[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH:10]([O:19][CH:20]1[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]1)[C:11]1[CH:12]=[C:13]([CH2:17]O)[CH:14]=[CH:15][CH:16]=1.C(N(CC)CC)C.[CH3:34][S:35](Cl)(=O)=O.C[S-].[Na+]>ClCCl.O.CO>[CH3:26][N:23]1[CH2:24][CH2:25][CH:20]([O:19][CH:10]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][S:35][CH3:34])[CH:12]=2)[C:2]2[NH:3][C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=3[N:1]=2)[CH2:21][CH2:22]1To a solution of {3-[(1H-benzimidazol-2-yl)(1-methylpiperidin-4-yloxy)methyl]phenyl}methanol (example 528B, 320 mg) in dichloromethane (3 mL) is added triethylamine (0.16 mL). The reaction mixture is cooled to 0° C., and methanesulfonyl chloride (84 μL) is added dropwise. The reaction mixture is stirred at room temperature for 3 h, then cooled to 0° C. and sodium thiomethoxide (191 mg) is added. After one night at room temperature, methanol (2 mL) is added to help solubilizing the suspension. The reaction mixture is stirred at room temperature overnight. Water is added and the aqueous phase is extracted by dichloromethane. The organic phase is washed by water, then dried over magnesium sulfate and concentrated. The residue is purified by chromatography on silica gel (gradient dichloromethane/methanol/ammonia from 90/10/0 to 90/10/0.1 then 80/20/0.1), followed by a purification by preparative thin-layer chromatography (dichloromethane/methanol/ammonia from 90/10/0.1) to give 2-[(1-methylpiperidin-4-yloxy)(3-methylsulfanylmethylphenyl)methyl]-1H-benzimidazole. MS, [M+H]+=382.1;
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