95881-82-6Relevant articles and documents
Palladium-catalyzed cross-coupling reactions of pyridylboronic acids with heteroaryl halides bearing a primary amine group: Synthesis of highly substituted bipyridines and pyrazinopyridines
Thompson, Amy E.,Hughes, Gregory,Batsanov, Andrei S.,Bryce, Martin R.,Parry, Paul R.,Tarbit, Brian
, p. 388 - 390 (2005)
(Chemical Equation Presented). A range of halogenated aromatics and heteroaromatics bearing a primary amine group are shown to be suitable substrates for Suzuki cross-coupling reactions with arylboronic acids and pyridylboronic acids under standard conditions, without the need for protection/deprotection steps. New amino-substituted arylpyridines, bipyridines, and pyrazinopyridines have thereby been obtained. Conditions for the efficient syntheses of 2-methoxy-5-pyridylboronic acid 1 and 2-methoxy-3-pyridylboronic acid 2 in ca. 75 g batches have been defined. A 2-fold reaction of 2-amino-5-bromopyrazine with 2,5-dimethoxy-1,4-benzenediboronic acid affords 1,4-dimethoxy-2,5-bis[2-(5-aminopyrazyl)]benzene 31. The X-ray crystal structures of 1 and 31·DMF are reported.
Zirconium-redox-shuttled cross-electrophile coupling of aromatic and heteroaromatic halides
Fu, Yue,Liu, Fang-Jie,Liu, Peng,Tang, Jian-Tao,Toste, F. Dean,Wu, Ting-Feng,Ye, Baihua,Zhang, Yue-Jiao
supporting information, p. 1963 - 1974 (2021/07/07)
Transition metal-catalyzed cross-electrophile coupling (XEC) is a powerful tool for forging C(sp2)–C(sp2) bonds in biaryl molecules from abundant aromatic halides. While the synthesis of unsymmetrical biaryl compounds through multimetallic XEC is of high synthetic value, the selective XEC of two heteroaromatic halides remains elusive and challenging. Herein, we report a homogeneous XEC method, which relies on a zirconaaziridine complex as a shuttle for dual palladium-catalyzed processes. The zirconaaziridine-mediated palladium (ZAPd)-catalyzed reaction shows excellent compatibility with various functional groups and diverse heteroaromatic scaffolds. In accord with density functional theory (DFT) calculations, a redox transmetallation between the oxidative addition product and the zirconaaziridine is proposed as the crucial elementary step. Thus, cross-coupling selectivity using a single transition metal catalyst is controlled by the relative rate of oxidative addition of Pd(0) into the aromatic halide. Overall, the concept of a combined reducing and transmetallating agent offers opportunities for the development of transition metal reductive coupling catalysis.
A highly efficient Suzuki-Miyaura methylation of pyridines leading to the drug pirfenidone and its CD3 version (SD-560)
Falb, Eliezer,Ulanenko, Konstantin,Tor, Andrey,Gottesfeld, Ronen,Weitman, Michal,Afri, Michal,Gottlieb, Hugo,Hassner, Alfred
supporting information, p. 5046 - 5053 (2017/11/09)
Efficient introduction of methyl or methyl-d3 into aromatic and heteroaromatic systems still presents a synthetic challenge. In particular, we were in search of a non-cryogenic synthesis of the 5-CD3 version of pirfenidone (4d, also known as Pirespa, Esbriet or Pirfenex), one of the two drugs approved to date for retarding idiopathic pulmonary fibrosis (IPF), a serious, rare and fatal lung disease, with a life expectancy of 3-5 years. The methyl-deuterated version of pirfenidone (4e, also known as SD-560) was designed with the objective of attenuating the rate of drug metabolism, and our goal was to find a green methylation route to avoid the environmental and economic impact of employing alkyllithium at cryogenic temperatures. The examination of several cross-coupling strategies for the introduction of methyl or methyl-d3 into methoxypyridine and pyridone systems culminated in two green and nearly quantitative Suzuki-Miyaura cross-coupling routes in the presence of RuPhos ligand: the first, using commercially available methyl boronic acid or its CD3 analog and the second, employing potassium methyl trifluoroborate or CD3BF3K, the latter obtained by a new route in 88% yield. This led, on a scale of tens of grams, to the synthesis of pirfenidone (4d) and its d3 analog, SD-560 (4e), at 99% isotopic purity.
A Magnesium-Based Diastereoselective Preparation of Pyridylic 1,3-Amino Alcohols Using the tert -Butyl Sulfinamide Auxiliary
Fjelbye, Kasper,Svenstrup, Niels,Püschl, Ask
, p. 3231 - 3240 (2015/10/19)
1,3-Amino alcohols were prepared by using a two-step approach and an interesting reversal in diastereoselectivity is discussed.
