Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines.

An efficient method for the synthesis of isoxazolo[4,5-b]pyridines has been developed on the basis of readily available 2-chloro-3-nitropyridines via the intramolecular nucleophilic substitution of the nitro group as a key step. The previously unknown base-promoted Boulton-Katritzky rearrangement of isoxazolo[4,5-b]pyridine-3-carbaldehyde arylhydrazones into 3-hydroxy-2-(2-aryl[1,2,3]triazol-4-yl)pyridines was observed.

Recent Developments in the Synthesis of HIV-1 Integrase Strand Transfer Inhibitors Incorporating Pyridine Moiety.

Human immunodeficiency virus (HIV) causes one of the most dangerous diseases-acquired immunodeficiency syndrome (AIDS). An estimated about 40 million people are currently living with HIV worldwide, most of whom are already on antiretroviral therapy. This makes the development of effective drugs to combat this virus very relevant. Currently, one of the dynamically developing areas of organic and medicinal chemistry is the synthesis and identification of new compounds capable of inhibiting HIV-1 integrase-one of the HIV enzymes. A significant number of studies on this topic are published annually. Many compounds inhibiting integrase incorporate pyridine core. Therefore, this review is an analysis of the literature on the methods for the synthesis of pyridine-containing HIV-1 integrase inhibitors since 2003 to the present.

Straightforward and Efficient Protocol for the Synthesis of Pyrazolo [4,3-b]pyridines and Indazoles.

An efficient method for the synthesis of pyrazolo [4,3-b]pyridines has been developed on the basis of readily available 2-chloro-3-nitropyridines via a sequence of SNAr and modified Japp-Klingemann reactions. The method offers a number of advantages including utilization of stable arenediazonium tosylates, operational simplicity as well as combining the azo-coupling, deacylation and pyrazole ring annulation steps in a one-pot manner. An unusual rearrangement (C-N-migration of the acetyl group) was observed and a plausible mechanism was proposed based on the isolated intermediates and NMR experiments. In addition, the developed protocol was successfully applied to the synthesis of 1-arylindazoles combining the Japp-Klingemann reaction and cyclization of the resulting hydrazone as a one-pot procedure.

Nucleophilic Functionalization of 2-R-3-Nitropyridines as a Versatile Approach to Novel Fluorescent Molecules.

A number of new 2-methyl- and 2-arylvinyl-3-nitropyridines were synthesized and their reactions with thiols were studied. It was found that 3-NO2 tends to be selectively substituted under the action of sulfur nucleophiles in the presence of another nucleofuge in position 5. Correlations between the substitution pattern and regioselectivity as well as photophysical properties were established. Some synthesized compounds possessed a large Stokes shift.

Nitropyridines as 2π-Partners in 1,3-Dipolar Cycloadditions with N-Methyl Azomethine Ylide: An Easy Access to Condensed Pyrrolines.

1,3-Dipolar cycloaddition reactions of 2-substituted 5-R-3-nitropyridines and isomeric 3-R-5-nitropyridines with N-methyl azomethine ylide were studied. The effect of the substituent at positions 2 and 5 of the pyridine ring on the possibility of the [3+2]-cycloaddition process was revealed. A number of new derivatives of pyrroline and pyrrolidine condensed with a pyridine ring were synthesized.

Synthesis and Facile Dearomatization of Highly Electrophilic Nitroisoxazolo[4,3-b]pyridines.

A number of novel 6-R-isoxazolo[4,3-b]pyridines were synthesized and their reactions with neutral C-nucleophiles (1,3-dicarbonyl compounds, π-excessive (het)arenes, dienes) were studied. The reaction rate was found to be dependent on the nature of the substituent 6-R. The most reactive 6-nitroisoxazolo[4,3-b]pyridines are able to add C-nucleophiles in the absence of a base under mild conditions. In addition, these compounds readily undergo [4+2]-cycloaddition reactions on aromatic bonds C=C(NO2) of the pyridine ring, thus indicating the superelectrophilic nature of 6-NO2-isoxazolo[4,3-b]pyridines.

Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds.

4-Aza-6-nitrobenzofuroxan (ANBF) reacts with 1,3-dicarbonyl compounds and other CH acids to give carbon-bonded 1,4-adducts - 1,4-dihydropyridines fused with furoxan ring. In the case of most acidic ß-diketones, which exist mainly in the enol form in polar solvents, the reactions proceed in the absence of any added base emphasizing the highly electrophilic character of ANBF. The resulting compounds combine in one molecule NO-donor furoxan ring along with a pharmacologically important 1,4-dihydropyridine fragment and therefore can be considered as prospective platforms for the design of pharmacology-oriented heterocyclic systems.