Зручний варіант синтезу 5-оксо-4,5-дигідро-1Н-[1,2,3]триазоло[4,5-b]піридин-6-карбонових кислот
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Date
2021
Authors
Сирота, Наталія
Кемський, Сергій
Вовк, Михайло
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Abstract
З’ясовано, що N-Boc-4-аміно-1,2,3-триазол-5-карбальдегіди в умовах реакції Фрідлендера піддаються циклоконденсації із малоновою кислотою або кислотою Мельдрума з утворенням 5-оксо-4,5-дигідро-1Н-[1,2,3]триазоло[4,5-b]піридин-6-карбонових кислот, та виявлено більшу ефективність у такому процесі кислоти Мельдрума.
Literature sources related to 2-oxopyridine-3-carboxylic acids, their benzo- and heteroannulated analogues as promising scafolds in the leader-oriented synthesis of bioactive compounds have been analyzed. Among 5-substituted 1,2-dihydro-2-oxo-pyridine-3-carboxylic acids, cytotoxic and antibacterial agents have been found and among corresponding 3-carboxamides substances with a wide range of affinity and functional activity against cannabinoid receptors have been discovered. These results have become the starting point for developing a synthetic approach to new structures, in which a fragment of the indicated acid is annulled with a pharmacophore 1,2,3-triazole ring. For this purpose, the reaction of N-Boc-4-amino-1,2,3-triazole-5-carbaldehyde with malonic acid was investigated. It was found that 4 hours of heating the reagents in acetic acid at 100 °C in the presence of 10% pyrrolidine leads to the obtainment of 5-oxo-4,5-dihydro-1H-[1,2,3]triazolo[4,5-b]pyridine-6-carboxylic acids with yields of 61–66%, which have not been described in the literature yet. Nevertheless, the use of Meldrum`s acid, a synthetic equivalent of malonic acid, in this process is much more effective and allows to increase the yields of target compounds to 91–94% in similar conditions. The paper describes the probable schemes of the revealed transformations and notes the influence of the corresponding intermediates on the selectivity of the cyclization stage. The structure of the synthesized compounds was confirmed by the results of measurements of IR, 1H (13C) NMR and chromato-mass spectra. In particular, the IR spectra are characterized by the bands of valence vibrations of the groups NH (3142–3154 cm-1), C = O (1707–1725 cm-1) and COOH (2645–2884 cm-1). An important proof of the formation of the pyridine nucleus during cyclization is the presence in the 1H NMR spectra of H7 protons in the range of 8.42-9.04 ppm, and in the 13C NMR spectra – five signals of this cycle.
Literature sources related to 2-oxopyridine-3-carboxylic acids, their benzo- and heteroannulated analogues as promising scafolds in the leader-oriented synthesis of bioactive compounds have been analyzed. Among 5-substituted 1,2-dihydro-2-oxo-pyridine-3-carboxylic acids, cytotoxic and antibacterial agents have been found and among corresponding 3-carboxamides substances with a wide range of affinity and functional activity against cannabinoid receptors have been discovered. These results have become the starting point for developing a synthetic approach to new structures, in which a fragment of the indicated acid is annulled with a pharmacophore 1,2,3-triazole ring. For this purpose, the reaction of N-Boc-4-amino-1,2,3-triazole-5-carbaldehyde with malonic acid was investigated. It was found that 4 hours of heating the reagents in acetic acid at 100 °C in the presence of 10% pyrrolidine leads to the obtainment of 5-oxo-4,5-dihydro-1H-[1,2,3]triazolo[4,5-b]pyridine-6-carboxylic acids with yields of 61–66%, which have not been described in the literature yet. Nevertheless, the use of Meldrum`s acid, a synthetic equivalent of malonic acid, in this process is much more effective and allows to increase the yields of target compounds to 91–94% in similar conditions. The paper describes the probable schemes of the revealed transformations and notes the influence of the corresponding intermediates on the selectivity of the cyclization stage. The structure of the synthesized compounds was confirmed by the results of measurements of IR, 1H (13C) NMR and chromato-mass spectra. In particular, the IR spectra are characterized by the bands of valence vibrations of the groups NH (3142–3154 cm-1), C = O (1707–1725 cm-1) and COOH (2645–2884 cm-1). An important proof of the formation of the pyridine nucleus during cyclization is the presence in the 1H NMR spectra of H7 protons in the range of 8.42-9.04 ppm, and in the 13C NMR spectra – five signals of this cycle.
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Keywords
4-аміно-1,2,3-триазол-5-карбальдегіди, малонова кислота, кислота Мельдрума, [1,2,3]триазоло[4,5-b]піридин-6-карбонові кислоти, реакція Фрідлендера, стаття, 4-amino-1,2,3-triazol-5-carbalehides, malonic acid, Meldrum’s acid, [1,2,3]-triazolo-[4,5-b]pyridine-6-carboxylic acid, Friedlander’s reaction
Citation
Сирота Н. О. Зручний варіант синтезу 5-оксо-4,5-дигідро-1Н-[1,2,3]триазоло[4,5-b]піридин-6-карбонових кислот / Н. Сирота, С. Кемський, М. Вовк // Вісник Львівського університету. Серія хімічна. - 2021. - Т. 62. - С. 191-196. - https:/doi.org/10.30970/vch.6201.191