Uses
4,6-Dichloropyridin-3-amine is an organic amine compound used in the synthesis of 2,4,5-Trichloropyridine and its derivatives. It is also used as a pharmaceutical intermediate component in the preparation of aromatic bridging cyclic amide derivatives for hepatitis B virus infection.
Synthesis
The general procedure for the synthesis of 2,4-dichloro-5-aminopyridine from 4,6-dichloropyridin-3-amide was as follows: sodium hydroxide (6.60 g, 165 mmol) was dissolved in water (31 mL) and cooled in an ice bath. Subsequently, bromine (2.08 mL, 40.6 mmol) was added dropwise and the resulting yellow solution was stirred for 15 minutes. A 1,4-dioxane (21 mL) solution of 4,6-dichloronicotinamide (7.27 g, 38.1 mmol) was slowly added dropwise to the above bromine solution over 30 minutes. The reaction mixture was allowed to gradually warm up to 25°C over 18 hours. Upon completion of the reaction, the volatiles were removed by distillation under reduced pressure and the remaining solution was diluted with brine and poured into ethyl acetate. The aqueous phase was separated and extracted twice with ethyl acetate. The organic layers were combined, dried with sodium sulfate, decanted and concentrated to give an orange colored oil. The oily substance was purified by passing through a 100 g silica gel fast column using 25% ethyl acetate-hexane as eluent to give 4,6-dichloropyridin-3-ylamine as a brown solid (4.54 g, 73% yield). Finally, 30% aqueous hydrogen peroxide solution (29 mL) was cooled in an ice bath.
