Hydrochloric Acid → 1-(3-chloro-4-methyl-phenyl)-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-thiourea

HRID 331642Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 331642
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.[Cl:26][C:27]1[CH:28]=[C:29]([N:34]=[C:35]=[S:36])[CH:30]=[CH:31][C:32]=1[CH3:33].Cl>C(#N)C>[Cl:26][C:27]1[CH:28]=[C:29]([NH:34][C:35]([NH:6][CH2:7][C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[C:13](=[O:17])[N:12]([CH:18]2[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:19]2=[O:25])[CH2:11]3)=[S:36])[CH:30]=[CH:31][C:32]=1[CH3:33]

Komponenten

5

Edukt 3

HCID 313Hydrochloric AcidHCID 1405053-Chloro-4-methylphenyl isothiocyanateHCID 866307653-(5-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione methanesulfonate

Produkt 1

HCID 577305151-(3-chloro-4-methyl-phenyl)-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-thioureaAusbeute 84 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

TEA (0.28 g, 2.8 mmol) was added to a mixture of 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione methanesulfonate (0.50 g, 1.4 mmol) and 3-chloro-4-methylphenyl isothiocyanate (0.26 g, 1.4 mmol) in acetonitrile (30 mL) at 0° C. 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-(3-chloro-4-methyl-phenyl)-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-thiourea as a white solid (0.52 g, 84% yield); mp 240-242° C.; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 ml/min, 240 nm, 40/60 CH3CN/0.1% H3PO4, 7.11 (97.48%); 1H NMR (DMSO-d6) δ 1.95-2.06 (m, 1H, CHH), 2.29 (s, 3H, CH3), 2.35-2.47 (m, 1H, CHH), 2.55-2.67 (m, 1H, CHH), 2.84-3.00 (m, 1H, CHH), 4.32 (d, 1H, CHH), 4.46 (d, 1H, CHH), 4.86 (d, J=5.1 Hz, 2H, CH, and CHH), 5.11 (dd, 1H, CH), 7.25 (dd, 1H, Ar), 7.28 (d, 1H, Ar), 7.47 (d, 1H, Ar), 7.54 (s, 1H, Ar), 7.61 (s, 1H, Ar), 7.70 (d, 1H, Ar), 8.37 (t, 1H, NH), 9.73 (s, 1H, NH), 11.00 (s, 1H, NH); 13C NMR (DMSO-d6) δ 18.96, 22.49, 31.20, 47.13, 51.58, 122.14, 122.88, 123.48, 127.13, 130.39, 130.97, 131.12, 132.67, 138.29, 142.27, 143.32, 167.92, 170.99, 172.86, 181.00; LCMS: MH=457/459; Anal. Calcd for C22H21ClN4O3S: C, 57.83; H, 4.63; N, 12.26. Found: C, 57.57; H, 4.51; N, 12.21.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-a47ae29587a1410f96c3773153b98ad0
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08877780B2

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