Naphthyridinecarboxamides

The available information on these esters is summarized in the following paragraphs. 

Most of these esters have been made by primary synthesis (see Chapter 8) others, by the Reissert reaction (see Section 9.1.3), esterification (see Section 14.1.2), or by passenger introduction. 

Note The hydrolysis of esters has been covered in Section 14.1.1 other reactions are exemplified here. 

Methyl 2-amino-l,6-naphthyridine-3-carboxylate (13, R = Me) underwent amino lysis to give 2-amino-l,6-naphthyridine-3-carbohydrazide (14, R = NH2) (neat H2NNH2 H20, reflux, 30 min 83%) or 2-amino-fV-amidino 1,6-naphthyridine-3-carboxamide [14, R = C( = NH)NH2] [HN=C(NH2)2, MeOH, reflux, 1 h 80%] 247 another example of such amide formation.108,946 

8-(2-Ethoxycarbonylethyl)-5-methoxy-1,2,3,4-tetrahydro-1,6-naphthyridine (15) underwent cyclization to give l-methoxy-4,5,9,10-tetrahydro-6//, 8H-pyrido[3,2,1 -ij [l,6]-naphthyridin-6-one (16) (MeONa, MeOH, reflux, 30 min 95%).1042 

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Although 1,8-naphthyridinecarboxamides have shown several interesting bioactivities,504 587 most of the described amides are in fact 1,8-naphthyridinecarbohy-drazides. 

Phenyl-l,8-naphthyridine-3-carbonitrile (24, R = CN) gave 2-phenyl-1,8-naphthyridinecarboxamide (24, R = CONH2) (KOH, H20, EtOH, reflux, 4 h 51% longer reflux gave the carboxylic acid).1100... 

Note 1,8-Naphthyridinecarbonitriles have been made by primary synthesis (see Chapter 22), by cyanolysis of halogeno-1,8-naphthyridines (see Section 24.2), from 1,8-naphthyridinamines (see Section 27.3.2), or by dehydration of 1,8-naphthyridinecarboxamides (see Section 28.4.2). 

Derivatives of annulated benzoindolo-l,5-naphthyridines attempting to improve memory were described (1985FRP2548667, 1987BCJ3797). These are benzo[Z>][l,5]nap-hthyridines, which are analogs of inhibitors of neurokinin NKi-receptors. Various 1,5-naphthyridine derivatives, in particular, 2-naphthyridinecarboxamide, possessing antiviral activity were also reported (1999PIAW09929318). 

Figure 15 Formula of several aromatic oligoamides and their crystal structures, (a) Double heUx of an oligo-pyridinecaboxamide. (b) Triple heUx of an oligo-naphthyridinecarboxamide. (c) Quadruple heUx of an oUgo-quinolinecarboxamide. (d) Branched structure comprised of two single helical quinolinecaboxamide oligomCTs connected by an ethylene glycol bridge.

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