Dimethylformamide → 1-[4-(2-(Azepan-1-yl)ethoxy)benzyl]-5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-3-methyl-1H-indole

Participants

Reaction Steps

To a slurry of NaH (20.0 g, 60% oil dispersion, 0.5 mol, 2.5 eq.) solution of 5-Benzyloxy-2-(4-benzyloxy-phenyl)-3-methyl-1H-indole (84 g, 0.2 mol, 1.0 eq.) in DMF (100 mL) was added at 0/+10° C. over 1 h. The reaction mixture was stirred for 30 min. A solution of the benzylchloride (synthesis shown in scheme 7 and details given in the following experimental) (67 g, 0.22 mol, 1.1 eq.) in DMF (200 mL) was added dropwise at 0/+10° C. over 2 h. The reaction mixture was stirred at 25° C. for 2 h. TLC at this point showed no starting material, mostly product (EtOAc/hexane 1:5). The reaction mixture was diluted with water (1 L), extracted with EtOAc (3×1 L), and dried over MgSO4. The solution was concentrated to 150 mL, poured in MeOH (750 mL), and stirred overnight. The precipitate was filtered and dried to give the title compound (99 g, 76%): Mp=106-107° C.; 1H NMR (DMSO) δ 7.47 (d, 4 H, J=8.3 Hz), 7.41-7.36 (m, 4 H), 7.36-7.30 (m, 2 H), 7.29 (d, 2 H, J=8.8 Hz), 7.19 (d, 1 H, J=8.8 Hz), 7.14-7.10 (m, 3 H, 6.80 (dd, 1 H, J=8.8 Hz), 6.73 (s, 4 H),5.15 (s, 2 H), 5.13 (s, 2 H), 5.11 (s, 2 H), 3.90 (t, 2 H, J=5.9 Hz), 2.76 (t, 2 H, J=5.9 Hz), 2.64-2.56 (m, 4 H), 2.15 (s, 3 H), 1.58-1.44 (m, 8 H); MS FAB m/z 651 (M+H+).

Provenance & Evidence