cis-5-Arylpyrrolidine-2,4-dicarboxylic acid monoamides undergo thermal intramolecular condensation with formation of bicyclic imides having a 3,6-diazabicyclo[3.2.1]octane skeleton. The use of copper(I) cyanide as catalyst ensures high yields of 3,6-diazabicyclo[3.2.1]octane-2,4-diones substituted at the 3-, 5-, 6-, and 7-positions. (1R*,5R*,7S*)-7-(4-Chlorophenyl)-5,6-dimethyl-3,6-diazabicyclo[3.2.1]octane-2,4-dione was found to inhibit thrombin in a buffer solution at a millimolar concentration.Numerous natural and physiologically active compounds contain a substituted azabicyclo[3.2.1]octane fragment in their molecules. Examples are alkaloids of the tropane [1] and calystegine series [2], which possess a 8-azabicyclo[3.2.1]octane (tropane) structural fragment. (-)-Cocaine (I) is the most known alkaloid of the tropane family. Due to broad spectrum of their neurological and psychiatric effects enantiomerically pure tropane derivatives are targets of synthetic schemes developed by different research teams [3]. 6-Azabicyclo[3.2.1]octane derivatives, e.g., actinobolamine (II) [4], are encountered in nature more rarely, but they also exhibit a broad spectrum of pharmacological activity [5]. Aplaminal (III) which is a functionalized 3,6,8-triazabicyclo[3.2.1]octane derivative was isolated from the sea hare Aplysia kurodai and was found to exhibit cytotoxicity against Hela S 3 tumor cells [6].One of the main approaches to pharmacotherapy of cocaine addiction is based on the use of cocaine antagonists which inhibit cocaine recognition and its binding to dopamine transporter (DAT) but retain other important functions of that membrane protein [7]. The simplest route to the development of cocaine antagonists is synthesis of its structural analogs that are still capable of binding to DAT but exhibit reduced ability to inhibit dopamine transport and low toxicity. Some progress in this line was achieved with the use of structural isomers of tropane and its aza analogs, 3-azabicyclo[3.2.1]octanes IV (X = Y = C; isotropanes) [8] and 3,8-diazabicyclo[3.2.1]octanes IV (X = N, Y = C) [9] as central fragment in cocaine antagonists. The present article reports on a new method of synthesis of 3,6-diazabicyclo[3.2.1]octanes IV (X = C, Y = N) with different substituents in four positions of the bicyclic skeleton. These compounds are isostructural to tropane but are more basic. The products were also tested for inhibitory activity against thrombin (factor IIA).The formation of a substituted 3,6-diazabicyclo-[3.2.1]octane skeleton was revealed when 5-(4-bromophenyl)pyrrolidine-2,4-dicarboxylic acid derivative V was heated in DMF in the presence of copper(I) cyanide (Scheme 1). This reaction was initially carried out with a view to replace the bromine atom in the aromatic ring of V by cyano group (a classical Rosenmund-von Braun procedure for the synthesis of benzonitriles via aromatic nucleophilic substitution of bromine by cyano group [10]) to obtain 5-(4-cyanophenyl)pyrrolidine-2,4-dicarboxylic acid derivative.