p-Toluenesulfonic acid → HCID 59442735、化合物

In a 100 mL round bottom flask to a solution of 2-chloro-5-fluoro-N-(2,2,6,6,-tetramethylpiperidin-4-yl)pyrimidin-4-amine (Compound 11; 0.16 g, 0.56 mmol) in 10 mL isopropanol, 3-cyclopropyl-5-(1H-tetrazol-1-yl)benzenamine (0.125 g, 0.622 mmol) and TosOH (0.085 g, 0.448 mmol) were added. The reaction mixture was heated at 100° C. for 3 hours. LCMS analysis indicated the complete consumption of the mono-SNAr product and appearance of Compound III-116. The reaction mixture was then cooled to room temperature and volatiles were removed under reduced pressure. The crude reaction mixture was purified by column chromatography using DCM/2 M NH3 in MeOH to obtain Compound III-116 as a tan solid that was further purified by trituration using DCM/hexanes.