- Synthesis of new organochalcogen (Se or Te) based multifunctional pyrimidine derivatives: X-ray structure determination of 2,4- bis(arylchalcogenyl)pyrimidine and 2-chloro-4,6-bis(arylchalcogenyl)pyrimidine compounds
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A new class of multinucleate pyrimidine chalcogen (Se/Te) derivatives, i.e. 2,4-bis(arylchalcogenyl)pyrimidine and 2-chloro-4,6-bis(arylchalcogenyl) pyrimidine compounds, has been synthesized for the first time by the nucleophilic substitution of chlorine at the C-2 and C-4 positions of 2,4-dichloropyrimidine and at the C-4 and C-6 positions of 2,4,6- trichloropyrimidine with a variety of chalcogen bearing aryl anions ArE - (Ar = phenyl, 1-naphthyl, p-tolyl). All the newly prepared pyrimidyl chalcogen compounds have been thoroughly characterized with the help of various spectroscopic techniques, viz, NMR (1H, 13C, 77Se), FT-IR and mass spectrometry (in representative cases). The crystal structures of 2,4-bis(naphthalen-1-ylselanyl)pyrimidine (1c), 2,4-bis(phenyltelluryl)pyrimidine (1d), 2-chloro-4,6-bis(phenylselanyl) pyrimidine (2a) and 4,6-bis(p-tolylselanyl)-2-chloropyrimidine (2b) were confirmed by X-ray crystallographic analysis.
- Arora, Ekta,Bhasin,Mehta,Sharma, Nidhi,Bhasin,Jacob, Claus,Félix, Vítor,Neogi, Subhadip
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- Synthesis of novel pyridine and pyrimidine derivatives as potential inhibitors of HIV-1 reverse transcriptase using palladium-catalysed C-N cross-coupling and nucleophilic aromatic substitution reactions
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Palladium-mediated cross-coupling reactions are used in the successful construction of a small library of flexible heteroatom-linked diarylpyridine target compounds, including pyridines bearing a secondary amide substituent. Heteroatom-linked diarylpyrimidine derivatives bearing a chlorine substituent are prepared by base-catalysed nucleophilic aromatic substitution reactions without the need for palladium catalysis.
- Changunda, Charles R.K.,Rousseau, Amanda L.,Basson, Adriaan E.,Bode, Moira L.
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p. 152 - 170
(2021/05/27)
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- Invariant and Variable Supramolecular Self-Assembly in 6-Substituted Uracil Derivatives: Insights from X-ray Structures and Quantum Chemical Study
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In this study, three new 6-(arylthio)uracil derivatives, namely, 6-(phenylthio)pyrimidine-2,4(1H,3H)-dione (1), C10H8N2O2S; 6-(p-tolylthio)pyrimidine-2,4(1H,3H)-dione (2), C11H10N2O2S; and 6-(3,5-dimethylphenylthio)pyrimidine-2,4(1H,3H)-dione (3), C12H12N2O2S, have been synthesized. Single-crystal structures of these compounds reveal an invariant molecular tape contains alternate R22(8) synthons formed by N-H···O hydrogen bonds in 1 and 3. This alternate hydrogen-bonded pattern disappeared in 2; instead, a new synthon is generated. The lattice energy calculation suggests that the methyl-substituted derivatives (2 and 3) have high stabilization energy than compound 1. The electrostatic potential map reveals the difference in the accepting tendency of the carbonyl oxygen. The Hirshfeld surface and 2D-fingerprint plots analyses demonstrate that the major intermolecular interactions come from H···O contacts in 1, and these contacts were reduced due to the presence of methyl substitutions in 2 and 3. This reduction is compensated by the increase of the same amount of H···H contacts in these structures. Further, the PIXEL energy and DFT calculations at the M06-2X-D3/cc-pVTZ level of theory were used to characterize the dimeric topology formed in structures of 1-3. The intermolecular interaction energies of dimers calculated by the PIXEL method were compared with the B97D3/def2-TZVP level of approximation. Although these molecules' crystal packing is somewhat different, the energy frameworks show similarities on the respective crystal structure's shortest axis. Furthermore, the nature and strength of various noncovalent interactions such as N-H···O, C-H···O/S/π, π···π, and a chalcogen bond of type C-S···O═C were evaluated using the Bader's quantum theory of atoms-in-molecules framework.
- Abdelbaky, Mohammed S. M.,Al-Wahaibi, Lamya H.,Bysani, Sai Ramya Sree,El-Emam, Ali A.,Garcia-Granda, Santiago,Percino, M. Judith,Tawfik, Samar S.,Thamotharan, Subbiah
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p. 3234 - 3250
(2021/05/29)
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- Efficient transposition of the sandmeyer reaction from batch to continuous process
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The transposition of Sandmeyer chlorination from a batch to a safe continuous-flow process was investigated. Our initial approach was to develop a cascade method using flow chemistry which involved the generation of a diazonium salt and its quenching with copper chloride. To achieve this safe continuous process diazotation, a chemometric approach (Simplex method) was used and extrapolated to establish a fully continuous-flow method. The reaction scope was also examined via the synthesis of several (het)aryl chlorides. Validation and scale-up of the process were also performed. A higher productivity was obtained with increased safety.
- D'Attoma, Joseph,Camara, Titi,Brun, Pierre Louis,Robin, Yves,Bostyn, Stéphane,Buron, Frédéric,Routier, Sylvain
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- Diverse combinatorial design, synthesis and in vitro evaluation of new HEPT analogues as potential non-nucleoside HIV-1 reverse transcription inhibitors
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New analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) were synthesized and evaluated for their in vitro activities against HIV-1 in MT-4 cell cultures. Chemical diversity was introduced in 4 of the six positions of the core and the influence of each substituent was studied. This library was built on the basis of a rational diversity analysis with the objective of maximizing diversity and thus, the activity range with a minimum number of synthesized compounds. Among them, 2{1,2,3,1} and 2{1,2,3,4} exhibited the most potent anti-HIV-1 activities (EC50 = 0.015 μg/mL; 0.046 μM, SI >1667) and (EC50 = 0.025 μg/mL; 0.086 μM, SI >1000), respectively, which were about 71-fold and 38-fold more active than the reference compound HEPT (EC50 = 1.01 μg/mL; 3.27 μM, SI >25).
- Puig-De-La-Bellacasa, Raimon,Gimenez, Laura,Pettersson, Sofia,Pascual, Rosalia,Gonzalo, Encarna,Este, Jose A.,Clotet, Bonaventura,Borrell, Jose I.,Teixido, Jordi
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experimental part
p. 159 - 174
(2012/09/05)
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- ANTIMICROBIAL COMPOSITIONS AND METHODS OF USE
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The present invention is directed to compounds of formula I, pharmaceutical compositions comprising the compounds, and methods for making and using the inventive compounds.
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Page/Page column 30
(2008/12/07)
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- Efficient synthesis of novel 6-Phenylthio-2,4-disubstituted pyrimidines
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6-Phenylthio-2,4-disubstituted pyrimidines were prepared in five steps starting from barbituric acid. Reaction of barbituric acid with POCl3 in presence of N, N-dimethylaniline furnishes the 2,4,6-trichloropyrimidine, which on reaction with aq. NaOH under reflux yielded the 6-chlorouracil. Reaction of 6-chlorouracil with thiophenol under basic condition furnishes the 6-phenylthiouracil, which on chlorination using excess POCl3 under reflux yielded the key synthon, 6-phenylthio-2,4-dichloropyrimidine. Aromatic nucleophilic substitution reaction of 6-phenylthio-2,4-dichloropyrimidine with a oxygen nucleophile like sodium benzylate and nitrogen nucleophiles like heterocyclic primary amines, aliphatic primary amines and substituted aromatic primary amines furnished the target compounds, 6-phenylthio-2,4-disubstituted pyrimidines respectively in 40-80% yield.
- Goudgaon,Ch, Upendar Reddy
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body text
p. 443 - 448
(2010/03/04)
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- Process for the preparation of 2,4,6-trichloropyrimidine
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Process for the preparation of 2,4,6-trichloropyrimidine, characterized in that barbituric acid is reacted in a first reaction step with phosphorus oxychloride in the presence or absence of a catalyst, and then, in a second reaction step, is reacted with phosphorus pentachloride or with reactants forming this, in particular phosphorus trichloride and chlorine, at a temperature of 20 to below 80° C.
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- Process for the preparation of polychloropyrimidines
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Polychloropyrimidines, in particular 4,6-dichloropyrimidine and 2,4,6-trichloropyrimidine, are obtained in a particularly advantageous manner from polyhydroxypyrimidines or tautomeric keto compounds thereof and excess phosphorus oxychloride in the presence of a tertiary amine if, in this reaction, a) 0.75 to 1.5 mol of phosphorus trichloride and 0.7 to 1.4 mol of chlorine per equivalent of hydroxyl groups to be replaced by chlorine are added such that an excess of phosphorus trichloride over chlorine is always present and b) phosphorus oxychloride and the polychloropyrimidine prepared are distilled off successively over a column under reduced pressure, or steps a) and b) are carried out in the reverse sequence, phosphorus trichloride also being distilled off before the phosphorus oxychloride in the case of b) after a) and phosphorus oxychloride which has formed again after step a) has been carried out being distilled off in the case of a) after b), and c) a strong base is added to the distillation residue which is then present, and the tertiary amine employed is recovered from this mixture by d) separating off the upper phase and e) purifying it by distillation, or carrying out steps d) and e) in the reverse sequence.
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- Process for preparing 2,4,6-trichloropyrimidine
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Process for preparing 2,4,6-trichloropyrimidine, characterized in that, in a first reaction step, barbituric acid is reacted, optionally in the presence of a catalyst, with phosphorus oxychloride and subsequently, in a second reaction step, with phosphorus pentachloride or with reactants forming the latter, in particular phosphorus trichloride and chlorine.
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- Process for preparing 2-amino-4,6-dichloropyrimidine
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A process comprising reacting 2-amino-4,6-dihydroxy-pyrimidine or its salt with phosphorus oxychloride without the use of a solvent or excessive quantities of phosphorus oxychloride.
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- Flame-resistant polycarbonates containing units deriving from halogenated pyrimidine compounds in their polymer chain
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Flame-resistant thermoplastic branched polycarbonates of high molecular weight are prepared from: (1) a carbonate precursor; (2) at least one dihydroxyaromatic compound of formula: where:, R is a single bond, or a substituted or non-substituted linear or branched C1-C5 alkylene radical, or a group chosen from O, S, SO2 and CO;, X and Y, which may be the same or different, are H or CH3;, m and n, which may be the same or different, are whole numbers from 1 to 4; (3) at last one halogenated pyrimidine compound of formula: where: R2, R3, R4, which may be the same or different, are chlorine or bromine or hydrogen, on condition that at least one is chlorine or bromine;, R1 is chlorine or bromine, or a radical of formula: where Z is NH or S or O; (4) at least one polyfunctional organic compound as branching agent, characterized by possessing at least three equal or different groups chosen from the groups OH, COOH, COCl and SO2Cl.
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- Reactions of 4a-Peroxides and 4a-Pseudobases of N10- and N5-Phenethylflavins
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A number of N5,N10-dialkylisoalloxazines have been synthesized in which either the N5 or the N10 substituent is a meta-substituted phenethyl group.Some of these compounds have been subjected to experiments in order to determine whether an intramolecular transfer of oxygen can occur between the flavin and the phenethyl group (a model of monooxygenase).When in the 1,5-dihydro reduced state, N5-alkyl-substituted isoalloxazines react with molecular oxygen to dive 4a-hydroperoxy derivatives.The hydroperoxides of the N5-ethyl-N10-phenethylflavins provide 4a-pseudobases on spontaneous decomposition.These in turn undergo ring contraction in base to yield 10a-spirohydantoins (Scheme V).The structure of 10a-spirohydantoin (28b) is as established by X-ray crystallographic technique.Spontaneous decomposition of 4a-hydroperoxides is not accompanied by intramolecular oxygen transfer to the phenethyl substituent groups at N10 or N5 (eq.4) 10a-Spirohydantoins may also be obtained by base treatment of 4a-pseudobases that have been prepared separately from the oxidized isoalloxazine (i.e., flavinium cation). 4a-(Allylperoxy)flavin derivatives, obtained by addition of alkyl peroxides to flavinium cations, undergo both spontaneous and photochemocal conversion to 10a-spirohydantoin.These findings are discissed in therms of proposals which have been made for the mechanism of action of flavoenzyme monooxygenases.
- Iwata, Masaki,Bruice, Thomas C.,Carrell, H. L.,Glusker, Jenny P,
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p. 5036 - 5044
(2007/10/02)
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