581076-59-7

Upstream product

• 109-01-3 1-methyl-piperazine 
• 1072105-05-5 N-(3-bromo-4-methylphenyl)-4-(chloromethyl)benzamide 
• 7745-91-7 3-bromo-4-methylaniline 
• 876-08-4 p-(chloromethyl)benzoyl chloride 
• 314268-40-1 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester 
• 1571-08-0 methyl 4-formylbenzoate 

Downstream Products

• 152459-95-5 imatinib 
• 1427026-56-9 C₂₆H₃₂N₆O 
• 1427026-57-0 C₂₆H₂₈N₆O₂ 
• 1427026-55-8 C₃₁H₃₂N₈O 
• 1427026-58-1 C₃₆H₃₅FN₆O 
• 917358-52-2 ¹⁴C-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)-4-((4-methylpiperazin-1-yl)methyl)benzamide 

Relevant academic research and scientific papers

Synthesis of imatinib, a tyrosine kinase inhibitor, labeled with carbon-14

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

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.

N-phenyl-2-pyrimidine-amine derivatives

The present invention relates to novel amides and a process for preparing these amides.

Design and Performance Validation of a Conductively Heated Sealed-Vessel Reactor for Organic Synthesis

A newly designed robust and safe laboratory scale reactor for syntheses under sealed-vessel conditions at 250 °C maximum temperature and 20 bar maximum pressure is presented. The reactor employs conductive heating of a sealed glass vessel via a stainless steel heating jacket and implements both online temperature and pressure monitoring in addition to magnetic stirring. Reactions are performed in 10 mL borosilicate vials that are sealed with a silicone cap and Teflon septum and allow syntheses to be performed on a 2-6 mL scale. This conductively heated reactor is compared to a standard single-mode sealed-vessel microwave instrument with respect to heating and cooling performance, stirring efficiency, and temperature and pressure control. Importantly, comparison of the reaction outcome for a number of different synthetic transformations performed side by side in the new device and a standard microwave reactor suggest that results obtained using microwave conditions can be readily mimicked in the operationally much simpler and smaller conventionally heated device.

Use of a "catalytic" Cosolvent, N,N-Dimethyl Octanamide, Allows the Flow Synthesis of Imatinib with no Solvent Switch

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.

A Practical Preparation of Imatinib Base

A practical preparation of imatinib base was reported in this article. Compared with reported works, the features of this work were the concise procedures, the industrially available starting materials, the avoidance of expensive or highly toxic transition-metal catalysts or reagents, and the genotoxic impurities 6-methyl-N 1-[4-(pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diamine and 4-(chloromethyl)-N-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)benzamide. The method was scalable to at least 100 mmol, and the products were separated by simple recrystallizations.

An expeditious synthesis of imatinib and analogues utilising flow chemistry methods

A flow-based route to imatinib, the API of Gleevec, was developed and the general procedure then used to generate a number of analogues which were screened for biological activity against Abl1. The flow synthesis required minimal manual intervention and was achieved despite the poor solubility of many of the reaction components.

A flow-based synthesis of Imatinib: The API of Gleevec

A concise, flow-based synthesis of Imatinib, a compound used for the treatment of chronic myeloid leukaemia, is described whereby all steps are conducted in tubular flow coils or cartridges packed with reagents or scavengers to effect clean product formation. An in-line solvent switching procedure was developed enabling the procedure to be performed with limited manual handling of intermediates. The Royal Society of Chemistry.