1.2.4- Triazolo triazepines

Of the various possible 1,2,4-triazolo-triazepines, only 1,2,4-triazolo-1,2,4-triazepines have been synthesized. 

Triazolo- 1, 2,4-triazepines Two ring systems, 548 and 549, have been synthesized. 

The reaction of the l-acylamino-2-methylthio-l,4-dihydropyrimidines (85) with 80% hydrazine in acetic acid resulted in ring enlargement with loss of methanethiol to give the 1,2,4-triazolo[4,3-/]-1,2,4-triazepines (86) (30-85% yields), probably via the mechanism indicated in Scheme 13 <90ZC9l>. The hydrazone derivative, derived from the 1,2,4-triazole (87), was also cyclized (70% yield) to the l,2,4-triazolo[3,2-c]-l,2,4-triazepine (88) <82KGSlil3>. 

In an effort to synthesize fused 7/5 heterocyclic ring system to obtain boosted bioactivity, Gupta et al. [102] condensed two heterocyclic systems, triazole and triazepine, into a single framework by the cyclocondensation of 5-aryl-3,4-diamino-l,2,4-triazoles with p-chlorocinnamaldehydes in the presence of catalytic amount of p-TsOH in DMF xmder microwave irradiation (also conventional oil bath heating) to afford 3,6-diaryl-5H-[l,2,4] triazolo[4,3-fc]-l,2,4-triazepines (103). Both the heterocyclic motifs (triazepine and triazole) are well-known core units of several drugs and bioactive compoxmds (Scheme 34). 

M. Gupta, S. Paul, R. Gupta, Efficient and novel one-pot synthesis of antifungal active l-substituted-8-aryl-3-alkyl/aryl-4H-pyrazolo[4,5-f] [l,2,4]triazolo[4,3-b][l,2,4]triazepines using solid support, Eur. J. Med. Chem. 46 (2011) 631-635. 

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