solid-phase synthesis of methyl n-(pyrimidin-2-yl)glycinate固相合成的甲基n -甘氨酸螯合铁(pyrimidin-2-yl).pdfVIP

Molecules 2003, 8, 467-471 molecules ISSN 1420-3049 Second Eurasian Meeting on Heterocyclic Chemistry “Heterocycles in Organic and Combinatorial Chemistry“ Solid-Phase Synthesis of Methyl N-(pyrimidin-2-yl)glycinate Denis S. Ermolatev and Eugene V. Babaev* Chemistry Department, Moscow State University, Moscow 119899, Russia. Tel.: (+7) 095-939-3020, Fax: (+7) 095-932-8846. * Author to whom correspondence should be addressed; e-mail: babaev@org.chem.msu.su, chemistry@hotbox.ru, Received: 13 May 2003; in revised form: 17 June 2003 / Accepted: 17 June 2003 / Published: 30 June 2003 Abstract: A versatile method for the preparation of N-heteroaryl substituted aminoacid derivatives is suggested. The method avoids facile diketopiperazine formation. Keywords: Solid-phase organic synthesis, N-substituted aminoacids. Introduction Aminoacid derivatives, in particular N-substituted α-aminoacids, are important synthetical precursors and building blocks in combinatorial chemistry. It is sometimes very difficult to obtain such N-substituted acids, especially for the cases when a heterocyclic substituent is attached to the amino group. 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) – also failed due to intramolecular self-condensation between the 2-a