Reaction Steps
To 5-(5,5-dimethyl-1,3-hexadienyl)-6-chloro-3-(1-BOC-2-(R)-pyrrolidinylmethoxy)pyridine from step 77a (145 mg, 0.34 mmol) was added formalin (37%, 4 mL) and formic acid (2 mL), and the mixture was heated at 70° C. for 3 hours. The solvent was concentrated, and solid NaHCO3 was added to the residue. At pH 8 the mixture was extracted with methylene chloride, which was dried over MgSO4 and concentrated. The residue was chromotographed on a silica gel column, eluting with methylene chloride:methanol 100:4 to afford to give the free base of the title compound (72.5 mg, 66% yield). MS (DCI/NH3) m/z 335 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.10 (s, 9H), 1.77 (m, 2H), 2.00 (m, 1H), 2.28 (m, 1H), 2.45 (m, 3H), 2.70 (m, 1H), 3.10 (m, 1H), 3.43 (m, 1H), 4.00 (m, 1H), 4.38 (m, 1H), 5.95 (m, 1H), 6.20 (m, 1H), 6.70 (m, 2H), 7.38 (m, 1H), 7.93 (m, 1H). The base was converted to the salt by treatment with hydrogen chloride in ether/THF to give the title compound. mp 194° C. (dec). MS (DCI/NH3) m/z 335 (M+H)+. 1 H NMR (D2O, 300 MHz) δ: 1.07 (s, 9H), 1.78-2.05 (m, 2H), 2.17-2.28 (m, 1H), 2.90 (dd, J=5.1, 31.9 Hz, 3H), 3.12 (m, 1H), 3.50 (m, 3H), 4.41 (m, 2H), 6.04 (d, J=15.6 Hz, 1H), 6.30 (dd, J=10.2, 15.2 Hz, 1H), 6.70 (d, J-15.6 Hz, 1H), 7.10 (ss, J=10.2, 15.6 Hz, 1H), 7.84 (d, J=3.0 Hz, 1H), 8.06 (d, J=3.1 Hz, 1H).
