The thermal transformation of an anthranilic acid into 4. Reactions in the presence of solvent and solventfree synthesis can be realised. There is provided a compound of formula iii, and a process for preparing a compound of formula v comprising converting a compound of formula iii to the compound v, wherein x is fluoro, chloro, bromo or iodo. Pyrrolo1,2aquinazolines are tricyclic compounds with great potential and combine the. The invention provides a kind of method of synthesis quinazoline 4 3hone heterogeneous ring compound, reaction expression is as follows, wherein r 1 for substituting group, can be h, f, no 2, alkyl, or alkoxyl group. The highly accelerated niementowski synthesis of quinazolin43hone and quinazolin2,4dione derivatives under microwave irradiation is reported. Niementowski quinazoline synthesis, cheminform on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. The niementowski quinazoline synthesis is the chemical reaction of anthranilic acids with amides to form 4oxo3,4dihydroquinazolines 3hquinazolin4ones. Synthesis and reactivity of some novel quinazoline.
Stephen j baker, steven m firestine, david smithrud, frank salinas, stephen j benkovic. The present procedure can provide efficient synthetic methods for the formation of both 2substituted and 2,3disubstituted quinazolin4one rings depending on the use of easily available starting. It has been applied to substitute quinozolines, for the preparation of 6,7dimethoxy quinazoline through the intermediate 6nitroveratradehyde. A niementowskitype cyclisation of 1a in a mixture of formic and sulfuric acid at reflux afforded 2a in sufficient yield to attempt the. Rutaecarpine type alkaloids constitute an important class of indolopyridoquinazolinone heterocycles, which belong to the subgroup of quinazoline type alkaloid, belonging to rutaceae family 1. Acaaddemmiicc ss ciieenncess international journal of. Syhthesis following methods were reported for the synthesis of oxoquinazolines. Implication of quinazoline 43hones in medicinal chemistry. Subsequent ring closure with acetic anhydride afford corresponding 1,3benzoxazin4one benzoxazinone which will be treated with different amines. Page 98 general papers arkivoc 2005 xiii 98108 niementowski reaction. Cn104016929b a kind of method of synthesis quinazoline4. Research has demonstrated that the niementowski quinazoline synthesis could be employed for.
This method offers the advantages of proceeding in neutral conditions, giving high to excellent isolated yields 8392% for niementowski synthesis with easy workup procedure. Niementowski synthesis an overview sciencedirect topics. Review article chemical characteristics, synthetic methods. These named traditional reactions were performed using microwave assisted synthesis on samsung domestic microwave, 1. Microwaves in drug discovery and multistep synthesis.
The synergy of combined use of dmso and bronsted acid. This strategy allows the use of both primary as well as secondary. The last two decades have brought new approaches to the synthesis of pyrrolo1,2a quinazoline framework and thus their. The highly accelerated niementowski synthesis of quinazolin43hone and. Rutaecarpine figure 1 shows a variety of pharmacological activities including. Compared to the conventional conditions, this new method shows the advantages of a good substrate tolerance, and a clean and rapid conversion. The first known synthesis of quinazoline was reported in 1895 by august bischler and lang through the decarboxylation of the 2carboxy derivative quinazoline 2carboxylic acid. Synthesis of some novel quinazoline derivatives having. A new rapid and versatile approach using ionic liquiddmso as a chemical reagent for the synthesis of fused heterocyclic compounds in a highly efficient way is described. Chemical characteristics, synthetic methods, and biological.
An expedient synthesis of oxazepino and oxazocino quinazolines. Media in category quinazolines the following 50 files are in this category, out of 50 total. Quinazolinone and its derivatives possess a large class of biologically active. Pdf new pyrido3,4gquinazoline derivatives as clk1 and. There is also provided a process for preparing a compound of formula xl comprising converting a compound of formula x to the compound xl. Synthesis of quinazoline compounds various methods were reported for the synthesis of oxoquinazolines. A highly employed method for 43hquinazolinone synthesis is based on acylation of anthranilic acid with acyl chloride. Cedira nib azd2171 shown in figure 1e, on the other hand, is an example of an nunsubstituted indoleether quinazoline hybrid that has been found to be a highly potent, orally bioavailable and selective vascular endothelial growth factor receptor vegfr inhibitor for the treatment of cancer,14. The pasty mass obtained was diluted with 50ml of water and treated with aqueous sodium bicarbonate solution. Also known as 1,3diazanaphthalene, quinazoline received its name from being an aza derivative of quinoline. Wo2008125867a2 process for the preparation of gefitinib.
Owing to the significant biological activities, quinazoline derivatives have drawn more and more attention in the synthesis and bioactivities research. In 1903, siegmund gabriel reported the synthesis of the parent quinazoline from onitrobenzylamine, which was reduced with hydrogen iodide and red phosphorus to 2aminobenzylamine. It is an aromatic heterocycle with a bicyclic structure consisting of two fused sixmembered aromatic rings, a benzene ring and a pyrimidine ring, it is a light yellow crystalline solid that is soluble in water. Quinazolin4ones with 2, 3disubstitution is reported to. Reacting the catalyzer used is mantoquita, can be cuprous iodide, cuprous chloride, red copper oxide.
A simple and efficient approach for the synthesis of 2. The quinazoline group could be partassembled via a number of reported 43hquinazolinone syntheses24, 25 such as the niementowski reaction. Using 2amino6fluorobenzonitrile, an s n ar reaction with a protected amino alcohol afforded the key starting material 1a in a modest yield. Desai department of chemistry, veer narmad south gujarat university, surat395007, india email. Abstract the thermal transformation of an anthranilic acid into 4. An efficient construction of quinazolin43hones under. Quinazoline and condensed quinazoline exhibit potent central nervous system cns activities like antianxiety, analgesic, antiinflammatory 10and anticonvulsant 11. It is a light yellow crystalline solid that is soluble in water.
The niementowski quinoline synthesis is the chemical reaction of anthranilic acids and ketones or aldehydes to form. Biological activities of quinazolines diverse biological activities were attributed to compounds possessing a quinazoline ring system. It is an aromatic heterocycle with a bicyclic structure consisting of two fused sixmembered aromatic rings, a benzene ring and a pyrimidine ring. Niementowski quinazolinone synthesis, named after its discoverer. Stefan niementowski zjovkva, 4 augustus 1866 warschau, juli 1925 was een pools scheikundige. A sustainable synthesis of quinazoline and 2aminoquinoline via acceptorless dehydrogenative annulation is catalyzed by earthabundant welldefined manganese complexes bearing nns ligands. It is an aromatic heterocycle with a bicyclic structure consisting of a two fused sixmembered aromatic rings, a benzene ring and a pyrimidine ring. Synthesis, biological evaluation and molecular docking of. A transitionmetalfree synthesis of quinazolin4ones by cs2co3promoted snar reaction of orthofluorobenzamides with amides followed by cyclization in dimethyl sulfoxide has been developed.
The quinazoline group could be partassembled via a number of reported 43hquinazolinone syntheses24,25 such as the niementowski reaction. A nickelcatalyzed sequential dehydrogenation and condensation process enables a sustainable synthesis of a wide range of polysubstituted quinolines from. Results and discussion the first step in this reaction involved the synthesis of pyrido2,3dpyrimidin4ones 2 which took place by reacting 2amino4,6disubstitutednicotinonitriles 1 with formic acid. Introduction 4 microwave irrigation for synthesis quinazolinone modifiation of niementowski reaction were carried out by microwave assisted synthesis,39 an equimolar amount of the reactants were mixed and irradiated under microwaves40 to provide the yield. The original conditions for this transformation, however, proved somewhat limiting as they required extended heating at. Various methods were reported for the synthesis of oxoquinazolines. Quinazoline is an organic compound with the formula c 8 h 6 n 2. The invention provides a kind of method of synthesis quinazoline4 3hone heterogeneous ring compound, reaction expression is as follows, wherein r 1 for substituting group, can be h, f, no 2, alkyl, or alkoxyl group. Molecular iodine catalyses a benzylic sp 3 ch bond amination of 2aminobenzaldehydes and 2aminobenzophenones with benzylamines to provide quinazolines in very good yields.
The niementowski quinazoline synthesis is the chemical reaction of anthranilic acids with amides to form 4oxo3, 4dihydroquinazolines. Quinazoline and quinazolinone are reported for their diversified biological activities and compounds with different substitutions bring together to knowledge of a target with understanding of the molecule types that might interact with the target receptors. When the effervescence ceased, the precipitate obtained was filtered and washed with water. Quinazoline derivatives with antitubercular activity. Niementowski was een voornaam scheikundige in zijn tijd. Here we describe the synthesis of new pyrido3,4g quinazoline derivatives and the evaluation of the inhibitory potencies of these compounds toward cdk5, ck1, gsk3, clk1 and dyrk1a.
Niementowski quinoline synthesis wikipedia niementowski quinazoline synthesis wikipedia. Efficient niementowski synthesis of novel 1 3,10,12tetra. Microwave assisted synthesis and molecular docking studies. Quinazoline is a organic compound with the formula c 8 h 6 n 2. Synthesis of some novel quinazoline derivatives having anticancer activity. The use of oxygen as an oxidant combined with the transitionmetal, additive and solvent. Pdf most of the drugs and pharmacologically relevant molecules possess heterocyclic. Synthesis of some new quinazolinone derivatives and. Pdf pyrrolo1,2aquinazolines have raised some interest as. The usual synthesis of quinazolines make use of an odisubstituted benzene structure from which the quinozoline. The current reaction is a variant of the classical niementowski quinazoline synthesis, which involved the cyclocondensation of an nalkylamide with anthranilic acid 11. Synthesis of two bifunctional ligands for the quest threehybrid system.
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