IMATINIB SYNTHESIS – EUREKAMOMENTS IN ORGANIC CHEMISTRY

As an example of research aimed at industrial production one involving imatinib. This cancer drug was one of the first offspring of rational drug design . A group of Northwest University researchers set out to improve the existing Novartis procedure DOI and here is how they did it.

2-acetylpyridine (1) was alkylated with the acetal of N,N-dimethylformamide 2 to enamine 3. A pyrimidine ring in 5was formed with base and reagent guanidine nitrate 4 and nitrotoluene fragment 6 was added in a Ullmann-type reaction with CuI generating secondary amine 7. The nitro group was reduced by hydrazine / FeCl₃/C to the amine which was then converted to amide 8 with acid chloride 9. The final step is addition of piperazine 10 to form imatinib11.

By DR ANTHONY MELVIN CRASTO Ph.D