Generation of 3-piperidine(methan)amines and cyclic 3-piperidine-methanamines as potential substance P antagonists

Article abstract of DOI:10.1016/S0040-4020(97)00791-6

A general method is described for the synthesis of 3-piperidine(methan)amines and their cyclic analogues. The 3,5-dichloro-2H-1,4-oxazin-2-ones 6 and 3-aryl substituted analogues are reacted with acetylenic dienophiles yielding pyridines. Further catalytic hydrogenation and functional group transformation (1) or substitution (2-3) with ring closure reactions (4) followed by hydrogenation provided the 2,3,5-cis substituted piperidines 1-3 and a cis substituted [3,4-c]pyrrolopiperidine 4. These compounds have recently raised great interest due to their Substance P antagonist profiles.