title: Integrated cross-coupling strategy for an α-carboline-based Aurora B kinase inhibitor.
abstract: An efficient and practical synthetic process for an α-carboline-based Aurora B kinase inhibitor was achieved using an integrated Pd-catalyzed cross-coupling strategy. The process features a mild and efficient method for construction of the α-carboline core by employing a Pd-catalyzed sequence of Buchwald-Hartwig amination and intramolecular direct C-H arylation at the ortho position of an unsubstituted aniline moiety, which is a key functionality for further derivatization with a Suzuki coupling via Sandmeyer iodination. The process has eliminated expensive starting materials and column chromatography purifications and enabled considerable enhancement of the total yield from 11% to 48%.
authors.affiliation: Chemical Development Laboratories, CMC Center, Takeda Pharmaceutical Company Limited , 17-85, Juso-honmachi 2-chome, Yodogawa-ku, Osaka 532-8686, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Mineno
authors.forename: Misayo
authors.initials: M
authors.lastname: Sera
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ueda
authors.forename: Hideya
authors.initials: H
authors.lastname: Mizufune
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Zanka
authors.forename: Colin
authors.initials: C
authors.lastname: O'Bryan
authors.forename: Jason
authors.initials: J
authors.lastname: Brown
authors.forename: Nick
authors.initials: N
authors.lastname: Scorah
mesh_terms: D000586:Amination; D000814:Aniline Compounds / Q000737:chemistry*; D064107:Aurora Kinase B / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D002243:Carbolines / Q000737:chemistry*; D002384:Catalysis; D006860:Hydrogen Bonding; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*
chemical_list: D000814:Aniline Compounds; D002243:Carbolines; C055571:alpha-carboline; D010165:Palladium; D064107:Aurora Kinase B; C023650:aniline