Palladium-mediated oxidative carbonylation reactions for the synthesis of C-11-radiolabelled ureas

TY - JOUR

T1 - Palladium-mediated oxidative carbonylation reactions for the synthesis of C-11-radiolabelled ureas

AU - Kealey, Steven

AU - Husbands, Stephen M.

AU - Bennacef, Idriss

AU - Gee, Antony D.

AU - Passchier, Jan

PY - 2014/4

Y1 - 2014/4

N2 - Palladium(II)-mediated oxidative carbonylation reactions have been used to synthesize C-11-radiolabelled ureas via the coupling of amines with [C-11]carbon monoxide, in a one-pot process. Following trapping of (CO)-C-11 in a solution of copper(I) tris(3,5-dimethylpyrazolyl)borate, homocoupling reactions of primary aliphatic amines proceed in the presence of Pd(PPh3)(2)Cl-2 to give the corresponding N,N-disubstituted [C-11]ureas. Secondary amines do not produce the corresponding N,N,N,N-tetrasubsituted [C-11]ureas under these conditions. This difference in reactivity allows for the formation of unsymmetrical N,N',N'-trisubstituted [C-11]ureas using a mixture of a primary amine and a reactive secondary amine. The potential use of this method in positron emission tomography (PET) was demonstrated by the synthesis of the M1 muscarinic acetylcholine receptor radiotracer, [C-11-carbonyl]GSK1034702.

AB - Palladium(II)-mediated oxidative carbonylation reactions have been used to synthesize C-11-radiolabelled ureas via the coupling of amines with [C-11]carbon monoxide, in a one-pot process. Following trapping of (CO)-C-11 in a solution of copper(I) tris(3,5-dimethylpyrazolyl)borate, homocoupling reactions of primary aliphatic amines proceed in the presence of Pd(PPh3)(2)Cl-2 to give the corresponding N,N-disubstituted [C-11]ureas. Secondary amines do not produce the corresponding N,N,N,N-tetrasubsituted [C-11]ureas under these conditions. This difference in reactivity allows for the formation of unsymmetrical N,N',N'-trisubstituted [C-11]ureas using a mixture of a primary amine and a reactive secondary amine. The potential use of this method in positron emission tomography (PET) was demonstrated by the synthesis of the M1 muscarinic acetylcholine receptor radiotracer, [C-11-carbonyl]GSK1034702.

KW - PET

KW - carbon-11

KW - carbon monoxide

KW - carbonylation

KW - palladium

KW - ureas

KW - POSITRON-EMISSION-TOMOGRAPHY

KW - SITU ACTIVATED AMINES

KW - EFFICIENT SYNTHESIS

KW - MILD CONDITIONS

KW - MONOXIDE

KW - COMPLEXES

KW - PRESSURE

KW - CATALYST

KW - AMIDES

U2 - 10.1002/jlcr.3151

DO - 10.1002/jlcr.3151

M3 - Article

SN - 0362-4803

VL - 57

SP - 202

EP - 208

JO - JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS

JF - JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS

IS - 4

ER -