(5S)-1-((2R)-2-(cyclopentylmethyl)-4-oxo-4-{[(phenylmethyl)oxy]amino}butanoyl)-N,N-dimethyl-4,5-dihydro-1H-pyrazole-5-carboxamide → (5S)-1-[(2R)-2-(cyclopentylmethyl)-4-(hydroxyamino)-4-oxobutanoyl]-N,N-dimethyl-4,5-dihydro-1H-pyrazole-5-carboxamide

HRID 1396982Notes

Reaction equation

HRID 1396982 reaction equation
[CH:1]1([CH2:6][C@H:7]([CH2:20][C:21](=[O:31])[NH:22][O:23]CC2C=CC=CC=2)[C:8]([N:10]2[C@H:14]([C:15]([N:17]([CH3:19])[CH3:18])=[O:16])[CH2:13][CH:12]=[N:11]2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1>CO.[OH-].[OH-].[Pd+2]>[CH:1]1([CH2:6][C@H:7]([CH2:20][C:21]([NH:22][OH:23])=[O:31])[C:8]([N:10]2[C@H:14]([C:15]([N:17]([CH3:19])[CH3:18])=[O:16])[CH2:13][CH:12]=[N:11]2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 1

HCID 86706401(5S)-1-((2R)-2-(cyclopentylmethyl)-4-oxo-4-{[(phenylmethyl)oxy]amino}butanoyl)-N,N-dimethyl-4,5-dihydro-1H-pyrazole-5-carboxamide

Product 1

HCID 86706402(5S)-1-[(2R)-2-(cyclopentylmethyl)-4-(hydroxyamino)-4-oxobutanoyl]-N,N-dimethyl-4,5-dihydro-1H-pyrazole-5-carboxamideYield 82.1%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

To a solution of (5S)-1-((2R)-2-(cyclopentylmethyl)-4-oxo-4-{[(phenylmethyl)oxy]amino}butanoyl)-N,N-dimethyl-4,5-dihydro-1H-pyrazole-5-carboxamide (120 mg, 0.28 mmol) in methanol (10 mL) was added Pearlman's catalyst (39 mg, 0.056 mmol). The resulting mixture 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 (5S)-1-[(2R)-2-(cyclopentylmethyl)-4-(hydroxyamino)-4-oxobutanoyl]-N,N-dimethyl-4,5-dihydro-1H-pyrazole-5-carboxamide (78 mg, 0.23 mmol, 82% yield) as a yellow solid. MS: 389 ([M+H]+). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.09-1.26 (m, 2H) 1.59 (br. s., 35H) 1.78-1.97 (m, 5H) 2.43-2.52 (m, 1H) 2.62-2.73 (m, 1H) 2.85-2.95 (m, 1H) 3.01 (s, 3H) 3.19 (s, 4H) 3.58-3.67 (m, 1H) 5.08-5.18 (m, 1H) 6.88-6.97 (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-1eb2385473a24ec3876542c890163ca9
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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