Trifluoroacetic acid → (S)-4-benzyloxycarbonylaminoacetyl-3-{3-(6-tert-butoxycarbonylaminohexanoylamino)propyl}-2-oxopiperazine-1-acetic acid

HRID 376535Notes

Reaction equation

HRID 376535 reaction equation
C([O:5][C:6](=[O:40])[CH2:7][N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:27])[CH2:15][NH:16][C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[C@@H:10]([CH2:28][CH2:29][CH2:30][NH:31]C(OC(C)(C)C)=O)[C:9]1=[O:39])(C)(C)C.C(O[NH:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][C:52]([OH:54])=O)(C)(C)C.Cl.C(N=C=N[CH2:61][CH2:62][CH2:63]N(C)C)C.ON1C2C=CC=CC=2N=N1.[CH2:77](N(CC)CC)C.FC(F)(F)[C:86]([OH:88])=[O:87]>CN(C=O)C.C(OCC)(=O)C>[CH2:20]([O:19][C:17]([NH:16][CH2:15][C:14]([N:11]1[CH2:12][CH2:13][N:8]([CH2:7][C:6]([OH:40])=[O:5])[C:9](=[O:39])[C@@H:10]1[CH2:28][CH2:29][CH2:30][NH:31][C:52](=[O:54])[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47][NH:46][C:86]([O:88][C:62]([CH3:63])([CH3:77])[CH3:61])=[O:87])=[O:27])=[O:18])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

9

Reactant 6

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10907851(S)-4-benzyloxycarbonylaminoacetyl-3-(3-t-butoxycarbonylaminopropyl)-2-oxopiperazine-1-acetic acid t-butyl esterHCID 193614876-Tert-butoxyaminocaproic acid

Product 1

HCID 11814156(S)-4-benzyloxycarbonylaminoacetyl-3-{3-(6-tert-butoxycarbonylaminohexanoylamino)propyl}-2-oxopiperazine-1-acetic acid

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

In 3.0 cc of trifluoroacetic acid was dissolved (S)-4-benzyloxycarbonylaminoacetyl-3-(3-t-butoxycarbonylaminopropyl)-2-oxopiperazine-1-acetic acid t-butyl ester (0.6 g, 1.07 mmol) produced in Reference Example 2. The solution was stirred for 30 minutes at room temperature, which was concentrated under reduced pressure. In 2.1 cc of DMF were dissolved 6-t-butoxyaminocaproic acid (0.26 g, 1.12 mmol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (0.22 g, 1.14 mmol) and 1-hydroxybenzotriazole (0.15 g, 1.12 mmol). The solution was stirred for one hour, to which was added 2.1 cc of a DMF solution of the concentrate obtained above and triethylamine (0.3 cc, 2.14 mmol). The mixture was stirred for 4 hours at room temperature. The reaction mixture was diluted with ethyl acetate, which was washed with a 5% aqueous solution of potassium hydrogensulfate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was concentrated under reduced pressure, which was purified by means of a silica gel column chromatography (ethyl acetate/methanol/acetic acid=20/10/0.6) to afford 0.42 g (y. 63.3%) of the titled compound as a colorless amorphous powdery product.

Workup

  1. customproduced in Reference Example 2
  2. concentrationwhich was concentrated under reduced pressure
  3. stirringThe solution was stirred for one hour, to which
  4. stirringThe mixture was stirred for 4 hours at room temperature
  5. washwas washed with a 5% aqueous solution of potassium hydrogensulfate
  6. concentrationThe organic layer was concentrated under reduced pressure, which
  7. customwas purified by means of a silica gel column chromatography (ethyl acetate/methanol/acetic acid=20/10/0.6)

Sources & evidence

ORD record
ord-89d6904bb4304f9aa8c508ea536a910c
Source dataset
uspto-grants-2000_02
Patent number
US06020334

Reaction notes

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