Dibenzyl ether → 4-[(S)-2-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-6-hydroxy-hexanoyl]-piperazine-1-carboxylic acid butyl ester

HRID 1970614Notes

Reaction equation

HRID 1970614 reaction equation
[CH2:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:58])[C@@H:15]([NH:28][C:29]([C:31]2[CH:35]=[C:34]([O:36][CH2:37][C:38]([N:40]3[CH2:44][CH2:43][CH2:42][C@H:41]3[C:45](=[O:51])[NH:46][CH:47]3[CH2:50][CH2:49][CH2:48]3)=[O:39])[N:33]([C:52]3[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=3)[N:32]=2)=[O:30])[CH2:16][CH2:17][CH2:18][CH2:19][O:20]CC2C=CC=CC=2)[CH2:10][CH2:9]1)=[O:7])[CH2:2][CH2:3][CH3:4].C(OCC1C=CC=CC=1)C1C=CC=CC=1>C(OCC)(=O)C>[CH2:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:58])[C@@H:15]([NH:28][C:29]([C:31]2[CH:35]=[C:34]([O:36][CH2:37][C:38]([N:40]3[CH2:44][CH2:43][CH2:42][C@H:41]3[C:45](=[O:51])[NH:46][CH:47]3[CH2:48][CH2:49][CH2:50]3)=[O:39])[N:33]([C:52]3[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=3)[N:32]=2)=[O:30])[CH2:16][CH2:17][CH2:18][CH2:19][OH:20])[CH2:10][CH2:9]1)=[O:7])[CH2:2][CH2:3][CH3:4]

Participants

4

Reactant 2

HCID 7657Dibenzyl etherHCID 668571284-[(S)-6-Benzyloxy-2-({5-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-hexanoyl]-piperazine-1-carboxylic acid butyl ester

Product 1

HCID 668562204-[(S)-2-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-6-hydroxy-hexanoyl]-piperazine-1-carboxylic acid butyl esterYield 1.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 819 mg 4-[(S)-6-Benzyloxy-2-({5-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-hexanoyl]-piperazine-1-carboxylic acid butyl ester in 20 ml ethyl acetate were added under argon 100 mg Pd/C (10%) and the suspension was stirred under an atmosphere of hydrogen (3 bar) for 12 h. The suspension was filtered over a plug of Celite® and washed with ethyl acetate. The crude product obtained after evaporation of the solvent was purified by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA) to give a mixture of the title compound (8 mg) and unreacted benzyl ether which was subjected to the same hydrogenolysis conditions described above to give the title compound.

Workup

  1. filtrationThe suspension was filtered over a plug of Celite®
  2. washwashed with ethyl acetate
  3. customThe crude product obtained
  4. customafter evaporation of the solvent
  5. customwas purified by preparative HPLC (
  6. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)
  7. customto give

Sources & evidence

ORD record
ord-2f9955f1299c417fa4b0f179a40cd6f3
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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