Imidazole → 3-(6,8-dichloro-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione

HRID 509523Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 509523
[NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][C:8]([Cl:12])=[CH:7][C:3]=1[C:4]([OH:6])=O.N1[CH:17]=[CH:16]N=C1.C(Cl)(=O)C.Cl.[NH2:23][CH:24]1[CH2:29][CH2:28][C:27](=[O:30])[NH:26][C:25]1=[O:31].P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>C(#N)C>[Cl:12][C:8]1[CH:7]=[C:3]2[C:2](=[C:10]([Cl:11])[CH:9]=1)[N:1]=[C:16]([CH3:17])[N:23]([CH:24]1[CH2:29][CH2:28][C:27](=[O:30])[NH:26][C:25]1=[O:31])[C:4]2=[O:6]

Komponenten

7

Edukt 5

HCID 795Imidazole2×HCID 6367Acetyl chlorideHCID 7540Triphenyl phosphiteHCID 760363,5-Dichloroanthranilic acidHCID 1345483-Aminopiperidine-2,6-dione hydrochloride

Produkt 1

HCID 252352263-(6,8-dichloro-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dioneAusbeute 58 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

To a stirred mixture of 2-amino-3,5-dichlorobenzoic acid (5.0 g, 24 mmol) and imidazole (1.9 g, 28 mmol) in acetonitrile (60 mL), was added acetyl chloride (2.0 mL, 28 mmol) at room temperature. The mixture was stirred at room temperature overnight. To the mixture, was added 3-amino-piperidine-2,6-dione hydrogen chloride (3.9 g, 24 mmol), imidazole (3.5 g, 52 mmol) and triphenyl phosphite (6.8 mL, 26 mmol) and heated to reflux for 22 hours. The suspension was filtered and washed with acetonitrile (30 mL), water (2×30 mL), and ethyl acetate (30 mL) to give 3-(6,8-dichloro-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (4.65 g, 58% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 40/60 CH3CN/0.1% H3PO4, 4.78 min (100%); mp: 238-240° C.; 1H NMR (DMSO-d6) δ 2.15-2.22 (m, 1H, CHH), 2.55-2.69 (m, 5H, CH, 2CHH), 2.78-2.91 (m, 1H, CHH), 5.33 (dd, J=6, 11 Hz, 1H, NCH), 7.96 (d, J=2 Hz, 1H. Ar), 8.15 (d, J=2 Hz, 1H, Ar), 11.09 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.63, 23.85, 30.54, 56.92, 122.55, 24.24, 130.51, 131.72, 134.38, 142.25, 156.80, 159.07, 169.12, 172.53; LCMS: MH=340, 342; Anal Calcd for C14H11N3O3Cl2: C, 49.43; H, 3.26; N, 12.35; Cl, 20.84. Found: C, 49.21; H, 3.11; N, 12.30; Cl, 19.43.

Aufarbeitung

  1. temperatureheated
  2. temperatureto reflux for 22 hours
  3. filtrationThe suspension was filtered
  4. washwashed with acetonitrile (30 mL), water (2×30 mL), and ethyl acetate (30 mL)

Quellen und Nachweise

ORD-Eintrag
ord-9d31227c88844b00bb1833ea23f0b304
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09096573B2

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