Scheme 5
From: Synthesis, biological evaluation and clinical trials of Cereblon-based PROTACs
Chemical synthesis of pomalidomide-based PROTACs with two-carbon spacer to facilitate linker attachment. Reagents and conditions: a DIPEA, DMF, 90 °C, 12 h; b Dichloromethane/trifluoroacetic acid (1:1), rt, 2 h; c1 i. Thionyl chloride, DMF or THF, reflux, 4 h; ii. THF, reflux, various times depending on the type of linker (4 h to overnight); c2 HOBT, EDC, triethylamine, THF or DMF, rt, 24 h (time varies depending on the type of linker); c3 HATU, DIPEA, DMF, rt, 24 h (time varies depending on the type of linker).
