Research On The Synthesis Process And Crystal Form Study Of Vidarabine Monophosphate

Vidarabine monophosphate,named as 9-?-D-arabino furanosyl-adnine-5' monopho sphoric acid,is a kind of anti DNA virus drug treating hepatitis B in clinic.In this dessertation,we firstly described the preparation of viadarbine monophosphate by using pyrophosphoryl chloride as starting material,and optimized the synthesis process by orthogonal experimental methods.We also developed a valuable new crystal form of vidarabine monophosphate and studied its crystallization process.The orthogonal experiment mainly investigate the influence of reaction temperature,reaction time,the ratio of volume of triethyl phosphate to mass of vidarabine,the mol ratio of pyrophosphoryl chloride to vidarabine on the yield of vidarabine monophosphate.The optimized condition of the process is: reaction time of 10h;The ratio of volume of triethyl phosphate to mass of vidarabine is 10 mL/g;reaction temperature of-5?;the mol ratio of pyrophophoryl chloride to vidarabine is 1.3:1.The average yield can reach 85.9% under such condition.The factors of influence on the reaction yield from large to small order is volume of reaction temperature,the ratio of volume of triethyl phosphate to mass of vidarabine,reaction time,the mol ratio of pyrophosphoryl chloride to vidarabine.Crystallization process experimental result shows that the original crystal form A can converse into desired crystal form D smoothly above 50? in an ethanol-water solution of concentration above 50% for1-3 h under rotating crystallization condition;Under reactive crystallization condition We finally confirm the boundary experimental conditions of these two crystallization experiment.Under rotating crystallization experimental condition,vidarabine monophosphate crude product or given crystal form product as starting material can converse into desired crystal form product smoothly in ethanol-water solution of concentration above 20%.