反应详情

To (R)-5-(2-aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione (2.36 g, 7.58 mmol) and benzaldehyde (0.85 ml, 8.34 mmol) in a mixture of methanol (15 ml), and dichloromethane (15 ml) sodium cyanoborohydride (0.67 g, 10.66 mmol) was added at 20-25° C. in portions. The mixture was stirred for 64 h, quenched with 1N HCl (12 ml) with stirring followed by 3N NaOH (12 ml). The mixture was extracted with DCM (100 ml), the organic phase was washed with brine (50 ml), dried (MgSO4) and evaporated to dryness. The residue was purified on a silica gel column with ethyl acetate and a mixture of ethyl acetate with methanol (9:1) as eluents. Fractions containing the product were collected, evaporated under reduced pressure to approx 20 ml then cooled on ice. The precipitate was collected, washed with ethyl acetate—petroleum ether (1:1) mixture, dried on air. Yield was 1.25 g (41%), the product having a mp 188-90° C. (2-propanol-DCM).

1. additionwas added at 20-25° C. in portions
2. customquenched with 1N HCl (12 ml)
3. stirringwith stirring
4. extractionThe mixture was extracted with DCM (100 ml)
5. washthe organic phase was washed with brine (50 ml)
6. dry with materialdried (MgSO4)
7. customevaporated to dryness
8. customThe residue was purified on a silica gel column with ethyl acetate
9. additiona mixture of ethyl acetate with methanol (9:1) as eluents
10. additionFractions containing the product
11. customwere collected
12. customevaporated under reduced pressure to approx 20 ml
13. temperaturethen cooled on ice
14. customThe precipitate was collected
15. washwashed with ethyl acetate—petroleum ether (1:1) mixture
16. customdried on air