Studies On Synthesis Technology Of Adefovir Dipivoxil

Adefovir dipivoxil is an HIV nucleoside inhibitor named [[2-(6-amino-9H-purine-9-yl) ethoxy] methyl]phosphoric acid 2-(Special E acyloxo methyl)ester which is developed first in the United States by the Gilead Sciences company at 2002. And named Hepsera. This product is the ester prodrug adefovir (2), with broad-spectrum antiviral activity, inhibit the hepatotropic virus, retrovirus and herpes virus.Adefovir dipivoxil is a new drug obtained by ours company, sales of substantial was good when after-market, and brought us huge economic benefits. We use the synthesis method of Holy modified. This product is amorphous powder, on the crystal form does not constitute patent infringement. We developed agents, are adefovir dipivoxil and the formation of solid polyethylene glycol 4000 inclusive thing, and does not constitute an infringement of the patent agents, and tablets can not exist in crystal form of adefovir dipivoxil problem.However, because of the low yield and unstable of the last step reaction to the ester, prevented our company to expand the scale of production, and affecting the cost of this goods. Therefore, I preferred reagents through the re-combination reaction sequence, optimization of reaction temperature and change the reaction time and other methods to re-modify or optimize the process.The results showed that the product yield and quality was improved by optimizing the conditions, and maked the process more stable.