Imidazole → 3-(7-Bromo-2-methyl-4-oxo-quinazolin-3-YL)piperidine-2,6-dione

HRID 453038

Reaktionsgleichung

Reaktionsgleichung von HRID 453038
[NH2:1][C:2]1[CH:10]=[C:9]([Br:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.N1[CH:16]=[CH:15]N=C1.C(Cl)(=O)C.Cl.[NH2:22][CH:23]1[CH2:28][CH2:27][C:26](=[O:29])[NH:25][C:24]1=[O:30].P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>C(#N)C.O>[Br:11][C:9]1[CH:10]=[C:2]2[C:3]([C:4](=[O:6])[N:22]([CH:23]3[CH2:28][CH2:27][C:26](=[O:29])[NH:25][C:24]3=[O:30])[C:15]([CH3:16])=[N:1]2)=[CH:7][CH:8]=1

Komponenten

8

Edukt 5

HCID 795Imidazole2×HCID 6367Acetyl chlorideHCID 7540Triphenyl phosphiteHCID 886912-Amino-4-bromobenzoic acidHCID 1345483-Aminopiperidine-2,6-dione hydrochloride

Produkt 1

HCID 252352203-(7-Bromo-2-methyl-4-oxo-quinazolin-3-YL)piperidine-2,6-dioneAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

To a stirred mixture of 2-amino-4-bromobenzoic acid (2.0 g, 9.3 mmol) and imidazole (0.8 g, 11 mmol) in acetonitrile (20 mL), was added acetyl chloride (0.8 mL, 11 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 (1.5 g, 9.3 mmol), imidazole (1.4 g, 20 mmol) and triphenyl phosphite (2.9 mL, 11 mmol) and heated to reflux for 22 hours. To the mixture, was added water (30 mL). The suspension was filtered and washed with water (2×50 mL), ethyl acetate (2×50 mL), and water (50 mL) to give 3-(7-bromo-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (2.4 g, 75% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 20/80 CH3CN/0.1% H3PO4, 18.65 min (98.9%); mp: 315-317° C.; 1H NMR (DMSO-d6) δ 2.08-2.22 (m, 1H, CHH), 2.62-2.79 (m, 5H, CH3, 2CHH), 2.80-2.91 (m, 1H, CHH), 5.28 (dd, J=6, 11 Hz, 1H, NCH), 7.66 (dd, J=2, 8 Hz, 1H, Ar), 7.84 (d, J=2 Hz 2H, Ar), 7.95 (d, J=8 Hz, 1H, Ar), 11.05 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.83, 23.53, 24.02, 30.58, 56.67, 119.36, 128.06, 128.29, 128.80, 129.67, 147.93, 156.69, 160.02, 169.33, 172.57; LCMS: MH=350, 352; Anal Calcd for C14H12N3O3Br: C, 48.02; H, 3.45; N, 12.00; Br, 22.82. Found: C, 47.94; H, 3.17; N, 11.85; Br, 20.65.

Aufarbeitung

  1. temperatureheated
  2. temperatureto reflux for 22 hours
  3. filtrationThe suspension was filtered
  4. washwashed with water (2×50 mL), ethyl acetate (2×50 mL), and water (50 mL)

Quellen und Nachweise

ORD-Eintrag
ord-039a3e1880764f9191e9e307b78b4fb1
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08492395B2

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