Réaction #10118

Équation de réaction

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

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

propyl isocyanate

→

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

Rendement 20.0%

Solvants

CH3CN

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGThe mixture was stirred at room temperature for 17 hours
2. 2
   AutreThe solvent was removed
3. 3
   workup.DISSOLUTIONthe residue was dissolved in CH2Cl2 (70 mL)
4. 4
   LavageThe CH2Cl2 solution was washed with 1N HCl (30 mL), H2O (30 mL), brine (30 mL)
5. 5
   Séchagedried (MgSO4)
6. 6
   AutreThe solvent was removed in vacuo
7. 7
   Autrethe residue was purified by chromatography (SiO2, CH2Cl2:CH3OH 100:3)

Mode opératoire

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, propyl isocyanate (0.24 g, 2.77 mmol) was added. The mixture was stirred at room temperature for 17 hours. The solvent was removed 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 100:3) to give N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}(propylamino)carboxamide (0.13 g, 20%) as a white solid: mp160–162° C.; 1H NMR (DMSO-d6) δ 11.14 (s, 1H), 7.86–7.69 (m, 3H), 6.44 (t, J=5.9 Hz, 1H), 6.16 (t, J=1H), 5.18–5.11 (dd, J=5.3 and 12.4 Hz, 1H), 4.63 (d, J=5.9 Hz, 2H), 2.99–2.83 (m, 3H), 2.64–2.50 (m, 2H), 2.08–2.04 (m, 1H), 1.42–1.32 (m, 2H), 0.83 (t, J=7.3 Hz, 3H); 13C NMR (DMSO-d6) δ 172.78, 169.84, 167.59, 167.05, 158.03, 141.16, 134.62, 133.34, 131.51, 126.96, 121.63, 48.82, 41.18, 30.94, 23.15, 21.99, 11.33; Anal. Calcd. For C18H20N4O5: C, 58.06; H, 5.41; N, 15.05. Found: C, 57.94; H, 5.31; N, 14.90.

Source