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.S(=O)(=O)(O)O.N([O-])=O.[Na+].[I-:38].[K+]>O>[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]([I:38])[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)(0.6 g, 1.51 mmol) in water (6 ml) in an ice-water bath (internal temperature at 5° C.) was added concentrated sulphuric acid specific gravity 1.84 (1 ml, 18.8 mmol). To the slight suspension was added a solution of sodium nitrite, super free flowing (0.125 g, 1.82 mmol, Aldrich) in water (3 ml) dropwise. The suspension was stirred in an ice-water bath for 20 min. To the mixture was added a solution of potassium iodide, extra pure briquettes (0.377 g, 2.27 mmol, Acros) in ice-cold approximately 1 M sulphuric acid (5.5 ml). The mixture was allowed to warm to ambient temperature and then heated to 80° C. for 30 min under nitrogen. The tarry suspension was partitioned between ethyl acetate (130 ml) and water (50 ml). The phases were separated and the organic phase washed with saturated aqueous sodium hydrogen carbonate (2×50 ml), dried (MgSO4), filtered and the solvent removed at reduced pressure to leave a dark red foam (0.77 g). The sample was loaded in dichloromethane and purified on silica 100 g using 0-100% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white foam (0.412 g); LCMS: (System 4) MH+=508 tRET=3.10 min.
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