Scalable syntheses of the BET bromodomain inhibitor JQ1

[Display omitted] 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...

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Bibliographic Details
Published in:Tetrahedron letters 2015-06, Vol.56 (23), p.3454-3457
Main Authors: Syeda, Shameem Sultana, Jakkaraj, Sudhakar, Georg, Gunda I.
Format: Article
Language:English
Subjects:
BET inhibitors
Bromodomains
Male contraceptive
One-pot method
Thionation
Triazolothienodiazepine (+)-JQ1
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Summary:[Display omitted] 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.
ISSN:0040-4039
1873-3581
DOI:10.1016/j.tetlet.2015.02.062