Synthesis of N-(3-(4-[ 11 C]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

• Published in: Applied radiation and isotopes 2018-02, Vol.132, p.6-12
• Main Authors: Wang, Xiaohong, Xu, Wenzhi, Miao, Caihong, Dong, Fugui, Li, Wei, Wang, Min, Gao, Mingzhang, Zheng, Qi-Huang, Xu, Zhidong
• Format: Article
• Language: English
• ISSN: 1872-9800
• DOI: 10.1016/j.apradiso.2017.11.005

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-[ C]methylpiperazin-1-yl)-1-(5-methylpyridin-2-yl)-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide ([ C]9) was prepared from its precursor with [ C]CH OTf through N-[ C]methylation and isolated by HPLC combined with SPE in 50-60% radiochemical yield, based on [ C]CO and decay corrected to EOB. The radiochemical purity was >99%, and the specific activity at EOB was 370-1110 GBq/μmol.