Reaktion #10161

Reaktionsgleichung

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

3-[4-(aminomethyl)-1-oxoisoindolin-2-yl]piperidine-2,6-dione hydrochloride

cyclopropanecarbonyl chloride

→

N-{[2-(2,6-dioxo(3-piperidyl))-1-oxoisoindolin-4-yl]methyl}cyclopropylcarboxamide

Ausbeute 50.2%

Lösungsmittel

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe mixture was stirred at room temperature for 17 hours
2. 2
   FiltrationThe mixture was filtered
3. 3
   Sonstigethe solid was recrystallized from methanol (100 mL)

Vorschrift

1,8-Diazabicyclo[5,4,0]undec-7-ene (0.7 g, 4.62 mmol) was added to a stirred suspension of 3-[4-(aminomethyl)-1-oxoisoindolin-2-yl]piperidine-2,6-dione hydrochloride (0.65 g, 2.10 mmol) in acetonitrile (50 mL). After stirring for 30 min, cyclopropanecarbonyl chloride (0.24 g, 2.31 mmol) was added. The mixture was stirred at room temperature for 17 hours. The mixture was filtered and the solid was recrystallized from methanol (100 mL) to afford N-{[2-(2,6-dioxo(3-piperidyl))-1-oxoisoindolin-4-yl]methyl}cyclopropylcarboxamide (0.36 g, 50%) as a white solid: mp 262–264° C.; 1H NMR (DMSO-d6) δ 11.02 (s, 1H), 8.63 (t, J=5.7 Hz, 1H), 7.65–7.47 (m, 3H), 5.18–5.11 (dd, J=5.0 and 13.2 Hz, 1H), 4.46 (d=17.3 Hz, 1H), 4.38–4.31 (m, 3H), 3.00–2.85 (m, 1H), 2.65–2.30 (m, 2H), 2.04–1.99 (m, 1H), 1.64–1.54 (m, 1H), 0.69–0.65 (m, 4H); 13C NMR (DMSO-d6) δ 172.82, 172.69, 170.96, 168.03, 140.08, 134.76, 131.66, 130.70, 128.30, 121.64, 51.54, 46.15, 31.16, 22.59, 13.47, 6.27; Anal. Calcd. For C18H19N3O4: C, 63.33; H, 5.61; N, 12.31. Found: C, 62.97; H, 5.55; N, 12.33.

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