Synthesis of 1-Arylethyl-2-arylethylamino-5-trifluoroacetyl-1,2,3,4-tetrahydropyridines and Related Compounds with Potential Cell Efflux Pump Inhibition

Haloacetylated Enol Ethers: a Way Out for the Regioselective Synthesis of Biologically Active Heterocycles

“…For comparison purposes, Scheme 18 shows the reactions of cyclic enones 4 with primary amines in the absence and presence of the alkoxy moiety neighboring the oxygen of the pyran ring. When the alkoxy group is absent, the corresponding α‐substituted β‐enaminone 63 is obtained, [89] and when present, the aldehyde moiety of 64 is rapidly transformed into the corresponding imine 65 , which spontaneously makes an intramolecular nucleophilic attack on the secondary amine, and, as a result, 1,2,3,4‐tetrahydropyridine motifs are obtained [90–94] . Given that several methods involving catalysts to prepare tetrahydropyridines using parent substrates have been reported, [95–98] the high reactivity of the push‐pull system on these fluorinated β‐enaminones 65 may be the main cause for the spontaneous cyclization observed.…”

“…For example, compounds 74 were readily obtained after stirring in EtOH or MeOH at room temperature for 5 min (Scheme 22). [94] The 1,2,3,4‐tetrahydropyridine ethylamines derivatives 74 were tested as efflux inhibitors in E. coli and Mycobacterium abscessus ( M. abscessus ) strains. Compound 70 was found to be a suitable efflux inhibitor in M. abscessus (Scheme 22).…”