Reacción #10060

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

propionyl chloride

→

N-{[2-(2,6-Dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}propanamide

Disolventes

CH3CN

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGThe mixture was stirred at room temperature for 17 hours
2. 2
   OtroSolvent was removed in vacuo
3. 3
   workup.DISSOLUTIONthe residue was dissolved in CH2Cl2 (60 ml)
4. 4
   Lavadowashed with 1N HCl (30 ml), H2O (30 ml), brine (30 ml)
5. 5
   Secadodried (MgSO4)
6. 6
   OtroThe solvent was removed
7. 7
   Otroto give
8. 8
   Filtraciónafter filtration N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}propanamide (0.41 g, 64%) as a white solid

Procedimiento

1,8-Diazabicyclo[5,4,0]undec-7-ene (0.65 g, 4.25 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, propionyl chloride (0.2 g, 2.13 mmol) was added. The mixture was stirred at room temperature for 17 hours. Solvent was removed in vacuo and the residue was dissolved in CH2Cl2 (60 ml) and washed with 1N HCl (30 ml), H2O (30 ml), brine (30 ml) and dried (MgSO4). The solvent was removed and the resulting solid was slurried in hot C2H5OH (10 ml) to give after filtration N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}propanamide (0.41 g, 64%) as a white solid: mp 219–221° C.; 1H NMR (DMSO-d6) δd 11.15 (s, 1H), 8.42 (t, J=5.8 Hz, 1H), 7.87–7.67 (m, 3H), 5.19–5.12 (dd, J=5.3 and 12.5 Hz, 1H), 4.72 (d, J=5.8 Hz, 2H), 2.98–2.84 (m, 1H), 2.65–2.48 (m, 2H), 2.26–2.17 (m, 2H), 2.09–2.04 (m, 1H), 1.05 (t, J=7.8 Hz, 3H); 13C NMR (DMSO-d6) δ d 173.52, 172.81, 169.79, 167.53, 167.01, 139.52, 134.79, 133.20, 131.55, 127.10, 121.86, 48.89, 37.69, 30.95, 28.43, 22.03, 9.90; Anal. Calcd. For C17H17N3O5+0.19 H2O: C, 58.88; H, 5.05; N, 12.12. Found: C, 58.77; H, 4.97; N, 12.12.

Fuente