[6-chloro-3-pyridylmethyl-3H]neonicotinoids as high-affinity radioligands for the nicotinic acetylcholine receptor: Preparation using NaB3H4 and LiB3H4

Article abstract of DOI:10.1002/(SICI)1099-1344(199611)38:11<971::AID-JLCR923>3.0.CO;2-U

NaB³H₄, and LiB³H₄ at 78% and 97% isotopic enrichments, respectively, were used in the synthesis of ³H-labeled 1-(6-chloro-3-pyridyl)-methyl-2-nitromethyleneimidazolidine (CH-IMI) and N'-[(6-chloro-3-pyridyl)methyl]-N''-cyano-N'-methylacetamide (acetamiprid) (two very potent insecticides) and of 1-(6-chloro-3-pyridyl)methyl-2-iminoimidazolidine (desnitro-IMI) (a metabolite of the commercial insecticide imidacloprid). 6-Chloronicotinoyl chloride was treated with either NaB³H₄ in methanol or LiB³H₄ in tetrahydrofuran and the resulting alcohol transformed to 2-chloro-5-chloromethylpyridine, which was then coupled to N-cyano-N'-methylacetamidine to give [³H]acetamiprid (45 Ci/mmol). 2-Chloro-5-chloro [³H]methylpyridine was also reacted with ethylenediamine and the product was either refluxed in absolute ethanol with 1,1-bis(methylthio)-2-nitroethylene to provide [³H]CH-IMI or reacted in toluene with a solution of cyanogen bromide to produce [³H]desnitro-IMI (each 55 Ci/mmol).