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 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.
Original language | English (US) |
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Pages (from-to) | 3454-3457 |
Number of pages | 4 |
Journal | Tetrahedron Letters |
Volume | 56 |
Issue number | 23 |
DOIs | |
State | Published - May 25 2015 |
Bibliographical note
Publisher Copyright:© 2015 The Authors. Published by Elsevier Ltd.
Keywords
- BET inhibitors
- Bromodomains
- Male contraceptive
- One-pot method
- Thionation
- Triazolothienodiazepine (+)-JQ1