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

Bioorg Med Chem Lett. 2013 Feb 15;23(4):1017-21. doi: 10.1016/j.bmcl.2012.12.027. Epub 2012 Dec 20.

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).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

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

Substances

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