2-(2,6-Dioxopiperidin-3-yl)-5-nitro-1H-isoindole-1,3(2H)-dione → 1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)-5-aminoisoindoline

HRID 651432Notes

Reaction equation

HRID 651432 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][C:7]([N+:11]([O-])=O)=[CH:8][CH:9]=2)[C:4](=[O:14])[N:3]1[CH:15]1[CH2:20][CH2:19][C:18](=[O:21])[NH:17][C:16]1=[O:22]>O1CCOCC1.[Pd]>[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][C:7]([NH2:11])=[CH:8][CH:9]=2)[C:4](=[O:14])[N:3]1[CH:15]1[CH2:20][CH2:19][C:18](=[O:21])[NH:17][C:16]1=[O:22]

Participants

4

Reactant 1

HCID 155520312-(2,6-Dioxopiperidin-3-yl)-5-nitro-1H-isoindole-1,3(2H)-dione2×

Product 1

HCID 98169581,3-dioxo-2-(2,6-dioxopiperidin-3-yl)-5-aminoisoindolineYield 69%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)-5-nitroisoindoline {alternatively named as N-(2.6-dioxopiperidin-3-yl)-4-nitrophthalimide} (1 g, 3.3 mmol) and 10% Pd/C (0.13 g) in 1,4-dioxane (200 mL) was hydrogenated at 50 psi for 6.5 hours. The catalyst was filtered through Celite and the filtrate concentrated in vacuo. The residue was crystallized from ethyl acetate (20 mL) to give 0.62 g (69%) of 1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)-5-aminoisoindoline {alternatively named as N-(2,6-dioxopiperidin-3-yl)-4-aminophthalimide} as an orange solid. Recrystallization from dioxane/ethyl acetate gave 0.32 g of yellow solid: mp 318.5-320.5° C.: HPLC (nova Pak C18,15/85 acetonitrile/0.1% H3PO4) 3.97 min (98.22%): 1H NMR (DMSO-d6) δ11.08(s, 1H), 7.53-7.50 (d, J=8.3 Hz, 1H), 6.94(s, 1H). 6.84-6.81(d, J=8.3 Hz,1H), 6.55(s,2H). 5.05-4.98(m, 1H), 2.87-1.99(m, 4H); 13C NMR (DMSO-d6) δ172.79, 170.16. 167.65, 167.14, 155.23, 134.21, 125.22 116.92, 116.17, 107.05, 48.58, 30.97, 22.22; Anal. Calcd for C13H11N3O4: C, 57.14; H, 4.06; N, 15.38. Found: C, 56.52- H, 4.17; N, 14.60.

Workup

  1. filtrationThe catalyst was filtered through Celite
  2. concentrationthe filtrate concentrated in vacuo
  3. customThe residue was crystallized from ethyl acetate (20 mL)

Sources & evidence

ORD record
ord-439fe3803da44078a2f0355035ddc60e
Source dataset
uspto-grants-2001_08
Patent number
US06281230B1

Reaction notes

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