- Regioselective Synthesis of 2° Amides Using Visible-Light-Induced Photoredox-Catalyzed Nonaqueous Oxidative C-N Cleavage of N, N-Dibenzylanilines
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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.
- Neerathilingam, Nalladhambi,Bhargava Reddy, Mandapati,Anandhan, Ramasamy
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supporting information
p. 15117 - 15127
(2021/10/25)
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- Competing HB acceptors: An extensive NMR investigations corroborated by single crystal XRD and DFT calculations
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A series of N-benzoylanthranilamide derivatives have been synthesized with the substitution of competitive HB acceptors and investigated by NMR spectroscopy and single crystal XRD. The interesting rivalry for HB acceptance between CO and X (F or OMe) is observed in the investigated molecules which leads to an unusual increase in the electron density at the site of one of the NH protons, reflecting in the high field resonance in the 1H NMR spectrum. The NMR experimental findings and single crystal XRD are further reinforced by the DFT studies.
- Tiwari, Surbhi,Arya, Neeru,Mishra, Sandeep Kumar,Suryaprakash
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p. 15195 - 15202
(2021/05/21)
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- Domino synthesis of pyrimido and imidazoquinazolinones
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A simple method for the synthesis of N-alkyl-2-arylquinazolin-4-amines, methyl 4-((2-arylquinazolin-4-yl)amino) butanoates, 6-aryl-2,3-dihydro-4H-pyrimido[1,2-c]quinazolin-4-ones, and 5-arylimidazo[1,2-c]quinazolin-3(2H)-ones has been described. It involves a simple reaction of N-(2-cyanophenyl)-substitutedbenzimidoyl chlorides with alkylamine, γ-aminobutyric acid, β-alanine, l-alanine, and glycine methyl esters hydrochloride in acetonitrile to afford the desired compounds after a series of instantaneous reactions that include Dimroth rearrangement. The reaction involves reflux for 12 hours, simple addition of reagents to an in situ generated benzimidoyl chloride, and simple workup, to form 21 examples of pure compounds in high yields. The active intermediate N-(2-cyanophenyl)-substitutedbenzimidoyl chlorides were formed by the reaction of N-(2-cyanophenyl)-substitutedbenzamides with thionyl chloride in a one-pot strategy. The alternative method described for this preparation deals with an exhausting multistep reactions starting from anthranilic acid.
- Fathalla, Walid,Nofal, Eman Y.,El-Moneim, Mohamed Abd
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p. 1266 - 1274
(2020/01/21)
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- N-Phenylbenzamide derivatives as alternative oxidase inhibitors: Synthesis, molecular properties, 1H-STD NMR, and QSAR
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In the present work, 117 N-phenylbenzamides (NPDs) were prepared and evaluated against recombinant AOX from the fungal pathogen Moniliophthora perniciosa. 1H, 13C NMR, FTIR, and mass spectra provided structural information on NPDs. The library compounds were tested as Alternative Oxidase inhibitors in two different assays using the model yeast Pichia pastoris: cell growth and oxygen consumption assays. The most active compound, 3FH, was further characterized by DRX and 1H-NMR-STD. Single crystal X-ray diffraction showed intra- and intermolecular interactions of 3FH in solid-state and elucidated its 3D structural configuration. 1H-NMR-STD allowed us to derive protein-ligand interactions in a membrane-mimetic system and evidenced an outstanding interaction of 3FH with this enzyme. Results of both biological assays were used as input to Quantitative Structure-Activity Relationship models, which highlighted the more important molecular fragments contributions for protein-ligand interaction.
- Barsottini, Mario R. O.,Carazzolle, Marcelo F.,Costa, Paulo C. S.,Evangelista, Joel S.,Miranda, Paulo C. M. L.,Nascimento, Andrey F. Z.,Pereira, Gon?alo A. G.,Pires, Bárbara A.,Rocco, Silvana A.,Sfor?a, Maurício L.,Silva, Jaqueline S.,Vieira, Maria L. L.,Zeri, Ana C. M.
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- Synthesis of 2-(2-Hydroxyaryl)-4H-benzo[e][1,3]oxazin-4-ones by Palladium-Catalyzed C(sp2)?H Hydroxylation via Electro-chemical Oxidation
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An electrochemical direct ortho-hydroxylation of 2-aryl-4H-benzo[e][1,3]oxazin-4-ones was developed with Pd(OAc)2 as catalyst, oxazine ring as a directing group and Oxone as the hydroxylation reagent. A series of hydroxylation products were obtained under mild conditions, and the yields were from medium to good. This method is characterized by good functional group tolerance and a wide range of substrates. More importantly, use anodic oxidation to avoid the use of potentially toxic and polluting oxidants. A gram-scale direct electrochemical hydroxylation of 2-phenyl-4H-benzo[e][1,3]oxazin-4-one was performed, and the hydroxylation product was applied to synthesize the drug deferasirox. In addition, the single crystal of 2-(2-hydroxyphenyl)-4H-benzo[e][1,3]oxazin-4-one was obtained and determined by X-ray diffraction. Finally, the reaction mechanism was proposed and verified by cyclic voltammetry (CV). This protocol also provides an alternative electrochemical hydroxylation methodology for the functionalization of molecules. (Figure presented.).
- Wu, Hongfeng,An, Qi,He, Chaoyin,Fan, Xiaodong,Guo, Weihao,Zuo, Minghui,Xu, Chunzhao,Guo, Rui,Chu, Wenyi,Sun, Zhizhong
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supporting information
p. 2459 - 2465
(2020/04/29)
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- Synthesis and Antimicrobial Activity of Methyl 2-(2-(2-Arylquinazolin-4-yl)oxy) Acetylamino Alkanoates
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A series of methyl 2-(2-(2-arylquinazolin-4-yl)oxy) acetylamino alkanoate have been developed via N,N′-dicyclohexylcarbodiimide coupling of (2-arylquinazolin-4-yloxy) acetic acids with amino acid ester hydrochlorides. The O-substituted carboxylic acids we
- Megahed,Fathalla,Alsheikh, Amer A.
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p. 2799 - 2808
(2018/11/23)
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- Photocatalytic benzene and benzene derivative direct hydroxylation or amination method
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The invention discloses a photocatalytic benzene and benzene derivative direct hydroxylation or amination method. The method is characterized by comprising the following steps: (1) adding a photo-sensitizer and a cobalt catalyst into a solvent to obtain a solution (A); (2) adding benzene (or benzene derivatives), water, ammonia gas, and amide derivatives (or sulfonamide derivatives) into the solution (A) to obtain a solution (B); and (3) in a N2 (or Ar) environment, radiating the solution (B) by a medium pressure mercury lamp, a high pressure mercury lamp, a xenon lamp, or an LED lamp to obtain phenols or amines and H2. For the first time, a photo-sensitizer and a cobalt catalyst are combined and applied to photocatalytic hydroxylation and amination of benzene. The conditions of the method are mild, light is taken as the driving energy, no oxidant is added, the only byproduct is H2, and the whole process is green, concise, and efficient. High selective benzene one-step hydroxylation to generate phenol or high selective phenol/benzene one-step amination to generate aniline is realized, and the method can be applied to the production of phenol and aniline.
- -
-
Paragraph 0148-0149
(2017/11/29)
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- One-pot synthesis of polyhydropyrido[1,2-a]indoles and tetracyclic quinazolinones from 2-arylindoles using copper-mediated oxidative tandem reactions
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We developed facile one-pot methods for the transformation of 2-arylindoles to polyhydropyrido[1,2-a]indoles and tetracyclic quinazolinones. The copper-catalyzed oxidation of 2-arylindoles to C-acylimines followed by aza-Diels–Alder reactions or oxidative
- Yamashita, Mitsuaki,Nishizono, Yukari,Himekawa, Seiya,Iida, Akira
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p. 4123 - 4131
(2016/07/06)
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- Anti-convulsant potential of quinazolinones
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A series of novel quinazoline derivatives were synthesized, virtually screened through different filters and evaluated for their anticonvulsant activity against electrically and chemically induced seizures, compared with that of the standard drugs methaqualone and sodium valproate. Compound 48, 3-(2-aminophenyl)-7-chloro-2-phenylquinazolin-4(3H)-one, was found to be the most potent compound of the series accompanied by relatively low neurotoxicity and low toxicity in the median lethal dose test as compared with the reference drugs. The obtained results showed that compounds 12, 48, 49 and 50 could be useful templates for future design, optimization, and investigation to construct more active analogs.
- Patel, Harun M.,Noolvi, Malleshappa N.,Shirkhedkar, Atul A.,Kulkarni, Abhijeet D.,Pardeshi, Chandrakantsing V.,Surana, Sanjay J.
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p. 44435 - 44455
(2016/06/09)
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- Structure-activity relationships of 2-arylquinazolin-4-ones as highly selective and potent inhibitors of the tankyrases
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Tankyrases (TNKSs), members of the PARP (Poly(ADP-ribose)polymerases) superfamily of enzymes, have gained interest as therapeutic drug targets, especially as they are involved in the regulation of Wnt signalling. A series of 2-arylquinazolin-4-ones with varying substituents at the 8-position was synthesised. An 8-methyl group (compared to 8-H, 8-OMe, 8-OH), together with a 4′-hydrophobic or electron-withdrawing group, provided the most potency and selectivity towards TNKSs. Co-crystal structures of selected compounds with TNKS-2 revealed that the protein around the 8-position is more hydrophobic in TNKS-2 compared to PARP-1/2, rationalising the selectivity. The NAD+-binding site contains a hydrophobic cavity which accommodates the 2-aryl group; in TNKS-2, this has a tunnel to the exterior but the cavity is closed in PARP-1. 8-Methyl-2-(4-trifluoromethylphenyl)quinazolin-4-one was identified as a potent and selective inhibitor of TNKSs and Wnt signalling. This compound and analogues could serve as molecular probes to study proliferative signalling and for development of inhibitors of TNKSs as drugs.
- Nathubhai, Amit,Haikarainen, Teemu,Hayward, Penelope C.,Mu?oz-Descalzo, Silvia,Thompson, Andrew S.,Lloyd, Matthew D.,Lehti?, Lari,Threadgill, Michael D.
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p. 316 - 327
(2016/05/19)
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- Formation of amides, their intramolecular reactions for the synthesis of N-heterocycles, and preparation of a marketed drug, sildenafil: A comprehensive coverage
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A unified approach to the tandem preparation of diverse nitrogen heterocycles via decarboxylative acylation of ortho-substituted amines with α-oxocarboxylic acids and subsequent intramolecular cyclizations has been developed. The key features of this work include: the first example of transition-metal-free decarboxylative amidation of α-oxocarboxylic acids with ortho-substituted amines, realization of intramolecular cyclization of amides employing nucleophiles that have previously been unexplored, mechanistic investigation of an unprecedented K2S2O8 promoted amide formation and its subsequent intramolecular cyclizations, and application to the synthesis of a best-selling marketed drug.
- Laha, Joydev K.,Patel, Ketul V.,Satyanarayana Tummalapalli,Dayal, Neetu
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supporting information
p. 10245 - 10248
(2016/08/23)
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- Photocatalytic Hydrogen-Evolution Cross-Couplings: Benzene C-H Amination and Hydroxylation
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We present a blueprint for aromatic C-H functionalization via a combination of photocatalysis and cobalt catalysis and describe the utility of this strategy for benzene amination and hydroxylation. Without any sacrificial oxidant, we could use the dual catalyst system to produce aniline directly from benzene and ammonia, and phenol from benzene and water, both with evolution of hydrogen gas under unusually mild conditions in excellent yields and selectivities.
- Zheng, Yi-Wen,Chen, Bin,Ye, Pan,Feng, Ke,Wang, Wenguang,Meng, Qing-Yuan,Wu, Li-Zhu,Tung, Chen-Ho
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supporting information
p. 10080 - 10083
(2016/09/04)
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- Oxidative synthesis of quinazolinones and benzothiadiazine 1,1-dioxides from 2-aminobenzamide and 2-aminobenzenesulfonamide with benzyl alcohols and aldehydes
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An interesting procedure for the zinc-catalyzed oxidative transformation of ready available 2-aminobenzamide, 2-aminobenzenesulfonamide with benzyl alcohols has been developed. Various quinazolinones and benzothiadiazine 1,1-dioxides were prepared in moderate to good yields under identical conditions. The reactions of both aromatic aldehydes and aliphatic aldehydes with 2-aminobenzamide under catalyst free conditions were described as well. In water media, the products were formed in good yields.
- Sharif, Muhammad,Opalach, Julita,Langer, Peter,Beller, Matthias,Wu, Xiao-Feng
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- Synthesis and biological activity of some novel substituted quinazoline derivatives
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A new series of 4-N-(substituted benzyl)-2-phenyl-N-propylquinazolines were synthesized. The structures of the synthesized compounds were confirmed by IR, 1H NMR, 13C NMR and mass spectral analysis. All the synthesized compounds were screened for their analgesic and anti-inflammatory activity. Among the synthesized compounds 5c, 5h and 5o exhibited significant analgesic activity at 60 and 90 minutes reading, while compounds 5g, 5k and 5l exhibited significant anti-inflammatory activity at 3rd and 4th hr reading.
- Srivastav, Maneesh Kumar,Rajeeva,Salahuddin, Md.,Srinivasulu,Shanta Kumar
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p. 115 - 118
(2019/01/21)
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- Palladium-catalyzed carbonylative synthesis of quinazolinones from 2-aminobenzamide and aryl bromides
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C from CO! A straightforward procedure for the carbonylative synthesis of quinazolinones from readily available 2-aminobenzamide and aryl bromides has been developed. In the presence of a palladium catalyst, various quinazolinones were produced in moderate to excellent yields. Remarkably, no chromatography was needed for purification (see scheme). Copyright
- Wu, Xiao-Feng,He, Lin,Neumann, Helfried,Beller, Matthias
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supporting information
p. 12635 - 12638
(2013/10/01)
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- Synthesis leading to novel 2,4,6-trisubstituted quinazoline derivatives, their antibacterial and cytotoxic activity against thp-1, hl-60 and a375 cell lines
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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.
- Chandrika, P Mani,Yakaiah,Narsaiah,Sridhar,Venugopal,Rao, J Venkateshwara,Kumar, K Pranay,Murthy,Rao, A Raghu Ram
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experimental part
p. 840 - 847
(2009/12/24)
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- The discovery of the potent aurora inhibitor MK-0457 (VX-680)
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The identification of a novel series of Aurora kinase inhibitors and exploitation of their SAR is described. Replacement of the initial quinazoline core with a pyrimidine scaffold and modification of substituents led to a series of very potent inhibitors of cellular proliferation. MK-0457 (VX-680) has been assessed in Phase II clinical trials in patients with treatment-refractory chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) containing the T315I mutation.
- Bebbington, David,Binch, Hayley,Charrier, Jean-Damien,Everitt, Simon,Fraysse, Damien,Golec, Julian,Kay, David,Knegtel, Ronald,Mak, Chau,Mazzei, Francesca,Miller, Andrew,Mortimore, Michael,O'Donnell, Michael,Patel, Sanjay,Pierard, Francoise,Pinder, Joanne,Pollard, John,Ramaya, Sharn,Robinson, Daniel,Rutherford, Alistair,Studley, John,Westcott, James
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scheme or table
p. 3586 - 3592
(2010/03/31)
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- Microwave-assisted synthesis in aqueous medium of new quinazoline derivatives as anticancer agent precursors
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Fast and eco-friendly microwave-irradiated reactions permitting the "green synthesis" of new 2-substituted quinazoline derivatives in aqueous medium via S-alkylation or SRN1 reaction from 2-chloromethyl-3-methylquinazolin-4(3H)-one derivatives with different benzenesulfinic acids and nitronate anions, are reported herein.
- Kabri,Gellis,Vanelle
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experimental part
p. 201 - 208
(2010/04/22)
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- Design of novel quinazoline derivatives and related analogues as potent and selective ALK5 inhibitors
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Starting from quinazoline 3a, we designed potent and selective ALK5 inhibitors over p38MAP kinase from a rational drug design approach based on co-crystal structures in the human ALK5 kinase domain. The quinazoline 3d exhibited also in vivo activity in an acute rat model of DMN-induced liver fibrosis when administered orally at 5 mg/kg (bid).
- Gellibert,Fouchet,Nguyen,Wang,Krysa,de Gouville,Huet,Dodic
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supporting information; experimental part
p. 2277 - 2281
(2009/12/07)
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- Synthesis of novel 4,6-disubstituted quinazoline derivatives, their anti-inflammatory and anti-cancer activity (cytotoxic) against U937 leukemia cell lines
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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.
- Chandrika, P. Mani,Yakaiah,Rao, A. Raghu Ram,Narsaiah,Reddy, N. Chakra,Sridhar,Rao, J. Venkateshwara
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p. 846 - 852
(2008/09/20)
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- The study of cyclization of N-acylphenacyl anthranilates with ammonium salts under various conditions
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N-Acylphenacyl anthranilates were heated with ammonium salts in organic acid or NMP, and formation of various heterocyclic compounds was observed. Reaction results are strongly influenced by reaction conditions. The most interesting are imidazole derivati
- Hradil, Pavel,Grepl, Martin,Hlavac, Jan,Lycka, Antonin
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p. 269 - 280
(2008/02/09)
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- Identification of chemokine receptor CCR4 antagonist
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The present study reports the identification and hits to leads optimization of chemokine receptor CCR4 antagonists. Compound 12 is a high affinity, non-cytotoxic antagonist of CCR4 that blocks the functional activity mediated by the receptor.
- Purandare, Ashok V.,Gao, Aiming,Wan, Honghe,Somerville, John,Burke, Christine,Seachord, Carrie,Vaccaro, Wayne,Wityak, John,Poss, Michael A.
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p. 2669 - 2672
(2007/10/03)
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- An expeditious and solvent-free route to the synthesis of 2-substituted quinazolin-4(3H)-ones under microwave conditions
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Ammonium acetate condenses with benzoxazinones (4b-e) or a mixture of anthranilic acid and orthoesters in the absence of solvent to produce the title compounds in a few minutes.
- Rad-Moghadam, Kurosh,Mohseni, Mehdi
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p. 487 - 488
(2007/10/03)
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- Kinetics and mechanism of the base-catalysed cyclisation of 2-(substituted benzoylamino)benzamides giving quinazolin-4-one and quinazolin-4-thione derivatives
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Acylation of 2-aminobenzamide and 2-(methylamino)benzamide with substituted benzoyl chlorides in acetone has been used to prepare the respective 2-(substituted benzoylamino)benzamides 1a-i, which were then subjected to sodium methoxide catalysed ring closure to give the respective 2-(substituted phenyl)quinazolin-4 -ones 2a-i. The kinetics of the cyclisation reactions were monitored by UV/Vis spectroscopy at 25 °C in methanolic solutions of sodium methoxide. In the case of 2-(substituted benzoylamino)benzamides 1a-i and 2-(substituted benzoylamino)thiobenzamides 3a-j, non-linear dependences of observed rate constants κobs on the sodium methoxide concentrations were obtained, the shape of them being typical of a reaction with rapid pre- equilibrium. All the cyclisation reactions satisfactorily obeyed the Hammett correlation. In the case of 2 - [(benzoyl) (methyl) amino] benzamides 1e-i, increasing sodium methoxide concentration resulted in a progressive increase in κobs values which is probably due to formation of dianion. In the case of 2-(substituted benzoylamino)thiobenzamides 3b and 3h, which differ in the presence of a methyl group on the nitrogen atom the values of the activation Gibbs energy ΔG? 25 °C, activation enthalpy ΔH? 25 °C, and activation entropy ΔS? 25 °C for their respective cyclisations to 2-(substituted phenyl)quinazoline-4-thiones 4b and 4h were determined. Whereas the ΔG? 25 °C values were very close for the two substances, the ΔH? 25 °C and ΔS? 25 °C distinctly differed. This was interpreted by the enthalpy and entropy factors operating against each other in the cyclisation. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002).
- Hanusek, Jiri,Sedlak, Milos,Simunek, Petr,Sterba, Vojeslav
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p. 1855 - 1863
(2007/10/03)
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- Mechanism of alkaline cyclization of 2-(substituted benzamido)benzamides to 4-quinazolinones
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The title amides cyclize rapidly to the corresponding quinazolin-4-ones in aqueous alkaline solution at 25°C; the pseudo-first-order rate constants fit the empirical equation k(obs) = k(max) [OH-]/(K(m) + [OH-] + [OH-]sup
- Gardner,Kanagasooriam,Smyth,Williams
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p. 6245 - 6250
(2007/10/02)
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