Реакция #10122

Уравнение реакции

1,8-Diazabicyclo[5,4,0]undec-7-ene

4-(aminomethyl)-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione hydrochloride

benzyl isocyanate

→

N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}(benzylamino)carboxamide

Выход 54.0%

Растворители

CH3CN

Условия реакции

Обработка

1. 1
   workup.STIRRINGThe mixture was stirred at room temperature for 17 hours
2. 2
   ДругоеThe solvent was removed in vacuo
3. 3
   workup.DISSOLUTIONthe residue was dissolved in CH2Cl2 (70 mL)
4. 4
   ПромывкаThe CH2Cl2 solution was washed with 1N HCl (30 mL), H2O (30 mL), brine (30 mL)
5. 5
   Сушкаdried (MgSO4)
6. 6
   ДругоеThe solvent was removed in vacuo
7. 7
   Другоеthe residue was purified by chromatography (SiO2, CH2Cl2:CH3OH 96:4)

Методика

1,8-Diazabicyclo[5,4,0]undec-7-ene (0.29 g, 1.90 mmol) was added to a stirred suspension of 4-(aminomethyl)-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione hydrochloride (0.6 g, 1.85 mmol) in CH3CN (50 mL). After stirring for 20 min, benzyl isocyanate (0.32 g, 2.41 mmol) was added. The mixture was stirred at room temperature for 17 hours. The solvent was removed in vacuo and the residue was dissolved in CH2Cl2 (70 mL). The CH2Cl2 solution was washed with 1N HCl (30 mL), H2O (30 mL), brine (30 mL) and dried (MgSO4). The solvent was removed in vacuo and the residue was purified by chromatography (SiO2, CH2Cl2:CH3OH 96:4) to give N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}(benzylamino)carboxamide (0.42 g, 54%) as a white solid: mp 192–194° C.; 1H NMR (DMSO-d6) δ 11.13 (s, 1H), 7.86–7.69 (m, 3H), 7.34–7.19 (m, 5H), 6.67 (t, J=5.8 Hz, 1H), 6.60 (t, J=5.9 Hz, 1H) 5.18–5.11 (dd, J=5.3 and 12.5 Hz, 1H, 4.67 (d, J=5.9 Hz, 2H), 4.23 (d, J=5.8 Hz, 2H), 2.97–2.83 (m, 1H), 2.63–2.50 (m, 2H), 2.07–2.03 (m, 1H); 13C NMR (DMSO-d6) δ 175.63, 172.75, 167.56, 167.03, 158.05, 141.01, 140.70, 134.61, 133.31, 131.52, 128.19, 126.98, 126.55, 121.66, 48.83, 42.99, 30.93, 21.98; Anal. Calcd. For C22H20N4O5: C, 62.85; H, 4.79; N, 13.33. Found: C, 62.78; H, 4.53; N, 13.18.

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