Synthesis and Properties of 1,3-Disubstituted Ureas and Their Isosteric Analogs Containing Polycyclic Fragments: IV.1 1-(Bicyclo[2.2.1]hept-5-en-2-yl)-3-(fluoro, chlorophenyl)ureas

Abstract

The reaction of bicyclo[2.2.1]hept-5-en-2-yl isocyanate with fl uoro-and chloro-substituted anilines was used to synthesize in a yield of 25-68% a series of 1,3-disubstituted ureas containing a lipophilic group in their structure. The synthesized ureas are promising as inhibitors of RNA virus replication and human soluble epoxide hydrolase.

Synthesis and Properties of 1,3-Disubstituted Ureas and Their Isosteric Analogs Containing Polycyclic Fragments: V. 1-(Bicyclo[2.2.1]heptan-2-yl)-3-R- and 1-(1,7,7-Tricyclo[2.2.1]heptan-2-yl)-3-R-ureas

“…Wang et al [14] reported the synthesis of unsymmetrical ureas with a 3-fold excess of CDI. For example, 1-(6-bromo [1,2,4]triazole[1,5-a]pyridin-2-yl)-3-methylurea was synthesized in a yield of 79.6% by heating a mixture of 6-bromo [1,2,4]triazole[1,5-a]pyridin-2-amine NaH and a 3-fold excess of CDI in DMF at 60°C followed by adding a 3,5-fold excess of methylamine and heating at 60°C for 6 h. The authors of the cited work did not mention whether they removed excess CDI before adding the second amine.…”

“…we studied the reaction of amine 2 with CDI in the absence of another amine. According to the GCMS data, mixing amine 2 with CDI at 25°C results in a fairly rapid (20 min) formation of intermediate carboxamide 6 [Scheme 3, reaction(1)]. However, this reaction, too, gave symmetrical urea 5f (yield 8%), which can…”

“…Yield 0.236 g (82%).b. Similarly to compound 4a, from 0.08 g (1.36 mmol) of compound 3e, 0.22 g (1.36 mmol) of CDI, 0.41 g (4.08 mmol) of triethylamine, and 0.2 g (1.36 mmol) of compound Yield 0.193 g (73%), mp 185-186°C 1. H NMR spectrum (DMSO-d 6 ), δ, ppm: 1.02-1.92 m (12H, 6CH 2 ), 1.22-1.26 m (4H, 2CH 2 ), 1.33 d (4H, 2CH 2 , J 8.4 Hz), 2.11 t (2H, 2CH, J 4.8 Hz), 2.18 t (2H, 2CH, J 4.2 Hz), 2.92-3.00 m (4H, 2CH 2 -NH), 3.75-3.81 m (2H, 2CH-NH), 5.65 t (1H, NH, J 5.4 Hz), 5.82 d (1H, NH, J 7.4 Hz).…”