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) δ 0.91 (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) δ 8.45 (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).
