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

Participants

Reaction Conditions

Reaction Steps

At 50° C. 12.5 g potassium carbonate and 16 g 8-methanesulphonyloxy-1,4-dioxa-spiro[4,5]decane (cf for example Journal of Medicinal Chemistry (1992), 35(12), 2243-7) are added 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) in 125 ml dimethylformamide and the mixture is stirred for 18 hours at 80° C. Another 4.7 g potassium carbonate and 4.0 g of 8-methanesulphonyloxy-1,4-dioxa-spiro[4,5]decane are added and the mixture is stirred for another 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.

Provenance & Evidence