3764-01-0Relevant articles and documents
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
Arora, Ekta,Bhasin,Mehta,Sharma, Nidhi,Bhasin,Jacob, Claus,Félix, Vítor,Neogi, Subhadip
, p. 316 - 322 (2014)
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.
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
Changunda, Charles R.K.,Rousseau, Amanda L.,Basson, Adriaan E.,Bode, Moira L.
, p. 152 - 170 (2021/05/27)
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.
Invariant and Variable Supramolecular Self-Assembly in 6-Substituted Uracil Derivatives: Insights from X-ray Structures and Quantum Chemical Study
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
, p. 3234 - 3250 (2021/05/29)
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.
Efficient transposition of the sandmeyer reaction from batch to continuous process
D'Attoma, Joseph,Camara, Titi,Brun, Pierre Louis,Robin, Yves,Bostyn, Stéphane,Buron, Frédéric,Routier, Sylvain
, p. 44 - 51 (2017/11/30)
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.
Diverse combinatorial design, synthesis and in vitro evaluation of new HEPT analogues as potential non-nucleoside HIV-1 reverse transcription inhibitors
Puig-De-La-Bellacasa, Raimon,Gimenez, Laura,Pettersson, Sofia,Pascual, Rosalia,Gonzalo, Encarna,Este, Jose A.,Clotet, Bonaventura,Borrell, Jose I.,Teixido, Jordi
experimental part, p. 159 - 174 (2012/09/05)
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).
Efficient synthesis of novel 6-Phenylthio-2,4-disubstituted pyrimidines
Goudgaon,Ch, Upendar Reddy
body text, p. 443 - 448 (2010/03/04)
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.
ANTIMICROBIAL COMPOSITIONS AND METHODS OF USE
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Page/Page column 30, (2008/12/07)
The present invention is directed to compounds of formula I, pharmaceutical compositions comprising the compounds, and methods for making and using the inventive compounds.
Process for the preparation of 2,4,6-trichloropyrimidine
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, (2008/06/13)
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.
Process for preparing 2,4,6-trichloropyrimidine
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, (2008/06/13)
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.
Process for the preparation of polychloropyrimidines
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, (2008/06/13)
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.
