3-Amino-3-methylpiperidine-2,6-dione hydrochloride → 4-(3-Chloro-benzylamino)-2-(3-methyl-2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione

HRID 2103570Notes

Reaction equation

HRID 2103570 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=1)[CH2:5][NH:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:9]([C:10]([OH:12])=O)[C:8]=1[C:16]([OH:18])=O.Cl.[NH2:23][C:24]1([CH3:32])[CH2:29][CH2:28][C:27](=[O:30])[NH:26][C:25]1=[O:31]>N1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=1)[CH2:5][NH:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:9]2[C:8]=1[C:16](=[O:18])[N:23]([C:24]1([CH3:32])[CH2:29][CH2:28][C:27](=[O:30])[NH:26][C:25]1=[O:31])[C:10]2=[O:12]

Participants

4

Reactant 2

HCID 219282523-Amino-3-methylpiperidine-2,6-dione hydrochlorideHCID 219886073-(3-Chloro-benzylamino)-phthalic acid

Product 1

HCID 219885594-(3-Chloro-benzylamino)-2-(3-methyl-2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dioneYield 41%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a stirred solution of 3-(3-Chloro-benzylamino)-phthalic acid (4 mmol) in pyridine (50 ml) was added 3-amino-3-methyl-piperidine-2,6-dione hydrochloride (0.71 g, 4 mmol). The reaction mixture was heated to reflux for 18 h. The solvent was evaporated in vacuo and the residue dissolved in methylene chloride (150 ml). The methylene chloride mixture was washed with water (2×100 ml), 0.1N HCl (2×100 ml), brine (1×100 ml), dried (magnesium sulfate), and filtered. The solvent was evaporated in vacuo to give a yellow semi-solid. The residue was purified by preparative HPLC (Symmetry C18, isocratic, 50% acetonitrile/water) to give 0.67 g (41%) of product as a yellow solid: mp 199-201° C.; 1H NMR (DMSO-d6) δ 10.99 (s, 1H), 7.52-7.28 (m, 6H), 6.97-6.89 (m, 2H), 4.54 (d, J=6.1 Hz, 1H), 2.78-2.50 (m, 3H), 2.08-1.98 (m, 1H), 1.89 (s, 3H); 13C NMR (DMSO-d6) δ 172.42, 172.19, 169.62, 167.92, 145.59, 141.82, 136.02, 133.14, 132.06, 130.35, 126.91, 126.78, 125.60, 117.23, 110.42, 109.49, 58.37, 44.74, 29.27, 28.62, 21.02; Anal. Calcd. For C21H18ClN3O4: C, 61.24; H, 4.41; N, 10.20. Found: C, 61.30; H, 4.28; N, 9.97.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 18 h
  3. customThe solvent was evaporated in vacuo
  4. dissolutionthe residue dissolved in methylene chloride (150 ml)
  5. washThe methylene chloride mixture was washed with water (2×100 ml), 0.1N HCl (2×100 ml), brine (1×100 ml)
  6. dry with materialdried (magnesium sulfate)
  7. filtrationfiltered
  8. customThe solvent was evaporated in vacuo
  9. customto give a yellow semi-solid
  10. customThe residue was purified by preparative HPLC (Symmetry C18, isocratic, 50% acetonitrile/water)

Sources & evidence

ORD record
ord-b5f8f16890ed46439183e413edcea1e1
Source dataset
uspto-grants-2009_08
Patent number
US07576104B2

Reaction notes

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