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

HRID 27085Notes

Reaction equation

HRID 27085 reaction equation
[Cl:1][C:2]1[N:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([N:12]3[CH:16]([OH:17])[C:15]4[S:18][CH2:19][CH2:20][S:21][C:14]=4[C:13]3=[O:22])=[N:9]2)=[CH:4][CH:3]=1.[H-].[Na+].[C:25]([N:28]1[CH2:33][CH2:32][N:31]([C:34](Cl)=[O:35])[CH2:30][CH2:29]1)(=[O:27])[CH3:26]>CN(C)C=O.O.C(Cl)(Cl)Cl>[C:25]([N:28]1[CH2:33][CH2:32][N:31]([C:34]([O:17][CH:16]2[N:12]([C:8]3[CH:7]=[CH:6][C:5]4[C:10](=[N:11][C:2]([Cl:1])=[CH:3][CH:4]=4)[N:9]=3)[C:13](=[O:22])[C:14]3[S:21][CH2:20][CH2:19][S:18][C:15]2=3)=[O:35])[CH2:30][CH2:29]1)(=[O:27])[CH3:26]

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 30347196-(7-Chloro-1,8-naphthyridin-2-yl)-2,3,6,7-tetrahydro-7-hydroxy-5H-1,4-dithiino[2,3-c]pyrrol-5-oneHCID 13728618HCID 13728618, compound

Product 1

HCID 137286255-(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]pyrroleYield 38.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
2 °C

Procedure

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.

Workup

  1. waitAfter 18 hours at 2° C.
  2. customThe precipitate formed
  3. filtrationis filtered off
  4. washwashed with distilled water (10 cc.)
  5. customdried in air
  6. customThe product obtained (3.5 g.)
  7. filtrationthe solution is filtered through silica gel (50.0 g.)
  8. washElution
  9. additiona mixture of chloroform and methanol (98-2 by volume; 400 cc.)
  10. washElution
  11. customThis eluate is evaporated to dryness under reduced pressure (20 mm.Hg)
  12. customThe chromatographed product is purified by recrystallisation from a mixture of dimethylformamide and ethanol (50-50 by volume; 20 cc.)

Sources & evidence

ORD record
ord-2f7b6daa79bd4d5683bd4907a9d0c2ba
Source dataset
uspto-grants-1980_09
Patent number
US04220646

Reaction notes

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