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A K2S2O8-promoted oxidative tandem cyclization of primary alcohols with 2-aminobenzamides to synthesize quinazolinones was successfully achieved under undivided electrolytic conditions without a transition metal and base. The key feature of this protocol is the utilization of K2S2O8 as an inexpensive and easy-to-handle radical surrogate that can effectively promote the reaction via a simple procedure, leading to the formation of nitrogen heterocycles via direct oxidative cyclization at room temperature in a one-pot procedure under constant current. Owing to the use of continuous-flow electrochemical setups, this green, mild and practical electrosynthesis features high efficiency and excellent functional group tolerance and is easy to scale up.

The development of protocols for synthesizing quinazolinones using biocompatible catalysts in aqueous medium will help to resolve the difficulties of using green and sustainable chemistry for their synthesis. Herein, using I2 in coordination with electrochemical synthesis induced a C-H oxidation reaction which is reported when using water as the environmentally friendly solvent to access a broad range of quinazolinones at room temperature. The reaction mechanism strongly showed that I2 cooperates electrochemically promoted the oxidation of alcohols, then effectively cyclizing amides to various quinazolinones.

Microwave-mediated N-arylation of 4-chloroquinazolines in THF/H2O rapidly and efficiently afforded a library of novel 6-halo-2- phenyl-substituted 4-anilinoquinazolines. The methodology was compatible with numerous ortho-, meta-, and para-substituted N-methylanilines as well as substituted anilines and furnished the corresponding 4-anilinoquinazolines in good yields. Preliminary screening of the synthesized compounds against tumor cells (HCT-116 and T98G) showed promising antiproliferative properties.

A visible-light-driven photoredox-catalyzed nonaqueous oxidative C-N cleavage of N,N-dibenzylanilines to 2° amides is reported. Further, we have applied this protocol on 2-(dibenzylamino)benzamide to afford quinazolinones with (NH4)2S2O8 as an additive. Mechanistic studies imply that the reaction might undergo in situ generation of α-amino radical to imine by C-N bond cleavage followed by the addition of superoxide ion to form amides.

In the present work, we have developed a novel and environmentally friendly method for the synthesis of quinazolinones using fluorescein as a photocatalyst via a condensation reaction of o-aminobenzamides and aldehydes under visible light irradiation. In this protocol, neither toxic oxidants nor transition-metal catalysts were needed, and a series of quinazolinones could be obtained in high efficiencies. In addition, this reaction can be extended to gram levels and has a large potential of wide application in future industrialization.

A general metal-free oxidative cyclization route was developed to synthesize quinazolinones under visible light. A series of substituted 2-aminobenzamides were reacted with aldehydes or ketones to produce the desired quinazolinones in good yields. Most importantly, the reaction did not require excess oxidant or high temperatures.

Three-component couplings have been realized for efficiently constructing various nitrogen-containing skeletons via C-H activation, where difluorocyclopropenes have been first identified as coupling partners. Many substrates including sp2 and sp3 C-H substrates were well tolerated, furnishing the corresponding products in good yields. Furthermore, a catalyst-dependent reaction was also developed, enabling divergent construction of two different frameworks. The application value of these reactions was demonstrated in gram-scale experiments with as little as 1 mol % catalyst.

The invention discloses a green synthesis method and application of a quinazolinone compound. The structure of the quinazolinone compound is shown as a formula I, the preparation method comprises the following steps: by taking an R1-substituted hexafluoroisopropanol 2-aminobenzoate compound and R2-substituted amidine hydrochloride as raw materials, alkali as an additive, and acetonitrile, dioxane, tetrahydrofuran, DMSO (dimethylsulfoxide) or DMF (dimethyl formamide) as a solvent, reacting at normal temperature to generate the quinazolinone compound shown in the formula I. The method provided by the invention has the advantages of no need of heating, no need of using a metal catalyst, mild reaction conditions, no generation of by-products in the reaction, 100% conversion of the raw materials and simple post-treatment process, can be used to obtain the high-purity quinazolinone product, and is a simple green synthesis method; and the quinazolinone compound has high antitumor activity, and can be used for preparing antitumor drugs.

Herein, we report a bioinspired catalytic system for the one-pot cascade oxidation of a native primary amine and anin situgenerated non-native secondary amine. The catalyst consists of ano-quinone cofactor phd (1,10-phenanthroline-5,6-dione) and a copper ion and operates under ambient air conditions. Quinazolin-4(3H)-ones, which are common pharmacophores present in numerous pharmaceuticals and bioactive compounds, were synthesized in high yields. A detailed kinetic and mechanistic study elucidates the role of the catalyst in the multi-step oxidative cascade reaction.

An efficient and straightforward approach has been demonstrated for 2-aryl quinazolinones synthesis from 2-iodoacetanilides using ammonium carbamate/ammonium carbonate and oxalic acid under heterogeneous Pd/C catalyzed conditions. Herein, we have carried

In this work, ruthenium(II)-catalyzed C?C/C?N annulation of 2-arylquinazolinones with vinylene carbonate is reported to synthesize fused quinazolinones. This catalytic system tolerates a wide range of substrates with excellent functional-group compatibility. In this transformation, the vinylene carbonate acts as an ethynol surrogate without any external oxidant involved. Furthermore, preliminary mechanistic studies were conducted, and a plausible catalytic cycle was also proposed.

Herein, we describe the novel reactivity of hexafluoroisopropyl 2-aminobenzoates. The metal-free synthesis of 1,4-benzodiazepines and quinazolinones from hexafluoroisopropyl 2-aminobenzoates has been developed at room temperature. These procedures feature

A linear-organic-polymer-supported iridium complex Cp*Ir@P4VP, which is designed and synthesized by the coordinative immobilization of [Cp*IrCl2]2 on poly(4-vinylpyridine), was proven to be an efficient heterogeneous autotandem catalyst for synthesizing quinazolinones via selective hydration/acceptorless dehydrogenative coupling from o-aminobenzonitriles. Furthermore, the synthesized catalyst was recycled five times without an obvious decrease in the catalytic activity.

An efficient and practical electrochemically catalyzed transition metal-free process for the synthesis of substituted quinazolinones from simple and readily availableo-aminobenzonitriles and aldehydes in water has been accomplished. I2/base and water play an unprecedented and vital role in the reaction. By electrochemically catalysed hydrolysis ofo-aminobenzonitriles, the synthesis of quinazolinones with benzaldehyde was first proposed. The synthetic utility of this method was demonstrated by gram-scale operation, as well as the preparation of bioactiveN-(2,5-dichlorophenyl)-6-(2,2,2-trifluoroethoxy) pteridin-4-amine, which enables straightforward, practical and environmentally benign quinazolinone formation.

The invention discloses a preparation method of a quinazolinone derivative, wherein the preparation method comprises the following steps: dissolving an anthranilonitrile compound represented by a formula I and an aldehyde represented by a formula II in a

Quinazolines and 1,2,4-triazoles are important class of nitrogen containing heterocyclic compounds having immense biological importance. From the literature review, pharmacokinetic properties of a drug can be modified or enhanced by building a triazole moiety into a compound like quinazoline. Therefore, the study of new hybrid systems which combines triazole system with quinazoline is still seemed warranted. In the present study, a sequence of novel 1,2,4-triazole derivatives containing quinazolinyl moiety were designed, synthesized and screened for their in vitro anticancer activity. Thirteen new hybrids are synthesized from readily accessible 5-bromoanthranilic acid. All the hybrid compounds were well explicated by IR,1H,13C NMR, and mass spectral data. Out of 13, some of the compounds manifested moderate to good antiproliferative activity against two cancer cell lines (HepG2 and MCF-7). Remarkably, compounds 8A, 16H and 16K displayed potent activity (14-49 μM) on both HepG2 (liver carcinoma) and MCF-7 (breast cancer) cell lines whereas compounds 8B, 8F, 16L, and 15 displayed substantial activity against HepG2 cancer cell line (34-65 μM). Synthetic approach described here is very simple and can be used for the syntheses of related compounds library which is useful for the exploration of further biological activities and is currently underway in our laboratory.

The method comprises the following steps: taking the compound of the formula (I) and the compound of the formula (II) as a solvent, adding a photocatalyst and a phase transfer catalyst to obtain the quinazolinone compound (III) under the condition of alkali and visible light. Compared with the prior art, the method not only can be applied to a large amount of functional groups, has high yield, few byproducts, and is simple and safe to operate, low in cost and environment-friendly. Wherein R is hydrogen or R1 Is H, C1 - C4 alkoxy, halogen or nitro; R2 Is H, substituted or unsubstituted phenyl, 2 - pyridyl or 2 - thienyl; the substituted phenyl is phenyl substituted by amino, nitro, C1 - C4 alkyl or C1 - C4 alkoxy. (by machine translation)

The invention discloses a method for synthesizing a quinazolinone compound by photo-catalyzing alcohol oxidation in a water phase, which comprises the following steps: by taking a compound shown as aformula (I) and a compound shown as a formula (II) as raw materials and water as a solvent, adding a visible light catalyst, and reacting under the conditions of alkali and visible light to obtain a quinazolinone compound (III). The method for preparing the quinazolinone compound is environmentally friendly, easy and convenient to operate, safe, cheap and efficient. Compared with the prior art, the method is applicable to a large number of functional groups, high in yield, few in byproducts, simple and safe to operate, low in cost and environment-friendly; wherein R1 is H, C1-C4 alkoxy, halogen or nitro; and R2 is H, substituted or unsubstituted phenyl, 2-pyridyl, 2-thienyl or 5-methylfuryl.

An efficient approach has been developed for the construction of quinazolin-4(3 H)-ones by the selective anodic dehydrogenative oxidation/cyclization of benzylic chlorides and 2-aminobenzamides. The method features acceptor-free and metal-free dehydrogenation of amines to imines; a subsequent intermolecular addition provides the products in moderate to good yields.

Neurotensin receptor 1 (NTR1) is a G protein coupled receptor that is widely expressed throughout the central nervous system where it acts as a neuromodulator. Neurotensin receptors have been implicated in a wide variety of CNS disorders, but despite extensive efforts to develop small molecule ligands there are few reports of such compounds. Herein we describe the optimization of a quinazoline based lead to give 18 (SBI-553), a potent and brain penetrant NTR1 allosteric modulator.

A convenient and efficient method has emerged for the one-pot synthesis of substituted quinazolin-4(3H)ones and nonaromatic alkaloids. 2-Substituted quinazolin-4(3H)-ones, 2,3-disubstituted quinazolin-4(3H)-ones, and 2,3-dihydroquinazolin-4(1H)-ones were obtained at yields of 46% to 95% by a one-pot reaction of N-(2-aminobenzoyl) benzotriazoles with amines and orthoesters or aldehydes under catalyst-free conditions.

An efficient and convenient strategy for the synthesis of diversely substituted quinazolinones from o-carbamoyl/cyano aniline and aryl iodides using oxalic acid as a CO source under polystyrene supported palladium (Pd?PS) nanoparticles (NPs) catalyzed con

Herein, we report chemoselective trifluoroethylation routes of unmasked 2-arylquinazolin-4(3H)-ones using mesityl(2,2,2-trifluoroethyl)iodonium triflate at room temperature. Homologous C-, O-, and N-functionalized subclasses are accessed in a straightforward manner with a wide substrate scope. These chemoselective branching events are driven by Pd-catalyzed ortho-selective C-H activation at the pendant aryl ring and base-promoted reactivity modulation of the amide group, leveraging the intrinsic directing capability and competing pronucleophilicity of the quinazolin-4(3H)-one framework. Furthermore, outstanding photostability of the quinazolin-4(3H)-one family associated with nonradiative decay is presented.

The invention discloses a method for synthesizing a quinazolinone derivative. According to the method for synthesizing the quinazolinone derivative,anthranilonitrile compounds and primary alcohols areused as raw materials, 2,2,6,6-tetramethylpiperidine ox

A mild and atom-economic method was developed for direct and efficient synthesis of quinazolinones through a transition-metal-free aerobic oxidative cascade annulation reaction of widely available o-aminoarylnitriles and alcohols. Air could be employed as an effective oxidant under mild conditions, generating water as the only byproduct. Possibly owing to the “cesium effect”, the water-soluble base CsOH was found to be crucial in all key steps of the reaction mechanism. Because a wide range of substrates can be used to prepare substituted quinazolinones without contamination by transition-metal residues, this method may be of interest for application in pharmaceutical synthesis. Possible reaction paths were also proposed according to control reactions.

The invention discloses a quinazolinone of heterocyclic compound synthetic method. In under the action of the water-soluble alkali using air as the oxidizing agent, and ortho-amino alcohol oxidation fragrant nitrile compound - cyclized - oxidation of high efficiency series reaction one-step preparation quinazolinone of heterocyclic compound synthetic method. This method does not need the use of expensive transition metal catalyst and ligand, but the use of water-soluble alkali as promoter, the alkali can be removed by water washing mode is convenient, so product transition metal-free residue, is suitable as a pharmaceutical preparation of the precursor, the method condition is simple, easy to operate, low requirement for the device, and can utilizes air as economic security green oxidizing agent, water-soluble alkali as promoter, the only by-product is water, atom economical high, has a certain research and industrial application prospect.

Microwave-assisted copper-catalyzed cascade reactions between 2-halobenzoic acids and amidines to synthesize quinazolinone derivatives in water are reported. A variety of target products were obtained in good to excellent yields up to 94%. Its application was performed by the synthesis of 4-(1H-benzo[d]imidazol-2-ylthio)-6-methoxypteridine, which displayed significant anti-proliferation effect.

The invention discloses a method for synthesizing quinazolinone method, which comprises the following steps: in the reaction container, adding O amino-benzene nitrile, transition metal catalyst, oxime, solvent xylene; the reaction mixture in the 60 - 70 °

Here we report a set of direct functionalization methods of unmasked 2-phenylquinazolin-4(3H)-ones, a privileged alkaloid core, without the installation/removal event of protecting groups or exogenous coordinating moieties. Divergent pathways were modulated with transition-metal catalysts by suppressing competitive reactivities, leading to N-arylation, annulative π-extension, or C-H fluorination.

A highly efficient, iron nitrate/TEMPO-catalyzed approach for the synthesis of quinazolinones has been achieved via a one-pot, tandem aerobic oxidative cyclization of primary alcohols with 2-aminobenzamides. This practical reaction tolerates a broad scope of substrates and could afford a variety of desirable products in good to excellent yields with air as the terminal green oxidant. Thus, the present synthetic protocol provides an efficient and concise strategy for the synthesis of quinazolinones.

A synergetic tert-butyl hydroperoxide/K3PO4-promoted oxidative cyclization has been developed for the facile synthesis of various functionalized quinazolin-4(3H)-ones from commercially available isatins and amidine hydrochlorides at room temperature. The synthetic utility of this strategy was illustrated by the convenient synthesis of tryptanthrin derivatives via a self-dimerization of isatins under the same conditions.

A new strategy for the direct synthesis of quinazolinones from o-aminobenzonitriles was proposed and accomplished. In the presence of [Cp?IrCl2]2 (Cp?=pentamethylcyclopentadienyl), a variety of desirable products was obtained easily through the one-pot sequential selective hydration/condensation/acceptorless dehydrogenation. This protocol is highly attractive because it uses readily available starting materials, has a high atom efficiency, good to excellent yields, and minimal consumption of chemicals and energy. Notably, this research exhibited new potential for the development of transition-metal-catalyzed one-pot sequential reactions that involve acceptorless dehydrogenation.

A novel copper-catalyzed synthesis of quinazolinones from easily available 2-arylindoles and amines or ammoniums has been developed, which provided various quinazolinones in up to 99% yields for 43 examples. This strategy features tolerance of a wide range of functional groups, easily available starting materials, simple operation, mild reaction conditions, and environmental friendliness.

The reaction of N-aryl benzamidines 1a, 1b, 1c, 1d, 1e, 1f, 1g, 1h, 1i, 1j, 1k, 1l, 1m, 1n with diphenyl carbonate 2a or ethyl phenyl carbonate 2b synthesized 2-arylquinazolin-4(3H)-ones 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h, 3i, 3j, 3k, 3l, 3m, 3n in simple and

A series of biologically important 4(3H)-quinazolinones were readily synthesized in good to excellent yields from 2-amino-N-methoxybenzamides and aldehydes via a cascade reaction consisting of AcOH-promoted cyclocondensation and elimination. The current m

A one-pot tandem procedure is described for the synthesis of quinazolinones from benzyl halides or benzyl alcohols and ortho-aminobenzamides leading to the production of quinazolinones with high yields under mild conditions in DMSO without requiring an additional oxidant. According to the current method benzyl chlorides, benzyl bromides and benzyl alcohols bearing a range of substituents are suitable substrates.

Novel 3-[4-(6-bromo-4-oxo-2-phenylquinazolin-3(4H)-yl)benzoyl]-2- substituted-1,3,4-thiazolium-5-thiolate 7(a-j) and 3-{4-[(6-bromo-2- phenylquinazolin-4-yl)amino] benzoyl}-2-substituted-1,3,4-thiadiazolium-5- thiolate 12(a-j) were synthesized from 6-brom

Quinazoline derivatives are reported to have anti-inflammatory, analgesic, antibacterial, and anticancer activities. The incorporation of "OCH 2CONH2" (oxymethylcarbamide) at 4th position of the quinazoline ring was found

Two series of some new 2,4,6-trisubstituted-quinazoline derivatives were prepared and screened for their analgesic, anti-inflammatory activity and acute toxicity. Four compounds were more potent analgesic agents than the reference drug Indomethacin and thirteen compounds showed significant anti-inflammatory activity. Seven compounds showed combined ability to inhibit both pain and inflammation. Compounds tested for acute toxicity showed no toxic symptoms or mortality rates 24 h post-administration implying their good safety margin.

Small molecule compounds and compositions containing said compounds useful for inhibiting signaling by certain Toll-like receptors (TLRs), particularly TLR9, are provided. The compounds and compositions can be used to inhibit immune responses, including unwanted immune responses in particular. Compounds, compositions, and methods are provided to treat a variety of conditions involving unwanted immune responses, including for example autoimmune disease, inflammation, transplant rejection, and sepsis.

A green, rapid, and efficient method was developed for synthesizing quinazolinone derivatives from substituted 2-halobenzoic acids and amidines via microwave-assisted iron-catalyzed cyclization with or without ligand in water (methods A and B) or DMF (methods C and D). With these methods, moderate to high yields of the desired products can be obtained from even inactive substrates, such as guanidines. To the best of our knowledge, this is the first report on the synthesis of N-heterocyclic compounds by iron-catalyzed C-N coupling in aqueous media. The Royal Society of Chemistry 2009.

A series of novel 2,4,6-trisubstituted quinazoline derivatives 6 have been synthesized from anthranilic acids 1 in five steps via benzoxazinones 2, N-benzoyl benzamides 3, quinazol-4-ones 4, 4-chloroquinazolines 5. Products 6 have been screened for antibacterial and cytotoxic activity, promising compounds have been identified.

In view of the link between use of NSAIDs and altered cancer incidence and a growing evidence of COX-II implication in angiogenesis, a novel series of 4,6-disubstituted quinazoline derivatives have been synthesized starting from anthranilic acid derivatives 1 through conventional methods. Initially acylation followed by cyclisation to obtain benz-oxazinones 2 which on further treatment with ammonia yielded the crucial intermediate, 2-substituted benzamide (3). The products were subsequently cyclised to obtain quinazolones 4, chlorinated 5, then hooked to various optically pure α-amino acids to have 4,6-disubstituted quinazoline derivatives 6. All the derivatives 6 are screened for anti-inflammatory and anti-cancer activity against U937 leukemia cell lines. Some of the compounds exhibited promising anti-cancer activity with reference to standard drug Etoposide.

Synthesis of quinazolin-4-(3H)-ones from o-amido-benzonitriles has been carried out by using urea-hydrogen peroxide as a mild, stable and non- hazardous reagent.