论文部分内容阅读
目的设计合成非甾体类抗炎镇痛药双氯芬酸的活性代谢物4’-羟基双氯芬酸的药物标准品——含4个氘原子标记的4’-羟基双氯芬酸。方法以氘标记苯乙酸为起始原料,经取代、酰胺化反应得4个氘原子标记的中间体4;再以苯酚为原料,经2步反应得中间体7;中间体4与中间体7经Ullmann缩合、脱甲基、水解反应得目标产物——氘标记的4’-羟基双氯芬酸。结果与结论目标化合物的总收率为15.1%,其结构经1H-NMR和MS谱确证,最终产物的同位素丰度超过98%;化学纯度经HPLC测定达98.5%。
OBJECTIVE To design a drug standard for 4’-hydroxy Diclofenac which is the active metabolite of Diclofenac which synthesizes non-steroidal anti-inflammatory analgesic drug - 4’-hydroxy Diclofenac with 4 deuterium atoms. Methods deuterium labeled phenylacetic acid as the starting material, after substitution, amidation reaction 4 deuterium atom labeled intermediate 4; then phenol as raw materials, through 2 steps to give intermediate 7; intermediate 4 and intermediate 7 After Ullmann condensation, demethylation, hydrolysis reaction of the target product - deuterium labeled 4’-hydroxy Diclofenac. Results and Conclusion The total yield of the target compound was 15.1%. Its structure was confirmed by 1H-NMR and MS. The isotopic abundance of the final product was over 98%. The chemical purity was 98.5% by HPLC.