Search

The use on a gold catalyst facilitates the Claisen rearrangement/cyclization of propargyloxyindoles (I) allowing to reduce the reaction temperature from 156°C to 101°C with better yields of the condensed heterocycles (II).

Intramolecular Diels-Alder reactions of 3-(ω-alkynyl)-1,2,4-triazines leads to 2,3-cyclopentenopyridines and 5,6,7,8-tetrahydroquinolines. This methodology can be viewed as complementary to intermolecular Diels-Alder reactions of 1,2,4-triazines with cyclopentenyl- and cyclohexenylenamines

A simple synthesis of indole-1-carboxylates, indole-1-thiocarboxylates and indole-1-carboxamides ( 1 ) under neutral conditions is described.

Direct displacement of –OH from 4- and 5-hydroxymethylimidazoles is achieved in good to excellent yields simply by heating a 4- or 5-hydroxymethylimidazole in the presence of an appropriate nucleophile in refluxing basic water.

Phosphodiesterase type 5 (PDE5) inhibitors with improved PDE isozyme selectivity relative to sildenafil may result in agents for the treatment of male erectile dysfunction (MED) with a lower incidence of PDE-associated adverse effects. This paper describes the discovery of 14, a PDE5 inhibitor with improved potency and selectivity in vitro compared to sildenafil. This compound shows activity in a functional assay of erectile function comparable to that of sildenafil.

A mechanism of the rearrangement of 5-propargyloxyindoles is proposed and supported by the formation of a novel tetracyclic indole derivative 12 as the major product in the cyclization of 5-propargyloxytryptophol 10 .

Sulfuryl chloride was used to chlorinate electron-rich arylalkyl amines in a mild and efficient one-pot transformation with simple product isolation via precipitation. Protection of the amine was not needed.

The design and synthesis of a novel scaffold for potent and selective PDE5 inhibitors are described. Compound 3a was more potent (PDE5 IC50=0.31 nM) and selective (>10,000-fold vs PDE1 and 160-fold selective vs PDE6) PDE5 inhibitor than sildenafil.

Hetero Diels–Alder reactions of heteroaromatic amidines and maleimide afforded novel fused pyridopyrrolidine dione scaffolds in moderate to good yields under mild conditions.

A practical and expedient synthesis of the title compounds is described. They were prepared by Stille reaction of nitro halopyridines 4 or nitro fluro-halobenzenes 10 , followed by Michael addition of tert -butyl 4-aminopiperidine-1-carboxylate to the resulting activated vinyl compounds 5 and 11 , hydrogenation (–NO 2 →–NH 2 ), cyclic urea formation, Boc removal, and HCl salt formation. However, N3 and F1 analogs could not be made by this general strategy. Activated vinyl compounds 5a and 5d when reacted with tert -butyl 4-aminopiperidine-1-carboxylate did not stop at the desired Michael addition stage; but proceeded to produce azaindolines 8 and 9 . Michael addition did not occur to compound 11d ; instead, the fluorine atom was displaced.

Enantioselective synthesis of constrained trans -aminobenzazepinone utilizing palladium-mediated Jeffery–Heck reaction and rhodium(II) catalyzed asymmetric hydrogenation as key steps are described. Diverse functional groups such as alkyl, aryl, basic or amino acid moieties were introduced with minimal racemization.

A method is presented for the one-pot synthesis of homotryptamines by the MacMillan reaction of indoles with acrolein followed by reductive amination.

Treatment of methyl α-(dimethylarninomethyleneamino)carboxylates 1 (from α-amino acids and dimethylformamide dimethylacetal) with hydrazine gives 5-substituted-4,5-dihydro-1,2,4-triazin-6-ones 2, which are smoothly dehydrogenated to 5-substituted-1,2,4-triazin-6-ones 3 with potassium permanganate in acetone/acetic acid.