Sodium Hydroxide → 8-Bromo-2-chloro-3-ethyl-7-fluoro-quinazolin-4-one

HRID 1056425Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1056425
[Br:1][C:2]1[C:3]([F:16])=[CH:4][CH:5]=[C:6]2[C:11]=1[NH:10][C:9](=O)[N:8]([CH2:13][CH3:14])[C:7]2=[O:15].P(Cl)(Cl)([Cl:19])=O.CCN(C(C)C)C(C)C.[OH-].[Na+]>O>[Br:1][C:2]1[C:3]([F:16])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([Cl:19])[N:8]([CH2:13][CH3:14])[C:7]2=[O:15]

Komponenten

6

Edukt 4

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 897939088-bromo-3-ethyl-7-fluoroquinazoline-2,4(1H,3H)-dione

Produkt 1

HCID 897939068-Bromo-2-chloro-3-ethyl-7-fluoro-quinazolin-4-oneAusbeute 98,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

A solution of 8-bromo-3-ethyl-7-fluoroquinazoline-2,4(1H,3H)-dione (512b, 2.20 g, 7.66 mmol), phosphorous oxychloride (Acros Organics, Geel, Belgium; 3.57 mL, 38.3 mmol), and DIPEA (5.34 mL, 30.6 mmol) was heated over a 130° C. oil bath for 4.5 h. The reaction mixture was then cooled to RT and poured onto ice, and the resulting mixture was diluted with water (250 mL) to provide a brown suspension. 10 N aqueous NaOH was added to the vigorously stirred suspension (maintaining the reaction mixture at 0° C.) until a pH of 10 was achieved. The precipitated solid was collected by vacuum filtration, washed with water (3×20 mL), and dried in vacuo to provide 8-bromo-2-chloro-3-ethyl-7-fluoroquinazolin-4(3H)-one (2.301 g, 7.53 mmol, 98% yield) as a tan solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.22 (1H, dd, J=8.9, 5.8 Hz), 7.23-7.29 (1H, m), 4.37 (2H, q, J=7.1 Hz), 1.41 (3H, t, J=7.0 Hz). 19F NMR (376 MHz, CDCl3) δ ppm −93.38 (1F, s). m/z (ESI, +ve) 304.7/306.8/308.7 (M+H)+.

Aufarbeitung

  1. additionpoured onto ice
  2. customto provide a brown suspension
  3. temperaturemaintaining the reaction mixture at 0° C.) until a pH of 10
  4. filtrationThe precipitated solid was collected by vacuum filtration
  5. washwashed with water (3×20 mL)
  6. customdried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-0b33daeee243425a81302eb3baf392f5
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09394297B2

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