Studies On New Synthetic Process Of Adefovir Dipivoxil

A Duff Vee ester(Adefovir Dipivoxil) adenine phosphate compounds(A Duff Vee Adefovir) prodrug, after oral administration, can be rapidly hydrolyzed to A Duff Vee and exert antiviral effect, broad-spectrum antiviral activity A Duff Vee with anti hepatic DNA virus, retrovirus and herpes virus. At present a lot of synthetic process of adefovir dipivoxil, in order to be used for production better, we design a new process route to synthesize of adefovir dipivoxil. 1) Chloroethanol and trioxane are mixed to react to prepare ethyl chloride chloromethyl methyl ether(I); 2) isopropyl alcohol reacts with phosphorus trichloride reaction to prepare three ISO propyl phosphite(II); and then 3) I and II condensation of prepared 2-[double(isopropoxy)- phosphono methoxy] ethyl chloride(III); 4) III was used to prepare adenine 9-[2-(two isopropoxy phosphonomethoxy) ethyl] adenine(IV); 5) IV was reacted with hydrobromic acid and then hydrolyzed to form PMEA(V) again;6) V and pivaloyl chloride methyl esterified to obtain the target product of adefovir dipivoxil. Each step of the synthetic products in the new process route required a large number of research and development work, and we successfully developed a new synthetic technology of adefovir dipivoxil with investment value,the technology have the following advantages.1)the quality of the products has a strong competitive advantage, product purity above 99.5%, product content above 99.5%; 2) safety and environment; 3) total yield reached 27.2% to adenine as the initial calculation;(4) the cost of raw materials only 1255.9 yuan RMB, with a strong cost advantage and investment prospects;(5) reaction conditions are mild;(6) has the advantages of simple operation, easy to production management and personnel health.