98796-53-3

131420-63-8

64325-78-6

98796-53-3

Synthesis of (2R,3S,5R)-5-(6-benzoylamino-9H-purin-9-yl)-2-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-4-hydroxytetrahydrofuran-2-yl)-9H-purin-6-yl)benzamide from N-(9-((2R,4S,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-4- hydroxytetrahydrofuran-2-yl)-9H-purin-6-yl)benzamide: The general procedure for synthesizing (2R,3S,5R)-5-(6-benzoylamino-9H-purin-9-yl)-2-((bis(4-methoxyphenyl)(phenyl) Methoxy)methyl)tetrahydrofuran-3-yl(2-cyanoethyl)diisopropylphosphoramidite was carried out in the following general steps: the nucleoside was phosphorylated using the N-methylimidazole salts of [O-β-cyanoethyl-N,N,N',N'-tetraisopropylphosphoramidite] and saccharin as the activators. This was done as follows: nucleoside (1.5 mmol) was added in a flask of appropriate size and the solid was dried by azeotropic distillation twice (using a rotary evaporator) with 20 mL of pyridine. After purging the flask with argon, 15 mL of acetonitrile was added. The mixture was stirred at room temperature until a clarified solution was formed. Subsequently, [O-β-cyanoethyl-N,N,N',N'-tetraisopropylphosphoramidite] (Tetraphos) was added to the solution, followed by the N-methylimidazole salt of saccharin. The reaction mixture was stirred continuously at room temperature and the progress of the reaction was monitored by HPLC. Upon completion of the reaction, the mixture was diluted with 30 mL of ethyl acetate and the organic phase was washed sequentially with 2 x 25 mL of saturated aqueous sodium bicarbonate and 25 mL of saturated aqueous sodium chloride. The organic layer was separated and dried with anhydrous magnesium sulfate. The dried suspension was filtered and the solvent was removed using a rotary evaporator. Finally, the residue was dried under vacuum to obtain the target product as a foamy solid.