Reacción #10148

Ecuación de reacción

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

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

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product

Rendimiento 41.0%

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

Rendimiento 41.0%

Disolventes

pyridine

Condiciones de reacción

Tratamiento posterior

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

Procedimiento

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.

Fuente