反应详情

A mixture of 4-bromo-3-formyl-1H-indole-7-carbonitrile (1.08 g, 4.34 mmol), ethyl 2-amino-3,3-diethoxypropanoate (prepared according to the procedure of U.S. Pat. No. 7,470,680; 1.780 g, 6.94 mmol), and molecular sieves (2.17 g, 2 g) in 1,2-dichloroethane (79 mL) and THF (29.6 mL) at 0° C. was treated with sodium triacetoxyborohydride (2.57 g, 12.14 mmol) and the resulting mixture was stirred at room temperature overnight. After 24 h, LCMS residual starting material, so additional sodium triacetoxyborohydride (1.38 g, 1.5 eq.) and molecular sieves (2 g) were added and stirring was continued for 4 h more. The mixture was diluted with EtOAc and filtered through a CELITE® pad and the solids were washed with EtOAc. The filtrates were diluted with EtOAc and washed with NaHCO3 (aq) and brine, dried and concentrated to afford a dark-colored oil. The residue was subjected to column chromatography on silica gel (40 g), eluting with EtOAc-hexane (gradient from 15:85 to 100:0) to provide the desired product as a brown syrup (0.67 g, 35% yield). LCMS (M+H)+ m/z 438.2, 440.2.

1. customprepared
2. waitAfter 24 h
3. additionwere added
4. stirringstirring
5. waitwas continued for 4 h
6. filtrationfiltered through a CELITE® pad
7. washthe solids were washed with EtOAc
8. additionThe filtrates were diluted with EtOAc
9. washwashed with NaHCO3 (aq) and brine
10. customdried
11. concentrationconcentrated
12. customto afford a dark-colored oil
13. washeluting with EtOAc-hexane (gradient from 15:85 to 100:0)