Reaction Steps
To a solution of 5-bromo-3-(1-methyl-2-(S)-pyrrolidinylmethoxy)pyridine (272 mg, 0.1 mmol) in 6 mL of CH2Cl2 was added triethylamine (0.4 mL), Pd(II) (18 mg), CuI (a catalytic amount) and 0.3 mL of 1-octyne (0.2 mmol). The reaction mixture was heated at reflux for 40 hours. The mixture was diluted with CH2Cl2, and 2 mL of 10% NaOH were added. The organic layer was separated and dried, and the solvent was removed under reduced pressure. The free was purified by chromatography, eluting with 1 to 2% MeOH in CH2Cl2. MS (CI/NH3) m/z 301 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ0.91 (m, 3H), 1.32 (m, 4H), 1.60 (m, 2H), 1.90 (m, 3H), 2.15 (m, 1H), 2.42 (m, 2H), 2.64 (s, 3H), 2.98 (br s, 1H), 3.34 (br s, 1H), 4.04 (m, 1H), 4.25 (m, 1H), 7.22 (m, 1H), 8.22 (m, 2H). The salt was prepared by treatment with HCl in Et2O, as described above, to give 110 mg of the title compound. MS (CI/NH3) m/z 301 (M+H)+. 1H NMR (D2O, 300 MHz) δ8.45 (d, J=2.6, 1H), 8.42 (d, J=1.1, 1H), 8.07 (m, 1H), 4.63 (dd, J=3.0, 11.1, 1H), 4.47 (dd, J=5.9, 11.4, 1H), 3.97 (m, 1H), 3.78 (m, 1H), 3.27 (m, 1H), 3.05 (s, 3H), 2.51 (t, J=7.0, 2H), 2.42 (m, 1H), 2.23 (m, 1H), 2.10 (m, 2H), 1.63 (m, 2H), 1.44 (m, 2H), 1.33 (m, 4H), 0.88 (m, 3H). Anal. Calcd for C19H28N2O·2.0 HCl: C, 61.12; H, 8.10; N, 7.50. Found: C, 60.99; H, 7.89; N, 7.28. [α]25D=-4.00° (c 1.75, MeOH).
