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The synthesis of various new structures of a library of 11-substituted 6-amino-11,12-dihydrobenzo[c]phenanthridines (BP) and 11-substituted 6-aminobenzo[c]phenanthridines (BP-D) is presented. These structures, further synthetic modifications, and the preparation of follow-up products which delivered about 40 new derivatives are described. Their potential as antiproliferative drug candidates was investigated by comparison of NCI 60 developmental therapeutics program (DTP) human tumor cell line screening data based on the results of in vitro tumor cell growth inhibition, including about 40 hitherto unpublished compound test results with up to 60 cancer cell lines. NCI-COMPARE studies helped to suggest the modes of action of the highly active antiproliferative drugs. These findings are supported by in vitro biological investigations showing either inhibition of tubulin polymerization and depolymerization or topoisomerase inhibition. Together with physicochemical parameters of the drug candidates, structure-activity relationships are critically discussed. Tubulin interaction or inhibition of topoisomerase I and IIα/β activity are two rationales that can explain the antiproliferative activity observed in the NCI 60 DTP human tumor cell line screen. However, it can also be reasonably assumed that these compounds address several targets, thus prohibiting the identification of simple structure-activity relationships. The new structures described herein are thought to act as so-called multitarget drugs, thus being of special interest in the area of multidrug resistance.

We herein describe a facile and versatile synthetic route to the tetracyclic system of 6-substituted 5,6-dihydro-11H-pyrido[3,2-i]-1-azacarbazoles with promising anticancer properties. These derivatives are built up by an elegant one-step base-catalyzed synthetic procedure from commercially available building blocks. One additional step provides the corresponding skeleton hitherto unknown in the literature. The possibility to synthesize a large library of compounds with various substitution patterns utilizing this method underlines the importance of this synthetic procedure.

Aryl methyl ketones can be easily converted to 1-aryl-2-dimethylaminomethylpropenones that are known as interesting lead structures for drug development. By reaction of these enone Mannich bases with benzamidines, a series of new 2-aryl-5-aroyl-3,4,5,6-tetrahydopyrimidines were synthesized. These structures were characterized according to their lipophilicity. Thirty five tetrahydropyrimidines were evaluated as nitric oxide synthase (NOS) inhibitors in usual screening assays. Some interesting members of this class of compounds were forwarded to more detailed tests determining mechanism of inhibition and inhibition of NADH consumption. The investigated structures showed modest activity of NOS inhibition. However, some new tetrahydropyrimidines bearing extended aromatic substituents such as the naphthyloyl or biphenyloyl residue displayed some activity of neuronal NOS and endothelial NOS inhibition but without selectivity for an isoform and should be of interest for further modifications.

The NMR spectroscopic data of a series of thirty-four 3-acylpyrido[1,2-a]pyrimidinium salts are analyzed, which were prepared as either perchlorates or chlorides. Methyl group substituted 3-aroyltetrahydropyrido[1,2-a]pyrimidines with the methyl substituent in positions 6, 8 and 9 as well as both in positions 6 and 8 were investigated bearing various aroyl substituents. Unequivocal assignment of all resonances was achieved via two-dimensional 1H,1H-COSY measurements, 1H,13C and 1H,15N HSQC as well as HMBC experiments, and important diagnostic CH and NH couplings in the heteroaromatic ring system are evaluated. The influence of the methyl substituents was analyzed on the proton, carbon and nitrogen shifts. A significant effect of the counter ion on some chemical shifts of the nuclei under discussion of the pyridopyrimidines is found, allowing the indirect detection of the anion, which is confirmed by direct measurement of the 35Cl nucleus of the perchlorates. Copyright © 2013 John Wiley & Sons, Ltd.

Based on the 6-aminobenzo[ c ]phenanthridines, a compound class showing noteworthy antitumor activity, an efficient one-step synthesis consisting of a base-catalyzed condensation of 2 equiv of 4-methylpyridine-3-carbonitrile and various aldehydes causing twofold ring closure is described. The obtained 6-amino-11,12-dihydropyrido[3,4- c ][1,9]phenanthrolines could be aromatized with Pd/C at high temperatures to form 6-aminopyrido[3,4- c ][1,9]phenanthrolines. All compounds were systematically characterized regarding both lipophilicity and solubility and a high cytotoxic potential was evaluated in preliminary in vitro studies. Compared to formerly described 6-aminobenzo[ c ]phenanthridines our newly developed phenanthrolines turned out to possess improved drugability, due to significantly increased water-solubility and decreased lipophilicity.

A series of new 3-aroylpyrido[1,2-a]pyrimidines were synthesized from aryl methyl ketones in a simple two-step procedure and evaluated as nitric oxide synthases (NOS) inhibitors. In order to perform a structure-activity relationship study, different aroyl groups were introduced in 3-position and methyl groups were introduced at different positions of the pyrimidine heterocycle. Compounds with a biphenyloyl, benzyloxybenzoyl or naphthoyl group displayed the highest inhibitory effects which were further increased by introduction of a methyl group in position 8 of the pyrido[1,2-a]pyrimidine moiety. Some of the compounds exhibited promising inhibitory effects with selectivity toward the purified inducible NOS (iNOS) and were also active against iNOS expressed in stimulated RAW 264.7 cells.

A synthetic access to novel cinnamoamides 6 was discovered by chance and explored following a two-step route. Compounds 3 were available from 6-amino-1,3-dimethyluracil (1) by acylation using benzoyl chlorides 2 and subsequently converted to 2-cyano-3-(N-methylamino)cinnamic acid methyl amides 6. This sodium methoxide-catalyzed reaction involves ring opening of the pyrimidine ring followed by elimination of CO to form dimethyl carbonate and rearrangement. The application of 6 as potential catecholamine-O-methyl transferase (COMT) inhibitors for the treatment of Parkinson’s disease is discussed.

Amino-substituted pyrido[2,3-d]pyrimidinediones have previously been found to bind to adenosine A1 and A2A receptors in micromolar concentrations. The present study was aimed at studying the structure–activity relationships of this class of compounds in more detail. Most of the investigated compounds were provided with polar substituents, such as ethoxycarbonyl groups and basic amino functions, in order to improve their water-solubility. The compounds were synthesized starting from 6-amino-1,3-dimethyluracil via different reaction sequences involving (cyano)acetylation, Vilsmeier formylation, or reaction with diethyl ethoxymethylenemalonate (EMME). The most potent and selective compound of the present series was 6-carbethoxy-1,2,3,4-tetrahydro-1,3-dimethyl-5-(2-naphthylmethyl)aminopyrido[2,3-d]pyrimidine-2,4-dione (11c) with a Ki value of 5 nM at rat and 25 nM at human A1 receptors. The compound was more than 60-fold selective versus A3 and more than 300-fold selective versus A2A receptors. It showed an over 300-fold improvement with respect to the lead compound. In GTPγS binding studies at membranes of Chinese hamster ovary cells recombinantly expressing the human adenosine A1 receptor, 11c behaved as an antagonist with inverse agonistic activity. A regioisomer of 11c, 6-carbethoxy-1,2,3,4-tetrahydro-1,3-dimethyl-7-(2- naphthylmethyl)aminopyrido[2,3-d]pyrimidine-2,4-dione (7a) in which the 2-naphthylmethylamino substituent at position 5 of 11c was moved to the 7-position, was a relatively potent (Ki = 226 nM) and selective (>20-fold) A3 ligand. In the series of compounds lacking an electron-withdrawing ethoxycarbonyl or cyano substituent in the 6-position, compounds with high affinity for adenosine A2A receptors were identified, such as 1,2,3,4-tetrahydro-1,3-dimethyl-5-(1-naphthyl)aminopyrido[2,3-d]pyrimidine-2,4-dione 16b (Ki human A2A = 81.3 nM, Ki human A1 = 153 nM, and Ki human A3 > 10,000 nM).

The readily available and highly reactive title compounds represent versatile building blocks in organic synthesis. Recent examples of 1,3-dipolar cycloadditions and Diels–Alder reactions and their applications are described. This microreview is especially devoted to cycloadducts formed between 1 and 2 and furans, and their transformations to give a variety of different classes of compounds, including derivatives of natural products. Here the conversion of oxanorbornadienes into bridged oxepines plays an important role in many cases. Different routes to enantiomerically pure compounds are also presented. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

1,2-Dihydro-5H-[1]benzopyrano[4,3-b]pyridine-2,5-diones 4a-j were synthesized from 4-alkylamino-coumarin-3-carbaldehydes 1 and 5(4H)-oxazolinones (azalactones) derived from N-acetylglycine (2a) and hippuric acid (2b). The intermediates 3 (3j isolated only) underwent spontaneous recyclization via opening of the azalactone and successive formation of the fused 2-pyridones 4. Attempts to synthesize the selected 2H-chromeno[3,4-f]-1,7-naphthyridine 6 by Vilsmeier reaction of 4e failed. Instead, N-deacetylation took place, followed by formylation of the amino group to the formamidine 7a. In addition, pyranopyridine 9a was obtained by condensation of the 3-formyl-2-pyridone 8 with the azalactone derived from 2a and acetic anhydride.

The reaction of 6-amino-1,3-dimethyluracil with equimolar amounts of arylalkanone Mannich bases under optimized reaction conditions leads to 7-aryl-5,6-dihydropyrido[2,3- d ]pyrimidines in a yield of 50–80%. Functionalization of these dihydropyridopyrimidine(1 H ,3 H )-2,4-diones with the Vilsmeier reagent affords, depending on the reaction conditions, either 6-dimethylaminomethylidene substituted 5 H -pyrido[2,3- d ]pyrimidine(1 H ,3 H )-2,4-diones or the corresponding pyridopyrimidine(1 H ,3 H )-2,4-diones bearing a carboxaldehyde function in position 6 of the heterocycle. Some further transformations of the aldehyde function demonstrate the synthetic potential of the synthesized structures, introducing pharmacologically relevant basic substituents into the side chain of these pyrido[2,3- d ]pyrimidine derivatives.

Diethylstilbestrol and other stilbene derivatives can provide some inhibition of the outwardly rectifying Cl- current (I(Cl-,OR)) in rat peritoneal mast cells. In order to elucidate structure-activity relationships of diethylstilbestrol, 12 stilbenes as well as 17beta-estradiol and hexestrol were tested in rat peritoneal mast cells using the nystatin-perforated patch approach of the whole-cell patch-clamp technique. Since trans-stilbene showed no effect, the substituents of diethylstilbestrol must be of importance. The introduction of only one hydroxy group in trans-stilbene produced potent inhibition of the I(Cl-,OR) (IC50: 3.3 microM). But in contrast, resveratrol with hydroxy groups at positions 4, 3', and 5' as well as methoxy substituted stilbene derivatives and 17beta-estradiol were ineffective. On the other hand, hexestrol potently inhibited I(Cl-,OR) indicating that the aromatic ring systems can also be connected by an ethyl bridge. In summary, a hydroxy group at position 4 (or 4') is a prerequisite for diethylstilbestrol-mediated inhibition of I(Cl-,OR).

The synthesis of novel 1,6-naphthyridines 6 with potential activity against tuberculosis is described using the reaction sequence 246. Depending on the ring N-substitution of the 4-alkylamino-6-methyl-2(1H)-pyridones 1 and 2 the electrophilic attack of the Vilsmeier reagent gives rise to the formation of the exocyclic N-formyl derivatives 3 from 1 and the corresponding 3-carbaldehydes 4 from 2. 1,2-Dihydro-2-imino-7-methyl-1,6(6H)-naphthyridin-5-ones 6a-j are prepared by the Knoevenagel reaction of 4 with CH-acidic nitriles 5. These reactions are carried out using a comparative study of conventional conditions (room temperature or reflux) versus microwave irradiation.

The classical Mannich reaction of aromatic methyl ketones with paraformaldehyde and dimethylamine hydrochloride resp. dimethyl(methylene)ammonium chloride has been extended to a few cases of 1-aryl-2-dimethylaminomethyl-prop-2-en-1-ones (ADMP reagents). They have gained remarkable attention in medicinal chemistry, but only more recently their properties as valuable building blocks for ring closure reactions to form either aroyl or dimethylaminomethyl substituted heterocyclic compounds has been evaluated. In this review, a collection of representative examples for their preparation (Scheme 2) and biological effects as well as the synthetic potential for the synthesis of heterocycles (Scheme 3—8) is given. The reaction of 4-hydroxycoumarin delivers with ADMP reagents, via the formation of detectable 3-(2-benzoylallyl)-4-hydroxycoumarins as secondary substitution products, after ring closure 3-benzoyl-3,4-dihy-dro-2H,5H-1-benzopyrano[4,3-b]pyran-5-ones (Scheme 4). The reaction of 4-hydroxy-6-methylpyran-2-one with ADMP reagents is investigated systematically in order to assess its suitability in carbon—carbon bond forming reactions as well as to provide the conditions for subsequent ring closure or intermolecular addition of further nucleophiles to the enone double bond of the intermediate 3-(2-benzoylallyl)-4-hy-droxy-6-methylpyran-2-ones yielding miscellaneous 3-substituted 2-pyrones (Scheme 5 and 8), and their application as building blocks for the combinatorial chemistry. The condensation of ADMP reagents with 2-aminopyridines gives rise to 3-benzoyl-3,4-dihydro-2H-pyrido[1,2-a]pyrimidines (Scheme 6) and the corresponding reaction using amidines affords 5-benzoyl-1,4,5,6-tetrahydropyrimidines (Scheme 7).

Starting from 4-hydroxycoumarins 4 and 1-aryl-2-(dimethylaminomethyl)prop-2-en-1-ones 2 the title compounds 6 have been synthesized. The reaction is initiated by addition of the C-3 carbon atom of 4-hydroxycoumarin to the enone double bond of the Mannich base, subsequent deamination affords the intermediate 3-(2-benzoylallyl)-4-hydroxycoumarin 8, followed by ring closure. Depending on the reaction time, varying proportions of the ketones 6 and 8 are formed and support the mechanism defined. The spectroscopic data of all products unambiguously distinguish between the coumarin and the chromone structures in favor of the former.

WOS: 000233656200228 In the title compound, C17H16N4O4, the dihedral angle between the planar nine-membered bicyclic ring system and the benzene ring is 81.9 (1)degrees. Intramolecular N-H center dot center dot center dot O and intermolecular N-H center dot center dot center dot O, N-H center dot center dot center dot N and C-H center dot center dot center dot N hydrogen bonds are effective in stabilizing the molecular and crystal structure.

The NMR spectroscopic data of a series of thirty-four 3-acylpyrido[1,2-a]pyrimidinium salts are analyzed, which were prepared as either perchlorates or chlorides. Methyl group substituted 3-aroyltetrahydropyrido[1,2-a]pyrimidines with the methyl substituent in positions 6, 8 and 9 as well as both in positions 6 and 8 were investigated bearing various aroyl substituents. Unequivocal assignment of all resonances was achieved via two-dimensional (1)H,(1)H-COSY measurements, (1)H,(13)C and (1)H,(15)N HSQC as well as HMBC experiments, and important diagnostic CH and NH couplings in the heteroaromatic ring system are evaluated. The influence of the methyl substituents was analyzed on the proton, carbon and nitrogen shifts. A significant effect of the counter ion on some chemical shifts of the nuclei under discussion of the pyridopyrimidines is found, allowing the indirect detection of the anion, which is confirmed by direct measurement of the (35)Cl nucleus of the perchlorates.

This work contains information on lipophilicity, solubility, drug-likeness, and cytotoxicity of the synthesized compounds.

Starting from 4-chlorocoumarin-3-carbaldehyde (1) and Wittig phosphoranes 2a-d the title compounds 6a-c have been synthesized via a four-step sequence. The intermediate 4-alkylamino-3-vinylcoumarins 5a-k have been prepared by the reaction of 4-chloro-3-vinylcoumarins 3a-d with primary amines 4a-h. The coumarin derivatives 5 (except 5k) underwent an unusual pyridine ring closure under Vilsmeier conditions to form the benzopyrano[4,3-b]pyridines 6. When the aminoaldehydes 7 were treated with the Wittig reagent 2b the fused N-alkyl-2(1H)-pyridinones 8 have been obtained as expected.

Starting from 7-alkoxy-4-aminocoumarins 5,6,8,12, and 13 as key intermediates, this paper describes two different methods for the preparation of azacannabinoidal 5H[1]benzopyrano[4,3-b]pyridin-5-ones 24–27, 38, and 39 containing typical structural requirements for ZNS activity. First, Michael addition of 6 and 8 to the double bonds of alkyl vinyl ketones 14 and 15 resulted in a mixture of tetrahydropyridines 24–27 and fused pyridines 20–23 the latter of which were reduced by sodium cyanoborohydride to give the target compounds 24–27. The second, pyridine ring closure was accomplished by a combination of Vilsmeier acetylation and formylation resulting in fused 4-chloropyridines 31–33 followed by reduction.

The temperature and concentration dependence of the 1 H NMR spectra of four anilinomethylenemalonic acid derivatives were determined in CDCl 3 and DMSO-d 6 to assign the E-Z isomers and to investigated the formation of intra- and intermolecular hydrogen bonds. Chemical shifts and coupling constant in the 13 C NMR spectra correspond with the results of the 1 H NMR investigations in the case of the cyanoacetate ester derivative. Contradictory results for the acetoacetate derivative were found by semi-empirical calculations

Starting from isoquinoline, the cyano substituted N-methoxyisoquinolinium salts 1.1 and 1.4 are prepared. Their behaviour in the presence of O-, C- and N-nucleophiles in different aprotic solvents is examined: from the 1-cyano substituted isoquinolinium derivative 1.1, 1- and 3-animals or 1-iminium salts are obtained depending on the amine used, and N-methoxyisocarbostyril 4.1.1 in H2O and OH−. The reaction of the 4-cyano-N-methoxyisoquinolinium salt 1.4 with amines yields 1-aminals and with OH− the corresponding hemiaminal. Conversion with CN− results in dinitrile derivatives and N-oxides. Synthese und nucleophile Substitutionsreaktionen cyansubstituierter N-Methoxyisochinoliniumsalze Ausgehend von Isochinolin werden die cyansubstituierten N-Methoxyisochinoliniumsalze 1.1 und 1.4 dargestellt. Ihr Reaktionsverhalten in Gegenwart von O-, C- und N-Nucleophilen in verschiedenen Losungsmitteln wird untersucht: aus dem 1-cyansubstituierten Isochinolinium-Derivat 1.1 werden 1- und 3-Aminale oder 1-Iminiumsalze in Abhangigkeit vom verwendeten Amin erhalten sowie N-Methoxyisocarbostyril 4.1.1 in H2O und OH−. Die Reaktion des 4-Cyan-N-methoxyisochinoliniumsalzes 1.4 mit Aminen ergibt 1-Aminale und mit OH− die entspr. Hemiaminale. Umsetzung mit CN− fuhrt zu Dinitril-Derivaten und N-Oxiden.

Two generally applicable syntheses of 2-bis-(dimethylaminomethyl)acetamides 9 are described. The first one involves reaction of N -mono substituted acetamides 3 with dimethyl(methylene)ammonium chloride in the presence of phosphorus oxychloride using diethyl ether as a solvent. Starting from ketoximes, the amines 9 are obtained under the same reaction conditions via Beckmann rearrangement. C -Aminomethylation observed in all cases may be the result of the formation of imidoyl chlorides 5 as intermediates.

The three-step synthesis of the title compounds, which have a high potential as adenosine receptors, is based on a Dieckmann cyclization of racemic cyano esters (V) and chiral cyano ester (IX).

Starting from 7-alkoxy-4-aminocoumarins 5,6,8,12, and 13 as key intermediates, this paper describes two different methods for the preparation of azacannabinoidal 5H[1]benzopyrano[4,3-b]pyridin-5-ones 24–27, 38, and 39 containing typical structural requirements for ZNS activity. First, Michael addition of 6 and 8 to the double bonds of alkyl vinyl ketones 14 and 15 resulted in a mixture of tetrahydropyridines 24–27 and fused pyridines 20–23 the latter of which were reduced by sodium cyanoborohydride to give the target compounds 24–27. The second, pyridine ring closure was accomplished by a combination of Vilsmeier acetylation and formylation resulting in fused 4-chloropyridines 31–33 followed by reduction.

2-Digitoxigenone amidinohydrazone (1), a compound with known digitalis-like activity, and Schiff bases 2-11 of 3-digitoxigenone were synthesized and tested pharmacologically in order to further determine possible structural requirements at the 3-position of digitalis compounds. The inotropic activity was screened using guinea-pig atria, and the interaction with the digitalis receptor was further examined using [3H]ouabain binding to cardiac membranes from guinea pig, rat, pit and man. All compounds revealed activities intermediate between 3-digitoxigenone and ouabain, and the potency of the derivatives covered approximately one order of magnitude. The absolute potency varied among species, but the rank order of potency was rather similar, yielding good correlations between species. This indicates no pronounced preference of these compounds for a particular (Na+/K+)-ATPase isoform of any of the species studied.

Two generally applicable syntheses of 2-bis-(dimethylaminomethyl)acetamides 9 are described. The first one involves reaction of N -mono substituted acetamides 3 with dimethyl(methylene)ammonium chloride in the presence of phosphorus oxychloride using diethyl ether as a solvent. Starting from ketoximes, the amines 9 are obtained under the same reaction conditions via Beckmann rearrangement. C -Aminomethylation observed in all cases may be the result of the formation of imidoyl chlorides 5 as intermediates.

1H and 13C NMR data for 1-cyano-, 4-cyano-, 4-bromo- and 4-bromo-5-nitro-substituted isoquinolines, isoquinoline N-oxides and N-methoxy and N-ethyl salts in different solvents are reported. The substituent chemical shifts are discussed with regard to the reactivity of the N-methoxy compounds in the presence of nucleophilic reagents.

Anilinoacrylic acid derivatives 2-4 are the key intermediates from which 1-alkyl substituted 4-aminoquinoline 10-15 as well as 4-alkylaminoquinoline derivatives 16-23 are synthesized and examined for positive inotropic activity on isolated left atria and papillary muscles from guinea-pig. Structure activity relationships indicate that the effect depends on the alkyl side chain of the target compounds.

The Mannich reaction of 7-aryl-5,6-dihydropyrido[2,3-d]pyrimidines 3, easily accessible by condensation of 6-amino-1,3-dimethyluracil (1) with Mannich bases 2a - c, gives rise to a mixture of 7-aryl-6-(N,N-dimethylaminomethyl)pyrido[2,3-d]pyrimidines 6 and 7 as well as 1,2-bis- (7-arylpyrido[2,3-d]pyrimidin-6-yl)ethane 13 the ratio of which depends on the reaction conditions and the amine used. 6-Alkylamino-1,3-dimethyluracils 15 - 18 were converted to the corresponding 5-(3-oxo-3-phenylpropyl)uracils 19 - 22 by condensation with the Mannich base 2a. Ring closure of 19 - 22 was performed by Vilsmeier formylation to afford the 8-alkyl- and 7,8-diaryl-5,8- dihydropyrido[2,3-d]pyrimidine-6-carbaldehydes 9 - 12 via the corresponding iminium salts 27 - 30

1,2-Dihydro-5H-[1]benzopyrano[4,3-b]pyridine-2,5-diones 4a-j were synthesized from 4-alkylamino-coumarin-3-carbaldehydes 1 and 5(4H)-oxazolinones (azalactones) derived from N-acetylglycine (2a) and hippuric acid (2b). The intermediates 3 (3j isolated only) underwent spontaneous recyclization via opening of the azalactone and successive formation of the fused 2-pyridones 4. Attempts to synthesize the selected 2H-chromeno[3,4-f]-1,7-naphthyridine 6 by Vilsmeier reaction of 4e failed. Instead, N-deacetylation took place, followed by formylation of the amino group to the formamidine 7a. In addition, pyranopyridine 9a was obtained by condensation of the 3-formyl-2-pyridone 8 with the azalactone derived from 2a and acetic anhydride.

The synthesis of 11-substituted 6-amino-11,12-dihydrobenzo[c]phenanthridines and 11-substituted 6-aminobenzo[c]phenanthridines through an efficient method is described. The antiproliferative activity of selected compounds against a wide panel of tumor cell lines was tested in the in vitro anticancer screening and the in vivo hollow fiber assay of the National Cancer Institute. Several compounds turned out to exhibit considerable cytotoxicity for tumor cells. For the study of structure-activity relationships different substituents were introduced in the 11-position. Compounds with methoxyphenyl substituents tended to show the highest potency. Several compounds exhibited noteworthy antitumor activity with GI(50) values across all cell lines1 microM. 6-Amino-11-(3,4,5-trimethoxyphenyl)benzo[c]phenanthridine perchlorate was the most potent agent in the NCI's in vivo hollow fiber assay. Most of the tested compounds showed a remarkable selectivity for leukemia, breast cancer, and prostate cancer.

N-(Pyridyl)pyridinium salts 7 and 8 as well as 4-phenylpyrido[1,2-a]pyrimidinium salts 4 and 12 have been prepared by reactions of 3-aryl-3-chloropropeniminium salts 5 with aminopyridines (6) using glacial acetic acid as solvent. 2-Phenylpyrido[1,2-a]pyrimidinium salts 2 are formed when ethanol is used as the solvent. The condensation of 2-aminopyridine (6a) with 3-chloro-2,3- dehydromorpholino-2-carbiminium salt 13 is described. The HSAB principle of Pearson is discussed to explain the different regioselective ring closure reactions.

WOS: 000220563800087 In the title molecule, C24H20N2O5, the cyclohexene ring adopts a half-chair conformation. The molecular structure shows some intra- and intermolecular hydrogen bonds.

Dependent on the reaction time, the three-component condensation of dimethyl acetonedicarboxylate (1), aromatic aldehydes 2, and malononitrile (3) gives rise to 4H-pyran derivatives 5 after reflux for 15 min. Moreover, using excess of benzaldehyde and prolonged heating for 150 min afforded multifunctional cyclohexanone derivatives 8. Different substitution patterns in the phenyl nucleus of 8 can be achieved by condensation of 4H-pyran derivatives 5 with benzaldehydes 2.