Efficient synthesis of [1,3]oxazino[2,3-a]quinoline derivatives by a novel 1,4-dipolar cycloaddition involving a quinoline-DMAD zwitterion and carbonyl compounds

An efficient synthesis of [1,3]oxazino[2,3-a]quinoline derivatives via a three-component reaction of quinoline, DMAD and carbonyl compounds is described.     

Highly efficient synthesis of triazolo[1,2-a]indazole-triones and novel spiro triazolo[1,2-a]indazole-tetraones under solvent-free conditions

A new, convenient, and high yielding procedure for the synthesis of triazolo[1,2-a]indazole-triones by the condensation reaction between dimedone, aryl aldehydes, and ueazoles in the presence of a catalytic amount of sulfonated polyethylene glycol (PEG-SO₃H) as a highly stable and reusable eco-friendly degradable polymeric catalyst is described under solvent-free conditions. This procedure has also been applied successfully for the synthesis of novel spiro triazolo[1,2-a]indazole-tetraones.     

An efficient synthesis of [1,4]pyridazinooxazine[3,4-a]tetrahydro isoquinolines

A series of fused isoquinoline-pyridazinooxazine chimera were prepared in good overall yield from phenethylamide 1 and 4,5-dichloropyridazin-3-one 2 via Smiles rearrangement and Pictet-Spengler cyclization.     

Copper-catalyzed tandem synthesis of [1,2,3]triazolo[5,1-a]isoquinolines and their transformation to 1,3-disubstituted isoquinolines

2-Azido-3-(2-iodophenyl)acrylates react with terminal alkynes in the presence of a copper(II) catalyst without ligands to give a wide range of [1,2,3]triazolo[5,1-a]isoquinolines in good yields. These compounds favor expulsion of N₂ in refluxed acetic acid to form 1,3-disubstituted isoquinolines. The procedure is simple, economical, and efficient.     

A novel isocyanide-based three-component synthesis of benzimidazo[1,2-a][1,4]diazepinones

3-(2-Formyl-1H-benzimidazol-1-yl)propanoic acid, as a bifunctional formyl acid was prepared in four steps. This compound underwent a one-pot reaction with amines and alkyl isocyanides via the Ugi 4-center-3-component condensation. A series of novel benzimidazole-fused 1,4-diazepine-5-ones were obtained via this method in moderate to excellent yields.     

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.     

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.     

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.     

An efficient synthesis of 2-cyano-2-phenyl-2,11b-dihydro-[1,3]oxazino[2,3-a]isoquinolines by reaction of isoquinoline with electron-deficient acetylenes in the presence of benzoylcyanide

Isoquinoline reacts with electron-deficient acetylenic compounds in the presence of benzoylcyanide to form 2-cyano-2-phenyl-2,11b-dihydro-[1,3]oxazino[2,3-a]isoquinolines in good yields. Correspondence: Issa Yavari, Chemistry Department, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran.     

Cyclisation of 3-alkenylpyrido[1,2-a]pyrimidines to furo[2,3-d]pyrido[1,2-a]pyrimidines

3-Alkenylpyrido[1,2-a]pyrimidines react under mild conditions to give novel tricyclic furo[2,3-d]pyrido[1,2-a]pyrimidines in high yields. The cyclisation takes place in the presence of an acid catalyst. The product yield is affected by the type and the strength of the acid used. Exceptionally high yields were obtained when an organic acid like trifluoromethanesulfonic acid and trifluoroacetic acid were used. On the other hand, sulfuric acid gave the best results of the inorganic acids examined.     

A synthesis of dihydroimidazo[5,1-a]isoquinolines using a sequential Ugi-Bischler-Napieralski reaction sequence

A flexible route to analogues of dihydroimidazo[5,1-a]isoquinolines is described. The synthesis hinges on a sequential Ugi coupling, followed by a Bischler-Napieralski reaction to form the imidazole isoquinoline core. This route facilitates the introduction of a range of substitutions throughout the carbon framework.     

Novel one pot synthesis of polysubstituted pyrazolo[1,5-a]- and imidazo[1,2-a]pyrimidines

We have described a convenient regioselective one-pot approach to pyrazolo[1,5-a]- and imidazo[1,2-a]pyrimidine derivatives from α,β-unsaturated imines generated in situ and amino heterocycles. Reaction is general with respect to all three components, namely (i) nitrile, (ii) aldehyde, and (iii) amino heterocycle reagents. Good yields (52-77%), convenient isolation of the targeted molecules are the distinct characteristics of the developed protocol.     

A convenient synthesis of linear pyridinoimidazo[1,2-a]pyridine and pyrroloimidazo[1,2-a]pyridine cores

Two new imidazo[1,2-a]pyridine derivatives, pyridinoimidazo[1,2-a]pyridine (10) and pyrroloimidazo[1,2-a]pyridine (16), were synthesised from 2-amino-4-methyl-5-nitropyridine (1) by linear cyclisation, making use of dimethylformamide dimethylacetal (DMFDMA) as an agent of vinylamine functionalisation. This report describes first the formation of pyridine and pyrroloimidazopyridine from (1), and then the formation of pyridine-fused and pyrrolo-fused pyridine by the Friedländer method and reductive cyclisation followed by treatment of the resulting adduct with chloroacetaldehyde.     

Studies of some hydrogenated thiazolo[2,3-a]isoquinoline S-oxides

Several hydrogenated thiazolo[2,3-a]isoquinolinone S-oxides have been prepared and their stereochemistry established on the basis of spectral data analysis combined with X-ray crystallography. A reversible syn/anti isomerization of diastereomeric sulfoxides has been postulated to occur via a 10b proton abstraction.     

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.     

Synthesis of dihydrobenzoimidazo[2,1-a]isoquinolines

A one-pot protocol toward several substituted 5,6-dihydrobenzo[4,5]imidazo[2,1-a]isoquinolines 1 starting with 2-allylbenzaldehydes 2 was described. The process was carried out the one-pot condensation/hydroamination reaction of substituted 2-allylbenzaldehydes 2 with 1,2-diaminobenzenes 3 in refluxing toluene in good yields. Skeleton 2 was prepared via one-pot ortho-metalative PhBCl₂-mediated double alkylation of hydroxybenzaldehyde 4 with LDA in moderate yields.     

Streamlined access to 2,3-dihydropyrazino[1,2-a]indole-1,4-diones via Ugi reaction followed by microwave-assisted cyclization

An efficient method is developed to construct drug-like 2,3-dihydropyrazino[1,2-a]indole-1,4-diones from 1H-indole-2-carboxylic acids, ethyl pyruvate, isocyanides, and primary amines via a one-pot, two-step procedure involving Ugi reaction and microwave-assisted cyclization.     

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.     

Synthesis of pyrrolo[2,1-a]isoquinolines from activated acetylenes, benzoylnitromethanes, and isoquinoline

Isoquinoline reacts smoothly with aroylnitromethanes in the presence of dialkyl acetylenedicarboxylates and dibenzoylacetylene to produce pyrrolo[2,1-a]isoquinolines in good yields. Quinoline and benzothiazole also react in a similar way. Pyridine and N-methylimidazole catalyze the reaction between nitromethane derivatives with electron-deficient acetylenes to produce highly functionalized isoxazoles.     

Facile synthesis of novel [1,3]oxazino[2,3-c][1,2,4] thiadiazin-12-one derivatives

Several novel fused heterocyclic systems which have rings containing N/O or N/S have been synthesized through a facile one-pot method by the treatment of substituted 2-(benzo[d]thiazol-2-yl)phenol and cyanogen bromide in THF and NEt₃. This one-pot method contains tough ring-opening of thiazole, special intermolecular rearrangement and ring-closing reactions. The newly synthesized compounds were characterized by HR-MS, ¹H-NMR, ¹³C-NMR spectral data and DFT calculation analysis. 2a was also determined by X-ray crystallographic analysis.