Cyclohexanecarbonyl chloride → n-{[2-(2,6-Dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}cyclohexylcarboxamide

HRID 10019

Reaktionsgleichung

Reaktionsgleichung von HRID 10019
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].[CH:34]1([C:40](Cl)=[O:41])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]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:40]([CH:34]3[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]3)=[O:41])[C:19]2=[O:24])[CH2:30][CH2:29][C:28](=[O:31])[NH:27]1

Komponenten

5

Edukt 3

HCID 75938Cyclohexanecarbonyl chlorideHCID 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

Produkt 1

HCID 10178926n-{[2-(2,6-Dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}cyclohexylcarboxamideAusbeute 72,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

1,8-Diazabicyclo[5,4,0]undec-7-ene (0.62 g, 4.08 mmol) was added to a stirred suspension of 4-(aminomethyl)-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione hydrochloride (0.60 g, 1.85 mmol) in CH3CN (50 mL). After stirring for 20 min, cyclohexanecarbonyl chloride (0.33 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 CH2C2 solution was washed with 1N HCL (30 mL), H2O (30 mL), brine (30 mL) and dried (MgSO4). The solvent was removed and the residue was purified by chromatography (SiO2, CH2Cl2:EtOAc 6:4) to give N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}cyclohexylcarboxamide (0.53 g, 72%) as a white solid: mp 142–144° C.; 1H NMR (DMSO-d6) δ 11.13 (s, 1H), 8.36 (t, J=5.8 Hz, 1H), 7.86–7.77 (m, 2H), 7.64–7.61 (m, 1H), 5.18–5.11 (dd, J=5.3 and 12.5 Hz, 1H), 4.70 (d, J=5.8 Hz, 2H), 2.97–2.83 (m, 1H), 2.63–2.47 (m, 2H), 2.26–2.17 (m, 1H), 2.08–2.0 (m, 1H), 1.79–1.61 (m, 5H), 1.43–1.12 (m, 5H); 13C NMR (DMSO-d6) δ 175.58, 172.75, 169.82, 167.49, 166.96, 139.68, 134.75, 132.76, 131.49, 126.99, 121.73, 48.83, 43.90, 37.43, 30.92, 29.20, 25.43, 25.24, 21.96; Anal. Calcd. For C21H23N3O5: C, 63.47; H, 5.83; N, 10.57. Found: C, 63.12; H, 5.68; N, 10.41.

Aufarbeitung

  1. stirringThe mixture was stirred at room temperature for 17 hours
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue was dissolved in CH2Cl2 (70 mL)
  4. washThe CH2C2 solution was washed with 1N HCL (30 mL), H2O (30 mL), brine (30 mL)
  5. dry with materialdried (MgSO4)
  6. customThe solvent was removed
  7. customthe residue was purified by chromatography (SiO2, CH2Cl2:EtOAc 6:4)

Quellen und Nachweise

ORD-Eintrag
ord-8282c79fceb34b179b50e433d37322d7
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07091353B2

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