Triethylamine → (S)-4-Amino-2-(6-oxopiperidin-3-yl)isoindoline-1,3-dione

Participants

Reaction Conditions

Reaction Steps

To a mixture of 3-amino phthalic acid hydrochloride (0.144 g, 0.664 mmol) and (S)-5-aminopiperidin-2-one hydrochloride (0.100 g, 0.664 mmol) in dry DMF (2.2 mL) was added triethylamine (0.933 mL, 6.64 mmol) and the reaction mixture was heated at 80° C. over 18 h. The crude mixture was quenched by the addition of a saturated aqueous NaHCO3 solution (30 mL) and extracted using DCM (3×20 mL). Combined organic phases were dried over MgSO4, filtered and concentrated. The crude residue was purified by preparative reverse phase HPLC to give the desired product 30 (0.08 g, 47%) as an off-white powder. 1H NMR (400 MHz, DMSO) δ 7.56 (s, 1H), 7.42 (dd, J=7.7, 7.7 Hz, 1H), 6.94 (m, 2H), 6.48 (br s, 2H), 4.32 (m, 1H), 3.60 (app t, J=11.3 Hz, 1H), 3.23-3.02 (m, 1H), 2.62-2.42 (obsc m, 1H), 2.42-2.21 (m, 2H), 1.86 (m, 1H). MS (ESI) m/z calcd for C13H14N3O3 [M+H]+ 260.3, found: 260.7.

Provenance & Evidence