N-Boc-4,7,10-Trioxa-1,13-tridecanediamine

This N-Boc-protected 4,7,10-trioxa-1,13-tridecanediamine linker is designed for constructing PROTACs that require a flexible, polar tether to connect E3 ligase and target-binding warheads. Its ether-rich internal scaffold can support favorable conformational behavior and solubility characteristics commonly leveraged in targeted protein degradation workflows. The detailed structural and synthetic reactivity considerations are provided below.

Structure: The molecule contains a Boc-protected primary amine and a second primary amine, separated by an ether-containing, aliphatic chain. Its backbone features C–N amide-forming functionality (after derivatization), multiple C–O ether linkages, and saturated carbon centers, contributing to polarity and conformational flexibility.

Reactivity: The Boc group enables orthogonal amine chemistry: deprotection under standard acidolysis conditions reveals the free amine for selective coupling. The remaining primary amine can participate in nucleophilic acyl substitution or amide-bond formation using activated carboxylic acids, NHS/activated esters, or carbodiimide-mediated coupling. Typical PROTAC linker assembly employs inert atmospheres when needed, polar aprotic solvents, and base/acid conditions compatible with amide formation while preserving ether stability.