Reaktion #10061

Reaktionsgleichung

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

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

nicotinoyl chloride

→

[(2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}-3-pyridylcarboxamide

Ausbeute 64.7%

Lösungsmittel

CH3CN

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGAfter stirring for 20 min
2. 2
   workup.STIRRINGThe mixture was stirred at room temperature for 17 hours
3. 3
   SonstigeThe solvent was removed in vacuo
4. 4
   workup.DISSOLUTIONthe residue was dissolved in CH2Cl2 (70 ml)
5. 5
   WaschenThe CH2Cl2 solution was washed with H2O (30 ml), brine (30 ml)
6. 6
   Trocknendried (MgSO4)
7. 7
   SonstigeThe solvent was removed in vacuo
8. 8
   Sonstigethe residue was purified by flash chromatography (SiO2, CH2Cl2:CH3OH 97.5:2.5)

Vorschrift

1,8-Diazabicyclo[5,4,0]undec-7-ene (0.98 g, 6.48 mmol) was added to 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, nicotinoyl chloride (0.41 g, 2.22 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 H2O (30 ml), brine (30 ml) and dried (MgSO4). The solvent was removed in vacuo and the residue was purified by flash chromatography (SiO2, CH2Cl2:CH3OH 97.5:2.5) to give N-{[(2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}-3-pyridylcarboxamide (0.47 g, 64%) as a white solid: mp 148–151° C.; 1H NMR (DMSO-d6) δ d 11.16 (s, 1H), 9.36 (t, J=5.6 Hz, 1H), 9.09 (d, J=1.25 Hz, 1H), 8.75–8.73 (m, 1H), 8.25 (d, J=8.0 Hz, 1H), 7.84–7.76 (m, 3H), 7.57–7.52 (m, 1H), 5.22–5.15 (dd, J=5.4 and 12.7 Hz, 1H), 4.96 (d, J=5.6 Hz, 2H), 2.92–2.85 (m, 1H), 2.65–2.50 (m, 2H), 2.11–2.06 (m, 1H); 13C NMR (DMSO-d6) δ d 172.72, 169.80, 167.51, 166.94, 165.23, 152.02, 148.44, 138.86, 135.10, 134.83, 133.20, 131.55, 129.48, 127.20, 123.49, 121.95, 48.89, 38.33, 30.93, 21.98; Anal. Calcd. For C20H16N4O5+0.28 H2O: C, 60.45; H, 4.20; N, 14.10. Found: C, 60.29; H, 4.28; N, 13.82.

Quelle