Three-Component Condensation of Methyl Acylpyruvates with Aromatic Aldehydes and Ethylenediamine. Chemical Properties of the Products

Abstract

Reactions of methyl acetyl-or benzoylpyruvates with aromatic aldehydes and ethylenediamine, depending on the reactant ratio, afforded 4-acyl-1-(2-aminoethyl)-5-aryl-3-hydroxy-2,5-dihydro-1H-pyrrol-2ones or 1,2-bis(4-acyl-5-aryl-3-hydroxy-2-oxo-2,5-dihydro-1H-pyrrol-1-yl)ethanes. Substituted 1-(2-aminoethyl)-3-hydroxy-2,5-dihydro-1H-pyrrol-2-one hydrochlorides were brought into reactions with p-methoxyaniline and hydrazine. IIa!IIe

Design of Drug‐Like Protein–Protein Interaction Stabilizers Guided By Chelation‐Controlled Bioactive Conformation Stabilization

“…Reaction of rac ‐ 2 with aqueous ammonia in acetic acid under microwave heating afforded only vinylogous amide rac ‐ 6 in 20 % yield, with no rac ‐ 9 observed (Scheme ). This contrasts with literature reports that 4‐aroyl substituents favor regiospecific endocyclic nucleophilic attack by sterically unencumbered amines to afford the regioisomers corresponding to 9 . Reaction of rac ‐ 2 with p ‐methoxybenzylamine under microwave heating afforded rac ‐ 7 (6 %) and rac ‐ 8 (26 %).…”

“…This contrasts with literature reports that 4-aroyl substituents favor regiospecific endocyclic nucleophilic attack by sterically unencumbered amines to afford the regioisomers corresponding to 9. [35][36][37][38][39][40] Reaction of rac-2 with p-methoxybenzylamine under microwave heating afforded rac-7 (6%) and rac-8 (26%). Removal of the PMB group of rac-8 using TFA afforded rac-9 in 53% yield.…”

Stereoselective, Multicomponent Approach to Quaternary Substituted Hydroindole Scaffolds

“…This rapid Mannich-type addition provides an intermediate capable of intramolecular lactamization to form the α-ketolactam that subsequently tautomerizes to the observed multicomponent product 4 . The mechanism is supported through the observations that preformed electron-deficient imines do not undergo this mild reaction in agreement with literature reports that require harsh reaction conditions for such reactions. − It is also possible that upon imine protonation a more concerted (albeit asynchronous) process ensues as we do not observe the amino ester in any of the reaction mixtures. Further exploration in the reaction mechanism and efforts to render it asymmetric are ongoing.…”

“…Among the various multicomponent approaches to access highly functionalized heterocycles, including pyrrolidinones, imines serve as a common intermediate. − In addition to our efforts, there has been a long history of elegant methods toward these versatile building blocks. Gein and co-workers have contributed significant efforts to the synthesis of these molecules via a similar multicomponent reaction that requires an acyl electron-withdrawing group and prolonged reaction time. − A number of other groups have used analogous strategies, all employing activated precursors and aggressive reaction conditions. − Joo and co-workers and Yavari and Souri independently synthesized related pyrrolidinones utilizing symmetrical alkynes. , …”

Design, Synthesis, and Structure−Activity Relationship Exploration of 1-Substituted 4-Aroyl-3-hydroxy-5-phenyl-1H-pyrrol-2(5H)-one Analogues as Inhibitors of the Annexin A2−S100A10 Protein Interaction

“… 33 − 35 Pyruvates 12 were then subjected in a second step to a three-component coupling reaction with the appropriate amines 7 and aldehydes 8 . 36 − 40 …”