Formamide as an Unconventional Amine Protecting Group for PET Radiochemistry

Abstract

We developed a versatile, rapid, and robust high‐yielding radiochemistry‐adapted protocol utilizing formamides as masking groups for secondary and tertiary amines. Selective reducing conditions were devised using borane reagents. In this protocol formamide functionalities were found to have an orthogonal reactivity to most other carbonyl functions, while effectively protecting amines from oxidative degradation. We exemplify the newly developed methodology by synthesizing a µ‐opioid PET radiotracer and a phenethylamine PET radiotracer analogue.

Amide Synthesis through the In Situ Generation of Chloro- and Imido-Phosphonium Salts

“…Using general method A (100 mg of 4-iodo-benzoic acid, 159 mg of triphenylphosphine, 110 mg of N -chlorophthalimide, 98 mg of N- benzylmethylamine, and 3 mL of MeCN), the product was purified by column chromatography ( R f = 0.48, DCM/hexane/EtOAc = 1:2.5:1) and isolated in 87% yield, 123 mg. Spectra data matched reported data …”

“…Using general method A (100 mg of 4-methoxy-benzoic acid, 259 mg of triphenylphosphine, 179 mg of N-chlorophthalimide, 211 mg of benzylamine, and 3 mL of toluene), the product was purified by column chromatography (R f = 0.14, hexane/EtOAc = 3:1) and isolated in 84% yield, 166 mg. Spectra data matched reported data. 41 1 H NMR (400 MHz, CDCl 3 ) δ 7.68 (d, J = 8.8 Hz, 2H), 7.29−7.11 (m, 4H), 6.82 (d, J = 8.9 Hz, 2H), 6.82 (d, J = 8.9 Hz, 2H), 6.40 (s, 1H), 3.75 (s, 3H). 13 C{1H} NMR (100 MHz, CDCl 3 ) δ 166.8, 162.3, 138.6, 128.8, 128.7, 127.9, 127.5, 126.7, 113.8, 55.4, 44.1.…”

Electron and Positron Scattering by the Formamide Molecule

“…In this way, it is interesting to understand the process of electron and positron scattering by the formamide molecule. In particular, obtaining cross sections from positron collision with formamide molecule is of paramount importance, since studies have been carried out to synthesize the formamide molecule to form radiotracers for clinical use . These studies have a direct application in the technique of positron emission tomography (PET), which is a powerful diagnostic imaging tool to detect anomalies in living tissue, such as tumors.…”