1,2-Dichloroethane → HCID 46893990, compound

Participants

Reaction Steps

To a stirred solution of [(3S,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}-2-oxopyrrolidin-3-yl]acetic acid (265 mg, 0.50 mmol) and HOBt (42 mg, 0.55 mmol) in 1,4-dioxane (3 mL) was added a solution of EDC (105 mg, 0.55 mmol) in CH2Cl2 (3 mL). The mixture was stirred for 10 min at room temperature. Isoindoline (65 mg, 0.55 mmol) in CH2Cl2 (2 mL) was added with stirring. After 16 h, the reaction mixture was washed with saturated aqueous NaHCO3 (10 mL), 1 N aqueous citric acid (10 mL), and brine (10 mL). The organic layers were dried over MgSO4, filtered, and concentrated. The residue was purified over silica gel using CH2Cl2/MeOH (98:2) as an eluent to yield compound 1 (128 mg, 0.35 mmol, 70%). 1H NMR (300 MHz, CDCl3): (6/1 mixture of trans/cis amide rotomers) δ 7.30-7.26 (m, 4H), 6.56 (s, 0.86H), 6.06 (s, 0.14H), 4.82-4.77 (m, 4.86H, overlapped two singlet at 4.82, 4.77), 4.60 (d, J=6.6 Hz, 0.14H), 4.55 (d, J=9.0 Hz, 0.14H), 4.40 (dd, J=3.0, 9.0 Hz, 0.86H), 3.61-3.04 (m, 2H), 3.02-2.88 (m, 2H), 2.68-2.36 (m, 3H), 2.29-2.12 (m, 4H). MS (ES+) m/z calcd. for C20H22N4O3: 366.17. found: 367.1 (M+H).

Provenance & Evidence