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| Home > Publications database > 2‐[18F]Fluoro‐5‐iodopyridine ([18F]FIPy): A novel reactive prosthetic group for the fast site specific radiolabeling via Pd‐catalyzed cross coupling reactions |
| Home > Publications database > 2‐[18F]Fluoro‐5‐iodopyridine ([18F]FIPy): A novel reactive prosthetic group for the fast site specific radiolabeling via Pd‐catalyzed cross coupling reactions |
| Conference Presentation (After Call) | FZJ-2019-05724 |
; ;
2019
Please use a persistent id in citations: http://hdl.handle.net/2128/23522
Abstract: Aim: Numerous Pd‐catalyzed cross‐couplings like Sonogashira, Suzuki‐Miyaura, Heck, and Stille reactions proved to be valuable tools for the site specific labeling of biopolymers. The aim of this work was the study of Pd‐catalyzed cross coupling reactions using [18F]FIPy as radiolabeled synthon and 2,2′‐(1,2‐phenylene)‐bis‐(4,4‐dimethyl‐4,5‐dihydrooxazole)‐N,N′‐palladium dichloride (Pd‐BOX‐1) as catalyst. Pd‐BOX‐1 demonstrated exceptional air and moisture stability and excellent catalytic activity in aqueous reaction media. MethodsThe direct reaction of 2‐bromo‐5‐iodopyridine with DABCO followed by anion metathesis using TMSOTf afforded 1‐(5‐iodopyridin‐2‐yl)‐1,4‐diazabicyclo[2.2.2]octan‐1‐ium triflate (1) used as precursor for the preparation of [18F]FIPy. The latter was produced using the “minimalist” protocol. Accordingly, [18F]fluoride was eluted from a QMA cartridge with a solution of 1 in MeOH. MeOH was evaporated at 45°C (250 mbar) within 4 min, DMSO was added, and the resulting solution was heated affording [18F]FIPy, which after the purification by SPE was conjugated to different model compounds by different Pd‐catalyzed (1% of Pd‐BOX‐1) cross‐couplings using aqueous MeCN or DMF as reaction solvent within 10 min. Results18F– recovery from an anion exchange resin using 1 (3 mg) amounted >98%. Heating of the resulting [18F]fluoride onium salt in DMSO at 100°C for 15 min afforded [18F]FIPy in excellent radiochemical conversions (RCCs) of 91 ± 3%. [18F]FIPy was isolated in 61 ± 5% radiochemical yield (RCY) and excellent radiochemical purity (RCP) of >98%. The subsequent Cu and phosphine free Pd‐BOX‐1 catalyzed Sonogashira cross‐coupling with phenylacetylene afforded the corresponding conjugate in an excellent RCC of >89%. Furthermore, Suzuki‐Miyaura, Heck, and Stille reactions with 4‐methylphenyl boronic acid, methyl acrylate, and trimethyl (phenyl)tin, respectively, applied as model coupling partners furnished the corresponding radiofluorinated conjugates in RCCs of 85–98%. Conclusion[18F]FIPy is a valuable radiolabeled prosthetic group easily accessible using the “minimalist” approach. Various Pd‐BOX‐1‐catalyzed cross coupling reactions with [18F]FIPy is a versatile procedure for a fast, high‐yielding, and site specific radiolabeling under relatively mild conditions.
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