Trisubstituted piperazinones, piperazines, tetrahydropyrazines, and dihydropyrazinones were prepared in a one‐step procedure from easily accessible polymer‐supported acyclic precursors containing either a masked aldehyde or ketone group. Acid‐mediated unmasking of the aldehyde triggered cyclic iminium formation followed by reduction with triethylsilane present in the cleavage cocktail. The effect of the substituent at the iminium‐forming nitrogen was evaluated: whereas complete conversion to the target compounds was observed with N‐alkyl, aryl, and phenylsulfonamido derivatives, the N‐acyl compound suffered from a partial reduction of the aldehyde to an alcohol. Similarly, ketones readily provided cyclic iminiums with N‐alkyl compounds, whereas their cyclization with N‐acyl precursors proceeded unwillingly. Interestingly, cleavage of the resin‐bound acyclic precursor at 60 °C in the presence of triethylsilane resulted in the decomposition of the amide bond and formation of a lactone. An analogous synthetic route was also successfully used for the preparation of piperazines and tested as an alternative route for the synthesis of diazepanones.
C(8)-H direct arylation of purine derivatives immobilized on Wang resin is described. The purine skeleton was immobilized via C(6)-regioselective substitution of 2,6-dichloropurine with polymer-supported amines. After N(9)-alkylation with two different alkyl iodides and C(2) substitution with two selected amines, reaction conditions for C(8)-H arylation were developed and optimized. Various aryl bromides and aryl iodides were used for the reaction affording the target 2,6,8,9-tetrasubstituted purines in very good purity. The same reaction conditions were also applied for the synthesis of 2,6,8-trisubstituted purines, however, yields were lower. The methodology is applicable for high throughput synthesis of chemical libraries comprised of purine scaffold.
Solid-phase synthesis of bisheterocyclic compounds that contain purine and the 3-hydroxyquinolin-4(1H)-one skeleton connected with an aliphatic spacer of a different length/structure is described. The reaction sequence started from the primary amines immobilized on aminomethylated polystyrene resin equipped with an acid-labile linker (4-(4-formyl-3-methoxyphenoxy)butyric acid). After the arylation of amines with 2,6-dichloropurine via its C(6), purine N(9) was alkylated and subsequently the chlorine at purine C(2) was substituted with aliphatic diamines. The resulting terminal amino group was used as the starting point for the synthesis of 3-hydroxyquinolin-4(1H)-one precursors based on the acylation with 3-amino-4-(methoxycarbonyl)benzoic acid followed by the saponification of the methyl ester and esterification of the resulting carboxylic acid with various haloketones. The intermediates were cleaved from the resin, and their cyclization to the target purine-hydroxyquinolinone bisheterocycles was accomplished by heating in acetic or trifluoroacetic acid.
The fluorescence properties of bisheterocyclic compounds that contain purine and the 3-hydroxyquinolin-4(1H)-one skeleton connected with an aliphatic spacer of a different length/structure (3HQP) were examined. It was found that the introducing of the spacer-purine scaffold led in the comparison to 3HQs themselves to (1) the possibility of the effectual excitation in the wider range of excitation wavelengths, moreover, some derivatives can be excited at relatively high wavelengths around 400 nm, (2) the lowering of the quantum yield and (3) the slight longer wavelength shift of the dual emission spectra. Tested organic solvents did not affect significantly the 3HQP fluorescence properties. The characters of emission spectra as well as the quantum yields of 3HQPs were notably influenced by the ratio of water and DMSO in their composed mixture applied as a solvent. With increasing water content in the mixture both I(1)/I(2) and the quantum yield decreased.
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