Potassium Carbonate → N-(4-chloro-2-fluorophenyl)-6-methoxy-7-[2-(pyrrolidin-1-yl)ethoxy]quinazolin-4-amine

HRID 2227916

Reaktionsgleichung

Reaktionsgleichung von HRID 2227916
Cl.N1CCCC1.[Cl:7][C:8]1[CH:27]=[CH:26][C:11]([NH:12][C:13]2[C:22]3[C:17](=[CH:18][C:19]([OH:25])=[C:20]([O:23][CH3:24])[CH:21]=3)[N:16]=[CH:15][N:14]=2)=[C:10]([F:28])[CH:9]=1.C(=O)([O-])[O-].[K+].[K+].Cl.Cl[CH2:37][CH2:38][N:39]1[CH2:43][CH2:42][CH2:41][CH2:40]1>CN(C=O)C>[Cl:7][C:8]1[CH:27]=[CH:26][C:11]([NH:12][C:13]2[C:22]3[C:17](=[CH:18][C:19]([O:25][CH2:37][CH2:38][N:39]4[CH2:43][CH2:42][CH2:41][CH2:40]4)=[C:20]([O:23][CH3:24])[CH:21]=3)[N:16]=[CH:15][N:14]=2)=[C:10]([F:28])[CH:9]=1

Komponenten

6

Edukt 4

HCID 11430Potassium CarbonateHCID 816681-(2-Chloroethyl)pyrrolidine hydrochlorideHCID 212848Pyrrolidine, hydrochloride (1:1)HCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Produkt 1

HCID 5329018N-(4-chloro-2-fluorophenyl)-6-methoxy-7-[2-(pyrrolidin-1-yl)ethoxy]quinazolin-4-amineAusbeute 10 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

1-2-Chloroethyl)pyrrolidine hydrochloride (200 mg, 1.2 mmol) was added to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (403 mg, 1.26 mmol), (prepared as described for the starting material in Example 2), and potassium carbonate (650 mg, 4.7 mmol) in DMF (4 ml). The mixture was heated to 100° C. and further portions of 1-(2-chloroethyl)pyrrolidine hydrochloride (800 mg in total) were added periodically over 4 hours while the reaction mixture was maintained at 100° C. The reaction was then allowed to cool and volatiles were removed by evaporation. The residue was partitioned between methylene chloride and water, separated and the organic phase passed through phase separating paper. Column chromatography eluting with methylene chloride/methanol (95/5) gave 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(pyrrolidin-1-yl)ethoxy)quinazoline (50 mg, 10%).

Aufarbeitung

  1. custom(prepared
  2. temperaturewas maintained at 100° C
  3. temperatureto cool
  4. customvolatiles were removed by evaporation
  5. customThe residue was partitioned between methylene chloride and water
  6. customseparated
  7. customseparating paper
  8. washColumn chromatography eluting with methylene chloride/methanol (95/5)

Quellen und Nachweise

ORD-Eintrag
ord-af3818c402424249bfaa01bdd6867d7c
Quelldatensatz
uspto-grants-2002_07
Patentnummer
US06414148B1

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