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DOI: 10.1055/s-2006-941995
The Parallel Solid-Phase Synthesis of Substituted Oxopiperazin Derivatives
A. Nefzi*, R. T. Santos
Torrey Pines Institute for Molecular Studies, San Diego, USA
Publication History
Publication Date:
21 July 2006 (online)
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Significance
Solid-phase synthesis of tetrasubstituted oxopiperazinium derivatives was demonstrated. p-Methylbenzhydrylamine (MBHA) resin-bound dipeptides 1 were protected with trityl chloride. The resin-bound protected dipeptides reacted with methyl iodide to give dimethylated products 2. The resulting 2 were deprotected with TFA followed by treatment with a variety of carboxylic acids to give triamides 3. The polymer-supported triamides 3 were reduced with BH3×THF to afford polymer-supported triamines 4. The secondary amine was coupled with bromoacetic acid in the presence of diisopropylcarbodiimide (DIC). The resulting bromoacetyl group underwent intramolecular cyclization to form cationic oxopiperazinium which was cleaved from the polymer supports to give an epimeric mixture of the desired tetrasubstituted-5-oxopiperazinium salts 5 (18 examples; 82-95% purity).