반응 #10115

반응 방정식

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

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

cyclohexanecarbonyl chloride

→

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

수율 72.1%

용매

CH3CN

반응 조건

후처리

1. 1
   workup.STIRRINGThe mixture was stirred at room temperature for 17 hours
2. 2
   기타The solvent was removed in vacuo
3. 3
   workup.DISSOLUTIONthe residue was dissolved in CH2Cl2 (70 mL)
4. 4
   세척The CH2C2 solution was washed with 1N HCL (30 mL), H2O (30 mL), brine (30 mL)
5. 5
   건조dried (MgSO4)
6. 6
   기타The solvent was removed
7. 7
   기타the residue was purified by chromatography (SiO2, CH2Cl2:EtOAc 6:4)

실험 절차

1,8-Diazabicyclo[5,4,0]undec-7-ene (0.62 g, 4.08 mmol) was added to a stirred suspension of 4-(aminomethyl)-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione hydrochloride (0.60 g, 1.85 mmol) in CH3CN (50 mL). After stirring for 20 min, cyclohexanecarbonyl chloride (0.33 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 CH2C2 solution was washed with 1N HCL (30 mL), H2O (30 mL), brine (30 mL) and dried (MgSO4). The solvent was removed and the residue was purified by chromatography (SiO2, CH2Cl2:EtOAc 6:4) to give N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}cyclohexylcarboxamide (0.53 g, 72%) as a white solid: mp 142–144° C.; 1H NMR (DMSO-d6) δ 11.13 (s, 1H), 8.36 (t, J=5.8 Hz, 1H), 7.86–7.77 (m, 2H), 7.64–7.61 (m, 1H), 5.18–5.11 (dd, J=5.3 and 12.5 Hz, 1H), 4.70 (d, J=5.8 Hz, 2H), 2.97–2.83 (m, 1H), 2.63–2.47 (m, 2H), 2.26–2.17 (m, 1H), 2.08–2.0 (m, 1H), 1.79–1.61 (m, 5H), 1.43–1.12 (m, 5H); 13C NMR (DMSO-d6) δ 175.58, 172.75, 169.82, 167.49, 166.96, 139.68, 134.75, 132.76, 131.49, 126.99, 121.73, 48.83, 43.90, 37.43, 30.92, 29.20, 25.43, 25.24, 21.96; Anal. Calcd. For C21H23N3O5: C, 63.47; H, 5.83; N, 10.57. Found: C, 63.12; H, 5.68; N, 10.41.

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