917358-52-2

Upstream product

• 109-01-3 1-methyl-piperazine 
• 917358-62-4 4-chloromethyl-N-(4-methyl-3-[4-(1-oxy-pyridin-3-yl)-[2-⁽¹⁴⁾C]pyrimidin-2-ylamino]-phenyl)-benzamide hydrochloride 
• 581076-59-7 N-(3-bromo-4-methylphenyl)-4-((4-methylpiperazin-1-yl)-methyl)benzamide 
• 1571-08-0 methyl 4-formylbenzoate 
• 314268-40-1 4-((4-methylpiperazin-1-yl)methyl)-benzoic acid methyl ester 
• 350-03-8 methyl-3-pyridylketone 

Downstream Products

• 917358-55-5 4-(4-methyl-4-oxy-piperazin-1-yl)methyl-N-[4-methyl-3-(4-pyridin-3-yl-[2-⁽¹⁴⁾C]pyrimidin-2-ylamino)-phenyl]-benzamide 
• 917358-53-3 4-(4-methyl-piperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl-[2-⁽¹⁴⁾C]pyrimidin-2-ylamino)-phenyl]-benzamide mesylate 

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%.

METHODS AND INTERMEDIATES FOR THE PREPARATION OF OPTIONALLY RADIO-LABELED IMATINIB

The invention relates to new processes for the manufacture of N-{5-[4-(4-methyl-piperazino- methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine of formula (I), new processes for the manufacture of metabolites of N-{5-[4-(4-methyl-piperazino-methyl)- benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine observed after administration of the compound to warm-blooded animals as well as to intermediates used in said processes. New starting materials as well as processes for the preparation thereof are likewise the subject of this invention. The processes described herein are especially suitable to furnish said compounds having isotopic labeling. The such obtained labeled compounds are in particular suitable to track and to investigate into the metabolism of N-{5-[4-(4-methyl- piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine and its pharmaceutically acceptable salts in clinical and pre-clinical studies.