反应详情

温度

130 °C

A suspension of 5-bromoindane (100.0 mg, 0.51 mmol), 5,5,5′,5′-tetramethyl-2,2′-bi-1,3,2-dioxaborinane (191 mg, 0.56 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (42.0 mg, 0.025 mmol) and potassium acetate (150 mg, 1.50 mmol) in 1,4-dioxane (1 mL) was sealed in a pressure tube and heated to 130° C. for 1 hour. To this mixture was added 5-bromo-6-chloro-1H-indazole-3-carboxylic acid (100 mg, 0.36 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (14.7 mg, 0.018 mmol), 2N aqueous potassium carbonate solution (0.5 mL, 1.0 mmol) and EtOH (2 mL). The reaction mixture was sealed and heated to 130° C. for 1 hour. Water (3 mL) was added to the reaction mixture, followed by 1N HCl solution to adjust the pH to 2. The layers were separated and the aqueous layer was extracted with EtOAc (3×5 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by reverse phase HPLC (Column: Waters XBridge C18 19×100 mm, 5 μm; Mobile phase A: 0.03% NH4OH in water (v/v); Mobile phase B: 0.03% NH4OH in MeCN (v/v); 80.0% H2O/20.0% MeCN linear to 70.0% H2O/30.0% MeCN in 8.5 min, 70.0% H2O/30.0% MeCN linear to 0% H2O/100% MeCN in 0.5 min HOLD at 0% H2O/100% MeCN from 9.0 to 10.0 min. Flow: 25 mL/min) to afford the title compound (6.2 mg, 6% yield). MS (ES+) 313.1 (M+H)+. Retention time=3.11 minutes (Column: Waters Atlantis dC18 4.6×50 mm, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in MeCN (v/v); Gradient: 95:5 A:B linear to 5:95 A:B in 4.0 min, hold at 5:95 A:B to 5.0 min. Flow: 2 mL/min).

1. customwas sealed in a pressure tube
2. customThe reaction mixture was sealed
3. temperatureheated to 130° C. for 1 hour
4. customThe layers were separated
5. extractionthe aqueous layer was extracted with EtOAc (3×5 mL)
6. dry with materialThe combined organic layers were dried over Na2SO4
7. concentrationconcentrated in vacuo
8. customThe crude material was purified by reverse phase HPLC (Column: Waters XBridge C18 19×100 mm, 5 μm; Mobile phase A: 0.03% NH4OH in water (v/v); Mobile phase B: 0.03% NH4OH in MeCN (v/v); 80.0% H2O/20.0% MeCN linear to 70.0% H2O/30.0% MeCN in 8.5 min, 70.0% H2O/30.0% MeCN linear to 0% H2O/100% MeCN in 0.5 min HOLD at 0% H2O/100% MeCN from 9.0 to 10.0 min. Flow: 25 mL/min)