Five-membered 2,3-dioxoheterocycles: LVIII. Reaction of methyl 1-Aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1H-pyrrol-2-carboxylates with substituted 1-methyl-3,4-dihydroisoquinolines. New approach to the synthesis of steroid 13-azaanalogs

Methyl 1-aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with substituted 1-methyl-3,4-dihydroisoquinolines with the formation of substituted 3-oxo-2,3,5,6-tetra-hydropyrrolo[2,1-a]-isoquinoline-2-spiro-2′-(1-aryl-3-aroyl-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrroles). A new approach was developed to the synthesis of 13-azagonanes, substituted benzo[f]pyrrolo[2,1-a]isoquinoline-9-spiro-2′-pyrroles.     

The synthesis of indolo- and pyrrolo[2,1-a]isoquinolines

The synthesis of fused isoquinolines from N-benzyl protected indoles and pyrroles is described. For example, treatment of t-butyl-2-(2-formyl-3,4-dihydro-1-naphthalenyl)-3-methyl-1H-indole-1-carboxylate with KOBu^t in DMF provided 14-methyl-8-phenylbenzo[h]indolo[2,1-a]isoquinoline in good yield. Analogous N-benzylpyrrole precursors could similarly be cyclized to give pyrrolo[2,1-a]isoquinolines.     

A rapid access to indolo[2,1-a]pyrrolo[4′,3′:4,5]pyrano[5,6-c]coumarin/[6,5-c]chromone derivatives by domino Knoevenagal intramolecular hetero Diels-Alder reactions

Knoevenagal condensation of indole-2-carbaldehyde containing an internal dienophile with coumarins, followed by domino intramolecular hetero Diels-Alder reaction, provides polycyclic heterocycles. Different approaches for stereo- and chemoselective synthesis of indolo[2,1-a]pyrrolo[4′,3′:4,5]pyrano[5,6-c]coumarin and indolo[2,1-a]pyrrolo[4′,3′:4,5]pyrano[6,5-c]chromone derivatives are described.     

One-pot two-step tandem reactions for selective synthesis of pyrrolo[2,1-a]isoquinolines and dihydro-, tetrahydro-derivatives

A sequential one-pot two-step tandem reaction for selective and efficient synthesis of pyrrolo[2,1-a]isoquinoline and its dihydro- and tetrahydro-derivatives has been developed. The tandem reactions of isoquinoline, α-halogenated methylene compounds, aromatic aldehydes, and cyanoacetamide firstly give tetrahydropyrrolo[2,1-a]isoquinolines as main products. The corresponding pyrrolo[2,1-a]isoquinolines and dihydropyrrolo[2,1-a]isoquinolines can be obtained directly by controlling oxidation with DDQ. The mechanism of this tandem reaction involved the 1,3-dipolar cycloaddition of isoquinolinium ylide as the key step. A unique elimination of the amido group preferring to the cyano group has been observed.     

Facile synthesis of 6,12b-diaza-dibenzo[a,h]azulen-7-ones and benzo[f]pyrrolo[1,2-a][1,4]diazepin-4-ones via CuI/l-proline catalyzed intramolecular N-arylation

Facile intramolecular N-arylation catalyzed by CuI/l-proline has been developed to prepare 6,12b-diaza-dibenzo[a,h]azulen-7-ones and benzo[f]pyrrolo[1,2-a][1,4]diazepin-4-ones in good to excellent yields.     

2-Oxobenzo[h]chromene: a novel entry for the synthesis of functionalized angular polycyclic azaarenes

An efficient and short synthesis of (5,6-dihydrobenzo[h]pyrido[2,1-b]quinazolin-2-ylidene)acetonitriles, (5,6-dihydrobenzo[h]pyrazino[2,1-b]quinazolin-2-ylidene)acetonitriles and (5,6-dihydrobenzimidazo[1,2-b]benzo[f]isoquinolin-7-yl)acetonitriles in good yields is delineated through base catalyzed ring transformation of 4-(piperidin-1-yl)-2-oxo-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles with 2-amino-pyridine, 2-aminopyrazine and (imidazo-2-yl)acetonitrile.     

Synthesis of new benzo[b]thieno fused ring systems via transition metal-mediated cyclisations

The compact synthesis of a new ring fused benzo[b]thieno derivative with an embedded nine-membered ring system via ring closing metathesis methodology is described. The preparation of the novel 11H-benzo[b]thieno[2,3-c]pyrrolo[2,3-a]indol-11-one via palladium-mediated oxidative cyclisation of benzo[b]thien-2-oyl indole derivatives is also reported.     

Solvent-free reaction between acenaphthoquinone, various benzils and ammonium acetate: synthesis of 9,10-diaryl-7H-benzo[d,e]imidazo[2,1-a]isoquinolin-7-ones

A simple synthesis of benzo[d,e]imidazo[2,1-a]isoquinolines is described. Heating a mixture of acenaphthoquinone, a benzil, and ammonium acetate under solvent-free conditions afforded 9,10-diaryl-7H-benzo[d,e]imidazo[2,1-a]isoquinolin-7-ones in good to excellent yields.     

Synthesis and some properties of N-unsubstituted pyrrolo[2,1-c]-1,3-diazacycloalkano[1,2-a]pyrazinones

Reactions of methyl 2-(2-formyl-1H-pyrrol-1-yl)alkanoates with unsubstituted aliphatic 1,2-, 1,3-, and 1,4-diamines gave N-unsubstituted pyrrolo[2,1-c]-1,3-diazacycloalkano[1,2-a]-pyrazinones. Some of them show ring-chain tautomerism. Transformations of these compounds led to a number of novel heterocyclic systems: 2,10-dihydro-3H,5H-imidazo[1,2-a]-pyrrolo[1,2-d]pyrazines, 2,3,4,11-tetrahydro-6H-pyrrolo[1??,2??:4,5]pyrazino[1,2-a]pyrimidines, 1,2,3,5,6,10b-hexahydroimidazo[1,2-a]pyrrolo[2,1-c]pyrazines, 1,3,4,6,7,11b-hexahydro-2H-pyrrolo[2??,1??:3,4]pyrazino[1,2-a]pyrimidines, and 2,3,4,5,6,7-hexahydro-1H-pyrrolo[2,1-c]-[1,4,7]triazacycloundecin-8(9H)-one.     

Synthesis of 9,10,12,13,14,14a-hexahydrodibenzo[f,h]pyrrolo-[2,1-a]isoquinoline

The synthesis of 9,10,12,13,14,14a-hexahydrodibenzo[f,h]pyrrolo[2,1-a]isoquinoline 6 has been accomplished by a sequence involving as a key step the Friedel-Crafts intramolecular acylation of the amino acid 9 to the corresponding pentacyclic aminoketone 10 . Compounds 7, 11 and 12 showed a significant protein synthesis inhibitory effect.     

Synthesis of novel imidazo[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepines and pyrimido[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepines

Several 1 1-amino-5H-pyrrolo[2,1-c][1,4]benzodiazepines have been used as starting material to prepare a number of derivatives of 9H-imidazo[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepines and 10H-pyrimido[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepines. The imidazole nucleus was built by reaction of amidines with ethyl bromopyruvate or aminoacetaldehyde dimethylacetal. Several derivatives of imidazo[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepine have been prepared by formylation of the pyrrole ring followed by formation of thioamides. Condensation of 11-amino-5H-pyrrolo[2,1-c][1,4]benzodiazepines with diethyl ethoxymethylenemalonate afforded intermediate diesters which were transformed into the corresponding 10H-pyrimido[1,2-a]pyrrolo[2,1-c]-benzodiazepines.     

Synthesis of novel benzo naphtho naphthyridines from 2,4-dicloroquinolines

A schematic study on the condensation of 2,4-dichloroquinolines ( 1 ) with 1-naphthyamine ( 2 ) in the presence of CuI as a catalyst to functionalized mono ( 3 ) and di ( 4 ) substituted naphthylamino quinolines was described. Consequently, these mono- and di-substituted amines on polyphosphoric acid-catalyzed cyclization reaction with p-toluic acid and acetic acid to yield the linear benzo[b]naphtho[2,1-g][1,8]naphthyridines ( 5 ) and angular benzo[b]naphtho[2,1-h] naphthyridines ( 6 ) in good yields. In addition to descried the similar synthesis of benzo[g]naphtho [2,1-b][1,8]naphthyridines ( 12 ) and benzo[h]naphtho[2,1-g][1,8]naphthyridines ( 13 ) from 2,4-dichlorobenzo[h]quinoline ( 8 ) with various anilines ( 9 ) through my intermediates ( 10 and 11 ).     

Synthesis of annulated dihydroisoquinoline heterocycles via their nitrogen ylides

3,4-Dihydro-6,7-dimethoxyisoquinoline-1-acetonitrile reacts with some α-bromoketones in dry benzene to give the corresponding isoquinolinium salts, which undergo intramolecular cyclization to give pyrrolo[2,1-a]isoquinolines. Cross-coupling of the latter compounds with some aryldiazonium chlorides resulted in the formation of 3-arylhydrazonopyrrolo[2,1-a]isoquinolines, 3-arylazopyrrolo[2,1-a]isoquinolines and 3-aryl-1,2,3-triazolo[5,1-a]isoquinolines, respectively. The structures of the products were established on the basis of their elemental and spectral analyses as well as X-ray single crystal studies.     

Contributions to syntheses of pyrrolo[2,1-a]phthalazines

Abstract  

Structural elucidation of the dihydro derivatives obtained as by-products in the classic salt method synthesis of pyrrolo[2,1-a]phthalazines and acetylenic dipolarophiles was achieved by X-ray diffraction analysis of a representative compound. In addition, new pyrrolo[2,1-a]phthalazines were obtained by a one-pot three-component reaction that avoids the formation of the dihydro derivative intermediates.     

Some novel heterocyclic systems derived from 7-amino-2,3-dihydro-8-nitro-1H-pyrrolo[1,2-α]benzimidazole and the corresponding diamine

The preparation of 7-amino-2,3-dihydro-8-nitro-1H-pyrrolo[1,2-a]benzimidazole from 1,4-diacetamido-2,3-dinitrobenzene is described. Reaction of this compound with 2,5-dimethoxytetrahydrofuran produces 2,3-dihydro-8-nitro-7-N-pyrrolo-1H-pyrrolo[1,2-a]benzimidazole, which can be cyclised to produce two new heterocyclic ring systems, 9,10-dihydro-8H-pyrrolo[1,2-a]pyrrolo(1′,2′:1,2]imidazo[5,4-f]quinoxaline and 9,10-dihydro-8H-pyrrolo[2,1-c]pyrrolo[1′,2′:1,2]imidazo[4,5-h][1,2,4]benzotriazine. The corresponding diamine, 7,8-diamino-2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazole undergoes a variety of condensation reactions to produce several new heterocyclic systems, for example, with formic acid, 1,7,8,9-tetrahydroimidazo-[4,5-e]pyrrolo[2,1-6]benzimidazole is formed and with diacetyl, 9,10-dihydro-2,3-dimethyl-8H-pyrrolo-[1′,2′:1,2]imidazo[5,4-y]quinoxaline is obtained.     

Synthesis of benzoindoloquinolizines via a Cu(I)-mediated C–N bond formation

An effective synthesis of the multi ring-fused benzoindoloquinolizines has been accomplished by Cu(I)-mediated and MW-assisted C–N_amide bond formation of benzo[a]quinolizin-4-ones. The deamination of tetrahydro-2H-pyrido[2,1-a]isoquinolines was also studied and was found to give benzoquinolizines. The benzo[a]quinolizin-4-ones were prepared based on the annulations of C-1 substituted 3,4-dihydroisoquinolines and azlactones.     

Heterocyclic quinones with bridgehead nitrogen atoms. Part I. Pyrrolo[1,2-a]quinoxaline-6,9-dione and pyrrolo[2,1-c][1,2,4]benzotriazine-6,9-dione

The synthesis and some reactions of pyrrolo[1,2-a]quinoxaline-6,9-dione and pyrrolo[2,1-c][1,2,4]benzotriazine-6,9-dione are described.     

First enantioselective synthesis of the antitumour alkaloid (+)-crispine A and determination of its enantiomeric purity by 1H NMR

A simple enantioselective synthesis of the pyrrolo[2,1-a]isoquinoline alkaloid (+)-crispine A, based on the use of an asymmetric transfer hydrogenation as the key step, is described. The enantiomeric excesses of the obtained alkaloid samples were determined from ¹H NMR spectra recorded in the presence of (+)-(R)-t-butylphenylphosphinothioic acid as a chiral solvating agent.     

Polycyclic systems: Synthesis of isoindolo[2,1-b]-pyrrolo[1,2-d][2,4]benzodiazocine and isoindolo-[1,2-d]pyrrolo[1,2-a] [1,5]benzodiazocine

The synthesis of isoindolo[2,1-b]pyrrolo[1,2-d][2,4]benzodiazocine 7 and isoindolo[1,2-d]pyrrolo[1,2-a]-[1,5]benzodiazocine 13 are described starting from 2-(2-methoxycarbonyl)benzylphthalimide 1a and ethyl α-bromohomophthalate 9 respectively.     

A synthesis of pyrrolo[2,1-a]isoquinolines through the reaction of activated acetylenes and isoquinoline in the presence of ethyl bromopyruvate

Isoquinoline reacts with ethyl bromopyruvate in the presence of dialkyl acetylenedicarboxylates or diaryloylacetylenes to produce dialkyl 1-(2-ethoxy-2-oxoacetyl)pyrrolo[2,1-a]isoquinoline-2,3-dicarboxylates or ethyl 2-[2,3-diaryloylpyrrolo[2,1-a]isoquinoline-1-yl]-2-oxoacetates in good yields.