3-Pyridinecarbonyl chloride, hydrochloride (1:1) → N-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)nicotinamide

HRID 9961

反応式

HRID 9961 の反応式
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4](=[O:20])[N:5]([CH:12]1[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:19])[C:6]2=[O:11].Cl.[C:22](Cl)(=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[N:25][CH:24]=1>O1CCCC1.O.CCOCC>[O:19]=[C:13]1[CH:12]([N:5]2[C:4](=[O:20])[C:3]3[C:7](=[CH:8][CH:9]=[CH:10][C:2]=3[NH:1][C:22]([C:23]3[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=3)=[O:29])[C:6]2=[O:11])[CH2:17][CH2:16][C:15](=[O:18])[NH:14]1

参加物

6

反応物 2

HCID 884383-Pyridinecarbonyl chloride, hydrochloride (1:1)HCID 134780Pomalidomide

生成物 1

HCID 10270982N-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)nicotinamide収率 79.3%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 3283Diethyl Ether溶媒2 回HCID 8028Tetrahydrofuran溶媒

実験手順

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.

後処理

  1. temperaturewas heated
  2. temperatureto reflux for 22 h
  3. filtrationThe suspension was filtered
  4. washwashed with tetrahydrofuran (20 ml) and ether (10 ml)
  5. customto yield a white solid
  6. filtrationThe suspension was filtered

出典と根拠

ORDレコード
ord-b5f01c76dcc04a9ab51771e818636cb8
出典データセット
uspto-grants-2006_08
特許番号
US07091353B2

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