4-Hydroxy-2-quinolones 120. Synthesis and structure of ethyl 2-hydroxy-4-oxo-4H-pyrido-[1,2-a]pyrimidine-3-carboxylate

Abstract

the synthesized compounds exist in DMSO solution in the 2-hydroxy-4-oxo form while in the crystal (at least for the case of the unsubstituted derivative) X-ray analysis shows that it occurs in the bipolar 2,4-dioxo form.Interest in 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives is principally due to their broad spectrum of biological activity. Based on this molecular system there have been synthesized bicyclic diaza sugars which inhibit β-glucosidase with high specificity [2]. 2-(Benzothiazol-2-yl) derivatives are novel, oral inhibitors of human leukocyte elastase suitable for treating chronic obstructive illnesses of the lungs, asthma, emphysema, cystic fibrosis, and various inflammatory reactions [3]. Substituted ethylenediamines containing the pyrido-[1,2-a]pyrimidine fragment are effective in the fight against microbacterial infection, not just tubercular [4]. 4-Oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxamides find use as agents for the prophylaxis of gastric problems arising from the use of nonsteroidal anti-inflammatory agents [5]. 2-Amino-4H-pyrido[1,2-a]pyrimidin-4-ones actively inhibit the aggregation of human thrombocytes [6] and their analogs with a tetrazole fragment in position 3 the synthesis of leukotrienes [7].We have continued our work on preparative methods of synthesis and a study of the structure, chemical reactivity, and biological properties of 4-hydroxy-2-quinolinones and heterocycles related to them. This report concerns ethyl 2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylate.

4-Hydroxy-2-quinolones 143. Synthesis, structure, and spectroscopic characteristics of ethyl 2-hydroxy-4-oxo-4H-pyrazino[1,2-a]pyrimidine-3-carboxylate

“…Hence, similarly to the previously reported pyridopyrimidine [2], electron impact ionization caused an initial cleavage of the C (4) -N (5) and C (2) -C (3) bonds which also markedly predominates over an alternative break up of the ethoxycarbonyl group in the pyrazinopyrimidine 1 (Sheme 1).…”

“…Following a detailed study of the various modifications of carrying out the condensation of 2-aminopyridines with triethyl methanetricarboxylate it was found that the most rational method for preparing ethyl 2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylates is to carry out the synthesis in refluxing xylene with a molar reagent ratio of 1:2 [2]. This same method was also used successfully in the preparation of an 8-aza analog of the heterocycles indicated above, namely ethyl 2-hydroxy-4-oxo-4H-pyrazino-[1,2-a]pyrimidine-3-carboxylate (1) which is of interest for the subsequent synthesis of biologically active materials structurally similar to the 4-hydroxyquinol-2-one derivatives extensively studied by us.…”

“…An X-ray structural analysis of ethyl 2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylate showed that it exists in the crystal in the bipolar 2,4-dioxo form with the proton on the nitrogen atom in position 1 [2]. It would seem that such an insignificant change in structure as the exchange of the carbon atom in position 8 for nitrogen would not influence the pyrimidine part of the molecule.…”

The synthesis and analgesic properties of N-(benzyl)-2-hydroxy-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxamides

“…These syntheses use commercially S(-)-and R(+)-1-phenyl-and 1-(4-methoxyphenyl)ethylamines from Fluka with the optical purity of at least 99.5 and 99.0%, respectively. The starting ethyl 2-hydroxy-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylate (2) was synthesized according to the literature procedure [21]. …”

Improved synthesis, spectral characteristics and spatial structure of ethyl 2-hydroxy-8-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylate

“…Также как и в аналогичном ранее изученном со-единении [25] в иминопиридиновом фрагменте бицикла наблюдается заметное альтернирова-ние связей: связи Длины связей (Å) в структуре эфира 1 Масс-и ЯМР-спектры хоть и дают важную и полезную информацию о строении эфира 1, но, в отличие от рентгеноструктурного анализа, не по-зволяют так однозначно её трактовать, посколь-ку в принципе не противоречат ни одной из при-веденных таутомерных форм. В частности, сиг-нал протона гидроксильной группы в протонном спектре сильно уширен, что препятствует про-ведению корреляционных экспериментов, а зна-чит и точному установлению его локализации.…”