Synthesis and properties of 1-[(3-fluoroadamantan-1-yl)methyl]-3-R-ureas and 1,1′-(alkan-1,n-diyl)bis{3-[(3-fluoroadamantan-1-yl)methyl]ureas} as promising soluble epoxide hydrolase inhibitors

A two-step procedure to synthesize (3-fluoroadamantan-1-yl)methyl isocyanate from (3-hydroxyadamantane)acetic acid that involves fluorination with Ishikawa's reagent on the first step of the synthesis was developed. The reaction of (3-fluoroadamantan-1-yl)methyl isocyanate with aliphatic diamines gave 1,3-disubstituted bis-diureas in 60-97% yields. A strong decrease in the melting points of the obtained ureas (up to similar to 70-144 degrees C) was observed upon introduction of the fluorine atoms at the bridgehead positions of the adamantane unit.

Automated summary

A two-step procedure for synthesizing (3-fluoroadamantan-1-yl)methyl isocyanate from (3-hydroxyadamantane)acetic acid was developed, involving fluorination with Ishikawa's reagent in the first step. The reaction of (3-fluoroadamantan-1-yl)methyl isocyanate with aliphatic diamines resulted in 1,3-disubstituted bis-diureas in yields of 60-97%. Introduction of fluorine atoms at the bridgehead positions of the adamantane unit led to a significant decrease in the melting points of the obtained ureas, ranging from approximately 70-144 degrees Celsius.