Reaction Steps
To the 5-phenyl-6-chloro-3-(1-BOC-2-(R)-pyrrolidinylmethoxy)pyridine compound from step 69b (262 mg) was added formalin (37%, 0.5 mL) and formic acid (0.25 mL), and the mixture was heated at 70° C. for 3 hours. The solvent was removed, and to the residue was added solid NaHCO3. When pH 7-8 was achieved, the mixture was extracted with CH2Cl2, which was dried over MgSO4 and concentrated. The residue was chromatographed on a silica gel column, eluting with CH2Cl2:MeOH:NH4OH 100:10:0.04 to afford to give the free base of the title compound (200 mg). MS (CI/NH3) m/z 303 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ 1.98 (m, 2H), 2.10 (m, 1H), 2.22 (m, 1H), 2.71 (m, 1H), 2.78 (s, 3H), 3.27 (m, 1H), 3.60 (m, 111), 4.18 (m, 1H), 4.47 (m, 1H), 7.46 (m, 5H), 8.10 (m, 1H), 8.30 (br s, 1H). The base was converted to the salt by treatment with HCl in THF to give the title compound. MS (CI/NH3) m/z 303 (M+H)+. 1H NMR (D2O, 300 MHz) δ: 2.05-2.17 (m, 2H), 2.19-2.27 (m, 1H), 2.35-2.45 (m, 1H), 3.04 (s, 3H), 3.30 (m, 1H), 3.74 (m, 1H), 3.94 (m, 1H), 4.37 (dd, J=6.1, 11.2 Hz, 1H), 4.54 (dd, J=3.3, 11.2 Hz, 1H), 7.56 (m, 6H), 8.15 (d, J=3.0 Hz, 1H). Anal. Calcd for C17H19N2OCl.1.1 HCl: C, 59.55; H, 5.91; N, 8.17. Found: C, 59.74; H, 6.04; N, 8.14. [α]25D=+7.17° (c 1.11, MeOH).
