Synthesis of 11C-amides using [11C]carbon monoxide and in situ activated amines by palladium-mediated carboxaminations

Abstract

[¹¹C]Carbon monoxide at low concentrations, aryl halides and amines were used in the palladium-mediated synthesis of twenty ¹¹C-amides. In the study several approaches to improve the radiochemical yield were explored. Eight of the selected amides were prepared by in situ activation of the amines using lithium bis(trimethylsilyl)amide and the radiochemical yields of these reactions were improved compared to utilising a previous reported method. In the synthesis of 1-[carbonyl-¹¹C]benzoyl-3-methyl-1H-indole (11) from 3-methyl-1H-indole (25), the corresponding organotin–amine was prepared prior to the acylation reaction. In a typical experiment, N-(4-hydroxyphenyl)[carbonyl-¹¹C]acetamide (5) was prepared in 15% radiochemical yield using 4-aminophenol (20) but the yield increased to 63% when the amine was activated by lithium bis(trimethylsilyl)amide.