Hydrochloric Acid → 5-(Aminomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione hydrochloride

HRID 331613Notes

Reaction equation

HRID 331613 reaction equation
[O:1]=[C:2]1[CH:7]([N:8]2[C:16](=[O:17])[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:18]#[N:19])[CH:14]=3)[C:9]2=[O:20])[CH2:6][CH2:5][C:4](=[O:21])[NH:3]1.[ClH:22].O>CN(C=O)C.[Pd]>[ClH:22].[NH2:19][CH2:18][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:20])[N:8]([CH:7]1[CH2:6][CH2:5][C:4](=[O:21])[NH:3][C:2]1=[O:1])[C:16]2=[O:17]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 670232172-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carbonitrile

Product 1

HCID 670197065-(Aminomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione hydrochlorideYield 85%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carbonitrile (1.00 g, 3.53 mmol), 4N HCl (4.5 mL), 10% Pd—C (0.1 g) and decolorizing carbon (0.06 g) in DMF (30 mL) was hydrogenated at 50 psi overnight. Water (5 mL) was added, and the reaction mixture was filtered through Celite. The filter was washed with methanol (10 mL). The filtrate was concentrated, and the residue was co-evaporated with ethanol (4×5 mL). The resulting solid was triturated with ethanol (5 mL) for 1 hour, filtered, washed with additional ethanol (10 mL), and dried to give 0.97 g of 5-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride as a white solid, in 85% yield; mp>260° C.; 1H NMR (DMSO-d6) δ 2.05-2.12 (m, 1H), 2.45-2.63 (m, 2H), 2.83-2.98 (m, 1H), 4.24 (s, 2H), 5.18 (dd, J=12.6 Hz, J=5.4 Hz, 1H), 7.96-8.03 (m, 2H), 8.11 (s, 1H), 8.73 (br, 3H), 11.15 (s, 1H); 13C NMR (DMSO-d6) δ 22.0, 30.9, 41.7, 49.1, 123.6, 123.9, 131.0, 131.5, 135.4, 141.5, 166.8, 166.9, 169.8, 172.7; Anal. Calcd for C14H14N3O4Cl+0.15H2O: C, 51.51; H, 4.42; N, 12.87. Found: C, 51.16; H, 4.40; N, 12.59.

Workup

  1. customwas hydrogenated at 50 psi overnight
  2. filtrationthe reaction mixture was filtered through Celite
  3. washThe filter was washed with methanol (10 mL)
  4. concentrationThe filtrate was concentrated
  5. customThe resulting solid was triturated with ethanol (5 mL) for 1 hour
  6. filtrationfiltered
  7. washwashed with additional ethanol (10 mL)
  8. customdried

Sources & evidence

ORD record
ord-2a0497e9febe4d419f562e7104e6cc32
Source dataset
uspto-grants-2014_11
Patent number
US08877780B2

Reaction notes

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