A mixture of 2-chloro-5-fluoro-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidin-4-amine hydrochloride (100 mg, 0.309 mmol, 1 equiv), 2-fluoro-5-(1H-tetrazol-1-yl)benzenamine (90 mg, 0.495 mmol, 1.6 equiv., Chembridge, San Diego, Calif.), and TFA (100 μL, 1.24 mmol, 4 equiv) in IPA (3 mL) were heated to 100° C. in shaker overnight affording a melt. LCMS indicated pyrimidine:product ratio=29:71. IPA (1 mL) and TFA (100 μL, 1.24 mmol, 4 equiv) were added and the mixture was heated to 100° C. in shaker overnight affording a melt. LCMS indicated pyrimidine:product=4:96. IPA (1 mL) and TFA (1000 μL, 12.4 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 96:4 using 1% 2M NH3/MeOH increments to provide the desired product (90 mg, 68%) as a solid.
