Aminosäureantagonisten. IV. Versuche zur Darstellung von [1‐Methyl‐5‐bis‐(β‐chloräthyl)‐amino‐benzimidazolyl‐(2)]‐essigsäure

Ozegowski, Werner; Krebs, D.

doi:10.1002/prac.19650290103

Cited by 17 publications

(3 citation statements)

References 5 publications

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“…The hetarylacetonitriles 3b-d were synthesized by the usual methods [47][48][49]. Phthaloylglycine and phthaloylalanine were obtained from the respective amino acids and were converted into the chlorides 4a,b by standard procedures.…”

Section: Methodsmentioning

confidence: 99%

Synthesis of 5-amino-4-hetaryl-2,3-dihydro-1h-3-pyrrolones

Tverdokhlebov

Lyashenko

Volovenko

et al. 2004

Chem Heterocycl Compd

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The interest in derivatives of 2-aminopyrrole has arisen in connection with their prospective use as medicines [1][2][3][4][5][6][7][8] and as components of dyes in photography [9][10][11]. The principal methods for the synthesis of these compounds are the condensation of methylene-active nitriles with derivatives of α-aminocarbonyl compounds [12][13][14][15][16][17] or amination of substituted 4-halobutyronitriles [18][19][20][21][22][23][24] or their synthetic equivalents [25][26][27]. Both approaches have been successfully applied to the synthesis of 1-R 1 -2,2-R 2 ,R 3 -5-amino-4-hetaryl-2,3-dihydro-3-pyrrolones [28][29][30][31][32][33][34][35][36][37]. However, they cannot be used for the production of similar derivatives unsubstituted at position 1 since, on the one hand, the N-unsubstituted α-aminocarbonyl compounds quickly dimerize to pyrazine derivatives and, on the other, the use of ammonia in the reaction together with the need for heat and a nonaqueous medium give rise to certain technical difficulties. For this reason we developed a different method for the synthesis of N-unsubstituted 2,3-dihydro-1H-3-pyrrolones 1a-h, and this method is described here.The key compounds in the synthesis of the dihydropyrrolones 1 are 2-hetaryl-3-oxo-4-phthalimidobutyronitriles 2a-e and the corresponding pentanonitriles 2f-h, obtained by acylation of the hetarylacetonitriles 3a-e with the chlorides of N-phthaloylglycine 4a and alanine 4b (see the scheme). It should be noted that acylation of the sodium salts of simple methylene-active compounds with the chlorides [38-41] and esters [17,42,43] of protected α-amino acids was used earlier for construction of the pyrrole ring. However, the acid chlorides often gave the products from bis-C,C-and bis-C,O-acylation [38,40] of complex mixtures [39], while the esters gave the enolates of the corresponding acyl derivatives. During transformation of the latter into the conjugate acids it was not always possible to avoid side processes associated with hydrolysis of the protecting groups [42,43]. We obtained the monoacyl derivatives 2a-h with yields of more than 90% as the only products (Scheme 1).The composition and structure of the nitriles 2a-h were confirmed by the results of elemental analysis (Table 1) and also by data from the IR and 1 H NMR spectra (Table 2). According to the spectral data, compounds 2a-h exist exclusively in the form of NH tautomers with an intramolecular hydrogen bond, as known for the acyl derivatives of hetarylacetonitriles [44]. Thus, the 1 H NMR spectra of the butyronitriles 2a-e

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Section: Methodsmentioning

confidence: 99%

Synthesis of 5-amino-4-hetaryl-2,3-dihydro-1h-3-pyrrolones

Tverdokhlebov

Lyashenko

Volovenko

et al. 2004

Chem Heterocycl Compd

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“…2-Acetyl-1-methyl-1H-benzimidazole (2) was prepared according to a literature procedure, 25,26 then treated with hydroxylamine hydrochloride in ethanol in the presence of potassium carbonate to give the corresponding oxime 3 27 (Scheme 1). The palladium(II) complex of this oxime 4 was prepared by dissolving the oxime 3 in methanol and adding an equimolar amount of sodium tetrachloropalladate in methanol at room temperature.…”

mentioning

confidence: 99%

“…Although the starting thiazole derivatives have never previously been employed in such transformations, we were able to use them in the preparation of libraries of new C-C cross-coupled products of potential biological interest. 25,27 and 2, 25,26 benzimidazole oxime 3, 27 4-(4-bromophenyl)-2-methyl-1,3-thiazole (5), 37 4-(4-chlorophenyl)-2-methyl-1,3-thiazole (6), 38 4-(4-bromophenyl)-N-methyl-1,3-thiazol-2amine (7), 20 and 4-(4-bromophenyl)-N-phenyl-1,3-thiazol-2-amine (8) 39 were prepared according to the procedures reported in the literature.…”

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confidence: 99%

Microwave-Assisted Synthesis of 2-Substituted 4-Biarylyl-1,3-thiazoles by Carbon-Carbon Cross-Coupling in Water

Dawood¹,

El‐Deftar²

2010

Synthesis

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Studies with Heterocyclic β‐Enaminoniriles: A Simple Route for the Synthesis of Polyfunctionally Substituted Thiophene, Imidazo[1,2:1′,6′]pyrimido[5,4‐b]thiophene and Thieno[3,2‐d]pyrimidine Derivatives

Raslan

Sayed

2003

J Chinese Chemical Soc

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Reaction of 3,5-diaminothiophene-2-carbonitrile derivatives 3a-c with ethoxycarbonylmethyl isothiocyanate and/or N-[bis(methylthio)methylene]glycine ethyl ester led to formation of 7-substituted-8-amino-5-thioxo-6H-imidazo[1,2:1¢,6¢]pyrimido[5,4-b]thiophene-2(3H)-one derivatives 6a-c and 7-substituted-8amino-5-(methylthio)imidazo[1,2:1¢,6¢]pyrimido[5,4-b]thiophene-2(3H)-one 7a-c, respectively. Also, the synthetic potential of the b-enaminonitrile moiety in 3a-c has been explored; it proved to be a promising candiate for the synthesis of 1,6-disubstituted-2,4-diamino-7,8-dihydro-8-oxopyrrolo[1,2-a]thieno[2,3-e]pyrimidine derivatives 10a-f and pyrido[2¢,3¢:6,5]pyrimido[3,4-a]benzimidazole derivatives 12a,b.

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Aminosäureantagonisten. IV. Versuche zur Darstellung von [1‐Methyl‐5‐bis‐(β‐chloräthyl)‐amino‐benzimidazolyl‐(2)]‐essigsäure

Cited by 17 publications

References 5 publications

Synthesis of 5-amino-4-hetaryl-2,3-dihydro-1h-3-pyrrolones

Synthesis of 5-amino-4-hetaryl-2,3-dihydro-1h-3-pyrrolones

Microwave-Assisted Synthesis of 2-Substituted 4-Biarylyl-1,3-thiazoles by Carbon-Carbon Cross-Coupling in Water

Studies with Heterocyclic β‐Enaminoniriles: A Simple Route for the Synthesis of Polyfunctionally Substituted Thiophene, Imidazo[1,2:1′,6′]pyrimido[5,4‐b]thiophene and Thieno[3,2‐d]pyrimidine Derivatives

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