Synthesis of bridged heterocycles from <Emphasis Type="Italic">cis</Emphasis>-pyrrolidine-2,4-dicarboxylic acids: I. 3,6-Diazabicyclo[3.2.1]octanes

cis-5-Arylpyrrolidine-2,4-dicarboxylic acid monoamides undergo thermal intramolecular condensation with formation of bicyclic imides having a 3,6-diazabicyclo3.2.1]octane skeleton. The use of copper(I) cyanide as catalyst ensures high yields of 3,6-diazabicyclo3.2.1]octane-2,4-diones substituted at the 3-, 5-, 6-, and 7-positions. (1R*,5R*,7S*)-7-(4-Chlorophenyl)-5,6-dimethyl-3,6-diazabicyclo3.2.1]octane-2,4-dione was found to inhibit thrombin in a buffer solution at a millimolar concentration.