A new practical tritium labelling procedure using sodium borotritide and tetrakis(triphenylphosphine)palladium(0)

Abstract

SummaryA simple, mild and versatile new tritium ( 3 H) labelling method on a micro scale using sodium borotritide (NaB 3 H 4 ) and a transition-metal complex catalyst is described. 3 H-labelled compounds were prepared effectively by 3 H hydrogenolysis of appendant functional groups in target compounds.The appendant functional group such as bromo, iodo or sulfonate in various target compounds can be replaced by tritium ( 3 H) in moderate yields. The new method was established by optimization of the reaction conditions and examination of its applicability using four types of model substrates in tracer runs. Then, various drug candidates and ligands for drug discovery were labelled with tritium on a micro scale. The specific radioactivity of the 3 H-labelled compounds used for the studies on receptor binding ranged from 12 to 20 Ci/mmol.

Design, Synthesis, and Pharmacokinetics of a Bone-Targeting Dual-Action Prodrug for the Treatment of Osteoporosis

“…It is preferred to introduce the label at as late a step as possible, and therefore, we contemplated tritiation via the reduction of an aryl halide as the last step to give the final conjugate. A recent publication 35 has described palladium-catalyzed reduction of aryl iodides by sodium borohydride (or tritiide), and this methodology seemed to meet to our needs as well as being a procedure operable on a lab scale in house. This approach required an iodo-substituted analogue of 5b.…”

Site-Selective Nickel-Catalyzed Hydrogen Isotope Exchange in N-Heterocycles and Its Application to the Tritiation of Pharmaceuticals

“…Overall, the site-selectivity of the nickel-catalyzed tritiation was consistent with the deuteration studies. The specific activity was >15 Ci/mmol (>0.5 T/molecule) in most cases and met the general requirement for labeled drug candidates in ADME studies . High specific activities of >20 Ci/mmol were obtained with [ 3 H]­varenicline, [ 3 H]­MK-6096, [ 3 H]­MK-7622, [ 3 H]­etoricoxib, and [ 3 H]­papaverine, resulting from exchange of multiple C–H bonds.…”

Multifunctional Deuterated and Tritiated ‘Click’ Molecular Probes via ­Palladium-Mediated Reductive Deiodination of 5-Iodo-1,2,3-Triazoles

“…Reductive deiodination of 5-iodotriazoles was initially explored using the triazole 3 (Table 1) as a model substrate and NaBD 4 or NaBD 3 CN as deuterium sources in the presence of Pd/C (Table 1, entries 1-4, 7, and 8), Pd(PPh 3 ) 4 (Table 1, entry 5), and Pd(PPh 3 ) 2 Cl 2 (Table 1, entry 6) as catalysts, which performed similarly. 23 The reaction was ineffective using NaBD 4 in anhydrous THF (Table 1, entry 1), while in protic solvents such as NMRgrade CD 3 OD (Table 1, entry 2) or D 2 O (Table 1, entry 3) vigorous bubbling was observed, and the expected 5-deutero-1,2,3-triazole 4 was obtained as the only product. Not surprisingly, using EtOH as a cosolvent (Table 1, entry 4) the major product was the 5H-1,2,3-triazole.…”