Synthesis
General procedure for the synthesis of 4-chloro-3-iodopyridin-2-ylamine from tert-butyl 4-chloro-3-iodopyridin-2-ylcarbamate: tert-butyl 4-chloro-3-iodopyridin-2-ylcarbamate (5.6 g, 15.8 mmol) was suspended in 48% hydrobromic acid and heated at 100 °C for 10 min until the solution clarified. Upon completion of the reaction, the mixture was cooled to room temperature and the reaction was quenched by the addition of crushed ice, followed by adjusting the pH to basic with 6 M sodium hydroxide solution. The precipitated white solid product was collected by vacuum filtration, washed with water and partially drained on a Büchner funnel. The crude product was dissolved in tetrahydrofuran and the solution was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 4-chloro-3-iodopyridin-2-ylamine (3.7 g, 93% yield) as a white solid. The product was characterized by 1H NMR (DMSO-d6): δ 7.84 (d, 1H, J = 5.1 Hz), 6.73 (d, 1H, J = 5.6 Hz), 6.51 (br s, 2H); mass spectrum (ESI+): m/z 254.97 ([M + H]+).
References
[1] Molecules, 2012, vol. 17, # 9, p. 10683 - 10707,25
[2] Molecules, 2012, vol. 17, # 9, p. 10683 - 10707
[3] Patent: US2005/245530, 2005, A1. Location in patent: Page/Page column 46
[4] Journal of Medicinal Chemistry, 2009, vol. 52, # 5, p. 1251 - 1254
[5] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 1, p. 114 - 120
