353272-15-8

5305-59-9

353272-15-8

General procedure for the synthesis of 6-chloro-5-iodopyrimidin-4-amine from 4-amino-6-chloropyrimidine: 3.03 g (23.39 mmol) of 6-chloropyrimidin-4-amine was dissolved in 60 mL of anhydrous dimethylformamide (DMF) under nitrogen protection and stirred until complete dissolution. Subsequently, 2.34 mL (46.70 mmol) of iodine monochloride (ICl) was dissolved in 40 mL of anhydrous DMF and slowly added dropwise to the above solution, with the rate of dropwise acceleration being controlled to maintain a stable reaction temperature. After dropwise addition, the reaction mixture was heated to 45 °C and the reaction was stirred at this temperature overnight (about 12 hours). Upon completion of the reaction, most of the DMF was removed by rotary evaporator under reduced pressure. the residue was transferred to a partition funnel and extracted by partition with dichloromethane (DCM) and 4% aqueous sodium bicarbonate. The organic layer was separated and washed sequentially with deionized water and saturated saline to remove water-soluble impurities and residual DMF.The organic layer was dried over anhydrous magnesium sulfate, filtered to remove the desiccant, and the filtrate was again concentrated to dryness by rotary evaporator. The crude product was purified by fast column chromatography using a solvent mixture of dichloromethane and methanol as eluent (methanol percentage was increased from 0% to 20% in a gradient) and fractions containing the target product were collected. Finally, the solvent was evaporated under reduced pressure to give 4.28 g of 6-chloro-5-iodopyrimidin-4-amine as a white solid in 72% yield. The product was confirmed by low resolution mass spectrometry (LRMS), m/z: 256 ([M+H]+).