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Alexander F. Khlebnikov - One of the best experts on this subject based on the ideXlab platform.
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1 2h azirine 2 carbonyl benzotriazoles building blocks for the synthesis of pyrrole containing heterocycles
Organic and Biomolecular Chemistry, 2020Co-Authors: Ekaterina E. Galenko, Mikhail S. Novikov, Vladimir A Bodunov, Firuza M Shakirova, Alexander F. KhlebnikovAbstract:A one-pot method was developed for the preparation of 2H-azirine-2-carbonylbenzotriazoles, formed by the reaction of benzotriazole with 2H-azirine-2-carbonyl chlorides, which were generated by the Fe(ii)-catalyzed isomerization of 5-chloroisoxazoles. The Co(ii)-catalyzed reaction of 2H-azirine-2-carbonylbenzotriazoles with 1,3-diketones provides 2-((benzotriazol-1-yl)carbonyl)pyrroles in moderate to good yields. Base-promoted annulations of 2-((benzotriazol-1-yl)carbonyl)pyrroles with aldehydes, ketones, isocyanates and isothiocyanates afford various substituted pyrrolo[1,2-c]oxazole and 1H-pyrrolo[1,2-c]imidazole derivatives in moderate to high yields. The 6-acyl group of these adducts can be removed by triflic acid, giving further new pyrrolo-fused O- and N-heterocycles, such as 6-unsubstituted pyrrolo[1,2-c]oxazol-1(3H)-one and 1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione, while the 6-acetyl substituent of 1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione, when treated with POCl3/pyridine, is transformed into the 6-ethynyl substituent.
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2h azirine 2 carbonyl azides preparation and use as n heterocyclic building blocks
Journal of Organic Chemistry, 2020Co-Authors: Liya D. Funt, Mikhail S. Novikov, Yulia V Krivolapova, Olesya V Khoroshilova, Alexander F. KhlebnikovAbstract:2H-Azirine-2-carbonyl azides, new reactive heterocyclic building blocks, were synthesized in high yield by the reaction of sodium azide with 2H-azirine-2-carbonyl chlorides, generated by the Fe(II)-catalyzed isomerization of 5-chloroisoxazoles. 2-(Azidocarbonyl)-1H-pyrroles, prepared by the Ni(II)-catalyzed reaction of 2-(azidocarbonyl)-2H-azirines with 1,3-diketones, easily undergo the Curtius rearrangement in boiling tBuOH to give Boc-protected α-aminopyrroles in high yield. Heating of 2-(azidocarbonyl)-1H-pyrroles for a short time in inert solvents leads to the high-yield formation of benzo- and hetero-fused 1H-pyrrolo[2,3-b]pyridin-6(7H)-ones, which are formed via a 6π electrocyclization involving the vicinal aryl or hetaryl substituent and the N═C bond of isocyanate, generated by the Curtius rearrangement of the azidocarbonyl group. The Pd-catalyzed cross-coupling reaction of 1-acetyl-2-methyl-3H-pyrrolo[2,3-c]isoquinolin-5-yl triflate, easily prepared from the corresponding pyrroloisoquinolone, leads to variously 5-substituted 3H-pyrrolo[2,3-c]isoquinolines in excellent yields.
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an azirine strategy for the synthesis of alkyl 4 amino 5 trifluoromethyl 1h pyrrole 2 carboxylates
Synthesis, 2018Co-Authors: Liya D. Funt, Mikhail S. Novikov, Olesya A. Tomashenko, Alexander F. KhlebnikovAbstract:1-(3,3,3-Trifluoro-2,2-dihydroxypropyl)pyridin-1-ium bromide serves as a trifluoromethyl-containing building block for the preparation of trifluoromethyl-substituted aminopyrroles based on the 2H-azirine ring expansion strategy. The primary products, 3-aryl-2-(methoxycarbonyl)-4-(pyridin-1-ium-1-yl)-5-(trifluoromethyl)pyrrol-1-ides, can be hydrogenated by H2/PtO2 to form alkyl 3-aryl-4-(piperidin-1-yl)-5-(trifluoromethyl)-1H-pyrrole-2-carboxylates and transformed into alkyl 4-amino-3-aryl-1-methyl-5-(trifluoromethyl)-1H-pyrrole-2-carboxylates via methylation/hydrazinolysis.
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Synthesis, Transformations of Pyrrole- and 1,2,4-Triazole-Containing Ensembles, and Generation of Pyrrole-Substituted Triazole NHC
2016Co-Authors: Liya D. Funt, Alexander F. Khlebnikov, Olesya A. Tomashenko, Mikhail S. Novikov, Alexander Yu. IvanovAbstract:Unprecedented pyrrole- and 1,2,4-triazole-containing ensembles, substituted 1-(1H-pyrrol-3-yl)-4H-1,2,4-triazol-1-ium bromides and 4-(1H-pyrrol-3-yl)-1H-1,2,4-triazol-4-ium bromides, were prepared from 2H-azirines and triazolium phenacyl bromides using a simple procedure. N-(1H-Pyrrol-3-yl)-N′-benzyltriazolium bromides undergo reductive debenzylation on Pd/C to give substituted 1-(1H-pyrrol-3-yl)-4H-1,2,4-triazoles and 4-(1H-pyrrol-3-yl)-1H-1,2,4-triazoles in high yields. Betaines (triazoliumylpyrrolides) and pyrrolyltriazole NHCs, which are possible products of dehydrobromination of pyrrolyltriazolium salts, have comparable thermodynamic stabilities in nonpolar solvents according to calculations at the DFT B3LYP/6-31G(d) level. The carbene forms can be easily trapped by the reaction of salts with base in the presence of sulfur. The corresponding 1- and 4-(1H-pyrrol-3-yl)-1H-1,2,4-triazole-5(4H)-thiones are formed in high yields. In the absence of sulfur as a trap, the opening of the triazole ring occurs with the formation of derivatives of N-cyanoformimidamide. According to the DFT calculations the latter is most probably formed via a pyrrolyltriazoliumide intermediate, which is the minor component of the equilibrium triazoliumylpyrrolide–pyrrolyltriazole NHC–pyrrolyltriazoliumide. Blocking of the pyrrolyltriazoliumide intermediate formation, by introduction of a substituent at the 3-position of the triazole ring, made it possible to generate the first pyrrole-substituted triazole NHC
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selective syntheses of 2h 1 3 oxazines and 1h pyrrol 3 2h ones via temperature dependent rh ii carbenoid mediated 2h azirine ring expansion
Tetrahedron, 2014Co-Authors: Kirill V Zavyalov, Alexander F. Khlebnikov, M S Novikov, V V PakalnisAbstract:Abstract The Rh(II)-catalyzed reaction of 2-carbonyl-substituted 2H-azirines with ethyl 2-cyano-2-diazoacetate or 2-diazo-3,3,3-trifluoropropionate provides an easy access to 2H-1,3-oxazines and 1H-pyrrol-3(2H)-ones. These compounds can be selectively prepared from the same starting material using temperature as the only varied parameter. The 2-azabuta-1,3-diene intermediate, a common precursor for both heterocyclic products, isomerizes into 2H-1,3-oxazine under kinetic control, while 1H-pyrrol-3(2H)-one is the sole product of the reaction at elevated temperatures. According to DFT-calculations a one-atom oxazine ring contraction involving ring-opening to a 2-azabuta-1,3-diene intermediate, followed by a 1,5- and 1,2-prototropic shift leads to the consecutive formation of imidoylketene and azomethine ylide, which then further undergo cyclization to the pyrrole derivative.
Mikhail S. Novikov - One of the best experts on this subject based on the ideXlab platform.
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1 2h azirine 2 carbonyl benzotriazoles building blocks for the synthesis of pyrrole containing heterocycles
Organic and Biomolecular Chemistry, 2020Co-Authors: Ekaterina E. Galenko, Mikhail S. Novikov, Vladimir A Bodunov, Firuza M Shakirova, Alexander F. KhlebnikovAbstract:A one-pot method was developed for the preparation of 2H-azirine-2-carbonylbenzotriazoles, formed by the reaction of benzotriazole with 2H-azirine-2-carbonyl chlorides, which were generated by the Fe(ii)-catalyzed isomerization of 5-chloroisoxazoles. The Co(ii)-catalyzed reaction of 2H-azirine-2-carbonylbenzotriazoles with 1,3-diketones provides 2-((benzotriazol-1-yl)carbonyl)pyrroles in moderate to good yields. Base-promoted annulations of 2-((benzotriazol-1-yl)carbonyl)pyrroles with aldehydes, ketones, isocyanates and isothiocyanates afford various substituted pyrrolo[1,2-c]oxazole and 1H-pyrrolo[1,2-c]imidazole derivatives in moderate to high yields. The 6-acyl group of these adducts can be removed by triflic acid, giving further new pyrrolo-fused O- and N-heterocycles, such as 6-unsubstituted pyrrolo[1,2-c]oxazol-1(3H)-one and 1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione, while the 6-acetyl substituent of 1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione, when treated with POCl3/pyridine, is transformed into the 6-ethynyl substituent.
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2h azirine 2 carbonyl azides preparation and use as n heterocyclic building blocks
Journal of Organic Chemistry, 2020Co-Authors: Liya D. Funt, Mikhail S. Novikov, Yulia V Krivolapova, Olesya V Khoroshilova, Alexander F. KhlebnikovAbstract:2H-Azirine-2-carbonyl azides, new reactive heterocyclic building blocks, were synthesized in high yield by the reaction of sodium azide with 2H-azirine-2-carbonyl chlorides, generated by the Fe(II)-catalyzed isomerization of 5-chloroisoxazoles. 2-(Azidocarbonyl)-1H-pyrroles, prepared by the Ni(II)-catalyzed reaction of 2-(azidocarbonyl)-2H-azirines with 1,3-diketones, easily undergo the Curtius rearrangement in boiling tBuOH to give Boc-protected α-aminopyrroles in high yield. Heating of 2-(azidocarbonyl)-1H-pyrroles for a short time in inert solvents leads to the high-yield formation of benzo- and hetero-fused 1H-pyrrolo[2,3-b]pyridin-6(7H)-ones, which are formed via a 6π electrocyclization involving the vicinal aryl or hetaryl substituent and the N═C bond of isocyanate, generated by the Curtius rearrangement of the azidocarbonyl group. The Pd-catalyzed cross-coupling reaction of 1-acetyl-2-methyl-3H-pyrrolo[2,3-c]isoquinolin-5-yl triflate, easily prepared from the corresponding pyrroloisoquinolone, leads to variously 5-substituted 3H-pyrrolo[2,3-c]isoquinolines in excellent yields.
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an azirine strategy for the synthesis of alkyl 4 amino 5 trifluoromethyl 1h pyrrole 2 carboxylates
Synthesis, 2018Co-Authors: Liya D. Funt, Mikhail S. Novikov, Olesya A. Tomashenko, Alexander F. KhlebnikovAbstract:1-(3,3,3-Trifluoro-2,2-dihydroxypropyl)pyridin-1-ium bromide serves as a trifluoromethyl-containing building block for the preparation of trifluoromethyl-substituted aminopyrroles based on the 2H-azirine ring expansion strategy. The primary products, 3-aryl-2-(methoxycarbonyl)-4-(pyridin-1-ium-1-yl)-5-(trifluoromethyl)pyrrol-1-ides, can be hydrogenated by H2/PtO2 to form alkyl 3-aryl-4-(piperidin-1-yl)-5-(trifluoromethyl)-1H-pyrrole-2-carboxylates and transformed into alkyl 4-amino-3-aryl-1-methyl-5-(trifluoromethyl)-1H-pyrrole-2-carboxylates via methylation/hydrazinolysis.
Thomas Gerstberger - One of the best experts on this subject based on the ideXlab platform.
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discovery of novel spiro 3h indole 3 2 pyrrolidin 2 1h one compounds as chemically stable and orally active inhibitors of the mdm2 p53 interaction
Journal of Medicinal Chemistry, 2016Co-Authors: Andreas Gollner, Dorothea Rudolph, Heribert Arnhof, Markus Johann Bauer, Sophia Blake, Guido Boehmelt, Xiaoling Cockroft, Georg Dahmann, Peter Ettmayer, Thomas GerstbergerAbstract:Scaffold modification based on Wang’s pioneering MDM2–p53 inhibitors led to novel, chemically stable spiro-oxindole compounds bearing a spiro[3H-indole-3,2′-pyrrolidin]-2(1H)-one scaffold that are not prone to epimerization as observed for the initial spiro[3H-indole-3,3′-pyrrolidin]-2(1H)-one scaffold. Further structure-based optimization inspired by natural product architectures led to a complex fused ring system ideally suited to bind to the MDM2 protein and to interrupt its protein–protein interaction (PPI) with TP53. The compounds are highly selective and show in vivo efficacy in a SJSA-1 xenograft model even when given as a single dose as demonstrated for 4-[(3S,3′S,3′aS,5′R,6′aS)-6-chloro-3′-(3-chloro-2-fluorophenyl)-1′-(cyclopropylmethyl)-2-oxo-1,2,3′,3′a,4′,5′,6′,6′a-octahydro-1′H-spiro[indole-3,2′-pyrrolo[3,2-b]pyrrole]-5′-yl]benzoic acid (BI-0252).
N. L. Racheva - One of the best experts on this subject based on the ideXlab platform.
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five membered 2 3 dioxo heterocycles xci reaction of 3 aroyl 1h pyrrolo 2 1 c 1 4 benzoxazine 1 2 4 triones with dimedone crystalline and molecular structure of 3 benzoyl 4 hydroxy 1 2 hydroxyphenyl 6 6 dimethyl 6 7 dihydrospiro 1 benzofuran 3 2 pyrr
Russian Journal of Organic Chemistry, 2013Co-Authors: N M Tutynina, N. L. Racheva, V A Maslivets, A N MaslivetsAbstract:3-Aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones reacted with 5,5-dimethylcyclohexane-1,3-dione to give 3′-aroyl-4′-hydroxy-1′-(2-hydroxyphenyl)-6,6-dimethyl-6,7-dihydrospiro[1-benzofuran-3,2′-pyrrole]-2,4,5′(1′H,5H)-triones. The crystalline and molecular structures of 3′-benzoyl-4′-hydroxy-1′-(2-hydroxyphenyl)-6,6-dimethyl-6,7-dihydrospiro[1-benzofuran-3,2′-pyrrole]-2,4,5′(1′H,5H)-trione were determined by X-ray analysis.
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five membered 2 3 dioxoheterocycles lix reaction of 3 aroyl 1h pyrrolo 2 1 c 1 4 benzoxazine 1 2 4 triones with acyclic β enaminoesters crystal and molecular structure of ethyl 3 benzoyl 4 hydroxy 1 o hydroxyphenyl 5 oxo 2 3 dihydro 1h pyrrolo 2 spir
Russian Journal of Organic Chemistry, 2008Co-Authors: N. L. Racheva, Z G Aliev, M. A. Belova, I V MashevskayaAbstract:3-Aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones react with substituted alkyl 3-amino-2-propenoates to form substituted alkyl 3-aroyl-4-hydroxy-1-o-hydroxyphenyl-5-oxo-2,5-dihydro-1H-pyrrole-2-spiro-3′-(2-oxo-2,3-dihydro-1H-pyrrole-4-carboxylates). Crystal and molecular structure of ethyl 3-benzoyl-4-hydroxy-1-o-hydroxyphenyl-5-oxo-2,5-dihydro-1H-pyrrole-2-spiro-3′-(5-methyl-2-oxo-2,3-dihydro-1H-pyrrole-4-carboxylate) was investigated.
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five membered 2 3 dioxo heterocycles liii reaction of 3 aroyl 1h pyrrolo 2 1 c 1 4 benzoxazine 1 2 4 triones with substituted 1 3 3 trimethyl 3 4 dihydroisoquinolines a new approach to 13 aza analogs of steroids
Russian Journal of Organic Chemistry, 2007Co-Authors: N. L. Racheva, Yurii V Shklyaev, Yu S Rozhkova, A N MaslivetsAbstract:3-Aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones reacted with substituted 1,3,3-trimethyl-3,4-dihydroisoquinolines to give the corresponding 3-aroyl-4-hydroxy-1-(2-hydroxyphenyl)-5′,5′-dimethyl-5′,6′-dihydro-1H-spiro[pyrrole-2,2′-pyrrolo[2,1-a]isoquinoline]-3′,5-diones. 7′,8′-Benzo derivatives of the latter may be regarded as 13-azagonane analogs having a spiro-fused pyrrole ring at C16.
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five membered 2 3 dioxo heterocycles li reaction of 3 aroyl 2 4 dihydro 1h pyrrolo 2 1 c 1 4 benzoxazine 1 2 4 triones with 3 amino 5 5 dimethylcyclohex 2 en 1 ones
Russian Journal of Organic Chemistry, 2007Co-Authors: N. L. Racheva, S N ShurovAbstract:3-Aroyl-2,4-dihydro-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones react with N-unsubstituted and N-substituted 3-amino-5,5-dimethylcyclohex-2-en-1-ones to give 3′-aroyl-4′-hydroxy-1′-(o-hydroxy-phenyl)-6,6-dimethyl-6,7-dihydrospiro[indole-3,2′-pyrrole]-2,4,5′(1H,1′H,5H)-triones. The molecular and crystalline structure of the 1-cyclohexyl-substituted derivative was studied by X-ray analysis.
A N Maslivets - One of the best experts on this subject based on the ideXlab platform.
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five membered 2 3 dioxo heterocycles xci reaction of 3 aroyl 1h pyrrolo 2 1 c 1 4 benzoxazine 1 2 4 triones with dimedone crystalline and molecular structure of 3 benzoyl 4 hydroxy 1 2 hydroxyphenyl 6 6 dimethyl 6 7 dihydrospiro 1 benzofuran 3 2 pyrr
Russian Journal of Organic Chemistry, 2013Co-Authors: N M Tutynina, N. L. Racheva, V A Maslivets, A N MaslivetsAbstract:3-Aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones reacted with 5,5-dimethylcyclohexane-1,3-dione to give 3′-aroyl-4′-hydroxy-1′-(2-hydroxyphenyl)-6,6-dimethyl-6,7-dihydrospiro[1-benzofuran-3,2′-pyrrole]-2,4,5′(1′H,5H)-triones. The crystalline and molecular structures of 3′-benzoyl-4′-hydroxy-1′-(2-hydroxyphenyl)-6,6-dimethyl-6,7-dihydrospiro[1-benzofuran-3,2′-pyrrole]-2,4,5′(1′H,5H)-trione were determined by X-ray analysis.
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synthesis of dispiro hetero analogs of pyrrolizidine alkaloids
Russian Journal of Organic Chemistry, 2012Co-Authors: V. V. Konovalova, Yurii V Shklyaev, A N MaslivetsAbstract:Reactions of spiro heterocyclic enamines with 1H-pyrrole-2,3-diones, including those fused at the N–C bond to nitrogen-containing heterocycles, were not studied. We have found that 3-aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones Ia and Ib react with an equimolar amount of 2′,5′,5′-trimethyl-4′,5′-dihydro-4H-spiro[naphthalene-1,3′-pyrrol]-4-one (II) (which may be regarded as potential 1,3-C,N-binucleophile) in boiling anhydrous benzene (reaction time 2–5 min, until bright violet color typical of the initial pyrrolobenzoxazinetriones disappeared) to give 3′′-aroyl-4′′-hydroxy-1′′-(2-hydroxyphenyl)-3′,3′-dimethyl-2′,3′-dihydrodispiro[naphthalene-1,1′-pyrrolizine-6′,2′′-pyrrole]-4,5′,5′′(1′′H)-triones IIIa and IIIb in almost quantitative yield. The spectral parameters of compounds IIIa and IIIb are very similar to those found for model ethyl 4-benzoyl-3-hydroxy-1-(2-hydroxyphenyl)-8-methyl-2,6-dioxo-1,7-diazaspiro[4.4]nona-3,8-diene-9-carboxylate whose structure was proved by X-ray analysis [1]. Presumably, the first step is addition of the activated β-CH group in the enamino tautomer of II at the C atom in Ia or Ib, followed by closure of pyrrole ring via intramolecular attack by the amino group of the enamine fragment on the lactone carbonyl carbon atom in the oxazine ring and opening of the latter at the C–O bond, as was reported by us previously for the reaction of pyrrolobenzoxazinetriones with 1-methyl3,4-dihydroisoquinolines [2]. The described reaction is an example of regioselective synthesis of previously inaccessible dispiro heterocyclic system with various substituents in several positions of both heterocyclic fragments. The products may be regarded as dispiro heterocyclic analogs of pyrrolizidine alkaloids [3]. 4′′-Hydroxy-1′′-(2-hydroxyphenyl)-3′,3′-dimethyl-3′′-(4-methylbenzoyl)-2′,3′-dihydrodispiro[naph-
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five membered 2 3 dioxo heterocycles liii reaction of 3 aroyl 1h pyrrolo 2 1 c 1 4 benzoxazine 1 2 4 triones with substituted 1 3 3 trimethyl 3 4 dihydroisoquinolines a new approach to 13 aza analogs of steroids
Russian Journal of Organic Chemistry, 2007Co-Authors: N. L. Racheva, Yurii V Shklyaev, Yu S Rozhkova, A N MaslivetsAbstract:3-Aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones reacted with substituted 1,3,3-trimethyl-3,4-dihydroisoquinolines to give the corresponding 3-aroyl-4-hydroxy-1-(2-hydroxyphenyl)-5′,5′-dimethyl-5′,6′-dihydro-1H-spiro[pyrrole-2,2′-pyrrolo[2,1-a]isoquinoline]-3′,5-diones. 7′,8′-Benzo derivatives of the latter may be regarded as 13-azagonane analogs having a spiro-fused pyrrole ring at C16.