Anton V. Tverdokhlebov

A base promoted multigram synthesis of aminoisoxazoles: valuable building blocks for drug discovery and peptidomimetics

A practical multigram metal free synthesis of isoxazole-containing building blocks from commercially available amino acids was elaborated. The key reaction was a regioselective [3 + 2]-cycloaddition of in situ generated nitrile oxides with alkynes/enamines. The obtained building blocks were used in the preparation of bioactive compounds and peptidomimetics.

Simple and convenient synthesis of 2,3,4,5-tetrahydro-1,5-dioxopyrrolo[1,2-a]quinazoline-3a(1H)-carboxylic acids in multi-gram scale

The title compounds were prepared in 70-100 grams scale by reaction of 2-amino-N-alkyl(aryl)benzamides with 2-oxoglutaric acid. Their structure was proved unambiguously by X-ray crystallographic study.

Pyrrolo〔2,1-b〕thiazoles

Synthesis and properties ofpyrrolo[2,1 -b]thiazoles have been reviewed. The literature from 1940 to 2005 is covered. Bibliography comprises 136 references.

Synthesis of 3-(pyrimidinyl)pyrrole derivatives

Alkylation of 4,6-dimethyl-2-pyrimidineacetonitrile and 2,6-dimethyl-4-pyrimidineacetonitrile with chloroacetic acid anilides was shown to give 5-amino-4-(4,6-dimethyl-2-pyrimidinyl)-2,3-dihydro-1-arylpyrrol-2-ones and 5-amino-4-(2,6-dimethyl-4-pyrimidinyl)-2,3-dihydro-1-arylpyrrol-2-ones, respectively. Corresponding isomeric compounds, 5-amino-4-pyrimidinyl-2,3-dihydropyrrol-3-ones were obtained by Claisen condensation of the mentioned pyrimidineacetonitriles with N-Boc α-aminoacids imidazolides followed by removal of the protecting group accompanied with simultaneous ring closure.

An Interaction of 2-Thiazoleacetonitriles with N-(2-Chloroacetyl)anthranilic Acid Ester

The title ester was found to react with 2-benzothiazoleacetonitrile yielding 3-( 2-benzothiazolyl)-2,4-dihydropyrrolo[1,2-a]quinazoline-1,5-drone. At the same time 4-aryl-2-thiazoleacetonitriles gave 3,4-dihydro-β,4-dioxo-α,δ-bis(4-aryl-2-thiazolyl)-2-quinazolinepentanenitriles potassium salts under identical conditions. These results were explained in terms of different solubility of the intermediate compounds. Upon acidification the obtained salts were shown to undergo intramolecular Thorpe addition leading to the 3-amino-2,4-bis(4-aryl-2-thiazolyl)-4-[4(3H)-oxo-2-quinazolinyl]-2-cyclopenten-1-ones. Above mentioned pyrrolo[1,2-a]quinazoline derivative was treated with benzylamines and active methylene nitriles to yield β-(2-benzothiazolyl)-N-arylmethyl-3,4-dihydro-4-oxo-2-quinazolinepropanamides and 2-substituted 3-amino-4-(2-benzothiazolyl)-4-[4(3H)-oxo-2-quinazolinyl]-2-cyclopenten-1-ones, respectively.

2‐Benzothiazolemethanol as Precursor of 2‐Aryl‐1‐(2‐benzothiazolyl)‐1‐ethanones

Abstract 2‐Benzothiazolemethanol was found to react with substituted benzaldehydes in the presence of excess chlorotrimethylsilane yielding the title ketones after aqueous work up.

Preparation of 5-amino-1,2-dihydro-4-(1-methyl-4-piperidinyl)pyrrol-3-ones

Acylation of (1-methyl-4(1H)-pyridinylidene)acetonitrile with chloroacetyl chloride was found to occur at the exocyclic carbon atom leading to 4-chloro-2-(1-methyl-4(1H)-pyridinylidene)-3-oxobutanenitrile. Its reaction with primary amines furnished 4-(2-amino-4,5-dihydro-4-oxo-1H-pyrrol-3-yl)-1-methylpyridinium chlorides. Hydrogenation of these quaternary salts afforded 5-amino-1,2-dihydro-4-(1-methyl-4-piperidinyl)-3H-pyrrol-3-ones in nearly quantitative yields.