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Straightforward protocol for the efficient synthesis of varied N(1)-acylated (aza)indole 2-/3-alkanoic acids and esters: optimization and scale-up.


AUTHORS

Liedtke AJAndy J , Kim K Kwangho , Stec DF Donald F , Sulikowski GA Gary A , Marnett LJ Lawrence J . Tetrahedron. 2012 12 2; 68(48). 10049-10058

ABSTRACT

A library of approximately 40 N(1)-acylated (aza)indole alkanoic esters and acids was prepared employing a microwave-assisted approach. The optimized synthetic route allows for parallel synthesis, variation of the indole substitution pattern and high overall yield. Additionally, the procedure has been scaled up to yield multi-gram amounts of preferred indole compounds, e.g.: 2′-des-methyl indomethacin 2. The reported compounds were designed as biomedical tools for primary and secondary in vitro and in vivo studies at relevant molecular targets.


A library of approximately 40 N(1)-acylated (aza)indole alkanoic esters and acids was prepared employing a microwave-assisted approach. The optimized synthetic route allows for parallel synthesis, variation of the indole substitution pattern and high overall yield. Additionally, the procedure has been scaled up to yield multi-gram amounts of preferred indole compounds, e.g.: 2′-des-methyl indomethacin 2. The reported compounds were designed as biomedical tools for primary and secondary in vitro and in vivo studies at relevant molecular targets.