43052-72-8Relevant articles and documents
Native Directed Site-Selective δ-C(sp3)-H and δ-C(sp2)-H Arylation of Primary Amines
Lin, Hua,Pan, Xiaohong,Barsamian, Adam L.,Kamenecka, Theodore M.,Bannister, Thomas D.
, p. 4887 - 4891 (2019)
A Pd(II)-catalyzed, selective δ-C(sp3)-H and δ-C(sp2)-H arylation method for free primary aliphatic amines using NH2 as a native directing group has been developed. A variety of free primary amines with adjacent quaternary
Photocatalytic Hydroaminoalkylation of Styrenes with Unprotected Primary Alkylamines
Askey, Hannah E.,Grayson, James D.,Tibbetts, Joshua D.,Turner-Dore, Jacob C.,Holmes, Jake M.,Kociok-Kohn, Gabriele,Wrigley, Gail L.,Cresswell, Alexander J.
supporting information, p. 15936 - 15945 (2021/10/12)
Catalytic, intermolecular hydroaminoalkylation (HAA) of styrenes provides a powerful disconnection for pharmacologically relevant γ-arylamines, but current methods cannot utilize unprotected primary alkylamines as feedstocks. Metal-catalyzed HAA protocols are also highly sensitive to α-substitution on the amine partner, and no catalytic solutions exist for α-tertiary γ-arylamine synthesis via this approach. We report a solution to these problems using organophotoredox catalysis, enabling a direct, modular, and sustainable preparation of α-(di)substituted γ-arylamines, including challenging electron-neutral and moderately electron-rich aryl groups. A broad range of functionalities are tolerated, and the reactions can be run on multigram scale in continuous flow. The method is applied to a concise, protecting-group-free synthesis of the blockbuster drug Fingolimod, as well as a phosphonate mimic of itsin vivoactive form (by iterative α-C-H functionalization of ethanolamine). The reaction can also be sequenced with an intramolecularN-arylation to provide a general and modular access to valuable (spirocyclic) 1,2,3,4-tetrahydroquinolines and 1,2,3,4-tetrahydronaphthyridines. Mechanistic and kinetic studies support an irreversible hydrogen atom transfer activation of the alkylamine by the azidyl radical and some contribution from a radical chain. The reaction is photon-limited and exhibits a zero-order dependence on amine, azide, and photocatalyst, with a first-order dependence on styrene.
Design, synthesis and biological evaluation of 8-(2-amino-1-hydroxyethyl)-6-hydroxy-1,4-benzoxazine-3(4H)-one derivatives as potent β2-adrenoceptor agonists
Yi, Ce,Xing, Gang,Wang, Siqi,Li, Xiaoran,Liu, Yichuang,Li, Jinyan,Lin, Bin,Woo, Anthony Yiu-Ho,Zhang, Yuyang,Pan, Li,Cheng, Maosheng
, (2019/11/26)
A series of β2-adrenoceptor agonists with an 8-(2-amino-1-hydroxyethyl)-6-hydroxy-1,4-benzoxazine-3(4H)-one moiety is presented. The stimulatory effects of the compounds on human β2-adrenoceptor and β1-adrenoceptor were characterized by a cell-based assay. Their smooth muscle relaxant activities were tested on isolated guinea pig trachea. Most of the compounds were found to be potent and selective agonists of the β2-adrenoceptor. One of the compounds, (R)-18c, possessed a strong β2-adrenoceptor agonistic effect with an EC50 value of 24 pM. It produced a full and potent airway smooth muscle relaxant effect same as olodaterol. Its onset of action was 3.5 min and its duration of action was more than 12 h in an in vitro guinea pig trachea model of bronchodilation. These results suggest that (R)-18c is a potential candidate for long-acting β2-AR agonists.
Carbon Dioxide-Driven Palladium-Catalyzed C-H Activation of Amines: A Unified Approach for the Arylation of Aliphatic and Aromatic Primary and Secondary Amines
Kapoor, Mohit,Chand-Thakuri, Pratibha,Maxwell, Justin M.,Liu, Daniel,Zhou, Hanyang,Young, Michael C.
, p. 519 - 524 (2019/03/07)
Amines are an important class of compounds in organic chemistry and serve as an important motif in various industries, including pharmaceuticals, agrochemicals, and biotechnology. Several methods have been developed for the C-H functionalization of amines
