title: An efficient synthesis of a 4'-phosphonodifluoromethyl-3'-formyl-phenylalanine containing SRC SH2 ligand.
abstract: A CuBr-mediated, regioselective cross-coupling between methyl 2,5-diiodobenzoate (4) and [(diethoxyphosphinyl)difluoromethyl]zinc bromide is reported. Palladium-catalyzed incorporation of an amino acid side chain, followed by subsequent modifications resulted in the rapid construction of 2. Compound 2 was designed to engage Cys188 of the Src SH2 domain, however, this was not observed spectroscopically.
authors.affiliation: ARIAD Pharmaceuticals, Inc., Cambridge, MA 02139-4234, USA.
authors.forename: W C
authors.initials: WC
authors.lastname: Shakespeare
authors.forename: R S
authors.initials: RS
authors.lastname: Bohacek
authors.forename: S S
authors.initials: SS
authors.lastname: Narula
authors.forename: M D
authors.initials: MD
authors.lastname: Azimioara
authors.forename: R W
authors.initials: RW
authors.lastname: Yuan
authors.forename: D C
authors.initials: DC
authors.lastname: Dalgarno
authors.forename: L
authors.initials: L
authors.lastname: Madden
authors.forename: M C
authors.initials: MC
authors.lastname: Botfield
authors.forename: D A
authors.initials: DA
authors.lastname: Holt
mesh_terms: D001665:Binding Sites; D003545:Cysteine / Q000737:chemistry; D017611:Fluorine Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D008024:Ligands; D015394:Molecular Structure; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000494:pharmacology; D010649:Phenylalanine / Q000031:analogs & derivatives*; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000737:chemistry; D018909:src Homology Domains
chemical_list: D017611:Fluorine Compounds; D008024:Ligands; D063065:Organophosphonates; D010649:Phenylalanine; D011505:Protein-Tyrosine Kinases; D003545:Cysteine