反应详情

4-Fluorobenzaldehyde (43.0 μL) was dissolved in MeOH (3.0 mL) and then propyl [(7R)-7-amino-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]acetate (231 mg) in MeOH (2.0 mL), sodium cyanoborohydride (50.6 mg) and acetic acid (92.0 μL) were added. The reaction mixture was stirred for overnight at room temperature then quenched with NaOH (1N). The aqueous phase was extracted with EtOAc. The organic layers were washed with brine, dried over magnesium sulfate, filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate/hexanes). The resulting benzylamine (48.0 mg) was dissolved in DCM (2.0 mL) and then DMAP (0.743 mg), (4-fluorophenyl)acetyl chloride (32.8 mg) and triethylamine (17.0 μL) were added to the solution under nitrogen atmosphere. The reaction mixture was stirred at room temperature for 2 h then quenched with ½(sat.) aqueous ammonium chloride. DCM (4.0 mL) was added and the two phases were separated by using a phase separator. The solvent was evaporated under reduced pressure and the residue was purified by column chromatography on silica gel (ethyl acetate/hexanes) to give the title compound as a yellow oil. The resultant material was dissolved in THF (4.0 mL) and MeOH (2.0 mL) then NaOH (0.283 mL, 1N) were added to the solution. The reaction was stirred for 2.5 h at room temperature and then quenched with HCl (1N). DCM was added and the two phases were separated with a phase separator. The organic layers were evaporated under reduced pressure to provide the title compound._MS (+ESI) m/z: 489.

1. customthen quenched with NaOH (1N)
2. extractionThe aqueous phase was extracted with EtOAc
3. washThe organic layers were washed with brine
4. dry with materialdried over magnesium sulfate
5. filtrationfiltered
6. customthe solvent was evaporated under reduced pressure
7. customThe residue was purified by column chromatography on silica gel (ethyl acetate/hexanes)
8. dissolutionThe resulting benzylamine (48.0 mg) was dissolved in DCM (2.0 mL)
9. additionDMAP (0.743 mg), (4-fluorophenyl)acetyl chloride (32.8 mg) and triethylamine (17.0 μL) were added to the solution under nitrogen atmosphere
10. stirringThe reaction mixture was stirred at room temperature for 2 h
11. customthen quenched with ½(sat.) aqueous ammonium chloride
12. additionDCM (4.0 mL) was added
13. customthe two phases were separated
14. customThe solvent was evaporated under reduced pressure
15. customthe residue was purified by column chromatography on silica gel (ethyl acetate/hexanes)