Preparation of Alkyl- and Aryl-1,8-Naphthyridines

Most known C-alkyl-1,5-naphthyridines have been made by primary syntheses (see Chapter 1) and most A-alkyl-1,5-naphthyridinium salts by quaternization. Other reported approaches are illustrated in Section 2.1.3 and by the following examples. 

Note Regular and Mannich-type reactions have been used. The alkylation of unsubstituted 1,5-naphthyridine has been exemplified in Section 2.1.3. 

3-Nitro-l,5-naphthyridine (27, R = H) gave 3-nitro-4-phenylsulfonylmethyl-l, 5-naphthyridine (28, R = H) (NaOH, Me2SO reactants) 20°C, 2 h 87%) 2-substituted substrates reacted similarly to give, for example, 2-chloro-3-nitroM-phenylsulfonylmethyl- 1,5-naphthyridine (28, R=C1) (73%).854 

5-Naphthyridin-3(57/)-one (29) underwent Mannich alkylation to give 4-dimethylaminomethyl-l,5-naphthyridin-3(5/7)-one (30) (Me2NH, CH20, EtOH, H20, 25°C, 4 h 73% analogs likewise).932 

3-Bromo-8-(p-hydroxyanilino)-1,5-naphthyridine underwent extranuclear Mannich alkylation to give 3-bromo-8-[4-hydroxy-3,5-bis(4-methylpiperazin-l-yl)ani-lino]- 1,5-naphthyridine (31) (substrate, CH20, 1-methylpiperazine, EtOH, reflux, 30 h 50%) analogs likewise.1379 

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