Parallel Synthesis of Tri- and Tetrasubstituted Ureas from Carbamoyl Imidazolium Salts

Title: Parallel Synthesis of Tri- and Tetrasubstituted Ureas from Carbamoyl Imidazolium Salts

Volume: 5 Issue: 3

Author(s): Robert A. Batey, Ming Shen, V. Santhakumar and Chiaki Yoshina-ishii

Affiliation:

Keywords: substituted ureas, carbamoylation reagent, building blocks

Abstract: A method for producing tri- and tetrasubstituted ureas from carbamoyl imidazolium salts is presented. Carbamoyl imidazolium salts are prepared from the reaction of N,N-carbonyldiimidazole (CDI) with secondary amines, followed by alkylation with iodomethane. These stable salts can be stored for extended periods and are effective electrophilic carbamoylation reagents. Primary and secondary amines add to carbamoyl imidazolium salts at room temperature to give tri- and tetrasubstituted ureas in excellent yields. This reaction was used to synthesize ureas using both liquid-liquid extraction and solid-phase extraction (cation exchange) purification techniques. Liquid-liquid extraction affords the product ureas more cleanly than cationic exchange. A series of urea compounds were synthesized using parallel synthesis techniques in high yields and with suitable purity for routine in vitro biological tests. These studies validate the utility of carbamoyl imidazolium salts as useful “building blocks” for combinatorial library synthesis.

Cite this article as:

Batey A. Robert, Shen Ming, Santhakumar V. and Yoshina-ishii Chiaki, Parallel Synthesis of Tri- and Tetrasubstituted Ureas from Carbamoyl Imidazolium Salts, Combinatorial Chemistry & High Throughput Screening 2002; 5 (3) . https://dx.doi.org/10.2174/1386207024607211