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New solventless and metal-free synthesis of the antiepileptic drug 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxamide (Rufinamide) and analogues

Author:
Bonacorso, Helio G., Moraes, Maiara C., Luz, Fábio M., Quintana, Pedro S., Zanatta, Nilo, Martins, Marcos A.P.
Source:
Tetrahedron letters 2015 v.56 no.2 pp. 441-444
ISSN:
0040-4039
Subject:
ammonium hydroxide, anticonvulsants, aqueous solutions, azides, catalytic activity, chemical structure, cycloaddition reactions, regioselectivity, triazoles
Abstract:
This work presents a new synthesis of the antiepileptic drug rufinamide—1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxamide) in chemical form—and some analogue compounds, through a one-pot reaction employing a solventless, metal-free catalysis and without any reducing reagent. The great novelty presented is the synthesis of 4-trichloroacetyl-1-(2,6-difluorobenzyl/benzyl/4-methoxybenzyl)-5-methyl(phenyl)-1H-1,2,3-triazoles as new precursors from a regioselective 1,3-dipolar cycloaddition reaction between 1,1,1-trichloro-4-alkoxyalk-3-en-2-ones and some benzyl azides, which are converted into rufinamide and the analogues by an addition–elimination reaction with an aqueous solution of NH4OH in good yields (42–52%).
Agid:
6024912