The Mannich reaction in the synthesis of N,S-containing heterocycles 11. Synthesis of 3,3′-(1,4-phenylene)-bis(8-aryl-6-oxo-3,4,7,8-tetrahydro-2H,6H-pyrido[2,1-b][1,3,5]thiadiazine-9-carbonitriles)

Dotsenko, V. V.; Кривоколыско, С. Г.; Литвинов, В. П.

doi:10.1007/s11172-012-0018-5

Cited by 15 publications

(4 citation statements)

References 11 publications

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“…HCHO and a set of various primary amines 9 { 1–31 } (Figure ). The required thiolates 7 { 1–47 } are easily accessible by one-pot condensation of aromatic aldehydes, cyanothioacetamide 10 and Meldrum’s acid (2,2-dimethyl-1,3-dioxane-4,6-dione) 11 in the presence of N -methylmorpholine following the consequent cyclization of the isolable Michael adduct, N -methylmorpholinium 5-(3-amino-1-aryl-2-cyano-3-thioxopropyl)-2,2-dimethyl-4-oxo-4H-1,3-dioxin-6-olate 12 , as outlined in Scheme . − As the starting 1,4,5,6-tetrahydropyridine-2-thiolates 7 have been prepared as racemic mixtures of (4 R )- and (4 S )-enantiomers, all the pyrido[2,1- b ][1,3,5]thiadiazine-9-carbonitriles 8 also were obtained as mixtures of (8 R )- and (8 S )-isomers.…”

Section: Resultsmentioning

confidence: 99%

“…The thiolates 7 { 1–47 } were obtained in a manner analogous to reported procedures − as follows: A 0.5 L round-bottom flask fitted with an overhead stirrer was charged with the corresponding aromatic aldehyde (0.1 mol), cyanothioacetamide 10 (10.0 g, 0.10 mol) and EtOH (100 mL). N -Methylmorpholine (0.8–1.0 mL) was added, and the mixture was stirred for 1 h at 20 °C (yellow/orange crystalline 3-aryl-2-cyanoprop-2-enethioamides may precipitate from the solution).…”

Section: Methodsmentioning

confidence: 99%

“…As we have shown in preliminary communications, , these pyrido[2,1- b ][1,3,5]thiadiazines could be easily prepared by Mannich-type reaction of N -methylmorpholinium 4-aryl-6-oxo-3-cyano-1,4,5,6-tetrahydropyridine-2-thiolates 7 with primary amines and excess formaldehyde (Scheme ). This effective and time-saving protocol is based on the use of inexpensive, readily available building blocks.…”

Section: Introductionmentioning

confidence: 99%

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Design and Synthesis of Pyrido[2,1-b][1,3,5]thiadiazine Library via Uncatalyzed Mannich-Type Reaction

Dotsenko

Фролов

Pekhtereva³

et al. 2014

ACS Comb. Sci.

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This Research Article describes the synthesis of an over 700-member library of (8R/8S)-3-R-8-aryl-6-oxo-3,4,7,8-tetrahydro-2H,6H-pyrido[2,1-b][1,3,5]thiadiazin-9-carbonitriles by uncatalyzed Mannich-type reaction of N-methylmorpholinium (4R/4S)-4-aryl-3-cyano-6-oxo-1,4,5,6-tetrahydropyridin-2-thiolates with a set of primary amines and excessive HCHO. The scope and limitations of the reaction were studied. Starting thiolates were obtained in yields of 53-82% by multicomponent reaction of aromatic aldehydes, cyanothioacetamide, 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid), and N-methylmorpholine, followed by heterocyclization of the resulting Michael adducts.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Design and Synthesis of Pyrido[2,1-b][1,3,5]thiadiazine Library via Uncatalyzed Mannich-Type Reaction

Dotsenko

Фролов

Pekhtereva³

et al. 2014

ACS Comb. Sci.

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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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ChemInform Abstract: The Mannich Reaction in the Synthesis of N,S‐Containing Heterocycles. Part 11. Synthesis of 3,3′‐(1,4‐Phenylene)‐bis(8‐aryl‐6‐oxo‐3,4,7,8‐tetrahydro‐2H,6H‐pyrido [2,1‐b][1,3,5]thiadiazine‐9‐carbonitriles) (IV).

2013

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The Mannich reaction in the synthesis of N,S-containing heterocycles 11. Synthesis of 3,3′-(1,4-phenylene)-bis(8-aryl-6-oxo-3,4,7,8-tetrahydro-2H,6H-pyrido[2,1-b][1,3,5]thiadiazine-9-carbonitriles)

Cited by 15 publications

References 11 publications

Design and Synthesis of Pyrido[2,1-b][1,3,5]thiadiazine Library via Uncatalyzed Mannich-Type Reaction

Design and Synthesis of Pyrido[2,1-b][1,3,5]thiadiazine Library via Uncatalyzed Mannich-Type Reaction

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

ChemInform Abstract: The Mannich Reaction in the Synthesis of N,S‐Containing Heterocycles. Part 11. Synthesis of 3,3′‐(1,4‐Phenylene)‐bis(8‐aryl‐6‐oxo‐3,4,7,8‐tetrahydro‐2H,6H‐pyrido [2,1‐b][1,3,5]thiadiazine‐9‐carbonitriles) (IV).

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