(5S)-1-((2R)-2-(cyclopentylmethyl)-4-oxo-4-{[(phenylmethyl)oxy]amino}butanoyl)-N-(6-ethyl-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide → (5S)-1-[(2R)-2-(cyclopentylmethyl)-4-(hydroxyamino)-4-oxobutanoyl]-N-(6-ethyl-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide

HRID 1396973Notes

Reaction equation

HRID 1396973 reaction equation
[CH:1]1([CH2:6][C@H:7]([CH2:26][C:27](=[O:37])[NH:28][O:29]CC2C=CC=CC=2)[C:8]([N:10]2[C@H:14]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][CH3:25])[N:19]=3)=[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]([CH2:26][C:27]([NH:28][OH:29])=[O:37])[C:8]([N:10]2[C@H:14]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][CH3:25])[N:19]=3)=[O:16])[CH2:13][CH:12]=[N:11]2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

4

Reactant 1

HCID 86706396(5S)-1-((2R)-2-(cyclopentylmethyl)-4-oxo-4-{[(phenylmethyl)oxy]amino}butanoyl)-N-(6-ethyl-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide

Product 1

HCID 86706397(5S)-1-[(2R)-2-(cyclopentylmethyl)-4-(hydroxyamino)-4-oxobutanoyl]-N-(6-ethyl-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamideYield 45.2%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

(5S)-1-((2R)-2-(Cyclopentylmethyl)-4-oxo-4-{[(phenylmethyl)oxy]amino}butanoyl)-N-(6-ethyl-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide (157 mg, 0.31 mmol) was dissolved in methanol (8 mL), and Pearlman's catalyst (43 mg, 0.06 mmol) was added to the solution. The mixture was stirred under 1 atm of H2 for 4 hours. After 4 hours, the reaction mixture was filtered, and the filtrate was 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-(6-ethyl-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide (62 mg, 0.14 mmol, 45% yield) as a white solid. 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.14 (m, J=5.81 Hz, 1H) 1.29 (t, J=7.58 Hz, 3H) 1.39-1.68 (m, 5H) 1.70-1.97 (m, 4H) 2.27 (dd, J=14.53, 6.19 Hz, 1H) 2.47 (dd, J=14.40, 9.09 Hz, 1H) 2.76 (q, J=7.66 Hz, 2H) 3.17 (m, J=5.68, 1.89 Hz, 1H) 3.87 (tt, J=8.62, 6.03 Hz, 1H) 5.00 (dd, J=11.12, 5.05 Hz, 1H) 7.04 (d, J=7.58 Hz, 1H) 7.12 (s, 1H) 7.72 (t, J=7.83 Hz, 1H) 7.87 (d, J=8.59 Hz, 1H). MS: 417 ([M+H]+).

Workup

  1. waitAfter 4 hours
  2. filtrationthe reaction mixture was filtered
  3. concentrationthe filtrate was concentrated
  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-3e77e2803deb4ab1878b28311d9607a5
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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