(5S)-1-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-N-(5-fluoro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide → (5S)-1-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(5-fluoro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide

HRID 1396937Notes

Reaction equation

HRID 1396937 reaction equation
[CH:1]1([CH2:6][C@H:7]([CH2:25][N:26]([CH:35]=[O:36])[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][C:21]([F:24])=[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>[OH-].[OH-].[Pd+2].CO>[CH:1]1([CH2:6][C@H:7]([CH2:25][N:26]([CH:35]=[O:36])[OH:27])[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:16])[CH2:13][CH:12]=[N:11]2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

4

Reactant 1

HCID 86706373(5S)-1-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-N-(5-fluoro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide

Product 1

HCID 86706372(5S)-1-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(5-fluoro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamideYield 83%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

A mixture of (5S)-1-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-N-(5-fluoro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide (104 mg, 0.210 mmol) and Pearlman's catalyst (29.5 mg, 0.042 mmol) in methanol (12.3 ml) was degassed and placed under 1 atm of H2 at ambient temperature. After 2 hrs, the reaction mixture was filtered and concentrated to give a residue which was purified by RP-HPLC to give (5S)-1-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(5-fluoro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide (71 mg, 0.173 mmol, 83% yield). MS (ES+) m/z 406.1 (MH+) 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.12 (dq, J=11.78, 8.12 Hz, 2H) 1.37-1.67 (m, 5H) 1.70-1.99 (m, 4H) 3.05-3.19 (m, 1H) 3.27 (s, 1H) 3.54 (dd, J=14.15, 4.55 Hz, 1H) 3.75-3.89 (m, 1H) 3.89-4.03 (m, 1H) 4.97 (dd, J=11.87, 5.81 Hz, 1H) 7.11 (s, 1H) 7.50-7.62 (m, 1H) 7.89 (s, 0.7H) 8.12 (dd, J=9.09, 4.04 Hz, 1H) 8.18 (d, J=3.03 Hz, 1H) 8.22 (s, 0.3H)

Workup

  1. customwas degassed
  2. customplaced under 1 atm of H2 at ambient temperature
  3. filtrationthe reaction mixture was filtered
  4. concentrationconcentrated
  5. customto give a residue which
  6. customwas purified by RP-HPLC

Sources & evidence

ORD record
ord-c9c6842917d642cc8902d7e36260f9a5
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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