Reaktion #473778

Reaktionsgleichung

potassium carbonate

8-methanesulphonyloxy-1,4-dioxa-spiro[4.5]decan

potassium carbonate

8-methanesulphonyloxy-1,4-dioxa-spiro[4.5]decan

4-[(3-chloro-2-fluoro-phenyl)amino]-6-hydroxy-7-methoxy-quinazoline

→

4-[(3-chloro-2-fluoro-phenyl)amino]-6-(1,4-dioxa-spiro[4.5]decan-8-yl-oxy)-7-methoxy-quinazoline

Lösungsmittel

water

ethyl acetate

dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe mixture is stirred for a further 7 hours at 80° C
2. 2
   TemperaturThe reaction mixture is cooled
3. 3
   Sonstigethe precipitate formed
4. 4
   Filtrationfiltered
5. 5
   Sonstigedried

Vorschrift

12.5 g potassium carbonate and 16 g 8-methanesulphonyloxy-1,4-dioxa-spiro[4.5]decan (cf. for example Journal of Medicinal Chemistry (1992), 35(12), 2243-7) in 125 ml dimethylformamide are added at 50° C. to 18.1 g 4-[(3-chloro-2-fluoro-phenyl)amino]-6-hydroxy-7-methoxy-quinazoline (cf. for example Bioorganic & Medicinal Chemistry Letters (2006), 16(18), 4908-4912) and the mixture is stirred for 18 hours at 80° C. Another 4.7 g potassium carbonate and 4.0 g 8-methanesulphonyloxy-1,4-dioxa-spiro[4.5]decan are added and the mixture is stirred for a further 7 hours at 80° C. The reaction mixture is cooled, diluted with water and ethyl acetate and the precipitate formed is suction filtered and dried.

Quelle