反应详情

A mixture of 4-chloro-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (12.9 g, 45.4 mmol) (prepared as in WO 2007/070514, Ex.65) and [1-(triisopropylsilyl)-1H-pyrrol-3-yl]boronic acid (Frontier Scientific) (10.4 g, 38.9 mmol) and sodium carbonate (4.36 g, 41.2 mmol) in 1,2-dimethoxyethane (100 mL) and water (35 mL) was degassed by purging with a stream of nitrogen for 20 minutes. Tetrakis(triphenylphosphine)palladium(0) (2.25 g, 1.94 mmol) was then added and the reaction was heated to reflux for 9 hours. As the coupling reaction proceeded, the TIPS protecting group was also slowly removed. The solvent was removed by rotary evaporation and the product was purified by flash column chromatography, eluting with a gradient from 10-50% ethyl acetate in hexanes to afford the desired product (7 g, 57%).

1. customwas degassed
2. customby purging with a stream of nitrogen for 20 minutes
3. temperaturethe reaction was heated
4. temperatureto reflux for 9 hours
5. customAs the coupling reaction
6. customthe TIPS protecting group was also slowly removed
7. customThe solvent was removed by rotary evaporation
8. customthe product was purified by flash column chromatography
9. washeluting with a gradient from 10-50% ethyl acetate in hexanes