39901-94-5Relevant articles and documents
A new pathway via intermediate 4-amino-3-fluorophenol for the synthesis of regorafenib
Du, Fangyu,Zhou, Qifan,Shi, Yajie,Yu, Miao,Sun, Wenjiao,Chen, Guoliang
, p. 576 - 586 (2019/02/01)
A practical synthetic route to regorafenib, in which the target compound was obtained via a 10-step synthesis starting from 2-picolinic acid, 4-chloro-3-(trifluoromethyl)aniline, and 3-fluorophenol, is reported. Crucial to the strategy is the preparation of 4-amino-3-fluorophenol via Fries and Beckman rearrangements using an economical and practical protocol. The main advantages of the route include inexpensive starting materials and an acceptable overall yield. A scale-up experiment was carried out to provide regorafenib with 99.96% purity in 46.5% total yield.
Copper-Catalyzed Electrochemical C-H Amination of Arenes with Secondary Amines
Yang, Qi-Liang,Wang, Xiang-Yang,Lu, Jia-Yan,Zhang, Li-Pu,Fang, Ping,Mei, Tian-Sheng
supporting information, p. 11487 - 11494 (2018/09/13)
Electrochemical oxidation represents an environmentally friendly solution to conventional methods that require caustic stoichiometric chemical oxidants. However, C-H functionalizations merging transition-metal catalysis and electrochemical techniques are, to date, largely confined to the use of precious metals and divided cells. Herein, we report the first examples of copper-catalyzed electrochemical C-H aminations of arenes at room temperature using undivided electrochemical cells, thereby providing a practical solution for the construction of arylamines. The use of n-Bu4NI as a redox mediator is crucial for this transformation. On the basis of mechanistic studies including kinetic profiles, isotope effects, cyclic voltammetric analyses, and radical inhibition experiments, the reaction appears to proceed via a single-electron-transfer (SET) process, and a high valent Cu(III) species is likely involved. These findings provide a new avenue for transition-metal-catalyzed electrochemical C-H functionalization reactions using redox mediators.
Synthesis and evaluation of N-(methylthiophenyl)picolinamide derivatives as PET radioligands for metabotropic glutamate receptor subtype 4
Kil, Kun-Eek,Poutiainen, Pekka,Zhang, Zhaoda,Zhu, Aijun,Kuruppu, Darshini,Prabhakar, Shilpa,Choi, Ji-Kyung,Tannous, Bakhos A.,Brownell, Anna-Liisa
supporting information, p. 133 - 139 (2015/12/18)
In recent years, mGlu4 has received great research attention because of the potential benefits of mGlu4 activation in treating numerous brain disorders, such as Parkinson's disease (PD). A specific mGlu4 PET radioligand could be an important tool in understanding the role of mGlu4 in both healthy and disease conditions, and also for the development of new drugs. In this study, we synthesized four new N-(methylthiophenyl)picolinamide derivatives 11-14. Of these ligands, 11 and 14 showed high in vitro binding affinity for mGlu4 with IC50 values of 3.4 nM and 3.1 nM, respectively, and suitable physicochemical parameters. Compound 11 also showed enhanced metabolic stability and good selectivity to other mGluRs. [11C]11 and [11C]14 were radiolabeled using the [11C]methylation of the thiophenol precursors 20a and 20c with [11C]CH3I in 19.0% and 34.8% radiochemical yields (RCY), and their specific activities at the end of synthesis (EOS) were 496 ± 138 GBq/μmol (n = 6) and 463 ± 263 GBq/μmol (n = 4), respectively. The PET studies showed that [11C]11 accumulated fast into the brain and had higher uptake, slower washout and 25% better contrast than [11C]2, indicating improved imaging characteristics as PET radiotracer for mGlu4 compared to [11C]2. Therefore, [11C]11 will be a useful radioligand to investigate mGlu4 in different biological applications.
