1,8-Diazabicyclo(5.4.0)undec-7-ene → [(2-(2,6-Dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}-3-pyridylcarboxamide

HRID 9965

反応式

HRID 9965 の反応式
N12CCCN=C1CCCCC2.Cl.[NH2:13][CH2:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[C:17](=[O:33])[N:18]([CH:25]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32])[C:19]2=[O:24].[C:34](Cl)(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[N:37][CH:36]=1>CC#N>[O:32]=[C:26]1[CH:25]([N:18]2[C:17](=[O:33])[C:16]3[C:20](=[CH:21][CH:22]=[CH:23][C:15]=3[CH2:14][NH:13][C:34]([C:35]3[CH:36]=[N:37][CH:38]=[CH:39][CH:40]=3)=[O:41])[C:19]2=[O:24])[CH2:30][CH2:29][C:28](=[O:31])[NH:27]1

参加物

5

反応物 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 82604Nicotinoyl chlorideHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

生成物 1

HCID 10222102[(2-(2,6-Dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}-3-pyridylcarboxamide収率 64.7%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

1,8-Diazabicyclo[5,4,0]undec-7-ene (0.98 g, 6.48 mmol) was added to stirred suspension of 4-(aminomethyl)-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione hydrochloride (0.6 g, 1.85 mmol) in CH3CN (50 ml). After stirring for 20 min, nicotinoyl chloride (0.41 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 CH2Cl2 solution was washed with H2O (30 ml), brine (30 ml) and dried (MgSO4). The solvent was removed in vacuo and the residue was purified by flash chromatography (SiO2, CH2Cl2:CH3OH 97.5:2.5) to give N-{[(2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}-3-pyridylcarboxamide (0.47 g, 64%) as a white solid: mp 148–151° C.; 1H NMR (DMSO-d6) δ d 11.16 (s, 1H), 9.36 (t, J=5.6 Hz, 1H), 9.09 (d, J=1.25 Hz, 1H), 8.75–8.73 (m, 1H), 8.25 (d, J=8.0 Hz, 1H), 7.84–7.76 (m, 3H), 7.57–7.52 (m, 1H), 5.22–5.15 (dd, J=5.4 and 12.7 Hz, 1H), 4.96 (d, J=5.6 Hz, 2H), 2.92–2.85 (m, 1H), 2.65–2.50 (m, 2H), 2.11–2.06 (m, 1H); 13C NMR (DMSO-d6) δ d 172.72, 169.80, 167.51, 166.94, 165.23, 152.02, 148.44, 138.86, 135.10, 134.83, 133.20, 131.55, 129.48, 127.20, 123.49, 121.95, 48.89, 38.33, 30.93, 21.98; Anal. Calcd. For C20H16N4O5+0.28 H2O: C, 60.45; H, 4.20; N, 14.10. Found: C, 60.29; H, 4.28; N, 13.82.

後処理

  1. stirringAfter stirring for 20 min
  2. stirringThe mixture was stirred at room temperature for 17 hours
  3. customThe solvent was removed in vacuo
  4. dissolutionthe residue was dissolved in CH2Cl2 (70 ml)
  5. washThe CH2Cl2 solution was washed with H2O (30 ml), brine (30 ml)
  6. dry with materialdried (MgSO4)
  7. customThe solvent was removed in vacuo
  8. customthe residue was purified by flash chromatography (SiO2, CH2Cl2:CH3OH 97.5:2.5)

出典と根拠

ORDレコード
ord-74d7240ff2e84224859a91ea47c8879c
出典データセット
uspto-grants-2006_08
特許番号
US07091353B2

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