Sulfonation of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-2-difluoromethoxyphenyl)-1,4-dihydropyridine (phoridone)

Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1568–1569, November, 1989.     

Bromination of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(2′-difluoromethoxyphenyl)-1,4-dihydropyridine (foridone)

The action of mild brominating agents (pyridinium bromide-perbromide, dioxan dibromide N-bromosuccinimide, and N-bromoacetamide) on 2,6-dimethyl-3,5-dimethoxy-carbonyl-4-(2-difluoromethoxyphenyl)-1,4-dihydropyridine (Foridone) has been studied. Depending on reaction conditions, furo-, difuro-, and dibromomethyl-1,4-dihydropyridines are obtained together with certain oxidized forms.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 948–952, July, 1989.     

Chlorination of 2,6-dimethyl-3,5-dicarbomethoxy-4-(2′-difluoromethoxyphenyl)-1,4-dihydropyridine (phoridone)

Chlorination of 2,6-dimethyl-3,5-dicarbomethoxy-4-(2-difluoromethoxyphenyl)-1,4-dihydropyridine gives 2,3,4,5-tetrahydropyridines with different degrees of chlorination dependent upon the quantitative ratio of reagents. The reaction proceeds without oxidation of the dihydropyridine ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 376–379, March, 1990.     

Mechanism of the antioxidant action of 2,6-dimethyl-3,5-dimethoxy-carbonyl-4-(2-nitrophenyl)1,4-dihydropyridine

A comparison of data on the kinetics of the accumulation of peroxides and the ESR spectra in the case of inhibition of the autooxidation of methyl oleate by 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(2-nitrophenyl)1,4-dihydropyridine (I) established that the antioxidant action of the latter is exerted by the formation of a nitroxyl radical. This radical is produced analogously to the well-known scheme from 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(2-nitrosophenyl)pyridine, which is generated in the reaction medium from I and methyl oleate.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1120–1122, August, 1984.     

Pseudosymmetry in the crystal structure of 2,6-dimethyl-3,5-dicarbomethoxy-4-(2′,3′-dichlorophenyl)-1,4-dihydropyridine

Within the framework of a detailed crystallochemical analysis a comparison of the structures of symmetrically independent molecules was performed and the energy of intermolecular interaction was calculated for a triclinic bisystem crystal, 2,6-dimethyl-3,5-dicarbomethoxy-4-(2′,3′-dichlorophenyl)-1,4-dihydropyridine. Pseudosymmetrical operations were detected and identified. The presence of highly efficient layers with pseudomonoclinic symmetry was disclosed in this structure.     

Effect of the solvent nature on the course of quaternization of 3,5-diethoxycarbonyl-2,6-dimethyl-4-(3-pyridyl)-1,4-dihydropyridine

The effect of the solvent nature and temperature on the quaternization of 3,5-diethoxycarbonyl-2,6-di- methyl-4-(3-pyridyl)-1,4-dihydropyridine by lipophilic alkyl bromides has been investigated. By comparison of the solvent effect (acetone, acetonitrile, and 2-butanone) on the alkylation of the pyridine fragment of 3,5-diethoxycarbonyl-2,6-dimethyl-4-(3-pyridyl)-1,4-dihydropyridine it was established that conducting the reaction in acetonitrile at 81 °C is the most optimal.     

Novel 1,4-dihydropyridine calcium antagonists. I. Synthesis and hypotensive activity of 4-(substituted pyridyl)-1,4-dihydropyridine derivatives

A series of 4-(substituted pyridyl)-1,4-dihydropyridine derivatives were synthesized and their hypotensive effects examined. Several compounds, 2-(N-benzyl-N-methylamino)ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitro-2-pyridyl)-3,5-pyridinedicarboxylate (2b), its 4-(4-nitro-2-pyridyl) analogue (2g), 4-(3-trifluoromethyl-2-pyridyl) analogue (2c), 4-(2-trifluoromethyl-3-pyridyl) analogue (3e), 4-(4-cyano-2-pyridyl) analogue (2e), 4-(2-cyano-3-pyridyl) analogue (3d), and 4-(6-bromo-2-pyridyl) analogue (2i), were found to have a hypotensive activity parallel to that of nicardipine; 2c and 3e, in particular, had approximately twice the duration of nicardipine, and 2e had the most potent hypotensive activity of all the derivatives synthesized.     

Formation of furo- and difuro-1,4-dihydropyridines in the bromination 0f 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o-nitrophenyl)-1,4-dihydropyridine

Furo- and difuro-1,4-dihydropyridines were obtained by bromination of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o-nitrophenyl)-1,4-dihydropyridine with mild brominating agents (pyridinium bromide perbromide, N-bromosuccinimide, and dioxane dibromide).Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1227–1232, September, 1987.     

Enantioselectivity of alcohol-treated Candida rugosa lipase in the kinetic resolution of racemic methyl 2-aryloxypropionates in water and aqueous organic media

Racemic methyl 2-aryloxypropionates (±)-1 were subjected to hydrolysis in water and in a series of two-phase aqueous organic media in the presence of Candida rugosa lipase (CRL). The biocatalytic material used was the enzyme of commercial CRL purified by treatment with different alcohols. The purification of CRL and the reaction medium play an important role in the enantioselection of racemates (±)-1. While it is not possible to use the same protocol for all substrates, by combining the different ways of purifying the enzyme with the various reaction media, it is possible to achieve high enantioselectivities of racemic esters.     

Lipase-catalyzed enantioselective hydrolysis of 4-alkyl-1,4-dihydropyridine derivatives: synthesis of (+)- and (-)-methyl 2-(phenylthio)ethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate (PCA 4248).

Asymmetric synthesis of (+)- and (-)-PCA 4248 (PAF antagonist) was achieved using lipase-catalyzed enantioselective hydrolysis of the acyloxymethyl esters. The enzymatic reaction proceeded under the mild conditions in an organic solvent.     

微波辐射下2,6-二甲基-3,5-二乙氧羰基-4-二茂铁基-1,4-二氢吡啶的合成和晶体结构

标题化合物C_23H_27FeNO_4是由二茂铁甲醛、乙酰乙酸乙酯、尿素负载于SiO2在微波辐射下干反应而得。用元素分析、IR、1H NMR对化合物进行了表征,并通过了单晶X-射线衍射法确定了晶体结构,其晶体属三斜晶系,空间群P,Mr = 437.32,a = 7.462(2),b = 8.3574(13),c = 16.491(3) , a = 78.36(2),b = 88.76(3),g = 86.11(2),V = 1004.9(3) 3,Z = 2,Dc = 1.445 g/cm3,m(MoKa) = 7.80 cm-1,F(000) = 460.00,最终的偏离因子为R = 0.063,wR = 0.180。该化合物是1个由二茂铁基和1,4-二氢吡啶环组成的双功能团化合物,其中吡啶环为船式结构。     

Hantzsch synthesis of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o-methoxyphenyl)-1,4-dihydropyridine; a novel cyclisation leading to an unusual formation of 1-amino-2-methoxy-carbonyl-3,5-bis(o-methoxyphenyl)-4-oxa-cyclohexan-1-ene

Hantzsch condensation of two equivalents of methyl-3-aminocrotonate with (m- and p)-methoxybenzaldehyde afforded the expected products 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(m-methoxyphenyl)-1,4-dihydropyridine and 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(p-methoxyphenyl)-1,4-dihydropyridine, whereas o-methoxy-benzaldehyde produced mainly 1-amino-2-methoxycarbonyl-3,5-bis(o-methoxy-phenyl)-4-oxa-cyclohexan-1-ene. The structure of the product, not previously reported in the literature, was determined by 1D and 2D NMR spectra and its MS fragmentation. This is the first example of cyclisation leading to a substituted pyran rather than 1,4-DHP under typical Hantzsch reaction conditions. A plausible mechanism for its formation is postulated.     

The synthesis of some dialkyl 4-(3-substituted amino)phenyl-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates

Dialkyl 4-(3-aminophenyl)-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates 1 were transformed into alkyl 4-(3-(((2-benzoylamino-2-methoxycarbonyl)ethenyl)amino)phenyl)-1,4-dihydro-2,6-dimethyl-pyridine-3,5-dicarboxylates 4 and with 2,2-disubstituted-1-dimethylaminoethenes 7 into dimethyl 4-(3-(((2,2-diacyl- or 2-acyl-2-alkoxycarbonyl)ethenyl)amino)phenyl)-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates 8 and their ethyl methyl analogues 9.     

N-(2-hydroxyethyl)-4-(p-nitrobenzylidene)-1,4-dihydropyridine (DHP) from the reaction of 4-(p-nitrobenzyl)pyridine (NBP) with ethylene oxide

The title reaction was carried out and characterization of the alkylation product (DHP, II) lead to the conclusion that it had a 1,4-dihydropyridine structure, rather than a pyridinium ion structure. The ¹³C- and ¹H-nmr spectra, and the colors were especially important in establishing the structure.     

Multicomponent synthesis of 2-alkylthio-6-amino-3,5-dicyano-1,4-dihydropyridine-4-spirocycloalkanes. Molecular and crystal structure of 6-amino-2-(2-methylbenzylthio)-3,5-dicyano-1,4-dihydropyridine-4-spirocyclopentane

2-Alkylthio-6-amino-3,5-dicyano-1,4-dihydropyridine-4-spirocycloalkanes were synthesized via the reaction of cycloalkylidene malononitriles with cyanothioacetamide and alkyl halides. The structure of 6-amino-2-(2-methylbenzylthio)-3,5-dicyano-1,4-dihydropyridine-4-spirocyclopentane was determined by the X-ray diffraction analysis.     

Use of pyridinium ionic liquids as catalysts for the synthesis of 3,5-bis(dodecyloxycarbonyl)-1,4-dihydropyridine derivative

The synthesis of cationic amphiphilic 1,4-dihydropyridine derivative, potential gene delivery agent is achieved via an efficient multi-step sequence. The key step of this approach is a two-component Hantzsch type cyclisation of 3-oxo-2-[1-phenylmethylidene]-butyric acid dodecyl ester and 3-amino-but-2-enoic acid dodecyl ester utilising bis(2-hydroxyethyl)ether as a solvent and 1-butyl-4-methylpyridinium chloride as a catalyst. The 1,4-dihydropyridine derivative with long alkyl ester chains at positions 3 and 5 of the 1,4-DHP ring — 3,5-bis(dodecyloxycarbonyl)-2,6-dimethyl-4-phenyl-1,4-dihydropyridine was obtained in substantially higher yield with respect to classical Hantzsch synthesis. Bromination of this compound followed by nucleophilic substitution of bromine with pyridine gave the desired cationic amphiphilic 1,4-dihydropyridine.