4-[(S)-4-Benzyloxy-2-({5-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-butyryl]-piperazine-1-carboxylic acid ethyl ester → 4-[(S)-2-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-4-hydroxy-butyryl]-piperazine-1-carboxylic acid ethyl ester

HRID 1970487Notes

Reaction equation

HRID 1970487 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:54])[C@@H:13]([NH:24][C:25]([C:27]2[CH:31]=[C:30]([O:32][CH2:33][C:34]([N:36]3[CH2:40][CH2:39][CH2:38][C@H:37]3[C:41](=[O:47])[NH:42][CH:43]3[CH2:46][CH2:45][CH2:44]3)=[O:35])[N:29]([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[N:28]=2)=[O:26])[CH2:14][CH2:15][O:16]CC2C=CC=CC=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]>C(OCC)(=O)C.[Pd]>[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:54])[C@@H:13]([NH:24][C:25]([C:27]2[CH:31]=[C:30]([O:32][CH2:33][C:34]([N:36]3[CH2:40][CH2:39][CH2:38][C@H:37]3[C:41](=[O:47])[NH:42][CH:43]3[CH2:46][CH2:45][CH2:44]3)=[O:35])[N:29]([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[N:28]=2)=[O:26])[CH2:14][CH2:15][OH:16])[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

4

Reactant 1

HCID 668547374-[(S)-4-Benzyloxy-2-({5-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-butyryl]-piperazine-1-carboxylic acid ethyl ester

Product 1

HCID 441290584-[(S)-2-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-4-hydroxy-butyryl]-piperazine-1-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 543 mg 4-[(S)-4-benzyloxy-2-({5-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-butyryl]-piperazine-1-carboxylic acid ethyl ester in 15 ml ethyl acetate were added 200 mg Pd/C (10%) and the suspension stirred under an atmosphere of hydrogen (1 bar) for 12 h. The reaction mixture was filtrated, washed with ethyl acetate and concentrated. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA). The fractions containing the product were lyophilized to yield the pure product. Yield: 178 mg MS (ES+): m/e=654.

Workup

  1. filtrationThe reaction mixture was filtrated
  2. washwashed with ethyl acetate
  3. concentrationconcentrated
  4. customThe crude product was purified by preparative HPLC (
  5. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)
  6. additionThe fractions containing the product
  7. customto yield the pure product

Sources & evidence

ORD record
ord-e0f20526ed4e4c2cbe9cdaad3355e085
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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