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 1693088Notes

Reaction equation

HRID 1693088 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) δ 11.08(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) δ 172.79, 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-663b26a066d948f0a526da541ce5f8ee
Source dataset
uspto-grants-2012_04
Patent number
US08158653B2

Reaction notes

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