2-hydroxyethyl)phenyl)urea

HRID 1842957Notes

Reaction equation

HRID 1842957 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([N:9]2[C:13]([CH2:14][NH2:15])=[CH:12][C:11]([C:16]([F:19])([F:18])[F:17])=[N:10]2)[CH:6]=[CH:7][CH:8]=1.[F:20][C:21]1[CH:22]=[C:23]([NH:30][C:31](=O)[O:32]C2C=CC=CC=2)[CH:24]=[CH:25][C:26]=1[CH2:27][CH2:28][OH:29]>C1COCC1>[Cl:2][C:3]1[CH:4]=[C:5]([N:9]2[C:13]([CH2:14][NH:15][C:31]([NH:30][C:23]3[CH:24]=[CH:25][C:26]([CH2:27][CH2:28][OH:29])=[C:21]([F:20])[CH:22]=3)=[O:32])=[CH:12][C:11]([C:16]([F:17])([F:18])[F:19])=[N:10]2)[CH:6]=[CH:7][CH:8]=1

Participants

4

Reactant 2

HCID 70816151(1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochlorideHCID 86672157Phenyl 3-fluoro-4-(2-hydroxyethyl)phenylcarbamate

Product 1

HCID 708164201-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(3-fluoro-4-(2-hydroxyethyl)phenyl)ureaYield 45%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochloride (227 mg, 0.73 mmol, 1.0 eq) in THF (10 mL) was added TEA (147 mg, 1.45 mmol, 2.0 eq) followed by phenyl 3-fluoro-4-(2-hydroxyethyl)phenylcarbamate (200 mg, 0.73 mmol, 1.0 eq) at RT and the mixture was stirred for 16 h. The reaction mixture was concentrated under vacuum and the residue purified by CC using neutral alumina and EtOAc/PE (3:2) as eluent), followed by preparative HPLC to get 1-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(3-fluoro-4-(2-hydroxyethyl)phenyl)urea (150 mg; 45%, white solid; TLC system: EtOAc/PE (3:2); Rf: 0.2).

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. customthe residue purified by CC

Sources & evidence

ORD record
ord-73c88d84f286423580b814ba0512d46a
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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