Reacción #10118

Ecuación de reacción

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

Rendimiento 20.0%

Disolventes

CH3CN

Condiciones de reacción

Tratamiento posterior

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

Procedimiento

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.

Fuente