Synthesis of derivatives of pyrrolo[1, 2-α]pyrmidine

Continuing investigations in the field of the synthesis of condensed heterocyclic systems containing pyrrole and indole fragments ¦1–3¦, we have condensed of 2-aminopyrrole derivatives with various 1, 3-dicarbonyl compounds. The reaction took place at the boil in solutions in pyridine or acetic acid, and also without a solvent at 150–160° C, forming in a single stage derivatives of pyrrolo[1, 2-a]pyrimidine (I–III) and pyrrolo[2, 1-b]-tetrahydroquinazoline (IV–VI). The condensation of 2-aminopyrrole with acetoacetic and substituted acetoacetic esters led to 4-oxo derivatives of pyrrolo[1, 2-β]pyrimidine (VII and VIII).     

Synthesis of 3-amino-1-benzyl-4-benzenesulfonyl-2-carbonitrilo-1H-pyrrole and preparation of related pyrrolo[3,2-d]pyrimidines

A method for the synthesis of a new 4-phenylsulfonyl-substituted 3-aminopyrrole was developed and related pyrrolo[3,2-d]pyrimidine derivatives were synthesized.     

Torp-Ziegler Cyclization in the Synthesis of 3-Amino-4-cyanopyrrole Derivatives

Polyfunctional derivatives of 3-aminopyrrole have been synthesized from several substituted -enamino nitriles using Torp-Ziegler cyclization. These compounds are starting materials for further conversions, particularly for the synthesis of pyrrolo[3,2-d]- and pyrrolo[3,4-d]pyrimidines.     

Research on lactams

2-OxO-3,3-dihydroxy-4-bromohexahydroazepine was obtained by bromination of an enamine of -oxocaprolactam and subsequent hydrolysis of the resulting bromoimmonium salt and by direct bromination of -oxocaprolactam. The reaction of the product with thiourea, N-substituted o-aminothiophenols, aminouracils, and acetoacetic ester gave derivatives of thiazolo[4,5-c] azepine, azepino[4,3-b][1,4]benzothiazine, azepino [3,4-b]pyrrolo [2,3-d] pyrimidine, and furo[2,3-c] azepine.See [1] for communication XXVIII.Translated from Khimiya Geterotsiklicheskikh Soedlnenii, No. 3, pp. 374–378, March, 1978.     

Synthesis and reactions of ethyl 3-acetyl-8-cyano-6,7-dimethylpyrrolo[1,2-a]pyrimidine-4-carboxylate and related compounds

The reactions of 3-acetyl-4-ethoxycarbonyl- or 3,4-diethoxycarbonylpyrrolo[1,2-a]pyrimidine derivatives 7a,b , which were prepared by condensation of the 2-aminopyrrole ( 4 ) with ethyl 3-ethoxymethylene-2,4-dioxovalerate ( 5a ) or ethyl ethoxymethyleneoxaloacetate ( 5b ), with diazomethane are described. Thus, reaction of 7a , with diazomethane gave ethyl 2a-acetyl-7-cyano-2a,3a-dihydro-5,6-dimethyl-3H -cyclopropa[e]pyrrolo[1,2-a]pyrimidine-3a-carboxylate ( 11 ) in 74% yield, which was readily transformed into the 1-pyrrol-2-yl-pyrrole ( 18 ) by treatment with potassium hydroxide. On the other hand, reaction of 7b with diazomethane afforded three products whose structures were assigned as diethyl 7-cyano-2a,3a-dihydro-5,6-dimethyl-3H-cyclopropa[e]pyrrolo[1,2-a]pyrimidine-2a,3a-carboxylate ( 20 ), 6-cyano-7,8-dimethyl-3a,3b,5,9a-tetrahydro-4H -aziridino[c]-1H or 3H-pyrazolo[3,4-e]pyrrolo[1,2-a]pyrimidine-3a,9a-dicarboxylates ( 21,22 ). Ring Transformation of 20 to 25 was not observed.     

Heterocyclization of functionalized heterocumulenes with C,N- and C,O-binucleophiles: IV. Reactions of 1-chloroalkylheterocumulenes and <Emphasis Type="Italic">N</Emphasis>-(1-chloroalkylidene)carbamates with 2-benzimidazolylacetonitriles and methyl 2-benzimidazolylacetates

1-Chloroalkyl isocyanates and 1-chloroalkylcarbodiimides undergo regioselective cyclization with nitriles and esters of 2-benzimidazolylacetic acid to give derivatives of 1-oxo and 1-arylimino-1,2,3,5-tetrahydrobenzo[4,5]imidazo[1,2-c]pyrimidine respectively. The cyclocondensation of 1,1-dichloroalkyl isocyanates or N-(1-chloroalkylidene)carbamates with nitriles and esters of 2-benzimidazolylacetic acid afforded 1,5-dihydrobenzo[4,5]imidazo[1,2-c]pyrimidin-1-one derivatives.Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 11, 2004, pp. 1715–1724.Original Russian Text Copyright © 2004 by Vovk, Lebed, Pirozhenko, Tsymbal.For communication III see [1].     

Protonation of pyrrolo [1,2-α] Pyrimidine derivatives

The protonation of pyrrolo [1,2-] pyrimidine and 6, 7, 8, 9-tetrahydropyrimido [1, 2-] indole derivatives in CF₃COOH (at –15 to +25° C) and in CF₃COOH/H₂SO₄ (at 25°) was studied by PMR spectroscopy. The investigated compounds form monocations, the structure of which corresponds to the addition of a proton to the carbon atom of th pyrrole fragment in the position to the bridge nitrogen atom.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 686–692, May, 1976.     

A new method for the synthesis of pyrrolo[1,2-a]pyrazines and pyrrolo[1,2-a] quinoxalines

A new method is proposed for the synthesis of pyrrolo[1,2-a]pyrazines and pyrrolo[1,2-a]-quinoxalines. By the alkylation of sodium derivatives of 2-acylpyrroles with -bromo carbonyl compounds or their acetals and subsequent treatment of the reaction products with ammonium acetate in acetic acid, a number of derivatives of pyrrolo[1,2-a]pyrazine, including the first member of the class, pyrrolo[1,2-a]pyrazine itself, have been obtained. Similarly, from 2-benzoylpyrrole and the dimethyl ketal of -bromocyclohexanone was obtained 4-phenyltetrahydropyrrolo[1,2-a]quinoxaline, which readily dehydrogenates in the presence of Raney nickel to form 4-phenylpyrrolo[1,2-a]quinoxaline.Translated from Khimiya Geterotsiklicheskikh Soedinenii, Vol. 6, No. 8, pp.1048–1050, August, 1970.     

Pyrrolopyrimidine nucleosides. IV. The synthesis of certain 4,5-disubstituted-7-(β-d-ribofuranosyl)pyrrolo[2,3-d]pyrimidines related to the pyrrolo[2,3-d]pyrimidine nucleoside antibiotics

The treatment of 4-chloro-7-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine ( 4 ) with N-bromoacetamide in methylene chloride has furnished the 5-bromo derivative of 4 which on subsequent deacetylation provided a good yield of 5-bromo-4-chloro-7-(β-D-ribo-furanosyl)pyrrolo[2,3-d] pyrimidine ( 6 ). Assignment of the halogen substituent to position 5 was made on the basis of pmr studies. Treatment of 6 with methanolic ammonia afforded 4-amino-5-bromo-7-(β-D-ribofuranosyl)pyrrolo[2,3-d ]pyrimidine ( 8 , 5-bromotubercidin) and a subsequent study has revealed that the 4-chloro group of 6 was replaced preferentially in a series of nucleophilic displacement reactions. The analogous synthesis of 4,5-dichloro-7-(β-D-ribo-furanosyl)pyrrolo[2,3-d]pyrimidine ( 13b ) and 4-chloro-5-iodo-7-(β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine ( 13a ) from 4 furnished 5-chlorotubercidin ( 15 ) and 5-iodotubercidin ( 14 ), respectively, on treatment of 13b and 13a with methanolic ammonia. The possible biochemical significance of these tubercidin derivatives is discussed.     

Synthesis of Functionally Substituted Pyrrolo[2,3-g]- and Pyrrolo[3,2-f]quinolines from 5-Amino-2-phenyl- and 5-Amino-1-methyl-2-phenylindoles

The behavior of 5-amino-2-phenyl- and 5-amino-1-methyl-2-phenylindoles in reactions with acetoacetic, trifluoroacetoacetic, and ethoxymethylenemalonic esters, leading to the preparation of pyrrolo[2,3-g]- and pyrrolo[3,2-f]quinolines with functional substituents has been studied.