1-Hydroxybenzotriazole → (2R)-N-(4-amino-3-hydroxy-4-oxo-1-phenylbutan-2-yl)-1-benzyl-5-oxopyrrolidine-2-carboxamide

HRID 2061657Notes

Reaction equation

HRID 2061657 reaction equation
[CH2:1]([N:8]1[C:12](=[O:13])[CH2:11][CH2:10][C@@H:9]1[C:14]([OH:16])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.[NH2:27][CH:28]([CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[CH:29]([OH:33])[C:30]([NH2:32])=[O:31].Cl.CN(C)CCCN=C=NCC.CCN(C(C)C)C(C)C>C1COCC1.CN(C=O)C>[NH2:32][C:30](=[O:31])[CH:29]([OH:33])[CH:28]([NH:27][C:14]([C@H:9]1[CH2:10][CH2:11][C:12](=[O:13])[N:8]1[CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:16])[CH2:34][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 138823553-Amino-2-hydroxy-4-phenylbutanamideHCID 23390401(R)-1-Benzyl-5-carboxy-2-pyrrolidinone

Product 1

HCID 66644773(2R)-N-(4-amino-3-hydroxy-4-oxo-1-phenylbutan-2-yl)-1-benzyl-5-oxopyrrolidine-2-carboxamideYield 92%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To the solution of (R)-1-benzyl-5-oxopyrrolidine-2-carboxylic acid (475 mg, 2.167 mmol) in a mixture of 15 ml of THF and 0.5 ml of DMF at 5° C. were successively added 1-hydroxybenzotriazole (365 mg, 2.383 mmol), 3-amino-2-hydroxy-4-phenylbutanamide (421 mg, 2.167 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC; 457 mg, 2.383 mmol) and DIPEA (0.416 mL; 308 mg, 2.383 mmol). After stirring overnight at room temperature the solvent was evaporated under reduced pressure, water was added to the remaining residue and after stirring for 30 minutes at about 5° C. the precipitate was filtered off. Drying under reduced pressure gave the title compound as an off-white powder (786 mg; yield: 92%) which was used without further purification in the next step.

Workup

  1. customwas evaporated under reduced pressure, water
  2. additionwas added to the remaining residue
  3. stirringafter stirring for 30 minutes at about 5° C. the precipitate
  4. filtrationwas filtered off
  5. customDrying under reduced pressure

Sources & evidence

ORD record
ord-aa50c58dd80d4def9288fc1f2aeb7df1
Source dataset
uspto-grants-2012_10
Patent number
US08283363B2

Reaction notes

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