33832-28-9Relevant articles and documents
Direct amide synthesis: via Ni-mediated aminocarbonylation of arylboronic acids with CO and nitroarenes
Shen, Ni,Cheung, Chi Wai,Ma, Jun-An
supporting information, p. 13709 - 13712 (2019/11/19)
Herein we describe an alternative and unconventional approach of an aminocarbonylation reaction to access aryl amides from readily available and low-cost arylboronic acids and nitroarenes. Nickel metal can serve as both reductant and catalyst in this direct aminocarbonylation. This protocol exhibits a good functional group compatibility and allows a variety of aryl amides to be synthesized, including several drug-like molecules.
Amide Synthesis from Thiocarboxylic Acids and Amines by Spontaneous Reaction and Electrosynthesis
Tang, Li,Matuska, Jack H.,Huang, Yu-Han,He, Yan-Hong,Guan, Zhi
, p. 2570 - 2575 (2019/06/13)
Amide bond formation is one of the most important basic reactions in chemistry. A catalyst-free approach for constructing amide bonds from thiocarboxylic acids and amines was developed. The mechanistic studies showed that the disulfide was the key intermediate for this amide synthesis. Thiobenzoic acids could be automatically oxidized to disulfides in air, thioaliphatic acids could be electro-oxidized to disulfides, and the resulting disulfides reacted with amines to give the corresponding amides. By this method, various amides could be easily synthesized in excellent yields without using any catalyst or activator. The successful synthesis of bioactive compounds also highlights the synthetic utility of this strategy in medicinal chemistry.
Urea Derivatives of 2-Aryl-benzothiazol-5-amines: A New Class of Potential Drugs for Human African Trypanosomiasis
Patrick, Donald A.,Gillespie, J. Robert,McQueen, Joshua,Hulverson, Matthew A.,Ranade, Ranae M.,Creason, Sharon A.,Herbst, Zackary M.,Gelb, Michael H.,Buckner, Frederick S.,Tidwell, Richard R.
supporting information, p. 957 - 971 (2017/02/19)
A previous publication from this lab (Patrick, et al. Bioorg. Med. Chem. 2016, 24, 2451-2465) explored the antitrypanosomal activities of novel derivatives of 2-(2-benzamido)ethyl-4-phenylthiazole (1), which had been identified as a hit against Trypanosoma brucei, the causative agent of human African trypanosomiasis. While a number of these compounds, particularly the urea analogues, were quite potent, these molecules as a whole exhibited poor metabolic stability. The present work describes the synthesis of 65 new analogues arising from medicinal chemistry optimization at different sites on the molecule. The most promising compounds were the urea derivatives of 2-aryl-benzothiazol-5-amines. One such analogue, (S)-2-(3,4-difluorophenyl)-5-(3-fluoro-N-pyrrolidylamido)benzothiazole (57) was chosen for in vivo efficacy studies based upon in vitro activity, metabolic stability, and brain penetration. This compound attained 5/5 cures in murine models of both early and late stage human African trypanosomiasis, representing a new lead for the development of drugs to combat this neglected disease.
