152955-68-5Relevant articles and documents
Systematic Investigation of the Scope of Transannular C-H Heteroarylation of Cyclic Secondary Amines for Synthetic Application in Medicinal Chemistry
Li, Zhe,Dechantsreiter, Michael,Dandapani, Sivaraman
, p. 6747 - 6760 (2020)
Transannular C-H heteroarylation of amines provides rapid access to complex scaffolds that are otherwise difficult to synthesize. Wide adaptation of this emerging reaction for medicinal chemistry requires a broad understanding of substrate scope and more robust experimental conditions. In this article, we report a new ligand to promote the transannular reaction of a range of fused- and bridged-bicyclic secondary amines with a broad set of heteroarenes. The method was also successfully applied to the arylation of one spiro-bicyclic amine, a class of substrates that has not been studied in the context of transannular C-H activation reactions. The broad application of this transannular C-H heteroarylation methodology is currently hampered by the difficulty of removing the directing group. The development of a new directing group that is easier to remove will expand the utility of this reaction.
Atom Transfer Radical Polymerization-Inspired Room Temperature (sp3)C-N Coupling
Coote, Michelle L.,Fung, Alfred. K. K.,Sherburn, Michael S.,Yu, Li-Juan
, p. 9723 - 9732 (2021/07/20)
A simple nonphotochemical procedure is reported for Cu(I)-catalyzed C-N coupling of aliphatic halides with amines and amides. The process is loosely based on the Goldberg reaction but takes place readily at room temperature. It uses Cu(I)Br, a commonly used and inexpensive atom transfer radical polymerization precatalyst, along with the cheap ligand N,N,N′,N″,N″-pentamethyldiethylenetriamine, to activate the R-X bond of the substrate via inner-sphere electron transfer. The procedure brings about productive C-N bond formation between a range of alkyl halide substrates with heterocyclic aromatic amines and amides. The mechanism of the coupling step, which was elucidated through application of computational methods, proceeds via a unique Cu(I) → Cu(II) → Cu(III) → Cu(I) catalytic cycle, involving (a) inner-sphere electron transfer from Cu(I) to the alkyl halide to generate the alkyl radical; (b) successive coordination of the N-nucleophile and the radical to Cu(II); and finally reductive elimination. In the absence of a nucleophile, debrominative homocoupling of the alkyl halide occurs. Control experiments rule out SN-type mechanisms for C-N bond formation.
Halogen Bond-Assisted Electron-Catalyzed Atom Economic Iodination of Heteroarenes at Room Temperature
Kazi, Imran,Guha, Somraj,Sekar, Govindasamy
, p. 6642 - 6654 (2019/06/14)
A halogen bond-assisted electron-catalyzed iodination of heteroarenes has been developed for the first time under atom economic condition at room temperature. The iodination is successful with just 0.55 equiv of iodine and 0.50 equiv of peroxide. The kinetic study indicates that the reaction is elusive in the absence of a halogen bond between the substrate and iodine. The formation of a halogen bond, its importance in lowering the activation barrier for this reaction, the presence of radical intermediates in a reaction mixture, and the regioselectivity of the reaction have been demonstrated with several control experiments, spectroscopic analysis, and quantum chemical calculations. Allowing the formation of the halogen bond may offer a new strategy to generate the reactive radical intermediates and to enable the otherwise elusive electron-catalyzed reactions under mild reaction conditions.
AMIDE SUBSTITUTED THIAZOLES AS PROTEIN SECRETION INHIBITORS
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Paragraph 00194, (2019/03/17)
Provided herein are thiazole carboxamide protein secretin inhibitors, such as inhibitors of Sec61, methods for their preparation, related pharmaceutical compositions, and methods for using the same. For example, provided herein are compounds of Formula (I): and pharmaceutically acceptable salts and compositions including the same. The compounds disclosed herein may be used, for example, in the treatment of diseases including inflammation and/or cancer.
Intramolecular Oxidative Arylations in 7-Azaindoles and Pyrroles: Revamping the Synthesis of Fused N-Heterocycle Tethered Fluorenes
Laha, Joydev K.,Bhimpuria, Rohan A.,Hunjan, Mandeep Kaur
supporting information, p. 2044 - 2050 (2017/02/18)
We revealed intramolecular oxidative arylations in 7-azaindoles and pyrroles that, for the first time, provided direct access to 7-azaindole- or pyrrole-fused isoindolines and tetrahydroisoquinolines. In addition, N-benzylation of 7-azaindoles or pyrroles with sterically hindered sec-benzyl alcohols by Mitsunobu reaction followed by intramolecular oxidative arylation allowed access to chiral congeners of fused isoindolines that have little precedence. A new opportunity in the design and synthesis of fluorene-based organic emitters is demonstrated in the preparation of novel fused N-heterocycle tethered fluorenes, including a chiral fluorene architecture.
Site-Selective Intermolecular Oxidative C-3 Alkenylation of 7-Azaindoles at Room Temperature
Kannaboina, Prakash,Kumar, K. Anil,Das, Parthasarathi
supporting information, p. 900 - 903 (2016/03/15)
A previously unexplored palladium-catalyzed C-3 selective alkenylation of 7-azaindoles, performed in the presence of Pd(OAc)2 as the catalyst, PPh3 as the ligand, Cu(OTf)2 as an oxidative cocatalyst, and molecular oxygen (O2) as the terminal oxidant at room temperature, has been reported. This direct alkenylation strategy offers a new approach in functionalizing pharmaceutically important 7-azaindoles.
Palladium-catalyzed regioselective C-2 arylation of 7-azaindoles, indoles, and pyrroles with arenes
Laha, Joydev K.,Bhimpuria, Rohan A.,Prajapati, Dilip V.,Dayal, Neetu,Sharma, Shubhra
supporting information, p. 4329 - 4332 (2016/03/22)
A palladium-catalyzed regioselective C-2 arylation of 7-azaindoles, indoles, and pyrroles with arenes has been developed. This study unveils that a critical substrate dependent acid concentration is essential for achieving exclusive C-2 selectivity as wel
Dual Catalysis in Domino N-Benzylation/Intramolecular C-H Arylation: Regio- and Chemoselective Synthesis of Annelated Nitrogen Heterocycles
Laha, Joydev K.,Dayal, Neetu,Singh, Swati,Bhimpuria, Rohan
, p. 5469 - 5475 (2014/10/15)
A general method has been developed for the synthesis of fused nitrogen heterocycles by using a domino N-benzylation/C-H arylation reaction sequence. The details and yields of the domino process were compared with those of the two-step literature protocol
Palladium-catalyzed direct and regioselective C-H bond functionalization/ oxidative acetoxylation of indoles
Choy, Pui Ying,Lau, Chak Po,Kwong, Fuk Yee
supporting information; experimental part, p. 80 - 84 (2011/03/22)
The first general examples of palladium-catalyzed direct and selective oxidative C3-acetoxylation of indoles are presented. The mild reaction conditions (70 °C and with weak base, KOAc) in this indole C-H-acetoxylation are notable.
Pd-catalyzed direct and selective C-H functionalization: C3-acetoxylation of indoles
Liu, Qiang,Li, Gang,Yi, Hong,Wu, Pan,Liu, Jie,Lei, Aiwen
supporting information; experimental part, p. 2353 - 2357 (2011/04/24)
Direct functionalization of C-H bonds has been a hot topic in organic chemistry during recent years. Arenes-one of the most abundant chemical motifs-usually have multiple C-H bonds. Although, some examples of direct functionalizations of arenes have been
