697300-78-0Relevant articles and documents
Modular Photocatalytic Synthesis of α-Trialkyl-α-Tertiary Amines
Henry Blackwell,Harris, Georgia R.,Smith, Milo A.,Gaunt, Matthew J.
supporting information, p. 15946 - 15959 (2021/10/12)
Molecules displaying an α-trialkyl-α-tertiary amine motif provide access to an important and versatile area of biologically relevant chemical space but are challenging to access through existing synthetic methods. Here, we report an operationally straightforward, multicomponent protocol for the synthesis of a range of functionally and structurally diverse α-trialkyl-α-tertiary amines, which makes use of three readily available components: dialkyl ketones, benzylamines, and alkenes. The strategy relies on the of use visible-light-mediated photocatalysis with readily available Ir(III) complexes to bring about single-electron reduction of an all-alkyl ketimine species to an α-amino radical intermediate; the α-amino radical undergoes Giese-type addition with a variety of alkenes to forge the α-trialkyl-α-tertiary amine center. The mechanism of this process is believed to proceed through an overall redox neutral pathway that involves photocatalytic redox-relay of the imine, generated from the starting amine-ketone condensation, through to an imine-derived product. This is possible because the presence of a benzylic amine component in the intermediate scaffold drives a 1,5-hydrogen atom transfer step after the Giese addition to form a stable benzylic α-amino radical, which is able to close the photocatalytic cycle. These studies detail the evolution of the reaction platform, an extensive investigation of the substrate scope, and preliminary investigation of some of the mechanistic features of this distinct photocatalytic process. We believe this transformation will provide convenient access to previously unexplored α-trialkyl-α-tertiary amine scaffolds that should be of considerable interest to practitioners of synthetic and medicinal chemistry in academic and industrial institutions.
5-Substituted Derivatives of 6-Halogeno-3-((2-(S)-azetidinyl)methoxy)pyridine and 6-Halogeno-3-((2-(S)-pyrrolidinyl)methoxy)pyridine with Low Picomolar Affinity for α4β2 Nicotinic Acetylcholine Receptor and Wide Range of Lipophilicity: Potential Probes for Imaging with Positron Emission Tomography
Zhang, Yi,Pavlova, Olga A.,Chefer, Svetlana I.,Hall, Andrew W.,Kurian, Varughese,Brown, LaVerne L.,Kimes, Alane S.,Mukhin, Alexey G.,Horti, Andrew G.
, p. 2453 - 2465 (2007/10/03)
Potential positron emission tomography (PET) ligands with low picomolar affinity at the nicotinic acetylcholine receptor (nAChR) and with lipophilicity (log D) ranging from - 1.6 to +1.5 have been synthesized. Most members of the series, which are derivatives of 5-substituted-6-halogeno-A-85380, exhibited a higher binding affinity at α4β2-nAChRs than epibatidine. An analysis, by molecular modeling, revealed an important role of the orientation of the additional heterocyclic ring on the binding affinity of the ligands with nAChRs. The existing nicotinic pharmacophore models do not accommodate this finding. Two compounds of the series, 6-[18F]fluoro-5-(pyridin-3-yl)-A-85380 ([18F]31) and 6-chloro-3-((2-(S)-azetidinyl)methoxy)-5-(2-[ 18F]fluoropyridin-5-yl)pyridine) ([18F]35), were radiolabeled with 18F. Comparison of PET data for [18F]31 and 2-[18F]FA shows the influence of lipophilicity on the binding potential. Our recent PET studies with [18F]35 demonstrated that its binding potential values in Rhesus monkey brain were ca. 2.5 times those of 2-[18F]FA. Therefore, [18F]35 and several other members of the series, when radiolabeled, will be suitable for quantitative imaging of extrathalamic nAChRs.
