5-Fluorouracil → 5-Fluoro-1-(2-methylpropyl)-2,4(1H,3H)-pyrimidinedione

To a solution of 5-fluoropyrimidine-2,4(1H,3H)-dione (5.0 g, 38 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU; 6.4 g, 42 mmol) in dry CH3CN (150 mL) at room temperature and under nitrogen was added 1-bromo-2-methylpropane (5.3 g, 38 mmol) dropwise. The reaction was then heated to reflux for 18 h. After cooling to room temperature, the solvent was removed in vacuo. The crude residue was purified by normal phase chromatography (gradient, 0 to 20% EtOAc/Petroleum ether), providing 5-fluoro-1-isobutylpyrimidine-2,4(1H,3H)-dione (2.5 g, 35%) as a white solid: mp 173-174° C.; 1H NMR (400 MHz, CDCl3) δ 8.61 (s, 1H), 7.21 (d, J=5.5 Hz, 1H), 3.53 (d, J=7.5 Hz, 2H), 2.13-2.01 (m, 1H), 0.98 (d, J=6.7 Hz, 6H); ESIMS m/z 185 ([M−H]−).

1. temperatureThe reaction was then heated
2. temperatureto reflux for 18 h
3. customthe solvent was removed in vacuo
4. customThe crude residue was purified by normal phase chromatography (gradient, 0 to 20% EtOAc/Petroleum ether)

ORD record

ord-2d45366fd21b4f1cb2822acd947eba87

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08916579B2