1,8-Diazabicyclo(5.4.0)undec-7-ene → 3-{[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-carbamoyl}-propyl-carbamic acid t-butyl ester

HRID 448302

Reaktionsgleichung

Reaktionsgleichung von HRID 448302
N12CCCN=C1CCCCC2.Cl.[NH2:13][CH2:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[CH2:17][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:33]([NH:40][CH2:41][CH2:42][CH2:43][C:44](O)=[O:45])([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34].Cl.CN(C)CCCN=C=NCC>CN(C=O)C>[C:36]([O:35][C:33](=[O:34])[NH:40][CH2:41][CH2:42][CH2:43][C:44](=[O:45])[NH:13][CH2:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[CH2:17][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])([CH3:39])([CH3:37])[CH3:38]

Komponenten

6

Edukt 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 2948944-(((Tert-butoxy)carbonyl)amino)butanoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 219885683-(4-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride

Produkt 1

HCID 161174773-{[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-carbamoyl}-propyl-carbamic acid t-butyl esterAusbeute 77,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

1,8-Diazabicyclo[5,4,0]-undec-7-ene (1.8 g, 11.8 mmol) was added to a stirred suspension of 3-(4-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hydrochloride (1.4 g, 4.5 mmol) in DMF (50 mL). After stirring for 10 minutes, 1-hydroxbenzotriazole (0.7 g, 5.4 mmol) and N—BOC-γ-aminobutyric acid (1.1 g, 5.4 mmol) were added. The reaction was initiated by addition of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (1.3 g, 6.8 mmol). The mixture was stirred at room temperature overnight. The mixture was concentrated, and the residue was stirred with EtOAc (50 mL) and H2O (40 mL) for 30 minutes. The mixture was filtered, and dried to give (3-{[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-carbamoyl}-propyl-carbamic acid t-butyl ester (1.6 g, 77%) as a white solid: mp 199-201° C.; 1H NMR (DMSO-d6) δ 1.37 (s, 9H, 3CH3), 1.58-1.66 (m, 2H, CH2), 1.99-2.16 (m, 3H), 2.36-2.49 (m, 1H), 2.58-2.64 (m, 1H), 2.86-2.94 (m, 3H), 4.31 (d, J=5.6 Hz, 2H, CH2), 4.38 (d, J=17.3 Hz, 1H), 4.46 (d, J=17.3 Hz, 1H), 5.10-5.18 (dd, J=5.0 and 13.1 Hz, 1H, CH), 6.81 (t, J=5.4 Hz, 1H, NH), 7.48-7.64 (m, 3H, Ar), 8.37 (t, J=5.7 Hz, 1H, NH), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.56, 25.72, 28.23, 31.18, 32.63, 38.95, 46.15, 51.56, 77.04, 121.60, 128.27, 130.55, 131.61, 134.70, 140.06, 155.55, 168.04, 170.97, 171.90, 172.82; Anal. calcd. for C23H30N4O6: C, 60.25; H, 6.59; N, 12.22. Found: C, 60.12; H, 6.55; N, 12.15.

Aufarbeitung

  1. stirringThe mixture was stirred at room temperature overnight
  2. concentrationThe mixture was concentrated
  3. stirringthe residue was stirred with EtOAc (50 mL) and H2O (40 mL) for 30 minutes
  4. filtrationThe mixture was filtered
  5. customdried

Quellen und Nachweise

ORD-Eintrag
ord-028d9c88c000478393c16547cc33c50f
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08481568B2

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