15783-48-9

Step 2-Synthesis of 2,4-dichlorofuro[3,4-d]pyrimidin-7(5H)-one (fq): to a suspension of 5-hydroxymethyl orotate lactone (fp) (550 mg, 3.3 mmol) in dichloromethane (2.5 mL) was added drop-wise triethylamine (TEA) (0.91 mL, 6.5 mmol), followed by phosphorus oxychloride (POCl3) ( 4.5 mL, 48 mmol). The reaction mixture was stirred at 90 °C overnight. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure. The residue was carefully poured into ice water and extracted with dichloromethane (3×). The organic phases were combined, dried over anhydrous magnesium sulfate (MgSO4), filtered and concentrated under reduced pressure to give 510 mg (76% yield) of the target product (fq) as a brown solid. The product could be used in subsequent reactions without further purification; LC-MS: m/z = 205 ([M+H]+).

[1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 7, p. 2565 - 2571
[2] Patent: US2010/331305, 2010, A1. Location in patent: Page/Page column 75
[3] Patent: US2011/21515, 2011, A1. Location in patent: Page/Page column 10
[4] Patent: WO2012/99581, 2012, A1. Location in patent: Page/Page column 21