(S)-BOC-2-(2-氰基)-2-甘酰胺

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-oxo-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid tert-butyl ester 1e (0.32 g, 1.42 mmol) was dissolved in 10 mL of dichloromethane, and trifluoroacetic acid (3.27 mL, 42.7 mmol) was then added to the solution in an ice-water bath. Upon completion of the addition, the reaction mixture was stirred at 0° C. for 30 minutes, then the solvent was evaporated to dryness to obtain the title compound hexahydro-cyclopenta[c]pyrrol-5-one triflutate 1f which was directly used in the further reaction. Upon completion of the addition the solvent was evaporated to dryness

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: [2-(2-Cyano-pyrrolidin-1-yl)-2-oxo-ethyl]-carbamic acid tert-butyl ester 1e (13.7 g, 54.2 mmol) was dissolved in the solvent mixture of 140 mL of ether and 40 mL of water, and 37% hydrochloride acid (90 mL) were then added dropwise to the solution. Upon completion of the addition, the reaction mixture was stirred for 1 hour in an ice-water bath, the solvent was evaporated, and ether was added to the residue to centrifuge to give 1-(2-amino-acetyl)-pyrrolidine-2-carbonitrile hydrochloride 1d (10 g, yield 98%) as a white powder. were then added dropwise to the solution Upon completion of the addition the solvent was evaporated ether was added to the residue to centrifuge

反应条件: temp:-35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a dry three-neck flask under a nitrogen atmosphere, 286 mL of pyridine, [2-(2-carbamoyl-pyrrolidin-1-yl)-2-oxo-ethyl]-carbamic acid tert-butyl ester 1b (13.5 g, 49.8 mmol) and imidazole (7.11 g, 104.6 mmol) were added successively. The reaction system was cooled down to −35° C., and phosphorus oxychloride (19 mL, 204.2 mmol) was then added dropwise to the solution with stirring. After stirring for 1 hour at −35° C., the reaction mixture was allowed to increase to room temperature, and stirred for another 0.5 hour. Pyridine was evaporated under low temperature, and the reaction mixture was diluted with water, then extracted with ethyl acetate (200 mL×3). The combined organic extracts were washed with 50 mL of saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound [2-(2-cyano-pyrrolidin-1-yl)-2-oxo-ethyl]-carbamic acid tert-butyl ester 1e (10.7 g, yield 84.9%) as a white powder. After stirring for 1 hour at −35° C. to increase to room temperature stirred for another 0.5 hour Pyridine was evaporated under low temperature the reaction mixture was diluted with water extracted with ethyl acetate (200 mL×3) The combined organic extracts were washed with 50 mL of saturated brine dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was purified by silica gel column chromatography