반응 #46278

반응 방정식

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

용매

ethyl acetate

DMSO

methanol

DMSO

반응 조건

후처리

1. 1
   기타Methanol was exhaustively removed under vacuum over 45 minutes
2. 2
   세척washed successively with 10% sodium thiosulfate and brine
3. 3
   추출The organic extract
4. 4
   건조was dried over anhydrous sodium sulfate
5. 5
   여과filtered
6. 6
   농축concentrated under vacuum
7. 7
   기타The residue was purified by reverse phase high pressure liquid chromatography
8. 8
   기타Collection and lyophilization of appropriate fractions

실험 절차

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.

출처