P1-0179 — Annual report 2009
1.
Bis-enaminone based parallel solution-phase synthesis of 1,4-dihydropyridine derivatives.

Two variations of parallel solution-phase synthesis of N-substituted dimethyl 4-oxo-1,4-dihydropyridine-3,5,-dicarboxylates and methyl 3-oxo-3,5-dihydro-2H-pyrazolo[4,3-c]pyridine-7-carboxylates from acetone-1,3-dicarboxylates were developped. The first synthetic method comprises preparation of bisenaminone reagents and their cyclization with primary amines, another method consists of preparation of monoenaminone reagents followed by substitution of the dimethylamino group with primary amines, followed by cyclization into dihydropyridinecarboxylates

COBISS.SI-ID: 30438661
2.
Diastereoselective synthesis of dimethyl 1-aryl-6´-benzoyl-4a´-methyl-5-oxo-hexahydrospiro[pyrazole-4,7´-pyrrolo[3, 4-c]pyridazine]-dicarboxylates.

Methyl (Z)-2-(benzoylamino)-3-(dimethylamino)propenoate reacts with trimethylenemethane to give methyl (Z)-2-[benzoyl-(2-methylallyl)amino]-3-(dimethylamino)propenoate, from which derivatives of pyrazole by substitution of dimethylamino group with hydazine and cyclization with ester group are formed. In the reaction of pyrazoles with 1,2,4,5-tetrazine-3,6-dicarboxylate diastereoisomeric 1-aryl-6´-benzoyl-4a´-methyl-5-oxo-hexahydrospiro[pyrazol-4,7´-pyrrolo[3,4-c]pyridazine]-dicarboxylates are formed. This transformation represens a simple method for preparation of new heterocyclic systems.

COBISS.SI-ID: 30103557
3.
[2+2] Cycloadditions of electron-poor acetylenes to (5Z)-5-[(dimethylamino)methylene]imidazolidine-2,4-diones

[2+2] Cykloadditions of 2-amino-3-dimethylaminopropenoates with acetylenecarboxylates under microwave irradiation are described. Polyfunctional derivatives of 1-amino-4-(dimethylamino)buta-1,3-dienes are formed in one isomeric form. Furthermore, [2+2] cycloadditions of acetylene mono in dicarboxylates to (5Z)-5-[(dimethylamino)methylene]imidazolidine-2,4-dione under microwave irradiation were also studied. In acetonitrile polyfunctional derivatives of imidazolidine-2,4-diones were produced, while in DMF partial hydrolysis was observed.

COBISS.SI-ID: 30316805
4.
A synthesis of 1-substituted 5-[2-(acylamino)ethyl]-1H-pyrazole-4-carboxamides.

A seven-step synthesis of 1-substituted 5-(2-acylaminoethyl)-1H-pyrazole-4-carboxamides as pyrazole analogs of histamine was developed. The synthesis starts with a three-step preparation of N1- substituted methyl 5-(2-tert-butoxycarbonylaminoethyl)-1H-pyrazole-4-carboxylates from commercially available Boc-ß-alanine. Subsequent four-step transformation of this intermediate was performed with acidolytic removal of Boc group, hydrolysis of the ester group, amidations of carboxylic group and acylation of amino group.

COBISS.SI-ID: 30656005
5.
Copper(i) iodide-catalyzed cycloadditions of (1Z,4R*, 5R*)-4-benzamido-5-phenylpyrazolidin-3-on-1-azomethine imines to ethyl propiolate.

Within this context, the following achievements can be pointed out: Regiospecific copper(I) iodide catalyzed cycloadditions of chiral pyrazolidin-3-on-1-azomethine imines to ethyl propyolate gave cycloadducts, derivates of 1,5,6,7-tetrahydropyrazolo[1,2-a]pyrazole-2-carboxylate as single diastereoismers. Stereoselectivity of copper(I) iodide-catalyzed cycloadditions was controlled by the stereodirecting phenyl group at position 5 and by the ortho-substituents at the 1'-aryl residue.

COBISS.SI-ID: 33490949