Dicyclohexylcarbodiimide → HCID 178427552, compound

HRID 647397Notes

Reaction equation

HRID 647397 reaction equation
[NH:1]([C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])[C@H:2]([C:9]([OH:11])=O)[CH2:3][O:4][C:5]([CH3:8])([CH3:7])[CH3:6].ON1C(=O)CCC1=O.C1(N=C=NC2CCCCC2)CCCCC1.[NH2:45][C@H:46]([C:64]([NH:66][C@H:67]([C:72]([OH:74])=[O:73])[CH2:68][CH:69]([CH3:71])[CH3:70])=[O:65])[CH2:47][CH2:48][CH2:49][NH:50][C:51](=[NH:63])[NH:52][S:53]([C:56]1[CH:62]=[CH:61][C:59]([CH3:60])=[CH:58][CH:57]=1)(=[O:55])=[O:54]>O1CCCC1.CN(C)C=O.C(N(CC)CC)C>[NH:1]([C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])[C@H:2]([C:9]([NH:45][C@H:46]([C:64]([NH:66][C@H:67]([C:72]([OH:74])=[O:73])[CH2:68][CH:69]([CH3:70])[CH3:71])=[O:65])[CH2:47][CH2:48][CH2:49][NH:50][C:51](=[NH:63])[NH:52][S:53]([C:56]1[CH:62]=[CH:61][C:59]([CH3:60])=[CH:58][CH:57]=1)(=[O:55])=[O:54])=[O:11])[CH2:3][O:4][C:5]([CH3:6])([CH3:7])[CH3:8]

Participants

8

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 80170N-HydroxysuccinimideHCID 1715617Z-Ser(tBu)-OHHCID 178427566HCID 178427566, compound2×

Product 1

HCID 178427552HCID 178427552, compoundYield 72.5%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

In 250 ml of tetrahydrofuran are dissolved 23.7 g (80.4 millimoles) of Z-Ser(But)-OH and 10.2 g of N-hydroxysuccinimide, and the solution is cooled to 0° C. and 16.6 g of dicyclohexylcarbodiimide is added to the solution. The mixture is stirred for 3 hours at the above temperature and then stirred in a low temperature chamber overnight. The formed precipitate is removed by filtration and the filtrate is concentrated under reduced pressure. The obtained oily substance is dissolved in 100 ml of dimethylformamide. This solution is mixed with a solution formed by dissolving 35.5 g (80.4 millimoles) of H-Arg(Tos)-Leu-OH prepared according to the process (ii) of Example 8 in 200 ml of dimethylformamide and adding 11.2 ml of triethylamine to the solution, and the mixture is stirred for 6 hours at 6° C., overnight in a low temperature chamber and for 5 hours at room temperature. The insoluble substances are removed by filtration and the filtrate is concentrated under reduced pressure. The residue is extracted with 700 ml of ethyl acetate, washed with 2% citric acid and water and dried with magnesium sulfate. The dried filtrate is concentrated under reduced pressure and ether is added to the residue to effect solidification. The solid is dissolved in a mixed liquid of chloroform and methanol, and the solution is concentrated under reduced pressure. Solidification is effected by ethyl acetate to obtain 41.9 g of intended Z-Ser(But)-Arg(Tos)-Leu-OH (the yield being 73%).

Workup

  1. stirringstirred in a low temperature chamber overnight
  2. customThe formed precipitate is removed by filtration
  3. concentrationthe filtrate is concentrated under reduced pressure
  4. dissolutionThe obtained oily substance is dissolved in 100 ml of dimethylformamide
  5. additionThis solution is mixed with a solution
  6. customformed
  7. customprepared
  8. stirringthe mixture is stirred for 6 hours at 6° C., overnight in a low temperature chamber and for 5 hours at room temperature
  9. customThe insoluble substances are removed by filtration
  10. concentrationthe filtrate is concentrated under reduced pressure
  11. extractionThe residue is extracted with 700 ml of ethyl acetate
  12. washwashed with 2% citric acid and water
  13. dry with materialdried with magnesium sulfate
  14. concentrationThe dried filtrate is concentrated under reduced pressure and ether
  15. additionis added to the residue
  16. dissolutionThe solid is dissolved in a mixed liquid of chloroform and methanol
  17. concentrationthe solution is concentrated under reduced pressure

Sources & evidence

ORD record
ord-1cd259e474a64adf98e4d7b15a10b9eb
Source dataset
uspto-grants-1983_10
Patent number
US04407745

Reaction notes

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