Reaktion #10148

Reaktionsgleichung

3-(3-Chloro-benzylamino)-phthalic acid

3-amino-3-methyl-piperidine-2,6-dione hydrochloride

→

product

Ausbeute 41.0%

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

Ausbeute 41.0%

Lösungsmittel

pyridine

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction mixture was heated
2. 2
   Temperaturto reflux for 18 h
3. 3
   SonstigeThe solvent was evaporated in vacuo
4. 4
   workup.DISSOLUTIONthe residue dissolved in methylene chloride (150 ml)
5. 5
   WaschenThe methylene chloride mixture was washed with water (2×100 ml), 0.1N HCl (2×100 ml), brine (1×100 ml)
6. 6
   Trocknendried (magnesium sulfate)
7. 7
   Filtrationfiltered
8. 8
   SonstigeThe solvent was evaporated in vacuo
9. 9
   Sonstigeto give a yellow semi-solid
10. 10
    SonstigeThe residue was purified by preparative HPLC (Symmetry C18, isocratic, 50% acetonitrile/water)

Vorschrift

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 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.

Quelle