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

HRID 63508

Reaktionsgleichung

Reaktionsgleichung von HRID 63508
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]1([N:36]=[C:37]=[O:38])[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH:29]=[CH:28][CH:27]=1.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:37]([NH:36][C:26]4[C:35]5[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=5)[CH:29]=[CH:28][CH:27]=4)=[O:38])[CH:9]=3)[C:13]2=[O:17])[CH2:23][CH2:22][C:21](=[O:24])[NH:20]1

Komponenten

5

Edukt 3

HCID 313Hydrochloric AcidHCID 66589alpha-Naphthyl isocyanateHCID 866307653-(5-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione methanesulfonate

Produkt 1

HCID 445389201-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-3-naphthalen-1-yl-ureaAusbeute 89 %

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 methanesulfonate (0.37 g, 1.00 mmol) and 1-naphthylisocyanate (0.17 g, 1.00 mmol) in acetonitrile (30 mL) at 0° C. was added TEA (0.20 g, 2.0 mmol) dropwise over 10 min. The mixture was stirred at ambient temperature for 3 h and then 10% aqueous HCl solution (30 mL) was added. The solid precipitate was filtered and dried in vacuo providing 1-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-3-naphthalen-1-yl-urea as a white solid (0.39 g, 89% yield); mp 250-252° C.; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 ml/min, 240 nm, 40/60 CH3CN/0.1% H3PO4, 6.96 (97.91%); 1H NMR (DMSO-d6) δ 1.94-2.06 (m, 1H, CHH), 2.29-2.47 (m, 1H, CHH), 2.54-2.67 (m, 1H, CHH), 2.84-3.00 (m, 1H, CHH), 4.26-4.46 (m, 2H, CHH), 4.50 (d, J=4.9 Hz, 2H, CH2 and CHH), 5.11 (dd, 1H, CH), 7.17 (t, 1H, NH), 7.38-7.62 (m, 6H, Ar), 7.72 (d, J=7.7 Hz, 1H, Ar), 7.90 (d, 1H, Ar), 8.01 (d, 1H, Ar), 8.12 (d, 1H, Ar), 8.69 (s, 1H, NH), 10.99 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.49, 31.20, 42.95, 47.13, 51.58, 116.73, 121.38, 121.98, 122.26, 123.00, 125.43, 125.61, 125.74, 125.89, 126.97, 128.34, 130.36, 133.69, 134.98, 142.45, 144.72, 155.66, 167.95, 170.99, 172.85; LCMS: MH=443; Anal. Calcd for C25H22N4O4: C, 67.86; H, 5.01; N, 12.66. Found: C, 67.50; H, 4.96; N, 12.34.

Aufarbeitung

  1. filtrationThe solid precipitate was filtered
  2. customdried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-460a445922eb4023b7ca1c30b9a71350
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09447070B2

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