Pyridine → tert-Butyl 4-((2-(5-cyanopyrazin-2-ylamino)-5-(3-hydroxy-3-methylbut-1-ynyl)pyridin-4-ylamino)methyl)piperidine-1-carboxylate

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A solution of tert-butyl 4-((2-chloro-5-iodopyridin-4-ylamino)methyl)piperidine-1-carboxylate (Synthesis 170-B) (0.100 g, 0.22 mmol), dichlorobis(triphenylphosphine)-palladium(II) (0.009 g, 0.01 mmol), trimethyl(2-methylbut-3-yn-2-yloxy)silane (0.048 mL, 0.24 mmol) and copper iodide (0.002 g, 0.01 mmol) was heated under microwave irradiation for 5 min at 120° C. The crude mixture was concentrated in vacuo and filtered through a pad of silica, eluting with hexane/ethyl acetate (8/2), to give the crude product which was used without further purification. The crude pyridine (0.085 g, 0.163 mmol), 2-amino-4-cyanopyrazine (0.023 g, 0.195 mmol), Xantphos (0.015 g, 0.026 mmol), cesium carbonate (0.106 g, 0.326 mmol), dichlorobis(triphenylphosphine)-palladium(II) (0.012 g, 0.013 mmol) in dioxane (1.2 mL) were stirred at room temperature under nitrogen for 10 min, then heated under microwave irradiation for 60 min at 150° C. The reaction mixture was purified by ion exchange on SCX-II acidic resin (2 g), eluting with methanol/dichloromethane (1/1), then 2M ammonia-methanol. The basic fractions were combined and solvent was removed in vacuo. The crude product was purified by preparative thin layer chromatography, eluting with methanol/dichloromethane (1/19), to give the title compound as a yellow solid (0.024 g, 27%).

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