Reaction equation
[CH3:1][C@:2]1([N:10]2[C:18](=[O:19])[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:20]#[N:21])[CH:16]=3)[C:11]2=[O:22])[CH2:7][CH2:6][C:5](=[O:8])[NH:4][C:3]1=[O:9].[ClH:23].O>CO.[Pd]>[ClH:23].[NH2:21][CH2:20][C:15]1[CH:16]=[C:17]2[C:12](=[CH:13][CH:14]=1)[C:11](=[O:22])[N:10]([C@@:2]1([CH3:1])[CH2:7][CH2:6][C:5](=[O:8])[NH:4][C:3]1=[O:9])[C:18]2=[O:19]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
A mixture of 2-[(3S)-3-methyl-2,6-dioxo-piperidin-3-yl]-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carbonitrile (4.70 g, 15.8 mmol), 4N HCl (21 mL), and 10% Pd—C (1.88 g) in CH3OH (200 mL) was hydrogenated under 50 psi of H2 for 16 hours. Water (24 mL) was added, and the reaction mixture was filtered through Celite. The filter was washed with additional methanol (50 mL). The filtrate was concentrated and dried to give 3.5 g of 5-aminomethyl-2-[(3S)-3-methyl-2,6-dioxo-piperidin-3-yl]-isoindole-1,3-dione hydrochloride, in 66% yield; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 mL/min, 240 nm, 30/70 CH3CN/0.1% H3PO4, 1.00 (97.70%); 1H NMR (DMSO-d6) δ 1.91 (s, 3H), 2.03-2.10 (m, 1H), 2.49-2.61 (m, 2H), 2.66-2.75 (m, 1H), 4.23 (s, 2H), 7.89-8.03 (m, 3H), 8.68 (br, 3H), 11.04 (s, 1H); 13C NMR (DMSO-d6) δ 20.9, 28.6, 29.0, 41.6, 58.9, 123.2, 123.5, 130.8, 131.4, 135.3, 141.2, 167.5, 167.6, 172.1, 172.2.
Workup
- filtrationthe reaction mixture was filtered through Celite
- washThe filter was washed with additional methanol (50 mL)
- concentrationThe filtrate was concentrated
- customdried
Sources & evidence
- ORD record
- ord-49ab76369e9a42038a213c698f3155fc
- Source dataset
- uspto-grants-2016_09
- Patent number
- US09447070B2
Linked notes
Loading…