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 1249765Notes

Reaction equation

HRID 1249765 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-dd61d46229bd4467a2d481259277ac05
Source dataset
uspto-grants-2002_01
Patent number
US06335349B1

Reaction notes

Loading…