The development of 11C-carbonylation chemistry: A systematic view

Radiosynthesis of a Bruton's tyrosine kinase inhibitor, [11C]Tolebrutinib, via palladium‐NiXantphos‐mediated carbonylation

“…13 [ 11 C]carbon monoxide ([ 11 C]CO) has become increasingly recognized as a versatile 11 C-labeling agent for radiotracer production. 6,11,[14][15][16][17][18] [ 11 C]CO has been extensively used to synthesize 11 C-labeled amides, esters, carboxylic acids, ketones, and ureas and less commonly for acid chlorides, carabamate esters and aldehydes. [14][15][16][17][18] While 11 C-aminocarbonylation reactions are among the most common reactions with [ 11 C]CO, only a few labeled compounds bearing the N-[ 11 C]acrylamide functionality are known.…”

“…6,11,[14][15][16][17][18] [ 11 C]CO has been extensively used to synthesize 11 C-labeled amides, esters, carboxylic acids, ketones, and ureas and less commonly for acid chlorides, carabamate esters and aldehydes. [14][15][16][17][18] While 11 C-aminocarbonylation reactions are among the most common reactions with [ 11 C]CO, only a few labeled compounds bearing the N-[ 11 C]acrylamide functionality are known. [19][20][21] Despite hundreds of labeled compounds prepared, only four PET radiopharmaceuticals synthesized by [ 11 C] CO have been administered for human use, and all reported examples have relied on a high-pressure autoclave methodology.…”

“…[19][20][21] Despite hundreds of labeled compounds prepared, only four PET radiopharmaceuticals synthesized by [ 11 C] CO have been administered for human use, and all reported examples have relied on a high-pressure autoclave methodology. 14,18 11 C-carbonylations that can be executed at atmospheric pressure have emerged in recent years to trap [ 11 C]CO in small volume vessels, including chemical complexation, use of soluble carrier gases, and ex situ production of [ 11 C]CO. 17,18 Two recent reviews have concluded that the lack of commercially available synthesis modules for 11 C-carbonylations and Good Manufacturing Practice (GMP) production is among the most important challenges to overcome for dissemination of [ 11 C]CO chemistry to the wider community and is attributed to the reason that so few PET tracers synthesized from [ 11 C]CO have been translated to human subjects. 17,18 Herein, we report the development of a novel Pd-NiXantphos-mediated 11…”

Development of a fully automated low‐pressure [11C]CO carbonylation apparatus

“…Although [ 11 C]carbon monoxide ([ 11 C]CO) has been applied in radiochemistry for several decades, it has not yet gained ground as a mainstream labeling agent in the positron emission tomography (PET) radiochemistry community 1,2 . Nevertheless, many important methodological developments have been made that have facilitated its use as a synthon in PET radiochemistry, 3–6 in particular in transition metal‐mediated 11 C‐carbonylation reactions 7–12 . The most explored methodology to date is probably the high‐pressure autoclave method, 13 but due to its technically sophisticated setup, the focus has recently been directed to different ways of performing 11 C‐carbonylation reactions at ambient pressure 14–16 .…”

Robust and General Procedure for Carbon Isotope Labeling of Linear Urea Derivatives with Carbon Dioxide

“…11 Nevertheless, its utilization is not trivial due to the inherent toxicity and the timeconsuming production, which might require harsh conditions. 12 In addition, [ 14 C]CO was described to undergo radiolysis and its limited stability prevents storage. 13 [ 11/14 C]Carbon dioxide 14 fulfills the handiest criteria as precursor: it is the primary radioactive carbon source from which derive all 11 C-and utilized both for 11 C and 14 C labeling, but it is limited by a moderate functional group compatibility.…”