反应详情

温度

50 °C

To a solution of 88 g (0.93 mol) of 4-aminopyridine in 1 L of tetrahydrofuran was added 21.2 g (2.67 mol) of lithium hydride. The reaction mixture was heated to 50° C. for 1 hour. To the stirred reaction mixture was added a solution of 318 g (0.89 mol) of 2-(methylsulfanyl)-6-(3,5-dimethoxyphenyl)-8-ethyl-8H-pyrido[2,3-d]pyrimidin-7-one in 1.8 L of tetrahydrofuran. The reaction solution was heated at reflux for 24 hours, and then cooled to 50° C. The reaction mixture was diluted by the slow addition of a mixture of 500 mL of water and 1 L of 6N hydrochloric acid. The reaction mixture was cooled to 24° C. and stirred for 16 hours. The reaction mixture was further diluted by addition of 250 mL of acetonitrile and 200 mL of water, and stirring was continued for an additional 2 hours. The mixture was then filtered, and the filter cake was dried at 45° C. in vacuo for 12 hours to provide 360 g (92%) of 2-(pyridin-4-ylamino)-6-(3,5-dimethoxyphenyl)-8-ethyl-8H-pyrido[2,3-d]pyrimidin-7-one hydrochloride, mp 295-300° C. (dec). HPLC established the purity at 98%. Mass Spec (APCI) 439.89 m/z.

1. customTo the stirred reaction mixture
2. temperatureThe reaction solution was heated
3. temperatureat reflux for 24 hours
4. temperaturecooled to 50° C
5. temperatureThe reaction mixture was cooled to 24° C.
6. stirringstirring
7. waitwas continued for an additional 2 hours
8. filtrationThe mixture was then filtered
9. customthe filter cake was dried at 45° C. in vacuo for 12 hours