反应 #10153

反应方程式

Diisopropylethylamine

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

piperidine

diisopropylethylamine

triphosgene

→

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

收率 145.3%

溶剂

acetonitrile

acetonitrile

acetonitrile

反应条件

后处理

1. 1
   workup.STIRRINGAfter a further 10 min of stirring
2. 2
   workup.STIRRINGThe mixture was stirred at room temperature for 17 hours
3. 3
   浓缩The mixture was concentrated
4. 4
   workup.DISSOLUTIONthe residue was dissolved in methylene chloride (80 mL)
5. 5
   洗涤The methylene chloride solution was washed with 10% KHSO4 (30 mL), H2O (2×30 mL), brine (30 mL)
6. 6
   干燥dried (MgSO4)
7. 7
   其他Solvent was removed
8. 8
   其他the residue was purified by chromatography (CH2Cl2:CH3OH 97.5:2.5)

实验过程

Diisopropylethylamine (0.88 g, 6.79 mmol) was added to a stirred suspension of 4-(aminomethyl)-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione hydrochloride (1.0 g, 3.09 mmol) in acetonitrile (50 mL). After stirring for 20 min, the mixture was slowly added to a stirred solution of triphosgene (0.34 g, 1.14 mmol) in acetonitrile (15 mL) over 30 min. After a further 10 min of stirring, a solution of piperidine (0.26 g, 3.09 mmol) and diisopropylethylamine (0.48 g, 3.71 mmol) in acetonitrile (10 mL) was added in one portion. The mixture was stirred at room temperature for 17 hours. The mixture was concentrated and the residue was dissolved in methylene chloride (80 mL). The methylene chloride solution was washed with 10% KHSO4 (30 mL), H2O (2×30 mL), brine (30 mL) and dried (MgSO4). Solvent was removed and the residue was purified by chromatography (CH2Cl2:CH3OH 97.5:2.5) to give N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4- yl]methyl}piperidylcarboxamide (0.66 g, 53%) as a white solid: mp 156–158° C.; 1H NMR (DMSO-d6) δ 11.14 (s, 1H), 7.86–7.75 (m, 2H), 7.69 (d, J=7.4 Hz, 1H), 7.12 (t, J=5.6 Hz, 1H), 5.18–5.11 (dd, J=5.3 and 12.5 Hz, 1H), 4.69 (d, J=5.5 Hz, 2H), 3.42–3.32 (m, 4H), 2.96–2.83 (m, 1H), 2.63–2.50 (m, 2H), 2.08–2.03 (m, 1H), 1.54–1.44 (m, 6H); 13C NMR (DMSO-d6) δ 172.74, 169.83, 167.60, 157.26, 141.46, 134.58, 132.82, 131.38, 126.74, 121.43, 48.82, 44.37, 30.93, 25.37, 24.12, 21.98; Anal. Calcd. For C20H22N4O5+0.22 H2O: C, 59.70; H, 5.62; N, 13.92. Found: C, 60.14; H, 5.59; N, 13.47.

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