反应详情

温度

90 °C

A stirred mixture of the bromide (Example 7) (100 mg, 0.26 mmol), thiophene-3-boronic acid (49 mg, 0.38 mmol) and cesium carbonate (167 mg, 0.51 mmol) in dioxan (20 mL) was degassed by evaporating under high vacuum until cold then refilled with N2 and allowed to thaw. This freeze/thaw procedure was repeated 3 times. Pd2(dba)3 (23 mg, 0.026 mmol) and tri-tert-butylphosphine (0.1M solution in dioxane) (0.6 mL, 0.06 mmol) were added and the degassing procedure repeated twice. The mixture was heated at 90° C. under a flow of nitrogen overnight. Further quantities of reagents were added at room temperature: thiophene-3-boronic acid (49 mg, 0.38 mmol), cesium carbonate (167 mg, 0.51 mmol), Pd2(dba)3 (23 mg, 0.026 mmol) and tri-tert-butylphosphine (0.6 mL, 0.06 mmol) followed by the degassing procedure 3 times. Heating was continued at 90° C. for a further 24 h. After cooling the mixture was filtered and the solid washed with EtOAc. The combined organic filtrates were washed with brine, dried (MgSO4) and evaporated. The residue was purified using silica plug chromatography eluting with 1% MeOH/DCM to give the title compound (35 mg, 37%) as a yellow solid. MS (ES+) 395 (M+1). 1H NMR (400 MHz, d6-DMSO) δ2.61 (3H, s), 3.96 (3H, s), 5.74, (2H, s), 7.15 (1H, s), 7.69-7.71 (1H, m), 7.74-7.78 (1H, m), 7.96 (1H, s), 8.03-8.05 (1H, m), 9.85 (1H, s).

1. customwas degassed
2. customby evaporating under high vacuum until cold
3. additionthen refilled with N2
4. additionFurther quantities of reagents were added at room temperature
5. temperatureHeating
6. temperatureAfter cooling the mixture
7. filtrationwas filtered
8. washthe solid washed with EtOAc
9. washThe combined organic filtrates were washed with brine
10. dry with materialdried (MgSO4)
11. customevaporated
12. customThe residue was purified
13. washeluting with 1% MeOH/DCM