Reaction Steps
A suspension of 2-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole (170 mg, 0.80 mmol; Example 4A), hydroquinone (9 mg, 0.08 mmol), and -32% sodium in paraffin (79 mg, 1.1 mmol; Aldrich) in anhydrous dimethyl sulfoxide (800 μL) was sealed in a septum-capped reaction tube. After thoroughly evacuating and purging the vessel with nitrogen, 2-methyl-5-vinylpyridine (143 mg, 1.2 mmol, International Publication No. WO2001/017968) was added, and the reaction was stirred at 100° C. for 48 hours. The thick mixture was cooled to room temperature, poured into water (5 mL), and extracted with ethyl acetate (3×). The combined organic phases were washed with water, filtered through diatomaceous earth, dried (Na2SO4), concentrated, and purified by chromatography on silica (0-5% gradient of concentrated aqueous ammonium hydroxide in acetonitrile). The resulting material was purified further by reverse-phase HPLC [Waters XBridge™ C18 5 μm OBD column, 30×100 mm, flow rate 40 mL/minute, 5-95% gradient of acetonitrile in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)] to afford the title compound: 1H NMR (300 MHz, methanol-d4) δ ppm 1.10-1.26 (m, 1H), 1.84-2.06 (m, 4H), 2.40 (s, 3H), 2.43 (s, 3H), 2.86 (dd, J=16, 4.6, 1H), 2.97 (ddd, J=14, 5.4, 5.4, 1H), 3.09 (ddd, J=14, 9.0, 6, 1H), 3.75-3.86 (m, 1H), 4.14 (ddd, J=15, 9.0, 5.4, 1H), 4.30 (ddd, J=15, 6, 5.4, 1H), 4.44 (d, J=4.6, 1H), 6.90 (d, J=8.3, 1H), 7.10 (d, J=7.9, 1H), 7.17 (d, J=8.3, 1H), 7.20-7.25 (m, 2H), 7.75 (d, J=2.1, 1H); MS (ESI) m/z 332 (M+H)+.
