General procedure for the synthesis of 4-chloro-5-iodo-2-aminopyridine from 2-amino-4-chloropyridine: 2-amino-4-chloropyridine (1.00 g, 7.78 mmol) was dissolved in N,N-dimethylformamide (DMF, 40 mL), and the reaction flask was covered with aluminum foil to avoid light. N-iodosuccinimide (NIS, 970 mg, 4.28 mmol) was subsequently added. The reaction mixture was stirred at room temperature for 19 hours, then NIS (970 mg, 4.28 mmol) was added again and stirring was continued for 24 hours. Upon completion of the reaction, the reaction was quenched by the addition of deionized water (200 mL) and extracted with ethyl acetate (EtOAc, 2 x 250 mL). The organic phases were combined, washed sequentially with deionized water (2 × 200 mL) and saturated saline (200 mL), dried over anhydrous sodium sulfate (Na2SO4), and concentrated under reduced pressure. The crude product was recrystallized with ethanol (EtOH), and the mother liquor was recrystallized again to obtain orange needle-like crystals of the target product 4-chloro-5-iodo-2-aminopyridine (1.45 g, 73% yield).
