Synthesis of novel 3D-rich α-amino acid-derived 3-pyrazolidinones

Jaka Glavač, Georg Dahmann, Franc Požgan, Sebastijan Ričko, Bogdan Štefane, Jurij Svete, Uroš Grošelj

Abstract


Synthetic approaches towards novel 3-pyrazolidinone derivatives functionalized at positions N(1) and/or C(5) were studied. 5-Aminoalkyl-3-pyrazolidinones were prepared in four steps from N-protected glycines via Masamune-Claisen homologation, reduction, O-mesylation, and cyclisation with a hydrazine derivative. The free amines were prepared by acidolytic deprotection. Title compound was also prepared by 'ring switching' transformation of N-Boc-pyrrolin-2(5H)-one with hydrazine hydrate. Hydrogenolytic deprotection of 5-(N-alkyl-N-Cbz-aminomethyl)pyrazolidine-3-ones followed by cyclisation with CDI gave two novel representatives of perhydroimidazo[1,5-b]pyrazole, which is an almost unexplored heterocyclic system. Amidation of 3-oxopyrazolidine-5-carboxylic acid gave the corresponding carboxamides in moderate yields. Diastereomeric non-racemic carboxamides obtained from (S)-AlaOMe and (S)-ProOMe were separated by MPLC.

Keywords


3-Pyrazolidinones; amino acids; cyclization; heterocycles; synthesis; imidazo[1,5–b]pyrazole

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DOI: http://dx.doi.org/10.17344/acsi.2017.3438

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