Synthesis Of 6,8,9-trisubstitute Purine Derivatives

Purine derivatives are a kind of antiviral drugs and a kind of pharmaceutical intermediate in preparation nucleotide. Some substitution group are introduced to 6,8,9-substiue of purines. Thus, these purines have the biomedicine activity of antiviral, anticancer and dropping blood pressure. A methodology which was developed for the efficient synthesis of novel purine derivatives provides efficient methods to access libraries of compounds based on privileged substructures that are of great interest in adjusting reagent of biological progress and new drug discovery.In this dissertation, using hydrochloric acid as catalyst in ethanol, the start material of 5-amino-4,6-dichloropyrimidine reacted with the corresponding amine to obtain 6-chloro- 4,5-diaminopyrimidine as the key intermediate. Then, purine derivatives were prepared through the reactions of 6-chloro-4,5-diaminopyrimidine and carboxylic acids catalyzed by polyphosphoric acid. Unfortunately, subjecting 6-chloro-4,5-diaminopyri- midine to the reaction conditions of acid aqueous will led to substantial hydrolysis of the 6-chloro to give 6-hydroxylpurine. In order to introduce C6 group, we must converted 6-hydroxyl purine to 6-chloro purine in presence of phosphrous oxychloride.The C8 group of purines was introduced successfully under mild condition and N9 group was introduced in the procedure of cyclization reaction. surprisingly, attempted substituted of 4-aminopyridine on C6 did not give desired products. Instead, an unexpected substituted reaction occurred to give 6-alkoxypurine, which can be viewed as a new method for 6-alkoxypurine synthesis. That method avoid sodium which the standard reaction conditions of obtaining 6-alkoxypurine.More than fifty new purine derivatives were synthesized in this paper, and the structures of all the synthesized compounds were characterized by 1H NMR, MS spectrum and elemental analysis.