Reaction Steps
To a solution of 3-[4-[2-(benzyloxy)ethyl]-1-piperidinyl]-5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine (120 mg, 0.24 mmol) in MeOH (0.5 mL) was added 2N anhydrous HCl/ether (2 mL) under Ar at room temperature. The mixture was stirred at room temperature overnight. After the solvent was evaporated, the residue was dissolved in deionized water. The aqueous solution was washed three times with EtOAc, then filtered over a cotton plug. The water was removed under reduced pressure at 35° C., and the residue was purified by preparative HPLC (ACE AQ 150×21.2 mm; UV detection at 254 and 280 nm; flow 10.0 mL/min; gradient of 0 to 50% CH3CN in water [both containing 0.05 vol % CF3COOH] in 25 min, to 100% in another 5 min; tR 12.8-19.4 min) to obtain, after evaporation, the trifluoroacetate (131 mg). This salt was treated with PL-HCO3 MP anion exchange resin (Polymer Laboratories) in MeOH to afford the free amine, which was dissolved in MeOH (0.5 mL) and treated again with 2N anhydrous HCl/ether (2 mL) under Ar protection at room temperature. The mixture was stirred at room temperature overnight. After the solvent was evaporated, the residue was dissolved in deionized water (approx. 25 mL). The solution was filtered over a cotton plug, and the water was removed under reduced pressure at 35° C. After lyophilization from water, the hydrochloride (103 mg) was obtained as a yellow glass. [α]20D+1.8 (c 0.555 g/L, MeOH). 1H NMR (D2O, 400 MHz) δ 7.89 (s, 1H), 6.67 (s, 1H), 7.32 (s, 1H), 7.26-7.18 (m, 5H), 4.49 (m, 3H), 4.37 (m, 1H), 4.17 (m, 1H), 3.63 (m, 2H), 3.44 (t, 2H, J=6.8 Hz), 3.27 (t, 2H, J=6.8 Hz), 2.82 (m, 2H), 2.16-2.13 (m, 1H), 2.02-1.93 (m, 2H), 1.90-1.79 (m, 1H), 1.60 (m, 2H), 1.42 (m, 1H), 1.38 (m, 2H), 1.11 (m, 2H). 13C NMR (D2O, 100 MHz) δ 156.4, 148.8, 137.0, 128.2, 128.0, 127.7, 121.8, 117.3, 114.3, 72.0, 67.2, 58.1, 47.5, 45.6, 34.5, 31.2, 30.0, 25.4, 23.0. HRMS (ESI) calcd for C24H34N3O2 (M+H+) m/z 396.2651, found 396.2637. Anal. Calcd. for C24H33N3O2.3.0HCl.0.85H2O: C, 55.41; H, 7.30; N, 8.08; Cl, 20.44. Found: C, 55.64; H, 7.57; N, 8.21; Cl, 20.43.
