Cl.[F:2][C:3]1[CH:4]=[C:5]([N:10]2[C:14]([CH2:15][NH2:16])=[CH:13][C:12]([C:17]([F:20])([F:19])[F:18])=[N:11]2)[CH:6]=[CH:7][C:8]=1[F:9].[F:21][C:22]1[CH:23]=[C:24]([NH:33][C:34](=O)[O:35]C2C=CC=CC=2)[CH:25]=[CH:26][C:27]=1[N:28]1[CH2:31][CH:30]([OH:32])[CH2:29]1>C(#N)C>[F:2][C:3]1[CH:4]=[C:5]([N:10]2[C:14]([CH2:15][NH:16][C:34]([NH:33][C:24]3[CH:25]=[CH:26][C:27]([N:28]4[CH2:29][CH:30]([OH:32])[CH2:31]4)=[C:22]([F:21])[CH:23]=3)=[O:35])=[CH:13][C:12]([C:17]([F:20])([F:18])[F:19])=[N:11]2)[CH:6]=[CH:7][C:8]=1[F:9]To a stirred solution of ((1-(3,4-difluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochloride (75 mg, 0.239 mmol, 1.0 eq) in acetonitrile (5.5 mL) was added TEA (0.13 mL, 0.96 mmol, 4.0 eq.) followed by phenyl 3-fluoro-4-(3-hydroxyazetidin-1-yl)phenylcarbamate (73 mg, 0.244 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 (4:1) as eluent) to get 1-((1-(3,4-difluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(3-fluoro-4-(3-hydroxyazetidin-1-yl)phenyl)urea (102 mg, 88%).
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