Reaction Steps
1-(4-Imidazol-1-yl-phenyl)-2-{2-[3-(3-morpholin-4-yl-propoxy)-phenyl]-pyrrolidin-1-yl}-ethanone. Prepared as described in Example 8, Step 1, on a 3.44 mmol scale, to give 1.77 g (>100%) of crude product. MS: exact mass calcd for C28H34N4O3, 474.3; m/z found, 475.5 [M+H]+. Step 2. 6-(4-Imidazol-1-yl-phenyl)-9-(3-morpholin-4-yl-propoxy)-2,3-dihydro-1H-pyrrolo[2,1-a]isoquinolinylium. Prepared as described in Example 17, Step 2, on a 3.43 mmol scale, to give 1.60 g (95%) of crude product. MS: exact mass calcd for C28H31N4O2+, 455.2; m/z found, 455.5 [M]+. Step 3. Prepared as described in Example 17, Step 3, on a 3.43 mmol scale, to give 579 mg (37%) of 48A and 63 mg (4%) of 48B after column chromatography and HPLC. 48A: Cis-6-(4-Imidazol-1-yl-phenyl)-9-(3-morpholin-4-yl-propoxy)-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinoline. MS: exact mass calcd for C26H33N4O2, 458.3; m/z found, 459.5 [M+H]+. 1H NMR (MeOH-d4): 9.52 (s, 1H), 8.10 (s, 1H), 7.79 (m, 3H), 7.57 (d, J=8.4, 2H), 6.93 (d, J=2.4, 1H), 6.82 (dd, J=1.8, 8.4, 1H), 6.71 (d, J=8.4, 1H), 4.92 (t, J=7.2, 1H), 4.61 (dd, J=4.2, 12.0, 1H), 4.12 (t, J=6.0, 2H), 4.05 (d, J=12.0, 2H), 3.92 (m, 1H), 3.82 (t, J=12.0, 2H), 3.69 (dd, J=4.8, 11.7, 1H), 3.57 (d, J=12.6, 2H), 3.51 (t, J=12.0, 1H), 3.45 (m, 1H), 3.39 (t, J=7.8, 2H),3.18 (m, 2H), 2.87 (m, 1H), 2.30 (br m, 5H). 48B: Trans-6-(4-Imidazol-1-yl-phenyl)-9-(3-morpholin-4-yl-propoxy)-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinoline
