137297-51-9Relevant articles and documents
Photoinduced Radical Borylation of Alkyl Bromides Catalyzed by 4-Phenylpyridine
Zhang, Li,Wu, Zhong-Qian,Jiao, Lei
supporting information, p. 2095 - 2099 (2019/12/24)
Utilizing pyridine catalysis, we developed a visible-light-induced transition-metal-free radical borylation reaction of unactivated alkyl bromides that features a broad substrate scope and mild reaction conditions. Mechanistic studies revealed a novel nucleophilic substitution/photoinduced radical formation pathway, which could be utilized to trigger a variety of radical processes.
Development of a gram-scale synthesis of pbrm, an irreversible inhibitor of 17beta-hydroxysteroid dehydrogenase type 1
Maltais, René,Poirier, Donald
, p. 2323 - 2335 (2019/10/14)
Efforts toward the development of a reliable gram scale synthesis of PBRM, a potent and selective steroidal covalent inhibitor of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), are described. Among the three synthetic routes (C-E) developed herein, route E is the most efficient one with only 6 chemical steps from commercially available estrone, and an overall yield of 13% leading to PBRM with a high HPLC grade purity (99.7%) after recrystallization. Important improvements have been achieved in this sequence from previous reported routes (A and B). Notably, we used a palladium catalyzed Suzuki-Miyaura cross-coupling reaction to rapidly install the requested C3 chain on estrone. Also, catalytic hydrogenation of the C16-enone was shortened by half using Pearlman's catalyst. Finally, we used a selective bromination through deoxygenation of alcohol at the last step of the sequence to provide PBRM without dehydration of its carboxamide functionality, a persistent problem observed in other routes. Crystals of PBRM were also obtained from recrystallization in acetonitrile and submitted to x-ray analysis, which confirmed the PBRM structure. This work now makes it possible to start a proof-of-principle in a non-human primate model for the treatment of endometriosis, while supporting its future pharmacological development.
Suzuki-Miyaura cross-coupling of potassium alkoxyethyltrifluoroborates: Access to aryl/heteroarylethyloxy motifs
Fleury-Bregeot, Nicolas,Presset, Marc,Beaumard, Floriane,Colombel, Virginie,Oehlrich, Daniel,Rombouts, Frederik,Molander, Gary A.
, p. 10399 - 10408 (2013/01/15)
The introduction of an alkoxyethyl moiety onto aromatic substructures has remained a long-standing challenge for synthetic organic chemists. The main reasons are the inherent instability of alkoxyethylmetallic species and the lack of general procedures to access them. A new method utilizing a cross-coupling strategy based on the exceptional properties of organotrifluoroborates has been developed, and the method allows an easy and efficient installation of this unit on a broad range of aryl and heteroaryl bromides.
