反应详情

1-Naphthaleneboronic acid (0.52 g, 3.00 mmol) was added to a mixture of (4-bromo-2-chlorophenyl)-(5H, 11H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-methanone of Step A (1.27 g, 3.15 mmol) and sodium carbonate (0.53 g, 4.98 mmol) in toluene (22.5 mL), ethanol (4.5 mL) and water (9 mL). The resultant solution was purged with nitrogen for 10 minutes, then tetrakis(triphenylphosphine)palladium (0.18 g, 0.06 mmol) was added. The reaction mixture was heated to reflux for 76 hours. The solution was cooled to ambient temperature, then filtered through a pad of Celite, which was subsequently rinsed with ethyl acetate. The combined filtrate was diluted to 100 mL water/ethyl acetate (1:1). The aqueous layer was extracted with ethyl acetate, and the combined organic layer was dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness to yield a brown oil. Purification by flash chromatography on silica gel eluting with hexane-ethyl acetate (5:1) resulted in a white solid which was dried under vacuum (0.62 g), m.p. 115–117.5° C.

1. customThe resultant solution was purged with nitrogen for 10 minutes
2. temperatureThe reaction mixture was heated
3. temperatureto reflux for 76 hours
4. filtrationfiltered through a pad of Celite, which
5. washwas subsequently rinsed with ethyl acetate
6. additionThe combined filtrate was diluted to 100 mL water/ethyl acetate (1:1)
7. extractionThe aqueous layer was extracted with ethyl acetate
8. dry with materialthe combined organic layer was dried over anhydrous magnesium sulfate
9. filtrationfiltered
10. customevaporated to dryness
11. customto yield a brown oil
12. customPurification by flash chromatography on silica gel eluting with hexane-ethyl acetate (5:1)
13. customresulted in a white solid which
14. customwas dried under vacuum (0.62 g), m.p. 115–117.5° C.