2. Academic Validation
  3. Scalable syntheses of the BET bromodomain inhibitor JQ1

Scalable syntheses of the BET bromodomain inhibitor JQ1

  • Tetrahedron Lett. 2015 Jun 3;56(23):3354-3457. doi: 10.1016/j.tetlet.2015.02.062.
Shameem Sultana Syeda 1,  Sudhakar Jakkaraj 1,  Gunda I Georg 1
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, Minneapolis, MN 55414, United States of America.
PMID: 26034331 DOI: 10.1016/j.tetlet.2015.02.062
Abstract

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 thioamde 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.

Keywords

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

Figures
Products