Sodium Carbonate → 5-chloro-1-{3-[4-(5-chloro-1,3-dihydro-2-oxo-2H-benzimidazol-1-yl)-1-piperidinyl]propyl}-1,3-dihydro-2H-benzimidazol-2-one

HRID 46880

Reaktionsgleichung

Reaktionsgleichung von HRID 46880
CS(O)(=O)=O.[Cl:6][C:7]1[CH:20]=[CH:19][C:10]2[N:11]([CH2:15][CH2:16][CH2:17]O)[C:12](=[O:14])[NH:13][C:9]=2[CH:8]=1.[Cl:21][C:22]1[CH:37]=[CH:36][C:25]2[N:26]([CH:30]3[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]3)[C:27](=[O:29])[NH:28][C:24]=2[CH:23]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O>[Cl:6][C:7]1[CH:20]=[CH:19][C:10]2[N:11]([CH2:15][CH2:16][CH2:17][N:33]3[CH2:32][CH2:31][CH:30]([N:26]4[C:25]5[CH:36]=[CH:37][C:22]([Cl:21])=[CH:23][C:24]=5[NH:28][C:27]4=[O:29])[CH2:35][CH2:34]3)[C:12](=[O:14])[NH:13][C:9]=2[CH:8]=1

Komponenten

5

Edukt 3

HCID 10340Sodium CarbonateHCID 1046075-Chloro-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-oneHCID 867353595-chloro-1,3-dihydro-1-(3-hydroxypropyl)-2H-benzimidazol-2-one methanesulfonate

Produkt 1

HCID 203855425-chloro-1-{3-[4-(5-chloro-1,3-dihydro-2-oxo-2H-benzimidazol-1-yl)-1-piperidinyl]propyl}-1,3-dihydro-2H-benzimidazol-2-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A mixture of 7.6 parts of 5-chloro-1,3-dihydro-1-(3-hydroxypropyl)-2H-benzimidazol-2-one methanesulfonate, 5.5 parts of 5-chloro-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one, 5 parts of sodium carbonate and 63 parts of N,N-dimethylformamide is stirred and heated in an oil-bath at 50°-60° C. for 2 hours. The reaction mixture is poured onto water. The precipitated product is filtered off, dried and purified by column-chromatography over silica gel using a mixture of trichloromethane and 10% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The solid residue is crystallized from 4-methyl-2-pentanone. The product is filtered off and recrystallized from a mixture of N,N-dimethylformamide and water. It is filtered off again and dissolved in a mixture of 4-methyl-2-pentanone and a small amount of N,N-dimethylformamide. The solution is filtered till clear and the filtrate is concentrated to a volume of about 10 parts. The concentrate is triturated in methanol. The precipitated product is filtered off and dried, yielding 1.27 parts of 5-chloro-1-{3-[4-(5-chloro-1,3-dihydro-2-oxo-2H-benzimidazol-1-yl)-1-piperidinyl]propyl}-1,3-dihydro-2H-benzimidazol-2-one; mp. 229°-236° C.

Aufarbeitung

  1. temperatureheated in an oil-bath at 50°-60° C. for 2 hours
  2. additionThe reaction mixture is poured onto water
  3. filtrationThe precipitated product is filtered off
  4. customdried
  5. custompurified by column-chromatography over silica gel using
  6. additiona mixture of trichloromethane and 10% of methanol as eluent
  7. customThe pure fractions are collected
  8. customthe eluent is evaporated
  9. customThe solid residue is crystallized from 4-methyl-2-pentanone
  10. filtrationThe product is filtered off
  11. customrecrystallized from a mixture of N,N-dimethylformamide and water
  12. filtrationIt is filtered off again
  13. dissolutiondissolved in a mixture of 4-methyl-2-pentanone
  14. filtrationThe solution is filtered till clear and the filtrate
  15. concentrationis concentrated to a volume of about 10 parts
  16. customThe concentrate is triturated in methanol
  17. filtrationThe precipitated product is filtered off
  18. customdried

Quellen und Nachweise

ORD-Eintrag
ord-997eb0b7830b4be892da03236499ac53
Quelldatensatz
uspto-grants-1979_11
Patentnummer
US04175129

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