Hydrochloric Acid → 4-(3-Chloro-2,4-difluoroanilino)-7-methoxy-6-[(piperidin-4-yl)oxy]quinazoline

HRID 1879952Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1879952
[Cl:1][C:2]1[C:3]([F:10])=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].Cl.Cl[C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:37][CH3:38])=[C:20]([O:23][CH:24]3[CH2:29][CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26][CH2:25]3)[CH:21]=2)[N:16]=[CH:15][N:14]=1>C(O)(C)C>[Cl:1][C:2]1[C:3]([F:10])=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH:5][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:37][CH3:38])=[C:20]([O:23][CH:24]3[CH2:25][CH2:26][NH:27][CH2:28][CH2:29]3)[CH:21]=2)[N:16]=[CH:15][N:14]=1

Komponenten

5

Edukt 3

HCID 313Hydrochloric AcidHCID 2230893-Chloro-2,4-difluoroanilineHCID 86599788Tert-butyl 4-[(4-chloro-7-methoxyquinazolin-6-yl)oxy]piperidine-1-carboxylate

Produkt 1

HCID 692294994-(3-Chloro-2,4-difluoroanilino)-7-methoxy-6-[(piperidin-4-yl)oxy]quinazolineAusbeute 85,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3776IsopropanolLösungsmittel2×

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

3-Chloro-2,4-difluoroaniline (1.7 g, 10.1 mmol) and 5N hydrogen chloride in isopropanol (2 ml) were added to a suspension of tert-butyl 4-[(4-chloro-7-methoxyquinazolin-6-yl)oxy]piperidine-1-carboxylate (4 g, 10.1 mmol, PCT Int. Appl. WO2003082831, AstraZeneca) in isopropanol (50 ml). The mixture was stirred at 80° C. for 3 hours. After evaporation of the solvents, the residue was purified by chromatography on silica gel (eluant: 5-10% 7N methanolic ammonia in dichloromethane) to give 4-(3-chloro-2,4-difluoroanilino)-7-methoxy-6-[(piperidin-4-yl)oxy]quinazoline (3.63 g, 85%) as a white solid.

Aufarbeitung

  1. customAfter evaporation of the solvents
  2. customthe residue was purified by chromatography on silica gel (eluant: 5-10% 7N methanolic ammonia in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-10051745993244af99cbce89c78a3b41
Quelldatensatz
uspto-grants-2012_11
Patentnummer
US08318752B2

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