First Scale-Up Synthesis of WAY-262398, a Novel, Dual-Acting SSRI/5HT1a Antagonist

Nikitenko, Antonia; Alimardanov, Asaf; Afragola, Jay; Schmid, Jean; Kristofova, Livia; Evrard, Deborah; Hatzenbuhler, Nicole T.; Marathias, Vasilios; Stack, Gary; Lenicek, Steve; Potoski, John

doi:10.1021/op8002085.s001

op8002085_si_001.pdf (86.79 kB)

First Scale-Up Synthesis of WAY-262398, a Novel, Dual-Acting SSRI/5HT1a Antagonist

journal contribution

posted on 2009-01-16, 00:00 authored by Antonia Nikitenko, Asaf Alimardanov, Jay Afragola, Jean Schmid, Livia Kristofova, Deborah Evrard, Nicole T. Hatzenbuhler, Vasilios Marathias, Gary Stack, Steve Lenicek, John Potoski

An alternative synthesis of WAY-262398, 1, a novel, dual-acting SSRI/5-HT_1A antagonist, has been developed. The target compound was initially synthesized as a part of diastereomeric mixture which was separated by chiral preparative HPLC. The new route was designed around intermediates suitable for chiral resolution and/or chiral reduction of a suitable intermediate. Both processes had to be employed to achieve the target optical purity.