Synthesis of some novel pyrazolo[1,5‐a]pyrimidine, 1,2,4‐triazolo[1,5‐a]pyrimidine,pyrido[2,3‐d]pyrimidine,pyrazolo[5,1‐c]‐1,2,4‐triazine and 1,2,4‐triazolo[5,1‐c]‐1,2,4‐triazine derivatives incorporating a thiazolo[3,2‐a]benzimidazole moiety

E‐3‐(N,N‐Dimethylamino)‐1‐(3‐methylthiazolo[3,2‐a]benzimidazol‐2‐yl)prop‐2‐en‐1‐one ( 2 ) was synthesized by the reaction of 1‐(3‐methylthiazolo[3,2‐a]benzimidazol‐2‐yl)ethanone ( 1 ) with dimethylformamide‐dimethylacetal. The reaction of 2 with 5‐amino‐3‐phenyl‐1H‐pyrazole ( 4a ) or 3‐amino‐1,2,4‐(1H)‐triazole ( 4b ) furnished pyrazolo[1,5‐a]pyrimidine and 1,2,4‐triazolo[1,5‐a]pyrimidine derivatives 6a and 6b , while the reaction of enaminone 2 with 6‐aminopyrimidine derivatives 7a,b afforded pyrido[2,3‐d]pyrimidine derivatives 9a,b , respectively. The diazonium salts 11a or 11b coupled with compound 2 to yield the pyrazolo[5,1‐c]‐1,2,4‐triazine and 1,2,4‐triazolo[5,1‐c]‐1,2,4‐triazine derivatives 13a and 13b . Some of the newly synthesized compounds exhibited a moderate effect against some bacterial and fungal species.     

Synthesis and structure characterization of new [1,2,4]triazolo[5,4‐d][1,5]benzothiazepine derivatives through 1,3‐dipolar cycloaddition reaction

Reaction of 1,5‐benzothiazepines 3 , obtained from chalcones 2 and o‐aminobenzenthiol, with the (phenylhydrazino) chloromethylenecarboxylates 4 in the presence of Et₃N leads to a series of new [1,2,4]triazolo[5,4‐d][1,5]benzothiazepine derivatives 5 . Their structures were established using spectroscopic methods and that of compound 5d was confirmed using X‐ray diffraction analysis. J. Heterocyclic Chem., (2011).     

New 1,2,3‐triazolo[4,5‐d]1,2,4‐triazolo[3,4‐b]pyridazine derivatives II

New tricyclic 1,2,3‐triazolo‐1,2,4‐triazolo‐pyridazine derivatives, bearing a methyl substituent on the 1,2,3‐triazole ring, were prepared as potential biological agents. N‐Methylation of dimethyl 1,2,3‐triazole‐4,5‐dicarboxylate allowed synthesis of the isomeric 1‐methyl‐4,7‐dihydroxy and 2‐methyl‐4,7‐dihydroxy triazolo‐pyridazines 4a and 4b which, by a chlorination reaction, gave the corresponding 1‐methyl‐4‐chloro‐( 6a ), 1‐methyl‐7‐chloro‐ ( 6b ) and 2‐methyl‐4‐chloro‐ ( 9 ) substituted 1,2,3‐triazolo‐pyridazines. The nucle‐ophilic substitution with hydrazine hydrate and the suitable cyclization to form the 1,2,4‐triazole ring, provided the expected tricyclic isomeric derivatives 8a, 8b and 11 respectively. The p‐methoxybenzyl substituent, introduced as a leaving group to obtain either v‐triazolo‐pyridazine or v‐triazolo‐s‐triazolo‐pyri‐dazine derivatives unsubstituted on the 1,2,3‐triazole ring, appeared inadequate. Some compounds underwent binding assays toward the adenosine A₁and A_2A receptors.     

8-氟-5-羟基-[1,2,4]三唑并[1,5-c]嘧啶-2-磺酰胺的合成

8-氟-5-羟基-[1,2,4]三唑并[1,5-c]嘧啶-2-磺酰胺（9）为重要的医药、农药等中间体,其合成方法暂无文献报道。以2,4-二氯-5-氟嘧啶为原料,经醚化、肼解、环合、重排、磺酰胺化、脱甲基化等反应合成了9,总收率27.2%,其结构经¹H NMR,¹³C NMR和MS（ESI）确证。     

New [g]-fused [1,2,4]triazolo[1,5-c]pyrimidines: Synthesis of pyrido[3,2-e] and [4,3-e][1,2,4]triazolo[1,5-c]pyrimidine,pyrimido[5,4-e][1,2,4]triazolo[1,5-c]pyrimidine and [1,2,4]triazolo[1,5-c]pteridine derivatives

A number of 2-aryl-substituted pyrido[3,2-e] and [4,3-e][1,2,4]triazolo[1,5-c]pyrimidines and [1,2,4]triazolo[1,5-c]pteridines 11,12a,b,e , their corresponding 5-carbonyl derivatives 7,8a,b,e and some pyrimido[5,4-e][1,2,4]triazolo[1,5-c]pyrimidin-5-ones 7,8c,d have been synthesized, according to different pathways. The new tricyclic heterocycles were prepared with the aim of studying their possible benzodiazepine receptors affinity.     

Differentiation between [1,2,4]triazolo[1,5‐a] pyrimidine and [1,2,4]triazolo[4,3‐a]‐ pyrimidine regioisomers by 1H?15N HMBC experiments

The condensation of malonoaldehyde derivatives with either a 3‐amino‐[1,2,4]‐triazole or a 3,5‐diamino‐[1,2,4]‐triazole precursor was studied. In agreement with previous reports, two different bicycles, namely, bearing the regioisomeric [1,2,4]triazolo[1,5‐a]pyrimidine ( 1 ) or[1,2,4] triazolo [4,3‐a]pyrimidine ( 2 ) structural surrogates, could be obtained. We found that, depending on the triazole precursor, only one regioisomer resulted, either of the 1 or 2 series. We also observed that these two structural surrogates could be unambiguously differentiated by indirectly measuring their ¹⁵N chemical shifts by ¹H? ¹⁵N HMBC experiments. The occasional conversion of [1,2,4]triazolo[4,3‐a]pyrimidines to the [1,2,4]triazolo[1,5‐a]pyrimidine counterparts could be unequivocally determined by ¹⁵N NMR data. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis and antitumor activities of 2‐(substituted)phenyl‐1,2,4‐triazolo[1,5‐a]pyridines

Twenty‐three 2‐(substituted)phenyl‐1,2,4‐triazolo[1,5‐a]pyridines have been synthesized by cycloadditison reaction between N‐amino methylpyridinium mesitylenesulfonates and substituted benzonitriles under the presence of potassium hydroxide at room temperature. The structures of all products were confirmed by ¹H NMR, MS and elemental analyses. The antitumor activities of these compounds were evaluated against human ovary cancer cell line (HO‐8910) in vitro by MTT method. The preliminary results showed that compound 1e (IC₅₀ 28μM) and compound 1w (IC₅₀ 31μM) exhibited stronger antitumor activities than cisplatin (IC₅₀ 35μM) in vitro. Hence, 1e and 1w have potential antitumor activities and are worth further investigation.     

Pyrrolo[3,4‐e][1,2,3]triazolo[1,5‐a]pyrimidine and pyrrolo[3,4‐d] [1,2,3]triazolo[1,5‐a]pyrimidine. New tricyclic ring systems of biological interest

Derivatives of the new ring system pyrrolo[3,4‐e][1,2,3] triazolo[1,5‐a]pyrimidine 6 were prepared in high yields in one step by reaction of 3‐azidopyrrole 3 and substituted acetonitriles. Compound 6b rearranged, upon heating in dimethyl sulfoxide in the presence of water, to pyrrolo[3,4‐d][1,2,3]triazolo‐[1,5‐a]pyrimidine 7.     

On triazoles XLV [1]. synthesis of 5,7‐diamino‐1,2,4‐triazolo[1,5‐a] [1,3,5]triazines

Dedicated to Professor András Messmer on the occasion of his 80^th birthday The reaction of differently substituted 5‐amino‐1,2,4‐triazoles ( 5 ) with isothiourea derivatives ( 3 ) to yield isomeric 5,7‐diamino‐1,2,4‐triazolo[1,5‐a][1,3,5]triazines ( 6 and 7 ), previously described as not proceeding in melt, was performed in different solvents as well as in the melt at 150‐160°. It was proved that the above reaction had rather general validity. The structure of isomers 6 and 7 were proved spectroscopically. The structure of 6/5 (Q = ethylamino) was corroborated with single crystal X‐ray diffraction determination, as well.     

Synthesis of 1,3,3a,5‐tetraaryl‐3a,4,5,6‐tetrahydro‐3H‐1,2,4‐triazolo[4,3‐a] [1,5]benzodiazepines

A series of 3a,5‐diaryl‐1,3‐diphenyl‐3a,4,5,6‐tetrahydro‐3H‐1,2,4‐triazolo[4,3‐a][1,5]benzo‐diazepines was synthesized by the cycloaddition reactions of 2,4‐diaryl‐2,3‐dihydro‐1H‐1,5‐benzo‐diazepines and N‐phenylbenzonitrileimine generated from N‐phenylbenzenecarbohydrazonic chloride in the presence of triethylamine in anhydrous tetrahydrofuran. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:557–559, 2001     

Synthesis and antifungal activity of novel 3,6‐diaryl‐5H‐[1,2,4]triazolo[4,3‐b][1,2,4]triazepines

5‐Aryl‐3,4‐diamino‐1,2,4‐triazoles 5 on treatment with β‐chlorocinnamaldehydes 7 in the presence of catalytic amount of p‐TsOH and N,N‐dimethylformamide as an energy transfer medium under microwave irradiation and as solvent with oil‐bath heating at 80 °C affords novel 3,6‐diaryl‐5H‐[1,2,4]triazolo[4,3‐b]‐1,2,4]triazepines 8 . The structures of the synthesized compounds were established on the basis of ¹H NMR, IR, mass spectral data and elemental analysis.     

New 1,2,3‐triazolo[4,5‐e]1,2,4‐triazolo[4,3‐c]pyrimidine derivatives II

The 7‐chloro‐3‐(2‐chlorobenzyl)‐ and 7‐chloro‐3‐(2‐fluorobenzyl)‐1,2,3‐triazolo[4,5‐d]pyrimidines ( 1 and 4 ), by nucleophilic replacement with some hydrazides, gave the corresponding 7‐hydrazidoderivatives ( 2a‐e and 5a‐e ). These, by heating in Dowtherm, underwent an intramolecular cyclization to form the new tricyclic 7‐substituted‐3‐(2‐chlorobenzyl)‐ and 3‐(2‐fluorobenzyl)‐1,2,3‐triazolo[4,5‐e]1,2,4‐triazolo[4,3‐c]pyrimidines ( 3a‐d and 6a‐d ). The 7‐hydrazino‐3‐(2‐chlorobenzyl)‐ and 7‐hydrazino‐3‐(2‐fluorobenzyl)‐triazolo‐pyrimidines ( 9a and 9b ) were also prepared via the corresponding mercapto ( 7a and 7b ) and thiomethyl ( 8a and 8b ) derivatives.     

Synthesis and anti-tumor activities of novel [1,2,4]triazolo[1,5-a]pyrimidines

A series of novel [1,2,4]triazolo[1,5-a]pyrimidine derivatives has been designed and synthesized in order to find novel anti-tumor compounds. The structures of all the compounds were confirmed by IR, 1H-NMR, MS and elemental analysis. Their anti-tumor activities against cancer cell lines (HT-1080 and Bel-7402) were tested by the MTT method in vitro. Among them, compound 19 displayed the best anti-tumor activity with IC50 values of 12.3 microM and 6.1 microM against Bel-7402 and HT-1080 cell lines respectively.     

Synthesis of Oxazolo[5,4‐d][1,2,4]triazolo[4,3‐a]pyrimidines as a New Class of Heterocyclic Compounds

Several new derivatives of oxazolo[5,4‐d]pyrimidine ( 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h ) have been synthesized through the reaction of 2,4‐dichloro‐6‐methyl‐5‐nitropyrimidine ( 2 ) with aryl carboxylic acids in refluxing POCl₃. Further treatment of compounds ( 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h ) with hydrazine hydrate gave the hydrazine derivatives ( 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h ) that were subsequently cyclized into a novel heterocyclic system, oxazolo[5,4‐d][1,2,4]triazolo[4,3‐a]pyrimidine ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j , 5k , 5l , 5m , 5n , 5o , 5p ) and ( 7a , 7b , 7c , 7d ) on treatment with triethylorthoesters or carbondisulfide and alkylhalides, respectively.     

Synthesis of pyrazolo[1,5‐a]‐, 1,2,4‐triazolo[1,5‐a]‐ and imidazo[1,2‐a]pyrimidines related to zaleplon,a new drug for the treatment of insomnia

This paper describes the preparation of some pyrazolo[1,5‐a]‐, 1,2,4‐triazolo[1,5‐a]‐ and imidazo[1,2‐a]‐pyrimidines substituted on the pyrimidine moiety by a 4‐[(N‐acetyl‐N‐ethyl)amino]phenyl group. A new synthesis of related benzo[h]pyrazolo[1,5‐a]‐, benzo[h]pyrazolo[5,1‐b]‐ and benzo[h]1,2,4‐triazolo[1,5‐a]‐quinazolines is also reported.     

Synthesis and bioactivity of novel triazolo [1,5‐a]pyrimidine derivatives[3]

In an attempt to discover novel compounds with high herbicidal activity and low toxicity, a series of novel 1,2,4‐triazolo[1,5‐a]pyrimidine derivatives, α‐(5,7‐dimethyl‐1,2,4‐triazolo[1,5‐a]pyrimidine‐2‐thio)acetamides 3 and α‐(5,7‐dimethyl‐1,2,4‐triazolo[1,5‐a]pyrimidine‐2‐sul‐fonyl)acetamides 4 , have been designed and synthesized by a three‐step synthetic route. The structures of all compounds prepared were confirmed by elemental analyses and by ¹H NMR and mass spectroscopy. The results of preliminary bioassay indicate that the title compounds possess good herbicidal activity against rape (Brassica campestris L.) and barnyardgrass (Echinochloca crusgalli L.) © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:491–496, 2001