title: Chemistry of brotizolam and its metabolites.
abstract: Of a series of azepines annelated with two 5-ring heterocycles, 1, brotizolam (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f]-1,2,4-triazolo [4,3-a]-1,4-diazepine, We 941), 2, was found to possess excellent hypnotic properties. A summary of the two different methods of preparation of 2 (routes A and B) is given. Synthesis of the major metabolites of 2, 6-hydroxy-brotizolam (We 1061), 14, obtained from the intermediates 9 and 10 by method B, 2-bromo-4-(2-chlorophenyl)-9-hydroxymethyl-6H-thieno [3,2-f]-1,2,4-triazolo-[4,3a]-1,4-diazepine (WE 964), 16, and 2-bromo-4-(2-chlorophenyl)-6-hydroxy-9-hydroxymethyl-6H-thieno- [3,2-f]-1,2,4-triazolo-[4,3-a]-1,4-diazepine (We 1073), 17, are described in detail. In contrast to the classical 3-hydroxy-1,4-benzodiazepines, e.g. oxazepam, 14 isomerizes easily in weak alkali. This isomerization is discussed.
mesh_terms: D000818:Animals; D001381:Azepines / Q000032:analysis* / Q000138:chemical synthesis / Q000378:metabolism; D001646:Bile / Q000032:analysis; D001711:Biotransformation; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans
chemical_list: D001381:Azepines; C020960:brotizolam