A Simple Method for the Synthesis of Unsymmetrical Ureas

Efficient Synthesis of a Highly Selective NPY-5 Receptor Antagonist: A Drug Candidate for the Treatment of Obesity

“…With both the spirolactone 2 and the phenylpyrazine 3 in hand, their coupling to the target molecule 1 was investigated. A number of methods for the synthesis of unsymmetrical ureas have been reported . We decided to use the phenyl chloroformate protocol 12g for ease of operation, low cost, and mildness of reaction conditions.…”

Bis(2,2,2-trifluoroethyl) Carbonate as a Condensing Agent in One-Pot Parallel Synthesis of Unsymmetrical Aliphatic Ureas

“…We then examined existing synthetic approaches looking for an optimal, cost- and time-effective method, that would account for the following requirements to parallel synthesis: (a) one-pot procedure with an easy purification protocol; (b) moisture stable starting reagents, which would allow creating highly diverse sets of compounds; and (c) addition of all components concurrently and without temperature control. These criteria made most reported approaches inapplicable for the parallel synthesis: phosgene, , triphosgene , are toxic reagents; gases CO 2 , H 2 are inconvenient in handling; many isocyanates , and carbamates , are commercially unavailable; highly active 1,1′-carbonyldiimidazole , and chloroformates − need special care to prevent formation of the side products (symmetrical ureas in case of highly nucleophilic alkyl amines or chlorinated compounds in case of functionalized amines, e.g., amino alcohols). We therefore focused on the methods utilizing carbonates, for example, diethyl carbonate, bis(phenyl) carbonate and bis( p -nitrophenyl) carbonate. − The typical two-step procedure includes the interaction of a carbonate with the first amine forming a carbamate, which further reacts with the second amine to form the urea (Scheme ).…”

Urea Derivatives in Modern Drug Discovery and Medicinal Chemistry

“…The aminolysis of a urethane derivative is a well-known procedure for the synthesis of ureas. Urethanes are usually generated from carbonates or chloroformates. , Urethanes can also be prepared by reacting amine derivatives with carbon dioxide or by utilizing other safer and more recent methodologies . Urethanes react with amines with varying efficacy, depending upon the nature of the leaving alkoxide group. ,, …”