An improved procedure for synthesis of lenalidomide as an active pharmaceutical ingredient
Year: 2025
Type: article
Abstract: Lenalidomide is a second-generation immunomodulatory drug widely used in the treatment of multiple myeloma and myelodysplastic syndromes. Market studies indicate that the demand for lenalidomide rising steadily due to the increasing prevalence of multiple myeloma. As a result of its high effectiveness in the treatment and improved survival rates, lenalidomide has become the second best-selling drug in the field of oncology. So far, many methods have been developed for synthesis of lenalidomide, but they are plagued by issues. Finding a method that ensures the highest efficiency, minimal impurity, and cost-effectiveness remains a challenge for researchers. In this study, we chose a three steps method for synthesis of lenalidomide: 1) bromination of 2-methyl-3-nitrobenzoate, 2) coupling reaction with 3-aminopiperidine-6,2-dione hydrochloride and 3) reduction of nitro group to an amine group. All three steps were optimized regarding to different key parameters such as: initiator, solvent, temperature, time, molar ratio of the reactants, reducing agents and also purification process. Then lenalidomide was synthesized in the optimized condition and characterized by different spectroscopic methods. The results showed desirable purity and yield which are comparable with the other methods published in literature. Using of solvent free condition for the first step, safe solvents for the other steps, economical and safe reducing agent for the last step, minimizing by-products, simplify purification process and good yield are advantages of our method. These consequences make this procedure cost-effective and compatible with the environment.
Source: Results in Chemistry
Institution: Shiraz University of Medical Sciences
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,870
Award: G1938799975
OpenAlex ID: W4413371257