A one-pot radioiodination of aryl amines via stable diazonium salts: preparation of <sup>125</sup>I-imaging agents

Sloan, Nikki L.; Luthra, Sajinder K.; McRobbie, Graeme; Pimlott, Sally L.; Sutherland, Andrew

doi:10.1039/c7cc06211g

Cited by 24 publications

(20 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To expand the range of substituted pyridyl side-chains, two nitro-analogues were subjected to a chemoselective reduction using tin dichloride, which allowed access to amino-analogues 7k and 7l. 19 Finally, various deprotection strategies to access the parent amino acids were explored, however, direct acid-mediated removal of both the amine and carboxylic acid protecting groups was found to be the most efficient approach, giving all 12 structural analogues 8a-l in high yields (86-99%). Scheme 2.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Fluorescent Properties of β-Pyridyl α-Amino Acids

et al. 2019

Self Cite

View full text Add to dashboard Cite

RESULTS AND DISCUSSIONThe first stage of the synthesis of the -pyridyl -amino acids involved the preparation of suitably protected enone-derived -amino acids (Scheme 1). Initially, N-trityl protected phosphonate ester 3 was prepared in three-steps (92% overall yield) from L-aspartic acid 1. 13 Following protection of the amino and carboxylic acid groups, the key step involved the highly regioselective reaction of the anion of dimethyl methylphosphonate with the sterically accessible -methyl ester of 2 to give phosphonate ester 3. Horner-Wadsworth-Emmons reaction of 3 with a wide range of aldehydes under mild conditions, gave enones 4a-j, exclusively as the E-isomers. 14,15 The focus of this project was to prepare aryl substituted pyridyl side-chains and therefore, benzaldehyde derivatives were mainly used to explore the scope of this reaction. As expected, the majority of these gave high yields of the E-enones (66-95%), although highly electron-rich aldehydes required longer reaction times (120 h) and gave more modest yields (e.g. 4e). Scheme 1. Synthesis of Enone-Derived -Amino Acids 4a-j a a Isolated yields are shown. peptide synthesizer using Rink Amide ChemMatrix® resin as the polymer support 22 and routine SPPS methodology (Scheme 3). On coupling Fmoc-L-Lys(Boc)-OH onto the polymer support using HCTU activation, successive rounds of piperidine-mediated N-deprotection and coupling using the next amino acid gave the pentapeptide. Following a subsequent N-terminal Fmoc-deprotection, the Fmoc-protected version of -pyridyl -amino acid 8d, compound 9 was coupled onto the polymer-supported pentapeptide. 23 After a final Fmoc-deprotection step, the N-terminus was acetyl capped and a TFA cleavage cocktail that included triisopropylsilane (TIPS) as a cation scavenger was used to remove the side-chain protecting groups and release the peptide from the polymer support. The resulting hexapeptide, 10 was purified by reverse phase-HPLC (>95% purity) and characterized by high-resolution electrospray ionization mass spectrometry (see Supporting Information for data). Scheme 3. SPPS of a -Pyridyl -Amino Acid Containing HexapeptideAs the -amino acids contained -deficient pyridine moieties, it was proposed that electron-rich conjugating groups may confer fluorescent properties through a charge-transfer (push-pull) mechanism. 24 Accordingly, the optical properties of -pyridyl -amino acids 8a-l were measured. As expected, pyridines with non-conjugating or electron-deficient substituents showed weak fluorescence, while compounds with electron-rich substituents showed strong fluorescence (Figure 2b and Table 1). In

show abstract

Section: Introductionmentioning

confidence: 99%

Synthesis and Fluorescent Properties of β-Pyridyl α-Amino Acids

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Another key objective was to show that the use of a polymer‐supported nitrite reagent would facilitate work‐up and purification of the benzotriazole product. In this study, the polymer‐supported nitrite reagent was prepared by ion exchange of the tetraalkylammonium functionalized resin, Amberlyst A‐26 with an aqueous solution of sodium nitrite . Following our previous work, diazotization and cyclization of 1a was attempted using 3 equivalents of both the polymer‐supported nitrite reagent and p ‐tosic acid in acetonitrile at 80 °C.…”

Section: Resultsmentioning

confidence: 99%

“…In this study, the polymer‐supported nitrite reagent was prepared by ion exchange of the tetraalkylammonium functionalized resin, Amberlyst A‐26 with an aqueous solution of sodium nitrite . Following our previous work, diazotization and cyclization of 1a was attempted using 3 equivalents of both the polymer‐supported nitrite reagent and p ‐tosic acid in acetonitrile at 80 °C. After a reaction time of 1.5 hours, this gave benzotriazole 2a in 46 % isolated yield (entry 1).…”

Section: Resultsmentioning

confidence: 99%

“…In 2008, Filimonov and co‐workers showed that a polymer‐supported nitrite reagent in combination with less harsh acidic conditions ( p ‐tosic acid) could be used for the preparation of stable aryl diazonium tosylate salts . More recently, we have shown that this safe, mild and operationally simple method for aryl diazonium salt formation can be combined in one‐pot multistep processes for (radio)iodination and Heck–Matsuda reactions of anilines , . We now report a general synthesis of benzotriazoles from 1,2‐aryldiamines using a polymer‐supported nitrite reagent, under mild conditions (Figure e).…”

Section: Introductionmentioning

confidence: 86%

See 1 more Smart Citation

Synthesis of Structurally Diverse Benzotriazoles via Rapid Diazotization and Intramolecular Cyclization of 1,2‐Aryldiamines

et al. 2019

Self Cite

View full text Add to dashboard Cite

An operationally simple method has been developed for the preparation of N‐unsubstituted benzotriazoles by diazotization and intramolecular cyclization of a wide range of 1,2‐aryldiamines under mild conditions, using a polymer‐supported nitrite reagent and p‐tosic acid. The functional group tolerance of this approach was further demonstrated with effective activation and cyclization of N‐alkyl, ‐aryl, and ‐acyl ortho‐aminoanilines leading to the synthesis of N1‐substituted benzotriazoles. The synthetic utility of this one‐pot heterocyclization process was exemplified with the preparation of a number of biologically and medicinally important benzotriazole scaffolds, including an α‐amino acid analogue.

show abstract

“…A new tandem method for the preparation of 125 I-labelled aryl compounds from anilines via stable diazonium salts has been reported. 32…”

mentioning

confidence: 99%

Hot off the press

Hill

Sutherland

2017

Nat. Prod. Rep.

Self Cite

View full text Add to dashboard Cite

show abstract

A one-pot radioiodination of aryl amines via stable diazonium salts: preparation of ¹²⁵I-imaging agents

Cited by 24 publications

References 34 publications

Synthesis and Fluorescent Properties of β-Pyridyl α-Amino Acids

Synthesis and Fluorescent Properties of β-Pyridyl α-Amino Acids

Synthesis of Structurally Diverse Benzotriazoles via Rapid Diazotization and Intramolecular Cyclization of 1,2‐Aryldiamines

Hot off the press

Contact Info

Product

Resources

About

A one-pot radioiodination of aryl amines via stable diazonium salts: preparation of 125I-imaging agents

Cited by 24 publications

References 34 publications

Synthesis and Fluorescent Properties of β-Pyridyl α-Amino Acids

Synthesis and Fluorescent Properties of β-Pyridyl α-Amino Acids

Synthesis of Structurally Diverse Benzotriazoles via Rapid Diazotization and Intramolecular Cyclization of 1,2‐Aryldiamines

Hot off the press

Contact Info

Product

Resources

About

A one-pot radioiodination of aryl amines via stable diazonium salts: preparation of ¹²⁵I-imaging agents