Phenylmethyl (3S)-3-{[(6-chloro-2-pyridinyl)amino]carbonyl}-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-pyrazolidinecarboxylate → (3S)-N-(6-chloro-2-pyridinyl)-2-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-3-pyrazolidinecarboxamide

HRID 1396873Notes

Reaction equation

HRID 1396873 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9]([C@@H:11]2[CH2:15][CH2:14][N:13](C(OCC3C=CC=CC=3)=O)[N:12]2[C:26](=[O:46])[C@@H:27]([CH2:34][N:35]([CH:44]=[O:45])[O:36]CC2C=CC=CC=2)[CH2:28][CH:29]2[CH2:33][CH2:32][CH2:31][CH2:30]2)=[O:10])[CH:5]=[CH:4][CH:3]=1>CO.[OH-].[OH-].[Pd+2]>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9]([C@@H:11]2[CH2:15][CH2:14][NH:13][N:12]2[C:26](=[O:46])[C@@H:27]([CH2:34][N:35]([CH:44]=[O:45])[OH:36])[CH2:28][CH:29]2[CH2:33][CH2:32][CH2:31][CH2:30]2)=[O:10])[CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 1

HCID 86706347Phenylmethyl (3S)-3-{[(6-chloro-2-pyridinyl)amino]carbonyl}-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-pyrazolidinecarboxylate

Product 1

HCID 66547576(3S)-N-(6-chloro-2-pyridinyl)-2-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-3-pyrazolidinecarboxamideYield 31.2%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

To a solution of phenylmethyl (3S)-3-{[(6-chloro-2-pyridinyl)amino]carbonyl}-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-pyrazolidinecarboxylate (268 mg, 0.413 mmol) in methanol (8 ml) was added 20% palladium hydroxide on carbon (80 mg, 0.413 mmol). The mixture was hydrogenated under balloon pressure for 1 h 20 min. and then filtered. The filtrate was purified by reverse-phase HPLC to yield (3S)—N-(6-chloro-2-pyridinyl)-2-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-3-pyrazolidinecarboxamide (55 mg, 0.129 mmol, 31% yield). LC/MS: (M+H)+: 423.9. 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.06-1.31 (m, 2H) 1.31-1.47 (m, 1H) 1.47-1.69 (m, 4H) 1.69-1.98 (m, 4H) 2.11-2.37 (m, 1H) 2.40-2.66 (m, 1H) 2.79-3.01 (m, 1H) 3.17-3.31 (m, 1H) 3.51 (dd, J=14.15, 4.55 Hz, 1H) 3.61-3.85 (m, 2H) 3.95 (td, J=9.54, 4.93 Hz, 1H) 4.60-4.76 (m, 1H) 7.14 (d, J=7.83 Hz, 1H) 7.75 (t, J=7.96 Hz, 1H) 7.88 (s, 1H) 8.08 (d, J=8.08 Hz, 1H).

Workup

  1. filtrationfiltered
  2. customThe filtrate was purified by reverse-phase HPLC

Sources & evidence

ORD record
ord-963039ae1701468abd66e73e8290ea3f
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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