Synthesis Of Tenofovir Disoproxil Fumarate

AIDS and hepatitis B had taken great pain to people's lives and health over the past years,and Tenofovir disoproxil fumarate as a new nucleoside reverse transcriptase inhibitor showed good Antiviral activity which can be a good inhibition of HIV virus and HBV virus.Tenofovir disoproxil fumarate has been listed in the United States in 2001 for the treatment of adult HIV infection,and approved by the FDA in 2008 for the treatment of HBV infection that is an important anti-HIV drugs and anti-hepatitis B Viral drugs.The industrialization of Tenofovir disoproxil fumarate has great social and economic benefits,and broad market prospect.It is very meaningful to study the technology of tenofovir fumarate.After a number of experiments,for Nuo Fuwei and chloromethyl isopropyl carbonate with phase transfer catalyst,direct condensation of the production of tenofovir two imidacloprid furosemide esters,and fumaric acid fumaric acid tenofovir two imidacloprid furosemide ester salt.The route selection is to R-epoxy propane as raw material,formation and condensation(adenine R(-9-)2-hydroxypropyl)adenine,and p-toluenesulfonyl methyl phosphonic acid ethyl ester two by etherification generation(R)-9-[2-(two ethoxylated phosphonic acid methoxy)propyl] adenine,hydrolyzed for Nuo Fuwei,the total yield of about 45%.R-route using propylene oxide as raw material by condensation.Etherification,hydrolysis were synthesized in three steps for Nuo Fuwei,less reaction steps.The steps are short,mild conditions,suitable for industrialization.After the test of IR,NMR(1HNMR,13CNMR),ESIMS spectra determination and analytical results,and fumaric acid tenofovir two imidacloprid furosemide ester molecular structure.To determine the molecular structure of fumaric acid tenofovir two imidacloprid furosemide esters.Our way on crystallization were studied in detail,found that: stirring crystallization,grain is fine,sticky and difficult to filter and static crystallization.When the grain size is larger,more loose,easy to filter,at 20~30 ? static crystallization,can further improve the filtering.So we choose cooled to 5~10 ? then,static crystallization.