Aryl-l,8-naphthyridines

Ialo-l,8-naphthyridin-2(17/)-ones, readily available from 2-chloronicotinic acid, were subjected to Suzuki coupling with aryl boronic acids to give a diversity of 4-aryl-l,8-naphthyridin-2(17/)-ones ((2003T6021). 

Similarly, a number of l-alkyl(aryl)-4-ehloro-3-nitro-l,8-naphthyridin-2 (IH)-ones (100) have been reported to reaet with ammonia or alkylamines to afford the eorresponding 4-amino eompounds [101, R = H, CH3, C2H5, CH(CH3)2, CH2 CfiHs] (91JHC2029, 91MI2 92JMC4866). 

Sodium hydrosulfite successfully reduced the iiitro group in a number of l-A -alkyl(aryl) 4-(substituted) amino-3-nitro-l,8-naphthyridin-2(lH)-ones (143) to give the corresponding 3-amino derivatives (144) (91JHC2029, 91MI2 92JMC4866). Tliese products could not be purified but were used in their crude form for further annelation into imidazonaphthyridin-4(5H)-ones (see Section III,G). 

Chloramine-T reacts with (2-oxo-3-phenyl-27/-[l,8]naphthyridine-l-yl)acetic acid arylidenehydrazides to generate 1-(5-aryl-[1,3,4]-oxadiazol-2-ylmethyl)-3-phenyl-17/-[l,8]naphthyridin-2-ones <2004IJB2014>. 

Aryl-l,2-dihydro-3-nitro[l,8]naphthyridines have been obtained by the 6jt-thermal electrocyclization of l-(2-arylide-neamino-3-pyridyl)-2-nitroethylenes, obtained in situ from aromatic aldehydes and l-(2-amino-3-pyridyl)-2-nitroethylene in xylene <2002SC747>. 2-Chlorotetrahydro[l,8]naphthyridines have also been obtained from 2,6-dichloropyridines using a free radical xanthate-mediated cyclization <20040L3671>. 

Pyrimido[l,2-a][l,8]naphthyridines synthesis, 2, 599 Pyrimido[5,4-c]oxadiazine purine synthesis from, 5, 591 Pyrimido[4,5-6][ l,4]oxazine synthesis, 3, 312 Pyrimido[2,1 -6]pteridine structure, 3, 284 Pyrimido[5,4-g]pteridine structure, 3, 284 Pyrimidopurines, 5, 566 Pyrimido[4,5-c]pyridazine, aryl- H NMR, 3, 335... 

Het)aryl-l,4-dihydro-l,8-naphthyridin-4-ones 288 were obtained by heating 2-(het)aryl-4//-pyrido[l, 2-a]pyrimidin-4-ones 287 at 350 °C (97JMC2266, 99JMC4081) and in Dowtherm A at 220-240 °C... 

Naphthyridine underwent self-arylation to give 2,2 -bi-l,8-naphthyridine (LiBu, dithiane then 02 69%).737... 

Claisen-Schmidt condensation of 3-acetyl-2-methyl-l,8-naphthyridine 394 with aromatic aldehydes occurs in ethanol in the presence of KOH to give cinnamoyl-substituted 1,8-naphthyridines 395. The latter undergo cyclization with hydrazine hydrate or phenylhydrazine to form 3-(5-aryl-2-pyrazolin-3-yl)-l,8-naphthyridines 396a (62-84% yields) or 3-(5-aryl-l-phenyl-2-pyrazolin-3-yl)-2-methyl-l,8-nap-hthyridines 396b (64-86% yields), respectively, which exhibit pronounced anti-fugicidal activity (1988CCC1543). 

Condensation of 2-amino-l,8-naphthyridine-3-carboxamide 400 with aromatic aldehydes in glacial acetic acid affords 2-aryl-l,2,3,4-tetrahydropyrimido[4,5-Z>][l,8]naphthyridin-4-ones 401, whose oxidation with nitrobenzene in glacial acetic acid gives 2-arylpyrimido[4,5-Z>][l,8]naphthyridin-4(3//)-ones 402. Compounds 402 were also synthesized without isolation of naphthyridones intermediate 401 formed by condensation of amide 400 with aromatic aldehydes on refluxing in a mixture of nitrobenzene and glacial acetic acid (1987IJC(B)1194). 

Aryl azides undergo indolization upon photolysis, and several examples are known (Scheme 8) [67-70]. Thus, p-phenyl-substituted (Me, OMe, Cl) azidopyrimi-dines 11 were converted to the corresponding 9H-pyrimido[4,5- ]indole (equation 1) [67, 68]. The azide precursor is in equilibrium with the ring-opened 8-phenyltetrazolo[l,5-c]pyrimidine (10) (in trifluoroacetic acid). Similarly, Da Settimo and colleagues synthesized the new ring system 67/-indolo[2,3- ][l,8]naphthyridine 12 by photolysis in trifluoroacetic acid of the equilibrium mixture of 4-phenyltetrazolo[l,5-fl][l,8]naphthyridines... 

Abbiati, G., Arcadi, A., Canevari, V, Capezzuto, L. and Rossi, E. (2005) Palladium-assisted multicomponent synthesis of 2-aryl-4 aminoquinolines and 2-aryl-4-amino[l,8]naphthyridines. 

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