反应详情

Compound 2 (0.156 g, 0.425 mmol) was dissolved in anhydrous ethanol (10 mL). To the solution was bubbled anhydrous HCl gas for 3 min. The reaction vessel was sealed and the mixture was stirred at room temperature for 48 h, and then concentrated to dryness under vacuum. The resulting residue was dissolved in anhydrous methanol (5 mL). To the newly formed solution was added 2,2-dimethoxyethylamine (0.097 mL, 0.891 mmol) in one portion. After stirring at room temperature overnight, temperature was raised to reflux which was maintained for another 3 h before the mixture was cooled to ambient temperature. Solvent was removed under vacuum and the residue was treated with 1.2 N HCl aqueous solution at 80° C. for 2 hours. The mixture was then cooled to ambient temperature again and neutralized to pH ˜9 with powder K2CO3. Water was completely removed under vacuum and the residue was dissolved in methanol. The methanol solution was loaded onto silica gel, and the product was eluted with a mixture of concentrated ammonium hydroxide/MeOH/CH2Cl2 (1.8:18:81.2, v/v), affording the product 21 (27 mg, 23% overall yield) as an off-white solid. 1H NMR (300 MHz, CD3OD): δ 1.60 (m, 4H), 2.14 (m, 2H), 2.56 (t, 2H), 2.76 (t, 2H), 2.86 (t, 2H), 3.94 (t, 2H), 6.79 (d, 2H), 6.91 (s, 2H), 7.08 (d, 2H). m/z (APCI): 274 [C16H23N3O+H]+.

1. customTo the solution was bubbled anhydrous HCl gas for 3 min
2. customThe reaction vessel was sealed
3. concentrationconcentrated to dryness under vacuum
4. dissolutionThe resulting residue was dissolved in anhydrous methanol (5 mL)
5. stirringAfter stirring at room temperature overnight
6. temperaturetemperature was raised
7. temperatureto reflux which
8. temperaturewas maintained for another 3 h before the mixture
9. temperaturewas cooled to ambient temperature
10. customSolvent was removed under vacuum
11. additionthe residue was treated with 1.2 N HCl aqueous solution at 80° C. for 2 hours
12. temperatureThe mixture was then cooled to ambient temperature again
13. customWater was completely removed under vacuum
14. dissolutionthe residue was dissolved in methanol
15. washthe product was eluted with a mixture of concentrated ammonium hydroxide/MeOH/CH2Cl2 (1.8:18:81.2