反应详情

A solution containing 16.32 g (0.08 mol) of 6-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acid and 12.4 ml (0.088 mol) of triethylamine in 480 ml of chloroform is cooled below -10° C. while stirring and cooling by ice-salt. To this mixture, 6.5 ml (0.08 mol) of methyl chloroformate dissolved in 40 ml chloroform are dropped at -20° C. during 10 minutes. After stirring for 5 minutes, a solution containing 2.5 g (0.08 mol) of methylamide (prepared from methylamine hydrochloride in chloroform by adding triethylamine) in 80 ml of chloroform is added dropwise to the reaction mixture at -18° C. during 30 minutes. After stirring below -10° C. for 1 hour, the reaction mixture is allowed to stand in the refrigerator overnight. Next day the reaction mixture is washed 3 times with 140 ml of 5% sodium hydrogen carbonate solution each and then with 140 ml of water. The organic phase is dried over anhydrous sodium sulfate and evaporated under reduced pressure. The residue is stirred with 150 ml of 10% hydrochloric acid at room temperature for 1 hour, then the precipitated starting material, 6-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acid weighing 10 g is filtered off. The pH value of the aqueous filtrate is adjusted to 9 by adding 20% sodium hydroxide solution and then extracted 3 times with 100 ml of chloroform each. The combined organic phase is dried over anhydrous sodium sulfate and evaporated. After recrystallization of the residue from ethanol, 3.2 g (45.5%) of the named lemon-yellow product are obtained, m.p.: 208°-210° C.

1. temperatureis cooled below -10° C.
2. additionare dropped at -20° C. during 10 minutes
3. stirringAfter stirring for 5 minutes
4. additionis added dropwise to the reaction mixture at -18° C. during 30 minutes
5. stirringAfter stirring below -10° C. for 1 hour
6. customto stand in the refrigerator overnight
7. washNext day the reaction mixture is washed 3 times with 140 ml of 5% sodium hydrogen carbonate solution each and then with 140 ml of water
8. dry with materialThe organic phase is dried over anhydrous sodium sulfate
9. customevaporated under reduced pressure
10. stirringThe residue is stirred with 150 ml of 10% hydrochloric acid at room temperature for 1 hour
11. filtrationis filtered off
12. additionby adding 20% sodium hydroxide solution
13. extractionextracted 3 times with 100 ml of chloroform each
14. dry with materialThe combined organic phase is dried over anhydrous sodium sulfate
15. customevaporated
16. customAfter recrystallization of the residue from ethanol, 3.2 g (45.5%) of the named lemon-yellow product
17. customare obtained