Réaction #55363

Équation de réaction

1-acetyl-4-chlorocarbonylpiperazine

6-(7-Chloro-1,8-naphthyridin-2-yl)-5-hydroxy-7-oxo-2,3,6,7-tetrahydro-5H-1,4-dithiino[2,3-c]pyrrole

sodium hydride

→

5-(4-Acetylpiperazin-1-yl)carbonyloxy-6-(7-chloro-1,8-naphthyridin-2-yl)-7-oxo-2,3,6,7-tetrahydro-5H-1,4-dithiino[2,3-c]pyrrole

Rendement 38.9%

Solvants

dimethylformamide

dimethylformamide

water

chloroform

Conditions de réaction

Traitement

1. 1
   workup.WAITAfter 18 hours at 2° C.
2. 2
   AutreThe precipitate formed
3. 3
   Filtrationis filtered off
4. 4
   Lavagewashed with distilled water (10 cc.)
5. 5
   Autredried in air
6. 6
   AutreThe product obtained (3.5 g.)
7. 7
   Filtrationthe solution is filtered through silica gel (50.0 g.)
8. 8
   LavageElution
9. 9
   workup.ADDITIONa mixture of chloroform and methanol (98-2 by volume; 400 cc.)
10. 10
    LavageElution
11. 11
    AutreThis eluate is evaporated to dryness under reduced pressure (20 mm.Hg)
12. 12
    AutreThe chromatographed product is purified by recrystallisation from a mixture of dimethylformamide and ethanol (50-50 by volume; 20 cc.)

Mode opératoire

6-(7-Chloro-1,8-naphthyridin-2-yl)-5-hydroxy-7-oxo-2,3,6,7-tetrahydro-5H-1,4-dithiino[2,3-c]pyrrole (2.5 g.) is added, at 0° C., to a suspension of sodium hydride (0.20 g.) in anhydrous dimethylformamide (10 cc.). The reaction mixture is stirred for 1 hour at 2° C., and then a solution of 1-acetyl-4-chlorocarbonylpiperazine (2.85 g.) in anhydrous dimethylformamide (20 cc.) is added. After 18 hours at 2° C., the reaction mixture is diluted with distilled water (100 cc.). The precipitate formed is filtered off, washed with distilled water (10 cc.) and dried in air. The product obtained (3.5 g.) is dissolved in chloroform (50 cc.), and the solution is filtered through silica gel (50.0 g.) contained in a column of diameter 4.1 cm. Elution is carried out using a mixture of chloroform and methanol (98-2 by volume; 400 cc.), and the eluate is discarded. Elution is continued using a similar mixture (400 cc). This eluate is evaporated to dryness under reduced pressure (20 mm.Hg). The chromatographed product is purified by recrystallisation from a mixture of dimethylformamide and ethanol (50-50 by volume; 20 cc.). 5-(4-Acetylpiperazin-1-yl)carbonyloxy-6-(7-chloro-1,8-naphthyridin-2-yl)-7-oxo-2,3,6,7-tetrahydro-5H-1,4-dithiino[2,3-c]pyrrole (1.40 g.), which melts at 271° C., is obtained.

Source