Glyoxylic acid (8.6 g, 95 mmol) was added to a solution of 2-(6-bromo-5-fluoro-1H-indol-3-yl)ethanamine (8.1 g 31 mmol) in 2 N HCl (150 ml), and the pH of the resulting solution was adjusted to pH 3.5 with 6 N NaOH solution. The reaction mixture was stirred at ambient temperature for 18 h. The solution was adjusted to pH 5.5 with 6 N NaOH solution. The resulting precipitate was collected by filtration and dried under vacuum to afford a yellow solid. The yellow solid was suspended in 2 N HCl (100 mL), and the resulting mixture was stirred at reflux for 4.5 h. The reaction mixture was cooled to ambient temperature and was adjusted to pH 10 by addition of 2 N sodium hydroxide solution. The resulting precipitate was collected by filtration and dried under vacuum to afford a crude mixture of 7-bromo-6-fluoro-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole and 6-bromo-7-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (2.0 g, 23%) as a yellow solid. The mixture (1.9 g, 7.1 mmol) was suspended in dichloromethane (100 mL) and di-tert-butyl carbonate (1.85 g, 8.7 mmol) was added, followed by addition of DMAP (100 mg, 0.82 mmol). The reaction mixture was stirred at ambient temperature for 18 h and concentrated under vacuum. The residue was purified twice by column chromatography (silica gel, hexanes/ethyl acetate, 0:1 to 1:1) to afford the title compound (300 mg, 12%) as a pale yellow solid: 1H NMR (300 MHz, CDCl3) δ 7.46 (d, J=5.7 Hz, 1H), 7.18 (d, J=9.0 Hz, 1H), 4.61 (s, 2H), 3.75 (br m, 2H), 2.73 (br m, 2H), 1.56 (s, 9H); ESI MS m/z 369 [M+H]+.
