Synthesis and characterization of functionalized dihydropyrimidinones via one-pot isocyanide-based three-component reaction of N-formyl urea and dialkyl ACETYLENEDICARBOXYLATES

Abstract

ABSTRACT. The reactive intermediate generated by the addition of alkyl isocyanides to dialkyl acetylenedicarboxylates was trapped by N-formyl urea to produce highly functionalized dihydropyrimidinones in fairly good yields.

Use of Dialkyl Acetylenedicarboxylates in the Multicomponent Synthesis of Heterocyclic Structures

“…The three‐component reaction of dialkyl acetylenedicarboxylate 1 , tert ‐butyl isocyanide 12 and N ‐formyl urea 111 was performed and the corresponding product were obtained in good to excellent yields (Scheme 47). [77] …”

“…Since pyridine rings are able to act as the bioisosteres of amines, amides, heterocyclic rings containing nitrogen atoms, and benzene rings, their replacement by pyridine moieties is significant in drug discovery. [77] The four-component domino reaction of propylamine 2, dimethyl acetylenedicarboxylate 1, pyruvic acid 91 and 4chrolobenzaldehyde 6 in the presence of iodine (10 mol %) in MeCN afforded various 1,4-dihydrooyridine derivatives 92. This effective synthetic method was developed by Rezvanian in 2016 (Scheme 37).…”

“…because of characteristics features of pyridine such as basicity, water solubility, stability, and hydrogen bond‐forming ability, and their small molecular size, they are often utilized in drugs. Since pyridine rings are able to act as the bioisosteres of amines, amides, heterocyclic rings containing nitrogen atoms, and benzene rings, their replacement by pyridine moieties is significant in drug discovery [77] …”