Aryl-1,7-naphthyridines

Ch. 2 1,5-Naphthyridine, Alkyl-1,5-naphthyridines, and Aryl-1,5-naphthyridines Ch. 3 Halogeno-1,5-naphthyridines Ch. 4 Oxy-1,5-naphthyridines Ch. 5 Thio-1,5-naphthyridines... 

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>. 

The three-component coupling of arylacetaldehydes, secondary amines, and (hetero)aryl azides in refluxing benzene gave triazolines which underwent thermal reanangement to quinolines and [l,7]naphthyridines <1996J(P1)1359>. 

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>. 

Bismuth(lll) chloride catalyzes the intramolecular hetero-Diels-Alder reaction of aldimines, generated in situ from aromatic amines and the A -allyl derivative of o-aminobenzaldehyde, in acetonitrile at reflux to generate [l,6]naphthyridine derivatives <2002TL1573>. The hetero-Diels-Alder reaction of 3-aryl-2-benzoyl-2-propeneni-triles and enol ethers yields 2-alkoxy, 6-diaryl-3,4-dihydro-2//-pyran-5-carbonitriles (Scheme 29) <1997M1157>. 

Substituted-3-aryl[l,6]naphthyridin-2-amines and 7-substituted-3-aryl[l,6]naphthyridin-2(l//)-ones have been prepared by diazotization of 3-aryl[l,6]naphthyridine-2,7-diamines, themselves obtained by the condensation cycli-zation of 4,6-diaminonicotinaldehyde and phenylacetonitrile <2000J(P1)1843>. Derivatives of cyanoacetic acid have rarely been used in the synthesis of naphthyridines, although a recent study has shown that they may be reacted with 4-piperidone derivatives to give [l,6]naphthyridines <2000CHE496>. 

A versatile and flexible route to naphthyridines, containing an isoquinolinic nitrogen, and their corresponding A -oxides, has been reported from various o-bromopyridinecarbaldehydes and ammonia <1999S306>. Highly functionalized naphthyridones (and quinolines) have been prepared from a common A -aryl pyridinone template (Scheme 39) <20020L2071>. 

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... 

Heterocyclic azides react with enamines31 1,8-naphthyridine azides give isolable triazolines.220 The bicyclic enamine 2-N-morpholinonorbornene with aryl and benzoyl azides furnishes stable, crystalline aminotri-azolines.39,213 Likewise, alkyl azidoformates yield stable triazolines.30,221... 

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... 

This chapter covers information on the preparation, physical properties, and reactions of 1,5-naphyhyridine and its C-alkyl, C-aryl, /V-alkyl, and /V-aryl derivatives as well as their respective ring-reduced analogs. In addition, it includes methods for introducing alkyl or aryl groups (substituted or otherwise) into 1,5-naphthyridines already bearing substituents and the reactions specific to the alkyl or aryl groups in such compounds. For simplicity, the term alkyl-l,5-naphthyridine in this chapter is intended to include alkyl-, alkenyl-, alkynyl-, aralkyl-, and cycloalkyl-1,5-naphthyridines likewise, aryl-l,5-naphthyridine includes both aryl-and heteroaryl-1,5-naphthyridines. 

Although alkyl and aryl groups attached to a heterocyclic nucleus can undergo a wide variety of reactions and do have significant steric and electronic effects on adjacent substituents, little such data on 1,5-naphthyridines can be found in the literature. 

Only reactions specific to the alkyl or aryl groups in such 1,5-naphthyridines are illustrated in the following examples. 

This section covers the insertion of alkyl or aryl groups into existing 1,6-naphthyridines and the reactions specific to the alkyl or aryl groups therein The HNMR spectra of C-methyl groups and the 13CNMR spectra of A-methyl groups attached to 1,6-naphthyridine have been examined in some detail 964,1319... 

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