3-Bromo-5-iodo-pyridin-4-ylamine

Synthesis

13534-98-0

902837-39-2

The general procedure for the synthesis of 3-bromo-5-iodopyridin-4-amine from 4-amino-3-bromopyridine was as follows: a solution was prepared by dissolving potassium iodide (2.88 g, 17.34 mmol) and iodine (2.75 g, 10.84 mmol) in water (21 mL). This solution was slowly added dropwise to a solution in water (10 mL) containing 4-amino-3-bromopyridine (2.5 g, 14.45 mmol) and sodium carbonate (0.919 g, 8.67 mmol). The reaction mixture was stirred under reflux conditions for 20 hours. After completion of the reaction, the mixture was diluted with water and ethyl acetate (EtOAc) and the aqueous and organic layers were separated. The aqueous layer was extracted three times with ethyl acetate and the organic layers were combined. The combined organic layers were washed three times with saturated sodium bicarbonate (NaHCO3) solution and sodium thiosulfate (Na2S2O3) solution sequentially. The organic layer was dried over anhydrous magnesium sulfate (MgSO4), then filtered and the filtrate was concentrated in vacuum. The brown oil obtained was purified by silica gel column chromatography (using a Biotage system with the eluent cyclohexane/ethyl acetate in a ratio of 50:50 gradient to 0:100) to afford the target product 3-bromo-5-iodopyridin-4-amine (951 mg, 22% yield) and the unreacted raw material 4-amino-3-bromopyridine (1.66 g) as a light yellow solid.

References