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Synthesis and radiofluorination of putative NMDA receptor ligands

Abstract

In the course of this work on the synthesis of radioligands for the NMDA receptor the authentic standards and labeling precursors of four compounds with an amidine structure was performed. Synthesis of the precursors followed reaction conditions given in the literature and was successful. The imidoesters used for the synthesis were obtained from their nitriles in a Pinner synthesis, while 2-hydroxybenzylamine was synthesized in a reduction of 2-hydroxybenzonitrile using borane as a reducing agent. After a coupling reaction of the amine and the imidoester in DMF using triethylamine as base the precursors were obtained in good yields and purified by crystallization from methanol. The cyclic standard compound was synthesized directly from 2-(bromomethyl)- benzonitrile and 2-hydroxybenzylamine in a ring closing reaction. Similar to the other precursors, crystallization from methanol produced a pure compound. The authentic standards were synthesized starting from salicylaldehyde. In a four step synthesis the desired ortho-fluoroethoxybenzylamine was obtained in good yield. Coupling of the amine with the respective imidoester or in the case of the cyclic compound 2-(bromomethyl)-benzonitrile gave the desired product which was then purified by column chromatography or by crystallization from ethanol and water. For the labeling procedure 1-bromo-2-[{sub 18}F]fluoroethane was synthesized following a previously published  More>>
Authors:
Publication Date:
Jan 15, 2011
Product Type:
Thesis/Dissertation
Report Number:
Juel-4338
Resource Relation:
Other Information: TH: Diss.; Also available from: http://www.fz-juelich.de/zb/juwel
Subject:
38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY; 62 RADIOLOGY AND NUCLEAR MEDICINE; AMIDINES; CENTRAL NERVOUS SYSTEM; DMSO; FLUORINATION; FLUORINE 18; IN VITRO; IN VIVO; LABELLING; LIGANDS; POSITRON COMPUTED TOMOGRAPHY; RADIOCHEMISTRY; RADIOPHARMACEUTICALS; RECEPTORS; SYNTHESIS
OSTI ID:
21472104
Research Organizations:
Forschungszentrum Juelich GmbH (Germany). Inst. fuer Neurowissenschaften und Medizin (INM), Nuklearchemie (INM-5); Koeln Univ. (Germany)
Country of Origin:
Germany
Language:
English
Other Identifying Numbers:
Other: ISSN 0944-2952; TRN: DE11F9524
Availability:
Commercial reproduction prohibited; INIS; OSTI as DE21472104
Submitting Site:
DEN
Size:
112 pages
Announcement Date:
Sep 02, 2011

Citation Formats

Kronenberg, U. Synthesis and radiofluorination of putative NMDA receptor ligands. Germany: N. p., 2011. Web.
Kronenberg, U. Synthesis and radiofluorination of putative NMDA receptor ligands. Germany.
Kronenberg, U. 2011. "Synthesis and radiofluorination of putative NMDA receptor ligands." Germany.
@misc{etde_21472104,
title = {Synthesis and radiofluorination of putative NMDA receptor ligands}
author = {Kronenberg, U}
abstractNote = {In the course of this work on the synthesis of radioligands for the NMDA receptor the authentic standards and labeling precursors of four compounds with an amidine structure was performed. Synthesis of the precursors followed reaction conditions given in the literature and was successful. The imidoesters used for the synthesis were obtained from their nitriles in a Pinner synthesis, while 2-hydroxybenzylamine was synthesized in a reduction of 2-hydroxybenzonitrile using borane as a reducing agent. After a coupling reaction of the amine and the imidoester in DMF using triethylamine as base the precursors were obtained in good yields and purified by crystallization from methanol. The cyclic standard compound was synthesized directly from 2-(bromomethyl)- benzonitrile and 2-hydroxybenzylamine in a ring closing reaction. Similar to the other precursors, crystallization from methanol produced a pure compound. The authentic standards were synthesized starting from salicylaldehyde. In a four step synthesis the desired ortho-fluoroethoxybenzylamine was obtained in good yield. Coupling of the amine with the respective imidoester or in the case of the cyclic compound 2-(bromomethyl)-benzonitrile gave the desired product which was then purified by column chromatography or by crystallization from ethanol and water. For the labeling procedure 1-bromo-2-[{sub 18}F]fluoroethane was synthesized following a previously published pathway starting from 1,2-dibromoethane. An alternative route of radiosynthesis for this prosthetic group was tested using ethyleneglycole- 1,2-ditosylate. The labeling reaction was performed on one of the precursors testing both DMF and DMSO as solvents and using NaOH as base. Yields of N-(2-fluoroethoxybenzyl)- cinnamamidine were about 78 % at 80 C after 30 minutes in DMSO. The desired product can now be synthesized in sufficient yields for in vitro and in vivo evaluation studies. Labeling on the cyclic precursor was attempted utilizing DMSO as solvent, but no product could be found. (orig.)}
place = {Germany}
year = {2011}
month = {Jan}
}