放射性同位素碳-14标记氯虫苯甲酰胺的合成与分析

以14C]碳酸钡为放射性同位素原料,通过格氏反应、亲核取代、胺化和缩合等8步放化反应制备了2种放射性同位素碳-14标记的氯虫苯甲酰胺粗品,经反相高效液相色谱(RPHPLC)纯化获得标记物纯品14C-氯虫苯甲酰胺3-溴-N-4-氯-2-甲基-6-(甲氨基羰基-14C]甲酰基)苯基]-1-(3-氯-2-吡啶基)-1H-吡唑-5-甲酰胺(2,55.6 mCi)和3-溴-N-4-氯-2-甲基-6-(甲氨基甲酰基)苯基]-1-(3-氯-2-吡啶基)-1H-吡唑-5-羰基-14C]甲酰胺(3,58.6 mCi)]。以14C]碳酸钡计,两种标记物的总放化收率分别为32%和52%。其结构经核磁共振氢谱、质谱和在线放射性高效液相色谱(HPLC-FSA)分析确认。放射性薄层成像分析(TLC-IIA)、离线放射性高效液相色谱分析(HPLC-LSC)、在线放射性高效液相色谱-二极管阵列检测器/质谱联用(HPLCFSA/PDA/MS)和LSC分析表明,两种14C-氯虫苯甲酰胺的放化纯度分别为99.8%和99.6%,化学纯度分别为99.1%和98.4%,比活度分别为52.45 mCi/mmol和52.30 mCi/mmol。这2种标记物可作为放射性示踪剂,可满足氯虫苯甲酰胺在中国的登记代谢试验研究的需要。

Synthesis and analysis of radioisotope carbon-14 labelled chlorantraniliprole

Two versions of radioisotope carbon-14 labelled chlorantraniliprole, 3-bromo-N-(4-chloro-2-methyl-6-(methylcarbonyl-14C]carbamoyl)phenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide ( 2 , 55.6 mCi, radiochemical purity 99.8%, chemical purity 99.1%, specific activity 52.45 mCi/mmol) and 3-bromo-N-(4-chloro-2-methyl-6-(methylcarbamoyl)phenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonyl-14C]carboxamide ( 3 , 58.6 mCi, radiochemical purity 99.6%, chemical purity 98.4%, specific activity 52.30 mCi/mmol), were synthesized from barium 14C]carbonate via eight-step radioactive reactions including Grignard reaction, nucleophilic substitution, amination reaction, condensation, and etc. Pure C-14 labelled products were obtained after RP-HPLC purification in the overall radiochemical yield of 32% and 52%, respectively. The products were characterized by ESI-MS, 1H NMR and HPLC-FSA. Their technical data was determined by TLC-IIA, HPLC-LSC, HPLC-FSA/PDA/MS and LSC, respectively. These products could be used as radiotracers and meet the requirement of the study on the metabolism of chlorantraniliprole for registration in China.