A. Synthesis of 4-chloro-2-iodo-6-nitroaniline: adapted from the method of Leeson, P.D. et al. (J. Med. Chem. 34:1243-1252 (1991)). 4-Chloro-2-nitroaniline (2.15 g, 12.45 mmol, Aldrich, direct use) was dissolved in glacial acetic acid (16 mL) followed by iodine monochloride (2.114 g, 12.90 mmol, Aldrich). The reaction mixture was heated at 120 °C for 5 h. After completion of the reaction, it was cooled to room temperature and poured into ice water (30 g). The precipitate was collected by filtration, washed with 10% sodium sulfite solution (20 mL), and finally recrystallized by methanol to give 4-chloro-2-iodo-6-nitroaniline (1.05 g, 28% yield) as long brown needle-like crystals with a melting point of 205 °C (literature values 134-135 °C). The NMR hydrogen spectrum (1H, CDCl3) data were as follows: δ 6.660 (s, 2H); 7.906 (d, 1H, J = 2.1 Hz); 8.188 (d, 1H, J = 1.8 Hz).
