反应详情

温度

-78 °C

To 2-(4-acetyl-5-fluoropyridin-3-yl)benzofuran-5-carbonitrile 11b (200 mg, 0.714 mmol) in THF (3.57 mL) at −78° C. was added methylmagnesium bromide (3M in Et2O, 0.714 mL, 2.142 mmol). The mixture was stirred for 1 hr at −78° C., and then for 1 hr at 0° C. The mixture was quenched with saturated NH4Cl and extracted with EtOAc two times, dried over magnesium sulfate, filtered and concentrated. The residue was purified via Biotage (10-40% EtOAc/heptane; SNAP25 column), and then purified on Waters mass directed preparative-HPLC (ACN—H2O—NR4OH, Xbridge Preparation C18 column, 30×100 mm) giving the title compound 11 (60 mg, 28%). 1H NMR (400 MHz, MeOD) δ ppm 1.70 (d, J=1.96 Hz, 6H) 6.94 (s, 1H) 7.55-7.71 (m, 2H) 8.00-8.11 (m, 1H) 8.39 (s, 1H) 8.53 (d, J=3.73 Hz, 1H). LC-MS (M+1) 297.1, t=1.50 min.

1. waitfor 1 hr at 0° C
2. customThe mixture was quenched with saturated NH4Cl
3. extractionextracted with EtOAc two times
4. dry with materialdried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified via Biotage (10-40% EtOAc/heptane; SNAP25 column)
8. custompurified on Waters mass
9. custom(ACN—H2O—NR4OH, Xbridge Preparation C18 column, 30×100 mm)