Synthesis of Complex Ureas with Brominated Heterocyclic Intermediates

• Published in: ChemistrySelect (Weinheim) Vol. 8; no. 5
• Main Authors: Vargas, Darío A., Santiago, Cintia C., Cánepa, Alicia S.
• Format: Journal Article
• Language: English
• Published: 03.02.2023
• Subjects: 3-Methylindole; Bromination; Organic synthesis; Substitution reaction; Urea
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202204416

Herein we present an efficient method to synthesize novel complex ureas from simple ureas, with potential pharmacological activity. First, 3‐methylindole ketones are protected via a two‐phase N‐tosylation reaction catalyzed by NBu4HSO4 as the PTC. Second, an NBS bromination of the terminal methyl group is performed with high selectivity and very good yields. Finally, complex novel and promising ureas are synthesized in 46 %–92 % yields using non‐base‐catalyzed substitution reactions with simple monosubstituted and disubstituted ureas. All products were easily purified through column chromatography and/or crystallization. The overall procedure produces very high yields and selectivity for bromination. We present an efficient method to synthesize novel complex ureas from simple ureas, with potential pharmacological activity. The methodology employs novel protected brominated heterocyclic intermediates derived from 3‐methylindole in non‐base‐catalyzed substitution reactions performed with simple monosubstituted and disubstituted ureas. The overall process produces very good yields and high bromination selectivity.