A straightforward, one-pot protocol for the synthesis of fused 3-aminotriazoles.
A simple protocol for the synthesis of 3-amino-[1,2,4]triazolo[4,3-a]pyridines is reported. The newly developed one-pot methodology involves the reaction of hydrazinopyridine with isothiocyanates to give the corresponding thiosemicarbazides, which are further desulfurized in situ using polymer-supported Mukaiyama's reagent to promote the final cyclization and formation of the central core. Aryl isothiocyanates bearing both electron-donating and electron-withdrawing groups are well tolerated, and the expected compounds were obtained in excellent purities and yields after removal of salts with a SPE-NH2 column. This methodology proved to be robust in the extension to 3-amino-[1,2,4]triazolo[4,3-a]-pyrazines and 3-amino-[1,2,4]triazolo[4,3-c]-pyrimidines, and no significant differences were noticed in terms of purities and yields. The straightforward protocol developed, mix, filter, and evaporate, is appropriate for performing multiple reactions in parallel fashion without need of purification.
Comas
Horacio
H
Chemistry Department, Merck Serono Geneva Research Center, 9 Chemin des Mines, Geneva 1202, Switzerland.
Bernardinelli
Gérald
G
Swinnen
Dominique
D
D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry
C545173:3-amino-(1,2,4)triazolo(4,3-a)pyridine; D011725:Pyridines; D014230:Triazoles