A Simple Synthesis of Polyfunctionalized 4‐Aminopyrazolidin‐3‐ones as ‘Aza‐deoxa’ Analogs of D‐Cycloserine

Abstract

A simple five‐step synthesis of fully substituted (4RS,5RS)‐4‐aminopyrazolidin‐3‐ones as analogs of D‐cycloserine was developed. It comprises a two‐step preparation of 5‐substituted (4RS,5RS)‐4‐(benzyloxycarbonylamino)pyrazolidin‐3‐ones, reductive alkylation at N(1), alkylation of the amidic N(2) with alkyl halides, and simultaneous hydrogenolytic deprotection/reductive alkylation of the primary NH2 group. The synthesis enables an easy stepwise functionalization of the pyrazolidin‐3‐one core with only two types of common reagents, aldehydes (or ketones) and alkyl halides. The structures of products were elucidated by NMR spectroscopy and X‐ray diffraction.

Cu 0 -catalysed 1,3-dipolar cycloadditions of α-amino acid derived N,N -cyclic azomethine imines to ynones

“…[11][12][13]14,16,17 The synthesis of azomethine imines 3a-j and chemsets 1a-d and 2a-e are presented in Scheme 1, while experimental data for dipoles 3a-j are given in Table 1. The (Z)-configuration around the C(1')=N(1) double bond in 3-oxopyrazolidin-1-ium-2-ides 3a-j and the trans configuration of 4,5-disubstituted pyrazolidinones 1a,b and dipoles 3a-j derived thereof were established previously.…”

Crystal Structure of the Chiral Azomethine Imine, (Z)-(S)-4-(tert-Butylcarbonylamino)-2-(2-methoxybenzylidene)-5-oxopyrazolidin-2-ium-1-ide, Obtained by the Cyclization of tert-Butyl (S)-2-[2-(methoxybenzylidene)hydrazine]-1-(hydroxymethyl)-2-oxocarbamate

“…In Table 3, selected data are provided for a number of 5-oxopyrazolidin-2-ium-1-ide derivatives, 12 of which contained an arylidene sbstituent [4,6,19,21,[25][26][27][28][29]. It is argued that the smaller this angle the greater possibilitythere will be for conjugation between the two fragments.…”

Recent advances in the synthesis of polysubstituted 3-pyrazolidinones

“…[40][41][42]44,47,[72][73][74][75][76][77] The 1 H-NMR spectroscopic data of the pyrazolidinones 4 and 25-33 and azomethine imines 24 revealed some interesting structural features of these compounds. In solution, these pyrazolidinone derivatives can equilibrate between two envelope conformers A and C via the planar conformer B (Scheme 21).…”

“…Schemes 1 and 6). [40][41][42] First, cycloadditions of 5-phenyl substituted dipoles 24a,b to tert-butyl acrylate were carried out under standard conditions, i.e. in refluxing anisole.…”