Reaction Steps
A stirred, cooled (-5° C.) solution of 3-(5-[1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl)propan-1-ol (260 mg, 1 mmol) in anhydrous tetrahydrofuran (20 ml), under a nitrogen atmosphere, was treated with triethylamine (0.17 ml, 1.2 mmol) and methanesulphonyl chloride (0.10 ml, 1.2 mmol). After 45 minutes the reaction mixture was filtered, then washed through the filter pad with tetrahydrofuran (10 ml). The resulting mesylate solution was treated with potssium carbonate (263 mg, 1.9 mmol), sodium iodide (285 mg, 1.9 mmol) and a solution of 4-benzyl-4-methoxypiperidine (400 mg, 1.9 mmol) in tetrahydrofuran (10 ml). The reaction mixture was stirred whilst heating at 50° C. for 24 hours. The solvent was evaporated, the residue partitioned between dichloromethane (40 ml) and water (20 ml). The organic layer was separated and the aqueous re-extracted with dichloromethane (40 ml). The combined organics were extracted with aqueous citric acid (1 g in 20 ml), the aqueous was basified to pH=12 with 40% aqueous soldium hydroxide then extracted with dichloromethane (3×30 ml). The organic extracts were combined, dried (potassium carbonate) then evaporated. The residue was purified by column chromatography on silica using dichloromethane/methanol/ammonia (9:1:0.1) to afford the title compound free base as a glass (332 mg, 75%). The hydrogen oxalate salt has mp 84°-87° C. (Found: C, 60.81: H. 6.34: N, 11.68. C27H33N5O. 1.75C2H2O4 requires C, 60.94; H, 6.12; N, 11.65%). δH (360 MHz, DMSO-d6) 1.6-5-1.78 (2H, m, 2×CH), 1.82 (2H, d, J=12 Hz, 2×CH), 1.94-2.04 (2H, m, CH2CH2CH2), 2.71 (2H, t, J=7 Hz, indole-CH2), 2.82 (2H, s, CH2Ph), 2.82-3.00 (2H, m, 2×CH), 3.02-3.12 (2H, m, CH2N), 3.22-3.32 (2H, m, 2×CH), 3.28 (3H, s, OCH3) 5.43 (2H, s, CH2 -triazole), 7.05 (1H, d, J=7 Hz, Ar-H), 7.18-7.34 (7H, m, C6H5, indole-H, Ar-H), 7.52 (1H, s, Ar-H), 7.94 (1H, s, triazole-H), 8.60 (1H, s, triazole-H), 10.92 (1H, s, indole-NH); m/z (ES) 444 (M+ +1).
