Synthesis
Triphenylchloromethane (15 g, 53.7 mmol) was slowly added to a solution of pyridine (40 mL) containing 1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidin-2,4(1H,3H)-dione (10 g, 41.3 mmol) under nitrogen protection, and the reaction mixture was kept at room temperature for The reaction mixture was stirred for 21.5 hours at room temperature. Upon completion of the reaction, the reaction was quenched by the addition of saturated aqueous sodium bicarbonate solution to the system, followed by extraction and separation with dichloromethane. The organic phase was washed sequentially with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate. The organic solvent was removed by concentration under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (eluent ratio of ethyl acetate:n-hexane=1:1) to afford the target compound 1-((2R,4S,5R)-4-hydroxy-5-((triphenylmethoxy)methyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione (19.4 g, 97.1% yield), as colorless acicular crystals. ), colorless needle-like crystals.
References
[1] Hernández A et al. Acyclic nucleoside analogues as novel inhibitors of human mitochondrial thymidine kinase. J Med Chem. 2002 Sep 12;45(19):4254-63. DOI:
10.1021/jm011128+[2] Golubovskaya V et al. A small-molecule inhibitor, 5'-O-tritylthymidine, targets FAK and Mdm-2 interaction, and blocks breast and colon tumorigenesis in vivo. Anticancer Agents Med Chem. 2013 May;13(4):532-45. DOI:
10.2174/1871520611313040002
