Synthesis of N-(3-(4-[11C]methylpiperazin-1-yl)−1-(5-methylpyridin-2-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide as a new potential PET agent for imaging of IRAK4 enzyme in neuroinflammation

Xiaohong Wang, Wenzhi Xu, Caihong Miao, Fugui Dong, Wei Li, Min Wang, Mingzhang Gao, Qi-Huang Zheng, Zhidong Xu

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The reference standard N-(3-(4-methylpiperazin-1-yl)−1-(5-methylpyridin-2-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (9) and its demethylated precursor N-(1-(5-methylpyridin-2-yl)−3-(piperazin-1-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-α]pyrimidine-3-carboxamide (8) were synthesized from pyrazolo[1,5-a]pyrimidine-3-carboxylic acid and ethyl 2-cyanoacetate with overall chemical yield 13% in nine steps and 14% in eight steps, respectively. The target tracer N-(3-(4-[11C]methylpiperazin-1-yl)−1-(5-methylpyridin-2-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide ([11C]9) was prepared from its precursor with [11C]CH3OTf through N-[11C]methylation and isolated by HPLC combined with SPE in 50–60% radiochemical yield, based on [11C]CO2 and decay corrected to EOB. The radiochemical purity was >99%, and the specific activity at EOB was 370–1110 GBq/μmol.

Original languageEnglish (US)
Pages (from-to)6-12
Number of pages7
JournalApplied Radiation and Isotopes
Volume132
DOIs
StatePublished - Feb 1 2018

Fingerprint

pyrimidines
enzymes
synthesis
methylation
carboxylic acids
tracers
purity
decay

Keywords

  • Interleukin-1 receptor-associated kinase 4 (IRAK4)
  • N-(3-(4-[C]methylpiperazin-1-yl)−1-(5-methylpyridin-2-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide
  • Neuroinflammation
  • Positron emission tomography (PET)
  • Radiosynthesis

ASJC Scopus subject areas

  • Radiation

Cite this

Synthesis of N-(3-(4-[11C]methylpiperazin-1-yl)−1-(5-methylpyridin-2-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide as a new potential PET agent for imaging of IRAK4 enzyme in neuroinflammation. / Wang, Xiaohong; Xu, Wenzhi; Miao, Caihong; Dong, Fugui; Li, Wei; Wang, Min; Gao, Mingzhang; Zheng, Qi-Huang; Xu, Zhidong.

In: Applied Radiation and Isotopes, Vol. 132, 01.02.2018, p. 6-12.

Research output: Contribution to journalArticle

@article{317dea9ba8a84045893f6b89df0dcd45,
title = "Synthesis of N-(3-(4-[11C]methylpiperazin-1-yl)−1-(5-methylpyridin-2-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide as a new potential PET agent for imaging of IRAK4 enzyme in neuroinflammation",
abstract = "The reference standard N-(3-(4-methylpiperazin-1-yl)−1-(5-methylpyridin-2-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (9) and its demethylated precursor N-(1-(5-methylpyridin-2-yl)−3-(piperazin-1-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-α]pyrimidine-3-carboxamide (8) were synthesized from pyrazolo[1,5-a]pyrimidine-3-carboxylic acid and ethyl 2-cyanoacetate with overall chemical yield 13{\%} in nine steps and 14{\%} in eight steps, respectively. The target tracer N-(3-(4-[11C]methylpiperazin-1-yl)−1-(5-methylpyridin-2-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide ([11C]9) was prepared from its precursor with [11C]CH3OTf through N-[11C]methylation and isolated by HPLC combined with SPE in 50–60{\%} radiochemical yield, based on [11C]CO2 and decay corrected to EOB. The radiochemical purity was >99{\%}, and the specific activity at EOB was 370–1110 GBq/μmol.",
keywords = "Interleukin-1 receptor-associated kinase 4 (IRAK4), N-(3-(4-[C]methylpiperazin-1-yl)−1-(5-methylpyridin-2-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide, Neuroinflammation, Positron emission tomography (PET), Radiosynthesis",
author = "Xiaohong Wang and Wenzhi Xu and Caihong Miao and Fugui Dong and Wei Li and Min Wang and Mingzhang Gao and Qi-Huang Zheng and Zhidong Xu",
year = "2018",
month = "2",
day = "1",
doi = "10.1016/j.apradiso.2017.11.005",
language = "English (US)",
volume = "132",
pages = "6--12",
journal = "Applied Radiation and Isotopes",
issn = "0969-8043",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Synthesis of N-(3-(4-[11C]methylpiperazin-1-yl)−1-(5-methylpyridin-2-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide as a new potential PET agent for imaging of IRAK4 enzyme in neuroinflammation

AU - Wang, Xiaohong

AU - Xu, Wenzhi

AU - Miao, Caihong

AU - Dong, Fugui

AU - Li, Wei

AU - Wang, Min

AU - Gao, Mingzhang

AU - Zheng, Qi-Huang

AU - Xu, Zhidong

PY - 2018/2/1

Y1 - 2018/2/1

N2 - The reference standard N-(3-(4-methylpiperazin-1-yl)−1-(5-methylpyridin-2-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (9) and its demethylated precursor N-(1-(5-methylpyridin-2-yl)−3-(piperazin-1-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-α]pyrimidine-3-carboxamide (8) were synthesized from pyrazolo[1,5-a]pyrimidine-3-carboxylic acid and ethyl 2-cyanoacetate with overall chemical yield 13% in nine steps and 14% in eight steps, respectively. The target tracer N-(3-(4-[11C]methylpiperazin-1-yl)−1-(5-methylpyridin-2-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide ([11C]9) was prepared from its precursor with [11C]CH3OTf through N-[11C]methylation and isolated by HPLC combined with SPE in 50–60% radiochemical yield, based on [11C]CO2 and decay corrected to EOB. The radiochemical purity was >99%, and the specific activity at EOB was 370–1110 GBq/μmol.

AB - The reference standard N-(3-(4-methylpiperazin-1-yl)−1-(5-methylpyridin-2-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (9) and its demethylated precursor N-(1-(5-methylpyridin-2-yl)−3-(piperazin-1-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-α]pyrimidine-3-carboxamide (8) were synthesized from pyrazolo[1,5-a]pyrimidine-3-carboxylic acid and ethyl 2-cyanoacetate with overall chemical yield 13% in nine steps and 14% in eight steps, respectively. The target tracer N-(3-(4-[11C]methylpiperazin-1-yl)−1-(5-methylpyridin-2-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide ([11C]9) was prepared from its precursor with [11C]CH3OTf through N-[11C]methylation and isolated by HPLC combined with SPE in 50–60% radiochemical yield, based on [11C]CO2 and decay corrected to EOB. The radiochemical purity was >99%, and the specific activity at EOB was 370–1110 GBq/μmol.

KW - Interleukin-1 receptor-associated kinase 4 (IRAK4)

KW - N-(3-(4-[C]methylpiperazin-1-yl)−1-(5-methylpyridin-2-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

KW - Neuroinflammation

KW - Positron emission tomography (PET)

KW - Radiosynthesis

UR - http://www.scopus.com/inward/record.url?scp=85033239292&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85033239292&partnerID=8YFLogxK

U2 - 10.1016/j.apradiso.2017.11.005

DO - 10.1016/j.apradiso.2017.11.005

M3 - Article

C2 - 29127936

AN - SCOPUS:85033239292

VL - 132

SP - 6

EP - 12

JO - Applied Radiation and Isotopes

JF - Applied Radiation and Isotopes

SN - 0969-8043

ER -