Reaction Steps
To a solution of 3-(7-methoxy-2,2-dimethyl-4-oxo-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester, which can be prepared as described in Example 14, (0.053 g, 0.147 mmol) and methoxyamine hydrochloride (0.038 g, 0.442 mmol) in isopropanol (1 mL) is added pyridine (0.118 g, 1.472 mmol). The mixture is heated to 50° C. and after 2 hours, is diluted with ethyl acetate, and washed twice with 1M aqueous sodium bisulfate, water, and brine. The organic phase is dried over MgSO4, filtered and concentrated. The resulting residue is purified by silica gel flash chromatography (elution with heptane-ethyl acetate, 4:1 to 7:3) to give 3-{7-methoxy-4-[(E)-methoxyimino]-2,2-dimethyl-1,2,3,4-tetrahydro-naphthalen-1-yl}-3H-imidazole-4-carboxylic acid isopropyl ester; MS: (ESI) m/z 386.0 (M+H)+. The HCl salt of the title compound can be prepared by dissolution in diethyl ether followed by treatment with an excess of 1N HCl in diethyl ether. The resulting heterogeneous solution is concentrated to furnish the HCl salt of 3-{7-Methoxy-4-[(E)-methoxyimino]-2,2-dimethyl-1,2,3,4-tetrahydro-naphthalen-1-yl}-3H-imidazole-4-carboxylic acid isopropyl ester; 1H NMR (400 MHz, MeOD) δ ppm 0.96 (s, 3 H), 1.12 (s, 3 H), 1.47 (d, J=6.1 Hz, 3 H), 1.49 (d, J=6.3 Hz, 3 H), 2.43 (d, J=17.9 Hz, 1 H), 3.01 (d, J=17.9 Hz, 1 H), 3.82 (s, 3 H), 4.04 (s, 3 H), 5.40 (sept, J=6.3 Hz, 1 H), 6.65 (s, 1 H), 6.79 (d, J=2.5 Hz, 1 H), 7.09 (dd, J=9.1, 2.5 Hz, 1 H), 8.16 (d, J=9.1 Hz, 1 H), 8.30 (s, 1 H), 8.53 (s, 1 H).
