An Efficient Synthesis of Nilotinib (AMN107)

Abstract

A concise synthesis of AMN107, a compound currently undergoing several phase II/III clinical trials for chronic myelogenous leukemia is described. The new procedure reduces the number of synthetic steps from eight to four, with an overall yield of 65%.

Key words

AMN107 - Abl kinase inhibitor - Cu-catalyzed N-arylation - Pd-catalyzed N-arylation - atom economy

References

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• After this manuscript was submitted for review, we became aware that Novartis published a patent on the synthesis of AMN107 based on the amide bond formation from 1 and 3. Several synthetic approaches to 3 were also reported, which included a Cu-catalyzed coupling of 3-bromo-(5-trifluoro­-methyl)aniline and 4-methylimidazole by using cyclo-hexanediamine as the ligand:
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• In addition, after the revised manuscript was submitted, the authors became aware of two recent patents which involve Cu-catalyzed coupling of 3-bromo-(5-trifluoromethyl)-aniline and 4-methylimidazole:
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