An efficient synthesis of a 4'-phosphonodifluoromethyl-3'-formyl-phenylalanine containing SRC SH2 ligand.
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.
Shakespeare
W C
WC
ARIAD Pharmaceuticals, Inc., Cambridge, MA 02139-4234, USA.
Bohacek
R S
RS
Narula
S S
SS
Azimioara
M D
MD
Yuan
R W
RW
Dalgarno
D C
DC
Madden
L
L
Botfield
M C
MC
Holt
D A
DA
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
D017611:Fluorine Compounds; D008024:Ligands; D063065:Organophosphonates; D010649:Phenylalanine; D011505:Protein-Tyrosine Kinases; D003545:Cysteine