HCID 86706412, compound → HCID 86706411, compound

HRID 1397000Notes

Reaction equation

HRID 1397000 reaction equation
[CH:1]1([CH2:6][C@H:7]([CH2:24][C:25](=[O:35])[NH:26][O:27]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]=[CH:20][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]([CH2:24][C:25]([NH:26][OH:27])=[O:35])[C:8]([N:10]2[C@H:14]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][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 86706412HCID 86706412, compound

Product 1

HCID 86706411HCID 86706411, compoundYield 96.2%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

To a 500 ml round bottom flask under N2 was added (5S)-1-((2R)-2-(cyclopentylmethyl)-4-oxo-4-{[(phenylmethyl)oxy]amino}butanoyl)-N-2-pyridinyl-4,5-dihydro-1H-pyrazole-5-carboxamide (15.2 g, 31.8 mmol) in methanol (220 mL), followed by Pearlman's catalyst (3.17 g, 4.5 mmol). The mixture was degassed and hydrogenated using a H2 balloon. After 4 hours, LCMS indicated completion of the reaction. The mixture was kept under N2 in a refrigerator overnight. The clear solution on the top was decanted and filtered through 4 Acrodisc CR 25 mm Syringe Filters. The catalyst on the bottom was washed thoroughly with methanol (2×30 mL) and filtered. The combined filtrates were concentrated to dryness to provide (5S)-1-[(2R)-2-(cyclopentylmethyl)-4-(hydroxyamino)-4-oxobutanoyl]-N-2-pyridinyl-4,5-dihydro-1H-pyrazole-5-carboxamide (11.84 g, 30.6 mmol, 96% yield) as a white solid. 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.05-1.23 (m, 2H) 1.37-1.68 (m, 5H) 1.70-2.00 (m, 4H) 2.20-2.33 (m, 1H) 2.44 (d, J=9.09 Hz, 1H) 3.11-3.24 (m, 1H) 3.29-3.37 (m, 1H) 3.81-3.93 (m, 1H) 4.96-5.08 (m, 1H) 7.11 (s, 2H) 7.73-7.83 (m, 1H) 8.08 (d, J=8.34 Hz, 1H) 8.25-8.35 (m, 1H) 8.30 (d, J=4.80 Hz, 1H). LCMS: [M+H]+: 388.2.

Workup

  1. customThe mixture was degassed
  2. customcompletion of the reaction
  3. customwas kept under N2 in a refrigerator overnight
  4. customThe clear solution on the top was decanted
  5. filtrationfiltered through 4 Acrodisc CR 25 mm Syringe Filters
  6. washThe catalyst on the bottom was washed thoroughly with methanol (2×30 mL)
  7. filtrationfiltered
  8. concentrationThe combined filtrates were concentrated to dryness

Sources & evidence

ORD record
ord-bfb5eefb339b4598948e7a0cc5856ee4
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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