- Facile access to 3,5-dihalogenated pyrazoles by sydnone cycloaddition and their versatile functionalization by Pd-catalyzed cross-coupling processes
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The 1,3-dipolar cycloaddition of diversely N-substituted 4-iodosydnones with 3-halopropiolates produces easily separable mixtures of dihalogenated pyrazolylcarboxylic esters at a preparative scale level, with the 3,5-dihalogenopyrazole regioisomers always predominating. Further decarboxylation of the major isomers provided the corresponding 3,5-dihalogenopyrazoles with a free C-4 position. These were found to be valuable scaffolds for the elaboration of unsymmetrically 1,3,5-trisubstituted pyrazole derivatives by site-selective Pd-catalyzed cross-coupling reactions. Notably, the flexible and site-selective introduction of different (hetero)aryl, vinyl, or alkyl substituents at the C-5 and C-3 positions of the pyrazole core could be achieved through sequential Suzuki-type reactions with various boron compounds. Copyright
- Delaunay, Thierry,Es-Sayed, Mazen,Vors, Jean-Pierre,Monteiro, Nuno,Balme, Genevieve
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- A convenient procedure for the preparation of 3-bromopropiolic esters
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3-Bromopropiolic esters are efficiently prepared by reaction of the corresponding propiolic esters with N-bromosuccinimide in acetone and silver nitrate as catalyst.
- Leroy
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- Ru(II)-mediated synthesis and bioactivity evaluation of 1,4,5-trisubstituted N-phthalimido protected 5-bromo-1,2,3-triazolic amino acid
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Background: In spite of significant progress made toward the synthesis of triazole amino acids as structural scaffolds of peptides and leading structures of new drugs, a need still exists for effective methods of trisubstituted triazole amino acid synthesis. Methods: A protocol based on ruthenium(II)-catalyzed alkyne-azide cycloaddition (RuAAC) was developed to synthesize 5-bromo-1,4,5-trisubstituted 1,2,3-triazole-based amino acid – tert-butyl 5-bromo-1-(2-(1,3-dioxo-2,3dihydro-1H-isoindol-2-yl)ethyl]-1H-1,2,3-triazole-4-carboxylate (5Br-TzlAA). Two other disubstituted regioisomers, 1,4- and 1,5-TzlAA, were also synthesized to evaluate the influence of the 5-bromo substituent for triazole ring bioactivity. Results: Under optimal conditions, 5Br-TzlAA was synthesized within 1 h with 93% yield. NMR confirmed the structure of 5Br-TzlAA and showed regioselectivity of the RuAAC reaction. None of the TzlAAs were cytotoxic for the human cell lines investigated and showed a small pro-proliferatory effect at the highest concentrations (50-100 μg/mL) studied. A small anti-proliferative effect was visible for 1,4-TzlAA. Conclusion: A simple and effective protocol for the synthesis of 5-bromo-1,4,5-trisubstituted TzlAA (5Br-TzlAA) was developed. Bioassay results show that N-phthalimido modifying the TzlAAs are well tolerated by human cells and may be used as leading or scaffold structures to design new biologically active molecules.
- Mucha, Piotr,Pieszko, Ma?gorzata,Miszka, Anna,Ruczyński, Jaros?aw,Rekowski, Piotr,Za?uska, Izabela,Koz?owska, Agnieszka,Schumacher, Adriana,Deptu?a, Milena,Piku?a, Micha?
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p. 282 - 289
(2018/04/20)
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- ISOXAZOLE DERIVATIVE AS MUTATED ISOCITRATE DEHYDROGENASE 1 INHIBITOR
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It has been found that a compound of the general formula (I) having an isoxazole skeleton has excellent inhibitory activity against mutant IDH1 protein and inhibits the production of 2-HG by this protein, while the compound is also capable of effectively inhibiting the growth of various tumors expressing the protein. In the formula, R1, R2, R3, Y, and Z are as defined in claim 1.
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Paragraph 0421; 0422
(2018/02/06)
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