反应详情

温度

70 °C

A mixture of timoprazole (0.51 g, 1.98 mmol) and 37% formaldehyde (0.80 ml) in acetonitrile (5 ml) was heated at 70° C. for 15 min. The reaction was evaporated to give a solid that was washed twice with ethyl ether/ethyl acetate (4:1) and dissolved in dichloromethane (10 ml). To this solution was added Example 1c (0.65 g, 2 mol), 4-(N—N-dimethylamino)pyridine (10 mg) and dicyclohexylcarbodiimide (1M in dichloromethane, 4 ml, 4 mmol). After stirring at room temperature for 3 hours, the reaction was concentrated under vacuum and the residue was purified by flash column chromatography (ethyl acetate/hexane, 4:1 to 7:1) to afford the title compound (0.65 g, 54.7%) as a green foam. 1H NMR (300 MHz, CDCl3): δ1.82 and 1.91 (2 s, 6H), 2.63 and 2.75 (2br s, 4H), 4.08 and 4.13 (2 s, 2H), 4.70 and 4.85 (2 s, 2H), 4.88 (d, J=14 Hz, 1H), 4.92 (d, J=14 Hz, 1H), 6.36 (d, J=11.4 Hz, 1H), 6.42 (d, =11.4 Hz, 1H), 7.00 and 7.06 (2 d, J=6.8 Hz, 2H), 7.207.64 (m, 9H), 7.81 (d, !=7.7 Hz, 1H), 8.54 (d, J=4 Hz, 1H); 13C NMR (75 MHz, CDCl): δ 27.29, 27.94, 28.88, 52.58, 55.29, 58.18, 62.22, 65.04, 110.73, 120.73, 122.97, 123.85, 125.21, 125.30, 125.58, 127.41, 128.76, 135.03, 135.79, 136.66, 141.70, 149.71, 150.20, 151.66, 171.80, 172.76; LCMS (m/e): 594 (M+1).

1. customThe reaction was evaporated
2. customto give a solid
3. washthat was washed twice with ethyl ether/ethyl acetate (4:1)
4. dissolutiondissolved in dichloromethane (10 ml)
5. concentrationthe reaction was concentrated under vacuum
6. customthe residue was purified by flash column chromatography (ethyl acetate/hexane, 4:1 to 7:1)