反应详情

温度

0 °C

Diisopropylamine (1.02 mL, 7.27 mmol) was added to a flask containing anhydrous THF (10 mL) and the mixture, while kept under an atmosphere of nitrogen, was cooled to −78° C. n-BuLi (2.5 M in hexanes, 2.9 mL, 7.27 mmol) was added dropwise to the mixture, which was stirred for 30 min. Thieno[2,3-c]pyridine (0.82 g, 6.06 mmol) dissolved in anhydrous THF (10 mL) was added to the reaction mixture dropwise. The reaction was stirred at −78° C. for 10 min and then at −40° C. for 20 min. 5-Bromo-2-chloropyrimidine, dissolved in anhydrous THF (5 mL) was added to the reaction slowly. The mixture was allowed to stir at −40° C. for 2 h and then was quenched with a 1:1 mixture of acetic acid/methanol (5 mL). The mixture was stirred for 15 min and a solution of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (1.72 g, 6.66 mmol) in 10 mL of THF was added. The reaction was stirred for an additional 15 min and then the cooling bath was removed. The mixture was stirred for 1 h and then cooled to 0° C. with an ice bath. 5 N sodium hydroxide (50 mL) was added to the reaction mixture, which was stirred for an additional 5 min. The reaction was then diluted with ethyl acetate (30 mL) and water (30 mL). The organic layer was washed with saturated aqueous sodium bicarbonate, water and brine. The organic layer was then dried with sodium sulfate, concentrated and purified by column chromatography using a gradient of 5 to 40% ethyl acetate in hexanes to obtain a light brown solid. Yield=0.5 g. MS (M+H)+ 326/328.

1. additionwas added dropwise to the mixture, which
2. additionwas added to the reaction mixture dropwise
3. stirringThe reaction was stirred at −78° C. for 10 min
4. waitat −40° C. for 20 min
5. additionwas added to the reaction slowly
6. stirringto stir at −40° C. for 2 h
7. customwas quenched with a 1:1 mixture of acetic acid/methanol (5 mL)
8. stirringThe mixture was stirred for 15 min
9. stirringThe reaction was stirred for an additional 15 min
10. customthe cooling bath was removed
11. stirringThe mixture was stirred for 1 h
12. addition5 N sodium hydroxide (50 mL) was added to the reaction mixture, which
13. stirringwas stirred for an additional 5 min
14. additionThe reaction was then diluted with ethyl acetate (30 mL) and water (30 mL)
15. washThe organic layer was washed with saturated aqueous sodium bicarbonate, water and brine
16. dry with materialThe organic layer was then dried with sodium sulfate
17. concentrationconcentrated
18. custompurified by column chromatography
19. customto obtain a light brown solid