Alkyl-1,5-naphthyridines amination

A wide variety of 1 -iV-alkylperhydro- 1,7-naphthyridines (68) were prepared100 by reacting the ether (67) with various alkyl amines. 

Note For alkylation/alkyludenation of existing amines, see Section 13.2.2. 13.2.2. Reactions of Amino-1,6-naphthyridines... 

Kelly et al. (51,52) designed a two-binding-site host that accelerates an Sn2 reaction between a primary aliphatic amine and an alkyl bromide. Their host (Figure 14) acts as a template for the two reactants, amino-methyl- and bromomethyl-naphthyridine each aminopyridone group of the host forms three hydrogen bonds to each reactant. This binding is rather strong (K s > 10 M ). The authors observed a sixfold acceleration of the Sn2 reaction but could not prove or disprove that turnover was catalytic. 

Chloro-5,7-dimethyl-l,8-naphthyridine reacts readily with meth-anolic methoxide (65°, 30 min) and with other alkoxides, benzyl-amine, and hydrazine. 4-Chloro-7-acetamino-l,8-naphthyridine (prepared in moderate yield from the 4-oxo analog) has been alkyl-aminated (150°, 9 hr, 62% yield). The degree of reactivity in... 

Condensation of substituted pyrano[4,3-Z>]pyridine-5-one 166 with dimethylform-amide dimethyl acetal in xylene yielded enamine 167, which underwent recyclization to 2-alkyl-5-cyano-8-phenacyl-2,7-naphthyridin-l (27/)-ones 168 on treatment with primary amines (1997IZV1079). A change in the sequence of addition of the reagents to the pyranone 168 (first, treatment with benzylamine and then condensation with dimethylformamide dimethyl acetal) resulted in 8-benzoyl-3-cyano-4-(2-dimethyl-aminovinyl)-2-phenyl-1,6-naphthyridin-5(6//)-one 169. 

The high reactivity is also understandable from the mild reaction conditions under which many cyclometalation reactions proceed with many kinds of metal elements, such as Ti, Fe, Ru, Os, Rh, Ir, Ni, Pd, Pt, B, and Cu, and with many kinds of substrates, such as amines, imines, 2-phenylpyridines, benzo[/ ]quinones, quinolines, diarylpyridines, naphthyridines, azobenzenes, oxazolines, aldehydes, ketones, amides, phosphines, phosphites, and alkyl sulfides, as shown in Figs. 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, and 5.9. 

---