Synthesis of 14C-labelled (R)-α-amino-6,7-dimethyl-3-(phosphonomethyl)-2-quinolinepropanoic acid

The NMDA antagonist (R)-α-amino-6,7-dimethyl-3-(phosphonomethyl)-quinolinepropanoic acid 1 was [ 14 C]-labelled at the 6-methyl group. The quinoline synthesis started from 4-bromo3-methylaniline and the radiolabel was introduced late in the synthetic scheme. The synthesis was accomplished by a NiCl2(dppp)2-catalyzed coupling of the 6-bromoquinoline derivative 6 with a zinc reagent made from [ 14 C]-methyl iodide.