The synthesis of tritium labelled neurokinin‐1 receptor ligands

Hamill, Terence G.; Burns, H. Donald

doi:10.1002/jlcr.802

Cited by 9 publications

(1 citation statement)

References 4 publications

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“…This can be done by displacing a halogen atom using tritium gas, as in the preparation of 51 2,3,4,9-tetrahydro-1H-carbazoles 52 or neurokinini-1 receptor ligands. 53 Another technique which gives very high specific activity products is tritiation by the catalytic reduction of acetylenic bonds, a method used in the synthesis of labelled 3-hydroxyoxylipins 54 and a pyrrolopyrimidine A (2B) antagonist. 55 Catalytic tritium reduction of 2-(5H)-furanone was used to make 56 labelled c-hydroxybutyric acid.…”

Section: Tritium [ 3 H]mentioning

confidence: 99%

27 Radiochemistry and radiopharmaceuticals

Urch

Welch

2005

Annu. Rep. Prog. Chem., Sect. A

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Section: Tritium [ 3 H]mentioning

confidence: 99%

27 Radiochemistry and radiopharmaceuticals

Urch

Welch

2005

Annu. Rep. Prog. Chem., Sect. A

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Fluoroiodomethane

Landelle¹,

Paquin²

2011

Encyclopedia of Reagents for Organic Synthesis

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Inherent Oxygen Preference in Enolate Monofluoromethylation and a Synthetic Entry to Monofluoromethyl Ethers

2010

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The control of regioselectivity in the alkylation of enolates is one of the oldest research areas in organic chemistry. [1] The ratio of regioisomers formed by C/O-alkylation is sensitive to the extent of substrate enolization, which is highly dependent on the structure of the carbonyl compound, but also on the nature of the alkylating reagent and the reaction conditions, in particular the solvent and base. It has been shown that more C-alkylation tends to be observed with softer nucleophiles, whereas O-alkylation is favored with harder electrophiles. [2,3] However, the complete control of C/O regioselectivity is still a challenge, for example, the regioselective Omethylation of b-ketoesters 1. [3, 4] In 2008, we reported that the trifluoromethylsulfoxinium salt 2 was very effective for the electrophilic trifluoromethylation of carbon-centered nucleophiles. [5] As an extension of our interest in the synthesis of organofluorine compounds, [6] we reveal herein that the electrophilic monofluoromethylation of 1,3-dicarbonyl compounds by the novel monofluoromethylsulfoxinium salts 3 occurs selectively at the oxygen atoms of enolates, rather than at the corresponding carbon atoms, to provide 4, whereas trifluoromethylation by enolate alkylation with 2 takes place at the carbon centers. The resulting previously unknown monofluoromethyl enol ethers 4 of b-ketoesters [7] can be conveniently transformed into monofluoromethyl ethers 5 in high yield by a reduction system based on Pd/C catalysis (Scheme 1). As a consequence, the approach not only constitutes one of the scarce examples of the selective Oalkylation of enolates, but also provides a new synthetic entry to biologically relevant monofluoromethyl ethers, which are of interest to the pharmaceutical and agrochemical industries, and which are difficult to obtain by the direct electrophilic fluoromethylation of alcohols. [8,9] We also described the monofluoromethylation of other oxygen-centered nucleophiles, such as carboxylic acids, phenols, naphthols, alcohols, and sulfonic acids, with the self-stable monofluoromethylating reagents 3. Thus, this approach provides access to a great number of biologically relevant monofluoromethyl esters, ethers, and sulfonates.The novel electrophilic monofluoromethylation reagents 3 were synthesized by the procedure shown in Scheme 2. Phenyl monofluoromethyl sulfoxide (7), [10a,b] prepared from thioanisole (6) in three steps, including nucleophilic substitution of chloride with KF, was converted into sulfoximine 8 under conventional conditions by treatment with NaN 3 / H 2 SO 4 . (Caution! This step involves the generation of explosive hydrogen azide). The stepwise methylation of 8 with Me 3 OBF 4 /K 2 CO 3 followed by methyl trifluoromethanesulfonate gave N,N-(dimethylamino)-S-phenyl-Smonofluoromethyloxosulfonium trifluoromethanesulfonate (3 a) via 9 [10c] as a viscous oil. The trifluoromethanesulfonate 3 a was transformed into the hexafluorophosphate 3 b as colorless crystals with KPF 6 in CH 2 Cl 2 in 88 % yield.We began our inves...

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The synthesis of tritium labelled neurokinin‐1 receptor ligands

Cited by 9 publications

References 4 publications

27 Radiochemistry and radiopharmaceuticals

27 Radiochemistry and radiopharmaceuticals

Fluoroiodomethane

Inherent Oxygen Preference in Enolate Monofluoromethylation and a Synthetic Entry to Monofluoromethyl Ethers

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