2163-44-2Relevant articles and documents
Synthesis and initial SAR studies of 3,6-disubstituted pyrazolo[1,5-a]pyrimidines: A new class of KDR kinase inhibitors
Fraley, Mark E.,Hoffman, William F.,Rubino, Robert S.,Hungate, Randall W.,Tebben, Andrew J.,Rutledge, Ruth Z.,McFall, Rosemary C.,Huckle, William R.,Kendall, Richard L.,Coll, Kathleen E.,Thomas, Kenneth A.
, p. 2767 - 2770 (2002)
We have synthesized and evaluated the activity of 3,6-disubstituted pyrazolo[1,5-a]pyrimidines as a new class of KDR kinase inhibitors. Starting with screening lead 1, potency against isolated KDR was fully optimized with 3-thienyl and 4-methoxyphenyl substituents at the 6- and 3-positions (3g, KDR IC50=19 nM), respectively. The synthesis and SAR of these compounds are described.
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Hajek,Malek
, p. 454 (1977)
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A Case Study in Catalyst Generality: Simultaneous, Highly-Enantioselective Br?nsted- And Lewis-Acid Mechanisms in Hydrogen-Bond-Donor Catalyzed Oxetane Openings
Strassfeld, Daniel A.,Algera, Russell F.,Wickens, Zachary K.,Jacobsen, Eric N.
supporting information, p. 9585 - 9594 (2021/07/19)
Generality in asymmetric catalysis can be manifested in dramatic and valuable ways, such as high enantioselectivity across a wide assortment of substrates in a given reaction (broad substrate scope) or as applicability of a given chiral framework across a variety of mechanistically distinct reactions (privileged catalysts). Reactions and catalysts that display such generality hold special utility, because they can be applied broadly and sometimes even predictably in new applications. Despite the great value of such systems, the factors that underlie generality are not well understood. Here, we report a detailed investigation of an asymmetric hydrogen-bond-donor catalyzed oxetane opening with TMSBr that is shown to possess unexpected mechanistic generality. Careful analysis of the role of adventitious protic impurities revealed the participation of competing pathways involving addition of either TMSBr or HBr in the enantiodetermining, ring-opening event. The optimal catalyst induces high enantioselectivity in both pathways, thereby achieving precise stereocontrol in fundamentally different mechanisms under the same conditions and with the same chiral framework. The basis for that generality is analyzed using a combination of experimental and computational methods, which indicate that proximally localized catalyst components cooperatively stabilize and precisely orient dipolar enantiodetermining transition states in both pathways. Generality across different mechanisms is rarely considered in catalyst discovery efforts, but we suggest that it may play a role in the identification of so-called privileged catalysts.
Computational and experimental studies on copper-mediated selective cascade C-H/N-H annulation of electron-deficient acrylamide with arynes
Chen, Chao,Hao, Yu,Zhang, Ting-Yu,Pan, Jin-Long,Ding, Jun,Xiang, Heng-Ye,Wang, Man,Ding, Tong-Mei,Duan, Abing,Zhang, Shu-Yu
supporting information, p. 755 - 758 (2019/01/21)
An efficient and convenient copper-mediated method has been developed to achieve direct cascade C-H/N-H annulation to synthesize 2-quinolinones from electron-deficient acrylamides and arynes. This method highlights an emerging but simple strategy to transform inert C-H bonds into versatile functional groups in organic synthesis to provide a new method of synthesizing 2-quinolinones efficiently. Mechanistic investigations by experimental and density functional theory (DFT) studies suggest that an organometallic C-H activation via a Cu(iii) intermediate is likely to be involved in the reaction.
