反应详情

5-Amino-5-methyl-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid dimethylamide 11c (1.3 g, 7.58 mmol), (2S,4S)-1-(2-chloroacetyl)-4-fluoropyrrolidine-2-carbonitrile 13g (1.74 g, 9.1 mmol), potassium carbonate (1.26 g, 9.1 mmol), 30 mL of N,N-dimethylformamide and 18 mL of dichloromethane were added to a flask under nitrogen atmosphere. The reaction mixture was reacted for overnight at 30° C. upon heating by an oil bath. The reaction was monitored by TLC until the disappearance of the starting materials. The mixture was concentrated to remove N,N-dimethylformamide. The resulting residue was purified by silica gel column chromatography to obtain the title compound 5-[2-((2S,4S)-2-cyano-4-fluoro-pyrrolidin-1-yl)-2-oxo-ethylamino]-5-methyl-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid dimethylamide 18a (1.39 g, yield 50%) as a white solid.

1. customThe reaction mixture was reacted for overnight at 30° C.
2. temperatureupon heating by an oil bath
3. concentrationThe mixture was concentrated
4. customto remove N,N-dimethylformamide
5. customThe resulting residue was purified by silica gel column chromatography