反应详情

温度

130 °C

A solution of 6-chloro-5-fluoro-9-(2-trimethylsilanylethoxymethyl)-9H-dipyrido[2,3-b;4′3′-d]pyrrole (12.2 g, 34.7 mmol) in DMF (120 mL) was treated with zinc cyanide (4.88 g, 41.7 mmol) and tetrakis(triphenylphosphine)palladium(0) (6 g, 5.2 mmol). The mixture was degassed and stirred under a nitrogen atmosphere at 130° C. for 3 hours. After cooling to ambient temperature the mixture was filtered through Celite© and the filter cake washed with DMF (10 mL). The filtrate was partitioned between ethyl acetate and water and the aqueous phase further extracted with ethyl acetate. The combined organic layer was washed with water (×2) and brine, dried (Na2SO4), filtered and evaporated. The resultant residue was dissolved in dichloromethane, stirred with flash silica gel, filtered to remove the solid and the solid washed well with dichloromethane. The filtrate was evaporated and the resultant residue triturated with pentane:diethyl ether (ca. 4:1) to afford the title compound as a white solid (8.15 g, 68%). The trituration liquors were evaporated and the resultant residue purified by flash chromatography to afford a second crop of title compound (0.92 g, 8%). Total yield=9.07 g, 76%. 1H NMR (400 MHz, CDCl3): 8.99 (d, J=2.1 Hz, 1H), 8.75 (dd, J=4.8, 1.7 Hz, 1H), 8.57 (dd, J=7.9, 1.7 Hz, 1H), 7.44 (dd, J=7.9, 4.8 Hz, 1H), 6.02 (s, 2H), 3.63-3.56 (m, 2H), 0.93 (t, J=8.2 Hz, 2H), −0.08 (d, J=0.6 Hz, 9H).

1. customThe mixture was degassed
2. temperatureAfter cooling to ambient temperature the mixture
3. filtrationwas filtered through Celite©
4. washthe filter cake washed with DMF (10 mL)
5. customThe filtrate was partitioned between ethyl acetate and water
6. extractionthe aqueous phase further extracted with ethyl acetate
7. washThe combined organic layer was washed with water (×2) and brine
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. customevaporated
11. dissolutionThe resultant residue was dissolved in dichloromethane
12. stirringstirred with flash silica gel
13. filtrationfiltered
14. customto remove the solid
15. washthe solid washed well with dichloromethane
16. customThe filtrate was evaporated
17. customthe resultant residue triturated with pentane