2106-49-2Relevant articles and documents
An Efficient Second-Generation Manufacturing Process for the pan-RAF Inhibitor Belvarafenib
Zell, Daniel,Dalziel, Michael E.,Carrera, Diane E.,Stumpf, Andreas,Bachmann, Stephan,Mercado-Marin, Eduardo,Koenig, Stefan G.,Zhang, Haiming,Gosselin, Francis
supporting information, p. 2338 - 2350 (2021/09/28)
Herein, the development of a streamlined manufacturing process for the pan-RAF inhibitor belvarafenib (GDC-5573) is reported. The process to belvarafenib features a number of efficient key reactions, including a robust and scalable Pd-catalyzed carbonylation reaction to generate thienopyrimidine 2 and a highly chemoselective Pt/V/C-catalyzed nitro group reduction to access the penultimate intermediate 3. The final amide coupling was accomplished by a mild and safe protocol employing N,N,N′,N′-tetramethylchloroformamidinium hexafluorophosphate as the coupling reagent, which afforded belvarafenib on a multikilogram production scale after recrystallization.
Design, synthesis, SAR, and biological evaluation of highly potent benzimidazole-spaced phosphono-α-amino acid competitive NMDA antagonists of the AP-6 type
Baudy,Fletcher III,Yardley,Zaleska,Bramlett,Tasse,Kowal,Katz,Moyer,Abou-Gharbia
, p. 1516 - 1529 (2007/10/03)
A series of 2-amino-(phosphonoalkyl)-1H-benzimidazole-2-alkanoic acids was synthesized and evaluated for NMDA receptor affinity using a [3H]CPP binding assay. Functional antagonism of the NMDA receptor complex was evaluated in vitro using a stimulated [3H]TCP binding assay and in vivo by employing an NMDA-induced seizure model. Several compounds of the AP-6 type demonstrated potent and selective NMDA antagonistic activity both in vitro and in vivo. In particular, [R(-)]-2-amino-3-(5-chloro-1-phosphonomethyl-1H-benzoimidazol-2-yl)-propionic acid (1) displayed an IC50 value of 7.1 nM in the [3H]CPP binding assay and an ED50 value of 0.13 mg/kg (ip) in the NMDA lethality model. Compound 1, when administered intravenously as a single bolus dose of 3 mg/kg following permanent occlusion of the middle cerebral artery in the rat, reduced the volume of infarcted brain tissue by 45%. These results support a promising therapeutic potential for compound 1 as a neuroprotective agent.
Process for preparing fluoronitrobenzenes
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, (2008/06/13)
Fluoronitrobenzenes are prepared in an advantageous way from the corresponding chloronitrobenzenes and an alkali metal fluoride by means of a chlorine-fluorine exchange reaction with replacement of a chlorine atom by a fluorine atom, by catalyzing the reaction with a quaternaryammonium compound which comprises at least one alkoxypolyoxyalkyl radical.