Reaktionsschritte
Compound 8 was prepared by the same procedure as that described for the preparation of Compound 7, except 2-chloro-4-methoxypyridine (259 mg, 1.80 mmol) was used in Step 1 in place of the 2-chloropyridine, and 2.0M HCl in ether was added to the concentrated Step 1 product in dichloromethane to give the hydrochloride salt in Step 2. The scale of Steps 2 and 3 were also adjusted based on the yields of the previous steps. Compound 8 (0.0290 g, 11.6% yield) was obtained as an off-white powder bis-TFA salt from reverse phase preparative HPLC. This compound was a single isomer. 1H NMR (500 MHz, MeOD) δ ppm 1.00 (d, J=6.71 Hz, 3H) 1.11 (d, J=6.71 Hz, 3H) 1.16 (dd, J=7.63, 2.75 Hz, 2H) 1.22-1.42 (m, 4H) 1.48 (dd, J=9.61, 5.34 Hz, 1H) 1.93-1.97 (m, 1H) 2.32 (q, J=8.85 Hz, 1H) 2.36-2.50 (m, 2H) 2.67 (dd, J=13.43, 7.02 Hz, 1H) 2.89 (s, 1H) 3.01 (ddd, J=12.82, 8.09, 4.73 Hz, 1H) 3.17-3.27 (m, 1H) 3.84 (s, 3H) 3.95 (s, 3H) 3.98-4.08 (m, 1H) 4.20 (dd, 1H) 4.26-4.33 (m, 2H) 4.70 (dd, J=10.38, 7.02 Hz, 1H) 5.17 (dd, J=10.53, 1.37 Hz, 1H) 5.36 (dd, J=17.09, 1.22 Hz, 1H) 5.77-5.87 (m, J=17.17, 9.58, 9.58 Hz, 1H) 5.97 (t, J=3.36 Hz, 1H) 6.32 (d, J=2.44 Hz, 1H) 6.55 (dd, J=7.32, 2.14 Hz, 1H) 7.14 (dd, J=9.16, 2.44 Hz, 1H) 7.22 (d, J=2.44 Hz, 1H) 7.30 (d, J=5.80 Hz, 1H) 7.72 (d, J=7.32 Hz, 1H) 7.93 (d, J=5.80 Hz, 1H) 8.01 (d, J=9.16 Hz, 1H); LC-MS, MS m/z 707 (M++H).
