Weber K H, Sirrenberg W, Spohn O, Daniel H
Arzneimittelforschung. 1986 Mar;36(3A):518-21.
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.
在一系列与两个五元杂环稠合的氮杂卓类化合物中，发现1. 溴替唑仑（2-溴-4-(2-氯苯基)-9-甲基-6H-噻吩并[3,2-f]-1,2,4-三唑并[4,3-a]-1,4-二氮杂卓，We 941），2. 具有优异的催眠特性。给出了制备2的两种不同方法（路线A和B）的总结。详细描述了由中间体9和10通过方法B得到的2的主要代谢产物6-羟基溴替唑仑（We 1061），14. 2-溴-4-(2-氯苯基)-9-羟甲基-6H-噻吩并[3,2-f]-1,2,4-三唑并[4,3a]-1,4-二氮杂卓（WE 964），16. 以及2-溴-4-(2-氯苯基)-6-羟基-9-羟甲基-6H-噻吩并[3,2-f]-1,2,4-三唑并[4,3-a]-1,4-二氮杂卓（We 1073），17. 与经典的3-羟基-1,4-苯二氮卓类化合物不同，例如奥沙西泮，14在弱碱中容易异构化。讨论了这种异构化。
