Ring transformation of 1,5-benzoxazepines into spirobenzoxazoles. Synthesis of pyrazolo[1′,5′:3,4][1,2,4]triazino-[5,6-b][1,5]benzoxazepines and spiro[benzoxazole-2′(3′H),4(1H)-pyrazolo[5,1-c][1,2,4]triazines]

The reactions of the 3-substituted 4-amino-8-ethoxycarbonyl[5,1-c][1,2,4]triazines 1 and 2 with o-amino-phenol hydrochloride gave the pyrazolo[1′,5′:3,4][1,2,4]triazino[5,6-b][1,5]benzoxazepines 5 and 8 . The alkylation of 5 with methyl iodide and isopropyl iodide afforded the 6-alkoxylpyrazolo[1′,5′:3,4][1,2,4]triazino-[5,6-b][1,5]benzoxazepines 6a and 6b , respectively. Refluxing of 5, 6a, 6b and 8 in hydrochloric acid/acetic acid resulted in ring transformation to produce the spiro[benzoxazole-2′(3′H),4(1H)pyrazolo[5,1-c][1,2,4]-triazines] 7a, 7b and 9 . The screening data of the above compounds was described.     

A new method for the synthesis of novel 3-substituted 4-amino-8-ethoxycarbonylpyrazolo[5,1-c][1,2,4]triazines and pyrazolo[1′,5′:3,4][1,2,4]triazino[5,6-b][1,5]benzodiazepines

Novel 3-substituted 4-amino-8-ethoxycarbonylpyrazolo[5,1-c][1,2,4]triazines 7,8 were synthesized by the reactions of malononitrile and ethyl cyanoacetate with the pyrazole-5-diazonium salt 3 . Moreover, compounds 7,8 were converted into the pyrazolo[1′,5′:3,4][1,2,4]triazino[5,6-b][1,5]benzodiazepines 9, 10 .     

Facile synthesis and antifungal activity of 3-substituted 4-amino-8-ethoxycarbonylpyrazolo[5,1-c][1,2,4]triazines and pyrazolo[1′,5′:3,4][1,2,4]triazino[5,6-b][1,5]benzodiazepines

The reactions of the pyrazole-5-diazonium salt 3 with malononitrile and ethyl cyanoacetate gave 4-amino-3-cyano-8-ethoxycarbonylpyrazolo[5,1-c][1,2,4]triazine 7 and 4-amino-3,8-bisethoxycarbonylpyrazolo[5,1-c]-[1,2,4]triazine 8 , whose reactions with p-chloroaniline hydrochloride afforded 4-amino-8-ethoxycarbonyl-3-(p-chlorophenyl)amidinopyrazolo[5,1-c][1,2,4]triazine 9 and 4-amino-8-ethoxycarbonyl-3-(p-chlorophenyl)car-bamoylpyrazolo[5,1-c][1,2,4]triazine 10 , respectively. The reactions of 7 and 8 with o-phenylenediamine di-hydrochloride provided 9-ethoxycarbonyl-13H-spiro[benzimidazole-2′(3′H),6(5H)-pyrazolo[1,5′:3,4][1,2,4]tri-azino[5,6-b][1,5]benzodiazepine] hydrochloride 11a and 9-ethoxycarbonyl-6-oxo-13H-5,6-dihydropyrazolo-[1′,5′:3,4][1,2,4]triazino[5,6-b][1,5]benzodiazepine 12 , respectively. The antifungal activity of the above compounds was described.     

A novel tetracyclic ring system. 10H-tetrazolo[5′,1′:3,4][1,2,4]triazino[5,6-b]indole

The reaction of 3-hydrazino-1,2,4-triazino[5,6-b]indole with nitrous acid affords a novel tetracyclic ring system: 10H-tetrazolo[5′,1′:3,4][1,2,4]triazino[5,6-b]indole. The mode of cyclization has been discussed.     

Synthesis of new halo-substituted pyrazolo[5,1-c][1,2,4]triazines

Ethyl 3-tert-butyl-4-oxo-7-X-4,6-dihydropyrazolo[5,1-c][1,2,4]triazine-8-carboxylates (X = H, Cl, Br) were synthesized for the first time by diazotization of 7-amino-3-tert-butyl-4oxo-8-ethoxycarbonyl-6H-pyrazolo[5,1-c][1,2,4]triazines with tert-butyl nitrite in the presence of trimethylsilyl halides. A new method was developed: a reaction between 7-amino-3-tert-butyl-4-oxo-6H-pyrazolo[5,1-c][1,2,4]triazine-8-carboxylic acid and I₂/TEA followed by treatment with NaBH₄ led to a mild decarboxylation. The acid reacts with N-halosuccinimides to give novel 8-halo-substituted derivatives. The amino groups of the latter were acylated by treatment with trifluoroacetic anhydride to give monoacylation products.

     

Synthesis of Pyrido[2′,3′: 3,4]pyrazolo[1,5‐a]pyrimidine,Pyrido[2′,3′:3,4]pyrazolo[5,1‐c][1,2,4]triazine,and Pyrazolyl Oxadiazolylthieno[2,3‐b]pyridine Derivatives

6‐(2‐Thienyl)‐4‐(trifluoromethyl)‐1H‐pyrazolo[3,4‐b]pyridine‐3‐amine reacted with different active methylene compounds to afford pyridopyrazolopyrimidine derivatives. On the other hand, it reacted with some halo compounds to give the imidazo[1′,2′:1,5]pyrazolo[3,4‐b]pyridine derivatives. Also, it diazotized to give the corresponding diazonium chloride that is coupled with several active methylene compounds to give the corresponding triazine derivatives. Furthermore, compound 3‐amino‐6‐(2(thienyl)‐4‐(trifluoromethyl)thieno[2,3‐b]pyridine‐2‐carbohydrazide reacted with some β‐dicarbonyl compounds and some sulfur‐containing compounds to afford the corresponding pyrazolyl oxadiazolylthieno[2,3‐b]pyridine derivatives.     

Aminopyrazoles. Part 3. Synthesis of the novel ring systems pyrazolo[4′,3′:5,6]pyrido[2,3-b][1,5]benzoxazepine and [1,5]benzothiazepine

Two-step synthesis of the novel fused heterocycles pyrazolo[4′,3′:5,6]pyrido[2,3-b][1,5]benzoxazepine ( 8 ) and pyrazolo[4′,3′:5,6]pyrido[2,3-b][1,5]benzothiazepine ( 9 ) from the pyrazolo[3,4-b]pyridine derivative 1 is described.     

Pyrazole-3(5)-diazonium salts in the synthesis of novel pyrazolo[5,1-c][1,2,4]triazines

Coupling of pyrazole-3(5)-diazonium salts with cyclic 1,3-dicarbonyl (active methylene) compounds followed by cyclocondensation of the resulting hetarylhydrazones gave novel pyrazolo[5,1-c][1,2,4]triazines.     

Synthesis of 6,8-substituted derivatives of imidazo[5,1-c][1,2,4]triazines and 1,4-dihydroimidazo[5,1-c][1,2,4]triazin-4-ones

The cyclization of imidazolylhydrazines, synthesized from 5-diazoimidazoles and cyanoacetic acid derivatives, to 4-aminoimidazo[5,1-c][1,2,4]triazines and imidazo[5,1-c][1,2,4]triazin-4-ones has been studied. It was established that electron-withdrawing substituents at position 4 of the imidazole ring had a weak effect on the cyclization process. On the other hand, electron-donating substituents at positions 4 or 2 of this ring inhibited and in some cases completely prevented the formation of bicyclic products.Urals State Technical University (UPI), Ekaterinburg 620002, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 805–815, June, 1998.     

Reduction of nitro derivatives of azolo[5,1-c][1,2,4]triazines

Reduction of6-nitro-7-oxo-4,7-dihydroazolo[5,1-c][1,2,4]triazines into the corresponding amines with sodium dithionite takes place smoothly in neutral aqueous solutions. The structural effects in reduction of nitroazoloazines were evaluated electrochemically.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 674–677, May, 1992.     

Microwave assisted convenient synthesis of quino[2,3-b][1,5]benzoxazepines

A convenient synthesis of quino[2,3-b][1,5]benzoxazepines from substituted 2-chloroquinoline-3-carbaldehyde and 2-hydroxy-aniline by using stable,non-toxic and inexpensive catalyst 1,8-diazabicyclo-undecan-7-ene (DBU)/silica gel is described.This method affords the quino[2,3-b][1,5]benzoxazepines under the influence of microwave irradiation (360 W) in solvent-free conditions within short reaction times (2-3 min),giving high yields of products (93-96%).     

Synthesis of a New Imidazo[4′,5′:3,4]pyrazolo[5,1‐c][1,2,4]triazine‐4,8‐dione Heterocyclic System

A novel imidazo[4′,5′:3,4]pyrazolo[5,1‐c][1,2,4]triazine‐4,8‐dione heterocyclic system was synthesized starting from available 4‐amino‐6‐tert‐butyl‐3‐methylthio‐1,2,4‐triazin‐5(4H)‐one in four steps with 28% overall yield.     

Synthesis,reactions, and antimicrobial activity of some novel pyrazolo[3,4-d]pyrimidine,pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine,and pyrazolo[4,3-e][1,2,4]triazolo[3,4-c]pyrimidine derivatives

Treatment of N-phenyl-substituted benzenecarbo-hydrazonoyl chlorides 1a - d with malononitrile in sodium ethoxide solution gave 5-amino-4-cyanopyrazole derivatives 2 - 5 . Compounds 2 - 5 were converted to formidate derivatives 6 - 9 upon treatment with TEOF in acetic anhydride. The reaction of the latter products 6 - 9 with hydrazine hydrate gave imino-amino derivatives 10 - 13 , which was converted to hydrazino derivatives 14 - 17 by refluxing with hydrazine hydrate. Hydrazino as well as imino-amino derivatives undergo condensation, cyclization, and cycloaddition reactions to give pyrazolo[3,4-d]pyrimidine 18 - 21 , pyrazolo[4,3-e][1,2,4]triazolo-[3,4-c]pyrimidine 22 - 27 , and pyrazolo[3′,4′:4,5]pyrimido[1,6-b][1,2,4]triazine 42 - 44 derivatives. Antimicrobial studies are performed using two Gram-positive bacteria and two Gram-negative bacteria. Data indicated that compounds 5 , 28D , 29B , and 31D are exploring elevated antibacterial effects against all strains tested. Compound 28D is the most promising antibacterial agent against the delicate bacterial strain Bacillus subtilis and Pseudomonas aeruginosa with high effectiveness (low minimum inhibitory concentration [MIC] value) 40 and 60 μg/mL, respectively.     

Naphtho[1′,2′:5,6]pyrano[2,3–6][1,5]benzodiazepine Derivatives

The reaction of 3-(dimethylamino)-1-oxo-1H-naphtho[2,1-b]pyran-2-carbaldehyde (Ia) with o-phenylenediamines or N-monosubstituted o-phenylenediamines in refluxing glacial acetic acid afforded the corresponding naphtho[1′,2′:5,6]pyrano[2,3-b][1,5]benzodiazepin-15-(8H)ones V in very good yields. A similar result was achieved when the reaction was carried out in refluxing pyridine, using N-monosubstituted o-phenylenediamine hydrochlorides. The isolation of a significant intermediate as well as the synthesis through a different univocal pathway confirmed the structure of the compounds V. Moreover the reaction of Ia with N-monosubstituted o-phenylenediamines in refluxing pyridine generally afforded only low yields of compounds V, sometimes together with naphtho[1′,2′:5,6]pyrano[2,3-b][1,5]benzodiazepin-15-(13H)ones VII, isomers of V.     

3-Cyanoazolo[5,1-c][1,2,4]triazines: synthesis and antiviral activity

Chemistry of Heterocyclic Compounds - A series of azolo[5,1-c][1,2,4]triazines containing a cyano group were prepared as analogs of the drug Triazavirin (riamilovir). Sodium...     

A new method for the synthesis of novel 6-quinoxalinylpyrazolo[5,1-c][1,2,4]triazines

The reaction of the quinoxaline 1 with 4-ethoxycarbonyl-1H-pyrazole-5-diazonium chloride 7 at room temperature gave 3-[α-(4-ethoxycarbonyl-1H-pyrazol-5-ylhydrazono)methoxycarbonylmethyl]-2-oxo-1,2-dihydroquinoxaline 8. The pmr spectrum of 8 in deuteriodimethylsulfoxide supported the presence of two tautomers 8-I and 8-II. Refluxing of 8 in N,N-dimethylformamide or acetic acid resulted in cyclization to afford 8-ethoxycarbonyl-4-oxo-3-(3-oxo-3,4-dihydroquinoxalin-2-yl)-1,4-dihydropyrazolo[5,1-c][1,2,4]triazine 9. Compound 9 was also obtained directly by the reaction of 1 with 7 under reflux in better yield. The reaction of 9 with hydrazine hydrate provided the hydrazinium salt 10 , while the reactions of 9 with triethyl and trimethyl orthoformates in the presence of 1,8-diazabicyclo[5,4,0]-7-undecene produced 8-ethoxycarbonyl-4-ethoxyl-3-(3-oxo-3,4-dihydroquinoxalin-2-yl)pyrazolo[5,1-c][1,2,4]triazine 11a and 8-ethoxycarbonyl-4-methoxyl-3-(3-oxo-3,4-dihydroquinoxalin-2-yl)pyrazolo[5,1-c][1,2,4]triazine 11b , respectively. The chlorination of 11a with phosphoryl chloride gave 3-(3-chloroquinoxalin-2-yl)-8-ethoxycarbonyl-4-ethoxylpyrazolo[5,1-c]-[1,2,4]triazine 12 , whose reaction with morpholine afforded 8-ethoxycarbonyl-4-ethoxyl-3-[3-(morpholin-4-yl)-quinoxalin-2-yl]pyrazolo[5,1-c][1,2,4]triazine 13.     

Synthesis of Certain 3-Aminopyrazolo[5,4-b]pyridine and 3,4-Substituted Pyrido[2′,3′：3,4]pyrazolo[5,1-c][1,2,4]triazine Derivatives

2-Thioxo-1,2-dihydropyridine derivatives 2a, 2b were reacted with methyl iodide to give 2-methylthiopyridines 3a, 3b, which were reacted with hydrazine hydrate to produce 3-aminopyrazolo[5,4-b]pyridines 4a, 4b. Compounds 4a, 4b were diazotized to afford the corresponding diazonium salts 5a, 5b, which were reacted with some active methylene compounds 6a-6h to give the corresponding pyrido[2′,3′ ： 3,4]pyrazole[5,1-c][1,2,4]triazines 7-14.     

On triazoles XLIV [1]. synthesis of new ring systems containing imidazo[2′,1′:3,4] [1,2,4] triazolo [1,5‐a]pyrimidine and imidazo[1′,2′:2,3][1,2,4]triazolo[1,5‐a]pyrimidine skeleton

Dedicated to Dr. János Császár on the occasion of his 70^th birthday Ring transformation of 2‐cyanoimido‐3‐methyl‐1,3‐oxazolidine ( 10 ) yielded 5‐amino‐3‐[N‐(2‐hydrox‐yethyl)‐N‐methyl]amino‐1H‐1,2,4‐triazole ( 6 ) that was ring closed with different β‐keto esters to 2‐[N‐(2‐hydroxyethyl)‐N‐methyl]amino‐1,2,4‐triazolo[1,5‐a]pyrimidinones ( 4 ). Cyclisation of derivatives 4 led to imidazo[2′,1′:3,4][1,2,4]triazolo[1,5‐a]pyrimidines ( 2 ) and imidazo[1′,2′:2,3][1,2,4]triazolo[1,5‐a]pyrim‐idines ( 3 ) representing 10 novel ring systems. Besides spectroscopical evidence of structure of derivatives 2 and 3 X‐ray diffraction analysis of derivative 2b was also performed.     

Synthesis of 3-tert-Butyl-4-hydroxy-1,4-dihydropyrazolo[5,1-c][1,2,4]triazines

Russian Journal of Organic Chemistry - Two new approaches have been proposed for the synthesis of 4-hydroxy-1,4-dihydropyrazolo[5,1-c]-[1,2,4]triazines via (1) borohydride reduction of...