New possibilities of the Mannich reaction in the synthesis of N-, S,N-, and Se,N-heterocycles

Dotsenko, V. V.; Фролов, К. А.; Chigorina, E. A.; Khrustaleva, A. N.; Bibik, E. Yu.; Кривоколыско, С. Г.

doi:10.1007/s11172-019-2476-5

Cited by 31 publications

(6 citation statements)

References 139 publications

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“…Previously, we found that aminomethylation of isostructural analogs of compound 11, 1,4-dihydropyridine-2-thiolates and -selenolates 14, under the action of an excess of HCHO and primary amines leads to the formation of new tricyclic system derivatives, namely 3,5,7,11-tetraazatricyclo[7.3.1.0 2.7 ]tridec-2-ene 15 [33,34]. Some of compounds 15 showed antiviral activity against tick-borne encephalitis virus [35].…”

Section: Doi: 101134/s1070363222050061mentioning

confidence: 99%

Synthesis and Aminomethylation of 2-Amino-4-(2-chlorophenyl)-6-(dicyanomethyl)-1,4-dihydropyridine-3,5-dicarbonitrile N-Methylmorpholinium Salt

et al. 2022

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Sequential reaction of 2-chlorobenzaldehyde, cyanothioacetamide, and malononitrile dimer in the presence of an excess of N-methylmorpholine resulted in the formation of N-methylmorphlinium salt of 2-amino-4-(2-chlorophenyl)-6-(dicyanomethyl)-1,4-dihydropyridine-3,5-dicarbonitrile. The resulting salt reacts under Mannich conditions with primary amines and an excess of formaldehyde to form substituted 2-alkylamino-4-(dicyanomethylene)-3,7-diazabicyclo[3.3.1]non-2-ene-1,5-dicarbonitriles. Structure of the key compound was confirmed by single crystal X-ray diffraction analysis.

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Section: Doi: 101134/s1070363222050061mentioning

confidence: 99%

Synthesis and Aminomethylation of 2-Amino-4-(2-chlorophenyl)-6-(dicyanomethyl)-1,4-dihydropyridine-3,5-dicarbonitrile N-Methylmorpholinium Salt

et al. 2022

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“…Possible products 2 hold promise as starting reagents for the synthesis of thieno [2,3-b]pyridine derivatives, many of which have pharmacologically useful properties [13][14][15][16]. On the other hand, compounds 2-4 are convenient and accessible substrates for preparing S, N-polyheterocyclic assemblies by the Mannich reaction (see, for example, [17][18][19][20][21]).…”

Section: Doi: 101134/s1070363221060013mentioning

confidence: 99%

Reactions of Malononitrile Dimer with Isothiocyanates

et al. 2021

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The reaction of 2-amino-1,1,3-tricyanopropene (malononitrile dimer) with isothiocyanates leads to 1-substituted 4,6-diamino-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitriles or 4,6-diamino-2-(phenylimino)-2H-thiopyran-3,5-dicarbonitrile, depending on the conditions. Quantum-chemical modeling of the IR spectra and reaction routes for the synthesized compounds was carried out. In silico predictive analysis of potential protein targets, compliance with bioavailability criteria, and ADMET parameters was performed.

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“…В первую очередь цианотиоацетамид 1 нашел применение в синтезе важных полупродуктов тонкого органического синтеза -2-меркапто(2тиоксо)никотинонитрилов и родственных им 3-цианопиридин-2-тиолатов [5][6][7][8][9][10][11][12]. Такие соединения, в свою очередь, активно используются в дальнейших гетероциклизациях в производные тиено [2,3-b]пиридина [13][14][15][16][17][18][19][20][21], тиазоло [3,2-а]пиридина [22][23][24][25][26][27][28][29][30], изотиазоло [5,4-b]пиридина [31][32][33][34], пиридо [2,1-b] [1,3,5]тиадиазина [35][36][37][38][39] и ряда других гетероциклических структур.…”

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Synthesis, anti-exudative and anti-inflammatory properties of substituted N-(2,4-dichlorophenyl)-5-cyano-4-(2-furyl)-2-methyl-1,4-dihydropyridin-3-carboxamides

Oleinik,

Bibik,

Dotsenko

et al. 2023

Chem

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One-pot reaction of cyanothioacetamide, N-(2,4-dichlorophenyl)acetoacetamide and furfural in the presence of excessive N-methylmorpholine in EtOH at 25 °C gives N-methylmorpholinium 5-[(2,4-dichlorophenyl)carbamoyl]-3-cyano-4-(2-furyl)-6-methyl-1,4-dihydropyridin-2-thiolate, yielding 82%. Subsequent S-alkylation of the prepared thiolate with N-substituted α-chloroacetamides occurs in a regiospecific way to form N-(2,4-dichlorophenyl)-5-cyano-4-(2-furyl)-2-methyl-6-[(2-oxo-2-{[substituted aryl]amino}ethyl)sulfanyl]-1,4-dihydropyridin-3-carboxamides 10–17. Compounds 10–17 were identified by means of IR and NMR spectroscopy, as well as by elemental analysis. Synthesized compounds 10–17 were examined for anti-exudative and anti-inflammatory activity. White laboratory rats numbering 112 individuals were divided into control (“acute formalin-induced paw edema”) and intact groups, 4 reference groups (acetylsalicylic acid, indomethacin, nimesulide, and paracetamol) and 8 experimental groups, according to the number of tested 1,4-dihydropyridine derivatives. The efficacy of the anti-inflammatory activity of the samples was evaluated in the model of “acute formalin paw edema” in rats, which was simulated by injecting 0.1 mL of 2% formalin solution into the aponeurosis of the right hind limb. The studied compounds were given intragastrically at a dose of 5 mg/kg 1.5 hours before the induction of the inflammatory process. Oncometric changes were measured quantitatively by limb girth. It was shown that the most pronounced anti-inflammatory activity was possessed by: N-(2,4-dichlorophenyl)-5-cyano-4-(2-furyl)-2-methyl-6-[(2-oxo-2-{[3-(trifluoromethyl)phenyl]-amino}ethyl)sulfanyl]-1,4-dihydropyridin-3-carboxamide 12 (1.09–1.81 times more effective than the reference drugs); 6-[(2-anilino-2-oxoethyl)sulfanyl]- N-(2,4-dichlorophenyl)-5-cyano-4-(2-furyl)-2-methyl-1,4-dihydropyridin-3-carboxamide 16, which reduced the induced paw edema by 42.91% compared to control; N-(2,4-dichlorophenyl)-5-cyano-4-(2-furyl)-2-methyl-6-({2-[(3-methylphenyl)amino]-2-oxoethyl}sulfanyl)-1,4-dihydropyridin-3-carboxamide 14 (1.65–2.85 times higher anti-inflammatory activity compared to the reference drugs in 18-hour experiments). N-(2,4-Dichlorophenyl)-5-cyano-4-(2-furyl)-2-methyl-6-({2-[(3,5-dimethylphenyl)amino]-2-oxoethyl}sulfanyl)-1,4-dihydropyridin-3-carboxamide 11 was found to be the most active, reducing paw edema 2.9 times more effectively than nimesulide

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New possibilities of the Mannich reaction in the synthesis of N-, S,N-, and Se,N-heterocycles

Cited by 31 publications

References 139 publications

Synthesis and Aminomethylation of 2-Amino-4-(2-chlorophenyl)-6-(dicyanomethyl)-1,4-dihydropyridine-3,5-dicarbonitrile N-Methylmorpholinium Salt

Synthesis and Aminomethylation of 2-Amino-4-(2-chlorophenyl)-6-(dicyanomethyl)-1,4-dihydropyridine-3,5-dicarbonitrile N-Methylmorpholinium Salt

Reactions of Malononitrile Dimer with Isothiocyanates

Synthesis, anti-exudative and anti-inflammatory properties of substituted N-(2,4-dichlorophenyl)-5-cyano-4-(2-furyl)-2-methyl-1,4-dihydropyridin-3-carboxamides

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