Pyridines 39-49 generally underwent 14 N → 15 N exchange when exposed to these modified conditions in moderate to high yield with a clear bias toward electron rich (and therefore more nucleophilic) pyridines (Figure ). Para-aryl and meta-aryl pyridines were well tolerated, though ortho-arylpyridines did not undergo N labeling, likely due to a steric congestion upon triflylation leading to a high barrier for the 6-exo-trig cyclization required for labeling. In these cases, the N to N 56 79% yield 78:22 N to N 59 80% yield 16:84 N to 14 N X = OMe: 48 70% yield 59:41 N to starting material was recovered; for example, when 2,2'-bipyridine and pyriproxyfen (a 2substituted bioactive pyridine) were subjected to the reaction conditions, the starting materials (i.e., the naturally abundant isotopologues) were recovered. Pyrazine 50 and 6/5 fused pyridine 51 also participated, demonstrating the application of the protocol to analogous heterocycles. Elaborated pyridines 52-63 were found to undergo labeling in moderate to high chemical and isotopic yields (Figure ). Since the pyridine nitrogen is more nucleophilic relative to the pyrimidine nitrogen atoms, competing reactive groups were better tolerated in these cases. In general, other aromatic heterocycles did not significantly impede the reaction. Importantly, several substrates bearing more than one pyridine (52, 53, and 54) underwent labeling selectively on the more electron-rich, sterically accessible heterocycle. Small substituents at the 2-position on the pyridine ring were somewhat tolerated (e.g., 53). However, the deleterious effect of 2-substitution is evident when comparing the isotopic yields of etoricoxib (53) and noretoricoxib (54), where the absence of the 2-methyl substituent leads to a five-fold improvement in isotopic labeling. Even electron-deficient pyridines (such as 3-chloropyridine 55 and 4-sulfonamidopyridine 59) participated in the reaction. Enolizable phenylalanine derivative 59 did not undergo racemization (as confirmed by chiral HPLC analysis). Solubility challenges were addressed by adding protective groups to some of the complex pyridines (e.g., acetylation of abiraterone to the prodrug 57) ; this approach, however, was not applicable to nifenazone (61). The use of a mild acid wash to remove unreacted starting material after transamination results in the isolation of the labeled pyridine product with high isotopic purity. This sequence is summarized on the model 4-phenylpyridine substrate in Figure . The isotopic distribution for the labeled product obtained by this method matched that of the labeled dimethyl aspartate nucleophile.