IMPROVED PROCESS FOR THE PREPARATION OF N6-2-(METHYLTHIO)ETHYL-2-(3,3,3-TRIFLUOROPROPYL)THIO-5'-ADENYLIC ACID, MONOANHYDRIDE WITH (DICHLOROMETHYLENE) BISPHOSPHONIC ACID AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS

摘要

The present invention relates to an improved process for the preparation of N6-[2- (methylthio)ethyl]-2-[(3,3,3,­trifluoropropyl)thio]-5'-adenylic acid, monoanhydride with (dichloromethylene)bisphosphonic acid of formula-(I), its pharmaceutically acceptable salts and its polymorphic forms. (Formula I) (I) The present invention also related to an improved process for the preparation of (2R,3R,4S,5R)- 2-(6-amino-2-((3,3,3-trifluoropropyl)thio)-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran- 3,4-diol of formula (IV) by greatly reducing the formation of dimer impurity of formula (XVII). The present invention also related to an improved process for the preparation of ((2R, 3S, 4R, 5R)-3, 4-dihydroxy-5-(6-((2-(methylthio)ethyl)amino)-2-((3,3,3-trifluoropropyl)thio)-9H-purin- 9-yl)tetrahydrofuran-2-yl)methyl dihydrogenphosphate of formula (IX) with more yield and high purity.