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 1267853Notes

Reaction equation

HRID 1267853 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 names 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, 125.2, 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-d20a29866d3e4035beb5338fff2a58bb
Source dataset
uspto-grants-2003_04
Patent number
US06555554B2

Reaction notes

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