Reaktion #46278

Reaktionsgleichung

tert-butyl (2-bromoethyl)carbamate

6-(3-chloro-4-fluorobenzyl)-3,4-dihydroxy-N,N-dimethyl-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxamide

magnesium methoxide

→

title compound

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

Lösungsmittel

ethyl acetate

DMSO

methanol

DMSO

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeMethanol was exhaustively removed under vacuum over 45 minutes
2. 2
   Waschenwashed successively with 10% sodium thiosulfate and brine
3. 3
   ExtraktionThe organic extract
4. 4
   Trocknenwas dried over anhydrous sodium sulfate
5. 5
   Filtrationfiltered
6. 6
   Einengenconcentrated under vacuum
7. 7
   SonstigeThe residue was purified by reverse phase high pressure liquid chromatography
8. 8
   SonstigeCollection and lyophilization of appropriate fractions

Vorschrift

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 tert-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.

Quelle