Scalable syntheses of the BET bromodomain inhibitor JQ1

TETRAHEDRON LETTERS

卷:56

Article

Georg, Gunda I.¹ 

[1] Univ Minnesota, Dept Med Chem, Minneapolis, MN 55414 USA

关键词: Bromodomains;    BET inhibitors;    Triazolothienodiazepine (+)-JQ1;    Male contraceptive;    Thionation;    One-pot method;   

DOI  :  10.1016/j.tetlet.2015.02.062

来源: Elsevier

【 摘 要 】

We have developed methods involving the use of alternate, safer reagents for the scalable syntheses of the potent BET bromodomain inhibitor JQ1. A one-pot three step method, involving the conversion of a benzodiazepine to a thioamide using Lawesson's reagent, followed by amidrazone formation and installation of the triazole moiety furnished JQ1. This method provides good yields and a facile purification process. For the synthesis of enantiomerically enriched (+)-JQ1, the highly toxic reagent diethyl chlorophosphate, used in a previous synthesis, was replaced with the safer reagent diphenyl chlorophosphate in the three-step one-pot triazole formation without effecting yields and enantiomeric purity of (+)-JQ1. (C) 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

【 授权许可】

Free