title: Scalable syntheses of the BET bromodomain inhibitor JQ1.
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.
authors.affiliation: Department of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, Minneapolis, MN 55414, United States of America.
authors.forename: Shameem Sultana
authors.initials: SS
authors.lastname: Syeda
authors.affiliation: Department of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, Minneapolis, MN 55414, United States of America.
authors.forename: Sudhakar
authors.initials: S
authors.lastname: Jakkaraj
authors.affiliation: Department of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, Minneapolis, MN 55414, United States of America.
authors.forename: Gunda I
authors.initials: GI
authors.lastname: Georg
keywords: BET inhibitors; Bromodomains; Male contraceptive; One-pot method; Thionation; Triazolothienodiazepine (+)-JQ1