反应详情

63.3 g of EDCI was added to a mixture of 16.5 g of 4-oxospiro[chroman-2,4′-piperidin]-6-ylacetamide TFA salt, 61.0 g of 4-methoxyquinoline-2-carboxylic acid, 45.9 g of HOBT, 50 mL of Et3N and 90 mL DMF, at 0° C., and the resulting mixture was stirred at room temperature for 14 hours. The reaction mixture was concentrated under reduced pressure, and the residue was partitioned between ethyl acetate and water. The organic layer was washed with water and aqueous saturated sodium carbonate solution successively, then dried over sodium sulfate, and then concentrated. The residue was purified through silica gel column chromatography (eluted with 3% MeOH/CHCl3), and the intended compound was obtained. 1H-NMR (300 MHz, CDCl3) δ: 8.21 (1H, dd, J=8.5, 1.3 Hz), 7.99 (1H, dd, J=8.5, 1.0 Hz), 7.94 (1H, dd, J=8.9, 2.7 Hz), 7.73 (1H, ddd, J=8.5, 6.9, 1.3 Hz), 7.67 (1H, d, J=2.7 Hz), 7.55 (1H, ddd, J=8.5, 6.9, 1.0 Hz), 7.34 (1H, br.s), 7.09 (1H, s), 7.01 (1H, d, J=8.9 Hz), 4.65-4.55 (1H, m), 4.09 (3H, s), 4.06-3.96 (1H, m), 3.58 (1H, dt, J=2.9, 12.7 Hz), 3.36 (1H, dt, J=2.9, 12.7 Hz), 2.83-2.69 (2H, m), 2.26-2.12 (1H, m), 2.17 (3H, s), 2.10-2.00 (1H, m), 1.96-1.75 (2H, m). MS [M+H]+=460.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. customthe residue was partitioned between ethyl acetate and water
3. washThe organic layer was washed with water and aqueous saturated sodium carbonate solution successively
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated
6. customThe residue was purified through silica gel column chromatography (eluted with 3% MeOH/CHCl3)
7. customthe intended compound was obtained