4-Amino-3-pyridinecarbaldehyde

Amino-3-pyridinecarbaldehyde (82) with ethyl cyanoacetate gave 2-oxo-1,2-dihydro-l,6-naphthyridine-3-carbonitrile (83) (reactants, trace piperidine, EtOH, reflux, 1 h 92%) 247 also analogs similarly.924... 

Note A great many such syntheses have been reported, most of them using 2-amino-3-pyridinecarbaldehyde or related substrates. 2-Amino-5,6-diphenyl-3-pyridinecarbaldehyde (32) with a-benzoyltoluene gave 2,3,6,7-tetraphenyl-l,8-naphthyridine (33) (EtOH, trace KOH 90%).284... 

Acetyltropolones 391 reacts with 2-amino-3-pyridinecarbaldehyde to afford the 3-(l,8-naphthyiidin-2-yl)tropolone in excellent yields. In a similar manner, l,6-naphth3nidin-2-yl- 392, l,7-naphthyridin-2-yl- 393,... 

A subclass of lyases, involved in amino acid metabolism, utilizes pyridoxal 5-phosphate (PLP, 3-hydroxy-2-methyl-5-[(phosphonooxy)methyl]-4-pyridinecarbaldehyde) as a cofactor for imine/ enamine-type activation. These enzymes are not only an alternative to standard fermentation technology, but also offer a potential entry to nonnatural amino acids. Serine hydroxymethyl-tansferase (SHMT EC 2.1.2.1.) combines glycine as the donor with (tetrahydrofolate activated) formaldehyde to L-serine in an economic yield40, but will also accept a range of other aldehydes to provide /i-hydroxy-a-amino acids with a high degree of both absolute and relative stereochemical control in favor of the L-erythro isomers41. 

Amino-3-pyridinecarbaldehyde (86) with limited 2,3-butanedione gave 2,2 -bi-l,6-naphthyridine (87) (substrate, NaOH, H20, EtOH, reflux synthon/ EtOHJ, dropwise during 3h reflux, 8h 81%).620... 

Amino-4-pyridinecarbaldehyde (29) reacted with acetone to give 2-methyl-1,7-naphthyridines (30, R = Me) (reactants, NaOH, EtOH, reflux, 1 h 80%), with acetophenone to give 2-phenyl-1,7-naphthyridine (30, R = Ph) (likewise, 24 h 80%), or with other such synthons to give appropriate analogs 1103 the Schiff base, 4-p-tolyliminomethyl-3-pyridinamine, has also been used as a substrate to give 2-phenyl-1,7-naphthyridine (30, R = Ph) (BzMe, AcOH, H20, EtOH, reflux, 8 h 84%).100... 

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