Dicyclohexylcarbodiimide → HCID 178513958, compound

HRID 442500Notes

Reaction equation

HRID 442500 reaction equation
[O:1]=C1N=C(C(O)=O)C=N1.[OH:10]N1C2C=CC=CC=2N=N1.O.[C:21]([NH:31][C@H:32]([C:39]([N:41]1[CH2:48][CH2:47][CH2:46][C@H:42]1[C:43]([NH2:45])=[O:44])=[O:40])[CH2:33][C:34]1[N:38]=[CH:37][NH:36][CH:35]=1)(=[O:30])[C:22]1[NH:29][C:27](=[O:28])[NH:26][C:24](=[O:25])C=1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O.C(N(CC)CC)C>[OH2:1].[OH2:10].[OH2:25].[O:28]=[C:27]1[N:29]=[C:22]([C:21]([NH:31][C@H:32]([C:39]([N:41]2[CH2:48][CH2:47][CH2:46][C@H:42]2[C:43]([NH2:45])=[O:44])=[O:40])[CH2:33][C:34]2[N:38]=[CH:37][NH:36][CH:35]=2)=[O:30])[CH:24]=[N:26]1

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 202038402-Oxo-2H-imidazole-4-carboxylic acidHCID 178513957HCID 178513957, compound

Product 1

HCID 178513958HCID 178513958, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
-5 °C

Procedure

To 100 ml of dimethylformamide are added 5.1 g of 2-oxo-imidazole-4-carboxylic acid, 5.8 g of 1-hydroxybenzotriazole and L-histidyl-L-prolinamide dihydrobromide (prepared as described in Example 2 from 15.4 g of N-benzyl-oxycarbonyl-L-histidyl-L-prolinamide). After chilling to -5° C. while stirring 11.1 ml of triethylamine and thereafter the solution of 8.3 g of N,N'-dicyclohexylcarbodiimide in 30 ml of dimethylformamide are added. The stirred mixture is chilled for 30 minutes longer and then it is stored for 12 hours at room temperature. The precipitate formed is sucked off and the solution is evaporated under reduced pressure and at a temperature of about 35° C. The residue is mixed with 100 ml of water, stored for 12 hours at 0° C. filtered and then the filtrate is treated with a cationic exchanger and thereafter with 1n ammonia as described in Example 2. The ammoniacal filtrates are combined, evaporated under reduced pressure to a small volume and finally lyophylized. The residue is subjected to countercurrent distribution in the system n-butanol/water. The fractions containing the main product are combined, evaporated to dryness and the residue is dissolved in 50 ml of methanol and reprecipitated by addition of 500 ml of chloroform, which treatment then is repeated once. After drying in vacuum 4.7 g (27% of the theoretical yield) of 2-oxo-imidazole-4-carbonyl-L-histidyl-L-prolinamide trihydrate are obtained. This substance on heating above 180° C. begins to sinter and on heating to 212° C. it is molten.

Workup

  1. temperatureThe stirred mixture is chilled for 30 minutes longer
  2. customThe precipitate formed
  3. customthe solution is evaporated under reduced pressure and at a temperature of about 35° C
  4. additionThe residue is mixed with 100 ml of water
  5. waitstored for 12 hours at 0° C.
  6. filtrationfiltered
  7. additionthe filtrate is treated with a cationic exchanger
  8. customevaporated under reduced pressure to a small volume
  9. additionThe fractions containing the main product
  10. customevaporated to dryness
  11. dissolutionthe residue is dissolved in 50 ml of methanol
  12. customreprecipitated by addition of 500 ml of chloroform, which treatment
  13. customAfter drying in vacuum 4.7 g (27% of the

Sources & evidence

ORD record
ord-2c79e6bd0f484cd1884049fc60ef611e
Source dataset
uspto-grants-1977_08
Patent number
US04045556

Reaction notes

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