Microwave-assisted regioselective direct C-H arylation of thiazole derivatives leading to increased σ1 receptor affinity

Artur Kokornaczyk, Dirk Schepmann, Junichiro Yamaguchi, Kenichiro Itami, Bernhard Wünsch

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


New thiazole analogues 2 of spirocyclic thiophenes 1, which are known to show high σ1 receptor affinities, have been developed as potentially better σ1 receptor ligands. To introduce an aryl group onto the thiazole core of 2 (C4 or C5 positions), we used Pd-catalyzed regioselective C-H arylation reactions. The Pd-catalyzed C5 arylation of 2a could be considerably improved by using microwave irradiation technique. The Pd-catalyzed C4 arylation of thiazole 2a with arylboronic acid 6 could be achieved in the presence of Pd(OAc)2, 1,10-phenanthroline, TEMPO, and LiBF4. Under these conditions, the tertiary amine and the tertiary alcohol were well-tolerated. The regioselective arylation of 2a led to new compounds 2b and 2c, with a 4-tolyl moiety in the C5- and C4-positions, displaying five to nine-fold increased σ1 affinity. The same σ1 affinity of the regioisomeric thiazoles 2b and 2c can be explained by fast rotation around the piperidine-thiazole bond. Compared to spirocyclic thiophenes 1, thiazoles 2 are considerably more polar.

Original languageEnglish
Pages (from-to)327-331
Number of pages5
Issue number2
Publication statusPublished - 2016 Feb 1
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Pharmaceutical Science


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