A novel and efficient synthesis of 3-carboxy-4-oxo-1,8-naphthyridines using magnesium chloride

A novel and efficient synthesis of 5-oxo-6-carboxy-naphthyridines is reported in this Letter along with a discussion of scope and limitations. Activated 3-nicotinic acids readily acylate the magnesium anion of 2-(benzothiazol-2-yl) or 2-(benzimidazol-2-yl) acetates. The corresponding product can then undergo cyclization spontaneously or under very mild conditions to give the desired naphthyridine products. Only near stoichiometric ratios of reactants are required for this approach and the products are isolated in pure form after a trituration making this an efficient process.     

Simple and highly diastereoselective access to 3,4-substituted tetrahydro-1,8-naphthyridines from Morita-Baylis-Hillman adducts

We disclose herein a facile and straightforward method to access 3,4-substituted tetrahydro-1,8-naphthyridines from Morita-Baylis-Hillman. The strategy is based on a tandem sequence involving a Michael addition reaction followed by an intramolecular S_NAr reaction on a silylated-Morita-Baylis-Hillman adduct. In a single step, a new cycle is formed and the relative stereochemistry of two new centers is controlled with good to excellent diastereoselectivity.     

Synthetic antibacterials. VIII. 7-(1′-alkylhydrazino)-1,8-naphthyridines and related compounds

Synthesis and in vitro antibacterial activity of 7-(1′-alkylhydrazino)-1,8-naphthyridines related to nalidixic acid were investigated. Namely, treatment of 7-alkylamino-1-ethyl-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids 1a-d with sodium nitrite in the presence of hydrochloric acid gave the 1-ethyl-1,4-dihydro-7-(N-nitrosoalkylamino)-4-oxo-1,8-naphthyridine-3-carboxylic acids 2a-d , which upon reacting with zinc dust in acetic acid gave the 7-(1′-alkylhydrazino)-1-ethyl-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacids 3a-d. The compound 3a was alternately obtained by the reaction of 7-chloro-1-ethyl-1,4-dihydro-4-oxo-1,8-naphth-yridine-3-carboxylic acid ( 4 ) with methylhydrazine. The reaction of 7-chloro-4-hydroxy-1,8-naphthyridine-3-carboxylic acid ( 5 ) with methylhydrazine gave the 4-hydroxy-7-(1′-methylhydrazino)-4-oxo-1,8-naphthyridine-3-carboxylic acid ( 6 ), which upon treatment with alkyl halides afforded the 1-alkyl-1,4-dihydro-7-(1′-methyl-hydrazino)-4-oxo-1,8-naphthyridines 3a and 3e-g. The reaction of the appropriate 3 with ketones gave the corresponding 7-(1′-methylalkylidenehydrazino)-1,8-naphthyridines 7a-c and 8a-b. Among the compounds prepared, certain 3 and 7 exhibited good activity against Gram-negative bacteria.     

Simple and efficient synthesis of 2,7-difunctionalized-1,8-naphthyridines

The syntheses in good yields of some new difunctionalized 1,8-naphthyridines 4, 6, 8 and 9 and a novel triethylene glycol ether-linked dinaphthyridine, 10a, along with the mononaphthyridine-linked ether alcohol 10b are described. An improved and milder method for the synthesis of 2,7-diamino-1,8-naphthyridine (14) is also reported.     

Synthesis of some substituted pyrido[1,2-a]pyrimidin-4-ones and 1,8-naphthyridines

The substituted 4H-pyrido[1, 2-a]pyrimidin-4-ones (I) were obtained by the condensation of substituted 2-aminopyridines with δ-ketocarboxylic esters in PPA. Some of the derivatives I were transformed into the corresponding 1, 8-naphthyridines II and III.     

Pd-catalyzed amidation of 2-chloro- and 2,7-dichloro-1,8-naphthyridines

[reactions: see text] The catalytic amidation between 2-chloro- and 2,7-dichloro-1,8-naphthyridines and primary amides bearing functional groups is reported. When Pd(OAc)2, xantphos, and K2CO3 are used, it is possible to obtain symmetric as well as nonsymmetric 2,7-diamido-1,8-naphthyridines in 50-90% yield with good functional-group tolerance. Monoamidation of 2,7-dichloro-1,8-naphthyridine using 0.9 equiv of the amide proceeded with good selectivity compared to the formation of the diamide, but as a result of the difficult isolation of the product, isolated yields were poor to moderate (22-42%).     

Synthesis of 7-aryl-1,8-naphthyridines via addition of aryl boronic acids to 1,8-naphthyridine N-oxides

Simply combining aryl boronic acids with 1,8-naphthyridine N-oxides and heating at 110 °C in toluene or dimethylformamide affords the corresponding 7-aryl-1,8-naphthyridines. The reaction is not sensitive to air or moisture and the process can be extended to other electron-deficient heteroaromatic N-oxides.     

The chemistry of caryophyllene and related compounds

A review is given of the literature over the period from the middle of the 1950s to the beginning of the 1980s on the distribution in nature, the biological activity, the conformation, and the chemical transformations of sesquiterpenes of the caryophyllene type.Novosibirsk Institute of Organic Chemistry, Siberian Branch of the USSR Academy of Sciences. Translated from Khimiya Prirodnykh soedinenii, No. 4, pp. 475–499, July–August, 1987.     

Nuclear chemistry of indium and related compounds

The activation of indium by gamma-ray source through absorption of photons of resonance energy and the threshold energy (appearance energy) determination in indium compounds as well as some results of hot atom chemistry studies of indium compounds and of implantation with indium ions are described.     

The chemistry of caryophyllene and related compounds

A review is given of the literature over the period from the middle of the 1950s to the beginning of the 1980s on the distribution in nature, the biological activity, the conformation, and the chemical transformations of sesquiterpenes of the caryophyllene type.     

1,5-naphthyridines. Synthesis of 7-chloro-4-(4-diethylamino-1-methylbutylamino)-2-methoxy-1,5-naphthyridine and related compounds

The synthesis of 7-chloro-4-(4-diethylamino-1-methylbutylamino)-2-methoxy-1,5-naphthyridine, a compound which incorporates the structure of both chloroquine (a schizontocidal drug) and pamaquine (a gametocytocidal drug), has been carried out. In addition, two structurally related derivatives, the, “5-azachloroquine” and the “5-azapamaquine,” have also been obtained by multi-step syntheses. “5-Azachloroquine” possesses good antimalarial activity against Plasmodium berghei. The compound was also found to be less toxic than the known 4-aminoquinoline and 8-aminoquinoline antimalarial drugs.     

1,2,3,4-Tetrahydro-1,5-naphthyridines and related heterocyclic scaffolds: exploration of suitable chemistry for library development

The chemistry of 1,2,3,4-tetrahydro-1,5-naphthyridines and 2,3,4,5-tetrahydro-1H-pyrido[3,2-b]azepines has been explored with the goal of discovering reactions at N1 suitable for library development. Epoxide openings, Pd-catalyzed N-arylations, DEPBT-promoted acylations, and urea formation through the reaction with isocyanates were all successful. The epoxide opening chemistry using homochiral epichlorohydrin followed by epoxide reclosure and a second nucleophilic opening led to the preparation of a small 24-membered library.     

Direct fluorination of polyester and related compounds

Polyethylene terephthalate and model compounds representing various aspects of polyethylene terephthalate have been treated with elemental fluorine. Polyester was found to react in a manner more resembling ethylene glycol dibenzoate than diethyl terephthalate or terephthalic acid. The degree of fluorine incorporation increases as the aliphatic character of the substrate is increased. The reaction was studied using fluorine incorporation, ir, ESCA and esr techniques.     

Structural chemistry of complex carbides and related compounds

Complex carbides formed in ternary systems of a transition element (M), a B-group element (M′), and carbon and having a formula M₂M′C (H-phase) or M₃M′C (perovskite carbide) occur frequently. This reflects the simple geometry of the atomic arrangement of the metals and the filling mode by an interstitial stabilizer such as carbon or nitrogen. The phase relationship of the ternary combinations {Ti, Zr, Hf, V, Nb, Ta, Cr, Mn, and Ni}-aluminum-carbon was investigated. New complex carbides were found with the corresponding zirconium, hafnium, and tantalum combinations. The crystal structures in the case of Zr- and Hf-containing complex carbides can be characterized by a twelve-metal-layer sequence and by a ten-metal-layer sequence with carbon atoms again filling octahedral voids. The transition of structure types from TiC, Ti₂AlC, Ti₃SiC₂, ZrAlC₂, Zr₂Al₃C₅, to Al₄C₃ is also discussed.     

Synthesis of 4-carboxy-4-pyridylpiperidines through palladium-catalyzed α-arylation of esters

A concise synthesis of 4-carboxy-4-pyridylpiperidines has been achieved. Key step is the palladium-catalyzed α-arylation of esters under basic conditions.     

Preparative access to medicinal chemistry related chiral alcohols using carbonyl reductase technology

Libraries of highly enantioenriched secondary alcohols in both enantiomeric forms were synthesised by enzymatic reduction of their parent ketones using selectAZyme? carbonyl reductase (CRED) technology. Commercially available CREDs were able to reduce a range of substrate classes efficiently and with very high enantioselectivity. Matching substrate classes to small subsets of CREDs enabled the fast development of preparative bioreductions and the rapid generation of 100–1500 mg samples of chiral alcohols in typically >95% ee and the majority in ?99.0% ee. The conditions for small scale synthesis were then scaled up to 0.5 kg to deliver one of the chiral alcohols, (S)-1-(4-bromophenyl)-2-chloroethanol, in 99.8% ee and 91% isolated yield.     

Ionic liquids accelerate access to N-substituted-1,8-naphthalimides

The synthesis of N-substituted-1,8-naphthalimides is accelerated in the presence of the room temperature ionic liquid [BMIM][NO₃]. Reaction times are reduced from 18 h in volatile organic compounds (VOCs) (PhCH₃, EtOH and THF) to 20 min in the ionic liquid [BMIM][NO₃]. The reaction yields are typically increased to >85% and the products are isolated by ethanol-mediated precipitation direct from the ionic liquid, requiring no further purification.