Synthesis of tetrahydropyrido[2,3-b]pyrazine scaffolds from 2,3,5,6-tetrafluoropyridine derivatives

Reactions between N,N′-dimethylethylene diamine and a range of 2,3,5,6-tetrafluoropyridine derivatives provided ready access to the corresponding tetrahydropyrido[2,3-b]pyrazine systems if the substituent located at the 4-position of the pyridine ring was either hydrogen or an electron withdrawing substituent. In contrast, the presence of electron donating substituents at the 4-position made the formation of ring-fused products much more difficult. The two-step sequential nucleophilic substitution procedures from pentafluoropyridine gave convenient and adaptable methodology for the synthesis of polyfunctional tetrahydropyrido[2,3-b]pyrazine scaffolds of interest to the life science discovery arenas.