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

Min Wang, Mingzhang Gao, Kathy Miller, Qi-Huang Zheng

Research output: Contribution to journalArticle

10 Citations (Scopus)

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-[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).

Original languageEnglish
Pages (from-to)1017-1021
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number4
DOIs
StatePublished - Feb 15 2013

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Imaging techniques
Neoplasms
Methylation
High Pressure Liquid Chromatography
benzamide
1H-pyrazolo(3,4-b)pyridine
2,6-difluorobenzoic acid
3-amino-5-hydroxypyrazole

Keywords

  • 2,6-Difluoro-N-(3-[C]methoxy-1H-pyrazolo[3,4-b]pyridine-5-yl)- 3-(propylsulfonamidio)benzamide ([C]9)
  • Automation
  • B-Raf
  • Cancer imaging
  • Positron emission tomography (PET)
  • Radiosynthesis

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

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title = "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",
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-[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).",
keywords = "2,6-Difluoro-N-(3-[C]methoxy-1H-pyrazolo[3,4-b]pyridine-5-yl)- 3-(propylsulfonamidio)benzamide ([C]9), Automation, B-Raf, Cancer imaging, Positron emission tomography (PET), Radiosynthesis",
author = "Min Wang and Mingzhang Gao and Kathy Miller and Qi-Huang Zheng",
year = "2013",
month = "2",
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language = "English",
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journal = "Bioorganic and Medicinal Chemistry Letters",
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TY - JOUR

T1 - 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

AU - Wang, Min

AU - Gao, Mingzhang

AU - Miller, Kathy

AU - Zheng, Qi-Huang

PY - 2013/2/15

Y1 - 2013/2/15

N2 - 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).

AB - 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).

KW - 2,6-Difluoro-N-(3-[C]methoxy-1H-pyrazolo[3,4-b]pyridine-5-yl)- 3-(propylsulfonamidio)benzamide ([C]9)

KW - Automation

KW - B-Raf

KW - Cancer imaging

KW - Positron emission tomography (PET)

KW - Radiosynthesis

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U2 - 10.1016/j.bmcl.2012.12.027

DO - 10.1016/j.bmcl.2012.12.027

M3 - Article

VL - 23

SP - 1017

EP - 1021

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 4

ER -