Facile one-pot synthesis of unsymmetrical ureas, carbamates, and thiocarbamates from Cbz-protected amines

Abstract

A novel one-pot synthesis of unsymmetrical ureas, carbamates and thiocarbamates from Cbz-protected amines has been developed. In the presence of 2-chloropyridine and trifluoromethanesulfonyl anhydride, isocyanates are generated in situ, which facilitate rapid reaction with amines, alcohols, and thiols to afford the corresponding ureas, carbamates and thiocarbamates in high yields.

Spontaneous and Direct Transformation of <i>N</i>,<i>O</i>-Diaryl Carbamates into <i>N</i>,<i>N</i>′-Diarylureas

“…2 ppm), and those of p-tolyl isocyanate and p-toluidine were not detected. The absence of p-tolyl isocyanate and p-toluidine peaks in the reaction mixture suggests that the formation of aryl isocyanate and aniline from carbamate is slow (rate-limiting step) and/or that the equilib- Based on the our findings and reported results, 13,17) we propose the reaction mechanism depicted in Chart 1. NR 3 (or Et 3 N) catalyzes the reaction of carbamate 3h to 9, which favors 3h in the equilibrium.…”

“…The use of dimethyl sulfoxide (DMSO) as the solvent resulted in the formation of a by-product, presumed to be the product of trimerization of isocyanate, and the yield of the desired 2 was only 32% ( [12][13][14][15].…”

“…Hz, 2H);13 C-NMR(75 MHz, CDCl 3 ) 55.6, 114.4, 118.7, 122.5, 123.8, 129.1, 137.4, 144.1, 152.0, 157.2; IR (KBr) 3344, 2924 2856, 1722, 1606, 1549, 1502, 1448, 1381, 1317, 1213, 1022, 904, 839, 758, 696, 663, 519 cm −1 ; high resolution (HR)-MS (electron ionization (EI) + ) Calcd for C 14 H 13 NO 3 (M + ) 243.0890. Found 243.0889.…”

Structural and chemical insights into the covalent-allosteric inhibition of the protein kinase Akt

“…One option was the ring-opening of the imidazolone moiety leading to phenylurea-based derivatives (Scheme 2B). After initial Cbz-protection of 3-nitro-4-chloroaniline ( 14 ), urea formation ( 16 ) occurred derived from literature procedure with 4-amino-Boc-piperidine under microwave conditions ( 18 ) 39. Acidic hydrolysis of the Boc-protecting group led to another fragment that was capable of attaching to the 1,6-naphthyridinone-scaffold by Leuckart–Wallach reaction.…”

A Simple, Mild and Straight forward Route for the Synthesis of α‐Ureidopeptidomimetics Using Cbz‐Protected Amino Acid Esters

“…Trifluoromethanesulfonic (triflic) anhydride‐pyridine conjunction upon activation of amides has found to show conversion to various functional groups on treatment with suitable nucleophiles . Inspired by the recent reports on the reaction of Boc and Cbz‐protected amines for the synthesis of unsymmetrical ureas,, herein, we report the one‐pot synthesis of α‐ureidopeptides from Cbz‐protected amino acid esters devoid of any coupling agents.…”