Synthesis of [11C]CX-6258 as a new PET tracer for imaging of Pim kinases in cancer

The reference standard CX-6258 {(E)-5-chloro-3-((5-(3-(4-methyl-1,4-diazepane-1-carbonyl)phenyl)furan-2-yl)methylene)indolin-2-one, 4a} and its desmethylated precursor N-desmethyl-CX-6258 {(E)-3-((5-(3-(1,4-diazepane-1-carbonyl)phenyl)furan-2-yl)methylene)-5-chloroindolin-2-one, 5} for radiolabeling were synthesized from 5-bromo-2-furaldehyde and 3-carboxybenzeneboronic acid in 3 and 4 steps with 29–49% and 24–32% overall chemical yield, respectively. The target tracer [11C]CX-6258 {(E)-5-chloro-3-((5-(3-(4-[11C]methyl-1,4-diazepane-1-carbonyl)phenyl)furan-2-yl)methylene)indolin-2-one, [11C]4a} was prepared from N-desmethyl-CX-6258 (5) with [11C]CH3OTf under basic condition (2 N NaOH) through N-[11C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 40–50% radiochemical yield based on [11C]CO2 and decay corrected to end of bombardment (EOB) with 370–1110 GBq/μmol specific activity at EOB.

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