Naphthyridines, Hantzsch

Formation of the central six-membered ring is the key to the synthesis of the highly substituted irnidazo[4,5-r]-[2,7]naphthyridines, 67 and 68 (Equations 15 and 16) the bicyclic precursors 65 and 66 are themselves the products of Hantzsch pyridine syntheses <1999PHA814>. 

The benzo-fused dihydrotetrazolo[2,7]naphthyridine 308 is a minor end-product of a mixed Hantzsch pyridine synthesis involving 2-azido-3-nitrobenzaldehyde, /3-aminocrotononi trile, and methyl /3-aminocrotonate in ethanol (Scheme 76) <2001TL4507>. 

Solid-phase syntheses have become increasingly popular during the period of this review, with examples including the synthesis of 5,6,7,8-tetrahydro[l,6]naphthyridines from Meldrum s acids derived from /3-amino alcohols via Hantzsch condensation and cyclization with cyclative cleavage from the resin (using 70% trifluoroacetic acid (TFA)/dichloromethane (DCM) followed by 5% triethylamine/DCM) <1999S1951> and also of isoquinolinones and 5-oxo-5,6-dihydro-[l,6]naphthyridines <1995JOC5748>. 

Hermecz and co-workers used the Hantzsch 1,4-dihydropyridine synthesis in their preparation of naphthyridines. Reaction of ethyl acetoacetate 8 and hexamethylenetetramine 221 as a novel source of nitrogen... 

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