.3,4 - Diamino-1h - Pyrazolo [5,4-d] Pyrimidine Solid Phase Synthesis And Antiviral Drugs The Vp-63843 Synthesis Research

The first part of this paper was focused on the solid phase synthesis of 3, 4-diamino-lH-pyrazolo[5,4-d]pyrimidines.The history of the medicine research has displayed that the nitrogen containing heterocyclic compounds are the main source of medicines due to their excellent biological absorption and pharmacokinetic properties. Therefore, using solid phase method to prepare this kind of compounds is of considerable Interest from the standpoint of searching for biologically active substances.Among the nitrogen containing molecules, pyrazolo[5,4-d]pyrimidine as analogues of biogenic purines, possesses a lot of valuable pharmacological features such as antivirus, anticancer etc., while the research of solid phase synthesis of this kind of compounds is deficient.The purpose of our research work was to find an efficient way to prepare these compounds. During our research work, the synthesis of a kind of derivatives of pyrazolo[5,4-d]pyrimidine via several steps including reductive animation, substitution, intramolecular nucleophilic addition and cleavage reaction starting from Merrifield resin was completed. The related linker was designed and synthesized, and its use in solid phase was studied. The conditions of the reactions were optimized by the way of solution mimicry using a secondary amine which has the similar structure to the linker and infrared spectroscopy analysis. The optimal concentration of TFA/CH2C12 for cleavage was determined by comparison. The preparation of the intermediates 4,6-dicloro-2-methylthio-5-pyrimidine carboxaldehyde oxime and 3-methoxy phenol were also improved.In the second part, we focused our work on the synthesis of VP-63843, a potent antiviral agent with activity against members of the Picornaviridea, which can cause a wide spectrum of human disease, including aseptic meningitis, encephalitis, febrile illness and a variety of respiratory illness. Firstly, a new route to prepare VP-63843 trough Mitsunobu reaction was designed and synthesized; secondly, the route reportedby the bibliography was improved. By contrasting some different methods to prepare the important intermediate 2, 6-dimethyl-4-nitrile phenol, the optimal synthetic route and reaction conditions were finally found.