Dimethylformamide → (2S,4S)-4-fluoro-1-[[N-[4-[(2R)-N-(2-heptyl)amino]carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]pyrrolidine-2-carbonitrile

Participants

Reaction Steps

(2S,4S)-1-[[N-(4-Carboxybicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (50.0 mg), 1-hydroxybenzotriazole (23.7 mg), JANDAJEL-1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (289 mg) and N,N-dimethylformamide (1 mL) were mixed together and the mixture was stirred at room temperature for 3 hours. Subsequently, (2R)-2-aminoheptane (46.6 μL) was added and the mixture was stirred at room temperature for 17 hours and 40 minutes. This was followed by addition of dichloromethane (0.5 mL) and (2R)-2-aminoheptane (11.6 μL), stirring at room temperature for 4.5 hours, addition of JANDAJEL-1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (96.6 mg) and additional stirring at room temperature for 17 hours. Subsequently, (isocyanatomethyl)polystyrene (232 mg) was added and the mixture was stirred at room temperature for 2 hours. The insoluble material was filtered and the filtrate was concentrated under reduced pressure. The resulting residue was then purified by silica gel column (eluant:ethyl acetate:methanol=10:1) to give (2S,4S)-4-fluoro-1-[[N-[4-[(2R)—N-(2-heptyl)amino]carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]pyrrolidine-2-carbonitrile (9.0 mg).

Provenance & Evidence