Propiolic Acid → 6-(7-Chloro-1,8-naphthyridin-2-yl)-7-oxo-5-(4-propioloylpiperazin-1-yl)carbonyloxy-2,3,6,7-tetrahydro-5H-1,4-oxathiino[2,3-c]pyrrole

HRID 27082

Reaktionsgleichung

Reaktionsgleichung von HRID 27082
[C:1]([OH:5])(=O)[C:2]#[CH:3].[Cl:6][C:7]1[N:16]=[C:15]2[C:10]([CH:11]=[CH:12][C:13]([N:17]3[CH:21]([O:22][C:23]([N:25]4[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]4)=[O:24])[C:20]4[S:31][CH2:32][CH2:33][O:34][C:19]=4[C:18]3=[O:35])=[N:14]2)=[CH:9][CH:8]=1.C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl.CO>[Cl:6][C:7]1[N:16]=[C:15]2[C:10]([CH:11]=[CH:12][C:13]([N:17]3[CH:21]([O:22][C:23]([N:25]4[CH2:26][CH2:27][N:28]([C:1](=[O:5])[C:2]#[CH:3])[CH2:29][CH2:30]4)=[O:24])[C:20]4[S:31][CH2:32][CH2:33][O:34][C:19]=4[C:18]3=[O:35])=[N:14]2)=[CH:9][CH:8]=1

Komponenten

6

Edukt 3

HCID 10110Propiolic AcidHCID 10868DicyclohexylcarbodiimideHCID 233436316-(7-chloro-1,8-naphthyridin-2-yl)-7-oxo-5-(piperazin-1-yl)carbonyloxy-2,3,6,7-tetrahydro-5H-1,4-oxathiino[2,3-c]pyrrole

Produkt 1

HCID 233436546-(7-Chloro-1,8-naphthyridin-2-yl)-7-oxo-5-(4-propioloylpiperazin-1-yl)carbonyloxy-2,3,6,7-tetrahydro-5H-1,4-oxathiino[2,3-c]pyrroleAusbeute 23,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel3×

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

A solution of propiolic acid (0.52 g.) in anhydrous methylene chloride (10 cc.) is added to a suspension of 6-(7-chloro-1,8-naphthyridin-2-yl)-7-oxo-5-(piperazin-1-yl)carbonyloxy-2,3,6,7-tetrahydro-5H-1,4-oxathiino[2,3-c]pyrrole (3 g.) and N,N'-dicyclohexylcarbodiimide (1.52 g.) in anhydrous methylene chloride (70 cc.). The mixture is stirred for one and a half hours at a temperature of about 25° C. and then the insoluble product (dicyclohexylurea) is filtered off and washed with methylene chloride (3×5 cc.). The filtrate is concentrated to dryness under reduced pressure and the residue is treated with boiling ethanol (100 cc.). After cooling, the insoluble product is filtered off and washed with ethanol (20 cc.). This product is then dissolved in methylene chloride (200 cc.) and the solution is washed by decantation successively with 0.1 N methanesulphonic acid (50 cc.) and with water (2×50 cc.). After drying, the organic solution is filtered through silica gel (45 g.) contained in a column of diameter 2.2 cm. Elution is carried out using pure methylene chloride (1,000 cc.). The eluate is discarded. Elution is then carried out using a mixture of methylene chloride and methanol (99.5-0.5 by volume; 350 cc.) and the corresponding eluate is concentrated to dryness under reduced pressure (20 mm. Hg). The residue obtained is dissolved in a mixture of methylene chloride and methanol (90-10 by volume; 300 cc.) and the solution obtained is filtered and then concentrated to dryness under reduced pressure. 6-(7-Chloro-1,8-naphthyridin-2-yl)-7-oxo-5-(4-propioloylpiperazin-1-yl)carbonyloxy-2,3,6,7-tetrahydro-5H-1,4-oxathiino[2,3-c]pyrrole (0.8 g.), which melts at 302° C. with decomposition, is thus obtained.

Aufarbeitung

  1. filtrationthe insoluble product (dicyclohexylurea) is filtered off
  2. washwashed with methylene chloride (3×5 cc.)
  3. concentrationThe filtrate is concentrated to dryness under reduced pressure
  4. additionthe residue is treated with boiling ethanol (100 cc.)
  5. temperatureAfter cooling
  6. filtrationthe insoluble product is filtered off
  7. washwashed with ethanol (20 cc.)
  8. dissolutionThis product is then dissolved in methylene chloride (200 cc.)
  9. washthe solution is washed by decantation successively with 0.1 N methanesulphonic acid (50 cc.) and with water (2×50 cc.)
  10. customAfter drying
  11. filtrationthe organic solution is filtered through silica gel (45 g.)
  12. washElution
  13. washElution
  14. additiona mixture of methylene chloride and methanol (99.5-0.5 by volume; 350 cc.)
  15. concentrationthe corresponding eluate is concentrated to dryness under reduced pressure (20 mm. Hg)
  16. customThe residue obtained
  17. customthe solution obtained
  18. filtrationis filtered
  19. concentrationconcentrated to dryness under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-baf9476d335d4f72903d51e89ae9e24b
Quelldatensatz
uspto-grants-1980_09
Patentnummer
US04220646

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