1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (S)-1-(1-(5-chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-3-(6-(pyrrolidine-1-carbonyl)pyridin-3-yloxy)pyrrolidin-2-one

Participants

Reaction Steps

(S)-5-(1-(1-(5-Chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)picolinic acid hydrochloride (0.027 g, 0.062 mmol), hydroxybenzotriazole hydrate (0.013 g, 0.084 mmol), EDCI (0.016 g, 0.084 mmol), and DIEA (0.016 mL, 0.093 mmol) were stirred in CH2Cl2 (0.5 mL) for five minutes. Pyrrolidine (0.010 mL, 0.12 mmol) was added and the solution was stirred overnight at ambient temperature. The mixture was partitioned between saturated aqueous NH4Cl (20 mL) and EtOAc (40 mL). The organic phase was washed successively with saturated aqueous NaHCO3 (20 mL) and brine (20 mL). The organics were dried over MgSO4, filtered and concentrated. The residue was purified on silica (eluting with 1:24 MeOH/EtOAc) to afford (S)-1-(1-(5-chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-3-(6-(pyrrolidine-1-carbonyl)pyridin-3-yloxy)pyrrolidin-2-one (24 mg, 0.049 mmol, 79%) as a colorless solid. Mass spectrum (apci) m/z=488 (M+H).

Provenance & Evidence