title: Multicomponent synthesis of 4-aminophthalazin-1(2H)-ones by palladium-catalyzed isocyanide insertion.
abstract: 4-Aminophthalazin-1(2H)-ones (APOs) are underexplored heterocyclic compounds with promising and diverse biological activities. The classical synthesis of these compounds is tedious and does not allow the regioselective introduction of substituents. Here, we present our full studies on the Pd-catalyzed cross-coupling of substituted o-(pseudo)halobenzoates and hydrazines with isocyanide insertion allowing straightforward access to diversely substituted APOs. We illustrate the advantages of this method compared to other approaches and describe solutions for the limitations we encountered. In addition, we have developed efficient diversifications of this heterocyclic scaffold that allow access to more diverse APOs as well as novel heterocyclic scaffolds.
authors.affiliation: Department of Chemistry & Pharmaceutical Sciences and Amsterdam Institute for Molecules Medicines and Systems (AIMMS), VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
authors.forename: Tjøstil
authors.initials: T
authors.lastname: Vlaar
authors.forename: Pieter
authors.initials: P
authors.lastname: Mampuys
authors.forename: Madeleine
authors.initials: M
authors.lastname: Helliwell
authors.forename: Bert U W
authors.initials: BU
authors.lastname: Maes
authors.forename: Romano V A
authors.initials: RV
authors.lastname: Orru
authors.forename: Eelco
authors.initials: E
authors.lastname: Ruijter
mesh_terms: D002384:Catalysis; D003486:Cyanides / Q000737:chemistry*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry*; D010793:Phthalazines / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C569979:4-aminophthalazin-1(2H)-one; D003486:Cyanides; D009942:Organometallic Compounds; D010793:Phthalazines; D010165:Palladium