5657-54-5Relevant academic research and scientific papers
Transition-metal-free oxidative cyclization reaction of enynals to access pyrane-2-one derivatives
Abbasi Kejani, Alireza,Ansari, Farzaneh,Armaghan, Mahsa,Balalaie, Saeed,Frank, Walter,Jafarpour, Farnaz,Khosravi, Hormoz
, p. 4263 - 4267 (2021/05/31)
A novel and efficient metal-free C-H functionalization of enynals is developed to synthesize α-pyrone derivatives via the formation of two C-O bonds. In this project, K2S2O8 has been introduced as an efficient oxygen source and C-H functionalization agent in regioselective oxidative cyclization reaction with a relatively broad substrate scope.
Modular synthesis of 3-substituted isocoumarinsviasilver-catalyzed aerobic oxidation/6-endoheterocyclization ofortho-alkynylbenzaldehydes
Wu, Hao,Wang, Yi-Chun,Shatskiy, Andrey,Li, Qiu-Yan,Liu, Jian-Quan,K?rk?s, Markus D.,Wang, Xiang-Shan
, p. 6657 - 6664 (2021/08/16)
A method involving silver-catalyzed aerobic oxidation/6-endoheterocyclization ofortho-alkynylbenzaldehydes to yield 3-substituted isocoumarins is described. The developed protocol allows convenient access to a range of synthetically useful 3-substituted isocoumarins and related fused heterocyclolactones in good to high yields, using silver tetrafluoroborate as the catalyst, and atmospheric oxygen as the terminal oxidant and the source of endocyclic oxygen. Mechanistic studies suggest the involvement of a free-radical pathway.
Structure-based design, synthesis and evaluation in vitro of arylnaphthyridinones, arylpyridopyrimidinones and their tetrahydro derivatives as inhibitors of the tankyrases
Kumpan, Katerina,Nathubhai, Amit,Zhang, Chenlu,Wood, Pauline J.,Lloyd, Matthew D.,Thompson, Andrew S.,Haikarainen, Teemu,Lehti?, Lari,Threadgill, Michael D.
, p. 3013 - 3032 (2015/08/03)
Abstract The tankyrases are members of the PARP superfamily; they poly(ADP-ribosyl)ate their target proteins using NAD+ as a source of electrophilic ADP-ribosyl units. The three principal protein substrates of the tankyrases (TRF1, NuMA and axin) are involved in replication of cancer cells; thus inhibitors of the tankyrases may have anticancer activity. Using structure-based drug design and by analogy with known 3-arylisoquinolin-1-one and 2-arylquinazolin-4-one inhibitors, series of arylnaphthyridinones, arylpyridinopyrimidinones and their tetrahydro-derivatives were synthesised and evaluated in vitro. 7-Aryl-1,6-naphthyridin-5-ones, 3-aryl-2,6-naphthyridin-1-ones and 3-aryl-2,7-naphthyridin-1-ones were prepared by acid-catalysed cyclisation of the corresponding arylethynylpyridinenitriles or reaction of bromopyridinecarboxylic acids with β-diketones, followed by treatment with NH3. The 7-aryl-1,6-naphthyridin-5-ones were methylated at 1-N and reduced to 7-aryl-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-ones. Cu-catalysed reaction of benzamidines with bromopyridinecarboxylic acids furnished 2-arylpyrido[2,3-d]pyrimidin-4-ones. Condensation of benzamidines with methyl 1-benzyl-4-oxopiperidine-3-carboxylate and deprotection gave 2-aryl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-ones, aza analogues of the known inhibitor XAV939. Introduction of the ring-N in the arylnaphthyridinones and the arylpyridopyrimidinones caused >1000-fold loss in activity, compared with their carbocyclic isoquinolinone and quinazolinone analogues. However, the 7-aryl-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-ones showed excellent inhibition of the tankyrases, with some examples having IC50 = 2 nM. One compound (7-(4-bromophenyl)-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-one) showed 70-fold selectivity for inhibition of tankyrase-2 versus tankyrase-1. The mode of binding was explored through crystal structures of inhibitors in complex with tankyrase-2.
Tandem palladium/charcoal-copper(I) iodide (Pd/C-CuI) catalyzed Sonogashira coupling and intramolecular cyclization from 2-bromonicotinic acid (=2-bromopyridine-3-carboxylic acid) and ethynylarenes to 4-azaphthalides (=furo[3,4-b]pyridin-5(7H)-ones) and 5-azaisocoumarins (=5H-pyrano[4,3-b] pyridin-5-ones)
Begouin, Agathe,Queiroz, Maria-Joaor P.
scheme or table, p. 1792 - 1801 (2011/12/02)
Several 4-azaphthalides (=furo[3,4-b]pyridin-5(7H)-ones) and 5-azaisocoumarins (=5H-pyrano[4,3-b]pyridin-5-ones) were prepared through a tandem heterogeneous Pd/C-mediated Sonogashira coupling and a 5-exo-dig or 6-endo-dig intramolecular cyclization of 2-bromonicotinic acid (=2-bromopyridine-3-carboxyclic acid) with various ethynylarenes or 3-ethynylthiophene. In the presence of Pd/C-Ph3P-CuI and Et 3N in dry dioxane under Ar at 90°, a mixture of 4-azaphthalides (usually the major product) and 5-azaisocoumarins was obtained after 3.5 h under normal heating (Schemes 3 and 4; Tables 1 and 2). This mixture of compounds was also obtained with the same catalytic system under microwave (MW) irradiation in only 25 min (Tables 3 and 4). The 1-ethynyl-3-methoxybenzene gave on heating only the corresponding 4-azaphthalide (Table 2), while under MW irradiation, both the 5-exo-dig and the 6-endo-dig products were obtained (Table 4). For the 3-ethynylthiophene, the regioselectivity for the corresponding 4-azaphthalide was achieved with both methods (Tables 2 and 4). Although the yields and the regioselectivity of the reaction generally remained the same with both methods, the use of MW allowed us to obtain the corresponding products in a shorter reaction time. From 4-ethynyl-N,N-dimethylaniline (=4-ethynyl-N,N- dimethylbenzenamine), the corresponding 4-azaphthalide and 5-isocoumarin were only obtained under MW irradiation (Tables 2 and 4). To the best of our knowledge, it is the first time that this kind of tandem reaction was applied to a pyridine derivative giving the corresponding 4-azaphthalides and 5-azaisocoumarins which are easily separated and may both show biological activity. Copyright
NHC-catalyzed oxidative cyclization reactions of 2-alkynylbenzaldehydes under aerobic conditions: Synthesis of O-Heterocycles
Park, Jong Hyub,Bhilare, Sachin V.,Youn, So Won
supporting information; experimental part, p. 2228 - 2231 (2011/07/09)
Chemical equations presented. An NHC-catalyzed, regio- and stereoselective oxidative cyclization of o-alkynylbenzaldehydes bearing an unactivated alkyne moiety as an internal electrophile has been developed to afford phthalides and isocoumarins. A single organocatalytic system enabled two sequential C-O bond formations to take place in an atom economical manner via highly efficient dual activation. Molecular oxygen in air could be utilized as a source of an oxygen atom for the oxidation of aldehydes to the corresponding benzoic acids under our newly developed reagent system.
One-pot synthesis of phthalides via regioselective intramolecular cyclization from ortho-alkynylbenzaldehydes
Li, Jim,Chin, Elbert,Lui, Alfred S.,Chen, Lijing
scheme or table, p. 5937 - 5939 (2010/11/21)
A one-pot synthesis of phthalides via an intramolecular 5-exo-dig cyclization of ortho-alkynylbenzaldehydes under mild NaClO2 oxidation conditions is described.
6-endo-dig Cyclization of heteroarylesters to alkynes promoted by Lewis acid catalyst in the presence of Br?nsted acid
Hellal, Malik,Bourguignon, Jean-Jacques,Bihel, Frédéric J.-J.
, p. 62 - 65 (2008/09/17)
We report a regiocontrolled 6-endo-dig cyclization of 2-(2-arylethynyl)heteroaryl esters occurred under Br?nsted acidic conditions and in the presence of a catalytic amount of Lewis acids such as Cu(OTf)2, AuCl3, or (CF3CO
Application of organolithium and related reagents in synthesis. Part XI. Metallation of 2-methyl- and 4-methylnicotinic acids. A useful method for preparation of aza-isocoumarins
Epsztajn,Plotka,Scianowski
, p. 1239 - 1247 (2007/10/02)
The metallation (LDA/THF) of 2-methyl- and 4-methylnicotinic acids (1) and (2), and the subsequent reaction of the lithiated species (3) and (4) with carbonyl electrophiles as a synthetic route of 5-aza- and 7-aza-isocoumarins (7), (8), (9) and (10), is d
EFFECTIVE SYNTHESIS OF 7-BENZYLIDENEFUROPYRIDIN-5-ONE
Nishiwaki, Nagatoshi,Komatsu, Mitsuo,Ohshiro, Yoshiki
, p. 1013 - 1016 (2007/10/02)
The tittle compound was synthesized by silica gel assisted cyclization of 2-phenylethynylpyridine-3-carboxylic acid (3).It was also synthesized from 3-cyano-2-phenylethynylpyridine (6) in good yield by basic cyclization and dehydration processes.
A facile synthesis of 1,6-naphthyridin-5(6H)-ones
Nishiwaki,Komatsu,Ohshiro
, p. 41 - 42 (2007/10/02)
3-Cyano-2-(phenylethynyl)pyridine (1) was cyclized intramolecularly under acidic conditions to give 1,6-naphthyridin-5(6H)-one (2) and 5H-pyrano[4,3-b]pyridine-5-one (4). Pyranopyridine 4 was readily transformed to 2 or naphthyridinone 9 having an alkyl substituent at 6-position.
