Forster, Michael published the artcileImproved Multigram Route to a Tricyclic Key Intermediate for Dibenzosuberone-Based p38 Inhibitors via an Optimized Early-Stage Heck Coupling, Application In Synthesis of 620-20-2, the publication is Organic Process Research & Development (2021), 25(8), 1831-1840, database is CAplus.
The p38α MAP kinase has been a heavily investigated target in the last two decades. The structural class of dibenzosuberone-based p38 inhibitors, exemplified by the promising candidate skepinone-L, was already successfully validated in several in vivo models of inflammatory as well as oncol. indications. The increasing demand of key intermediates and final compounds caused by the ongoing development of this inhibitor class urged the conception of an optimized route for the preparation of the core dibenzosuberone scaffold in multigram quantities. Rerouting of the initial discovery route resulted in an almost 4-fold increase of overall yield to 46%, the elimination of chromatog. purification, and the substitution of two critical reaction steps, which hindered a feasible scale-up. The key modification was the introduction and optimization of an early-stage Heck coupling based on Buchwald precatalysts allowing consistently high yields (ca. 90%) at multigram scales with a favorably low Pd loading of 0.1 mol %. This newly developed synthetic access to the dibenzosuberone intermediate 2-chloro-7-hydroxy-10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-one is capable of ensuring the supply of skepinone-L and other candidates during further development.
Organic Process Research & Development published new progress about 620-20-2. 620-20-2 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Benzyl chloride,Benzene, name is 3-Chlorobenzylchloride, and the molecular formula is C7H6Cl2, Application In Synthesis of 620-20-2.
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https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics