3258-07-9

1-(a-D-ribofuranosyl)uracil is a purine nucleoside analog. Purine nucleoside analogs have broad antitumor activity targeting indolent lymphoid malignancies. Anticancer mechanisms in this process rely on inhibition of DNA synthesis, induction of apoptosis, etc[1].

The general procedure for the synthesis of 1-((2S,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione (Product A) from Compound D (CAS:3258-15-9) was as follows: 98 g of Compound D was dissolved in 500 mL of 0.1N hydrochloric acid solution at 20-25 °C The reaction was stirred at 20-25 °C for 24 h, during which the progress of the reaction was monitored by HPLC until the content of the remaining substance decreased to 0.21%. Upon completion of the reaction, the pH of the reaction system was adjusted to 7-8 using concentrated ammonia, followed by concentration under reduced pressure at 50±5°C until the volume was not reduced. Next, 500 mL of anhydrous acetonitrile was added to the concentrated residue and stirred at 70±5 °C until complete dissolution. Insoluble impurities were removed by filtration and the filtrate was crystallized by stirring at 0±5°C for 12 hours. The white solid product A was collected by filtration and analyzed by HPLC showing a purity of 99.92%. Finally, the product was blown dry at 45 °C for 24 h to give 71.8 g of the target compound.

[1] Robak T, Robak P. Purine nucleoside analogs in the treatment of rarer chronic lymphoid leukemias. Curr Pharm Des. 2012;18(23):3373-88. DOI:10.2174/138161212801227005