A. S. Shestakov

Reaction of cyanamides with N,N-binucleophiles

Reactions of 4,6-dimethylpyrimidin-2-yl-and aroylcyanamides with benzene-1,2-diamine, ethylenediamine, cyclohexane-1,2-diamine, and naphthalene-1,8-diamine leads to 1H-benzimidazol-2-amine, imidazolidin-2-imine, perhydrobenzimidazol-2-imine, and 1H-perimidin-2-amine derivatives, respectively.

3-aryl(alkyl)quinazoline-2,4(1H,3H)-diones and their alkyl derivatives

Two-stage reaction of methyl anthranilate with aryl(alkyl) isocyanates in keeping with the quantumchemical calculations and XRD analysis resulted in 3-aryl(alkyl)quinazoline-2,4(1H,3H)-diones that by treatment with alkyl halides, phenacyl bromides, esters and amides of chloroacetic acid were converted into the corresponding 1-alkyl derivatives.

One-pot synthesis of 4-aryl-2-cyanoimino-3,4-dihydro-1H-pyrimidines and their reactions

A series of 4-aryl-2-cyanoimino-3,4-dihydro-1H-pyrimidines was obtained as a result of a multicomponent Biginelli reaction using 1,3-dicarbonyl compounds, aromatic aldehydes, and cyanamide. Alkylation of the obtained compounds with benzyl chloride takes place at the two nitrogen atoms of the tetrahydropyrimidine ring, while oxidation with manganese dioxide leads to the corresponding 1-(pyrimidin-2-yl)carbamides or pyrimidine-2-amines, depending on the conditions.

Cyanamides in the synthesis of 1,3-thiazole and 1,3-thiazine derivatives

Hetaryl, aroyl, and aryl cyanamides react with 2-sulfanylbenzoic acid, 2-aminobenzenethiol, and 2-aminoethanethiol to give derivatives of 2-amino-4H-1,3-benzothiazin-4-one, 1,3-benzothiazol-2-amine, and 4,5-dihydro-1,3-thiazol-2-amine.

Synthesis of polyazaheterocycles containing linearly bound 1,2,4-thiadiazole using enaminones

A reaction of N-substituted 5-amino-3-(2-oxopropyl)-1,2,4-thiadiazoles with dimethylformamide dimethyl acetal gave 3-(5-amino-1,2,4-thiadiazol-3-yl)-4-(dimethylamino)but-3en-2-ones, whose cyclization with hydrazine, guanidine, 1H-pyrazol-5-amines and 6-aminopyrimidin-4(3H)-ones led to 3-methyl-1H-pyrazole, 4-methylpyrimidin-2-amine, 5-methyl3-arylpyrazolo[1,5-a]pyrimidines, and 5-methyl-2-R-pyrido[2,3-d]pyrimidin-4(3H)-ones containing a 5-amino-1,2,4-thiadiazole fragment linearly bound at position 3.

Three-component condensation of 4-aryl-1,4-dihydro-benzo[4,5]imidazo[1,2-a][1,3,5]triazin-2-amines with formaldehyde and primary amines

Three-component cyclization of 4-aryl-1,4-dihydrobenzo[4,5]imidazo[1,2-a][1,3,5]triazin-2-amines with formaldehyde and primary amines gave the corresponding 6-unsubstituted or 6-aryl-2-alkyl-2,3,4,6-tetrahydro-1H-[1,3,5]triazino[1′,2′:3,4][1,3,5]triazino[1,2-a]benzimidazoles.

Methyl 3-amino-1H-indole-2-carboxylates in the synthesis of 5H-pyrimido[5,4-b]indole derivatives

Reactions of methyl 3-amino-1H-indole-2-carboxylates with aryl isocyanates, aryl isothiocyanates, and cyanamides led to the formation of 5H-pyrimido[5,4-b]indole derivatives. In the reaction with isocyanates formed 3-aryl-1H-pyrimido[5,4-b]indole-2,4(3H,5H)-diones that were involved into the alkylation at two nitrogen atoms. The reaction with isothiocyanates afforded 3-aryl-2-thioxo-2,3-dihydro-1H-pyrimido[5,4-b]indol-4(5H)-ones undergoing alkylation at the sulfur atom. The reactions with benzoylcyanamide and N-(4,6-dimethylpyrimidin-2-yl)cyanamide resulted in N-(4-oxo-4,5-dihydro-3H-pyrimido-[5,4-b]indol-2-yl)benzamides and 2-(4,6-dimethylpyrimidin-2-ylamino)-3H-pyrimido[5,4-b]indol-4(5H)-ones respectively.

Guanidines Based on Tryptamine and Histamine in Reactions with Electrophiles

Reactions of 4,6-dimethylpyrimidin-2-ylcyanamide with tryptamines and histamine gave the corresponding disubstituted guanidines. The molecular parameters of the products were calculated using GAUSSIAN 03 software package. The direction of electrophilic attack on these compounds was predicted on the basis of the geometric shape of their highest occupied molecular orbital (HOMO) and molecular electrostatic potential (MEP) maps. Acyl, carbamoyl, and cyclic derivatives were obtained, whose structure was consistent with the results of quantum-chemical calculations.

Synthesis of the novel heterocyclic system 8,13,13b,14-tetrahydroindolo-[2,3-a]pyrimido[5,4-g]quinolizin-5(7H)-one

In continuing our study of ethyl 2-R-4-(2-dimethylaminovinyl)pyrimidine-5-carboxylates 1a,b reactivity with primary amines [1, 2] we have unexpectedly discovered that treatment of enamines 1a,b with 5-methoxytryptamine (2) in DMF gives the condensed pentacyclic 2-R-10-methoxy-8,13,13b,14-tetrahydroindolo[2,3-a]pyrimido-[5,4-g]quinolizin-5(7H)-ones 4a,b instead of the expected pyridopyrimidinones 3a,b. Although it was not possible to identify the intermediates in this reaction it was quite apparent that it occurs through an intramolecular addition of the indole fragment to the double bond of the pyridinone ring in the initially formed pyridopyrimidinones 3a,b. The H NMR spectra of compounds 4a,b show the absence of the characteristic doublet signals for two pyridopyrimidinone protons and contain multiplets for the CH and CH2 groups of the tetrahydroquinolizinone ring. The H–H NOESY spectra show strong correlation peaks for the CH and CH2 protons of the quinolizine ring. The structure of the obtained compounds was also confirmed by elemental analytical and mass spectrometric data. H NMR and H–H NOESY spectra were recorded on a Bruker DRX-500 spectrometer (500 MHz) using DMSO-d6 with TMS as internal standard. Mass spectra were recorded on an LKB-9000 spectrometer using 70 eV ionization energy. Elemental analysis was carried out on a Carlo Erba NA 1500 instrument and melting points were determined on a Koffler block. 10-Methoxy-2-(morpholin-4-yl)-8,13,13b,14-tetrahydroindolo[2,3-a]pyrimido[5,4-g]quinolizin5(7H)-one (4a). The starting ethyl 4-(2-dimethylaminovinyl)-2-morpholinopyrimidine-5-carboxylate (1a) was prepared as reported in [1] and, without isolation of the product, the reaction mixture was treated with an equimolar amount of the tryptamine hydrochloride (2) (4 mmol) and refluxed for 5 h. The precipitate formed was filtered off, washed with DMF, and then ethanol. Yield 1.1 g (68%); mp 295-297oC. H NMR spectrum, , ppm (J, Hz): 2.70 (1H, m) and 2.83 (1H, dd, J = 15.0, J = 3.9, 8-CH2); 2.92 (1H, dd, J = 12.5, J = 3.9, 7-CH2);

Synthesis of 2-iminoimidazolidin-4-one derivatives by cyclization of 2-aryl-1-(4,6-dimethylpyrimidin-2-yl)guanidines with ethyl bromoacetate, dimethyl acetylenedicarboxylate, and maleic anhydride

Derivatives of 2-iminoimidazolidin-4-one, (E)-methyl (2-imino-5-oxoimidazolidin-4-ylidene)acetate, and (2-imino-5-oxo-imidazolidin-4-yl)acetic acid were synthesized by the cyclization of 2-aryl-1-(4,6-dimethylpyrimidin-2-yl)guanidines with ethyl bromoacetate, dimethyl acetylenedicarboxylate, and maleic anhydride, respectively.