Abstract
Herein we report an expeditive C-3 vinylation of unprotected 3-iodoindazoles under microwave irradiation. Ten C-5 substituted 3-vinylindazole derivatives, nine of them novel, were synthesized through this method, which proceeds in moderate to excellent yields starting from C-5 substituted 3-iodoindazole derivatives. In all cases, the C-3 vinylated derivative was the only isolated product. This methodology allows access to 3-vinylated indazoles selectively and directly without the need of N-protection. 3-Vinylindazoles could be interesting synthetic intermediates allowing access to biologically active molecules.
Highlights
The indazole ring is a heterocycle which, being an isostere of the indole ring, exhibits a very interesting medicinal chemistry potential
C-5 substituted commercial indazoles the in a N,N-dimethyl3-iodinated derivatives of several
Noteworthy that in the experiment with the N-Boc protected 5-bromo derivative (2c), we achieved to isolate a 5% of the 5-bromo-3-vinyl-N-protected derivative as only coproduct of the reaction, without observation of the C-5 vinylation product
Summary
The indazole ring is a heterocycle which, being an isostere of the indole ring, exhibits a very interesting medicinal chemistry potential. The indazole nucleus is scarcely found in Nature, and to date, only three natural products containing this unit have been isolated: nigellicine [2], nigeglanine [3], and nigellidine [4]. For these reasons, the development of synthetic methodologies aimed at this aromatic moiety is an active area of research. Our research group has been conducting efforts to develop novel 5-HT6 receptor antagonists [5,6,7] In this sense, we are very interested in preparing 5-HT6 receptor ligands based on the indazole nucleus, where a key intermediate in the envisaged synthetic route of these serotonergic ligands is 3-vinylindazole.
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