GENERATION OF 3-PIPERIDINE(METHAN)AMINES AND CYCLIC 3-PIPERIDINEMETHANAMINES AS POTENTIAL SUBSTANCE-P ANTAGONISTS

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-o nes 6 and 3-aryl substituted analogues are reacted with acetylenic die nophiles yielding pyridines. Further catalytic hydrogenation and funct ional group transformation (1) or substitution (2-3) with ring closure reactions (4) followed by hydrogenation provided the 2,3,5-cis substi tuted piperidines 1-3 and a cis substituted [3,4-c]pyrrolopiperidine 4 . These compounds have recently raised great interest due to their Sub stance P antagonist profiles. (C) 1997 Elsevier Science Ltd.