2,7-Naphthyridinones reactions

The adducts from the Diels-Alder reaction of 2(17/)-pyrazinones with 3-butynylaminomethyl side chains undergo thermolysis to give either [l,7]naphthyridinones or [2,7]naphthyridines <1996T9161>. The intramolecular... 

The reaction of 1,5-naphthyridine with methyl iodide gave, as expected, the monomethiodide (134). Oxidation of the salt, under basic conditions, with potassium ferricyanide, afforded the A-methyl naphthyridinone (135).16 Repetition of this sequence yielded,... 

The reaction of 142 with hydrogen peroxide and acetic acid afforded a mono-A-oxide. However, the position of the A-oxide function was not established.70 The l,6-dimethyl-2-naphthyridinone (143) on similar treatment gave the 5-oxide (144).70... 

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. 

The reductive deoxygenation (Section 2.1.1) and halogenolysis (Section 3.1.2) of such naphthyridinones have been covered already. Their other reactions are illustrated in the following examples. 

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. 

The halogenolysis of 1,6-naphthyridinones and extranuclear hydroxy-1,6-naphthyridines has been covered in Section 10.1.2. Other reactions are illustrated in the following classified examples. 

The most important reaction of tautomeric 1,7-naphthyridinones, halogenolysis, has been covered in Section 17.1. Only a few of the other possible reactions have been reported, as illustrated by the following examples. 

Note This reaction amounts to the conversion of a nontautomeric to a tautomeric 1,7-naphthyridinone. 

Note The hydrolysis of alkoxy-l,8-naphthyridines to 1,8-naphthyridinones has been exemplified in Section 25.1.1. No other reactions appear to have been reported. 

An analogous reaction of 7-methylpyrano[4,3-6]pyridines 64 with ammonia or aliphatic primary amines afforded 1,6-naphthyridinones 65 (1989IJC173). 

Chloronicotinoyl chloride 95 was used as the starting compound in the synthesis of hetaryl annulated 1,6-naphthyridines. Its reactions with 4,5-dihydro-1//-imidazolines 96a or tetrahydropyrimidines 96b gave the corresponding A-acyl derivatives 97a,b, which underwent cyclization with potassium Arf-butoxide to yield imidazo- 98a or pyrimido[l,2-gr[[l,6]naphthyridinones 98b, respectively. Compounds 98a,b exhibit antiallergic and anti-inflammatory activitives (1990JHC189, 1990USP5070086). 

With the aim of searching for synthetic approaches to new l,8-naphthyridin-2-one derivatives, transformations of ethyl 7-amino-l,4-dimethyl-2-oxo-l,2-dihydro-l,8-naphthyridine-6-carboxylate 363 were studied. Refluxing this compound with N,N-dimethylformamide dimethyl acetal in dry toluene afforded 7-[(Ar,Wdimethylami-nomethylene)amino]-l,8-naphthyridinone 364. The reaction of naphthyridone 363 with triethyl orthoformate produced ethoxymethyleneamino derivative 365. The reaction with hydrazine hydrate gave 7-amino-3-cyano-l,4-dimethyl-2-oxo-l,2-dihy-dro-l,8-naphthyridine-6-carbohydrazide 366 (2001S103). 

Seleno ester 31b, which bears a benzyl group on the indole nitrogen, underwent smooth cyclization under noiu eductive conditions - hexabutylditin with a 300 W sun lamp - to give the tetracyclic indole 178 in 65% as the sole product [103], Analogous seleno esters, with 3- or 4-pyridylmethyl moieties attached to the indole nitrogen, also cyclized under similar reaction conditions, but afforded indolo[ 1,2-6] naphthyridinones in considerably lower yields (35% and 15%, respectively) [104],... 

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