Work

Multigram Synthesis of 3‐Azabicyclo[3.1.1]heptane Derivatives Including Bicyclic Thalidomide Analogs

Year: 2024

Type: article

Abstract: An efficient approach to the multigram synthesis of 3‐azabicyclo[3.1.1]heptanes is described. The method relied on the intramolecular imide formation in the properly 1,3‐functionalized cyclobutane derivative. In turn, the latter compound was obtained via the diastereoselective Strecker reaction of readily accessible 3‐oxocyclobutanecarboxylate. The resulting synthetic intermediate – 1‐amino‐3‐azabicyclo[3.1.1]heptane‐2,4‐dione – was used to synthesize several monoprotected bicyclic diamines valuable as building blocks for medicinal chemistry, as well as a series of bridged analogs of Thalidomide, a known anticancer drug and a component of proteolysis‐targeting chimeras (PROTACs).

Source: European Journal of Organic Chemistry

DOI: 10.1002/ejoc.202400938