Synthesis of 6H-pyrrolo[3′,4′:2,3][1,4]diazepino[6,7,1-hi]indole-8,10(7H,9H)-diones using 3-bromo-4-(indol-1-yl)maleimide scaffold

Lakatosh, S. A.; Luzikov, Yu. N.; Preobrazhenskaya, M. N.

doi:10.1039/b211163b

Cited by 35 publications

(13 citation statements)

References 7 publications

(11 reference statements)

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“…A series of derivatives of bis(indolyl)maleimides are undergoing clinical testing at present [1, 2]. Derivatives of bis(indol-1-yl)-, 2-alkylamino-3-(indol-1-yl)maleimides (for example compounds 1 and 2 ) were synthesized previously [3]. It was shown that under the action of protic acids these compounds are cyclized with the formation of a diazepine seven-membered ring with annelated indoline and maleimide fragments (3 and 4 respectively) in difference to bis(indol-3-yl)maleimides 5, which form compounds with a six-membered central ring 6 under similar conditions [4] (Scheme 1).…”

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confidence: 99%

Synthesis of 2-hetaryl-3-(indol-1-yl)-and -(3-pyrrol-1-yl)maleimides and study of their conversions under the action of protic acids*

Lakatosh

Bykov

Preobrazhenskaya

2011

Chem Heterocycl Comp

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A series of 3-(indol-1-yl)maleimides has been synthesized, substituted at position 2 by residues of amines or various nitrogenous heterocycles. The possibility of obtaining new polycondensed heterocyclic structures from them has been studied. Experimental investigations confirmed theoretical predictions made on the basis of results of quantum-chemical calculations.Keywords: indole, indolylmaleimides, quantum chemistry, cyclization reaction.2-Aryl-3-indolylmaleimides, and also 2-aminoaryl-3-indolylmaleimides and their derivatives are of interest as potential inhibitors of protein kinases, which may serve as a basis for constructing new medicinal preparations. A series of derivatives of bis(indolyl)maleimides are undergoing clinical testing at present [1, 2]. Derivatives of bis(indol-1-yl)-, 2-alkylamino-3-(indol-1-yl)maleimides (for example compounds 1 and 2 ) were synthesized previously [3]. It was shown that under the action of protic acids these compounds are cyclized with the formation of a diazepine seven-membered ring with annelated indoline and maleimide fragments (3 and 4 respectively) in difference to bis(indol-3-yl)maleimides 5, which form compounds with a six-membered central ring 6 under similar conditions [4] (Scheme 1).In the present work the preparation is described of various 3,4-bis(hetaryl)maleimides, including 2-hetaryl-3-(indol-1-yl)maleimides, and also 2-amino-3-(indol-1-yl)maleimides, and the transformation of some of them under the action of protic acids has been studied. For the purpose of predicting the direction of cyclization of 2-hetaryl-3-(indol-1-yl)maleimides under the action of protic acids, quantum-chemical calculations were carried out of the electron density distribution at the reaction centers of hetarylmaleimides and their indoleninium cations formed on protonation, and also of the energy parameters of the respective cyclization reactions.

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confidence: 99%

Synthesis of 2-hetaryl-3-(indol-1-yl)-and -(3-pyrrol-1-yl)maleimides and study of their conversions under the action of protic acids*

Lakatosh

Bykov

Preobrazhenskaya

2011

Chem Heterocycl Comp

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“…Another example of cyclization involving the α-methylene atom of the amino group was demonstrated by Preobrazhenskaya's group [74,75]. In the presence of strong acids, 2-(dialkylamino)-3-(indol-1-yl)maleimides 97 underwent cyclization to 1,4-diazepines 98 annelated to an indole ring [75,76].…”

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confidence: 99%

tert-Amino effect: the Meth-Cohn and Reinhoudt reactions (Review)

Platonova

Глухарева

Zimovets

et al. 2013

Chem Heterocycl Comp

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The term "tert-amino effect" was proposed in 1972 [1] for the cyclization reactions of tertiary anilines containing various double bonds at the ortho position. Meth-Cohn and Suschitzky [1] referred to the first observation of the tert-amino effect by Pinnow in 1895 [2]. Many different examples of reactions involving the tert-amino effect have now accumulated, and it clearly is a convenient method for the synthesis of an impressive number of nitrogen-containing heterocycles that otherwise might be difficult to obtain. Reviews were published by Reinhoudt in 1990 [3] and by Meth-Cohn in 1996 [4] on heterocyclization reactions that take place by the mechanism of the tert-amino effect. Another review dedicated to 1,6-and 1,8-naphthiridine derivatives was published in 2003 by Quintela [5]. In the review [6] that we published in 2005, attention was focused on the use of such reactions for the synthesis of spiro compounds. In the review [7], published in 2006, the cyclization reactions of ortho-vinylanilines and their heterocyclic aza analogs were considered, and classification according to the method of ring formation was proposed.

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“…1,2 Earlier, 3,4 it was shown that intramolecular cy clizations of 3,4 bis(indol 3 yl)maleimides 1, 3 (indol 1 yl) 4 (indol 3 yl)maleimides 2, and 3,4 bis(indol 1 yl)maleimides 3 under the action of protic acids proceed differently and result in different types of compounds. 3,4 Bis(indol 3 yl)maleimides 1 under acid catalysis con ditions and after dehydrogenation form indolo [2,3]carb azole derivatives 4 (Scheme 1). In the absence of oxidant (DDQ) intermediate 5 undergoes isomerization into aminophenylcarbazole 6 (see Scheme 1).…”

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“…Research on the chemical properties and reactivity of 3,4 bisindolylmaleimides is of interest in connection with the fact that some compounds of this series and related indolo [2,3]carbazoles possess valuable biological proper ties. 1,2 Earlier, 3,4 it was shown that intramolecular cy clizations of 3,4 bis(indol 3 yl)maleimides 1, 3 (indol 1 yl) 4 (indol 3 yl)maleimides 2, and 3,4 bis(indol 1 yl)maleimides 3 under the action of protic acids proceed differently and result in different types of compounds.…”

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confidence: 99%

Transformations of 3,4-bisindolylmaleimides with differently bonded indole and maleimide moieties under the action of protic acids: A quantum chemical study

2006

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Intramolecular cyclization reactions of 3,4 bis(indol 3 yl)maleimides 1, 3 (indol 1 yl) 4 (indol 3 yl)maleimides 2, and 3,4 bis(indol 1 yl)maleimides 3 under the action of protic acids were studied in order to estimate the parameters of the interaction between protonated and unprotonated indole moieties. Geometric parameters, charge distributions, energy characteris tics, and information concerning the frontier orbitals of bisindolylmaleimides 1-3 were ob tained from density functional B3LYP/6 31G(d) quantum chemical calculations. Alternative pathways of protonation of bisindolylmaleimides with differently bonded indole and maleimide moieties were studied and pathways of cyclization of corresponding conjugated acids leading to polyannelated compounds were analyzed. All the key intermediates of the cyclization reactions correspond to stationary points on the potential energy surfaces (minima and transition states). Analysis of the potential energy surfaces revealed almost linear dependences of the activation energies of the cyclization reactions under study on the distances between the reaction centers, on the angle of approach of intramolecular electrophile, and on the energy gap (energy differ ence between frontier orbitals). The key role in the cyclization reactions is played by structural similarity between the starting indoleninium cations and the activated complexes of the reac tions under study.Research on the chemical properties and reactivity of 3,4 bisindolylmaleimides is of interest in connection with the fact that some compounds of this series and related indolo[2,3]carbazoles possess valuable biological proper ties. 1,2 Earlier, 3,4 it was shown that intramolecular cy clizations of 3,4 bis(indol 3 yl)maleimides 1, 3 (indol 1 yl) 4 (indol 3 yl)maleimides 2, and 3,4 bis(indol 1 yl)maleimides 3 under the action of protic acids proceed differently and result in different types of compounds. 3,4 Bis(indol 3 yl)maleimides 1 under acid catalysis con ditions and after dehydrogenation form indolo[2,3]carb azole derivatives 4 (Scheme 1). In the absence of oxidant (DDQ) intermediate 5 undergoes isomerization into aminophenylcarbazole 6 (see Scheme 1). Possible mecha nisms of the cyclization and isomerization of system 1 are shown in Scheme 2.Unlike 3,4 bis(indol 3 yl)maleimides 1, 3 (indol 1 yl) 4 (indol 3 yl)maleimides 2 and 3,4 bis(indol 1 yl)maleimides 3 under the action of protic acids undergo 2-4´ or 2-7´ cyclization to give 8b,9 dihydroin dolo [4´,3´:3,4,5]pyrrolo[3´,4´:6,7][1,4]azepino[1,2 a]in dol 1,3(2H,5H ) diones 7 or 9b,10 dihydroindo lo[1´,7´:4,5,6]pyrrolo[3´,4´:2,3][1,4]diazepino[1,7 a]in dol 1,3 diones 8, respectively (Scheme 3). Compounds 7 and 8 under the action of DDQ in toluene were converted to indolo[4´,3´:3,4,5]pyrrolo[3´,4´:6,7]azepino[1,2 a]in dol 1,3(2H,5H ) diones 9 and 1H indolo[1´,7´:4,5,6]pyr rolo[3´,4´:2,3][1,4]diazepino[1,7 a]indol 1,3(2H ) diones 10, respectively. Possible cyclization mecha nisms 3,4 are shown in Scheme 3.Since the cyclization reactions of differently fused bisind...

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Synthesis of 6H-pyrrolo[3′,4′:2,3][1,4]diazepino[6,7,1-hi]indole-8,10(7H,9H)-diones using 3-bromo-4-(indol-1-yl)maleimide scaffold

Cited by 35 publications

References 7 publications

Synthesis of 2-hetaryl-3-(indol-1-yl)-and -(3-pyrrol-1-yl)maleimides and study of their conversions under the action of protic acids*

Synthesis of 2-hetaryl-3-(indol-1-yl)-and -(3-pyrrol-1-yl)maleimides and study of their conversions under the action of protic acids*

tert-Amino effect: the Meth-Cohn and Reinhoudt reactions (Review)

Transformations of 3,4-bisindolylmaleimides with differently bonded indole and maleimide moieties under the action of protic acids: A quantum chemical study

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