反应详情

温度

90 °C

Prepared according to the method described in Example 12b) from (1S,2R)-4-(2-hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acid (0.197 g, Example 33), 4-iodo-1,2-dicyanobenzene (0.421 g, Can. J. Chem., 1985, 63, 3057), 2M aqueous sodium carbonate (0.50 ml) and tetrakis(triphenylphosphine)palladium (0) (0.054 g) in ethanol (3 ml). The reaction mixture was heated in a sealed vial at 90° C. for 4 hours. After cooling, the solution was concentrated under reduced pressure and the residue purified by chromatography over silica eluting with ethyl acetate. The residue was further purified by chromatography over silica gel eluting with dichloromethane:2-propanol (19:1). The residue was then further purified by reverse-phase HPLC eluting a gradient of 25-100% acetonitrile in 0.1 w/v aqueous ammonium acetate solution. The HPLC fractions were concentrated under reduced pressure, the residue dissolved in dichloromethane, filtered and concentrated under reduced pressure. The residue was triturated with ether to give the title to compound as a solid (0.060 g).

1. customPrepared
2. temperatureAfter cooling
3. concentrationthe solution was concentrated under reduced pressure
4. customthe residue purified by chromatography over silica eluting with ethyl acetate
5. customThe residue was further purified by chromatography over silica gel eluting with dichloromethane:2-propanol (19:1)
6. customThe residue was then further purified by reverse-phase HPLC
7. washeluting a gradient of 25-100% acetonitrile in 0.1 w/v aqueous ammonium acetate solution
8. concentrationThe HPLC fractions were concentrated under reduced pressure
9. dissolutionthe residue dissolved in dichloromethane
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customThe residue was triturated with ether