[Br:1][C:2]1[CH:3]=[C:4]([CH:8]([C:10]2[NH:14][C:13]3[CH:15]=[CH:16][C:17]([F:19])=[CH:18][C:12]=3[N:11]=2)[OH:9])[CH:5]=[CH:6][CH:7]=1.[CH3:20][N:21]1[CH2:26][CH2:25][CH:24](O)[CH2:23][CH2:22]1.O.[OH-].[Na+]>CS(O)(=O)=O>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]([O:9][CH:24]2[CH2:25][CH2:26][N:21]([CH3:20])[CH2:22][CH2:23]2)[C:10]2[NH:14][C:13]3[CH:15]=[CH:16][C:17]([F:19])=[CH:18][C:12]=3[N:11]=2)[CH:5]=[CH:6][CH:7]=1A mixture of (3-bromophenyl)(5-fluoro-1H-benzimidazol-2-yl)methanol (example 437E, 3.30 g) and 1-methylpiperidin-4-ol (2.37 g) in methanesulfonic acid (10 mL) is heated overnight in a sealed tube at a temperature close to 140° C. The mixture is cooled back to room temperature, poured into water which is then made alkaline with concentrated sodium hydroxide solution. The aqueous phase is extracted with ethyl acetate. Pooled extracts are dried over magnesium sulfate, concentrated under reduced pressure. The residue is purified by column chromatography over silica gel (gradient dichloromethane/methanol/ammonia from 100/0/0 to 90/10/1) to afford 2-[(3-bromophenyl)(1-methylpiperidin-4-yloxy)methyl]-5-fluoro-1H-benzimidazole. 1H NMR: 9.92 (sl, 1H), 7.60 (s, 1H), 7.55-6.85 (m, 6H), 5.80 (s, 1H), 3.65-3.50 (m, 1H), 2.80-2.65 (m, 2H), 2.34 (s, 3H), 2.15-1.65 (m, 6H).
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