A facile synthesis of pyrrolo[1,2-a]pyrimidines and pyrrolo[1,2-a]imidazoles

The one-step synthesis of 8-t-butoxycarbonyl-6,7-dimethyl-2-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrimidine from acetyl methyl carbinol, 3-aminopropionic acid, and t-butyl cyanoacetate is reported. Utilizing a similar technology under basic conditions, 7-substituted 5,6-dimethyl-2-oxo-2,3-dihydro-(1H)-pyrrolo[1,2-a]imidazole is synthesized from acetyl methyl carbinol, ethyl glycinate, and the appropriate acetonitrile.     

One-pot multicomponent synthesis of novel tricyclic pyrrolo[2, 1-c][1, 4]benzoxazines

A simple and efficient synthetic protocol has been developed using a one-pot multicomponent reaction （MCR） involving 2-aminophenols, dialkyl acetylenedicarboxylates, and ethyl bromopyruvate in poly（ethyleneglycol）. This protocol was utilized to prepare novel pyrrolo[2,1-c][1,4]benzoxazines in excellent yields.     

Diastereoselective intermolecular ene reactions: synthesis of 4,5,6,7-tetrahydro-1H-benzo[d]imidazoles

The Diels-Alder cycloadducts of 4-vinylimidazoles and N-phenylmaleimide are shown to undergo facile intermolecular ene reactions. Overall the reaction of three simple molecules (a diene, a dienophile and an enophile) in a two-step process gives 4,5,6,7-tetrahydro-1H-benzo[d]imidazoles with high yields, high atom economy and diastereocontrol of up to 5 new stereocentres.     

One-pot synthesis of novel 1,2,3-triazole-pyrimido[4,5-c]isoquinoline hybrids and evaluation of their antioxidant activity

A series of novel pyrimido[4,5-c]isoquinolines (3a–3h) and 1,2,3-triazole-coupled pyrimido[4,5-c]isoquinolines (4a–4h) were synthesized in good to excellent yields in the one-pot method. The reaction of 6-amino-1,3-dimethyluracil with different 2-iodo benzoyl chlorides using Pd catalyst in dimethylformamide afforded corresponding pyrimido[4,5-c]isoquinolines (3a–3h). One-pot reaction of pyrimido[4,5-c]isoquinolines with propargyl bromide and benzyl azide in THF at room temperature furnished 1,2,3-triazole-coupled pyrimido[4,5-c]isoquinoline (4a–4h). In vitro antioxidant activity examination revealed that compounds 4d and 4c found to exhibit potent antioxidant activity as compared to the standard drug Trolox with IC₅₀ values 6.02?±?0.6 and 12.18?±?0.9?µM, respectively.     

RuCl3/SnCl2 mediated synthesis of pyrrolo[2,3-c]carbazoles and consequent preparation of indolo[2,3-c]carbazoles

A simple method for the synthesis of pyrrolo[2,3-c]carbazoles from N-alkylated-3-aminocarbazole derivatives and ethylene glycol has been developed via heteroannulation reaction using RuCl₃/SnCl₂ system. Moreover indolo[2,3-c]carbazoles were prepared from various pyrrolo[2,3-c]carbazoles in good yields.     

Directed synthesis of alkyl-substitued pyrrolo[3,4-c]pyrrole-1,3,4,6-tetraones

Reactions of 3-amino-8-hydroxy-1,6-dioxo-2,7-diazaspiro[4.4]non-3-ene-4-carbonitriles with aqueous hydrohalic acid led to the formation of alkyl-substituted pyrrolo[3,4-c]-pyrrole-1,3,4,6-tetraones.     

Synthesis of new substituted chromen[4,3-c]pyrazol-4-ones and their antioxidant activities

A series of new coumarin derivatives 4 containing a 4-arylbut-3-en-2-one moiety were synthesized by condensation of 3-acetylcoumarin 1 with aryl aldehydes 2 in chloroform in the presence of piperidine. The interactions of 3-formyl-4-chlorocoumarin (3) with nitrogen-containg nucleophiles leading to the corresponding substituted chromen-[4,3-c]pyrazol-4-ones 5 are described. The structures of the obtained compounds were established on the basis of 1D NMR, 2D NMR and IR and further the compounds were evaluated for possible antioxidant activities. The coumarinic chalcone 4a has been found to be the most active (IC?? = 2.07 μM) in this study.     

The synthesis of [1]benzothieno[2,3-c]quinolines, [1]benzothieno[2,3-c][1,2,4]triazolo[4,3-a]quinoline,and [1]benzothieno[2,3-c]tetrazolo[1,5-a]quinoline

Photocyclization of 3-chloro-N-phenylbenzo[b]thiophene-2-carboxamide 10 afforded [1]benzothieno[2,3-c]-quinolin-6(5H)-one 11 which was chlorinated to 6-chloro[1]benzothieno[2,3-c]quinoline 12 followed by dechlorination to give [1]benzothieno[2,3-c]quinoline 5 . A series of 6-substituted alkoxy and thioalkoxy[1]benzothieno[2,3-c]quinoline derivatives were prepared along with the N-methyl quaternary salt 13 of 5 . 6-Chloro[1]-benzothieno[2,3-c]quinoline 12 was converted into 6-hydrazino[1]benzothieno[2,3-c]quinoline 23 which upon treatment with formic acid yielded [1]benzothieno[2,3-c][1,2,4]triazolo[4,3-a]quinoline 6 . Treatment of 23 with nitrous acid resulted in [1]benzothieno[2,3-c]tetrazolo[1,5-a]quinoline 7 . Compounds 6 and 7 are novel heterocyclic ring systems.     

Synthesis of aryl- and heteroaryl[a]pyrrolo[3,4-c]carbazoles

Synthesis of aryl- and hetero[a]pyrrolo[3,4-c]carbazoles by photochemical oxidation and Heck cyclization are described. Photochemical oxidation of 2-naphthyl indolyl maleimide affords two different carbazole regioisomers, depending on the reaction conditions. The regiochemistry of the cyclization can be controlled using the Heck reaction.     

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.     

A selective synthesis of novel isoxazolo[2, 3-a]-quinoxalines and pyrrolo[1, 2-a]quinoxalines

The isoxazolo[2, 3-a]quinoxalines 11a, b and pyrrolo[1, 2-a]quinoxalines 12a, b were selectively synthesized from the 2-substituted 6-chloroquinoxaline 4-oxides 10a, b . The pyrrolo[1, 2-a]quinoxalines 12a, b were clarified to be produced by the ring transformation of the isoxazolo[2, 3-a]quinoxalines 11a, b .     

Design,synthesis, antitubercular and antibacterial activities of pyrrolo[3,2-b]pyridine-3-carboxamide linked 2-methoxypyridine derivatives and in silico docking studies

Abstract

A novel series pyrrolo[3,2-b]pyridine-3-carboxamide linked 2-methoxypyridine derivatives have been designed, synthesized and confirmed by FT-IR, ¹H NMR, ¹³C NMR, ¹⁹F NMR, MS, and elemental analysis. The synthesized compounds were screened for their antitubercular activity using microplate alamar blue assay method and antibacterial activity. Among the tested compounds, 4- fluorophenyl (8m), 4- chlorophenyl (8n) and 4-methoxyphenyl (8i) showed potent anti-TB activity (3.12?µg/mL) in comparison with reference drug, Pyrazinamide ((3.12?µg/mL). In addition, all compounds were docked into DprE1 (PDB code: 4KW5) to explore their binding interactions at the active site. The compounds exhibited essential key interactions as that of reported DprE1 inhibitors and hence, the synthesized compounds may be considered as molecular scaffolds for antitubercular activity. Compounds, 4-chlorophenyl (8n) and 4-flurophenyl (8m) showed significant antibacterial activity against Escherichia coli and Staphylococcus aureus strains. In silico prediction of toxicities, druglikeness and drug score profiles of the tested compounds are promising.     

The synthesis of difluoro[1]benzothieno[2,3-c]quinolines and their N-methyl quaternary salts

A series of difluoro[1]benzothieno[2,3-c]quinolines has been prepared by photocyclization of the appropriate carboxamides. The lactams obtained were converted into the corresponding chloro derivatives which were catalytically dechlorinated into the difluoro[1] benzothieno[2,3-c]quinolines. The latter compounds were transformed into the N-methyl quaternary salts.     

Polymethyl derivatives of furo[3,4-c]pyran4-one,furo[3,4-c] pyridin-4-one and pyrrolo[3,4-c]pyran-4-one

The: title compounds were prepared from Michael adducts, obtained from acetoacetic esters and trans-3-hexene-2,5-dione, and from the corresponding dehydration products, by direct cyclization to oxygen rings or by reaction with ammonia (or methylamine) to give nitrogen rings.     

Condensation reaction of 3,4-dibenzoyl-1-methyl-2,5-diphenylpyrrole and -1-phenylpyrazole with methylamine derivatives affording pyrrolo [3,4-c]pyridine and 2H-pyrazolo[3,4-c]- and [4,3-c]pyridines

The reaction of 3,4-dibenzoyl-1-methyl-2,5-diphenylpyrrole ( 1 ) and -1-phenylpyrazole ( 2 ) with methylamines ( 3a-c ) afforded pyrrolo[3,4-c]pyridine ( 4 ), and isomeric 2H-pyrazolo[3,4-c]pyridines ( 5a-c ) and [4,3-c]pyridines ( 6a-c ), respectively.     

The synthesis of substituted [1]benzothieno[2,3-c]quinolines and their N-methyl quaternary salts

Four substituted [1]benzothieno[2,3-c]quinolines 14a-14d were prepared by photocyclization of the appropriate carboxamides 8a-8d to the corresponding [1]benzothieno[2,3-c]quinolin-6(5H)-ones 12a-12d followed by chlorination to 6-chloro[1]benzothieno[2,3-c]quinolines 13a-13d and dechlorination resulting in the title compounds. Treatment of 14a-14d with iodomethane furnished the corresponding N-methyl quaternary salts 5a-5d .     

Diastereoselective synthesis of enantioenriched homopropargyl amino alcohols from α-dibenzylamino aldehydes and their use as chiral synthons

Homochiral α-dibenzylamino aldehydes, prepared from the corresponding α-amino acids, react with propargyl bromide and zinc in DMF/THF (1:1) or DMF/Et₂O (1:1) at 20 °C to afford, in good yields and dr, homopropargylic 1,2-amino alcohols. anti Diastereomers were always formed as major products in this reaction. These compounds are versatile intermediates for a variety of synthetic targets: γ-amino-β-hydroxy-ketones, 4-amino-1,3-diols, 1,7-diamino-2,6-diols, and ω-amino-δ-hydroxy esters.     

Studies on immunostimulating derivatives: synthesis of some pyrrolo[1,2-c]pyrimidines.

In a search for potential immunomodulating agents novel pyrrolo[1,2-c]pyrimidines were synthesized and their structures elucidated by spectroscopic means. Unfortunately, most of them were cytotoxic and devoid of effects on T lymphocyte lymphoblastic transformation. Furthermore, they were inactive in the locomotor activity test in mice.     

Synthesis of furo[2,3-c]pyran and some properties of 2-amino derivatives of furo- and pyrrolo[2,3-c]pyrans

Thesynthesisof2-amino-5,5-dimethyl-3-cyano-4,5-dihydro-7H-furo[2,3-c]pyrananditspyrroleanalog was accomplished on the basis of 2,2-dimethyltetrahydro-4-pyranone. Their reaction with maleic anhydride, which leads to the formation of 3-amino-4-cyano-6,6-dimethyl-5,6-dihydro-8H-pyrano[c]-phthalic anhydride, was studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 316–318, March, 1991.