title: Synthesis of vaniprevir (MK-7009): lactamization to prepare a 20-membered [corrected] macrocycle.
abstract: Development of a practical synthesis of MK-7009, a 20-membered [corrected] macrocycle, is described. A variety of ring-closing strategies were evaluated, including ring-closing metathesis, intermolecular palladium-catalyzed cross-couplings, and macrolactamization. Ring closure via macrolactamization was found to give the highest yields under relatively high reaction concentrations. Optimization of the ring formation step and the synthesis of key intermediates en route to MK-7009 are reported.
authors.affiliation: Department of Process Chemistry, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, United States. zhiguo_song@merck.com
authors.forename: Zhiguo J
authors.initials: ZJ
authors.lastname: Song
authors.forename: David M
authors.initials: DM
authors.lastname: Tellers
authors.forename: Michel
authors.initials: M
authors.lastname: Journet
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Kuethe
authors.forename: David
authors.initials: D
authors.lastname: Lieberman
authors.forename: Guy
authors.initials: G
authors.lastname: Humphrey
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Peng
authors.forename: Marjorie S
authors.initials: MS
authors.lastname: Waters
authors.forename: Daniel
authors.initials: D
authors.lastname: Zewge
authors.forename: Andrew
authors.initials: A
authors.lastname: Nolting
authors.forename: Dalian
authors.initials: D
authors.lastname: Zhao
authors.forename: Robert A
authors.initials: RA
authors.lastname: Reamer
authors.forename: Peter G
authors.initials: PG
authors.lastname: Dormer
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Belyk
authors.forename: Ian W
authors.initials: IW
authors.lastname: Davies
authors.forename: Paul N
authors.initials: PN
authors.lastname: Devine
authors.forename: David M
authors.initials: DM
authors.lastname: Tschaen
mesh_terms: D002384:Catalysis; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D003500:Cyclization; D003521:Cyclopropanes; D006865:Hydrogenation; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry*; D054833:Isoindoles; D007769:Lactams / Q000737:chemistry*; D047029:Lactams, Macrocyclic; D007930:Leucine / Q000031:analogs & derivatives; D047028:Macrocyclic Compounds / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry; D011392:Proline / Q000031:analogs & derivatives; D013449:Sulfonamides
chemical_list: D003521:Cyclopropanes; D007211:Indoles; D054833:Isoindoles; D007769:Lactams; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D013449:Sulfonamides; D010165:Palladium; D011392:Proline; C540393:vaniprevir; D007930:Leucine