1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 17-{3-[(2-Benzyloxycarbonylethyl)tert-butoxycarbonylamino]propionylamino}heptadecanoic acid tert-butyl ester

HRID 2369795Notes

Reaction equation

HRID 2369795 reaction equation
[CH2:1]([O:8][C:9]([CH2:11][CH2:12][N:13]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14][CH2:15][C:16]([OH:18])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C.[C:56]([O:60][C:61](=[O:79])[CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][NH2:78])([CH3:59])([CH3:58])[CH3:57]>CN(C=O)C.C1COCC1>[C:56]([O:60][C:61](=[O:79])[CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][NH:78][C:16](=[O:18])[CH2:15][CH2:14][N:13]([CH2:12][CH2:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])([CH3:59])([CH3:57])[CH3:58]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 687356593-[(2-Benzyloxycarbonylethyl)tert-butoxycarbonylamino]propionic acidHCID 8664712917-Aminoheptadecanoic acid tert-butyl ester

Product 1

HCID 6876904917-{3-[(2-Benzyloxycarbonylethyl)tert-butoxycarbonylamino]propionylamino}heptadecanoic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

3-[(2-Benzyloxycarbonylethyl) tert-butoxycarbonylamino]propionic acid (0.17 g, 0.48 mmol) was dissolved in DMF (2 mL) and HOBt (0.065 g, 0.48 mmol) and EDAC (0.093 g, 0.48 mmol) were added. The mixture was stirred for 30 min., and DIEA (0.083 mL, 0.48 mmol) was added and 17-aminoheptadecanoic acid tert-butyl ester (0.15 g, 0.44 mmol) dissolved in THF (3 mL)+DMF (0.5 mL) was added. The reaction was stirred for 2 days. The reaction was concentrated and the residue was dissolved in AcOEt (50 mL) and washed with 0.2 N HCl (2×15 mL). The organic phase was dried over MgSO4 and concentrated under vacuum. The product was purified by flash chromatography (Silica) eluting with AcOEt/Heptane (1:1, 7:3, 8:2) then DCM, DCM:methanol (8:2) and 5% AcOH in DCM. The appropriate fractiones were pooled and concentrated under vacuum. The residue was dissolved in DCM. Silica was added and the product was concentrated onto the silica under vacuum. The silica was used in another flash chromatography, eluting with AcOEt/heptane (3:7 and 1:1). The appropriate fractiones were pooled and concentrated under vacuum to yield 135 mg.

Workup

  1. additionwas added
  2. stirringThe reaction was stirred for 2 days
  3. concentrationThe reaction was concentrated
  4. dissolutionthe residue was dissolved in AcOEt (50 mL)
  5. washwashed with 0.2 N HCl (2×15 mL)
  6. dry with materialThe organic phase was dried over MgSO4
  7. concentrationconcentrated under vacuum
  8. customThe product was purified by flash chromatography (Silica)
  9. washeluting with AcOEt/Heptane (1:1, 7:3, 8:2)
  10. concentrationconcentrated under vacuum
  11. dissolutionThe residue was dissolved in DCM
  12. additionSilica was added
  13. concentrationthe product was concentrated onto the silica under vacuum
  14. washeluting with AcOEt/heptane (3:7 and 1:1)
  15. concentrationconcentrated under vacuum
  16. customto yield 135 mg

Sources & evidence

ORD record
ord-2cea4335d3da45378452756561315e41
Source dataset
uspto-grants-2014_04
Patent number
US08710000B2

Reaction notes

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