123629-22-1Relevant academic research and scientific papers
The remarkable effect of a simple ion: Iodide-promoted transfer hydrogenation of heteroaromatics
Wu, Jianjun,Wang, Chao,Tang, Weijun,Pettman, Alan,Xiao, Jianliang
, p. 9525 - 9529 (2012)
I can do it! Accelerated by simple iodide ions, rhodium-catalysed transfer hydrogenation can be readily performed on quinolines, isoquinolines and quinoxalines, affording the tetrahydro products in high yields with low catalyst loading (see scheme). Copyright
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.
, 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.
Chiral phosphoric acid catalyzed oxidative kinetic resolution of cyclic secondary amine derivatives including tetrahydroquinolines by hydrogen transfer to imines
Saito, Kodai,Miyashita, Hiromitsu,Akiyama, Takahiko
supporting information, p. 16648 - 16651 (2015/11/25)
A chiral Bronsted acid catalyzed dehydrogenative kinetic resolution of tetrahydroquinoline derivatives, which are representative of cyclic secondary amines, based on their hydrogen transfer to aromatic imines was efficiently achieved with high enantioselectivities. This hydrogen transfer of tetrahydroquinolines to imines was not driven by their aromatization to quinolines. This dehydrogenative kinetic resolution could be also applied to the asymmetric synthesis of various benzofused heterocycles containing secondary amine cores.
Design, synthesis, and structure-activity relationship study of conformationally constrained analogs of indole-3-carboxamides as novel CB1 cannabinoid receptor agonists
Kiyoi, Takao,York, Mark,Francis, Stuart,Edwards, Darren,Walker, Glenn,Houghton, Andrea K.,Cottney, Jean E.,Baker, James,Adam, Julia M.
scheme or table, p. 4918 - 4921 (2010/11/04)
Novel tricyclic indole-3-carboxamides were synthesized as structurally restricted analogs of bicyclic indoles, and found to be potent CB1 cannabinoid receptor agonists. The CB1 agonist activity depended on the absolute configuration of the chiral center of the tricyclic ring. The preferred enantiomer was more potent than the structurally unconstrained lead compound. Structure-activity relationships in the amide side chain of the indole C-3 position were also investigated.
TRICYCLIC 1-[(3-INDOL-3-YL)CARBONYL] PIPERAZINE DERIVATIVES AS CANNABINOID CB1 RECEPTOR AGONISTS
-
Page 23, (2010/02/12)
The invention relates to tricyclic 1-[(indol-3-yl)carbonyl]piperazine derivative having the general Formula (I) wherein X is CH2, O or S; R represents 1-3 substituents independently selected from H, (C1-4)alkyl, (C1-4)alky
Synthesis, Structure-Activity Relationships, and Pharmacological Evalaution of Pyrroloquinoline Derivatives: Potent Histamine and Platelet Activating Factor Antagonism and 5-Lipoxygenase Inhitory Properties. Potential Therapeutic Application in Asthma
Paris, Dominique,Cottin, Michel,Demonchaux, Patrice,Augert, Guy,Dupassieux, Pierre,et al.
, p. 669 - 685 (2007/10/02)
A series of pyrroloquinoline derivatives was synthesized and evaluated for their in vitro and in vivo activities against histamine, platelet activating factor (PAF), and leukotrienes which are recognized to be of importance in asthma.The structure-activity relationship studies have shown that the optimum moiety on the 1-position of the pyrroloquinoline nucleus is a 2-ethyl chain in conjuction with a methyl group on the 2-position for potent antagonism of both histamine and PAF.The introduction of substituents on the 8- and 4-positions was also investigated in order to increase the potency of 5-lipoxygenase inhibition while retaining or improving the activities against histamine and PAF.This series is exemplified by 4-n-butyl-5,6-dihydro-8-hydroxy-2-methyl-1-ethyl>-4H-pyrroloquinoline (24, KC 11404) which was found to be active against all three of the selected mediators.Compound 24 was found to be orally active in guinea pig models against the histaminic phase of antigen-induced bronchospasm and PAF-induced bronchoconstriction (ED50=1.9 and 2.1 μmol/kg, respectively).When tested against the leukotriene-dependent phase of the antigen-induced bronchoconstriction, compound 24 showed the same potency as zileuton.
