1,8-Diazabicyclo(5.4.0)undec-7-ene → 4-Quinazolineacetic acid, 8-fluoro-3,4-dihydro-2-[4-(3-methoxyphenyl)-1-piperazinyl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-, methyl ester

HRID 2410226Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2410226
Cl[C:2]1[N:11]([C:12]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:13]=2[O:22][CH3:23])[CH:10]([CH2:24][C:25]([O:27][CH3:28])=[O:26])[C:9]2[C:4](=[C:5]([F:29])[CH:6]=[CH:7][CH:8]=2)[N:3]=1.[CH3:30][O:31][C:32]1[CH:33]=[C:34]([N:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)[CH:35]=[CH:36][CH:37]=1.C1CCN2C(=NCCC2)CC1>O1CCOCC1.C(OCC)(=O)C.O>[F:29][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:4]=1[N:3]=[C:2]([N:41]1[CH2:40][CH2:39][N:38]([C:34]3[CH:35]=[CH:36][CH:37]=[C:32]([O:31][CH3:30])[CH:33]=3)[CH2:43][CH2:42]1)[N:11]([C:12]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:13]=1[O:22][CH3:23])[CH:10]2[CH2:24][C:25]([O:27][CH3:28])=[O:26]

Komponenten

7

Edukt 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 81430N-(3-methoxyphenyl)piperazineHCID 120020734-Quinazolineacetic acid, 2-chloro-8-fluoro-3,4-dihydro-3-[2-methoxy-5-(trifluoromethyl)phenyl]-, methyl ester

Produkt 1

HCID 119836914-Quinazolineacetic acid, 8-fluoro-3,4-dihydro-2-[4-(3-methoxyphenyl)-1-piperazinyl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-, methyl esterAusbeute 87,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

Methyl {2-chloro-8-fluoro-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl}acetate (52.5 g) is dissolved in 1,4-dioxane (100 ml), 3-methoxyphenylpiperazine (25.8 g) and DBU (20.4 g) are added at room temperature, the temperature increasing. The mixture is stirred under reflux for 22 h, then cooled to room temperature, diluted with ethyl acetate (500 ml) and water (200 ml) and the phases are separated. The organic phase is washed with 0.2N hydrochloric acid (three times 100 ml) and water (200 ml), dried over sodium sulphate and concentrated in a rotary evaporator. A total of 62.5 g of methyl {8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl}acetate is obtained as a solidified foam, which is reacted as the crude product without further purification.

Aufarbeitung

  1. temperaturethe temperature increasing
  2. temperatureunder reflux for 22 h
  3. customthe phases are separated
  4. washThe organic phase is washed with 0.2N hydrochloric acid (three times 100 ml) and water (200 ml)
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated in a rotary evaporator

Quellen und Nachweise

ORD-Eintrag
ord-9209e425aac941c883aec1d48514c9a3
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08816075B2

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