Jian Zhigang, Ray Tapan, Wu Amy, Jones Lawrence, Forseth Ry
Novartis Pharmaceuticals Corp, NIBR-DMPK-DMBA-IL, East Hanover, NJ, 07936, USA.
J Labelled Comp Radiopharm. 2014 Oct;57(12):670-3. doi: 10.1002/jlcr.3226. Epub 2014 Oct 14.
The proton exchange reaction was applied to the preparation of stable isotope-labeled LCQ908. For this synthesis, a suitable intermediate with protons alpha to a carbonyl group was first subjected to the H-D exchange reaction; subsequent coupling of a carbonyl group with [(13)C2 ]triethyl phosphonoacetate, followed by hydrogenation and hydrolysis, led to the stable labeled compound. Incorporation of two carbon-13 atoms in the molecule eliminated the presence of undesired M+0.
质子交换反应被应用于制备稳定同位素标记的LCQ908。对于该合成，首先使具有与羰基相邻α位质子的合适中间体进行H-D交换反应；随后羰基与[(13)C2]三乙基膦酰基乙酸酯偶联，接着进行氢化和水解，得到稳定的标记化合物。分子中两个碳-13原子的引入消除了不需要的M+0的存在。
