Development of Versatile Routes for the Preparation of an Intermediate to Immuno-Oncology Agonist BMS-986299

The development and optimization of two efficient and convenient routes for the construction of synthetic equivalents of 2-chloro-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)aniline, a key intermediate to immuno-oncology agonist (BMS-986299), is described. The developed routes started from commercial available reagents into the desired pyrazole scaffolds smoothly with different substituents such as THP-, Bn-, and PMB-group tolerance. Finally, to further demonstrate the practicability, a large-scale process (10–30 g on a laboratory scale) was obtained through a simple crystallization or filtration without any column chromatography needed and may be suitable for the scalable production of the key intermediate for industrial applications.