p-Toluenesulfonic acid monohydrate → Ammonia methanol

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-chloro-5-fluoro-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidin-4-amine hydrochloride (0.196 g, 0.58 mmol, 1 equiv), 4-cyclopropyl-2-fluoro-5-(1H-tetrazol-1-yl)benzenamine (0.140 g, 0.64 mmol, 1.1 equiv), and para-toluenesulfonic acid monohydrate (0.090 g, 0.47 mmol, 0.8 equiv) in IPA (15 mL) were heated to 100° C. overnight. After cooling to ambient temperature, the crude mixture was quenched with 2M NH3/MeOH followed by concentrating to dryness and repeating once. The crude product was purified by flash chromatography and eluted with DCM:2M NH3/MeOH (100:0 to 95:5 using 1% 2M NH3/MeOH increments) to provide the desired product which was titurated with DCM/Hexane to give the title compound (0.100 g, in 36% yield) as a solid.

Provenance & Evidence