반응 #10057

반응 방정식

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

nicotinoyl chloride hydrochloride

→

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

수율 79.3%

용매

water

ether

tetrahydrofuran

ether

반응 조건

후처리

1. 1
   온도was heated
2. 2
   온도to reflux for 22 h
3. 3
   여과The suspension was filtered
4. 4
   세척washed with tetrahydrofuran (20 ml) and ether (10 ml)
5. 5
   기타to yield a white solid
6. 6
   여과The suspension was filtered

실험 절차

A stirred mixture of 4-amino-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione (1.09 g, 4.0 mmol) and nicotinoyl chloride hydrochloride (1.42 g, 8.0 mmol) in tetrahydrofuran (60 ml) was heated to reflux for 22 h. The suspension was filtered and washed with tetrahydrofuran (20 ml) and ether (10 ml) to yield a white solid. The solid was slurried in pH 7 buffer (40 ml) and ether (30 ml) for 1 h. The suspension was filtered and washed with water (20 ml) and ether (20 ml) to N-[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]-3-pyridylcarboxamide as a white solid (1.2 g, 79% yield): mp, 176–178° C.; 1H NMR (DMSO-d6) δ 2.06–2.10 (m, 1H, CHH), 2.49–2.65 (m, 2H, CH2), 2.83–2.97 (m, 1H, CHH), 5.18 (dd, J=5.3, 12.5 Hz, 1H, NCH), 7.64 (dd, J=4.9, 7.9 Hz, 1H, Ar), 7.71 (d, J=7.3 Hz, 1H, Ar), 7.92 (t, J=7.8 Hz, 1H, Ar), 8.29–8.34 (m, 1H, Ar), 8.45 (d, J=8.2 Hz, 1H, Ar), 8.83 (dd, J=1.2, 4.8 Hz, 1H, Ar), 9.15 (d, J=1.7 Hz, 1H, Ar), 10.55 (s, 1H, NH), 11.17 (s, 1H, NH); 13C NMR (DMSO-d6) δ 21.99, 30.93, 49.00, 119.06, 119.34, 123.91, 127.36, 129.17, 131.55, 135.24, 135.94, 136.20, 148.47, 152.95, 163.85, 166.59, 167.54, 169.69, 172.72; Anal Calcd for C19H14N4O5+0.13 H2O: C, 59.95; H, 3.78; N, 14.72; H2O, 0.62. Found: C, 59.83; H, 3.66; N, 14.68; H2O, 0.64.

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