Synthesis of doubly 15-nitrogen labelled N-[4-hydroxybutyl]-N-nitrosobutylamine, a potent urinary bladder carcinogen in animals

The labelled precursors for the amino nitrogen atom was ¹⁵N-potassium phthalimide which was condensed with triphenylmethoxychlorobutane. The phthalimide group was then cleaved with hydrazine and the primary amine obtained was condensed with butyraldehyde followed by sodium borohydride reduction to give the secondary amine N-[4-triphenylmethyloxybutyl]butyl-[ ¹⁵N]amine. After deprotection of the triphenylmethyl group with trifluoroacetic acid, the amino alcohol obtained was nitrosated with ¹⁵N-sodium nitrite in hydrochloric acid medium to give N-[4-hydroxybutyl]-N-[ ¹⁵N]nitrosobutyl[ ¹⁵N]amine. The two 15-nitrogen atoms were incorporated in order to obtain a tool useful for studying the metabolic activation of this compound. The evolution of labelled molecular nitrogen will be used to quantify the extent of nitrosamine hydroxylation at the carbon atom α to the nitroso moiety.