Synthesis of Annelated Azaheterocycles Containing a 5‐Carbamoylpyrazin‐3‐one Fragment by a Modification of the Four‐Component Ugi Reaction

Ilyin, A.P.; Kobak, V. V.; Дмитриева, И. Г.; Peregudova, Yulia N.; Kustova, Veronika A.; Mishunina, Yulia S.; Ткаченко, С. Е.; Ivachtchenko, Alexandre V.

doi:10.1002/ejoc.200500522

Cited by 12 publications

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“…The parent heterocycle I was synthesized in 1957 by the reductive cyclization of 3-nitro-2-thienylpyruvic acid, followed by decarboxylation of the product, namely, thieno[3,2- b ]pyrrole-5-carboxylic acid, and also by the reduction of 2 H ,3 H -thieno[3,2- b ]pyrrol-3-one obtained via cyclization of pyrrole-3-thioacetic acid . The general synthetic approach to the substituted alkyl thieno[3,2- b ]pyrrole-5-carboxylates includes transformation of compounds II into numerous derivatives III under treatment of different reagents. − For example, the reported works describe synthesis of alkyl thieno[3,2- b ]pyrrole-5-carboxylates III with the following substituents: 2-formyl, , 2-acetyl, 2-bromo, 2,6-dibromo, 2,3,6-tribromo, 2-nitro, 2,6-dinitro, 3-formyl, 4-benzyl, 4-(2-nitrobenzyl), , 6-dimethylaminomethyl, 6-(1-piperidinylmethyl), 6-cyanomethyl, 6-formyl, , 2-methyl-3-acyl, − 2-methyl-3,6-diacyl, , 2-methyl-4-(2-oxopropyl), and 2-methyl-4-(2-oxo-2-phenylethyl) . Some of the mentioned esters were then hydrolyzed to the corresponding acids, which usually served as convenient starting materials in subsequent tran...…”

Section: Introductionmentioning

confidence: 99%

“…Syntheses of several annulated heterocycles possessing the 4 H -thieno[3,2- b ]pyrrole moiety have been previously described, for example, thieno[2,3- b ]indolizine IV , 5,6,7,8-tetrahydro-4 H -thieno[3‘,2‘:2,3]pyrrolo[4,5- c ]pyridine V , 8-oxo-5,6,7,8-tetrahydrothieno[2‘,3‘:4,5]pyrrolo[1,2- a ]pyrazine VI , 3 H ,4 H ,5 H -thieno[3‘,2‘:2,3]pyridazin-4-ones VII , , and 5-oxo-6,11-dihydro-5 H -benzo[e]thieno[2‘,3‘:4,5]pyrrolo[1,2- a ] 1,4 diazepine VIII . Among the synthesized compounds containing the thieno[3,2- b ]pyrrole moiety, several physiologically active agents were described.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of Heterocyclic Compounds Possessing the 4H-Thieno[3,2-b]Pyrrole Moiety

et al. 2006

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A series of novel heterocyclic combinatorial libraries containing 4H-thieno[3,2-b]pyrrole, thieno[2',3':4,5]-pyrrol[1,2-d][1,2,4]triazine and thieno[2',3':4,5]pyrrolo[1,2-a]pyrazine heterocyclic moieties were obtained by parallel solution-phase synthesis. Key steps include different reactions of initial alkyl 4H-thieno[3,2-b]-pyrrole-5-carboxylates, such as alkylation with alkylating agents; transformation of the carboxylate group into different reactive functionalities, followed by reactions with electrophilic species; intramolecular cyclizations; and amide bond formation. Simple manual techniques for parallel reactions were coupled with easy purification procedures to give high-purity final products.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis of Heterocyclic Compounds Possessing the 4H-Thieno[3,2-b]Pyrrole Moiety

et al. 2006

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“…Such examples are cyclization of imidazolecarboxamides, 5 ring opening of theophyllin-7-acetic acid with subsequent cyclization, 6 cyclization of chiral hydroxyethylaminocarbonyl substituted imidazole derivatives, 7 and a modification of the Ugi reaction with 4-methoxycarbonyl-1-(2-oxopropyl)-1H-imidazole-5-carboxylic acid. 8 Furthermore, some fused imidazo [1,5-a]pyrazines have also been investigated. For example, such compound is the 5,10-methylenetetrahydrofolate, a very important coenzyme.…”

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Synthesis of Highly Functionalized Imidazo[1,5-a]pyrazines

Trček¹,

Vercek²

2006

Synthesis

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Four 'one-pot' syntheses of highly substituted imidazo[1,5-a]pyrazines 7-9, starting from diaminomaleonitrile derivatives 1 and 2, and imidazoles 3 and 5, are described.The imidazo[1,5-a]pyrazine system has attracted considerable interest during the last few decades mainly due to the intensive search for biologically active compounds. 1 Its derivatives have been usually prepared from suitably substituted pyrazines such as (aminomethyl)pyrazines, 2 cyano substituted dihydropyrazinecarboxamide, 3 and (ureidomethyl)pyrazines 4 by the closure of the imidazole ring. On the other hand, this bicyclic system is also accessible from some imidazole derivatives. Such examples are cyclization of imidazolecarboxamides, 5 ring opening of theophyllin-7-acetic acid with subsequent cyclization, 6 cyclization of chiral hydroxyethylaminocarbonyl substituted imidazole derivatives, 7 and a modification of the Ugi reaction with 4-methoxycarbonyl-1-(2-oxopropyl)-1H-imidazole-5-carboxylic acid. 8 Furthermore, some fused imidazo[1,5-a]pyrazines have also been investigated. For example, such compound is the 5,10-methylenetetrahydrofolate, a very important coenzyme. 9 In addition, several synthetic imidazo[1,5-a]quinoxalines have been proven as biologically important and medicinally useful compounds. 10 A few years ago, we began to investigate the use of diaminomaleonitrile, an excellent synthetic tool in heterocyclic synthesis, 11,12 in the preparation of heteroaryl-substituted amino acid derivatives and other compounds. In these investigations, the compound 1 was prepared from diaminomaleonitrile and 4-ethoxymethylidene-2-phenyl-1,3-oxazole-5(4H)-one and transformed further with alcohols into 2. 13,14 Moreover, the imidazole 3 was synthesized from 1 and transformed further into a series of 5. 15 We published a preliminary communication on the synthesis of the imidazo[1,5-a]pyrazines 7 and 8, existing as the tautomers A and B. 16 Herein, we wish to give a full description of various one-pot possibilities for the preparations of the imidazo[1,5-a]pyrazines 7-9 starting from the compounds 1-6 ( Figure 1).As reported previously, heating of various 3-[(2-amino-1,2-dicyanovinyl)amino]-2-(benzoylamino)propenoates 2a-g in triethyl orthoformate resulted in the formation of the corresponding 8-benzoylimino-3-cyano-7,8-dihydroimidazo[1,5-a]pyrazine-6-carboxylates 7a-g. 17 In order to extend the scope of this interesting transformation, the esters 2 were then treated with triethyl orthoacetate affording the 3-methyl substituted imidazopyrazines 8a-g. This methodology was then also used for the preparation of the chloromethyl substituted imidazopyrazine 9f, which was obtained in 66% yield when 2f was heated with trimethyl orthochloroacetate for 3.5 hours (Scheme 1). Figure 1Scheme 1 One-pot transformation of 2 into imidazopyrazines 7-9. Reagents and conditions: i) for products 7a-g: HC(OEt) 3 , D, 2-8 h, 48-78%); for products 8a-g: MeC(OEt) 3 , D, 3.5-5 h, 65-89%; for product 9f: R = pentyl, R¢ = CH 2 ClClCH 2 C(OMe) 3 , D, 3.5 h, 66%.

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A Half‐Century of the Ugi Reaction: Modified Variants

Ullrich

Kazmaier

2023

Organic Reactions

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The classic Ugi reaction is a four‐component coupling process involving a carboxylic acid, a carbonyl compound, an amine, and an isocyanide, resulting in an N ‐acylamino acid amide product. Modified Ugi reactions employ special, often multifunctional, reaction components, and can involve fewer than or more than four components. This reaction exhibits broad scope and can be used to prepare complex heterocycles. As a result, this method has been employed to prepare diverse libraries of structurally related products, and in addition, is often applied to the synthesis of drugs, drug‐like molecules, and natural products. Applications in target‐directed synthesis are presented, as are comparisons to other related multicomponent reactions and heterocycle syntheses; modifications leading to achiral heteroaromatic ring systems are not included. This chapter covers the literature from the early days of the Ugi reaction in 1961 through the end of 2012.

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Synthesis of Annelated Azaheterocycles Containing a 5‐Carbamoylpyrazin‐3‐one Fragment by a Modification of the Four‐Component Ugi Reaction

Cited by 12 publications

References 19 publications

Synthesis of Heterocyclic Compounds Possessing the 4H-Thieno[3,2-b]Pyrrole Moiety

Synthesis of Heterocyclic Compounds Possessing the 4H-Thieno[3,2-b]Pyrrole Moiety

Synthesis of Highly Functionalized Imidazo[1,5-a]pyrazines

A Half‐Century of the Ugi Reaction: Modified Variants

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