To a solution of N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl]methanesulfonamide hydrochloride salt (Preparation 53, 100 mg, 0.33 mmol) in ethylene glycol dimethyl ether (10 ml) was added sodium hydrogen carbonate (1.5 g, 18 mmol) and 4-[(methylsulfonyl)amino]phenethyl methanesulfonate (P. E. Cross, J. E. Arrowsmith, G. N. Thomas, R. P. Dickinson, DD 281 599 A5, 97 mg, 0.33 mmol) and the reaction mixture was heated at 60° C. for 20 h. After cooling, diethyl ether (15 ml) and water (15 ml) were added and the reaction mixture was stirred vigorously for 5 min. The phases were separated and the aqueous layer was further extracted with diethyl ether (2×10 ml). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. The residual oil was purified by flash column chromatography using a Sep-Pak™ cartridge packed with silica gel (10 g) eluting with dichloromethane:ethanol:0.88 ammonia solution (200:8:1) to afford the title compound as an oil. The oil was further purified by preparative HPLC (condition 9) to give the title compound as a colourless glass (11 mg, 7%).
