反应详情

To a solution of the (4-bromo-2-chloro-phenyl)-(5,11-dihydro-pyrido[2,3-b][1,5] benzodiazepin-10-yl)-methanone of Example 7, Step A (0.5 g, 1.23 mmol), thiophene-3-boronic acid (0.158 g, 1.23 mmol) and sodium carbonate (0.568 g, 5.36 mmol) in toluene (20 mL), ethanol (10 mL) and water (10 mL) under nitrogen was added the tetrakis (triphenylphosphine) palladium(0) catalyst (0.06 g, 0.052 mmol). The reaction was heated at reflux for 20 hours, cooled, and filtered through Celite, which was then rinsed with ethyl acetate. The organic layer was washed with water, dried over sodium sulfate and evaporated to dryness. The residue (blue-green oil) was dissolved in dichloromethane and absorbed onto a silica Merck-60 flash column. Elution with 25% ethyl acetate in hexane yielded a foam (0.24 g) which was triturated with diethyl ether-hexane to provide the title compound as a white solid, m.p. 125-130° C.

1. temperatureThe reaction was heated
2. temperatureat reflux for 20 hours
3. temperaturecooled
4. filtrationfiltered through Celite, which
5. washwas then rinsed with ethyl acetate
6. washThe organic layer was washed with water
7. dry with materialdried over sodium sulfate
8. customevaporated to dryness
9. dissolutionThe residue (blue-green oil) was dissolved in dichloromethane
10. customabsorbed onto a silica Merck-60 flash column
11. washElution with 25% ethyl acetate in hexane