1005161-99-8Relevant academic research and scientific papers
p-TSA-Based DESs as “Active Green Solvents” for Microwave Enhanced Cyclization of 2-Alkynyl-(hetero)-arylcarboxylates: an Alternative Access to 6-Substituted 3,4-Fused 2-Pyranones
Curti, Fabiola,Tiecco, Matteo,Pirovano, Valentina,Germani, Raimondo,Caselli, Alessandro,Rossi, Elisabetta,Abbiati, Giorgio
, p. 1904 - 1914 (2019/02/26)
In this paper, we describe the use of p-TSA based Deep Eutectic Solvents (DESs) as alternative environmental-friendly “active” solvents for the microwave-mediated synthesis of 6-substituted 3,4-fused 2-pyranones, and in particular isocoumarins, starting from 2-alkynyl-(hetero)arylcarboxylates. When the alkyne terminus bears a neutral or an electron-donating group (EDG), the reactions are fast, clean and highly regioselective, to give the 6-endo-dig cyclization products in good to excellent yields. For substrates bearing an electron-withdrawing group (EWG) on the alkyne end, the regioselectivity can be tuned by adding a small amount of silver(I) triflate as co-catalyst. DES was demonstrated to be reusable without loss of efficiency in terms of reaction yields. Based on experimental evidence and previous findings, two competitive mechanisms working simultaneously are proposed to explain the outcomes and the regioselectivity issues.
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.
experimental part, 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
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
