Potassium Carbonate → tert-Butyl 5-fluoro-4-(2-(4-(4-phenylphthalazin-1-ylamino)phenoxy)pyridin-3-yl)pyrimidin-2-ylcarbamate

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Reaction Conditions

Reaction Steps

The title compound was prepared according to the procedure described in Garnier, E.; Andoux, J.; Pasquinet, E.; Suzenet, F.; Poullain, D.; Lebret, B.; Guillaumet, G. J Org. Chem. 2004, 69, 7809. Xantphos (281 mg, 486 μmol) and 1,4-dioxane (12151 μl, 2430 μmol) were added into a sealed tube. The tube was purged with argon, then palladium(II) acetate (55.0 mg, 243 μmol) was added. The mixture was stirred under argon for 10 min. In a separate sealed tube, N-(4-(3-(2-chloro-5-fluoropyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-phenylphthalazin-1-amine (1.27 mg, 2.43 mmol), tert-butyl carbamate (712 mg, 6.08 mmol), potassium carbonate (10.1 g, 72.9 mmol), and 1,4-dioxane (12.2 ml, 2.43 mmol) were added. Then Pd(OAc)2/Xantphos solution was added via a syringe. The resulting mixture was heated to 110° C. under argon with vigorous stirring. After 3.5 h, LCMS showed mainly product at 1.793 min as [M+H]+=602 and deBoc product at 1.602 min as [M+H]+=502. The reaction was cooled to RT, diluted with DCM, passed through a pad of celite and silica gel (1 cm thick each) with an aid of DCM and a bit of MeOH. The filtrate was concentrated to afford tert-Butyl 5-fluoro-4-(2-(4-(4-phenylphthalazin-1-ylamino)phenoxy)pyridin-3-yl)pyrimidin-2-ylcarbamate, which was carried on without further purification. MS Calcd for C34H28FN7O3: [M]+=601. Found: [M+1]+=602.

Provenance & Evidence