Synthesis of New Piperidine based N(2)-Alkylated 1,2,3-Triazole Hybrids in Basic Medium

Abstract

The nucleophilic reaction of 1H-triazole derivatives with piperidines under basic conditions is the essential step in the synthesis of a new series of dibenzyl N(2)-C-linked triazolyl piperidines. The triazole derivative was synthesized via the CuAAc reaction of 1-phenylprop-2-yn-1-ol (1a-b) with azidomethyl pivalate. Compound 3a-b underwent dehydroxylation and deprotection reactions using TFA, triethyl silane and 1 M NaOH respectively, yielding monobenzyl 1H-1,2,3-triazole (4a-b). The N(2)-piperidinyltriazoles (6a-j) were synthesized in significant amounts by nucleophilically reacting 1H-triazole derivatives (4a-b) with 4-mesyl-1-boc-piperidine (5) under basic conditions using sodium hydride, which further on acidic deprotection followed by benzylation reaction furnished dibenzyl N(2)-C-linked triazolyl piperidines (9a-j).