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Scalable and green process for the synthesis of anticancer drug lenalidomide

A new process for the synthesis of anticancer drug lenalidomide was developed, using platinum group metal-free and efficient reduction of nitro group with the iron powder and ammonium chloride. It was found that the bromination of the key raw material, methyl 2-methyl-3-nitrobenzoate, could be carried out in chlorine-free solvent methyl acetate without forming significant amounts of hazardous by-products. We also have compared the known synthetic methods for cyclization of methyl 2-(bromomethyl)-3-nitrobenzoate and 3-aminopiperidinedione to form lenalidomide nitro precursor.

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This work was performed in accordance with marketoriented study ''Development of technology for cytostatic and immunomodulating drugs preparation'' with financial support from Ministry of Education and Science of the Republic of Latvia, JSC ''Grindex'', and Latvian Institute of Organic Synthesis. The authors also wish to acknowledge the financial support of the InnovaBalt (Latvian Institute of Organic Synthesis) project.

The authors are grateful to Anatoly Mishnev (Latvian Institute of Organic Synthesis) for determination of polymorphic forms.

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Correspondence to Yuri Ponomaryov.

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Published in Khimiya Geterotsiklicheskikh Soedinenii, 2015, 51(2), 133–138

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Ponomaryov, Y., Krasikova, V., Lebedev, A. et al. Scalable and green process for the synthesis of anticancer drug lenalidomide. Chem Heterocycl Comp 51, 133–138 (2015). https://doi.org/10.1007/s10593-015-1670-0

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Keywords

  • lenalidomide
  • thalidomide
  • multiple myeloma
  • bromination
  • reduction