二乙胺是一种重要的有机化工原料, 常应用于医药中间体的合成;同时, 二乙胺基也常成为药物分子中重要的活性结构片段。将N-烷基的氢(H)原子替换为氘(D)原子, 可显著改善药物分子的药代动力学性质。本文发展了使用乙醇-d6为原料, 通过三步反应制得二乙胺-d10的合成方法, 总收率大于40%, 氘代丰率大于98%, 期望能够应用于新型氘代药物的研发过程中。
Diethylamine, one of the important organic chemicals, is widely used in preparation of pharmaceutical intermediates, and is often an important candidate of active fragments of drugs. It is reported that replacing H atom of N-alkyl with D atom would improve drug pharmacokinetic properties. This paper further develops the diethylamine-d10 synthetic process which uses ethanol-d6 as the starting material, with an overall yield of more than 40% for the three reaction steps and the deuterium abundance of diethylamine-d10 being more than 98%. These results are useful for development of novel deuterium drug candidates containing diethylamine-d10 fragments.
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