反应详情

Combine 3-Isopropylidene-1-(4-methoxy-benzyl)-piperidine (227.0 mg, 0.92 mmol), Ethanol (50 mL), 20% Pd(OH)2/C (75.0 mg), and a Hydrogen at 30° C. under 50-60 psi for 12 hours on a Parr shaker. Filter the reaction mixture and then add 5% AcOH/MeOH (3 mL), 6-(4-Formyl-phenoxy)-nicotinonitrile (Intermediate 51) (104.0 mg, 0.43 mmol), and NaCNBH3 (49.0 mg, 0.78 mmol). Stir the reaction at room temperature for 72 hours and then concentrate the reaction mixture under reduced pressure. Add the reaction mixture to an SCX Column (2 g), wash with methanol, and elute with 1N NH3 MeOH. Concentrate under reduced pressure and purify by reverse phase chromatography using 5 to 95% 0.001% TFA in CH3CN/H2O to give 37.2 mg (11% yield) of the title compound: 1H NMR (500 MHz, d-MeOH); 0.9 (6H, dd), 0.9-1.1 (1H, m), 1.3-1.6 (3H, m), 1.7-1.9 (3H, m), 1.9-2.0 (1H, m), 2.9 (1H, d) 3.0 (1H, d), 3.5 (2H, dd), 6.9 (1H, d), 7.1 (2H, d), 7.4 (2H, d), 8.2 (1H, d), 8.6 (1H, s); MS m/z 354 (M+1).

1. filtrationFilter the reaction mixture
2. customthe reaction at room temperature for 72 hours
3. concentrationconcentrate the reaction mixture under reduced pressure
4. additionAdd the reaction mixture to an SCX Column (2 g)
5. washwash with methanol
6. washelute with 1N NH3 MeOH
7. concentrationConcentrate under reduced pressure
8. custompurify by reverse phase chromatography