Progress of the synthesis of condensed pyrazole derivatives (from 2010 to mid-2013).

5-Amino-pyrazoles have proven to be a class of fascinating and privileged organic tools for the construction of diverse heterocyclic or fused heterocyclic scaffolds. This review presents comprehensively the applications of 5-amino-pyrazoles as versatile synthetic building blocks in the synthesis of remarkable organic molecules with an emphasis on versatile functionalities. Following a brief introduction of synthesis methods, planning strategies to construct organic compounds, particularly diverse heterocyclic scaffolds, such as poly-substituted heterocyclic compounds and fused heterocyclic compounds via 5-amino-pyrazoles, have been summarized. Fused heterocycles are classified as bicyclic, tricyclic, tetracyclic, and spiro-fused pyrazole derivatives. These outstanding compounds synthesized via wide variety of approaches include conventional reactions, one-pot multi-component reactions, cyclocondensation, cascade/tandem protocols, and coupling reactions. 5-Amino-pyrazoles represent a class of promising functional reagents, similar to the biologically active compounds, highlighted with diverse applications especially in the field of pharmaceutics and medicinal chemistry. Notably, this critical review covers the articles published from 1981 to 2018.

5-Amino-pyrazoles: potent reagents in organic and medicinal synthesis

Solid-phase synthesis of sulfur containing heterocycles

Catalyzing the Erlenmeyer Plöchl reaction: organic bases versus sodium acetate

Traceless solid-phase synthesis represents an ultimate sophisticated synthetic strategy on insoluble supports. Compounds synthesized on solid supports can be released without a trace of the linker that was used to tether the intermediates during the synthesis. Thus, the target products are composed only of the components (atoms, functional groups) inherent to the target core structure. A wide variety of synthetic strategies have been developed to prepare products in a traceless manner, and this review is dedicated to all aspects of traceless solid-phase organic synthesis. Importantly, the synthesis does not need to be carried out on a linker designed for traceless synthesis; most of the synthetic approaches described herein were developed using standard, commercially available linkers (originally devised for solid-phase peptide synthesis). The type of structure prepared in a traceless fashion is not restricted. The individual synthetic approaches are divided into eight sections, each devoted to a different methodology for traceless synthesis. Each section consists of a brief outline of the synthetic strategy followed by a description of individual reported syntheses.

Traceless Solid-Phase Organic Synthesis

Herein we report the polymer-supported synthesis of 3,4-dihydro-2H-1,4-oxazine-3-carboxylic acid derivatives using immobilized Fmoc-Ser(tBu)-OH and Fmoc-Thr(tBu)-OH as the starting materials. After the solid-phase-synthesis of N-alkyl-N-sulfonyl/acyl intermediates, the target dihydrooxazines were obtained using trifluoroacetic acid-mediated cleavage from the resin. This approach was also studied for the preparation of dihydrothiazines from immobilized Fmoc-Cys(Trt)-OH. Inclusion of triethylsilane in the cleavage cocktail resulted in the stereoselective formation of the corresponding morpholine/thiomorpholine-3-carboxylic acids. Stereochemical studies revealed the specific configuration of the newly formed stereocenter and also the formation of stable N-acylmorpholine rotamers.

Stereoselective Polymer-Supported Synthesis of Morpholine- and Thiomorpholine-3-carboxylic Acid Derivatives.

Herein, we report the stereoselective synthesis of trisubstituted benzoxazino[4,3-b][1,2,5]thiadiazepinone 6,6-dioxides from polymer-supported Fmoc-Ser(tBu)-OH and Fmoc-Thr(tBu)-OH. After the solid-phase synthesis of N-alkylated-N-sulfonylated intermediates using various 2-nitrobenzenesulfonyl chlorides and bromoketones, the target compounds were obtained via trifluoroacetic acid (TFA)-mediated cleavage from the resin, followed by cyclization of the diazepinone scaffold. Except for the threonine-based intermediates, the inclusion of triethylsilane (TES) in the cleavage cocktail yielded a specific configuration of the newly formed C3 chiral center. The final cyclization resulted in minor or no inversion of the C12a stereocenter configuration.

Polymer-Supported Stereoselective Synthesis of Benzoxazino[4,3-b][1,2,5]thiadiazepinone 6,6-dioxides

Herein, we report a stereoselective formation of tetrahydro-6H-benzo[e][1,4]oxazino[4,3-a][1,4]diazepine-6,12(11H)-diones. Their preparation consisted in solid-phase synthesis of linear intermediates starting from polymer-supported Ser(tBu)-OH. Using various 2-nitrobenzoic acids and bromoketones, the key intermediates were obtained in five steps and subjected to trifluoroacetic acid-mediated cleavage from the resin, followed by stereoselective reduction with triethylsilane. Subsequent catalytic hydrogenation of the nitro group and cyclization yielded the target compounds with full retention of the C12a stereocenter configuration.

Stereoselective Synthesis of Benzo[e][1,4]oxazino[4,3-a][1,4]diazepine-6,12-diones with Two Diversity Positions.

Several variously substituted 1H-pyrazol-5-yl hydrazones were prepared in order to study their cyclisation reactions. It has been found that the pathway of the cyclisation depends on the nature of the cyclisation medium and the position of substitution in the pyrazole ring.

Cyclisation reactions of hydrazones XXXII. Synthesis of some pyrazolylhydrazones and study of their cyclisation

Cyclocondensation reactions of heterocyclic carbonyl compounds XI . Synthesis and study of cyclocondensation reactions of some 3-substituted-5-(2-aminobenzyl)-1H-[1,2,4]triazine-6-ones†

Michal Maloň

Papers

Stereoselective Polymer-Supported Synthesis of Morpholine- and Thiomorpholine-3-carboxylic Acid Derivatives.

Polymer-Supported Stereoselective Synthesis of Benzoxazino[4,3-b][1,2,5]thiadiazepinone 6,6-dioxides

Stereoselective Synthesis of Benzo[e][1,4]oxazino[4,3-a][1,4]diazepine-6,12-diones with Two Diversity Positions.

Cyclisation reactions of hydrazones XXXII. Synthesis of some pyrazolylhydrazones and study of their cyclisation

Cyclocondensation reactions of heterocyclic carbonyl compounds XI . Synthesis and study of cyclocondensation reactions of some 3-substituted-5-(2-aminobenzyl)-1H-[1,2,4]triazine-6-ones†