Reacción #46270

Ecuación de reacción

1-bromo-4-chlorobutane

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

Methyl 2-(4-chlorobutyl)-6-(3-chloro-4-fluorobenzyl)-4-hydroxy-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxylate

Disolventes

ethyl acetate

DMSO

methanol

DMSO

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroMethanol was exhaustively removed under vacuum over 45 minutes
2. 2
   Lavadowashed with dilute hydrochloric acid
3. 3
   ExtracciónThe organic extract
4. 4
   Lavadowas washed with 10% aqueous potassium carbonate
5. 5
   Secadodried over anhydrous sodium sulfate
6. 6
   Filtraciónfiltered
7. 7
   Concentraciónconcentrated under vacuum
8. 8
   OtroThe residue was triturated with diethyl ether
9. 9
   OtroThe solid precipitated
10. 10
    Filtraciónwas collected by filtration

Procedimiento

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 (0.80 g, 2.19 mmol) and magnesium methoxide in methanol (10.6 mL, 6-10% methanol solution available from Aldrich) in DMSO (22 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 1-bromo-4-chlorobutane (1.80 g, 10.50 mmol) and stirred at 60° C. under an atmosphere of nitrogen for one hour. The reaction mixture was diluted with ethyl acetate and washed with dilute hydrochloric acid. The organic extract was washed with 10% aqueous potassium carbonate, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was triturated with diethyl ether. The solid precipitated was collected by filtration to provide the title compound. ES MS M+1=471

Fuente