反应详情

温度

110 °C

To 1-cyclopropyl-3-(2-fluoro-4-iodophenyl)-pyrimidine-2,4,6-trione 49 (59.0 g) obtained in Step 2 were added phosphorus oxychloride (85.0 ml) and dimethylaniline (29.0 ml), and water (8.3 ml) was added dropwise to the mixture at room temperature with stirring. After the completion of the dropwise addition, the mixture was stirred with heating at 110° C. for 1 hr. After allowing to cool to room temperature, the reaction mixture was added dropwise to ice water-toluene [2:1 (volume ratio), 900 ml] with stirring. The mixture was stirred at room temperature for 1 hr. The organic layer was separated, and washed successively with water (300 ml) and brine (300 ml). Anhydrous magnesium sulfate and activated carbon were added and the mixture was stirred. Anhydrous magnesium sulfate and activated carbon were filtered off, and the filtrate was concentrated under reduced pressure to give a 1:2 mixture (62.9 g) of 6-chloro-3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-1H-pyrimidine-2,4-dione 50 and 6-chloro-1-cyclopropyl-3-(2-fluoro-4-iodophenyl)-1H-pyrimidine-2,4-dione 51 as a yellow foamy oil, which was used for the next step without purification.

1. additionwas added dropwise to the mixture at room temperature
2. additionAfter the completion of the dropwise addition
3. stirringthe mixture was stirred
4. temperatureto cool to room temperature
5. stirringwith stirring
6. stirringThe mixture was stirred at room temperature for 1 hr
7. customThe organic layer was separated
8. washwashed successively with water (300 ml) and brine (300 ml)
9. additionAnhydrous magnesium sulfate and activated carbon were added
10. stirringthe mixture was stirred
11. filtrationAnhydrous magnesium sulfate and activated carbon were filtered off
12. concentrationthe filtrate was concentrated under reduced pressure