Dicyclohexylcarbodiimide → HCID 178429388, Verbindung

HRID 442501Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 442501
[CH3:1][C:2]1[C:10](=[O:11])[NH:9][C:8](=[O:12])[NH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH:13]N1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1.O.C([NH:49][C@H:50]([C:57]([N:59]1[CH2:66][CH2:65][CH2:64][C@H:60]1[C:61]([NH2:63])=[O:62])=[O:58])[CH2:51][C:52]1[N:56]=[CH:55][NH:54][CH:53]=1)(=O)C1NC(=O)NC(=[O:43])C=1>CN(C)C=O.C(N(CC)CC)C>[OH2:5].[OH2:13].[OH2:43].[CH3:1][C:2]1[C:10](=[O:11])[NH:9][C:8](=[O:12])[NH:7][C:3]=1[C:4]([NH:49][C@H:50]([C:57]([N:59]1[CH2:66][CH2:65][CH2:64][C@H:60]1[C:61]([NH2:63])=[O:62])=[O:58])[CH2:51][C:52]1[N:56]=[CH:55][NH:54][CH:53]=1)=[O:6]

Komponenten

7

Edukt 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 776125-Methylorotic acidHCID 178513957HCID 178513957, Verbindung

Produkt 1

HCID 178429388HCID 178429388, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittel3×HCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

To 100 ml of dimethylformamide are added, while stirring at room temperature, 17.0 g of 5-methyl orotic acid, 14.4 g of 1-hydroxybenzotriazole and 27.8 ml of triethylamine. After 10 minutes the mixture is chilled in an ice bath and 10 minutes later a solution of 20.6 g of N,N'-dicyclohexyl-carbodiimide in 30 ml of dimethylformamide and then L-histidyl-L-prolinamide dihydrobromide (obtained as described in Example 2 from 38.5 g of N-benzyloxycarbonyl-L-histidyl-L-prolinamide) and a further amount of 100 ml of dimethylformamide are added. The mixture is stirred for 30 minutes in the ice bath and then for 12 hours at room temperature and thereafter worked up as described in Example 2 until and including the preliminary purification with a cationic exchanger. The residue of the ammoniacal solution is recrystallized from 110 ml of ethanol. After chilling for 24 hours to 0° C. the product is filtrated by suction and dried over phosphorous pentoxide. 2 g portions of this material are dissolved in methanol/water (1:1) and chromatographed over a column of 350 g basic aluminium oxide. The elution is controlled by measuring the ultraviolet absorption spectrum at 254 nm and the fractions containing the pure main product are combined and evaporated under reduced pressure. The residue is dissolved in methanol, filtered, evaporated to dryness, redissolved in water and lyophylized. Thus, 14.4 g (30.4% of the theoretical yield) of 5-methyl-orotyl-L-histidyl-L-prolinamide trihydrate melting at 222° - 227° C. with decomposition are obtained.

Aufarbeitung

  1. customthe preliminary purification with a cationic exchanger
  2. customThe residue of the ammoniacal solution is recrystallized from 110 ml of ethanol
  3. temperatureAfter chilling for 24 hours to 0° C. the product
  4. filtrationis filtrated by suction
  5. dry with materialdried over phosphorous pentoxide
  6. dissolution2 g portions of this material are dissolved in methanol/water (1:1)
  7. customchromatographed over a column of 350 g basic aluminium oxide
  8. washThe elution
  9. customthe ultraviolet absorption spectrum at 254 nm
  10. additionthe fractions containing the pure main product
  11. customevaporated under reduced pressure
  12. dissolutionThe residue is dissolved in methanol
  13. filtrationfiltered
  14. customevaporated to dryness
  15. dissolutionredissolved in water

Quellen und Nachweise

ORD-Eintrag
ord-4a62923dbfdf46e88058df0c6fb35e44
Quelldatensatz
uspto-grants-1977_08
Patentnummer
US04045556

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