Potassium Carbonate → 4-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(2-(4-pyridyloxy)ethoxy)quinazoline

HRID 1384541Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1384541
[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([OH:19])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1.Cl.Cl[CH2:25][CH2:26][O:27][C:28]1[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=1.C(=O)([O-])[O-].[K+].[K+]>CN1C(=O)CCC1.O>[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:25][CH2:26][O:27][C:28]4[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=4)=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 226249204-(2-Chloroethoxy)pyridine hydrochlorideHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Produkt 1

HCID 98245494-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(2-(4-pyridyloxy)ethoxy)quinazolineAusbeute 7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (300 mg, 0.94 mmol), (prepared as described for the starting material in Example 15), 4-(2-chloroethoxy)pyridine hydrochloride (155 mg, 0.79 mmol) and potassium carbonate (260 mg, 1.9 mmol) in NMP (20 ml) was heated at 90° C. for 2 hours, allowed to cool to ambient temperature and stirred for a further 18 hours. The mixture was diluted with water and extracted with ethyl acetate. The extract was washed with water, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol mixtures (100/0 increasing to 95/5) to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(4-pyridyloxy)ethoxy)quinazoline (20 mg, 7%), m.p. 200-202° C. 1H NMR Spectrum: (DMSOd6) 3.90(s, 3H); 4.50(s, 4H); 7.04(d, 2H); 7.26(s, 1H); 7.33(dd, 1H); 7.5-7.6(m, 2H); 7.80(s, 1H); 8.35(s, 1H); 8.39(d, 2H); 9.52(s, 1H) MS-ESI: 441 [MH]+

Aufarbeitung

  1. custom(prepared
  2. temperatureto cool to ambient temperature
  3. extractionextracted with ethyl acetate
  4. washThe extract was washed with water
  5. dry with materialdried (MgSO4)
  6. customthe solvent removed by evaporation
  7. customThe residue was purified by column chromatography
  8. washeluting with methylene chloride/methanol mixtures (100/0 increasing to 95/5)

Quellen und Nachweise

ORD-Eintrag
ord-85d592544d1946fdbdd3620622294dac
Quelldatensatz
uspto-grants-2001_07
Patentnummer
US06258951B1

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