581076-59-7Relevant articles and documents
Synthesis of imatinib, a tyrosine kinase inhibitor, labeled with carbon-14
Kang, Julie,Lee, Jun Young,Park, Jeong-Hoon,Chang, Dong-Jo
, p. 174 - 182 (2020/02/13)
Imatinib (Gleevec) is a multiple tyrosine kinase inhibitor that decreases the activity of the fusion oncogene called BCR-ABL (breakpoint cluster region protein-Abelson murine leukemia viral oncogene homolog) and is clinically used for the treatment of chronic myelogenous leukemia and acute lymphocytic leukemia. Small molecule drugs, such as imatinib, can bind to several cellular proteins including the target proteins in the cells, inducing undesirable effects along with the effects against the disease. In this study, we report the synthetic optimization for 14C-labeling and radiosynthesis of [14C]imatinib to analyze binding with cellular proteins using accelerator mass spectroscopy. 14C-labeling of imatinib was performed by the synthesis of 14C-labeld 2-aminopyrimidine intermediate using [14C]guanidine·HCl, which includes an in situ reduction of an inseparable byproduct for easy purification by HPLC, followed by a cross-coupling reaction with aryl bromide precursor. The radiosynthesis of [14C]imatinib (specific activity, 631 MBq/mmol; radiochemical purity, 99.6%) was achieved in six steps with a total chemical yield of 29.2%.
Spectroscopic Studies of the Chan-Lam Amination: A Mechanism-Inspired Solution to Boronic Ester Reactivity
Vantourout, Julien C.,Miras, Haralampos N.,Isidro-Llobet, Albert,Sproules, Stephen,Watson, Allan J. B.
supporting information, p. 4769 - 4779 (2017/04/11)
We report an investigation of the Chan-Lam amination reaction. A combination of spectroscopy, computational modeling, and crystallography has identified the structures of key intermediates and allowed a complete mechanistic description to be presented, including off-cycle inhibitory processes, the source of amine and organoboron reactivity issues, and the origin of competing oxidation/protodeboronation side reactions. Identification of key mechanistic events has allowed the development of a simple solution to these issues: manipulating Cu(I) → Cu(II) oxidation and exploiting three synergistic roles of boric acid has allowed the development of a general catalytic Chan-Lam amination, overcoming long-standing and unsolved amine and organoboron limitations of this valuable transformation.
Use of a "catalytic" Cosolvent, N,N-Dimethyl Octanamide, Allows the Flow Synthesis of Imatinib with no Solvent Switch
Yang, Jeffrey C.,Niu, Dawen,Karsten, Bram P.,Lima, Fabio,Buchwald, Stephen L.
, p. 2531 - 2535 (2016/02/18)
A general, efficient method for C-N cross-coupling has been developed using N,N-dimethyloctanamide as a catalytic cosolvent for biphasic continuous-flow applications. The described method was used to generate a variety of biarylamines and was integrated into a two-step sequence which converted phenols into biarylamines via either triflates or tosylates. Additionally, the method was applied to a three-step synthesis of imatinib, the API of Gleevec, in good yield without the need of solvent switches. Going with the flow: A general flow method developed for C-N cross-coupling using N,N-dimethyloctanamide as a catalytic cosolvent was integrated into a two-step sequence which converted phenols into biarylamines via either triflates or tosylates. It was applied to a three-step synthesis of imatinib, the API of Gleevec, in good yield without the need of solvent switches.
