Asymmetric Synthesis of a 5,6,7,8-Tetrahydro-1,6-naphthyridine Scaffold Leading to Potent Retinoid-Related Orphan Receptor γt Inverse Agonist TAK-828F
Year: 2020
Type: article
Abstract: An asymmetric synthesis of the tetrahydronaphthyridine scaffold of TAK-828F as a RORγt inverse agonist has been developed. The synthesis features a newly discovered atom-economical protocol for Heck-type vinylation of chloropyridine using ethylene gas, an unprecedented formation of dihydronaphthyridine directly from 2-vinyl-3-acylpyridine mediated by ammonia, and a ruthenium-catalyzed enantioselective transfer hydrogenation as key steps. This represents the first example of the enantioselective synthesis of a 5,6,7,8-tetrahydro-1,6-naphthyridine compound. The new synthesis is also free of chromatography or distillation purification processes and therefore qualifies for extension to large-scale manufacture.
Source: The Journal of Organic Chemistry
Authors: Ryoji Tsuruoka, Naoki Yoshikawa, Takahiro Konishi, Mitsuhisa Yamano
Institution: Takeda (Japan)
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $5,000
OpenAlex ID: W3043838544