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.
