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

HRID 1417184Notes

Reaction equation

HRID 1417184 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 was concentrated under reduced pressure. In 2.1 cc of DMF was 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, washed with a 5% aqueous solution of potassium hydrogen sulfate and a saturated aqueous solution of sodium hydrogen carbonate. The organic layer was concentrated under reduced pressure purified by silica gel column chromatography (ethyl acetate/methanol/acetic acid=20/10/0.6) to afford 0.42 g (y. 63.3%) of the title compound as a colorless amorphous powdery product.

Workup

  1. customproduced in Reference Example 2
  2. concentrationwas 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. washwashed with a 5% aqueous solution of potassium hydrogen sulfate
  6. concentrationThe organic layer was concentrated under reduced pressure
  7. custompurified by silica gel column chromatography (ethyl acetate/methanol/acetic acid=20/10/0.6)

Sources & evidence

ORD record
ord-24d53486c8454201b09f86a962b985dc
Source dataset
uspto-grants-1999_03
Patent number
US05876756

Reaction notes

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