Synthesis of 2,6-difluoro-N-(3-[11C]methoxy-1H-pyrazolo[3,4-b] pyridine-5-yl)-3-(propylsulfonamidio)benzamide as a new potential PET agent for imaging of B-RafV600E in cancers

摘要

The authentic standard 2,6-difluoro-N-(3-methoxy-1H-pyrazolo[3,4-b] pyridine-5-yl)-3-(propylsulfonamidio)benzamide was synthesized from 2,6-difluorobenzoic acid and 3-amino-5-hydroxypyrazole in 9 steps with 1% overall chemical yield. Direct desmethylation of the reference standard with TMSCl/NaI gave the precursor 2,6-difluoro-N-(3-hydroxy-1H-pyrazolo[3,4-b] pyridine-5-yl)-3-(propylsulfonamidio)benzamide for radiolabeling in 70% yield. The target tracer 2,6-difluoro-N-(3-[11C]methoxy-1H-pyrazolo[3,4-b] pyridine-5-yl)-3-(propylsulfonamidio)benzamide was prepared from the precursor with [11C]CH3OTf through O-[11C]methylation and isolated by HPLC combined with SPE in 40-50% decay corrected radiochemical yields with 370-740 GBq/μmol specific activity at end of bombardment (EOB).