Methods and compounds useful in the synthesis of orexin-2 receptor antagonists

摘要

The present disclosure provides compounds and methods that are useful for the preparation of compounds useful as orexin-2 receptor antagonists.

主权项

1. A process for making a compound of Formula IX: wherein: Ar is phenyl, which phenyl may be unsubstituted, or substituted 1-3 times with substituents independently selected from the group consisting of: halo, C1-6alkyl, C1-6alkoxy, and haloC1-6alkyl; R2 and R3 are each independently selected from the group consisting of: hydrogen, C1-6alkyl, haloC1-6 alkyl, C1-6alkoxy, and hydroxyC1-6alkyl; and Ar′ is a pyridine group: wherein:
R4 is selected from the group consisting of: hydrogen, halo, C1-6alkyl, C1-6alkoxy, and (C1-6alkoxy)C1-6alkyl;R5 is selected from the group consisting of: hydrogen, halo, C1-6alkyl, and haloC1-6alkyl; andR6 is selected from the group consisting of: hydrogen, halo, C1-6alkyl, haloC1-6alkyl, C1-6alkoxy, (C1-6alkoxy)C1-6alkyl, and cyano,comprising the step of reacting a compound of Formula VII: wherein Ar, R2 and R3 are as given above,with a compound of Formula X: wherein R4, R5, and R6 are as given above,said reacting carried out in an organic solvent in the presence of an organic amine and an amide coupling agent,to prepare said compound of Formula IX,wherein said amide coupling agent is an alkyl phosphonic anhydride.