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

HRID 1396935Notes

Reaction equation

HRID 1396935 reaction equation
[CH:1]1([CH2:6][C@H:7]([CH2:24][N:25]([CH:34]=[O:35])[O:26]CC2C=CC=CC=2)[C:8]([N:10]2[C@H:14]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][N: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>[OH-].[OH-].[Pd+2].CO>[CH:1]1([CH2:6][C@H:7]([CH2:24][N:25]([CH:34]=[O:35])[OH:26])[C:8]([N:10]2[C@H:14]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][N: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 86706371(5S)-1-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-N-4-pyrimidinyl-4,5-dihydro-1H-pyrazole-5-carboxamide

Product 1

HCID 60200596(5S)-1-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-4-pyrimidinyl-4,5-dihydro-1H-pyrazole-5-carboxamideYield 93.1%

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-4-pyrimidinyl-4,5-dihydro-1H-pyrazole-5-carboxamide (76 mg, 0.159 mmol) and Pearlman's catalyst (22.30 mg, 0.032 mmol) in methanol (8.8 ml) was degassed and placed under 1 atm of H2 at ambient temperature. After 1 h 50 min, 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-4-pyrimidinyl-4,5-dihydro-1H-pyrazole-5-carboxamide (58 mg, 0.148 mmol, 93% yield). MS (ES+) m/z 389.2 (MH+). 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.04-1.21 (m, 2H) 1.37-1.67 (m, 5H) 1.70-1.99 (m, 4H) 3.05-3.20 (m, 1H) 3.35 (d, J=11.87 Hz, 1H) 3.55 (dd, J=14.02, 4.67 Hz, 1H) 3.75-3.90 (m, 1H) 3.90-4.02 (m, 1H) 4.99 (dd, J=11.87, 5.81 Hz, 1H) 7.11 (s, 1H) 7.89 (s, 0.7H) 8.14 (d, J=5.31 Hz, 1H) 8.22 (s, 0.3H) 8.60 (d, J=5.81 Hz, 1H) 8.83 (s, 1H)

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-abd92ba09a0a4eff84c8d6139428305e
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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