Fluorinated [1,2,4]triazolo[1,5-a]pyrimidines and [1,2,4]triazolo[5,1-c][1,2,4]triazines*

Synthetic approaches to 1,2,4-triazolo[5,1-c][1,2,4]triazin-7-ones as basic heterocyclic structures of the antiviral drug Riamilovir (“Triazavirin®”) active against SARS-CoV-2 (COVID-19)

“…28 The synthesis of 6-fluoro-1,2,4-triazolo[5,1-c]-1,2,4-triazin-7ones 32 was carried out using the Japp-Klingemann reaction by means of azo-coupling between 1,2,4-triazolyl-5-diazonium 19 and ethyl 2-fluoroacetoacetate followed by deacetylation and cyclization. 38 Alkyl fluoroacetates themselves do not react in azo-coupling reactions due to their low CH acidity. In this case, the authors used a method for the activation of fluorine-containing synthons by introducing an acetyl moiety in their structure, which easily leaves during the azo-coupling reaction.…”

Bicyclic 5-6 Systems With One Bridgehead (Ring Junction) Nitrogen Atom: Four Extra Heteroatoms 2:2

“…A significant downfield shift has been noticed for 33 (from -114 to -115 ppm) compared to triazolopyrimidinones 34 (from -169 to -171 ppm) which has been rationalized by the electron-withdrawing effect of the triazine nitrogen atom N2 (Figure 3). 11 <Figure Figure 3 11. 19…”

“…Interestingly, heating hydrazones 458 in pyridine furnished pyridinium 461. The latter could be also directly obtained by treating diazonium salts 436 with diethyl -pyridinium malonate 460 in pyridine under reflux 11. Polyfluoroalkyl-containing 1,3dicarbonyl reagents 462 have been used to access various 7-hydroxy-7-polyfluoroalkyl dihydrotriazolotriazines 463 in moderate to good yields (Scheme 92) [201][202][203].…”

Fluorinated Triazines

“…]triazin-7(4H)-ones 10 has been recently described [ 16 ]. The coupling of 1,2,4-triazolyl-5-diazonium salts 11 with ethyl 2-fl uoroacetate and the accompanied deacetylation leads to the formation of hydrazones 12 followed by cyclization on heating in aqueous alcohol in the presence of sodium acetate into the target fl uoro compounds 10 (Scheme 9 ).…”