Synthesis
GENERAL METHOD: N-Iodosuccinimide (NIS, 24.75 g, 110.0 mmol) was added to a solution of 5-bromo-3-aminopyridine (12.85 g, 100.0 mmol) in acetonitrile (MeCN, 400 mL). The mixture was stirred and reacted under reflux conditions overnight. After completion of the reaction, it was cooled to room temperature (r.t.) and the solvent was removed under vacuum. The residue was partitioned between ethyl acetate (EtOAc, 250 mL), saturated aqueous sodium bicarbonate (NaHCO3), sodium thiosulfate (Na2S2O3, 100 mL) and water (H2O, 250 mL). The organic layer was separated and washed with water (2 x 250 mL), and after separating the organic layer again, the solvent was removed under vacuum to give an orange colored oil. The oily substance was purified by silica gel column chromatography using a petroleum ether (PE) solution of 30-50% ethyl acetate as eluent to give an orange solid. The solid was washed with a 25% petroleum ether (80 mL) solution of ethyl acetate, collected by filtration and blotted dry to give 5-bromo-2-iodo-3-pyridinamine (7.32 g). The mother liquor was concentrated to dryness under vacuum and the residue was further purified by silica gel column chromatography using a 30-50% petroleum ether solution of ethyl acetate as eluent to give a purer product (1.90 g) as an off-white solid.
References
[1] Synlett, 2015, vol. 26, # 18, p. 2570 - 2574
[2] Patent: WO2014/60768, 2014, A1. Location in patent: Page/Page column 94; 95
[3] Patent: WO2014/60767, 2014, A1. Location in patent: Page/Page column 107
[4] Patent: WO2014/60770, 2014, A1. Location in patent: Page/Page column 126
[5] Journal of Organic Chemistry, 2015, vol. 80, # 21, p. 10806 - 10816
