Synthesis Of 2, 6, 9-Substitute Purine Derivatives

Purine derivatives are very important of nucleoside pharmaceutical intermediates, such as anticancer and antitumor drug. In this dissertation, a series of purine derivatives are synthesized via guanine as the material, which will superinduce the structural type and search of new original active compounds.The start material of guanine reacted with acetic anhydride in acetic anhydride and pyridine at 135℃to give N2,9-diacetylguanine. Through chloridization and hydrolyzation, 2-amino-6-chloropurine was prepared in acetonitrile and dichloroethane solvents. Then, 2-amino-6-chloropurine as the key intermediate, using NaNO2, through diazotization, 2,6-dichloropurine was prepared in hydrochloric acid. 6-chloropurine derivatives as the raw material, through alkoxylate reaction, 6-alkoxypurine derivatives were prepared in DMF. This improved method compared with the original method shows the environmentally friendly advantage.Under nitrogen atmosphere, 6-chloropurine derivatives reacted with aromatic amines in n-butanol at 80℃in the presence of triethylamine to give 6-arylaminopurine derivatives. Then, 2-chloro-6-arylaminopurine derivatives as the key intermediates, through N-alkylation, 2,6-disubstituted-arylaminopurine derivatives were prepared in n-butanol at 117℃in the presence of Lewis acid. This method make purine ring 2,6-amino access to the process of choosing a different temperature and catalyst, an effective solution to the reaction selectivity. This One-Pot-Synthesis method provides several advantages such as environmental friendliness, low cost, simple workup procedure and so on.2,6-disubstituted purine derivatives reacted with alkyl halides in DMF at room temperature in the presence of anhydrous potassium carbonate to give 9-alkyl purine derivatives. This synthesis method provides several advantages such as environmental friendliness, low cost, simple workup procedure and so on.More forty new Purine derivatives were synthesized in this paper, and the structures of all the synthesized compounds were characterized by IR, 1H NMR, MS spectrum and elemental analysis.