A mixture of 2-chloro-5-fluoro-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidin-4-amine hydrochloride (100 mg, 0.296 mmol, 1 equiv), 2-fluoro-5-(1H-tetrazol-1-yl)benzenamine (85 mg, 0.474 mmol, 1.6 equiv), and TFA (100 μL, 1.19 mmol, 4 equiv) in IPA (3 mL) were heated to 100° C. in shaker overnight affording a melt. LCMS indicated pyrimidine:product=5:95. IPA (1 mL) and TFA (100 μL, 1.19 mmol, 4 equiv) were added and the mixture was heated to 100° C. in shaker ON affording a melt. LCMS indicated pyrimidine:product=2:98. IPA (1 mL) and TFA (1000 uL, 11.9 mmol, 40 equiv) were added and the mixture was heated to 100° C. in shaker for an additional 5 hours affording a melt. LCMS indicated complete conversion to product. The crude solid was quenched with 2M NH3/MeOH (1-2 mL), and diluted with DCM (3-5 mL), then loaded into a column packed with silica and filled with DCM. The crude product was purified by flash chromatography and eluted with DCM:2M NH3/MeOH=100:0 to 97:3 using 1% 2M NH3/MeOH increments to provide the desired product (91 mg, 69%) as a solid.
