11C-labelling of heterocyclic aromatic compounds in ring positions: synthesis of [2-11C]indole

Abstract

A first synthetic method for 11C‐labelling of the indole ring has been developed. The route involves the synthesis of β,2‐dinitro‐[β‐11C]styrene 3 by condensation of nitro‐[11C]methane 1 with o‐nitro‐benzaldehyde 2. This reaction was carried out either in ethanol with sodium hydroxide as a catalyst or in glacial acetic acid with ammonium acetate. The subsequent reduction of β,2‐dinitro‐[β‐11C]styrene 3 using titanium(III) chloride yielded [2‐11C]indole 4. The synthesis time was 22 min, starting from nitro‐[11C]methane 1. © 1998 John Wiley & Sons, Ltd.

Acyl Amidines by Pd-Catalyzed Aminocarbonylation: One-Pot Cyclizations and 11C Labeling

“…Heterocyclic derivatives such as 11 C-indole, 35 substituted 11 C-quinoxaline-2,3-diones, 36 a substituted 11 C-quinazoline-…”

“…Heterocyclic derivatives such as 11 C-indole, 35 substituted 11 C-quinoxaline-2,3-diones, 36 a substituted 11 C-quinazoline-2,4(1 H ,3 H )-dione, 37 a substituted 11 C-1,2,4-thiadiazolidine-3,5-dione, 37 [ carbonyl - 11 C]7-methyl-8-phenyl-3-trimethylsilyl-pyrazolo[5.1-c][1,2,4]triazine-(1 H )4-one, 38 and 2-[ 11 C]thymidine 39 have previously been synthesized from 11 C precursors such as [ 11 C]nitromethane, diethyl [ 11 C]oxalate, [ 11 C]carbon dioxide, [ 11 C]lithium trimethylsilyl ynolate, and [ 11 C]phosgene. This is, however, to the best of our knowledge, the first time that [ 11 C]CO has been used in the synthesis of labeled acyl amidines (with 11 C) and the first example of the synthesis of a 11 C-labeled oxadiazole or a ring-atom-labeled heterocycle using [ 11 C]CO.…”

Palladium-Mediated Synthesis of [Carbonyl-11C]acyl Amidines from Aryl Iodides and Aryl Bromides and Their One-Pot Cyclization to 11C-Labeled Oxadiazoles

“…Through a palladium-mediated reaction in 1,4-dioxane, aryl iodides and amidines afforded [carbonyl- 11 C]acyl amidines, which could be cyclized to 11 C-labeled 1,2,4-oxadiazoles without the isolation of the intermediate [carbonyl- 11 C]acyl amidine. The successful adaption of a two-step, one-pot approach is exciting because it provides another route to carbon-11-labeled heterocycles through the use of [ 11 C]carbon monoxide instead of other carbon-11 precursors such as [ 11 C]nitromethane, 34 [ 11 C]carbon dioxide, 35 and [ 11 C]phosgene. 36 …”

An efficient and practical synthesis of [2-11C]indole via superfast nucleophilic [11C]cyanation and RANEY® Nickel catalyzed reductive cyclization

“…9 Starting from Na 14 CN, they first synthesized p-chlorophenoxy [1-14 C]acetonitrile which was reacted with benzyl-protected 3-nitrophenol via a vicarious nucleophilic substitution reaction to afford a 2-(2-nitrophenyl) acetonitrile derivative, which was reduced and cyclized to form 14 C-labeled 4-hydroxyindole. 11 Additionally, two methods for synthesis of 11 C-labeled indole, [2-11 C]indole, were reported in 1998 and 1999 (Scheme 1): 12,13 in the first report, the radioprecursor [ 11 C] CH 3 NO 2 (synthesized from [ 11 C]CH 3 I) was condensed with 2-nitrobenzaldehyde to form β,2-dinitro-[β- 11 C]styrene which when treated with titanium(III) chloride underwent reductive cyclization to form desired [2-11 C]indole. 11 Additionally, two methods for synthesis of 11 C-labeled indole, [2-11 C]indole, were reported in 1998 and 1999 (Scheme 1): 12,13 in the first report, the radioprecursor [ 11 C] CH 3 NO 2 (synthesized from [ 11 C]CH 3 I) was condensed with 2-nitrobenzaldehyde to form β,2-dinitro-[β- 11 C]styrene which when treated with titanium(III) chloride underwent reductive cyclization to form desired [2-11 C]indole.…”

“…10 More recently, Czeskis incorporated carbon-14 into the 2-position on the indole ring through the reaction of 2-nitrobenzyl bromide with Na 14 CN to form 2-(2-nitrophenyl)-[1-14 C]acetonitrile followed by reductive cyclization. 11 Additionally, two methods for synthesis of 11 C-labeled indole, [2- 11 C]indole, were reported in 1998 and 1999 (Scheme 1): 12,13 in the first report, the radioprecursor…”