Dimethylformamide → HCID 7350179, compound

HRID 989575Notes

Reaction equation

HRID 989575 reaction equation
F[C:2](F)(F)[C:3]([OH:5])=[O:4].[CH3:8][N:9]1CCOCC1.[CH2:15]1CCC(N=C=NC2CCCCC2)CC1.[CH:30]1[CH:31]=[CH:32][C:33]2N(O)N=N[C:34]=2[CH:35]=1.[NH:40]([C:45]([O:47][CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=[O:46])[CH2:41][C:42]([OH:44])=O.C[N:56]([CH:58]=[O:59])C>C(OCC)(=O)C>[NH:40]([C:45]([O:47][CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=[O:46])[CH2:41][C:42]([NH:9][CH2:8][C:58]([NH:56][C@H:2]([C:3]([OH:5])=[O:4])[CH2:15][C:34]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:35]=1)=[O:59])=[O:44]

Participants

8

Reactant 6

HCID 6228DimethylformamideHCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 14349BenzyloxycarbonylglycineHCID 757711-Hydroxybenzotriazole

Product 1

HCID 7350179HCID 7350179, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

BOC-Phe (manufactured and sold by PEPTIDE INSTITUTE INC., Japan, 10.6 g) was dissolved in 100 ml of ethyl acetate, to thereby obtain a solution. To the obtained solution were added 10.0 g of phenacyl bromide and 5.1 g of triethylamine while cooling over ice, followed by stirring. The reaction temperature was elevated to room temperature, followed by stirring overnight to effect a reaction, thereby obtaining a reaction mixture. The obtained reaction mixture was evaporated to dryness, to thereby obtain a residue. The obtained residue was dissolved in 50 ml of ethyl acetate and the resultant solution was washed with a saturated aqueous sodium hydrogencarbonate solution and then with saturated saline. The washed solution was dried with magnesium sulfate and concentrated under reduced pressure, to thereby obtain 13.4 g of BOC-Phe phenacyl ester. Further, to 1.9 g of BOC-Phe phenacyl ester was added 5 ml of trifluoroacetic acid (TFA), followed by stirring for 10 minutes. The resultant reaction mixture was evaporated to dryness under reduced pressure for removing TFA, to thereby obtain a residue. To the obtained residue were added 20 ml of DMF, 0.61 g of N-methylmorpholine, 1.24 g of DCC, 0.81 g of HOBT and BOC-Gly (manufactured and sold by PEPTIDE INSTITUTE INC., Japan 1.05 g), followed by stirring overnight at room temperature, to thereby obtain a reaction mixture. The obtained reaction mixture was concentrated under reduced pressure, to thereby obtain a residue. The obtained residue was dissolved in 50 ml of ethyl acetate, and the resultant solution was washed with 0.1 N hydrochloride cooled with ice, saturated saline, a saturated aqueous sodium hydrogencarbonate solution and again saturated saline successively. The washed solution was dried with magnesium sulfate and concentrated under reduced pressure, to thereby obtain 1.5 g of BOC-Gly-Phe phenacyl ester. Further, to 1.6 g of BOC-Gly-Phe phenacyl ester was added 5 ml of trifluoroacetic acid (TFA), followed by stirring for 10 minutes, to thereby obtain a reaction mixture. The obtained reaction mixture was evaporated to dryness under reduced pressure for removing TFA, to thereby obtain a residue. To the obtained residue were added 20 ml of DMF, 0.40 g of N-methylmorpholine, 0.83 g of DCC, 0.54 g of HOBT and 0.84 g of Z-Gly (manufactured and sold by Kokusan Chemical Works Ltd., Japan), followed by stirring overnight at room temperature, to thereby obtain a reaction mixture. The obtained reaction mixture was concentrated under reduced pressure, to thereby obtain a residue. The obtained residue was dissolved in 50 ml of ethyl acetate and the resultant solution was washed with 0.1 N solution hydrochloride cooled with ice, saturated saline, a saturated aqueous sodium hydrogencarbonate solution and again saturated saline successively. The washed solution was dried with magnesium sulfate and concentrated under reduced pressure, to thereby obtain 1.1 g of Z-Gly-Gly-Phe phepacyl ester. 1.1 g of Z-Gly-Gly-Phe phenacyl ester was dissolved in 30 ml of 90% acetic acid, to obtain a mixture. To the obtained mixture was added 4 g of zinc dust, followed by stirring at room temperature for 5 hours, to thereby obtain a reaction mixture. The obtained reaction mixture was subjected to filtration and evaporated to dryness, to thereby obtain a residue. The obtained residue was dissolved in 30 ml of ethyl acetate and the resultant solution was washed with 10% citric acid and then with saturated saline successively, dried with magnesium sulfate and concentrated under reduced pressure, to thereby obtain 0.62 g of Z-Gly-Gly-Phe.

Workup

  1. customto thereby obtain a reaction mixture
  2. customThe obtained reaction mixture
  3. customwas evaporated to dryness under reduced pressure
  4. customfor removing TFA
  5. customto thereby obtain a residue
  6. stirringby stirring overnight at room temperature
  7. customto thereby obtain a reaction mixture
  8. customThe obtained reaction mixture
  9. concentrationwas concentrated under reduced pressure
  10. customto thereby obtain a residue
  11. washthe resultant solution was washed with 0.1 N solution hydrochloride
  12. temperaturecooled with ice, saturated saline
  13. dry with materialThe washed solution was dried with magnesium sulfate
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-45c55d5397a84a4e81416398794832ce
Source dataset
uspto-grants-2002_10
Patent number
US06458347B1

Reaction notes

Loading…