(S)-4-benzyloxycarbonylaminoacetyl-3-(3-t-butoxycarbonylaminopropyl)-2-oxopiperazine-1-acetic acid t-butyl ester → (S)-4-aminoacetyl-3-aminopropyl-2-oxopiperazine-1-acetic acid

HRID 1417194Notes

Reaction equation

HRID 1417194 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(OCC2C=CC=CC=2)=O)[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>FC(F)(F)C(O)=O.CO.[C].[Pd]>[NH2:16][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][NH2:31])=[O:27]

Participants

5

Reactant 1

HCID 10907851(S)-4-benzyloxycarbonylaminoacetyl-3-(3-t-butoxycarbonylaminopropyl)-2-oxopiperazine-1-acetic acid t-butyl ester

Product 1

HCID 10956654(S)-4-aminoacetyl-3-aminopropyl-2-oxopiperazine-1-acetic acid

Reagents, catalysts & solvents 3

HCID 178418390HCID 178418390, compoundCatalystHCID 887MethanolSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

In 5 ml of trifluoroacetic acid was dissolved 500 mg of (S)-4-benzyloxycarbonylaminoacetyl-3-(3-t-butoxycarbonylaminopropyl)-2-oxopiperazine-1-acetic acid t-butyl ester. The solution was stirred for one hour at room temperature. The reaction mixture was concentrated under reduced pressure to leave an oily product, which was dissolved in 10 ml of methanol. To the solution was added 10 mg of 10% palladium-carbon. The mixture was stirred for one hour at room temperature under hydrogen atmosphere. The catalyst was filtered off, and the filtrate was concentrated under reduced pressure to leave a crude product of (S)-4-aminoacetyl-3-aminopropyl-2-oxopiperazine-1-acetic acid. This product was dissolved in a mixture of 10 ml of water and 10 ml of dioxane. To the solution was added 400 mg of sodium hydrogen carbonate. Subsequently, 420 mg of 3-(4-carboxyphenylamino)-1,2,4-oxadiazolin-4H-5-one produced in Reference Example 25 and 250 mg of N-hydroxysuccinimide were dissolved in 5 ml of dimethylformamide. To the solution was added 450 mg of dicyclohexyl carbodiimide. The mixture was stirred for 3 hours at room temperature, then concentrated under reduced pressure to leave an oily substance. This substance was dissolved in 5 ml of dioxane, and added to the solution of (S)-4-aminoacetyl-3-aminopropyl-2-oxopiperazine-1-acetic acid prepared as above. The mixture was stirred for 6 hours at room temperature. The reaction mixture was neutralized with 1N HCl, then concentrated under reduced pressure to give a crude product, followed by purification by means of a sephadex LH-20 column to afford 230 mg of the title compound as a colorless amorphous powdery product.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto leave an oily product, which
  3. stirringThe mixture was stirred for one hour at room temperature under hydrogen atmosphere
  4. filtrationThe catalyst was filtered off
  5. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-fc588c8ec40142279e171994fd9e16dc
Source dataset
uspto-grants-1999_03
Patent number
US05876756

Reaction notes

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