3-Fluoro-4-sulfamoylbenzoic acid → 4-fluoro-2-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]benzenesulfonamide

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The title compound was prepared from a mixture of 2-(aminosulfonyl)-5-fluorobenzoic acid and 4-(aminosulfonyl)-3-fluorobenzoic acid 6b and endo 2-methyl-1-{8-[2-(4-phenylpiperidin-4-yl)ethyl]-8-aza bicyclo[3.2.1]oct-3-yl}-1H-benzimidazole dihydro-chloride II following the general procedure for tert-butyl {2-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]phenyl}sulfonylcarbamate 1c. The desired regioisomer was purified by column chromatography on silica gel eluting with 20% methanol in ethyl acetate to afford 4-fluoro-2-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]benzenesulfonamide 6 as a white solid (9.8 mg, 20% yield). 1H NMR (400 MHz, CDCl3) δ 7.90 (t, 1H. J=7.7 Hz), 7.64 (m, 1H), 7.39 (m, 2H), 7.30-7.12 (m, 8H), 5.69 (broad s, 2H), 4.59 (m, 1H), 4.20 (m, 1H), 3.48-3.19 (m, 5H), 2.52 (s, 3H), 2.40-2.32 (m, 3H), 2.18 (m, 1H), 2.04-1.70 (m, 10H), 1.62 (m, 2H). ES-LCMS m/z 630.19 (M+H). Analytical HPLC (Method Y) Rt 4.16 (90.0%).

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