反应详情

温度

40 °C

6 ml phosphorus oxychloride are added dropwise to 12.1 g 3,4-dihydro-4-oxo-6-(1,4-dioxa-spiro[4,5]decan-8-yl-oxy)-7-methoxy-quinazoline in 120 ml acetonitrile and the mixture is heated to an internal temperature of 40° C. Then 9.3 ml triethylamine are added dropwise and the reaction mixture is refluxed for 3 hours. The mixture is cooled to ambient temperature and after standing overnight half the solution of the intermediate product (4-chloro-6-(1,4-dioxa-spiro[4,5]decan-8-yl-oxy)-7-methoxy-quinazoline, see Example IX) is combined dropwise with 2.7 ml of 2-fluoro-5-methylaniline in 5 ml acetonitrile. The reaction mixture is heated to 40° C. for 3 hours, then cooled and evaporated down. The residue is mixed with water and stirred. The precipitate formed is suction filtered and divided between 1M sodium hydroxide solution and dichloromethane. The organic phase is separated off, dried, evaporated down and stirred with diisopropylether. The solid is suction filtered and dried.

1. temperaturethe reaction mixture is refluxed for 3 hours
2. temperatureThe mixture is cooled to ambient temperature
3. temperatureThe reaction mixture is heated to 40° C. for 3 hours
4. temperaturecooled
5. customevaporated down
6. additionThe residue is mixed with water
7. customThe precipitate formed
8. filtrationfiltered
9. customThe organic phase is separated off
10. customdried
11. customevaporated down
12. stirringstirred with diisopropylether
13. filtrationfiltered
14. customdried