Synthesis of pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles by Curtius reaction in Morita-Baylis-Hillman derivatives

Synthesis of substituted pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles from the Morita-Baylis-Hillman derivatives of acrylates via saponification followed by Curtius reaction is described.     

Diversity-oriented decoration of pyrrolo[1,2-a]pyrazines

Diversity-oriented synthesis of a chemical library based on a pyrrolo[1,2-a]pyrazine core is described by using palladium-catalyzed direct C6 arylation of pyrrolo[1,2-a]pyrazines with various aryl bromides. The starting materials, pyrrolo[1,2-a]pyrazines, were easily synthesized by the base-mediated N-alkylation of pyrrole-2-carboxaldehyde with several 2-bromoacetophenones followed by dehydrative cyclization with incorporation of nitrogen by the action of ammonium acetate. Introduction of other functional groups on this chemical scaffold is also discussed herein.     

A facile synthesis of pyrrolo[1,2-a]benzimidazoles and pyrazolo[3,4:4′,3′]pyrrolo[1,2-a]benzimidazole derivatives

Reaction of 2-cyanomethylbenzimidazole 1 with hydrazonoyl halides 2 led to formation of pyrrolo[1,2-a]benzimidazole derivatives 7. Similar reaction of 1 with halides 3 afforded 5-amino-4-(benzimidazol-2-yl)pyrazole derivatives 11 or 1-amino-2-arylpyrazolo[3,4:4′,3′]pyrrolo[1,2-a]benzimidazol-4-one 14 depending on the reaction conditions. The mechanisms of the studied reactions are discussed.     

Synthesis and transformations of pyrrolo[1,2-a][1,3,5]-triazines

Pyrrolotriazines and related fused azaheterocycles have high potential for the synthesis of bioactive compounds, especially as a purine base isoster in carbon linked nucleosides. Although many structurally related compounds have already been synthesized and used in medicinal chemistry, pyrrolo[1,3,5]triazines have barely been described. The present work describes the synthesis of such heterocycles via condensation of 2-amino-3-ethoxycarbonylpyrrole with ethoxycarbonyliso(thio)cyanate. In a brief reactivity study of the obtained fused pyrroles, O- and S-alkylation, ester hydrolysis as well as regioselective bromination at the 6-position was demonstrated.     

Synthesis and isomerization recyclization of pyrazino[1,2-α]indoles

A method for synthesis of pyrazinol[1,2-a]indoles with alkyl substituents in position 1 was developed based on indole and isomerization recyclization of their quaternary salts into 9-aminopyrido[1,2-a]indole derivatives was conducted.M. V. Lomonosov Moscow State University, Moscow 119899. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 331–335. March, 1995. Original article submitted February 1, 1995.     

Synthesis of pyrazino[1,2-a]benzimidazol-1(2H)ones via a microwave assisted Buchwald-Hartwig type reaction

A convenient synthesis of substituted pyrazino[1,2-a]benzimidazol-1(2H)ones starting from 3,5-dichloropyrazinones has been accomplished. Various 3-anilino-pyrazinones were easily converted to the desired tricyclic structures by applying a microwave assisted Buchwald-Hartwig type cyclization.     

Synthesis and X-ray crystal structure of pyrrolo[1,2-a]benzimidazoles

Reaction of nitrilimines 1 with 2-cyanomethylbenzimidazole 2 gave the 3-arylazo-2-methylpyrrolo[1,2-a]benzimidazole 4a rather than the reported 2-arylazo-3-methylpyrrolo[1,2-a]benzimidazole 3a. The correct structure of the product was determined using X-ray crystal structure analysis. The similar reaction of nitrilimines with 2-aminobenzimidazole 5 gave the acyclic nucleophilic addition product 6.     

Synthesis and properties of pyrrolo[1,2-a]pyrazines (review)

The synthesis and properties of pyrrolo[1,2-a]pyrazines are reviewed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1299–1311, October, 1991.     

Morita-Baylis-Hillman route to 4H-pyrrolo[1,2-a][1]benzazepine derivatives

A simple method for synthesizing substituted 4H-pyrrolo[1,2-a][1]benzazepines using acid-assisted cyclization of the Morita-Baylis-Hillman adducts of 2-(1H-pyrrol-1-yl)benzaldehydes with methyl acrylate or methyl vinyl ketone as a key step has been developed.     

Short and efficient access to imidazo[1,2-a]pyrrolo[3,2-c]pyridine derivatives

Access to N-protected or N-free imidazo[1,2-a]pyrrolo[3,2-c]pyridine derivatives as potential antiviral compounds was achieved in good yields from N-protected 7-amino-8-halo-2-methylimidazo[1,2-a]pyridines by catalytic coupling of terminal acetylenes under mild conditions using [PdCl₂(PPh₃)₂] or [Cu(Phen)(PPh₃)₂]NO₃.     

Synthesis of novel 1,2-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one derivatives

The iodolactonization product obtained from methyl 7-allylpyrrolo[2,3-d]pyrimidine-6-carboxylate was used for the synthesis of novel 1,2-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one derivatives, containing carboxamide- and methylamine-groups on the pyrrole ring of the heterocycle.     

Concise diastereospecific pyrrolo[1,2-a][1,4]benzodiazepinone synthesis

A concise synthesis of the novel pyrrolo[1,2-a]benzodiazepine system, by using the metallo carbenoid/spiro-[6,5]-ammonium ylide/Stevens[1,2]-shift with ring-expansion approach, was reported. The overall cascade process resulted stereospecific.     

Selective synthesis of N-substituted pyrrolo[1,2-a]pyrazin-1(2H)-one derivatives via alkyne cyclization

A novel and efficient synthesis of N-substituted pyrrolo-pyrazinone derivatives has been developed. A trichloroacetyl group connected to the pyrrole ring was converted into the desired carboxamide derivatives. Promoted by NaH, the pyrrole carboxamide derivatives underwent a tandem reaction with propargyl bromide to afford pyrrolo-pyrazinones with high efficiency under very mild conditions. The mechanism for the formation of the products is discussed and supported by DFT calculations.     

Formation of the same pyrimido[1,2-a]indoles from 1-(oxiran-2-ylmethyl)-1H-indole or [1,3]oxazolo[3,2-a]indole derivatives in its reactions with aromatic amines

Reactions of two isomers—2-chloro-1-(oxiran-2-ylmethyl)-1H-indole-3-carbaldehyde or 2-(chloromethyl)-2,3-dihydro[1,3]oxazolo[3,2-a]indole-9-carbaldehyde with aromatic amines lead to the same products in both cases—hydrochlorides of pyrimido[1,2-a]indole derivatives containing two fragments of an amine per one part of the indole nucleus. Its structure was confirmed by X-ray analysis of the crystals base, obtained by alkali treatment of the reaction product (when aryl is 4-MeOC₆H₄).     

Solid-phase synthesis of imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrimidines

The synthesis of imidazo[1,2-a]pyridine and imidazo[1,2-a]pyrimidine derivatives by condensation between an α-bromoketone bound to solid support and various 2-aminopyridine or 2-aminopyrimidine derivatives was described. Either an acid labile linker or a base labile linker was used in this study.     

Palladium-catalyzed double allylic alkylation of indole-2-hydroxamates: easy access to pyrazino[1,2-a]indole derivatives

The synthesis of pyrazino[1,2-a]indoles via a palladium-catalyzed double allylic alkylation of indole-2-hydroxamates is described. The reaction conditions are very mild and allow for a wide variety of substitutions on the indole core.     

Tandem synthesis of functionalized tetrahydro-4aH-benzo[c]isoquino[1,2-t]pyrrolo[1,2-a][1,6]naphthyridines

An effective route to fused hexacyclic derivatives of isoquinoline is described via tandem reaction of isoquinoline, dialkyl acetylenedicarboxylates, and 3-chloropentane-2,4-dione or alkyl 3-chloroacetoacetates.