Amino-1,6-naphthyridines reviews

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>. 

The Chichibabin reaction is exemplified by the amination of 2-methylpyridine (308) by sodium amide in toluene via intermediate 309 to yield 6-amino-2-methylpyridine (310). This reaction has been applied to pyridines, quinolines, isoquinolines, and naphthyridine as well as to benzimidazole, and was reviewed in great detail (66AHC229 78RCRI042 88AHC1). 

A good illustration of the te/e-amination reactions is interaction of 5-bromo-l,7-naphthyridine with KNH2 in liquid ammonia, leading to a mixture of 8-amino- and 2-amino-1,7-naphthyridines in 42 and 3% yields, respectively (Scheme 59) [126]. During the reaction the amide ion attacks C-2 and C-8 atoms, which are activated by the adjacent aza groups. The intermediate hydrogen bromide. Two excellent reviews on the tele-substitution reactions were published in 2001 and 2011 [104, 127]. 

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