First Scale-Up: Problems and Resolutions on the Synthesis of WAY-253752, a Novel, Dual-Acting SSRI/5HT_1A Antagonist

Abstract

An alternative synthesis of WAY-253752, 1, a novel, dual-acting SSRI/5HT 1A antagonist, was developed and used for the first scaleup. Initially, the target compound was synthesized as part of a diasteromeric mixture separated by chiral preparative HPLC. The new route was designed around intermediates suitable for chiral resolution, and its conditions were successfully determined.

Asymmetric Diels–Alder Reaction of 2-Methyl-3-indolylmethanols via in Situ Generation of o-Quinodimethanes

“…Chiral tetrahydrocarbazoles have been recognized as important structural motifs in a diversity of natural products and pharmacological compounds (Figure ) . A number of asymmetric methodologies have been developed for the construction of this type of cyclic architectures .…”

Enantioselective gold-catalyzed intermolecular [2+2] versus [4+2]-cycloadditions of 3-styrylindoles with N-allenamides: observation of interesting substituent effects

“…5 b However, to the best of our knowledge, a cycloaddition mode which depends on the electronic nature of the substituent is unprecedented in asymmetric gold catalysis. As a part of our continual program in developing asymmetric gold-catalyzed cycloadditions, 9 we report the gold catalyzed enantioselective [2+2] and [4+2] cycloadditions of 3-styrylindoles with N -allenamides ( Scheme 1b ), furnishing synthetically valuable tetrahydrocarbazole 10 , 11 and 3-cyclobutylindole 12 , 13 scaffolds, respectively, which frequently appear in natural products and bioactive compounds ( Fig. 1 ).…”

Enantioselective Intramolecular Crossed Rauhut–Currier Reactions through Cooperative Nucleophilic Activation and Hydrogen‐Bonding Catalysis: Scope and Mechanistic Insight

“…[32] This architecture widely exists in various naturally occurring alkaloids and synthetic analogues of medicinal importance, [33] some of which can be potentially used as tumor-growth inhibitors and protein kinase C inhibitors. [34] Notably, trebenzomine analogue 7 can be easily synthesized in 54 % overall yield through an operationally simple three-step procedure from 2 h, [35] thus indicating that potentially medicinal candidates can be readily accessed from simple starting materials.…”