反应详情

温度

47.5 °C

4.8 kg of 4-ethylamino-2-methylsulfanyl-pyrimidine-5-carboxaldehyde and 5.5 kg of (3,5-dimethoxyphenyl)-acetic acid ethyl ester were dissolved in 10 L of DMSO at room temperature and stirred. 4.4 kg of 1,8-diazabicyclo[5.4.0]undec-7-ene was added to the reaction mixture. The mixture was heated at about 45-50° C. for at least 3 hours. The reaction was monitored by reverse-phase HPLC (YMC-AQ column, 60:40 CH3CN/0.02 M SDS, pH 2.2, 1.0 mL/min, 254 nm). When the reaction was completed, ethyl alcohol (3 L) was added to the reaction vessel, which was cooled to 5-15° C. The yellow product was precipitated and collected by filtration, washed with a mixture of isopropyl alcohol and water (3 L+3 L), and dried in a vacuum tray dryer at about 40-45° C. for at least 12 hours using a house vacuum (˜30 in Hg) to provide 7.3 kg (84% yield) of 2-(methylsulfanyl)-6-(3,5-dimethoxyphenyl)-8-ethyl-8H-pyrido[2,3-d]pyrimidine-7-one. Proton NMR is consistent with the structure.

1. temperaturewas cooled to 5-15° C
2. customThe yellow product was precipitated
3. filtrationcollected by filtration
4. washwashed with a mixture of isopropyl alcohol and water (3 L+3 L)
5. customdried in a vacuum tray dryer at about 40-45° C. for at least 12 hours