Dicyclohexylcarbodiimide → HCID 178455825, compound

HRID 1439709Notes

Reaction equation

HRID 1439709 reaction equation
[NH:1]1[C:5](=[O:6])[CH2:4][CH2:3][C@H:2]1[C:7]([NH:9][C@H:10]([C:17]([N:19]1[CH2:26][CH2:25][C@@H:24]([CH2:27][CH3:28])[C@@H:20]1[C:21]([NH2:23])=[O:22])=[O:18])[CH2:11][C:12]1[N:16]=[CH:15][NH:14][CH:13]=1)=[O:8].C([C@@H]1CCN[C@H]1C(N)=O)C.C(OC(N1C(=O)CC[C@H]1C(N[C@H](C(O)=O)CC1N=CNC=1)=O)=O)C1C=CC=CC=1.OC1C2N=NNC=2C=CC=1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O>[NH:1]1[C:5](=[O:6])[CH2:4][CH2:3][C@H:2]1[C:7]([NH:9][C@H:10]([C:17]([N:19]1[CH2:26][CH2:25][C@@H:24]([CH2:27][CH3:28])[C@@H:20]1[C:21]([NH2:23])=[O:22])=[O:18])[CH2:11][C:12]1[N:16]=[CH:15][NH:14][CH:13]=1)=[O:8]

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 178418300HCID 178418300, compoundHCID 178455826HCID 178455826, compoundHCID 178525814HCID 178525814, compound

Product 1

HCID 178455825HCID 178455825, compoundYield 97.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

L-Pyroglutamyl-L-histidyl-trans-3-ethyl-dl-prolineamide trans-3-Ethyl-dl-prolineamide (288 mg, 2 mM), benzyloxycarbonyl-L-pyroglutamyl-L-histidine (822 mg, 2 mM), and hydroxybenzotriazole (550 mg, 4 mM) were dissolved in dimethylformamide (6 ml), the solution cooled to 0°, dicyclohexylcarbodiimide (480 mg, 2.2 mM) added and the mixture stirred for 18 hrs. The mixture was then filtered and the filtrate evaporated. The resulting oil was dissolved in tetrahydrofuran - water (1 : 1, 80 ml), palladium on carbon (10%, 60 mg) added and the solution hydrogenated for 4 hrs at atmospheric pressure. The catalyst was then removed by filtration and the filtrate evaporated to dryness. The resulting gum was distributed between ethyl acetate (50 ml) and water (80 ml). The aqueous phase was separated, evaporated to dryness and the residue dissolved in aqueous solution containing 1% acetic acid/0.05% pyridine. This was applied to a column of S.P. - Sephadex C 25 resin (pyridinium form) which was equilibrated with aqueous 1% acetic/0.05% pyridine. The column was eluted by a gradient technique using aqueous 1% acetic acid/1% pyridine via a 500 ml spherical mixing vessel filled with aqueous 1% acetic acid/0.05% pyridine. The fractions containing product (as detected by t.l.c) were combined and evaporated to yield L-pyroglutamyl-L-histidyl-trans-3-ethyl-dl-prolineamide (205 mg) as a white amorphous solid m.p. 156°-160°. RF 3A 0.27, RF 3B 0.50. Amino acid analysis after acidic hydrolysis gave the following ratios: Histidine 0.95 glutamic acid 0.99 3-ethyl proline 1.06.

Workup

  1. temperaturethe solution cooled to 0°
  2. filtrationThe mixture was then filtered
  3. customthe filtrate evaporated
  4. dissolutionThe resulting oil was dissolved in tetrahydrofuran - water (1 : 1, 80 ml)
  5. additionpalladium on carbon (10%, 60 mg) added
  6. waitthe solution hydrogenated for 4 hrs at atmospheric pressure
  7. customThe catalyst was then removed by filtration
  8. customthe filtrate evaporated to dryness
  9. customThe aqueous phase was separated
  10. customevaporated to dryness
  11. dissolutionthe residue dissolved in aqueous solution
  12. additioncontaining 1% acetic acid/0.05% pyridine
  13. washThe column was eluted by a gradient technique
  14. additionfilled with aqueous 1% acetic acid/0.05% pyridine
  15. additionThe fractions containing product (as detected by t.l.c)
  16. customevaporated

Sources & evidence

ORD record
ord-fcee29cd8d134af2bba2bd21fae4b235
Source dataset
uspto-grants-1977_11
Patent number
US04060603

Reaction notes

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