3-Aminopiperidine-2,6-dione hydrochloride → 2-(2,6-Dioxopiperidin-3-yl)-4-(3-hydroxy-4-methoxyphenylamino)-isoindole-1,3-dione

HRID 448344Notes

Reaction equation

HRID 448344 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:19]=[CH:18][CH:17]=[C:13]([C:14]([OH:16])=O)[C:12]=2[C:20]([OH:22])=O)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].Cl.[NH2:24][CH:25]1[CH2:31][CH2:30][C:29](=[O:32])[NH:28][C:26]1=[O:27]>N1C=CC=CC=1>[O:27]=[C:26]1[CH:25]([N:24]2[C:20](=[O:22])[C:12]3[C:13](=[CH:17][CH:18]=[CH:19][C:11]=3[NH:10][C:4]3[CH:5]=[CH:6][C:7]([O:8][CH3:9])=[C:2]([OH:1])[CH:3]=3)[C:14]2=[O:16])[CH2:31][CH2:30][C:29](=[O:32])[NH:28]1

Participants

4

Reactant 2

HCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 583071623-(3-Hydroxy-4-methoxyphenylamino)phthalic acid

Product 1

HCID 588272852-(2,6-Dioxopiperidin-3-yl)-4-(3-hydroxy-4-methoxyphenylamino)-isoindole-1,3-dioneYield 58%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A mixture of 3-(3-hydroxy-4-methoxyphenylamino)phthalic acid (0.60 g, 2.0 mmol) and rac-α-aminoglutarimide hydrochloride (0.33 g, 2.0 mmol) in pyridine (10 mL) was heated to reflux for 16 hours. The mixture was cooled and evaporated under vacuum. The residue was dissolved in ethyl acetate (150 mL), washed with dilute aqueous HCl (2×100 mL) and water (2×100 mL), was dried (MgSO4) and evaporated. The residue was triturated in 1:1 acetonitrile-water (15 mL) and filtered, and the resulting solid was washed with additional 1:1 acetonitrile-water and dried under high vacuum, providing 0.45 g of the product, in 58% yield: mp 225-227° C.; 1H NMR (DMSO-d6) δ 2.03-2.08 (m, 1H), 2.52-2.63 (m, 2H), 2.83-2.92 (m, 1H), 3.77 (s, 3H), 5.11 (dd, J=12.5 Hz, J=5.4 Hz, 1H), 6.69-6.76 (m, 2H), 6.94 (d, J=8.5 Hz, 1H), 7.14-7.23 (m, 2H), 7.56 (t, J=7.8 Hz, 1H), 8.15 (s, 1H), 9.21 (s, 1H), 11.13 (s, 1H); 13C NMR (DMSO-d6) δ 22.1, 31.0, 48.6, 55.9, 110.7, 111.5, 112.5, 113.0, 114.2, 118.8, 132.1, 132.3, 136.1, 144.2, 145.2, 147.2, 167.1, 168.4, 170.0, 172.8; Anal. calcd for C20H17N3O6: C, 60.76; H, 4.33; N, 10.63. Found: C, 60.76; H, 4.11; N, 10.42.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 16 hours
  3. temperatureThe mixture was cooled
  4. customevaporated under vacuum
  5. dissolutionThe residue was dissolved in ethyl acetate (150 mL)
  6. washwashed with dilute aqueous HCl (2×100 mL) and water (2×100 mL)
  7. dry with materialwas dried (MgSO4)
  8. customevaporated
  9. customThe residue was triturated in 1:1 acetonitrile-water (15 mL)
  10. filtrationfiltered
  11. washthe resulting solid was washed with additional 1:1 acetonitrile-water
  12. customdried under high vacuum

Sources & evidence

ORD record
ord-9266f215a5714cd3bb0ce22648ad8776
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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