Synthesis
The general procedure for the synthesis of 4-amino-5-bromo-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one from cytidine was as follows: using a typical method of bromination of unprotected nucleosides, 1,3-dibromo-5,5-dimethylglycolactonium (DBH, 323 mg, 1.13 mmol ) was added to a stirred solution of cytidine (1d, 500 mg, 2.05 mmol) in N,N-dimethylformamide (DMF, 5 mL). The reaction mixture was stirred at room temperature for 20 min or monitored by thin layer chromatography (TLC) until the starting material completely disappeared and a less polar product was formed. Subsequently, the volatile solvent was evaporated under reduced pressure and the residue was co-evaporated with acetonitrile (MeCN) to remove the residual DMF.The resulting light-colored solid was recrystallized from hot acetone to give the target product 2d (500 mg, 75% yield) as colorless crystals with physicochemical properties consistent with those reported in the literature.
References
[1] Organic and Biomolecular Chemistry, 2014, vol. 12, # 30, p. 5634 - 5644
[2] Synthesis, 2009, # 23, p. 3957 - 3962
[3] Tetrahedron Letters, 2012, vol. 53, # 26, p. 3333 - 3336
[4] Molecules, 2013, vol. 18, # 10, p. 12740 - 12750
[5] Journal of the American Chemical Society, 1995, vol. 117, # 2, p. 704 - 714
