反应详情

温度

0 °C

The residue was suspended in THF (30 mL) and cooled to 0° C. A solution of (R)-3-[4-(4-methoxy-phenylamino)-piperidin-1-yl]-butyronitrile (1.09 g, 1 eq.) and DIPEA (1.5 mL, 2 eq.) in THF (10 mL) was added drop-wise and the mixture was stirred at 0° C. for 30 min. The reaction was quenched with saturated NaHCO3 (50 mL) and extracted with DCM (150 mL in 3 extracts). The organic layer was washed once with saturated NaHCO3 (20 mL), dried with Na2SO4 and filtered through a silica plug (35 mL glass frit, 1 cm). The plug was washed with 50 mL 5:1 Et2O-MeOH, and the filtrate was concentrated. The residue was purified by flash chromatography on 150 mL silica using 10:1 Et2O-MeOH as the eluent to give N-[(R)-1-(2-cyano-1-methyl-ethyl)piperidin-4-yl]-N-(4-methoxy-phenyl)-nicotinamide (1.23 g, 81%) as light brown thick oil. 1H NMR (δ, CDCl3): 8.44 (1H, s), 8.39 (1H, d, J=4.8 Hz), 7.53 (1 H, d, J=7.5 Hz), 7.08 (1 H, dd, J=7.5, 4.8 Hz), 6.90 (2 H, d, J=8.7 Hz), 6.72 (2 H, d, J=8.7 Hz), 4.69 (1 H, t, br, J=12.9 Hz), 3.73 (3 H, s, and an overlapping 1 H, m), 3.05-2.95 (1 H, m), 2.95-2.75 (2 H, dd, J=20, 11), 2.53-2.25 (4 H, m), 1.96-1.80 (3 H, m), 1.50 (2 H, qd, J=11.4, 2.4 Hz), 1.77(3 H, d, J=6.9 Hz), 1.01 (2 H, d, J=6.3 Hz).

1. customThe reaction was quenched with saturated NaHCO3 (50 mL)
2. extractionextracted with DCM (150 mL in 3 extracts)
3. washThe organic layer was washed once with saturated NaHCO3 (20 mL)
4. dry with materialdried with Na2SO4
5. filtrationfiltered through a silica plug (35 mL glass frit, 1 cm)
6. washThe plug was washed with 50 mL 5:1 Et2O-MeOH
7. concentrationthe filtrate was concentrated
8. customThe residue was purified by flash chromatography on 150 mL silica using 10:1 Et2O-MeOH as the eluent