反应详情

温度

102.5 °C

Combine 4-[4-(7-Chloro-imidazo[1,2-a]pyridin-3-yl)-phenyl]-N-(3-trifluoromethyl-phenyl)-butyramide (0.15 g, 0.32 mmol), 4-pyridine boronic acid (0.04 g, 0.35 mmol), S-Phos (0.02 g, 0.04 mmol) and K3PO4 (0.13 g, 0.63 mmol) with dioxane (3.5 mL) and water (1.5 mL) and stir at room temperature while the reaction contents are de-gassed with nitrogen for 5 minutes. Add palladium diacetate (0.01 g, 0.04 mmol). Heat to 100-105° C. for 20 hours. Cool and dilute with water (10 mL) and dichloromethane. The organic layer are then filtered onto a pre-equilibrated in methanol Varian SCX column (10 g), washed with 30 mL each of water, methanol, dichloromethane and methanol. Elute crude product with 2N methanolic ammonia (50 mL). Concentrate the ammonia solution in vacuo to dryness to yield a residue that is chromatographed on silica (0→3% methanol in ethyl acetate over 30 min) to yield 4-[4-(7-Pyridin-4-yl-imidazo[1,2-a]pyridin-3-yl)-phenyl]-N-(3-trifluoromethyl-phenyl)-butyramide (0.10 g, 0.19 mmol). MS(ESI), m/z 501 (M+1).

1. customare de-gassed with nitrogen for 5 minutes
2. temperatureCool
3. filtrationThe organic layer are then filtered onto a pre-equilibrated in methanol Varian SCX column (10 g)
4. washwashed with 30 mL each of water, methanol, dichloromethane and methanol
5. washElute crude product with 2N methanolic ammonia (50 mL)
6. concentrationConcentrate the ammonia solution in vacuo to dryness
7. customto yield a residue that
8. customis chromatographed on silica (0→3% methanol in ethyl acetate over 30 min)