271-63-6Relevant articles and documents
Ruthenium-Catalyzed Regioselective C(sp2)-H Activation/Annulation of N-(7-Azaindole)amides with 1,3-Diynes Using N-Amino-7-azaindole as the N, N-Bidentate Directing Group
Pati, Bedadyuti Vedvyas,Sagara, Prateep Singh,Ghosh, Asit,Das Adhikari, Gopal Krushna,Ravikumar, Ponneri Chandrababu
, p. 9428 - 9443 (2021)
The ruthenium(II)-catalyzed regioselective annulation of N-(7-azaindole)amides with 1,3-diynes has been demonstrated. Bioactive N-amino-7-azaindole has been used as a new bidentate directing group to furnish an array of 3-alkynylated isoquinolones. Furthermore, the developed protocol works efficiently for both aryl- and heteroaryl-substituted amides producing a range of pharmacologically useful 7-azaindole-based isoquinolones with a wide range of functionality.
Photochemistry of Transient Tautomer of 7-Azaindole H-Bonded Dimer Studied by Two-Step Laser Excitation Fluorescence Measurements
Tokumura, Kunihiro,Watanabe, Yukari,Udagawa, Masahiro,Itoh, Michiya
, p. 1346 - 1350 (1987)
Formation of the monomeric tautomer (7H-pyrrolopyridine) in the photodissociation of the transient groun-state dimeric tautomer, generated via excited-state double proton transfer of 7-azaindole H-bonded dimer in 3-methylpentane (MP), was confirmled by transient absorption and two-step laser excitation (TSLE) fluorescence spectroscopies.The intense XeCl laser pulse (308-nm) excitation of the H-bonded dimer in MP at room temperature produced short- (17 μs) and a long-lived (47 μs) transients.The former and latter were ascribed to the dimeric and monomeric tautomers in the ground state, respectively.It is suggested that the second pulse excitation of the short-lived dimeric tautomer induces efficient dissociation to form a monomeric tautomer in the xcited state together with that in the ground state.One-color (308-nm) biphotonic processes within the XeCl laser pulse are therefore responsible for the long-lived monomeric tautomer in the ground state.The decay of the monomeric tautomer in the dark is attributable to the H-transfer reaction to yield 7-azaindole.Significant deuterium isotope effects were found for H-transfer of the monomeric tautomer as well as for photodissociation of the dimeric tautomer.
Solvation of 7-azaindole in alcohols and water: Evidence for concerted, excited-state, double-proton transfer in alcohols
Chen,Gai,Petrich
, p. 10158 - 10166 (1993)
The proton inventory technique is used for the first time to investigate excited-state proton-transfer processes. The nonradiative pathways of the biological probe, 7-azaindole, in methanol, ethanol, and water are examined. Results in methanol and ethanol demonstrate the involvement of two protons in the transition state for the excited-state double-proton transfer process. These data provide the first experimental evidence suggesting a concerted tautomerization reaction of 7-azaindole in alcohols. The data for 7-azaindole in water are interpreted in terms of a nonradiative pathway that is qualitatively different from that in alcohols. We propose abstraction of the N1 hydrogen by water as a possible nonradiative decay process.
Development and Scale-Up of an Improved Manufacturing Route to the ATR Inhibitor Ceralasertib
Graham, Mark A.,Askey, Hannah,Campbell, Andrew D.,Chan, Lai,Cooper, Katie G.,Cui, Zhaoshan,Dalgleish, Andrew,Dave, David,Ensor, Gareth,Galan Espinosa, Maria Rita,Hamilton, Peter,Heffernan, Claire,Jackson, Lucinda V.,Jing, Dajiang,Jones, Martin F.,Liu, Pengpeng,Mulholland, Keith R.,Pervez, Mohammed,Popadynec, Michael,Randles, Emma,Tomasi, Simone,Wang, Shenghua
, p. 43 - 56 (2021/01/09)
Ceralasertib is currently being evaluated in multiple phase I/II clinical trials for the treatment of cancer. Its structure, comprising a pyrimidine core decorated with a chiral morpholine, a cyclopropyl sulfoximine and an azaindole, makes it a challenging molecule to synthesize on a large scale. Several features of the medicinal chemistry and early development route make it unsuitable for the long-term commercial manufacture of the active pharmaceutical ingredient. We describe the investigation and development of a new and improved route which introduces the cyclopropyl moiety in a novel process from methyl 2,4-dibromobutyrate. Following construction of the pyrimidine ring, large-scale chlorination with phosphoryl chloride was performed with a safe and robust work-up. An SNAr reaction required an innovative work-up to remove the unwanted regio-isomer, and then a Baeyer-Villiger monooxygenase enzyme was used to enable asymmetric sulfur oxidation to a sulfoxide. A safe and scalable metal-free sulfoximine formation was developed, and then optimization of a Suzuki reaction enabled the manufacture of high-quality ceralasertib with excellent control of impurities and an overall yield of 16%.
Highly Chemoselective Deoxygenation of N-Heterocyclic N-Oxides Using Hantzsch Esters as Mild Reducing Agents
An, Ju Hyeon,Kim, Kyu Dong,Lee, Jun Hee
supporting information, p. 2876 - 2894 (2021/02/01)
Herein, we disclose a highly chemoselective room-temperature deoxygenation method applicable to various functionalized N-heterocyclic N-oxides via visible light-mediated metallaphotoredox catalysis using Hantzsch esters as the sole stoichiometric reductant. Despite the feasibility of catalyst-free conditions, most of these deoxygenations can be completed within a few minutes using only a tiny amount of a catalyst. This technology also allows for multigram-scale reactions even with an extremely low catalyst loading of 0.01 mol %. The scope of this scalable and operationally convenient protocol encompasses a wide range of functional groups, such as amides, carbamates, esters, ketones, nitrile groups, nitro groups, and halogens, which provide access to the corresponding deoxygenated N-heterocycles in good to excellent yields (an average of an 86.8% yield for a total of 45 examples).