(3R)-3-(cyclopentyl methyl)-4-[(5S)-5-(4-morpholinylcarbonyl)-4,5-dihydro-1H-pyrazol-1-yl]-4-oxo-N-[(phenylmethyl)oxy]butanamide → (3R)-3-(cyclopentylmethyl)-N-hydroxy-4-[(5S)-5-(4-morpholinylcarbonyl)-4,5-dihydro-1H-pyrazol-1-yl]-4-oxobutanamide

HRID 1396986Notes

Reaction equation

HRID 1396986 reaction equation
[CH:1]1([CH2:6][C@@H:7]([C:20]([N:22]2[C@H:26]([C:27]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[O:28])[CH2:25][CH:24]=[N:23]2)=[O:21])[CH2:8][C:9]([NH:11][O:12]CC2C=CC=CC=2)=[O:10])[CH2:5][CH2:4][CH2:3][CH2:2]1>CO.[OH-].[OH-].[Pd+2]>[CH:1]1([CH2:6][C@@H:7]([C:20]([N:22]2[C@H:26]([C:27]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[O:28])[CH2:25][CH:24]=[N:23]2)=[O:21])[CH2:8][C:9]([NH:11][OH:12])=[O:10])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 1

HCID 86706403(3R)-3-(cyclopentyl methyl)-4-[(5S)-5-(4-morpholinylcarbonyl)-4,5-dihydro-1H-pyrazol-1-yl]-4-oxo-N-[(phenylmethyl)oxy]butanamide

Product 1

HCID 86706404(3R)-3-(cyclopentylmethyl)-N-hydroxy-4-[(5S)-5-(4-morpholinylcarbonyl)-4,5-dihydro-1H-pyrazol-1-yl]-4-oxobutanamideYield 39.2%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

To a solution of (3R)-3-(cyclopentylmethyl)-4-[(5S)-5-(4-morpholinylcarbonyl)-4,5-dihydro-1H-pyrazol-1-yl]-4-oxo-N-[(phenylmethyl)oxy]butanamide (57 mg, 0.12 mmol) in methanol (5 mL) was added Pearlman's catalyst (17 mg, 0.024 mmol). The mixture then was stirred under 1 atm of H2 for 1 hour. After 1 hour, the mixture was filtered, concentrated, and purified by Gilson HPLC (Sunfire Column 19×50 mm, flowrate 25 mL/min, 10 min, 5-65% MeCN:H2O) to afford (3R)-3-(cyclopentylmethyl)-N-hydroxy-4-[(5S)-5-(4-morpholinylcarbonyl)-4,5-dihydro-1H-pyrazol-1-yl]-4-oxobutanamide (19 mg, 0.047 mmol, 39% yield) as a white solid. MS: 381 ([M+H]+). 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.07-1.29 (m, 2H) 1.36-1.48 (m, 1H) 1.50-1.69 (m, 4H) 1.72-2.03 (m, 5H) 2.19-2.30 (m, 1H) 2.36-2.53 (m, 1H) 2.77-3.01 (m, 2H) 3.46-3.98 (m, 10H) 5.15-5.29 (m, 1H) 7.03-7.07 (m, 1H).

Workup

  1. waitAfter 1 hour
  2. filtrationthe mixture was filtered
  3. concentrationconcentrated
  4. custompurified by Gilson HPLC (Sunfire Column 19×50 mm, flowrate 25 mL/min, 10 min, 5-65% MeCN:H2O)

Sources & evidence

ORD record
ord-94a6042cd51048dc9fbdc3ff3198f7f0
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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