Synthesis of 3-Aminoazaindazoles via Cu-Catalyzed Cross Coupling of Isocyanides.
| Autor: | Plunkett S; Discovery Process Research, Janssen R&D, Spring House, Pennsylvania 19477, United States., Diccianni JB; Global Discovery Chemistry, Janssen R&D, Spring House, Pennsylvania 19477, United States., Panish R; Discovery Process Research, Janssen R&D, San Diego, California 92121, United States., Balsells J; Discovery Process Research, Janssen R&D, Spring House, Pennsylvania 19477, United States. |
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| Jazyk: | angličtina |
| Zdroj: | Organic letters [Org Lett] 2024 Aug 16; Vol. 26 (32), pp. 6933-6938. Date of Electronic Publication: 2024 Aug 05. |
| DOI: | 10.1021/acs.orglett.4c02707 |
| Abstrakt: | Nitrogen-containing heterocycles are commonly encountered in drug discovery, but the synthesis of such ring structures is not always efficient. Fused heterocyclic rings, in particular, can be challenging to synthesize. Herein, we report a highly convergent synthesis of 3-aminoazaindazoles via a Cu-catalyzed reaction between isocyanides and 3-halo-2-hydrazineylpyridines (and analogues). Reaction optimization through high-throughput experimentation (HTE) identified a novel set of exogenous ligand-free Cu conditions utilizing a cheap and readily available catalyst. The reaction displays high functional group tolerance and has the potential to be highly enabling for medicinal chemistry efforts. A putative mechanism is described as well as preliminary mechanistic experiments. |
| Databáze: | MEDLINE |
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