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

HRID 1419721Notes

Reaction equation

HRID 1419721 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 acidYield 63.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

(S)-4-benzyloxycarbonylaminoacetyl-3-(3-tert-butoxycarbonylaminopropyl)-2-oxopiperazine-1-acetic acid tert-butyl ester as obtained in Reference Example 2 (0.6 g, 1.07 mmol) was dissolved in 3.0 ml of trifluoroacetic acid, followed by stirring at room temperature for 30 minutes, after which the reaction mixture was concentrated under reduced pressure. Separately, 6-tert-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) were dissolved in 2.1 ml of DMF, followed by stirring for 1 hour. To this solution, of the above residue and 2.1 ml of a DMF solution comprising triethylamine (0.3 ml, 2.14 mmol) was added, followed by stirring at room temperature for 4 hours. The reaction mixture was diluted with ethyl acetate and washed with 5% aqueous potassium hydrogen sulfate and saturated aqueous sodium bicarbonate. The organic layer was concentrated under reduced pressure; the residue was purified by silica gel column chromatography (ethyl acetate/methanol/acetic acid=20/10/0.6) to yield 0.42 g (63.3%) of the title compound as a colorless amorphous powder.

Workup

  1. concentrationafter which the reaction mixture was concentrated under reduced pressure
  2. stirringby stirring for 1 hour
  3. additionwas added
  4. stirringby stirring at room temperature for 4 hours
  5. washwashed with 5% aqueous potassium hydrogen sulfate and saturated aqueous sodium bicarbonate
  6. concentrationThe organic layer was concentrated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (ethyl acetate/methanol/acetic acid=20/10/0.6)

Sources & evidence

ORD record
ord-2829c595d94944e5bbdd2aacc7c2d6c4
Source dataset
uspto-grants-1999_03
Patent number
US05888531

Reaction notes

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