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

Series of methyl 3- and 5-(N-Boc-piperidinyl)-1H-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 beta-keto esters, which were then treated with N,N-dimethylformamide dimethyl acetal. The subsequent reaction of beta-enamine diketones with various N-mono-substituted hydrazines afforded the target 5-(N-Boc-piperidinyl)-1H-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)-1H-pyrazole-4-carboxylates. The structures of the novel heterocyclic compounds were confirmed by H-1-, C-13-, and N-15-NMR spectroscopy and HRMS investigation.

Automated summary

A series of novel heterocyclic amino acid compounds were developed and regioselectively synthesized as N-Boc protected esters, serving as achiral and chiral building blocks. The structures of these compounds were confirmed through H-1, C-13, and N-15-NMR spectroscopy and HRMS investigation.