2-CHLORO-5-FLUOROPYRIMIDIN-4-ONE

Dimethylaniline (195 mL, 1.54 mol) was added to a slurry of 5-fluorouracil (99.73 g, 0.77 mol) in phosphorus oxychloride (215 mL, 2.31 mol) at 95 °C under a nitrogen atmosphere. The reaction mixture was stirred at this temperature for 3.5 h, cooled to room temperature and then slowly added to a stirred mixture of ice (200 g) and 6 M HCl (200 mL). The resulting slurry was extracted with dichloromethane (2 x 400 mL) and the combined organic extracts were washed with DI water (4 x 275 mL), dried over MgSO4 and concentrated under reduced pressure to afford 111.77 g (87percent, 98.1percent AUC by HPLC) of 5-fluoro-2, 4-dichloro-pyrimidine as an amber oil. A molar solution of sodium hydroxide (1.34 L) was slowly added to a solution of the 5-fluoro-2, 4-dichloro-pyrimidine (111.77 g, 0.67 mol) in THF (377 mL) at 0 °C. After the reaction mixture was stirred for about 30 min at room temperature, the pH was adjusted to 6 by a slow addition of 1.0 M HCl. The aqueous solution was extracted with ethyl acetate (440 mL) to remove impurities following which the pH was adjusted to 1 with 1.0 M HCl. The acidic aqueous solution was extracted with ethyl acetate (4 x 555 mL) and the combined organic extracts were washed with brine (111 mL), dried over MgSO4 and concentrated under reduced pressure to produce 88.35 g (89percent, 99.2percent AUC by HPLC) of 2-chloro-5-fluoro-3H-pyrimidin-4-one as an off-white powder.To a solution of 5-fluoro-2, 4-dichloro-pyrimidine (1 g, 5.99mmol) in THF (3.3 mL) was added NaOH (1 M in water, 11.7 mL) at 0 °C. The reaction mixture was stirred at room temperature for 3 h before it was acidified (pH 1) with 1 M HCl. The product was extracted with EtOAc (3x10 mL), the combined organic extracts were dried over Na2SO4 and the solvent was removed under reduced pressure providing crude 84 (638 mg, 72percent), which was used for the next step without further purification.2-Chloro-5-fluoro-3H-pyrimidin-4-one The title compound was prepared in 56percent yield from 2, 4-dichloro-5-fluoro-pyrimidine as described in U.S. patent application Ser. No. 10/918, 317. Specifically, 5-Fluoro-2, 4-dichloro-pyrimidine was stirred in THF (10 mL) with 1N NaOH at r.t. for 3 h. The solution was made slightly acidic with 1N HCl and was extracted with CHCl

Molecular Weight:148.52
XLogP3:0.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:147.9839685
Monoisotopic Mass:147.9839685
Topological Polar Surface Area:41.5
Heavy Atom Count:9
Complexity:211
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes