5-Amino-2-chloro-4-fluorophenol → HCID 22646597, Verbindung

HRID 393633Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 393633
Cl.[Cl:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH2:16][CH2:17][CH2:18][N:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]=[CH:5][CH:4]=1.[Cl:24][C:25]1[C:31]([OH:32])=[CH:30][C:28]([NH2:29])=[C:27]([F:33])[CH:26]=1>CC(O)CCC.CN(C=O)C>[ClH:2].[Cl:24][C:25]1[C:31]([OH:32])=[CH:30][C:28]([NH:29][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:15][CH2:16][CH2:17][CH2:18][N:19]4[CH2:23][CH2:22][CH2:21][CH2:20]4)=[C:10]([O:13][CH3:14])[CH:11]=3)[N:6]=[CH:5][CH:4]=2)=[C:27]([F:33])[CH:26]=1

Komponenten

5

Edukt 2

HCID 1586545-Amino-2-chloro-4-fluorophenolHCID 22646629HCID 22646629, Verbindung

Produkt 1

HCID 22646597HCID 22646597, VerbindungAusbeute 54,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 223862-PentanolLösungsmittel

Versuchsvorschrift

A solution of 4-chloro-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinoline hydrochloride (325 mg, 0.82 mmol) and 4-chloro-2-fluoro-5-hydroxyaniline (133 mg, 0.82 mmol), (as described in EP 61741 A2), in 2-pentanol (10 ml) and DMF (1 ml) was heated at reflux for 5 hours. The volatiles were removed by evaporation and the residue was purified by column chromatography eluting with acetonitrile/water containing 1% TFA (30/70). Concentrated hydrochloric acid was added to the fractions and the solvents were removed by evaporation. The residue was azeotroped with toluene, and triturated with isopropanol. The solid was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinoline hydrochloride (215 mg, 50%).

Aufarbeitung

  1. temperatureat reflux for 5 hours
  2. customThe volatiles were removed by evaporation
  3. customthe residue was purified by column chromatography
  4. washeluting with acetonitrile/water containing 1% TFA (30/70)
  5. additionConcentrated hydrochloric acid was added to the fractions
  6. customthe solvents were removed by evaporation
  7. customThe residue was azeotroped with toluene
  8. customtriturated with isopropanol
  9. filtrationThe solid was collected by filtration
  10. washwashed with ether
  11. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-564b68063bc94d72a13c033e183533d0
Quelldatensatz
uspto-grants-2004_10
Patentnummer
US06809097B1

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