66715-65-9Relevant articles and documents
Development of a robust ring-closing metathesis reaction in the synthesis of SB-462795, a cathepsin K inhibitor
Wang, Huan,Goodman, Steven N.,Dai, Qunying,Stockdale, Gregory W.,Clark Jr., William M.
, p. 226 - 234 (2008)
The development of a robust and high-yielding ring-closing metathesis (RCM) reaction and its demonstration on multikilogram scale are described. A detailed understanding of the impact of impurities on the RCM reaction was achieved using a variety of chemical and statistical methods. Specifically, individual impurities were evaluated in spiking studies to identify those that negatively affected the RCM reaction. Projection methods (PCA and PLS) were applied to historical data to identify the main sources of variation in starting material quality and determine the main detrimental impurities that impeded the RCM reaction. The synthesis of the starting material was then modified to adequately control these key impurities, which in turn ensured a robust RCM process. Finally, the robustness of the RCM reaction was assessed using a probability-based approach.
Nickel-Catalyzed Intramolecular Desulfitative C - N Coupling: A Synthesis of Aromatic Amines
Chen, Xuemeng,Jia, Xiuwen,Kramer, S?ren,Li, Yue,Lian, Zhong,Liu, Jiangjun,Sun, Haotian
, p. 5702 - 5711 (2020/05/19)
A nickel-catalyzed intramolecular C - N coupling reaction via SO2 extrusion is presented. The use of a catalytic amount of BPh3 allows the transformation to take place under much milder conditions (60 °C) than previously reported C - N coupling reactions by CO or CO2 extrusion (160-180 °C). In addition, this method displays good functional group tolerance and versatility, as it can be applied to the synthesis of dialkyl aryl amines, alkyl diaryl amines, and triaryl amines. The robustness of the desulfitative C - N coupling is demonstrated by three high-yielding gram-scale reactions.
Cyanide-Free Synthesis of Air Stable N-Substituted Li and K Cyanamide Salts from Tetrazoles. Applications toward the Synthesis of Primary and Secondary Cyanamides as Precursors to Amidines
Duchamp, Edouard,Hanessian, Stephen
supporting information, p. 8487 - 8491 (2020/11/12)
A practical two-step synthesis of N,N′-disubstituted cyanamides consists in the low-temperature metalation of N-substituted 5H-tetrazoles that undergo spontaneous cycloreversion at 0 °C releasing dinitrogen, and forming N-metalated cyanamides that can be reacted in situ with a variety of electrophiles. Remarkably, the N-substituted Li and K cyanamides are air stable white solids at room temperature. Addition of lithium organometallics to the N,N′-disubstituted cyanamides provides a new method for accessing N,N′-disubstituted amidines.
Transition-Metal-Catalyzed Transformation of Sulfonates via S-O Bond Cleavage: Synthesis of Alkyl Aryl Ether and Diaryl Ether
Chen, Xuemeng,Xiao, Xue,Sun, Haotian,Li, Yue,Cao, Haolin,Zhang, Xuemei,Yang, Shengyong,Lian, Zhong
supporting information, p. 8879 - 8883 (2019/11/14)
The catalytic conversion of sulfonates, a versatile class of pharmaceutical intermediates, is usually based on C-O bond cleavage. In this paper, however, we discover a rare transformation of sulfonates via S-O bond cleavage catalyzed by transition metal, through which alkyl sulfonates could undergo an intramolecular desulfitative C-O coupling to form aryl alkyl ethers in the presence of a nickel catalyst. Meanwhile, aryl sulfonates perform similarly to give diaryl ethers catalyzed by a palladium complex. This transformation could tolerate a wide range of functionalities. Controlled experiments reveal that the 2-pyridyl group is necessary to promote the reaction as designed. Crossover experiments proved that this transformation might proceed partly in an intermolecular pathway.
