Reaction Steps
To a three-necked 125 mL round-bottomed flask equipped with nitrogen (N2) inlet and septum were added 15 mL dry dimethylformamide and 50 mg (1.3 mmol) sodium hydride (washed with hexane). The reaction was cooled to 0° C., and a solution of 200 mg (0.6 mmol) 2-(2,5-dimethylpyrrolyl)-6-[4-hydroxy-5,6,7,8-tetrahydro-naphthalen-1-yl]-pyridine in 5 mL dry dimethylformamide added dropwise. The reaction was stirred 30 min at room temperature, then a solution of 234 mg (1.3 mmol) diethylaminoethoxy-ethyl chloride (J. Med. Chem., 34, 3159 (1991)) in 5 mL dry dimethylformamide added dropwise and the reaction heated at 100° C. for 20 hour, followed by more sodium hydride and chloride and heating another 24 hour The reaction was cooled, poured into aqueous sodium hydroxide solution, and extracted into ethyl acetate. The organic layer was washed with water, aqueous sodium bicarbonate solution, and brine, dried over sodium sulfate, and evaporated. The residue was chromatographed on silica gel using methanol/methylene chloride as eluant to afford 83 mg (30%) of an oil. 1H-NMR (δ, CDCl3): 1.03 (t, J=7, 6H), 1.67 (m, 2H), 1.76 (m, 2H), 2.155 (s, 6H), 2.59 (q, J=7, 4H), 2.7-2.9 (m, 6H), 3.67 (t, J=7, 2H), 3.84 (t, J=6, 2H), 4.14 (t, J=6, 2H), 5.87 (s, 2H), 6.73 (d, J=8, 1H), 7.11 (d, J=8, 1H), 7.185 (d, J=8, 1H), 7.35 (d, J=8, 1H), 7.82 (t, J=8, 1H); 13C-NMR (δ, CDCl3): 11.68, 13.33, 22.30, 22.87, 23.68, 28.66, 47.61, 52.34, 67.65, 69.67, 70.10, 106.52, 107.80, 119.48, 122.95, 126.59, 127.68, 128.62, 132.55, 136.58, 137.84, 151.21, 156.85, 160.34; MS (%): 462 (parent+1, 100).
