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

• Published in: Molecules (Basel, Switzerland) Switzerland), 2021-06, Vol.26 (13), p.3808
• Main Authors: Matulevičiūtė, Gita, Arbačiauskienė, Eglė, Kleizienė, Neringa, Kederienė, Vilija, Ragaitė, Greta, Dagilienė, Miglė, Bieliauskas, Aurimas, Milišiūnaitė, Vaida, Sløk, Frank A., Šačkus, Algirdas
• Format: Article
• Language: English
• Subjects: Alkylation; Amino acids; Carboxylates; Carboxylic acids; Connectivity; Diketones; Dimethyl acetals; enamines; Esters; Experiments; Halides; heterocyclic amino acids; Heterocyclic compounds; Hydrazine; Hydrazines; Magnetic resonance spectroscopy; Nitrogen; NMR; NMR spectroscopy; Nuclear magnetic resonance; Peptides; Piperidine; piperidines; Pyrazole; Pyrazoles; Spectrum analysis; β-keto esters
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26133808

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 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)-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 1H-, 13C-, and 15N-NMR spectroscopy and HRMS investigation.