Imatinib Drug Synthesis Lab Report

Figure 6: Imatinib The first imatinib drug synthesis was done by Zimmermann (figure 7) in 1993, he used a chain of the reaction to reach to imatinib but the important part is that both guanidinium nitrate 7 and aminopyrimidine 8 are precipitated from the respective reaction mixtures by the addition of

Figure 7: imatinib synthesis by Zimmermann insolubilizing solvents, so we got a condensation reaction between guanidinium salt 7 with enone “9” to form the aminopyrimidine “8” then “8” is reduced in the presence of palladium then refluxed for 21 hrs to form amine group which is replaced by nitro group, finally they added acid chloride 6 to 17 then the amine group attack the electrophilic carbon (the carbon near to Cl) and eliminate Cl
reduction reaction of the nitro group to form amine, and they reduced the synthesis time from 21 hr to 2-4 hrs, and after that the resulting aniline 17 coupled with dihydrochloride salt of acid chloride to get imatinib with its tri-hydrochloride salt see figure 9. Figure 9: Cipla’s alternative reduction of intermediate 8.
7. Molecular mechanism of ABL/BCR inhibition Imatinib was discovered in 1992 by using medicinal chemistry methods 45. The activity of imatinib was studied by applying docking studies on the ATP-binding site of ABL, by using X-ray crystal structure of the fibroblast growth factor receptor (FGFR) kinase in complex with the pyrido pyrimidine inhibitor PD173074 43,