Pyrazolo - 1,8-naphthyridines

Reaction of the tosylhydrazone 238 with base gives a mixture of four products, two of which are the pyrazolo[l,5]-and pyrazolo[l,6]naphthyridines 239 and 240 (Equation 65) <1999CHE703>. 

The presence or absence of the dioxolane protecting group in dienes dictates whether they participate in normal or inverse-electron-demand Diels-Alder reactions.257 The intramolecular inverse-electron-demand Diels-Alder cycloaddition of 1,2,4-triazines tethered with imidazoles produce tetrahydro-l,5-naphthyridines following the loss of N2 and CH3CN.258 The inverse-electron-demand Diels-Alder reaction of 4,6-dinitrobenzofuroxan (137) with ethyl vinyl ether yields two diastereoisomeric dihydrooxazine /V-oxide adducts (138) and (139) together with a bis(dihydrooxazine A -oxide) product (140) in die presence of excess ethyl vinyl ether (Scheme 52).259 The inverse-electron-demand Diels-Alder reaction of 2,4,6-tris(ethoxycarbonyl)-l,3,5-triazine with 5-aminopyrazoles provides a one-step synthesis of pyrazolo[3,4-djpyrimidines.260 The intermolecular inverse-electron-demand Diels-Alder reactions of trialkyl l,2,4-triazine-4,5,6-tricarboxylates with protected 2-aminoimidazole produced li/-imidazo[4,5-c]pyridines and die rearranged 3//-pyrido[3,2-[Pg.460]

Note Only a typical example is given here. Crude 5-amino-7-hydrazino-2,4-dimethyl-l,6-naphthyridine-8-carbonitrile (28) gave 2,4-dimethyl-7//-pyrazolo-[3,4-h [l,6]naphthyridine-2,9-diamine (29) (EtOH, reflux, 6 h 72%) analogs likewise.895... 

In the laboratory of N. Suzuki, the synthesis of several heterocyclic condensed 1,8-naphthyridine derivatives with potential antimicrobial activity was executed. The preparation of pyrazolo[3,4-b][1,8]naphthyridines required 7-chloro-6-formyl-3-ethyl ester as the precursor that was obtained by the Stephen reduction of the corresponding aromatic nitrile. The solution of the aromatic nitrile in chloroform was added to the solution of SnC /dry HCI gas in ether. After two days of stirring, the aldimine hexachlorostannane product was treated with warm water to obtain the desired aromatic aldehyde in modest yield. Heating of the aldehyde with methyl hydrazine afforded the pyrazole derivative. 

Naphthyridines 18 (R2=H) without substituents at nitrogen have served as the starting compounds to pyrazolo[3,4-c]naphthyridines, which act as modulators of benzodiazepine receptors and possess sedative and antispasmodic activities (1984EUP115469, 1986EUP168350, 1986USP4560691). 

Procedures for the synthesis of compounds containing a five-membered heterocycle with a linearly fused 1,8-naphthyridine fragment (thiazolo[5,4-Z>]- (1979CPB410), imidazolo[4,5-Z>]-, triazolo[4,5-Z>]- (1980CPB235), oxazolo[5,4-/ ]-, thiadiazolo[5,4-b]-, isothiazolo[5,4-Z>]-, pyrazolo[3,4-Z>]-, thieno[2,3-Z>]-, furo[2,3-/ ]-l,8-naphthyridines (1980CPB761, 1984CPB4914)) were described and the antibacterial activity of these compounds was studied. 

Microwave-Assisted Synthesis of Pyrazolo[3,4-b](luinolines Containing 1,8-naphthyridine Moiety... 

Mogilaiah et al. have synthesized 1,8-naphthyridinyl pyrazolo [3,4-Z)]quinolines (20) by the reaction of 2-hydrazino-3-(4-methoxyphenyl)-1,8-naphthyridine (19) with aldehydes (1) followed by cyclization with DMF/KOH either by MWI or by conventional methods. The reaction rate is enhanced tremendously under MWI as compared to conventional method with improved yields (Scheme 6.9) [47]. 

Mogilaiah K, Sudhakar GR, Reddy NV (2003) Microwave assisted synthesis of pyrazolo[3,4-6]quinolines containing 1,8-naphthyridine moiety. Indian J Chem 42B 1753-1755... 

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