HCID 178520769, compound → HCID 178520768, compound

HRID 1396978Notes

Reaction equation

HRID 1396978 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][C:21]([F:24])=[CH:20][N+:19]=3[O-:25])=[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][C:21]([F:24])=[CH:20][N+:19]=3[O-:25])=[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 178520769HCID 178520769, compound

Product 1

HCID 178520768HCID 178520768, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

(5S)-1-((2R)-2-(Cyclopentylmethyl)-4-oxo-4-{[(phenylmethyl)oxy]amino}butanoyl)-N-(5-fluoro-1-oxido-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide (90 mg, 0.18 mmol) was dissolved in methanol (8 mL), and Pearlman's catalyst (24 mg, 0.03 mmol) was added to the solution. The mixture was stirred under 1 atm of H2 (balloon) for 1 hour. After 1 hour, the reaction 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-(5-fluoro-1-oxido-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide (38 mg, 0.09 mmol, 50% yield) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.79-0.94 (m, 1H) 1.04-1.24 (m, 3H) 1.41-1.68 (m, 7H) 1.72-2.32 (m, 18H) 2.39-2.52 (m, 2H) 2.58-2.74 (m, 2H) 3.21-3.31 (m, 1H) 3.39-3.50 (m, 1H) 3.69-3.81 (m, 1H) 5.08-5.22 (m, 1H) 7.03-7.07 (m, 1H) 7.17-7.24 (m, 2H) 8.23-8.29 (m, 1H) 8.42-8.49 (m, 1H) 10.92-11.05 (m, 1H). MS: 422 ([M+H]+).

Workup

  1. waitAfter 1 hour
  2. filtrationthe reaction 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-5a12b1cbef28446998bb6d826e48a016
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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