Cyclohexyl isocyanate → 1-Cyclohexyl-3-[2-(2,6-dioxo-piperidin-3-YL)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-urea

HRID 448277

Reaktionsgleichung

Reaktionsgleichung von HRID 448277
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].[CH:33]1([N:39]=[C:40]=[O:41])[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1>C(#N)C>[CH:33]1([NH:39][C:40]([NH:13][CH2:14][C:15]2[CH:23]=[CH:22][CH:21]=[C:20]3[C:16]=2[CH2:17][N:18]([CH:25]2[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]2=[O:32])[C:19]3=[O:24])=[O:41])[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1

Komponenten

5

Edukt 3

HCID 18502Cyclohexyl isocyanateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 219885683-(4-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride

Produkt 1

HCID 161169551-Cyclohexyl-3-[2-(2,6-dioxo-piperidin-3-YL)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-ureaAusbeute 16 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

1,8-Diazabicyclo[5,4,0]undec-7-ene (0.4 g, 2.9 mmol) was added to a stirred suspension of 3-(4-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hydrochloride (0.6 g, 1.9 mmol) in acetonitrile (100 mL). The mixture was heated for 30 minutes, then cooled to room temperature. Cyclohexyl isocyanate (0.4 g, 2.9 mmol) was added and the mixture was stirred at room temperature overnight. The mixture was filtered and the solid was stirred with water (25 mL) to give 0.9 g of crude product. The crude product was recrystallized from methanol to give 1-cyclohexyl-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-urea (0.12 g, 16%) as a white solid: mp 309-311° C.; 1H NMR (DMSO-d6) δ 0.97-1.75 (m, 10H), 1.99-2.04 (m, 1H), 2.32-2.64 (m, 3H), 2.86-2.98 (m, 1H), 4.27-4.51 (m, 4H), 5.11-5.18 (dd, J=4.9 and 13.1 Hz, 1H, CH), 5.86 (d, J=7.9 Hz, 1H), 6.26 (t, J=5.5 Hz, 1H, NH), 7.47-7.62 (m, 3H, Ar), 11.01 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.64, 24.44, 25.29, 31.16, 33.32, 46.09, 47.50, 47.85, 51.47, 121.36, 128.18, 130.26, 131.61, 136.28, 139.77, 157.20, 168.09, 170.97, 172.82; Anal. calcd. for C21H26N4O4: C, 63.30; H, 6.58; N, 14.06. Found: C, 63.18; N, 6.58; N, 13.99.

Aufarbeitung

  1. temperatureThe mixture was heated for 30 minutes
  2. filtrationThe mixture was filtered
  3. stirringthe solid was stirred with water (25 mL)
  4. customto give 0.9 g of crude product
  5. customThe crude product was recrystallized from methanol

Quellen und Nachweise

ORD-Eintrag
ord-7d078c0149cb4941b58fba04b2384487
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08481568B2

Verknüpfte Notizen

Wird geladen…