Synthesis Of2-Alkylthio-6-Amino-9-Substituted Purines

Thrombotic disease is one of the largest causes of disease deaths in the world, which has great threat to human’s life. Researchers have always been working to discover safe and effective antithrombotic drugs. The purine compounds are widespread in nature which have good biological activity in terms of anti-thrombotic, and therefore become the focus of the study.As the starting material2-amino-6-chloropurine was treated with2-bromoethyl acetate to obtain9-acetoxyethyl-2-amino-6-chloropurine (2).2was diazotized and reacted with disulfides to produce9-acetoxyethyl-2-alkythio-6-chloropurine (3). NaN3was reacted with3to acquire9-acetoxyethyl-2-alkythio-6-triazopurine (4). The NMR test of4showed that there were azido tautomer and tetrazolyl tautomer in the solution. PPh3-HCl-DMSO was used as the reaction solvent, the trizao group was reduced to amino and the ester group was hydrolyzed completely to afford the2-alkylthio-6-amino-9-(2-hydroxylethyl)purine (6) in good yield in one pot.Intermediate9-acetoxyethyl-2-alkoxythio-6-azido purine (4) as the starting material was hydrolyzed by2M HC1to give9-(2-hydroxyethyl)-2-alkylthio-6-azido purine (7);7was treated with tert-butyl bromoacetate to product6-azido-2-alkylthio-9-substituted purine (8); then8was reduced to6-amino-2-alkylthio-9-acyclic substituted purine (9) in Zn/CH3COOH system. Finally,9was hydrolyzed to obtain10in dilute hydrochloric acid. In this thesis, twenty9-substituted-6-amino-2-alkylthio purines which have not been reported in the literature were obtained. All the compounds were comfirmed through IR,1H NMR,13C NMR and HRMS.