反应详情

温度

100 °C

A mixture of 9-benzenesulfonyl-3-bromo-5-(1-ethyl-piperidin-4-yloxy)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (215 mg, 0.40 mmol), trimethylboroxine (167 μL, 1.2 mmol), cesium carbonate (156 mg, 0.48 mmol) and tetrakis(triphenyl-phosphine)palladium(0) (96 mg, 0.04 mmol) in dioxane (2.0 mL) was degassed with argon and heated under microwave irradiation at 100° C. for 90 minutes. The reaction mixture was allowed to cool to ambient temperature, diluted with saturated aqueous ammonium chloride (10 mL) and extracted with dichloromethane (3×10 mL). The combined organic phase was washed with brine (2×10 mL) and concentrated in-vacuo. The resultant residue was diluted with THF (10 mL), 1N aqueous potassium hydroxide (1 mL) added and the reaction mixture was then heated at 50° C. for 1 hour. The solvent was evaporated in-vacuo and the resultant residue was purified by chromatography (silica, 2 g column, Si-SPE, 0-10% 2-propanol in dichloromethane). The appropriate fractions were combined and evaporated in-vacuo and the resultant residue triturated with pentane (2×2 mL) to afford the title compound as an off-white solid (69 mg, 52%). LCMS (Method A): RT=2.46 min, M+H+=336.2. 1H NMR (400 MHz, CD3OD): 8.71 (s, 1H), 8.52 (dd, J=2.1, 0.7 Hz, 1H), 8.47 (dd, J=2.1, 0.9 Hz, 1H), 4.91-4.88 (m, 1H), 3.02-2.99 (m, 2H), 2.57 (s, 3H), 2.50 (q, J=7.2 Hz, 2H), 2.26-2.19 (m, 4H), 2.12-2.11 (m, 2H), 1.13 (t, J=7.2 Hz, 3H).

1. customwas degassed with argon
2. temperatureto cool to ambient temperature
3. additiondiluted with saturated aqueous ammonium chloride (10 mL)
4. extractionextracted with dichloromethane (3×10 mL)
5. washThe combined organic phase was washed with brine (2×10 mL)
6. concentrationconcentrated in-vacuo
7. additionThe resultant residue was diluted with THF (10 mL), 1N aqueous potassium hydroxide (1 mL)
8. additionadded
9. temperaturethe reaction mixture was then heated at 50° C. for 1 hour
10. customThe solvent was evaporated in-vacuo
11. customthe resultant residue was purified by chromatography (silica, 2 g column, Si-SPE, 0-10% 2-propanol in dichloromethane)
12. customevaporated in-vacuo
13. customthe resultant residue triturated with pentane (2×2 mL)