2,7-Naphthyridinones alkylation

The conversion of a tautomeric 1,5-naphthyridinone into the corresponding chloro- or bromo-l,5-naphthyridine is usually done by heating for several hours with neat phosphoryl chloride or phosphoryl bromide, respectively. A mixture of phosphoryl chloride and phosphorus pentachloride has been used for a few difficult cases. In addition, exceptional reactions have been reported in which a nontautomeric /V-alkyl-1,5-naphthyridinone or a hydroxymethyl-1,5-naphthyridine was used successfully as substrate. The following examples illustrate the foregoing possibilities. 

Note The alkylation of tautomeric 1,5-naphthyridinones usually gives /V-alkyl derivatives, but (9-alkylation has been achieved by treatment of the substrate silver salt with an alkyl halide the other likely route to (9-alkylation, treatment with an diazoalkane, has not been used in this series. 

Note. All known alkoxy-l,5-naphthyridines have been made by primary synthesis (see Chapter 1), by alcoholysis of halogeno-l,5-naphthyridines (see Section 3.2.1), or by alkylation of 1,5-naphthyridinones (see Section 4.1.2). 

Note For their apparent rearrangement into C-alkyl-1,5-naphthyridinones, see Section 2.2.1 for their hydrolysis, see Section 4.1.1 and for other reactions, see the following examples. 

Note Alkylation or arylation of any tautomeric 1,6-naphthyridinone probably affords a mixture of O- and /V-derivatives, but the latter usually predominates. 

Naphthyridinones are usually tautomeric with corresponding naphthyridi-nols, but they may be fixed (become nontautomeric) by /V-alkylation. As in related series, 1,8-naphthyridinones prefer to exist as oxo rather than hydroxy... 

Note Such alkylation of 1,8-naphthyridinones is seldom reported and then only in poor yield in contrast, 1,8-naphthyridin-3/6-ols, which cannot undergo N-alkylation, readily form their Oalkylated derivatives in good yield. 

Note Alkylation of 1,8-naphthyridinones usually affords iV-alkyl derivatives, at least predominantly. 

These have been made by alcoholysis of halogeno substrates (see Section 30.3.2) and by alkylation of 2,7-naphthyridinones (see earlier in this section). 

---