反应详情

温度

-78 °C

A round-bottomed flask was charged with 5-chloro-4-iodo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (3.5 g, 8.05 mmol, Adesis) in THF (161 mL) to give a colorless solution. The solution was cooled to about −78° C. and n-BuLi (1.6 M in hexanes, 6.54 mL, 10.46 mmol) was added drop-wise over about 15 min. After addition of the n-BuLi solution was complete, (3S)-3-(dibenzylamino)cyclopentanecarbaldehyde (2.48 g, 8.45 mmol) in THF (10 mL) was added drop-wise over about 5 min. The reaction mixture was stirred for about 4 h at about −78° C. Saturated aqueous NH4Cl (40 mL) was added slowly and the mixture was stirred for about 5 min. The organic solvent was removed under reduced pressure and EtOAc (100 mL) was added. The layers were separated and the organic layer was washed with brine (3×50 mL), dried over MgSO4, filtered, and the solvent was removed under reduced pressure to give a yellow oil that was purified by silica gel chromatography eluting with a gradient of 5-10% EtOAc in heptane. The product containing fractions were combined and concentrated to give (5-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)((3S)-3-(dibenzylamino)cyclopentyl)methanol (3.5 g, 72%): LC/MS (Table 2, Method n) Rt=2.97 min; MS m/z: 603 (M+H)+.

1. customto give a colorless solution
2. stirringthe mixture was stirred for about 5 min
3. customThe organic solvent was removed under reduced pressure and EtOAc (100 mL)
4. additionwas added
5. customThe layers were separated
6. washthe organic layer was washed with brine (3×50 mL)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. customthe solvent was removed under reduced pressure
10. customto give a yellow oil that
11. customwas purified by silica gel chromatography
12. washeluting with a gradient of 5-10% EtOAc in heptane
13. additionThe product containing fractions
14. concentrationconcentrated