Реакция #46278

Уравнение реакции

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

Растворители

ethyl acetate

DMSO

methanol

DMSO

Условия реакции

Обработка

1. 1
   ДругоеMethanol was exhaustively removed under vacuum over 45 minutes
2. 2
   Промывкаwashed successively with 10% sodium thiosulfate and brine
3. 3
   ЭкстракцияThe organic extract
4. 4
   Сушкаwas dried over anhydrous sodium sulfate
5. 5
   Фильтрацияfiltered
6. 6
   Концентрированиеconcentrated under vacuum
7. 7
   ДругоеThe residue was purified by reverse phase high pressure liquid chromatography
8. 8
   ДругоеCollection and lyophilization of appropriate fractions

Методика

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.

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