反应详情

A stirred solution of Intermediate 2b (17.20 g, assumed to be 95.49 mmol) and (5-fluoro-pyridin-2-yl)-hydrazine (12.14 g, 95.51 mmol) in DCM (300 mL) at RT was treated with DIPEA (34 mL, 195.18 mmol) during 5 min. This mixture was continued to be stirred at RT for 4 days before being added to water (500 mL) and phases separated. The aqueous layer was further extracted into DCM (4×100 mL), combined extracts washed with brine, dried (MgSO4), passed through a phase separation cartridge and concentrated in vacuo to give a residual solid. This product was treated with Et2O-pentane and the resultant solids filtered off and dried to give Intermediate 2c (18.74 g, 77%). LCMS (Method 3) Rt 2.26 min, m/z 253 [MH+]. 1H NMR (300 MHz, CDCl3): 1.23 (3H, d, J 6.9), 1.40-1.74 (6H, m), 2.97 (1H, td, J 13.1, 3.0), 3.82-3.91 (1H, m), 4.27-4.38 (1H, m), 6.54 (1H, s), 6.78 (1H, ddd, J 9.1, 3.7, 0.6), 7.30 (1H, ddd, J 9.1, 7.8, 2.9), 8.00 (1H, d, J 2.6).

1. customseparated
2. extractionThe aqueous layer was further extracted into DCM (4×100 mL)
3. washcombined extracts washed with brine
4. dry with materialdried (MgSO4)
5. custompassed through a phase separation cartridge
6. concentrationconcentrated in vacuo
7. customto give a residual solid
8. filtrationthe resultant solids filtered off
9. customdried