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Synthesis 2006(2): 243-246  
DOI: 10.1055/s-2005-918503
PAPER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of 4-Arylethynyl-2-methyloxazole Derivatives as mGluR5 Antagonists­ for Use in the Treatment of Drug Abuse

Yasuyoshi Iso*, Alan P. Kozikowski
Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612, USA
Fax: +1(312)9967107; e-Mail: yasuyoshi.isou@shionogi.co.jp;
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Publication History

Received 6 June 2005
Publication Date:
21 December 2005 (online)

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Abstract

In structure-activity relationship studies directed toward the use of mGluR5 antagonists in the treatment of drug abuse, we sought a convenient means for gaining access to the oxazole analogues of MTEP. Toward this end, the aldehyde group in 2-meth­yloxazole-4-carboxaldehyde was successfully converted to a trimethylsilylethynyl group via the preparation of a dibromoolefin, conversion to acetylide using NaHMDS and MeLi, and trapping with TMSCl. The resulting versatile intermediate, 2-methyl-4-[(trimethylsilyl)ethynyl]oxazole, was subjected to a modified Sonogashira coupling reaction involving an in situ desilylation reaction with Bu4NF and palladium-catalyzed coupling with an aryl or heteroaryl iodide to give the desired oxazole analogues.

Key words

alkynes - cyclizations - lithiation - palladium - cross-coupling