Reaction Steps
This compound was prepared via Scheme 6 in a multistep synthesis as follows: 4-methoxy-l,2-phenylene diamine dihydrochloride (4.2 g, 30.43 mmol) was dissolved in NaOH (3N) and extracted with CH2Cl2. The organic layer was dried over MgSO4 and the solvent removed in vacuo to yield an oil. 1H NMR showed the free base to be pure. To this was added nitrobenzene (100 mL), orthonitrobenzaldehyde (1.09 g, 7.24 mmol) and the reaction was heated overnight. The reaction mixture was cooled to RT and poured onto ethanolic HCl (7.2M). Et2O was added and a red solid precipitated. The precipitate was collected and dissolved in methanol, charcoal was added and the mixture was filtered. The methanol was concentrated on a steam bath and the product was allowed to precipitate as a beige solid. 1H NMR (DMSO-d6) confirmed this to be 4-methoxy-2-(2-nitrophenyl) benzimidazole (3.89 g, 48% yield). This material (2.90 g, 12.1 mmol), along with PtO 2 (0.1 g) was suspended in EtOH (150 mL) and charged with H2 (60 psi). The mixture was shaken for 1 h on a Parr hydrogenation apparatus; the mixture was filtered through a pad of celite and the solvent concentrated in vacuo to a yellow solid shown to be 4-methoxy-2-(2-aminophenyl)benzimidazole. This was acetylated according to General Procedure A and purified by recrystallization from methanol, m.p. 212°-213° C. 1H NMR (300 MHz, DMSO-d6) δ mixture of conformational isomers, 8.66 (d, J=9 Hz, 1H), 8.05 (d, J=9 Hz, 1H), 7.61 (d, J=9 Hz, 0.5H), 7.44 (m, 1.5H), 7.28 (bs, 0.5H), 7.20 (t, J=7 Hz, 1H), 7.01 (d, J=1.5 Hz, 0.5H), 6.86 (m, 1H), 3.81 (s, 3H), 2.22 and 2.25 (s 3H); δ13C NMR (75 MHz, DMSO-d6) δ (mixture of conformational isomers), 168.43, 156.69, 155.81, 150.90, 149.95, 142.90, 138.23, 138.01, 136.55, 134.22, 130.35, 130.14, 127.81, 126.88, 122.64, 119.69, 119.25, 115.30, 113.46, 111.80, 100.87, 94.32, 55.48, 25.20; IR (KBr) 3300-2600, 2750, 1635, 1545, 1270, 815 cm-1 ; MS (DCI) m/e MH+ =281; Analysis calc'd for C16H14N3O2 : C, 68.56; H, 5.03; N, 14.99; found: C, 68.23; H, 5.42; N, 14.8.
