Synthesis and Characterization of Novel Methyl (3)5-( N-Boc-piperidinyl)-1 H-pyrazole-4-carboxylates

Abstract

Series of methyl 3- and 5-( N-Boc-piperidinyl)-1 H-pyrazole-4-carboxylates were developed and regioselectively synthesized as novel heterocyclic amino acids in their N-Boc protected ester form for achiral and chiral building blocks. In the first stage of the synthesis, piperidine-4-carboxylic and ( R)- and ( S)-piperidine-3-carboxylic acids were converted to the corresponding β-keto esters, which were then treated with N, N-dimethylformamide dimethyl acetal. The subsequent reaction of β-enamine diketones with various N-mono-substituted hydrazines afforded the target 5-( N-Boc-piperidinyl)-1 H-pyrazole-4-carboxylates as major products, and tautomeric NH-pyrazoles prepared from hydrazine hydrate were further N-alkylated with alkyl halides to give 3-( N-Boc-piperidinyl)-1 H-pyrazole-4-carboxylates. The structures of the novel heterocyclic compounds were confirmed by ¹H-, ¹³C-, and ¹⁵N-NMR spectroscopy and HRMS investigation.