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

HRID 718719Notes

Reaction equation

Cl.[NH2:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:5]([C:6]([OH:8])=O)[C:4]=1[C:12]([OH:14])=O.Cl.[NH2:16][C@@H:17]1[CH2:22][NH:21][C:20](=[O:23])[CH2:19][CH2:18]1.C(N(CC)CC)C>CN(C=O)C>[NH2:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:5]2[C:4]=1[C:12](=[O:14])[N:16]([C@H:17]1[CH2:18][CH2:19][C:20](=[O:23])[NH:21][CH2:22]1)[C:6]2=[O:8]

Participants

Conditions

Temperature: 80 °C

Procedure

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.

Workup

customThe crude mixture was quenched by the addition of a saturated aqueous NaHCO3 solution (30 mL)
extractionextracted
dry with materialCombined organic phases were dried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe crude residue was purified by preparative reverse phase HPLC

Sources & evidence

ORD record: ord-2b63d42d527247d594f7a35fe5f3c9cf
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09193989B2

Reaction notes

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