Carbon‐14 labeling of hydrochlorothiazide via [¹⁴C]formaldehyde production from [¹⁴C]carbon dioxide at ambient temperature

Abstract

[14C]Formaldehyde was synthesized by reducing 14CO2 at ambient temperature with Schwartz's reagent. The [14C]formaldehyde was then used in the radiosynthesis of high specific activity (2.1 GBq/mmol) [14C]hydrochlorothiazide via cyclization of 4‐amino‐5‐chloro‐1,3‐benzenedisulfonamide.

Late-Stage Carbon-14 Labeling and Isotope Exchange: Emerging Opportunities and Future Challenges

“…Using an excess of [ 14 C]CO 2 in the presence of the Schwartz reagent, 59 14 C-formaldehyde was generated in situ and immediately reacted with the sulfonamide precursor 1 to obtain the [ 14 C]hydrochlorothiazide 2 , a diuretic drug ( Scheme 3 , top). 60 Though the radiochemical yield (RCY) from labeled CO 2 was modest (18%), the advantage of this one-pot strategy is not negligible.…”

“…In 2012, radiochemists at AstraZeneca published two strategies based on the partial reduction of CO 2 and its subsequent utilization for ring closure reactions (Scheme ). Using an excess of [ 14 C]­CO 2 in the presence of the Schwartz reagent, 14 C-formaldehyde was generated in situ and immediately reacted with the sulfonamide precursor 1 to obtain the [ 14 C]­hydrochlorothiazide 2 , a diuretic drug (Scheme , top) . Though the radiochemical yield (RCY) from labeled CO 2 was modest (18%), the advantage of this one-pot strategy is not negligible.…”