反应详情

温度

95 °C

To a 6:5 mixture (59.6 g) of 1-(2-fluoro-4-iodophenyl)-3-methyl-6-methylamino-1H-pyrimidine-2,4-dione 67 and 3-(2-fluoro-4-iodophenyl)-1-methyl-6-methylamino-1H-pyrimidine-2,4-dione 68 obtained in Step 4 and 2-methyl-malonic acid 54 (20.7 g) was added acetic anhydride (180 ml), and the mixture was stirred with heating at 95° C. for 1 hr. After allowing to cool to room temperature, the mixture was concentrated under reduced pressure. Tetrahydrofuran (350 ml) was added to the residue, and the mixture was stirred with heating under reflux for 1 hr. After allowing to cool to room temperature, the crystals were filtered off. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (chloroform:tetrahydrofuran=18:1). Toluene (150 ml) was added to the obtained solid, and the mixture was stirred with heating under reflux for 30 min. After allowing to return to room temperature, the crystals were collected by filtration and dried to give 1-(2-fluoro-4-iodophenyl)-5-hydroxy-3,6,8-trimethyl-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione 69 (27.0 g, yield 37%) as colorless crystals.

1. temperatureto cool to room temperature
2. concentrationthe mixture was concentrated under reduced pressure
3. additionTetrahydrofuran (350 ml) was added to the residue
4. stirringthe mixture was stirred
5. temperaturewith heating
6. temperatureunder reflux for 1 hr
7. temperatureto cool to room temperature
8. filtrationthe crystals were filtered off
9. concentrationThe filtrate was concentrated under reduced pressure
10. customthe residue was purified by column chromatography (chloroform:tetrahydrofuran=18:1)
11. additionToluene (150 ml) was added to the obtained solid
12. stirringthe mixture was stirred
13. temperaturewith heating
14. temperatureunder reflux for 30 min
15. customto return to room temperature
16. filtrationthe crystals were collected by filtration
17. customdried