Microwave assisted synthesis and molecular docking studies. Review article chemical characteristics, synthetic methods, and biological potential of quinazoline and quinazolinone derivatives mohammadasif department of pharmacy, grd pg institute of management and technology, dehradun, uttarakhand, india. Owing to the significant biological activities, quinazoline derivatives have drawn more and more attention in the synthesis and bioactivities research. Wo2008125867a2 process for the preparation of gefitinib. The niementowski quinazoline synthesis is the chemical reaction of anthranilic acids with amides to form 4oxo3,4dihydroquinazolines 3hquinazolin4ones. Pdf new pyrido3,4gquinazoline derivatives as clk1 and. Various methods were reported for the synthesis of oxoquinazolines. The synergy of combined use of dmso and bronsted acid. Implication of quinazoline 43hones in medicinal chemistry. Synthesis of nheterocycles benzofused nheterocycles synthesis of quinazolines. Niementowski quinoline synthesis wikipedia niementowski quinazoline synthesis wikipedia. Niementowski was een voornaam scheikundige in zijn tijd.
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 last two decades have brought new approaches to the synthesis of pyrrolo1,2a quinazoline framework and thus their. Quinazoline is an organic compound with the formula c 8 h 6 n 2. The niementowski quinoline synthesis is the chemical reaction of anthranilic acids and ketones or aldehydes to form. An efficient construction of quinazolin43hones under. This strategy allows the use of both primary as well as secondary. Rutaecarpine figure 1 shows a variety of pharmacological activities including. The quinazoline group could be partassembled via a number of reported 43hquinazolinone syntheses24,25 such as the niementowski reaction. It is an aromatic heterocycle with a bicyclic structure consisting of a two fused sixmembered aromatic rings, a benzene ring and a pyrimidine ring. Biological activities of quinazolines diverse biological activities were attributed to compounds possessing a quinazoline ring system. In 1903, siegmund gabriel reported the synthesis of the parent quinazoline from onitrobenzylamine, which was reduced with hydrogen iodide and red phosphorus to 2aminobenzylamine. Quinazoline and condensed quinazoline exhibit potent central nervous system cns activities like antianxiety, analgesic, antiinflammatory 10and anticonvulsant 11. 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.
A nickelcatalyzed sequential dehydrogenation and condensation process enables a sustainable synthesis of a wide range of polysubstituted quinolines from. The use of oxygen as an oxidant combined with the transitionmetal, additive and solvent. There is also provided a process for preparing a compound of formula xl comprising converting a compound of formula x to the compound xl. Page 98 general papers arkivoc 2005 xiii 98108 niementowski reaction. Using 2amino6fluorobenzonitrile, an s n ar reaction with a protected amino alcohol afforded the key starting material 1a in a modest yield. Quinazolinone and its derivatives possess a large class of biologically active. Niementowski synthesis an overview sciencedirect topics. This method offers the advantages of proceeding in neutral conditions, giving high to excellent isolated yields 8392% for niementowski synthesis with easy workup procedure. Desai department of chemistry, veer narmad south gujarat university, surat395007, india email.
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. Niementowski quinazoline synthesis, cheminform on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. A niementowskitype cyclisation of 1a in a mixture of formic and sulfuric acid at reflux afforded 2a in sufficient yield to attempt the. Pdf pyrrolo1,2aquinazolines have raised some interest as.
The pasty mass obtained was diluted with 50ml of water and treated with aqueous sodium bicarbonate solution. A transitionmetalfree synthesis of quinazolin4ones by cs2co3promoted snar reaction of orthofluorobenzamides with amides followed by cyclization in dimethyl sulfoxide has been developed. Review article chemical characteristics, synthetic methods. Chemical characteristics, synthetic methods, and biological. Stefan niementowski zjovkva, 4 augustus 1866 warschau, juli 1925 was een pools scheikundige.
Quinazoline derivatives with antitubercular activity. Quinazoline is a organic compound with the formula c 8 h 6 n 2. An expedient synthesis of oxazepino and oxazocino quinazolines. Cn104016929b a kind of method of synthesis quinazoline4. Quinazolin4ones with 2, 3disubstitution is reported to. Reacting the catalyzer used is mantoquita, can be cuprous iodide, cuprous chloride, red copper oxide. Niementowski quinazolinone synthesis, named after its discoverer. Compared to the conventional conditions, this new method shows the advantages of a good substrate tolerance, and a clean and rapid conversion. 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. Synthesis of some new quinazolinone derivatives and.
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. Efficient niementowski synthesis of novel 1 3,10,12tetra. Synthesis of quinazoline compounds various methods were reported for the synthesis of oxoquinazolines. Also known as 1,3diazanaphthalene, quinazoline received its name from being an aza derivative of quinoline.
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. The thermal transformation of an anthranilic acid into 4. Acaaddemmiicc ss ciieenncess international journal of. 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. 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. Research has demonstrated that the niementowski quinazoline synthesis could be employed for. A simple and efficient approach for the synthesis of 2. Stephen j baker, steven m firestine, david smithrud, frank salinas, stephen j benkovic. The niementowski quinazoline synthesis is the chemical reaction of anthranilic acids with amides to form 4oxo3, 4dihydroquinazolines. The usual synthesis of quinazolines make use of an odisubstituted benzene structure from which the quinozoline. A highly employed method for 43hquinazolinone synthesis is based on acylation of anthranilic acid with acyl chloride. 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.
It is an aromatic heterocycle with a bicyclic structure consisting of two fused sixmembered aromatic rings, a benzene ring and a pyrimidine ring. Rutaecarpine type alkaloids constitute an important class of indolopyridoquinazolinone heterocycles, which belong to the subgroup of quinazoline type alkaloid, belonging to rutaceae family 1. Microwaves in drug discovery and multistep synthesis. When the effervescence ceased, the precipitate obtained was filtered and washed with water. Abstract the thermal transformation of an anthranilic acid into 4.
Synthesis of some novel quinazoline derivatives having. It has been applied to substitute quinozolines, for the preparation of 6,7dimethoxy quinazoline through the intermediate 6nitroveratradehyde. Pyrrolo1,2aquinazolines are tricyclic compounds with great potential and combine the. The quinazoline group could be partassembled via a number of reported 43hquinazolinone syntheses24, 25 such as the niementowski reaction. A sustainable synthesis of quinazoline and 2aminoquinoline via acceptorless dehydrogenative annulation is catalyzed by earthabundant welldefined manganese complexes bearing nns ligands.
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. These named traditional reactions were performed using microwave assisted synthesis on samsung domestic microwave, 1. The highly accelerated niementowski synthesis of quinazolin43hone and quinazolin2,4dione derivatives under microwave irradiation is reported. Synthesis, biological evaluation and molecular docking of. The original conditions for this transformation, however, proved somewhat limiting as they required extended heating at. Synthesis and reactivity of some novel quinazoline. It is a light yellow crystalline solid that is soluble in water. Reactions in the presence of solvent and solventfree synthesis can be realised. Syhthesis following methods were reported for the synthesis of oxoquinazolines. The current reaction is a variant of the classical niementowski quinazoline synthesis, which involved the cyclocondensation of an nalkylamide with anthranilic acid 11.
Subsequent ring closure with acetic anhydride afford corresponding 1,3benzoxazin4one benzoxazinone which will be treated with different amines. The highly accelerated niementowski synthesis of quinazolin43hone and. Media in category quinazolines the following 50 files are in this category, out of 50 total. 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. 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. Synthesis of two bifunctional ligands for the quest threehybrid system. Methyl, ethyl, isopropyl, benzyl, tbutyl and phenyl magnesium halides and phenyl lithium also add across the 3, 4 double bond to give the corresponding 4 substituted 3, 4dihydroquinazolines. Synthesis of some novel quinazoline derivatives having anticancer activity. Reacting the catalyzer used is mantoquita, can be cuprous iodide, cuprous chloride, red copper oxide, cuprous acetate etc. Pdf most of the drugs and pharmacologically relevant molecules possess heterocyclic.