[5‐¹⁴C]‐4‐methyltriazolepyridines via facile preparation of methyl‐[¹⁴C]‐isothiocyanate

Abstract

A fast and convenient microwave assisted one‐pot synthesis of methyl‐[14C]‐isothiocyanate 4 was shown. The continued one‐pot synthesis with 4 to a highly refined material like [5‐14C]‐dimethylsulfanyltriazolepyridines 8 and 13 without any intermediate purification, six steps in the same pot from [14C]KCN. Oxidation of the sulfur provided access to triazole‐ethers upon reaction with alcohols. The triazole‐ethers, 15, were obtained at fair to good yields and specific activities above 2 GBq/mmol. Copyright © 2008 John Wiley & Sons, Ltd.

Imaging agents for myeloperoxidase

“…A 14 C‐label in the thiocarbonyl position was needed to investigate the binding of 1 and 2 to MPO. Use of [ 14 C]potassium thiocyanate 3 to prepare benzoyl [ 14 C]isothiocyanate 5 provided a good starting point for the preparation of xanthine derivatives with the label in the 2‐position. The syntheses of [2‐ 14 C]xanthine derivatives of 1a and 1b were initiated by coupling the correspondingly substituted 1° amine with 5 to give benzamides 6a and 6b , respectively (Scheme ).…”

Preparation of two D2 partial agonists in C‐14 and stable isotope labeled forms

“…The preparation started with the reaction of KS 14 CN with aniline 3 in acetic acid followed immediately by a bromine‐induced cyclization (Scheme ). The cyclization could potentially produce the linear product 4 or the angular product 4b and not surprisingly, we obtained a 54% yield of 4 and 4b in a ratio of 4:1.…”

“…Reductive amination with amine 10 proceeded smoothly, and column chromatography on basic alumina and SFC purification gave [ 13 C 2 , 15 N 2 ]-2 in a 77% yield. (5), 5-bromo-2,3-dihydro-1H-inden-2-ylcarbamate (11), and 6,7,8,9-Tetrahydro-5H-1-thia-3,7-diaza-cyclohepta[f]inden-2-ylamine 2HCl (10) were provided by AstraZeneca CNS-Chemistry, Wilmington, DE. All other reagents were obtained from Acros, Sigma-Aldrich, Fisher and Strem and were used without purification.…”

“…HPLC analysis using method A showed 80% radiochemical purity with a single 20% radiolabeled impurity. This impurity co-eluted on HPLC with (S)-benzyl [2][3][4][5][6][7][8][9][10][11][12][13][14]…”

Development of rapid multistep carbon-11 radiosynthesis of the myeloperoxidase inhibitor AZD3241 to assess brain exposure by PET microdosing

“…AZD3241 and related pyrrolo-pyrimidone compounds have previously been labeled with carbon-14 in the thio-carbonyl position in a 4-step reaction starting from [ 14 C]potassium cyanide [9,15]. The previously demonstrated rapid transformation of [ 14 C]potassium cyanide to benzoyl [ 14 C]isothiocyanate via [ 14 C]potassium thiocyanate and the scope for optimizing reaction times in subsequent steps (Malmquist, personal communication) suggested that a similar route could have a potential also for 11 C-radiolabeling.…”