Triethylamine → 6-(3-Ethylureido)-4-(4-(1-methyl-1h-pyrazol-4-yl)thiazol-2-yl)pyridin-3-ylboronic acid

Participants

Reaction Conditions

Reaction Steps

In a 100 mL flask 1-(5-bromo-4-(4-(1-methyl-1H-pyrazol-4-yl)thiazol-2-yl)pyridin-2-yl)-3-ethylurea (Intermediate 97, 1.28 g, 3.14 mmol) was dissolved in 1,4-dioxane (15 mL) at 40° C. and degassed with argon. Bis(triphenylphosphine)palladium chloride (0.221 g, 0.31 mmol) was added and allow it to react for 10 minutes while heating at 40° C. 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (2.394 g, 9.43 mmol) was added and stirred for 10 minutes while heating at 100° C. Triethylamine (1.314 mL, 9.43 mmol) and potassium acetate (0.925 g, 9.43 mmol) were added and the solution was heated at 100° C. for 15 h. The reaction mixture was cooled to room temperature, filtered through a pad of Celite and partitioned between water and ethyl acetate. The layers were separated and the aqueous layer was back extracted three times with ethyl acetate. The organic layers were combined and washed with water and brine, then dried over sodium sulfate and concentrated under reduced pressure, and purified by column chromatography (Silica gel, 0-10% MeOH in CH2Cl2). Isolation gave 400 mg of the title compound as an off-white solid.

Provenance & Evidence