Synthesis of 2-chloro-4,6-di(heteroaryl)pyrimidines
TL;DR: In this article, a practical method for the preparation of 2-chloro-4,6-di(heteroaryl)pyrimidines and their 5-methyl homologues from readily available 2chloropyrimidine and 2chloro -5-methylpyrimidine, respectively, is described.
About: This article is published in Journal of Heterocyclic Chemistry.The article was published on 1990-07-01. It has received 39 citations till now. The article focuses on the topics: Dehydrogenation & Addition reaction.
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TL;DR: A reaction pathway where the lithium amide and zinc diamide present in solution behave synergically was proposed for the deprotonation reaction, taking account of NMR and DFT studies carried out on the basic mixture.
Abstract: Deprotonation of benzoxazole, benzothiazole, benzo[b]thiophene, benzo[b]furan, N-Boc-protected indole and pyrrole, and N-phenylpyrazole using an in situ mixture of ZnCl(2).TMEDA (0.5 equiv) and lithium 2,2,6,6-tetramethylpiperidide (1.5 equiv) in THF at room temperature is described. The reaction was evidenced by trapping with iodine, regioselectively giving the expected functionalized derivatives in 52-73% yields. A mixture of mono- and disubstituted derivatives was obtained starting from thiazole. Cross-coupling reactions of 2-metalated benzo[b]thiophene and benzo[b]furan with heteroaromatic chlorides proved possible under palladium catalysis. A reaction pathway where the lithium amide and zinc diamide present in solution behave synergically was proposed for the deprotonation reaction, taking account of NMR and DFT studies carried out on the basic mixture.
119 citations
TL;DR: In this article, a review of the transition metal-free direct (hetero)arylation reactions of hetero-arenes is presented, which provides a thorough insight into the synthetic and mechanistic aspects of these atom economic and environmentally benign reactions also highlighting their advantages and possible disadvantages compared to conventional methods for the synthesis of arylheteroarenes.
Abstract: In recent years, environmental and economic reasons have motivated the development of transition metal-free carbon-carbon bond forming reactions and some excellent reviews have covered this research area of particular interest for the pharmaceutical industry. However, none of these reviews has been specifically dedicated to summarize and discuss the results achieved in the rapidly growing field of the transition metal-free direct (hetero)arylation reactions of heteroarenes. This review, which covers the literature from 2008 to 2014, aims to provide a thorough insight into the synthetic and mechanistic aspects of these atom economic and environmentally benign reactions also highlighting their advantages and possible disadvantages compared to conventional methods for the synthesis of arylheteroarenes and biheteroaryls via transition metal-catalyzed reactions.
84 citations
01 Jan 2008
TL;DR: The chemistry of pyrimidines and their benzo derivatives, including quinazolines, perimidines, and benzo[gh]perimidine is reviewed in this article, with particular attention paid to work published between 1996 and 2007.
Abstract: The chemistry of pyrimidines and their benzo derivatives, including quinazolines, perimidines and benzo[gh]perimidines is reviewed in this chapter, with particular attention paid to work published between 1996 and 2007, which covers the period since the publication of the second edition of Comprehensive Heterocyclic Chemistry. Fully aromatic, and both partially and fully reduced species are included, and oxo derivatives, including nucleosides and nucleotides are also covered. New routes to the synthesis of many of these heterocycles, as well as modern synthetic techniques, including microwave assisted procedures, are described. Both ring synthesis and substituent modification procedures are covered. The relative reactivity of different substituent groups and/or substituent positions is also discussed, including several examples of selective metal catalyzed cross-coupling reactions. Metal catalyzed amination and amidation reactions are also described. The importance of pyrimidine and quinazoline heterocyclic compounds in biological systems is also emphasized, since two of the four DNA bases are pyrimidine derivatives, and many modern pharmaceutical agents contain either pyrimidine or quinazoline fragments. Several examples of biologically important pyrimidine and quinazoline derivatives are identified, and in this context the signal transduction inhibitor imatinib (gleevec) is highlighted as one of the most significant new pyrimidine derivatives to have been identified in the last few years.
76 citations
Patent•
09 May 2013TL;DR: In this article, the authors present methods of synthesizing heteroaryl compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods for their use for the treatment, prevention, and management of various disorders such as CNS disorders and metabolic disorders, including, but not limited to, e.g., neurological disorders, psychosis, schizophrenia, obesity, and diabetes.
Abstract: Provided herein are heteroaryl compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. In one embodiment, the compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, such as CNS disorders and metabolic disorders, including, but not limited to, e.g., neurological disorders, psychosis, schizophrenia, obesity, and diabetes.
70 citations
TL;DR: In this paper, a series of star and banana-shaped oligomers with a pyrimidine unit as the central core and π-conjugated arms consisting of aromatics bearing electron-donor substituents were synthesized.
60 citations
References
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TL;DR: The results indicate that intercalation and groove-binding modes should be viewed as two potential wells on a continuous energy surface and suggest design strategies for intercalators that can optimally complement DNA base pair propeller twist or that can induce bends in DNA at the interCalation site.
Abstract: Unfused tricyclic aromatic ring systems 1-6 with one or two cationic side chains have been synthesized and their interactions with DNA and synthetic polymers probed with a variety of techniques. Molecular mechanics calculations indicate that the torsional angle between ring planes in the minimum energy conformation of the tricyclic molecules can range from 0 degree to as high as 50 degrees depending on the type of rings and substituents. Viscometric titrations with linear and supercoiled DNA, linear dichroism, and NMR studies indicated that all compounds with torsional angles of approximately 20 degrees or less bind to DNA by intercalation. The more highly twisted intercalators caused significant perturbation of DNA structure. Unfused intercalators with twist angles of approximately 20 degrees have reduced binding constants, suggesting that they could not form an optimum interaction with the DNA base pairs. Unfused intercalators with twist less than 20 degrees formed strong complexes with DNA. The structures of these unfused intercalators are more analogous to typical groove-binding molecules, and an analysis of their interaction with DNA provides a better understanding of the subtle differences between intercalation and groove-binding modes for aromatic cations. The results indicate that intercalation and groove-binding modes should be viewed as two potential wells on a continuous energy surface. The results also suggest design strategies for intercalators that can optimally complement DNA base pair propeller twist or that can induce bends in DNA at the intercalation site.
66 citations
TL;DR: Pyrimidin erhalt man in guter Ausbeute in einer kontinuierlichen Gasphasen-reaktion aus β-funktionellen Carbonylverbindunen as discussed by the authors.
Abstract: Pyrimidin erhalt man in guter Ausbeute in einer kontinuierlichen Gasphasen-reaktion aus β-funktionellen Carbonylverbindunen. Reaktionen an den N-Atomen des Pyrimidins fuhren zu Additionsverbindungen, quartaren Salzen und N-Oxyden. Metallorganische Verbindungen geben mit Pyrimidin 4-substituierte Derivate. Die Bromierung fuhrt in guter Ausbeute zum 5-Brompyrimidin, das zu weiteren Umsetzungen befahigt ist. Es wird ein Uberblick uber die Chemie des Pyrimidins gegeben.
62 citations
61 citations
TL;DR: In this paper, the cyclopentadiene adducts are formed by flash vacuum pyrolysis over the temperature range 460- 570° and detection of the components present in the pyrolysate by mass spectrometry.
Abstract: Oxidation of 2,2,5-trimethyl-5-phenylseleno-1,3-dioxan-4,6-dione with m-chloroperbenzoic acid in methylene chloride gives a solution containing 2,2-dimethylspiro[1,3-dioxan-5,2'-oxiran]-4,6-dione and the unstable 2,2-dimethyl-5-methylene-1,3-dioxan-4,6-dione, which forms stable adducts with cyclohexadiene and cyclopentadiene. Flash vacuum pyrolysis of the cyclopentadiene adduct over the temperature range 460- 570° and detection of the components present in the pyrolysate by mass spectrometry showed that cyclopentadiene, acetone, carbon dioxide and methyleneketene (CH2=C=C=O) are formed; the last breaks down into acetylene and carbon monoxide at higher temperatures (520-570°). Infrared measurements on the pyrolysis products kept at liquid nitrogen temperature showed absorption near 2100 cm-1 which is attributed to methyleneketene. Reaction of the pyrolysate with aniline vapour or methanol vapour yielded acrylanilide and methyl acrylate respectively. Pyrolysis in the absence of trapping agents gave a glassy solid on an uncooled glass surface. This solid is considered to be formed by addition of methyleneketene to 2,2-dimethyl-5-methylene-1,3-dioxan-4,6- dione. Methanolysis of the solid and esterification with diazomethane gave dimethyl 2-methoxycarbonyl-4-methylenepentanedioate.
60 citations
TL;DR: In this paper, the reactivity typical of the individual species is enhanced in open-chain combinations (ArNu)n and (ArE)n, respectively; the opposite situation is mostly encountered in the case of ArNuAE combinations, and the only heterocyclopolyaromatic system yet have been studied in detail, proved surprisingly inclined to undergo monosubstitution reactions.
Abstract: Organometallic linkage of heteroaromatic compounds provided a means of synthesizing complicated combinations of heteroaromatic compounds; not only nucleophilic aromatic substitution, but also “ArCu/ArHal linkage”, “organometallic oxidative linkage”, and “metal amide linkage” have been employed. The heterocyclopolyaromatic compounds are made of one, two, or three kinds of heteroaromatic species as ring members. These syntheses illustrate the construction of heterocycles from large, performed structural units. Competition experiments showed that the reactivity typical of the individual species is enhanced in open-chain combinations (ArNu)n and (ArE)n (ArNu, ArE: nucleo- and electrophilic heteroaromatic systems, respectively); the opposite situation is mostly encountered in the case of ArNuAE combinations.—Cycloocta[1,2-b:4,3-b′5,6-b″:8,7-b‴]tetrathiophene, the only heterocyclopolyaromatic system yet to have been studied in detail, proved surprisingly inclined to undergo monosubstitution reactions.
59 citations