New synthesis route for the preparation of pomalidomide

Daowei Huangab, Chengwu Shenc, Wenya Wangab, Lei Huangab, Feng Niab & Jianqi Liab*a Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, Shanghai, Chinab Shanghai Engineering Research Center of Pharmaceutical Process, Shanghai, Chinac Shandong Provincial Hospital, Shandong University, Jinan, ChinaCONTACT Jianqi Li lijianqb@126.com Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, Shanghai, 201203, China.Daowei Huang and Chengwu Shen contributed equally to this paper.Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.Supplemental data (Full experimental details; physical and spectral data of the compounds 11 and pomalidomide 1; HPLC purity of compound 9, 11, and 1; and the analysis of palladium content of product 1) can be accessed on the publisher’s website.ABSTRACTA new route for the preparation of pomalidomide is described in the study. The synthetic procedure starts from 4-nitroisobenzofuran-1,3-dione and 3-aminopiperidine-2,6-dione hydrochloride via a three-step reaction resulting in a total yield of 65% with a high-performance liquid chromatographic (HPLC) purity of 99.56% and a low palladium residue level of 2 ppm. This method can be deemed as an efficient, practical, and environmentally friendly synthetic route for the preparation of pomalidomide.GRAPHICAL ABSTRACT