153559-98-9Relevant articles and documents
A one-pot synthesis of tetrazolones from acid chlorides: Understanding functional group compatibility, and application to the late-stage functionalization of marketed drugs
Duncton, Matthew A. J.,Singh, Rajinder
, p. 9338 - 9342 (2016)
A one-pot and scalable synthesis of tetrazolones (tetrazol-5-ones) from acid chlorides using azidotrimethylsilane is presented. The reaction tolerates many functional groups and can furnish aryl-, heteroaryl-, alkenyl-, or alkyl-substituted tetrazolone products in moderate to excellent yield (14-94%). No reduction in yield was observed when the reaction was undertaken on a larger-scale (20-36 g). The method could be used for the late-stage functionalization of pharmaceuticals, to provide tetrazolone congeners of the marketed drugs aspirin, indomethacin, probenecid, telmisartan, bexarotene, niacin (vitamin B3), and the active metabolite of the recently-launched immuno-modulatory agent, BG-12 (Tecfidera). The ability of a tetrazolone group to serve as a bioisostere of a carboxylic acid, and to improve drug pharmacokinetic profiles is also highlighted.
New highly cytotoxic organic and organometallic bexarotene derivatives
Nosova, Yulia N.,Karlov, Dmitry S.,Pisarev, Sergey A.,Shutkov, Ilya A.,Palyulin, Vladimir A.,Baquié, Mathurin,Milaeva, Elena R.,Dyson, Paul J.,Nazarov, Alexey A.
, p. 91 - 97 (2017)
A series of bifunctional ruthenium(II) arene compounds modified with bexarotene, a retinoid that selectively activates retinoid X receptors inducing cell differentiation and apoptosis and preventing drug resistance, are described. The bexarotene is tethered to the ruthenium(II) arene fragment via an imidazole linker. Both the bexarotene-imidazole ligand and ruthenium(II) arene complexes are considerably more cytotoxic than the parent drug bexarotene. Docking studies show that the interactions of these compounds with possible targets are significantly different to the binding mode of the parent drug.
Decarbonylative Suzuki-Miyaura Cross-Coupling of Aroyl Chlorides
Zhou, Tongliang,Xie, Pei-Pei,Ji, Chong-Lei,Hong, Xin,Szostak, Michal
supporting information, p. 6434 - 6440 (2020/09/02)
Herein, we report a catalyst system for Pd-catalyzed decarbonylative Suzuki-Miyaura cross-coupling of aroyl chlorides with boronic acids to furnish biaryls. This strategy is suitable for a broad range of common aroyl chlorides and boronic acids. The synthetic utility is highlighted in the direct late-stage functionalization of pharmaceuticals and natural products capitalizing on the presence of carboxylic acid moiety. Extensive mechanistic and DFT studies provide key insight into the reaction mechanism and high decarbonylative cross-coupling selectivity.
Palladium-Catalyzed Decarbonylative Difluoromethylation of Acid Chlorides at Room Temperature
Pan, Fei,Boursalian, Gregory B.,Ritter, Tobias
supporting information, p. 16871 - 16876 (2018/11/23)
Methods for the direct synthesis of difluoromethylated arenes are sparse, despite the importance of the difluoromethyl group in medical, agro-, and materials chemistry. A palladium-catalyzed decarbonylative cross-coupling reaction of acid chlorides with a difluoromethyl zinc reagent is achieved to access difluoromethylated compounds. The transformation proceeds at room temperature and shows broad functional group tolerance, thus providing a general and efficient method for decarbonylative difluoromethylation of a wide range of aromatic carboxylic acids.
