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

• Published in: Russian chemical bulletin Vol. 71; no. 1; pp. 107 - 113
• Main Authors: Danilov, D. V., D’yachenko, V. S., Burmistrov, V. V., Butov, G. M., Novakov, I. A.
• Format: Journal Article
• Language: English
• Published: New York Springer US 2022; Springer Nature B.V
• Subjects: Acetic acid; Chemical synthesis; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Diamines; Fluorination; Fluorine; Full Articles; Industrial accidents; Inorganic Chemistry; Melting points; Methyl isocyanate; Organic Chemistry; Reagents; Ureas; Ishikawa’s reagent; inhibitors; fluorinated adamantane derivatives; ureas; soluble epoxide hydrolase
• ISSN: 1066-5285; 1573-9171
• DOI: 10.1007/s11172-022-3383-8

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 ∼70–144 °C) was observed upon introduction of the fluorine atoms at the bridgehead positions of the adamantane unit.