Dmitrii L. Obydennov

Regioselective synthesis of 2- and 5-trifluoromethyl-or 2- and 5-difluoromethylpyrazolo[1,5-c]pyrimidines based on 7,7,7-trifluoro-or 7,7-difluoro-2,4,6-trioxoheptanoic and 6-trifluoromethyl-or 6-difluoromethylcomanic acids

Abstract6-Tri- and 6-difluoromethylcomanic acids and their ethyl esters reacted with aminoguanidine, predominantly giving 5-RF-pyrazolo[1,5-c]pyrimidines, whereas the reaction of the openchain synthetic equivalents, i.e., ethyl 7,7,7-trifluoro- and 7,7-difluoro-2,4,6-trioxoheptanoates, with this polynucleophile allowed us to obtain regioselectively 2-RF-pyrazolo[1,5-c]pyrimidines.

Reactions of 2-Mono- and 2,6-Disubstituted 4-Pyrones with Phenylhydrazine as General Method for the Synthesis of 3-(N-Phenylpyrazolyl)Indoles

Phenylhydrazine reacted regioselectively with 6-substituted 4-pyrone-2-carboxylic acids (or esters) in protic and aprotic solvents, leading to phenylhydrazones of 3-(3-R-1-phenylpyrazol-5-yl)- or 3-(5-R-1-phenylpyrazol-3-yl)pyruvic acids (or esters), respectively. 6-Di(tri)fluoromethylcomanic acids (or esters) reacted analogously, forming the corresponding phenylhydrazones with RF group in the side chain. The obtained phenylhydrazones underwent Fischer reaction under acidic conditions, forming the respective 3-(N-phenylpyrazolyl)indoles. In contrast to comanic acid and its ester, the reactions of 2-substituted 4-pyrones occurred non-selectively and gave mixtures of regioisomeric pyrazoles with phenylhydrazone group in the side chain or 3-(N-phenylpyrazolyl)indoles. A mechanism was proposed to explain the effect of solvent on the course of reaction.

3-(1H-1,5-Benzodiazepin-2(3H)-ylidenemethyl)-quinoxalin-2(1H)-ones in reactions with nucleophiles. Synthesis and structure of 3-(hetarylmethyl)quinoxalin-2-ones

3-(1Н-1,5-Benzodiazepin-2(3Н)-ylidenemethyl)quinoxalin-2(1H)-ones react with hydrazines and hydroxylamine in acidic medium, leading to conversion of seven-membered ring to five-membered ring and formation of the respective dihetarylmethanes in 40–79% yields. The starting materials containing an electron-donating substituent (R = Ph, 4-ClC6H4, 2-naphthyl, 2-thienyl, Me) at position 4 of the benzodiazepine ring reacted predominantly at the С-4 atom, while another starting material containing an electron-withdrawing substituent (R = CF3) at the same position reacted at the С-2 atom. The synthesized 3-(hetarylmethyl)quinoxalin-2-ones existed in DMSO-d6 solution as tautomeric imine and enamine forms, the ratio of which depended on the possibility of a strong intramolecular hydrogen bond and indicated regioselective formation of pyrazole or isoxazole rings. Acidic hydrolysis of the benzodiazepinоquinoxaline system resulted in loss of the diazepine ring and formation of diketoquinoxalines in 41–82% yields, having a different reactivity than their synthetically equivalent benzodiazepine analogs.

Preparative synthesis of ethyl 5-acyl-4-pyrone-2-carboxylates and 6-aryl-, 6-alkyl-, and 5-acylcomanic acids on their basis

A simple and efficient method for the synthesis of ethyl 5-alkanoyl- and 5-aroyl-4-pyrone-2-carboxylates was developed, which is based on the condensation of 1-R-2-(dimethyl-aminomethylidene)butane-1,3-diones, obtained from 1,3-diketones and dimethylformamide dimethyl acetal, with diethyl oxalate in the presence of NaH in THF. Ethyl 5-acyl-4-pyrone-2-carboxylates were used in the synthesis of 6-R- and 5-RCO-comanic acids.

The reaction of 6-substituted 4-pyrone-2-carboxylic acids with o-phenylenediamine. Synthesis and structure of 3-(1H-1,5-benzodiazepin-2(3Н)-ylidenemethyl)quinoxalin-2(1H)-ones

6-Aryl(alkyl)-4-pyrone-2-carboxylic acids upon refluxing in n-BuOH react with two equivalents of о-phenylenediamine, giving 26–85% yields of 3-(1H-1,5-benzodiazepin-2(3H)-ylidenemethyl)quinoxalin-2(1H)-ones, which exist in two tautomeric forms. The direction of the initial nucleophilic attack on the pyrone ring and the tautomeric composition of the obtained products is mainly determined by the substituent at the С-6 atom. Quantum-chemical calculations were used to estimate the stability of tautomers in the gas phase.

The Interaction of 2,5-Diethoxycarbonyl-and 5-Benzoyl-2-Ethoxycarbonyl-4-Pyrones with o-Phenylenediamine*

The esters of chelidonic [1] and comanic [2] acids, as well as 5-benzyloxycomanic acid [3], are known to react with о-phenylenediamine, forming the respective pyrido[1,2-a]quinoxalines. The reaction proceeds by pyrone ring opening, with a subsequent recyclization into derivatives of N-(2-aminophenyl)-4-pyridone, which further cyclize to the final products, pyrido[1,2-a]quinoxalines. However, the intermediates of this process have not been described in the literature. Recently we reported a simple method for the synthesis of 2,5-diethoxycarbonyl-4-pyrone 1а [4] and 5-benzoyl-2-ethoxycarbonyl-4-pyrone 1b [5], providing access to these previously scarce compounds for a wide range of investigations. Here we report the first data regarding the interaction of 4-pyrones 1a,b with о-phenylenediamine. It was found that after 1-2 h in ethanol at 0°C the reaction stopped at the stage of pyrone ring opening and gave 85-89% yields of the products 2a,b, which resulted from an attack by amino group at the С-6 atom activated by two carbonyl groups. As indicated by Н NMR spectra, these polyfunctional compounds exist in CDCl3 as three open-chain tautomeric forms in a 76:18:6 ratio (compound 2a) and 76:15:9 ratio (compound 2b). Two of these tautomers (the major forms А and B) are shown in the Scheme, while the structure of the third tautomer was not established. The intermediates 2a,b easily cyclized upon treatment with MeSO3H or refluxing in ethanol, giving new pyrido[1,2-a]quinoxaline derivatives 3a,b (in 55% and 69% yields, respectively), which present interest for medicinal chemistry as potential antimicrobial [1] and antiviral agents [6-8]. This class of compounds also includes the recently introduced anti-HIV drug dolutegravir [6-8]. The Н NMR spectrum of the intermediate 2a features a main set of signals due to the tautomer A with a 2Z,5E configuration of double bonds, which consists of a doublet for the NH proton (δ 12.41 ppm, J = 13.1 Hz), apparently involved in a strong intramolecular hydrogen bond with the ketone carbonyl, a doublet for the

Bio-based triacetic acid lactone in the synthesis of azaheterocycles via a ring-opening transformation

In the present article a new way of converting bio-based triacetic acid lactone (TAL) into azaheterocyclic compounds, such as 4-pyridones, pyrazoles, isoxazolines and isoxazoles, has been found. The main strategy involves the transformation of TAL into reactive and multifunctional polycarbonyl intermediates serving as C-6 building blocks for the construction of organic compounds. TAL undergoes a ring opening transformation with aliphatic and aromatic amines, including bioavailable amines, under solvent free conditions or in EtOH to give carbamoylated enaminones (40–98%). These polyfunctional compounds have been converted into biologically important pyridone-3-carboxamides (91–99%) with dimethylformamide dimethyl acetal and also react regioselectively with hydrazines and hydroxylamine to form pyrazolyl- (72–96%) and (isoxazolinyl)acetoamides (60–91%). The conversion of TAL into hetarylacetic acid amides can be performed as one-pot reactions without isolation of polycarbonyl intermediates.

Noncatalytic destruction of 5-acylcomanic acid esters in the presence of 2-methylindoles as a new method for the synthesis of indolylchalcones

Ethyl esters of 5-acylcomanic acids reacted with 2-methylindoles in 3:1 propanol–water mixture in the absence of catalyst, resulting in pyrone ring opening and destruction of the molecular framework and leading to trans-indolylchalcones in 52–70% yields.