SYNTHESIS OF 5,6-DISUBSTITUTED THIENO[2,3-d]PYRIMIDINES FROM 4-CHLOROPYRIMIDINES

摘要

Facile reaction sequences for the preparation of 5,6-disubstituted thieno[2,3-d]pyrimidines starting with 4-chloropyrimidines have been developed. 4-Chloro-6-methoxypyrimidines were aroylated at the 5-positions via lithiation with LDA and subsequent treatment with benzaldehyde or N-methoxy-N-methylbenzamides to give aryl(4-chloro-6-methoxypyrimidin-5-yl)methanones. These pyrimidinyl ketones were transformed in one-pot into 5,6-disubstituted 4-methoxythieno[2,3-d]pyrimidines by a successive treatment with sodium sulfide, BrCH2EWGs, and sodium hydride. Lithiation of 4,6-dichloro-2-(methylsulfanyl)pyrimidine at the 5-position was followed by treatment with tertiary formamides to give 4-chloro-6-(dialkylamino)pyrimidine-5-carboxaldehydes, which could be transformed into 5,6-disubstituted 4-(dialkylamino)thieno[2,3-d]pyrimidines via aryl[4-chloro-6-(dialkylamino)-pyrimidin-5-yl]methanones using the same one-pot thiophene ring forming sequence.