Propyl isocyanate → n-{[2-(2,6-Dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}(propylamino)carboxamide

HRID 10022

反応式

HRID 10022 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].[CH2:34]([N:37]=[C:38]=[O:39])[CH2:35][CH3:36]>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:38]([NH:37][CH2:34][CH2:35][CH3:36])=[O:39])[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 61033Propyl isocyanateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

生成物 1

HCID 21988618n-{[2-(2,6-Dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}(propylamino)carboxamide収率 20%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

1,8-Diazabicyclo[5,4,0]undec-7-ene (0.29 g, 1.90 mmol) was added to a 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, propyl isocyanate (0.24 g, 2.77 mmol) was added. The mixture was stirred at room temperature for 17 hours. The solvent was removed and the residue was dissolved in CH2Cl2 (70 mL). The CH2Cl2 solution was washed with 1N HCl (30 mL), H2O (30 mL), brine (30 mL) and dried (MgSO4). The solvent was removed in vacuo and the residue was purified by chromatography (SiO2, CH2Cl2:CH3OH 100:3) to give N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}(propylamino)carboxamide (0.13 g, 20%) as a white solid: mp160–162° C.; 1H NMR (DMSO-d6) δ 11.14 (s, 1H), 7.86–7.69 (m, 3H), 6.44 (t, J=5.9 Hz, 1H), 6.16 (t, J=1H), 5.18–5.11 (dd, J=5.3 and 12.4 Hz, 1H), 4.63 (d, J=5.9 Hz, 2H), 2.99–2.83 (m, 3H), 2.64–2.50 (m, 2H), 2.08–2.04 (m, 1H), 1.42–1.32 (m, 2H), 0.83 (t, J=7.3 Hz, 3H); 13C NMR (DMSO-d6) δ 172.78, 169.84, 167.59, 167.05, 158.03, 141.16, 134.62, 133.34, 131.51, 126.96, 121.63, 48.82, 41.18, 30.94, 23.15, 21.99, 11.33; Anal. Calcd. For C18H20N4O5: C, 58.06; H, 5.41; N, 15.05. Found: C, 57.94; H, 5.31; N, 14.90.

後処理

  1. stirringThe mixture was stirred at room temperature for 17 hours
  2. customThe solvent was removed
  3. dissolutionthe residue was dissolved in CH2Cl2 (70 mL)
  4. washThe CH2Cl2 solution was washed with 1N HCl (30 mL), H2O (30 mL), brine (30 mL)
  5. dry with materialdried (MgSO4)
  6. customThe solvent was removed in vacuo
  7. customthe residue was purified by chromatography (SiO2, CH2Cl2:CH3OH 100:3)

出典と根拠

ORDレコード
ord-cf4e3707b536411c9d42a3b2becaf890
出典データセット
uspto-grants-2006_08
特許番号
US07091353B2

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