N[C:2]1[CH:3]=[CH:4][C:5]([C:25]([F:28])([F:27])[F:26])=[C:6]([CH2:8][N:9]2[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:24])[C:16]3[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=3[F:23])=[N:10]2)[CH:7]=1.N([O-])=[O:30].[Na+].NC(N)=O>O.ClCCl.S([O-])([O-])(=O)=O.[Cu+2]>[F:23][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]([F:22])[C:16]=1[C:15]([NH:14][C:11]1[CH:12]=[CH:13][N:9]([CH2:8][C:6]2[CH:7]=[C:2]([OH:30])[CH:3]=[CH:4][C:5]=2[C:25]([F:28])([F:27])[F:26])[N:10]=1)=[O:24]To a suspension of N-(1-{[5-amino-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)-2,6-difluorobenzamide (for a preparation see Intermediate 41) (1.0 g, 2.52 mmol) in water (15 ml) in an ice-water bath was added a solution of sodium nitrite (0.346 g, 5.01 mmol, Aldrich) in water (3 ml). The solution was maintained at 0-10° C. for 20 min. To the solution was added urea (0.94 g, 15.65 mmol, Aldrich) and then copper (II) sulphate (0.139 g, 0.868 mmol, Fluka). The mixture was heated to 90° C. for 30 min. The mixture was partitioned between water (150 ml) and ethyl acetate (130 ml). The phases were separated and the aqueous phase washed with ethyl acetate (50 ml). The combined organic extracts were dried (MgSO4), filtered and the solvent removed in vacuo to leave an oil. The residue was loaded in dichloromethane and purified on silica 100 g using a 0-100% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as an orange solid (0.462 g); LCMS: (System 4) MH+=398, tRET=2.36 min.
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