Hydrochloric Acid → HCID 131727621, compound

HRID 731520

Reaction equation

HRID 731520 reaction equation
[NH:1]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:2]([C:7]([OH:9])=O)[CH2:3][C:4](=[O:6])[NH2:5].C1C=CC2N(O)N=NC=2C=1.CC(C)N=C=NC(C)C.[NH2:36][C@H:37]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:38][C:39]1[CH:44]=[CH:43][C:42]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[CH:41][CH:40]=1.Cl.CN1CCOCC1>ClCCl.CN(C=O)C>[NH:1]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:2]([C:7]([NH:36][C@H:37]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:38][C:39]1[CH:40]=[CH:41][C:42]([O:45][C:46]([CH3:49])([CH3:47])[CH3:48])=[CH:43][CH:44]=1)=[O:9])[CH2:3][C:4](=[O:6])[NH2:5]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 12734DiisopropylcarbodiimideHCID 757711-Hydroxybenzotriazole2×HCID 82035N2-((tert-Butoxy)carbonyl)-L-asparagineHCID 7350495Tert-butyl (2S)-2-amino-3-[4-(tert-butoxy)phenyl]propanoate

Product 1

HCID 131727621HCID 131727621, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

Boc-Asn-OH (3.5 g 15 mmol) is dissolved in dichloromethane (100 ml amylene stabilised free of alcohol) and HOBt (2.24 g dry 16.5 mmol) is added. The mixture is cooled in an ice/water bath and DIC (2.45 ml 16 mmol) is added. The mixture will be allowed to react for 20 min. The HOBt on the bottom will react and a precipitate of DIU (on top) will form. H-Tyr(tBu)-OtBu×HCl (5.1 g 15.4 mmol) is dissolved in DMF (30 ml dry). The dichloromethane mixture containing the activated ester is filtered from the DIU directly into the DMF solution. The combined mixture is cooled in ice/water and NMM (1.75 ml 15.8 mmol) is added. The mixture is allowed to react over night. The solvents will be removed in vacuo. Ethyl acetate 200 ml is added and a precipitate is removed and the solution is washed with citric acid (2×50 ml 10%), sodium hydrogen carbonate (2×50 ml saturated) and brine (2×50 ml). The solution is dried with magnesium sulfate and the solvent removed in vacuo ending at 0.2 mBar for 30 min. The raw product will be suspended in pentane (40 ml) and filtered from a precipitate of DIU. The pentane will be removed in vacuo yielding the title compound.

Workup

  1. temperatureThe mixture is cooled in an ice/water bath
  2. customto react for 20 min
  3. customa precipitate of DIU (on top) will form
  4. filtrationis filtered from the DIU directly into the DMF solution
  5. temperatureThe combined mixture is cooled in ice/water
  6. customto react over night
  7. customThe solvents will be removed in vacuo
  8. additionEthyl acetate 200 ml is added
  9. customa precipitate is removed
  10. washthe solution is washed with citric acid (2×50 ml 10%), sodium hydrogen carbonate (2×50 ml saturated) and brine (2×50 ml)
  11. dry with materialThe solution is dried with magnesium sulfate
  12. customthe solvent removed in vacuo
  13. filtrationfiltered from a precipitate of DIU
  14. customThe pentane will be removed in vacuo

Sources & evidence

ORD record
ord-149181ff9f0b411ab915340f7bedcfde
Source dataset
uspto-grants-2009_09
Patent number
US07585839B2

Linked notes

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