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-Raf(V600E) in cancers.

Abstract

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-[(11)C]methoxy-1H-pyrazolo[3,4-b]pyridine-5-yl)-3-(propylsulfonamidio)benzamide was prepared from the precursor with [(11)C]CH(3)OTf through O-[(11)C]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).

• Authors: Min Wang, Mingzhang Gao, Kathy D Miller, Qi-Huang Zheng
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 23 Issue 4 Pg. 1017-21 (Feb 15 2013) ISSN: 1464-3405 [Electronic] England
• PMID: 23294704 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Benzamides
• Pyrazoles
• Pyridines
• Radiopharmaceuticals
• BRAF protein, human
• Proto-Oncogene Proteins B-raf

Topics

• Benzamides (chemical synthesis, chemistry)
• Humans
• Neoplasms (diagnostic imaging, metabolism)
• Positron-Emission Tomography (methods)
• Proto-Oncogene Proteins B-raf (analysis)
• Pyrazoles (chemistry, pharmacology)
• Pyridines (chemical synthesis, chemistry)
• Radiopharmaceuticals (chemical synthesis)