1-Bromo-2-Chloroethane → 9-(3-Chloro-4-fluorobenzyl)-7-hydroxy-3,4,10,11-tetrahydro[1,4]oxazino[3,4-a]-2,6-naphthyridine-1,6,8(9H)-trione

HRID 2066584

Reaktionsgleichung

Reaktionsgleichung von HRID 2066584
[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:12]([C:16](N(C)C)=[O:17])=[N:11][C:10]([OH:21])=[C:9]([OH:22])[C:8]=2[C:7]1=[O:23].C[O-:29].[Mg+2].C[O-].Br[CH2:34][CH2:35]Cl>CO.CS(C)=O.C(OCC)(=O)C.Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([OH:22])[C:10](=[O:21])[N:11]3[CH2:35][CH2:34][O:29][C:16](=[O:17])[C:12]3=2)[C:7]1=[O:23]

Komponenten

8

Edukt 3

HCID 78491-Bromo-2-ChloroethaneHCID 164537Methanol, magnesium salt (2:1)HCID 178484497HCID 178484497, Verbindung

Produkt 1

HCID 593446999-(3-Chloro-4-fluorobenzyl)-7-hydroxy-3,4,10,11-tetrahydro[1,4]oxazino[3,4-a]-2,6-naphthyridine-1,6,8(9H)-trione

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 313Hydrochloric AcidLösungsmittelHCID 679Dimethyl SulfoxideLösungsmittel2×HCID 887MethanolLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

A mixture of 6-(3-chloro-4-fluorobenzyl)-3,4-dihydroxy-N,N-dimethyl-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxamide (0.15 g, 0.39 mmol; Example 1, Step 9) and magnesium methoxide in methanol (2 mL, 6-10% methanol solution available from Aldrich) in DMSO (4 mL) was heated at 60° C. for 30 minutes. Methanol was exhaustively removed under vacuum over 45 minutes. The resultant DMSO solution was treated with 1-bromo-2-chloroethane (0.28 g, 1.97 mmol) and stirred at 60° C. under an atmosphere of nitrogen overnight. The reaction mixture was diluted with ethyl acetate and dilute hydrochloric acid. The organic extract was washed with aqueous sodium sulfite, brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified by reverse phase high pressure liquid chromatography. Collection and lyophilization of appropriate fractions provided the title compound, which was recrystallized from a mixture of ethyl acetate and hexane

Aufarbeitung

  1. customMethanol was exhaustively removed under vacuum over 45 minutes
  2. extractionThe organic extract
  3. washwas washed with aqueous sodium sulfite, brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by reverse phase high pressure liquid chromatography
  8. customCollection and lyophilization of appropriate fractions

Quellen und Nachweise

ORD-Eintrag
ord-facb6da1b0fb43f88e0a3ece8ce21271
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08293731B2

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