反应详情

温度

95 °C

To a mixture of methyl 1-(3,4-dichlorophenyl)-4-hydroxy-6-oxo-1,6-dihydropyridazine-3-carboxylate (315 mg, 1.0 mmol) in DMF (3 mL) at room temperature under argon was added K2CO3 (415 mg, 3.0 mmol) and tert-butyl 4-(methylsulfonyloxy)piperidine-1-carboxylate (419 mg, 1.5 mmol). The reaction mixture was heated at 95° C. overnight. EtOAc (20 mL) and water (20 mL) were added to the reaction mixture. Layers were separated. Organic layer were washed with water (15 mL), and brine (15 mL). Organic phase was dried (MgSO4), filtered and concentrated. The crude product was dissolved in a small amount of DCM (˜2 ml) and loaded onto a 40 g ISCO silica gel column which was eluted with a 20 min gradient from 20% to 100% EtOAc/Hexanes. 72 mg (14.2%) of methyl 4-(1-(tert-butoxycarbonyl)piperidin-4-yloxy)-1-(3,4-dichlorophenyl)-6-oxo-1,6-dihydropyridazine-3-carboxylate was obtained as a gum. 1H NMR (400 MHz, CDCl3) δ ppm 1.40-1.50 (m, 9H) 1.68-1.82 (m, 1H) 1.92 (d, J=3.08 Hz, 3H) 3.23-3.45 (m, 2H) 3.49-3.59 (m, 1H) 3.59-3.73 (m, 1H) 3.82-4.03 (m, 3H) 4.48-5.43 (m, 1H) 6.12-6.38 (m, 1H) 7.38-7.64 (m, 2H) 7.75 (dd, J=7.91, 2.20 Hz, 1H). MS (ESI) 442 (M+H-tBu).

1. customLayers were separated
2. washOrganic layer were washed with water (15 mL), and brine (15 mL)
3. dry with materialOrganic phase was dried (MgSO4)
4. filtrationfiltered
5. concentrationconcentrated
6. dissolutionThe crude product was dissolved in a small amount of DCM (˜2 ml)
7. washwas eluted with a 20 min gradient from 20% to 100% EtOAc/Hexanes