Synthesis of deuterium-labeled 1-(4-methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea (AR-A014418) as an internal standard for LC–MS analysis

AR-A014418, 1-(4-methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea is a potential drug with potent activities against cancer cell, nociceptive pain and neurodegenerative disorders. In this paper, the stable deuterium-labeled [ 2 H 3 ]AR-A014418 was synthesized in seven steps with 21% overall yield starting from the commercially available [ 2 H 4 ]methanol, p -hydroxybenzaldehyde and 2-amino-5-nitrothiazole. The chemical and isotope purity of the title compound were over 99% and 98%, respectively. This labeled [ 2 H 3 ]AR-A014418 can be used as an internal standard for LC–MS analysis in drug absorption, distribution and other pharmacokinetics studies. Graphic abstract