1.8- Naphthyridinones cyclizations

The intramolecular cyclizations of the cyanopyridines (253) and (254) using polyphos-phoric acid resulted in the formation of the 2,7-naphthyridinones (255) and (256) which were subsequently converted into the phenyl-substituted 2,7-naphthyridines (64JOC2298, 65JA5198). 

The coupling of o-aroylbenzoic or nicotinic acids with phosphorylated amines using dicyclohexylcarbodiimide (DCC)/4-dimethylaminopyridine (DMAP) followed by deprotonation with potassium bis(trimethylsilylamide) and cyclization gave isoquinolines or naphthyridinones in good yields (Scheme 43) <1996T4433>. 

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). 

A methyl group in the diester (91) condenses readily with DMFDMA to give the enamine (92), which cyclizes on treatment with ammonia to give the 1,6-naphthyridinone (93), Scheme 15 [86JCS(P1)753]. 

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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