SAR of 2-benzyl-4-aminopiperidines NK1 antagonists. Part 2. Synthesis of CGP 49823

Article abstract of DOI:10.1016/S0960-894X(96)00563-X

CGP 49823 is a potent NK₁ antagonist which is centrally active after oral administration. The SAR of the C-2 substituent was investigated with respect to the affinity to the NK₁ receptor. A practical synthesis of CGP 49823, suitable for scale-up, was developed. The key-step, a tandem acyliminium ion cyclization/Ritter reaction, gave trans-2-benzyl-4-acetamido-piperidines with high diastereoselectivity.