Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC

• Bingnan Wang,
• Yong Lu and
• Chuo Chen

Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28

• Bingnan Wang Yong Lu Chuo Chen Department of Biochemistry, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9038, USA 10.3762/bjoc.21.28 Abstract Chemically induced dimerization is a powerful tool for studying protein function, wherein the IMiD (the “immunomodulatory

• contamination. Keywords: glutarimide; IMiD; impurity; nucleophilic acyl substitution; PROTAC; Introduction Targeted protein degradation capitalizing on the concept of chemically induced dimerization has emerged as a new therapeutic approach recently [1]. In particular, the modularity of proteolysis targeting

• addition intermediate is stabilized by an oxygen atom only. As such, the erosion of 3 by taurine was minimal. Conclusion Nucleophilic aromatic substitution of 4-fluorothalidomide (1) has provided a convenient entry to the IMiD class of PROTAC molecules. Although the yield of the desired product is