A new heterocyclic structure. The [1,2,3]triazolo[1,5-d][1,2,4]triazine

The hydrazone derivatives of 4-benzoyl-1,2,3-triazole can easily be cyclised by reaction with various organic reagents (ortho esters, aldehyde and ketone compounds, phosgene, etc) which result in the incorporation of the introduced reagent's carbon atom into the new six membered ring. The newly created C-N bond of the resulting [1,2,3]triazolo[1,5-d][1,2,4]triazines displays a particular sensitivity due to the electron attracting effect of the triazole ring. Some mechanistic considerations are proposed to account for the observed results.     

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 mesoionic[1,2,3]triazolo[5,1-d][1,2,5]triazepines

Intramolecular cyclization of 1-amino-3-phenacyl-4-carbohydrazido-1,2,3-triazolium-5-olates has been shown to take place via selective interaction of the carbonyl group with the terminal amino function of the hydrazido group to form a 1,2,5-triazepine ring. Minor products, resulting from the interaction of the α-nitrogen atom of the hydrazido group with the carbonyl function, having a N-amino-pyridazine structure were also detected and isolated. A general method for the synthesis of novel mesoionic 2-amino-7-aryl-4-oxo-2,4,5,8-tetrahydro[1,2,3]triazolo[5,1-d][1,2,5]triazepin-9-ium-3-olates was developed.     

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.     

A new method for the synthesis of novel 1,2,4-triazolo[3,4-f][1,2,4]triazines

Novel compounds 8-(quinoxalin-2-yl)-1,2,4-triazolo[3,4-f][1,2,4]triazines 3a,b were obtained by a new annulation method in the 1,2,4-triazine synthesis.     

Synthesis of 1,2,3-thiadiazolo[4,5-d] pyridazines,A new heterocyclic ring system

A method was developed for the synthesis of 5-carbethoxy-4-formyl-1,2,3-thiadiazole (I), its isomer (II); 5-benzoyl-4-formyl-1,2,3-thiadiazole (III), and its isomer (IV). It was demonstrated that although compounds I, III and IV with hydrazine gave 7H-1,2,3-thiadiazolo[4,5-d]-pyridazin-7-one (XXII), 7-phenyl-1,2,3-thiadiazolo[4,5-d]pyridazine (XXIII) and 4-phenyl-1,2,3-thiadiazolo[4,5-d]pyridazine (XXV), respectively; however, compound I gave its corresponding hydrazone (XXIV).     

Discovery and process synthesis of novel 2,7-pyrrolo[2,1-f][1,2,4]triazines

The synthesis of a new kinase inhibitor template 2-anilino-7-aryl-pyrrolo[2,1-f][1,2,4]triazine is described which includes a late stage orthogonally reactive key intermediate amenable to rapid diversification as well an optimized in situ triflate displacement to install the C2-aniline. Furthermore, an efficient scalable process approach will be highlighted which begins with tert-butyl carbazate to provide the key N-N bond and generates the pyrrolotriazine core through a stable bromoaldehyde intermediate followed by condensation with ammonium carbonate.     

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...     

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 and transformations of 4-phenylethynyl- and 4-styrylpyrazolo[5,1-c][1,2,4]triazines

Chemistry of Heterocyclic Compounds - Rearrangements of 3-tert-butyl-8-methyl-4-phenylethynyl-1,4-dihydropyrazolo[5,1-c][1,2,4]triazine derivatives by the action of bases led to the formation of...     

Nitroazines. 19. Prototropic tautomerism in 6-nitro-7-oxo-4,7-dihydro-1,2,4-triazolo[5,1-c][1,2,4]triazines

Prototropic reactions of 6-nitro-7-oxo-4,7-dihydro-1,2,4-triazolo[5,1-c][1,2,4]triazines is tautomeric as established from photoionization results. The ratios of the tautomers in the gas phase and in solution have been determined by mass and ¹³C NMR spectroscopy.For Communication 18 see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1555–1559, November, 1992.     

Synthesis of 8-alkylthio- and 8-selanyl-3-tert-butylpyrazolo[5,1-c][1,2,4]triazines

Abstract

Interaction of 8-lithio-3-tert-butyl-4-oxopyrazolo[5,1-c][1,2,4]triazin-1-ide with elemental sulfur or selenium in THF with further in situ alkylation at –97?°C followed by warming to room temperature furnished a series of 3-tert-butyl-8-X-pyrazolo[5,1-c][1,2,4]triazin-4(6H)-ones (X?=?n-BuS, n-BuSe, MeSe, PhCH₂S) in good yields. 8,8'-Diselanediylbis(3-tert-butylpyrazolo[5,1-c][1,2,4]triazin-4(1H)-one) was also isolated as a by-product in these reactions. One-pot interaction of the n-BuSe substituted derivative with diborane/boron trifluoride led to reduction of the 1,2,4-triazine core and partial elimination of the alkylselanyl moiety. The structures of the synthesized products were established on the basis of IR, ¹H, 13C, 2D HMBC ¹H–⁷⁷Se NMR and high resolution mass spectra, as well as X-ray single crystal diffraction analyses. Two of the prepared compounds were also tested for antimicrobial and antifungal activities.     

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.