title: Remote electronic control in the regioselective reduction of succinimides: a practical, scalable synthesis of Ep4 antagonist MF-310.
abstract: A practical large-scale chromatography-free synthesis of EP4 antagonist MF-310, a potential new treatment for chronic inflammation, is presented. The synthetic route provided MF-310 as its sodium salt in 10 steps and 17% overall yield from commercially available pyridine dicarboxylate 7. The key features of this sequence include a unique regioselective reduction of succinimide 2 controlled by the electronic properties of a remote pyridine ring, preparation of cyclopropane carboxylic acid 3 via a Corey-Chaykovsky cyclopropanation, and a short synthesis of sulfonamide 5.
authors: Department of Process Research, Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Highway, Kirkland, Quebec, Canada, H9H 3L1. carmela_molinaro@merck.com
authors: Carmela
authors: C
authors: Molinaro
authors: Danny
authors: D
authors: Gauvreau
authors: Gregory
authors: G
authors: Hughes
authors: Stephen
authors: S
authors: Lau
authors: Sophie
authors: S
authors: Lauzon
authors: Rémy
authors: R
authors: Angelaud
authors: Paul D
authors: PD
authors: O'Shea
authors: Jacob
authors: J
authors: Janey
authors: Michael
authors: M
authors: Palucki
authors: Scott R
authors: SR
authors: Hoerrner
authors: Conrad E
authors: CE
authors: Raab
authors: Rick R
authors: RR
authors: Sidler
authors: Michel
authors: M
authors: Belley
authors: Yongxin
authors: Y
authors: Han
mesh_terms: D002264:Carboxylic Acids / Q000737:chemistry; D002625:Chemistry, Organic / Q000295:instrumentation / Q000379:methods*; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D003460:Crystallization; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry; D015195:Drug Design; D004581:Electronics; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors*; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013237:Stereoisomerism; D013388:Succinimides / Q000737:chemistry*; D013449:Sulfonamides / Q000737:chemistry; D013678:Technology, Pharmaceutical
chemical_list: D002264:Carboxylic Acids; D003521:Cyclopropanes; D006575:Heterocyclic Compounds, 3-Ring; C545573:MF-310; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013388:Succinimides; D013449:Sulfonamides