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

HRID 63475Notes

Reaction equation

HRID 63475 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-c1b82bd690964335800ea9c0ea73edb6
Source dataset
uspto-grants-2016_09
Patent number
US09447070B2

Reaction notes

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