Methanol, magnesium salt (2:1) → 9-(3-Chloro-4-fluorobenzyl)-7-hydroxy-3,4,10,11-tetrahydro-2H-pyrazino[2,1-a]-2,6-naphthyridine-1,6,8(9H)-trione

HRID 2426455Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2426455
[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:18]([CH3:20])C)=[O:17])=[N:11][C:10]([OH:21])=[C:9]([OH:22])[C:8]=2[C:7]1=[O:23].C[O-].[Mg+2].C[O-].Br[CH2:34]CNC(=O)OCCCC>CO.CS(C)=O.C(OCC)(=O)C>[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[CH2:34][CH2:20][NH:18][C:16](=[O:17])[C:12]3=2)[C:7]1=[O:23]

Komponenten

7

Edukt 3

HCID 164537Methanol, magnesium salt (2:1)HCID 23033729Butyl (2-bromoethyl)carbamateHCID 178484497HCID 178484497, Verbindung

Produkt 1

HCID 593447509-(3-Chloro-4-fluorobenzyl)-7-hydroxy-3,4,10,11-tetrahydro-2H-pyrazino[2,1-a]-2,6-naphthyridine-1,6,8(9H)-trione

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 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 (1.00 g, 2.63 mmol; Example 1, Step 9) and magnesium methoxide in methanol (13.1 mL, 6-10% methanol solution available from Aldrich) in DMSO (26 mL) was heated at 60° C. for one hour. Methanol was exhaustively removed under vacuum over 45 minutes. The resulting DMSO solution was treated with tort-butyl (2-bromoethyl)carbamate (2.94 g, 13.13 mmol) and stirred at 60° C. under an atmosphere of nitrogen for one hour. The reaction mixture was diluted with ethyl acetate and washed successively with 10% sodium thiosulfate and brine. The organic extract was 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.

Aufarbeitung

  1. customMethanol was exhaustively removed under vacuum over 45 minutes
  2. washwashed successively with 10% sodium thiosulfate and brine
  3. extractionThe organic extract
  4. dry with materialwas dried 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-9efdab718ca7455b8ee9877182461b31
Quelldatensatz
uspto-grants-2011_06
Patentnummer
US07968564B2

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