DIRECTED AMINOMETHYLATION OF 3-HYDROXY-2(1H)-PYRIDINONES AND 3-HYDROXY-4(1H)-PYRIDINONES - SYNTHESIS OF ISO-DEFERIPRONE

The site of aminomethylation of N-unsubstituted 3-hydroxy-2-(1H)-pyrid inones and 3-hydroxy-4-(1H)-pyridinones, under Mannich reaction condit ions, is directed by the hydroxyl group when this is unprotected and b y the keto group when the hydroxyl is protected as an ether, This offe rs a convenient route to a variety of Mannich base synthons useful in the synthesis of derivatives of these clinically important, bidentate, metal-ion chelators. This is exemplified by reactions of 3-hydroxy-2- (1H)-pyridinone, 3-methoxy-2(1H)-pyridinone, 2-hydroxymethyl-5-hydroxy - 4(1H)pyridinone and 3-benzyloxy-2-methyl-4(1H)-pyridinone.