Microwave-accelerated fluorodenitrations and nitrodehalogenations: expeditious routes to labeled PET ligands and fluoropharmaceuticals

LaBeaume, Paul; Placzek, Michael S.; Daniels, Mathew; Kendrick, Ian; Ng, Patrick; McNeel, Melissa; Afroze, Roushan; Alexander, Abigail Louise; Thomas, Rhiannon; Kallmerten, Amy E.; Jones, Graham B.

doi:10.1016/j.tetlet.2010.02.042

Cited by 33 publications

(11 citation statements)

References 21 publications

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“…The 4-thia precursor 5 was synthesized analogously to previously published methyl 3-(12-iodododecylthio)propionate [6] by coupling 1,12-dibromododecane to methyl 3-mercaptopropanoate.…”

Section: Resultsmentioning

confidence: 99%

Microwave-assisted radiosynthesis of [18F]fluorinated fatty acid analogs

Belanger

Pandey

DeGrado

2011

Nuclear Medicine and Biology

118

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Microwave reactors remain largely underutilized in the field of PET chemistry. This is particularly unfortunate since microwave synthesis elegantly addresses two of the most critical issues of PET radiochemistry with short-lived radionuclides: reaction rate and side-product formation. In this study we investigate the efficiency of synthesis of terminally [ 18 F]fluorinated fatty acid analogs using a commercial microwave reactor in comparison with conventional heating.Methods-The labeling precursors were methyl esters of terminally substituted alkyl bromides and iodides. Duration and temperatures of the [ 18 F]fluorination reaction were varied. Chemical and radiochemical purities, and radiochemical yields were investigated for conventional (CH) and microwave-assisted (MW) radiosyntheses.Results-The results demonstrate that microwave heating enhanced [ 18 F]fluoride incorporation to >95% (up to 55% improvement), while reducing reaction times to 2 min (~10-fold reduction) or temperatures to 55-60°C (20°C reduction). Overall decay-corrected radiochemical yields of purified [ 18 F]fluoro fatty acids were higher (MW=49.0 ± 4.5%, CH=23.6 ± 3.5%, p<0.05) with microwave heating and side-products were notably fewer.Conclusion-For routine synthesis of [ 18 F]fluoro fatty acid analogs, microwave heating is faster, milder, cleaner, less variable and higher yielding than conventional heating and therefore the preferred reaction method.

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“…The 4-thia precursor 5 was synthesized analogously to previously published methyl 3-(12-iodododecylthio)propionate [6] by coupling 1,12-dibromododecane to methyl 3-mercaptopropanoate.…”

Section: Resultsmentioning

confidence: 99%

Microwave-assisted radiosynthesis of [18F]fluorinated fatty acid analogs

Belanger

Pandey

DeGrado

2011

Nuclear Medicine and Biology

118

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“…Finally, and with a potential view to studying biodistribution of these ligands via in vivo imaging methods, proof (＃（ 3 CN can be used) of principal was demonstrated for installation of a fluoro group via nucleophilic displacement. Following extensive optimization of parameters (temp, time, and stoichiometry), nitroarene 17 was subjected to MW induced fluorodenitration to give 18 in good yield within 15 mins at 140 ∘ C using 2 equivalents of TBAF in DMSO (Scheme 5) [19]. Given the half-life of its emitting sister 18 F isotope (∼120 mins) this rapid transformation is compatible with late stage labeling for PET imaging.…”

Section: Resultsmentioning

confidence: 99%

Flow and Microwave Induced Pellizzari Reactions: Synthesis of Heterocyclic Analogues of the Benzoxazepine Antipsychotic Agents Loxapine and JL-13

Ranasinghe

Mongeau

Yuan

et al. 2017

Advances in Chemistry

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An expeditious route to fused triazolo-pyrido benzoxazepines has been developed using flow and microwave-mediated cyclization chemistry. A range of substituted aryl hydrazides are coupled with a core chloroimine in good to excellent yield via a Pellizzari type process, producing 1,2,4-triazolo-pyrido [2,3-b] [1,5] benzoxazepines with structural similarity to known antipsychotic agents. Modifications allow for strategically functionalized derivatives, and installation of a fluoro group for use in PET imaging is also demonstrated. Given the affinity of the tricyclic core for 5-HT and dopamine receptors, the derivatives are expected to find utility in CNS research.

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“…In 2010, Jones and co-workers further extended this methodology through the development of the microwave-accelerated copper-catalyzed nitrodehalogenation of 5-bromoindoles. 222 In 2021, the Waldvogel group showed that tetrabutylammonium nitrite is also a safe NO 2 source in the electrochemical nitration of aromatic compounds 388 (Scheme 107). 223 The reaction proceeded mainly with electron-rich arenes; the yields were significantly dependent on the na-ture of the substrate.…”

Section: Organic Nitritesmentioning

confidence: 99%

Organic Nitrating Reagents

Patra¹,

Mosiagin²,

Katayev³

et al. 2022

Synthesis

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Nitro compounds are vital raw chemicals that are widely used in academic laboratories and industries for the preparation of various drugs, agrochemicals, and materials. Thus, nitrating reactions are of great importance for chemists and are even taught in schools as one of the fundamental transformations in organic synthesis. Since the discovery of the first nitrating reactions in the 19th century, progress in this field has been constant. Yet, for many years the classical electrophilic nitration approach using a mixture of strong mineral acids dominated the field. However, in recent decades, the attention of researchers has focused on new reactivity and new reagents that can provide access to nitro compounds in a practical and straightforward way under mild reaction conditions. Organic nitrating reagents have played a special role in this field since they have enhanced reactivity. They also allow nitration to be carried out in an ecofriendly and sustainable manner. This review examines the development and application of organic nitrating reagents.1 Introduction2 Organic Nitrating Reagents2.1 Alkyl Nitrites2.2 Nitroalkanes2.3 Alkyl Nitrates2.4 N-Nitroamides2.5 N-Nitropyrazole2.6 N-Nitropyridinium Salts3 Organic Nitrating Reagents Generated In Situ3.1 Acyl Nitrates3.2 Trimethylsilyl Nitrate3.3 Nitro Onium Salts4 Organic Nitronium Salts5 Organic Nitrates and Nitrites5.1 Ammonium Nitrates5.2 Heteroarylium Nitrates5.3 Other Organic Nitrates5.4 Organic Nitrites6 Conclusion and Outlook

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Microwave-accelerated fluorodenitrations and nitrodehalogenations: expeditious routes to labeled PET ligands and fluoropharmaceuticals

Cited by 33 publications

References 21 publications

Microwave-assisted radiosynthesis of [18F]fluorinated fatty acid analogs

Microwave-assisted radiosynthesis of [18F]fluorinated fatty acid analogs

Flow and Microwave Induced Pellizzari Reactions: Synthesis of Heterocyclic Analogues of the Benzoxazepine Antipsychotic Agents Loxapine and JL-13

Organic Nitrating Reagents

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