Hydrochloric Acid → N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-benzamide

HRID 331561

Reaktionsgleichung

Reaktionsgleichung von HRID 331561
CS(O)(=O)=O.[NH2:6][CH2:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[C:13](=[O:17])[N:12]([CH:18]1[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:19]1=[O:25])[CH2:11]2.[C:26](Cl)(=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(N(CC)CC)C.Cl>C(#N)C>[O:25]=[C:19]1[CH:18]([N:12]2[CH2:11][C:10]3[C:14](=[CH:15][CH:16]=[C:8]([CH2:7][NH:6][C:26](=[O:33])[C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH:9]=3)[C:13]2=[O:17])[CH2:23][CH2:22][C:21](=[O:24])[NH:20]1

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 7412Benzoyl chlorideHCID 8471TriethylamineHCID 866307653-(5-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione methanesulfonate

Produkt 1

HCID 44539606N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-benzamideAusbeute 64 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

To a stirred mixture of 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione methane sulfonate (0.50 g, 1.80 mmol) and benzoyl chloride (0.25 g, 1.80 mmol) in acetonitrile (20 mL), was added triethylamine (0.51 mL, 3.60 mmol) at room temperature under nitrogen. After 1 h, 1N aq. HCl (20 mL) was added and the mixture was stirred for 10 min. The product was isolated by filtration, washed with 1N aq. HCl (20 mL), acetonitrile (20 mL) and dried overnight in vacuo to give N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-benzamide as a white solid (0.43 g, 64% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 30/70 CH3CN/0.1% H3PO4, 3.17 min (99.25%); mp: 266-268° C.; 1H NMR (DMSO-d6) δ 1.93-2.06 (m, 1H), 2.27-2.47 (m, 1H), 2.53-2.68 (m, 1H), 2.79-3.05 (m, 1H), 4.31 (d, J=17.4 Hz, 1H), 4.45 (d, J=17.4 Hz, 1H), 4.60 (d, J=5.9 Hz, 2H), 5.11 (dd, J=5.0, 13.1 Hz, 1H), 7.42-7.62 (m, 5H), 7.70 (d, J=7.7 Hz, 1H), 7.91 (d, J=7.0 Hz, 2H), 9.16 (t, J=5.9 Hz, 1H), 10.99 (s, 1H); 13C NMR (DMSO-d6) δ 22.5, 31.2, 42.7, 47.1, 51.6, 122.1, 122.9, 127.1, 127.2, 128.3, 130.3, 131.3, 134.2, 142.4, 144.0, 166.3, 167.9, 171.0, 172.8; LCMS: MH=378; Anal Calcd for C21H19N3O4: C, 66.83; H, 5.07; N, 11.13. Found: C, 66.75; H, 5.08; N, 11.18.

Aufarbeitung

  1. customThe product was isolated by filtration
  2. washwashed with 1N aq. HCl (20 mL), acetonitrile (20 mL)
  3. customdried overnight in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-da6aed4029ff4a85946a1201b57bf697
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08877780B2

Verknüpfte Notizen

Wird geladen…