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

10 December 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

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 synthe¬size 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).

Keywords

bicyclic compounds
imides
cyclobutane
thalidomide
building blocks

Supplementary materials

Title
Description
Actions
Title
Supporting Information
Description
Supporting Information containing experimental details, compound characterization data, and copies of NMR spectra.
Actions

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.