反应详情

温度

0 °C

To a stirred solution of N,N-diisopropylamine (0.610 mL, 4.25 mmol) in tetrahydrofuran (2.0 mL) at −78° C., n-butyllithium (2.5 M in hexanes, 1.70 mL, 4.25 mmol) was added dropwise. After the white precipitate formed, the mixture was warmed up to 0° C. for 10 minutes. The resulting resulted solution was added to a stirred solution of 2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine (1.30 g, 3.07 mmol) in tetrahydrofuran (10 mL) at 78° C. After 30 min, a solution of 1,2-dibromo-1,1,2,2-tetrachloroethane (1.10 g, 3.38 mmol) in tetrahydrofuran (6 mL) was added dropwise. After another 1 hour, the reaction mixture was quenched with saturated aq. NH4Cl, then extracted with methylene chloride. The combined organic layers were dried over MgSO4, and then concentrated. The residue was purified on silica gel (eluting with 0 to 50% EtOAc in hexanes) to give the desired product (1.30 g, 84%). LCMS calculated for C22H21BrN3O4S (M+H)+: m/z=502.0. Found: 502.0; 1H NMR (400 MHz, CDCl3): δ 8.15-8.12 (m, 3H), 7.68-7.58 (m, 1H), 7.51-7.47 (m, 2H), 6.88 (s, 1H), 6.31 (d, J=2.0 Hz, 2H), 6.28 (t, J=2.5 Hz, 1H), 3.72 (s, 6H), 3.16-3.12 (m, 2H), 2.99-2.96 (m, 2H) ppm.

1. customAfter the white precipitate formed
2. customThe resulting resulted solution
3. waitAfter another 1 hour
4. customthe reaction mixture was quenched with saturated aq. NH4Cl
5. extractionextracted with methylene chloride
6. dry with materialThe combined organic layers were dried over MgSO4
7. concentrationconcentrated
8. customThe residue was purified on silica gel (eluting with 0 to 50% EtOAc in hexanes)