Abstract
A versatile method for the preparation of N-heteroaryl substituted aminoacid derivatives is suggested. The method avoids facile diketopiperazine formation.
Highlights
Aminoacid derivatives, in particular N-substituted α-aminoacids, are important synthetical precursors and building blocks in combinatorial chemistry
The first route (A) is the Dimroth rearrangement of 1-alkylpyrimidinium salts, which in turn can be prepared by alkylation of the endocyclic nitrogen atom of 2-aminopyrimidine
The second route to prepare the target compound I is the nucleophilic substitution in the pyrimidine ring bearing a good leaving group in the alpha position by amines
Summary
In particular N-substituted α-aminoacids, are important synthetical precursors and building blocks in combinatorial chemistry. Attempting to prepare ethyl N-(pyrimidin-2-yl)glycinate via reaction of 2-chloropyrimidine and ethyl glycinate we observed predominant formation of diketopiperazine. An alternative strategy – alkylation of the endocyclic nitrogen of 2-aminopyrimidine with chloroacetic acid (or its esters) followed by Dimroth rearrangement (which usually is a safe route to 2-alkylaminopyrimidines) – failed due to intramolecular self-condensation between the 2-amino group and the acetic acid fragment.
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