S(=O)(=O)(O)O.[CH2:6]([N:8]1[C:12]2[N:13]=[N:14][CH:15]=[C:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[C:11]=2[N:10]=[CH:9]1)[CH3:7].[I:24]N1C(C)(C)C(=O)N(I)C1=O.[OH-].[Na+]>C(Cl)Cl>[CH2:6]([N:8]1[C:12]2[N:13]=[N:14][CH:15]=[C:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[C:19]([I:24])[CH:18]=3)[C:11]=2[N:10]=[CH:9]1)[CH3:7]Concentrated sulphuric acid (10 mL) was carefully added to 7-ethyl-4-(4-fluorophenyl)-7H-imidazo[4,5-c]pyridazine (Preparation 9, 825 mg, 2.4 mmol) surrounded by an ice bath, and the resultant reaction mixture was gently stirred at room temperature until a homogeneous solution was observed. To this was added 1,3-diiodo-5,5-dimethylhydantoin (1.36 g, 3.58 mmol) portion-wise, and stirring was continued for 5 minutes. The viscous mixture was then slowly poured into an aqueous sodium hydroxide solution (1M, 10 mL) at 0° C. with stirring. The black suspension slowly dissolved to give a blue solution. CH2Cl2 (20 mL) was added and the layers were separated. The organic layer was washed with saturated aqueous sodium bisulfite solution (20 mL) then concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with heptane:EtOAc 1:1 to 0:100 to afford the title compound as a white solid in 95% yield, 1.19 g.
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